Organic Chemistry II Laboratory Manual By Stephen Anderson and Robert Shine Edited by Sarah Carberry and Jay Carreon Ramapo College of New Jersey Mahwah, New Jersey January 2010 © 2010 Anderson, Shine, Carberry, and Carreon Organic Chemistry II Laboratory Manual Dr. Stephen Anderson Dr. Robert Shine Ramapo College of New Jersey Contents and Schedule: Lab 1 Check In, Safety and Procedures Lab 2 Acid-Catalyzed Dehydration of Cyclohexanol Lab 3 Williamson Ether Synthesis Lab 4 Sodium Borohydride Reduction Lab 5 Hypochlorite Oxidation Green Chemistry Lab 6 Grignard Reaction Lab 7 Diels-Alder Reaction Lab 8 Nitration of Methyl Benzoate Lab 9 Friedel-Crafts Alkylation Lab 10 Qualitative Organic Analysis and Sim-Org Lab 11 Aldol Condensation Reactions Lab 12 Hydrolysis of Methyl Benzoate Green Metrics Lab 13 Analysis of Carbohydrates Lab 14 Review – Checkout and Laboratory Final Examination © 2010 Anderson, Shine, Carberry, and Carreon 2 Organic Chemistry II Laboratory Manual Appendices Appendix List: Appendix A: Qualitative Organic Analysis and Sim-Org Appendix B: Safety Issues Appendix C: Comments About Writing Style Appendix D: Measurements and Significant Figures Appendix E: Percent Yield Calculation Method Appendix F: Green Metrics Appendix G: Chemical Data Acknowledgements: The Authors wish to thank the following people for their assistance with this manual: Carol Ichinco (Laboratory Coordinator), Thomas Drwiega (Laboratory Technician), Gurpreet Kaur (Honors Research Student), Benjamin Barrios (Research Student), and all the other Instructors who have taught Organic Chemistry Laboratory sections for the past few years. Dr. Scott Frees and Jeffrey Ludwig are acknowledged for their work in writing and developing the Sim-Org qualitative organic analysis simulation program. © 2010 Anderson, Shine, Carberry, and Carreon 3 LAB 1: LABORATORY PROCEDURES ORGANIC CHEMISTRY LABORATORY PROCEDURES SCOPE OF THE COURSE This course offers a comprehensive introduction to laboratory techniques in organic chemistry for science majors. Chemistry is a mature science that continues to expand and evolve in step with recent developments in science and technology. Students will perform experiments that put into practice the ideas discussed in lecture. E-MAIL AND INTERNET USE Use will be made of e-mail (Luminis) and the Internet to provide important instructions to students concerning laboratory material. Students are encouraged to contact the Instructor in person or by e-mail for additional help, if needed. Information about the course may be transmitted periodically by the Instructor via a web site for the course. Students should check this web site at least once a week. Students may not submit lab reports via e-mail or e-mail attachments or by fax. Lab reports must be submitted as paper copy. ATTENDANCE Each lab session will begin at the scheduled time. Attendance at all laboratory sessions is mandatory and will be recorded. If you are late, it will be noted and recorded. A missed laboratory experiment cannot be made up at another time and any missed laboratory session will result in a grade of zero (0) for that experiment unless an alternate library report is completed. During the course of the semester you will be allowed to substitute one alternate report for any one lab period you cannot attend. You must discuss the content and deadline of the alternate report with the Instructor as soon as possible after your absence. SPECIAL NEEDS Students with special needs who are registered with the Office of Specialized Services and require special accommodations should notify the Instructor as soon as possible. GRADING Each laboratory session will be graded by a procedure explained to you by your laboratory instructor. Your in-lab work and your report will be used to determine your grade. The final laboratory exam will account for about 20% to 30% of your final laboratory course grade. In grading laboratory sessions, the following will be considered: meeting deadlines, submitting the necessary forms and reports on time and in good order, being on time for lab, and working in a safe and efficient manner. Your practical bench skills and laboratory results will also be analyzed, along with your ability to effectively explain and discuss them in your lab report. SAFETY As with many activities in daily life, working in the organic chemistry laboratory poses some hazards that you must recognize. Many of the chemicals used can be toxic if not used correctly. Also, many substances you will use are flammable and must be kept away from sources of heat that could cause them to ignite and start a fire. Glassware can be broken and cause cutting hazards. You must always come to the laboratory prepared so that you will be 4 aware of the unique hazards you will confront. You must consult the MSDS forms for the chemicals you will use so that you will know their toxic and flammability properties. You can find MSDS data on the Internet by typing the chemical name, a space followed by MSDS in a Google search box (for example: acetone MSDS). If you have any questions about the experiment you are performing or the chemicals you are using, please ask the Instructor before you begin work. When you are done with the experiment, the chemicals you have should be discarded as hazardous waste or reclaimed material and placed in the proper containers. If you are pregnant or expect that you may become pregnant, you should consult with a medical doctor about the potential hazards involved with exposure to organic chemicals. See Appendix B for more information about safety. EYE PROTECTION Students are required to have department approved lab goggles that must be worn at all times in the laboratory when experimental work is being done. Students who fail to wear eye protection could be asked to leave the lab by any employee of the College. It is not recommended that you wear contact lens in the laboratory. PRE-LABORATORY PREPARATION It is imperative that students be prepared to perform the scheduled experiments. An unprepared student is a hazard in a chemistry laboratory. In order to prepare for the experiment, students are expected to read the appropriate laboratory experiment prior coming to the lab. Students may be tested at the beginning of the lab period to ensure they are prepared to begin work. The Instructor also may require students to answer pre-laboratory questions in the lab notebook. LABORATORY NOTEBOOK Students should have a notebook that will be used in the lab for recording all experimental data. A title should appear at the top of the page for each new experiment. Data obtained during an experiment should always be neatly and clearly recorded in this notebook. You should use the department approved notebook for this course. You will be required to turn in a copy of your experimental data sheet before you leave the lab at the end of the period. You must include your name, the name of the experiment, and the date of the lab period on the data page you submit which will graded as part of your report grade. Any measurement data must have the numerical value recorded to the correct number of significant figures and the units of that measurement, such as 1.234 g for a weight measurement. LAB REPORTS Before leaving the laboratory, each student must submit a laboratory data sheet as described above. Lab reports can only be submitted for labs that have been attended and must be submitted at the beginning of the lab session following the lab that is being reported. Points will be deducted for lateness or for an incomplete lab report. No lab report for a given experiment will be accepted after graded reports for that lab have been returned to the class. Generally, graded lab reports will be returned in the next class meeting after the report is submitted. A score of zero is assigned for a report if the lab report is not submitted. 5 FORMAT OF LAB REPORT Laboratory reports must be typed on 8.5 11-inch white paper. The report should have a professional appearance and it must demonstrate that much thought and care went into its preparation. Some comments about report writing style appear in Appendix C. Spelling and grammar count. All laboratory reports must be written in the following format that conforms to the guidelines set forth by the American Chemical Society: COVER PAGE Place the following information in the upper right hand corner of the title page or first page of the report: Title of the experiment, your name, date of submission ABSTRACT The abstract consists of two to five sentences that concisely inform the reader of the nature of the experiment that was performed and a brief summary of your final results. Note that the abstract is read immediately after the title and hence need not repeat any information that already appears in the title. Though the abstract appears at the beginning of the lab report, it should be the last section of the report that is composed. The abstract should be about 50 to 100 words and should give a concise description of the experiment and the important results that were obtained. It should not be too general or too specific. INTRODUCTION The introduction consists of three to five paragraphs that relate only the most essential elements of theory to the reader. Consult other sources such as a chemistry textbook for this information. Include only enough theory so that the reader is made to understand the basic physical and chemical principles involved in this experiment. If applicable, any pertinent mathematical and chemical equations must be given in this section. The introduction should conclude with a one- or two-sentence paragraph that explains the objective or goal of the experiment. SAFETY Students shall describe all relevant safety precautions that were observed during the course of the experiment. Information about the hazards that may be encountered is particularly important. Material Safety Data Sheet information should be included. You should give a summary of the pertinent data (such as: toxicology, flammability, and physical properties) and not just a copy of the MSDS. EXPERIMENTAL For our purposes, the experimental section will consist of a short paragraph that includes a sentence that refers the reader to some source for the procedure. For example, the student may write: "The procedure for this experiment appears in the web page for the course (#)." The number in brackets refers to the citation number. This number is used to refer the reader to the citation in the References section where the full reference (including information such as the name of the author, title of book or web site, date of publication, and page number or exact web address) will appear next to the appropriate number. In addition to the reference citation, any deviations from the published procedure and any experimental hints or tips that may aid the 6 reader in understanding and repeating the experiment should be included. For example, ‘In this experiment, the instructor requested that 0.05M HCl be used instead of 0.10M as specified in the module.’ RESULTS This section consists of a written paragraph that refers the reader to tables, graphs, data sheets, and figures that contain your data. It is especially important to inform your reader how your experimental data were used to calculate your final results. You must explain how you determined your final results. Include sample calculations with an accompanying explanation. The use of a spreadsheet program (such as Microsoft Excel) for calculations, tabulation of results, and graphing is encouraged. DISCUSSION This section is used to indicate to the reader how the results relate to the theory and whether or not the objective was met. In addition, the final results must be compared to literature values, if available. Reasonable sources of error should be listed and discussed with respect to their contribution to the final results. The discussion provides a good indication of the student's comprehension of the material. A good discussion should show that the student was able to correctly interpret the data and to relate the results to the scientific principles being tested by the experiment. If the experiment was not successful, then the discussion is equally important in stating the reasons for the outcome. A good discussion can be written regardless of the success of the experiment. CONCLUSION This section should include a summation of the Results and Discussion sections. It should only be about 1 paragraph long and is intended to draw together all the pertinent information that has been determined from the experiment. REFERENCES This section consists of a numbered listing of literature or Internet references that were used to perform the experiment and that were used to write the lab report. This includes a full reference to the lab module and any other publications or correct web page URLs that you may have used to obtain literature values and supplemental theory. Note that the reference numbers must correspond to the reference citations used in the text of the report. © 2010 Anderson, Shine, Carberry, and Carreon 7 LAB 2: ACID-CATALYZED DEHYDRATION OF CYCLOHEXANOL PURPOSE: You will run a synthesis reaction using the techniques of reflux and distillation. An infrared spectrum of the product will be obtained to assess the success of the reaction. BACKGROUND INFORMATION: Organic synthesis is very important in that it allows the experimenter to make new compounds from compounds that might be more readily available. Sometimes a synthesis reaction is easy to do and other times great effort and care must be given. This experiment will require good technique as the cyclohexene product is volatile and can be easily lost by evaporation thus lowering your yield. The reaction to be done in this laboratory period will be the acid-catalyzed dehydration of cyclohexanol to give cyclohexene, which is an example of an E1 reaction. OH Cyclohexanol MW 100.16 g/mol bp 160-161°C H3PO4 H2O Cyclohexene, MW 82.14 g/mol bp 83°C (distilled from the mixture) Cyclohexanol is a secondary alcohol, which can be protonated by a strong acid. The protonated alcohol then loses a water molecule to form a secondary carbocation. Loss of a hydrogen atom on an adjacent carbon atom results in the formation of cyclohexene. It is possible that a substitution reaction could compete in this synthesis. To minimize this, a strong acid is used so that the accompanying anion is a weak nucleophile. The acids of choice for this dehydration reaction are concentrated sulfuric acid and concentrated phosphoric acid. We will use concentrated phosphoric acid in this experiment as it causes less charring of the organic materials. Recall that this reaction is a reversible one in that water can be added to an alkene in the presence of an acid to give an alcohol. Hence, we should be mindful of LeChatelier’s principle in order to move the equilibrium in the direction we want. If you look at the balanced equation it becomes obvious that water must be avoided to minimize the undesired reverse reaction. This is why concentrated acids are used. Concentrated phosphoric acid is 85% pure whereas concentrated sulfuric acid can be obtained in 100% purity. So, phosphoric acid may be slightly less advantageous than sulfuric acid. Since this reaction is not immediate, the reagents must be heated for a period of time to allow significant amounts of product to form. Reaction times are shortened as the temperature is increased. So the higher the temperature we can use, the shorter the reaction time. The limit we are able to achieve is the boiling point of the solution. In order to allow the reaction to proceed at its boiling point, we must condense and collect the distillate back into the reaction vessel. This is called reflux. We will do a modified reflux by using a fractional distillation setup. At the beginning of the heating process, the distillate will condense and flow back into the reaction vessel. Over time, the hot vapors will reach the thermometer and side arm of the distilling head and begin to distill over. The success of this method lies in the fact that cyclohexene has a low 8 boiling point (83°C) compared to cyclohexanol (bp of 160-161°C) and will distill over first. If the mixture is not overheated, no cyclohexanol will distill. While this is a good method theoretically, significant cyclohexene is lost (as mechanical loss) in the fractionating column, which will lower the yield substantially. To correct this problem, a chaser solvent of toluene (bp of 110°C) will be used near the end of the fractional distillation to push cyclohexene over into the collection vessel. This experiment has many facets that demonstrate concerns and compromises that must be considered in the synthesis of a desired compound. EXPERIMENTAL PROCEDURE: Place 10.0 mL of cyclohexanol (density = 0.948 g/mL) in a 50 mL round bottom flask along with 2.0 mL of 85% phosphoric acid and a few black boil easers. Use care in handling the phosphoric acid. Carefully swirl the flask to ensure the liquids mix. Place the flask in a 50 mL heating mantle and arrange a fractional distillation apparatus on the flask. Be sure the receiving vessel is well immersed in an ice bath. Also try not to have much of the receiving vessel opening exposed to air as the cyclohexene product is very volatile and could be easily lost. If you smell cyclohexene, which has a characteristic odor, you are losing product and your percent yield will be lower. Heat the mixture and note the temperature as the distillation proceeds. You may need to wrap the fractionating column in aluminum foil so that the hot vapors do not become too cool to distill over. Also, be sure that you do not pass water through the fractionating column as this will certainly destroy the fractional distillation. The water should only circulate through the distilling condenser near the receiving vessel. Cyclohexanol has a boiling point of 160-161°C and cyclohexene has a boiling point of 83°C. After the cyclohexene that has formed is distilled, you should observe the temperature rise to distill the unreacted cyclohexanol (which is not desired) or the temperature may drop if no liquid is distilling over. You should observe that there are a few mL of liquid in the distilling vessel (unreacted cyclohexanol and phosphoric acid). Turn off the heat and, when possible, remove the thermometer and its adapter and carefully add 10 mL of toluene, which boils at 110°C (as a chaser solvent) to drive over the cyclohexene that is held up in the fractionating column. Continue distilling until there is very little liquid in the distilling flask or the temperature has risen to 110°C. The material that has distilled over must now be purified. During these procedures keep the product mixture cold and covered as much as possible. Do all work in the hood. Pour the product mixture into a separatory funnel and use a small amount of toluene to thoroughly remove all the liquid from the distillation product vessel. About 3 mL of toluene should be sufficient. Extract the organic layer in the separatory funnel with an equal volume of saturated sodium chloride solution to remove some of the dissolved water. Drain off and discard the lower layer keeping the upper organic layer in the separatory funnel. Now place the organic layer in a suitable container and add some solid anhydrous drying agent such as calcium chloride or sodium sulfate. This will remove the last traces of dissolved water from the cyclohexene-toluene solution. After about 5 minutes, quickly filter this mixture using gravity filtration and a glass wool or cotton plug to catch the solid drying agent. The filtrate should be collected into a suitable round bottom flask for the final distillation. 9 While the above work-up procedures are being done, the fractionating apparatus should have been carefully cleaned and dried using acetone. Now do a final fractional distillation collecting the distillate that boils below 90°C. Weigh your product and be sure to report your percent yield calculation in your report. The final distillate should be clear. If it is cloudy, the water was not completely removed. Your Instructor may wish to take an infrared spectrum of your product. IMPORTANT INFORMATION ABOUT THE REPORT: This will be another report that will require a percent yield calculation. Be sure to carefully show how you calculate the percent yield and use the proper number of significant figures. Draw a mechanism using the curved arrow formalism for the conversion of cyclohexanol to cyclohexene in the presence of catalytic phosphoric acid. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 10 LAB 3: WILLIAMSON ETHER SYNTHESIS PURPOSE: This experiment is an example of the Williamson ether synthesis which follows the S N2 mechanism. Here, one analgesic will be converted into another analgesic. IMPORTANT REACTION: H N HO Me O Acetaminophen MW 151.16 g/mol mp 168-172°C H N K2CO3 CH3CH2I 2-butanone Ethyl Iodide MW 155.97 g/mol bp 69-73ºC EtO Me O Phenacetin MW 179.22 g/mol mp 133-136°C BACKGROUND INFORMATION: There are many over-the-counter non prescription medications to reduce pain (analgesic), reduce fever (antipyretic) and reduce inflammation. Salicylic acid, obtained from willow tree bark, was used more than 100 years ago for its medicinal properties. Since it had undesirable side effects, much early research was done to find a better alternative. The Bayer Company in Germany found that, by acetylating salicylic acid, a better pain reliever was obtained. This compound, acetylsalicylic acid, is well known as aspirin. Over the years, many different kinds of NSAIDs (non-steroidal anti-inflammatory drugs) were developed. These include aspirin, acetaminophen, ibuprofen and naproxen sodium. While much research has been done in developing these profitable drugs, much still needs to be done to fully understand the biochemical cause of pain and how pain can be relieved. Pain relief and drug dependence is another area of active research. EXPERIMENTAL PROCEDURE: Add 1.300 g of acetaminophen, 2.500 g of powdered anhydrous potassium carbonate, 15.00 mL of 2-butanone, and 1.800 g of ethyl iodide carefully to a 50 mL round bottom flask. Heat the mixture under reflux for 1 hour. After cooling, add 15 mL of diethyl ether to the flask and transfer the reaction mixture to a separatory funnel. Extract with two 10 mL portions of 5% NaOH to remove unreacted acetaminophen. Dry the organic layer with anhydrous sodium sulfate. Separate the drying agent from the solution by decantation or gravity filtration through a cotton plug. Evaporate the solvent. Weigh the crude product, calculate the percent yield and obtain its melting point. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will follow the usual format for synthesis experiments. Show the complete mechanism of the reaction. Be sure the percent yield calculation is carefully done. Record the melting point range of the final product and compare the experimental value to the reported melting point of phenacetin. Using these data, discuss the relative success of the experiment. Draw a mechanism for the conversion of acetaminophen to phenacetin in the presence of potassium carbonate using the curved arrow formalism. © 2010 Anderson, Shine, Carberry, and Carreon LAB 4: SODIUM BOROHYDRIDE REDUCTION PURPOSE: You will use a reduction reaction in the synthesis of hydrobenzoin from benzil using sodium borohydride as the reducing agent and you will characterize the product by melting point. Your Instructor may substitute benzophenone for hydrobenzoin in this experiment. Benzophenone (MW 182 g/mol, mp 47°C) would give benzhydrol (MW 184 g/mol, mp 6567°C) as the reduction product. IMPORTANT REACTIONS: O Ph HO H Ph NaBH4 Ph OH H Ph O Benzil MW 210.23 g/mol HO H Ph (1R,2S)-(meso)-Hydrobenzoin MW 214.26 g/mol mp 137-139°C O Ph Benzophenone MW 182.22 g/mol mp 47-51°C Ph H (1R,2R)-Hydrobenzoin mp 146-149°C HO Ph H OH H Ph (1S,2S)-Hydrobenzoin mp 146-149°C OH NaBH4 Ph OH Ph Ph Benzhydrol MW 184.23 g/mol mp 65-67°C BACKGROUND INFORMATION: Oxidation and reduction reactions are very important in organic chemistry in the synthesis of desired compounds. There are many oxidizing and reducing agents that can be used to achieve the desired product. Some of these redox reagents are general in that they can react with a large number of functional groups. Other redox reagents are very specific and have limited but specific reactivity and can cleanly do the conversion that is desired. Sodium borohydride is such a specific reducing reagent. It can be safely used to reduce an aldehyde or ketone to an alcohol. Hydride type reagents are rather basic and can often be vigorously decomposed in water or alcohol. Extreme care should be exercised whenever you work with any type of hydride. However, sodium borohydride is reasonably safe to use. It does not undergo the decomposition as vigorously as other hydrides. Further, the reaction can be run in alcohol and yields are very good. The reaction that will be done in this experiment is generally fast and almost quantitative. EXPERIMENTAL PROCEDURE: Dissolve 0.5 g of benzil (or benzophenone) in a 25 mL Erlenmeyer flask using 5 mL of 95% ethanol. Slight heating may be required but cool to room temperature before adding 0.12 g of sodium borohydride. In about 3 minutes the reaction is complete as noted by the disappearance of the yellow color of benzyl (if that reactant were used). After about 5 more minutes, add 5 mL of water and heat the solution to decompose the large excess of sodium borohydride. While still warm, add approximately 10 mL of water. Let the solution cool to allow the product to crystallize. Suction filter the product, dry and weigh it and take its melting point. IMPORTANT INFORMATION ABOUT THE REPORT: This experiment is another example of a synthesis reaction. You must calculate the percent yield as you did before. Be sure to use the correct number of moles from the balanced equation in your calculation to determine the theoretical yield. Be sure to record both the observed and reported melting point ranges for your product. Draw a mechanism using the curved arrow formalism for the conversion of the ketone to the corresponding alcohol in the presence of sodium borohydride in ethanol. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 13 LAB 5: OXIDATION OF BENZALDEHYDE-GREEN CHEMISTRY PURPOSE: This experiment will introduce the student to the new area of Green Chemistry. Green Chemistry tries to use new reagents or less toxic familiar reagents to be more environmental friendly. In this experiment, dilute hydrogen peroxide and Clorox (which both present some hazards) will be used in place of the more usual, more toxic dichromate reagents. IMPORTANT REACTIONS: O O H [O] OH H2O2 or NaClO Benzoic acid MW 122.12 g/mol mp 121-125°C Benzaldehyde MW 106.12g/mol bp 178-179°C O OH bleach Benzhydrol MW 184.23 g/mol bp 65-67°C Benzophenone MW 182.22 g/mol mp 47-51°C BACKGROUND INFORMATION: Green chemistry is that new aspect of chemistry in which environmentally friendly reagents are used in place of more hazardous traditional reagents. A great deal of research is currently being done in this area and major success stories have been written. Links to green chemistry web sites can be found on Robert Shine’s web page for this course (see http://phobos.ramapo.edu/~bshine/). One difficulty with green chemistry is finding reagents that perform as well as the older reagents. It is our hope that we will be able to introduce better experiments in this course as future studies are done. We can start with a simple reaction such as the oxidation of benzaldehyde to benzoic acid. Aldehydes are very easy to oxidize so it was thought that simple household oxidants could be used in place of the traditional hazardous dichromate reagents. Our study is investigating the use of dilute hydrogen peroxide and Clorox. In the past few years at Ramapo College, there has been success using these reagents but the yields have been low. Your data in this experiment will be used to find the optimum conditions for future classes to use. In place of benzaldehyde, your Instructor may use benzohydrol or acetophenone in this experiment. The green advantage of using benzohydrol would be that it may have been the product from the prior experiment (if your Instructor chose that starting material) and we would be recycling reagents. Acetophenone should be easily oxidized to benzoic acid by hypochlorite via a haloform reaction. 14 Clorox, a mild oxidant, is a dilute solution of sodium hypochlorite (NaOCl). Clorox should never be mixed with ammonia solutions or ammoniated cleansers as a reaction that releases deadly chlorine gas occurs. The other oxidant that will be tried is dilute hydrogen peroxide. We have found that a 3% solution that can be purchased in a drug store is too dilute to give a meaningful reaction. When a 10% solution was used, results were better but still not adequate. In addition, if the 10% solution comes in contact with the skin, it turns it white for a few hours. More concentrated solutions exist but the hazard level rises as the concentration is increased. Your careful observations and well written laboratory reports for this experiment will be very useful in determining if this experiment could be successful in the future. EXPERIMENTAL PROCEDURE: The entire synthetic procedure should be carried out in the fume hood. Although these are household chemicals, you still need to be careful handling them. If you get any on your hands, you will not feel it immediately, but white patches will soon appear. PART 1: Oxidation using Household Bleach A: Oxidation of Benzaldehyde Place benzaldehyde (2 mL) and glacial acetic acid (1 mL) in a 125 mL Erlenmeyer flask, add a magnetic stirrer bar and gently heat on a stirrer-hotplate. To the reaction mixture add household bleach (30 mL) in approx. 5 mL portions over a 2-3 min. period. After addition is complete, heat the reaction to approximately 80-90°C (with stirring) for 45 minutes. It is very important that you do not allow the solution to boil. Remove the flask from the stirrer-hotplate, allow it to cool to room temperature. Then place it in an ice bath. Filter off the product using a Buchner funnel, wash the product and reaction flask with ice-cold water, and allow the solid to dry. Measure the mass of benzoic acid produced, calculate the percent yield, and record its melting point range. B: Oxidation of Benzhydrol Place 1.00 g of benzhydrol, 15 mL of household bleach, 15 mL of ethyl acetate and 0.100 g of tetrabutylammonium hydrogen sulfate in a 125 mL beaker. Using a magnetic stirrer bar, stir the mixture for 30 minutes. Remove the stir bar and the lower aqueous layer (using a Pasteur pipette). Extract the organic layer with 10 mL of saturated sodium chloride and then 10 mL of water. Dry the organic layer over anhydrous sodium sulfate. Decant or gravity filter to remove the solid drying agent and then evaporate the organic solvent. Determine the melting point and the percent yield of the benzophenone product. PART 2: Oxidation using Hydrogen Peroxide Place benzaldehyde (2 mL) and glacial acetic acid (1 mL) in a 125 mL Erlenmeyer flask, add a magnetic stirrer bar and gently heat on a stirrer-hotplate. To the reaction mixture add 20% hydrogen peroxide (30 mL) in approx. 5 mL portions over a 2-3 min. period. After addition is complete, heat the reaction to approximately 80-90°C (with stirring) for 45 minutes. It is very important that you do not allow the solution to boil. Remove the flask from the stirrer-hotplate, allow it to cool to room temperature. Then place it in an ice bath. Filter off the product using a Buchner funnel, wash the product and reaction flask with ice-cold water, and allow the solid to 15 dry. Measure the mass of benzoic acid produced, calculate the percent yield, and record its melting point range. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will follow the usual format. Discuss the importance of Green chemistry. Be sure the percent yield calculation for each method is carefully done. Also, record the melting point range of the final products and compare the melting point data to the reported melting point of benzoic acid. Using these data, discuss the relative success of each experiment. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 16 LAB 6: GRIGNARD REACTION PURPOSE: This experiment will introduce the student to the synthesis of a sensitive organometallic intermediate (the Grignard reagent) which is very useful in the synthesis of a large number of different functional groups. IMPORTANT REACTIONS: Part 1: Br MgBr Et2O Mg Phenylmagnesium bromide Bromobenzene MW 157.01 g/mol bp 156°C Part 2: MgBr O H3O+ OH Benzophenone MW 182.22 g/mol mp 47-51°C Triphenylmethanol MW 260.33 g/mol mp 160-163°C BACKGROUND INFORMATION: The Grignard reaction was discovered and developed by a French Nobel laureate in the early 1900’s. It is an example of an organometallic compound which has a carbon magnesium bond. Grignard reagents have been extremely useful in the synthesis of a large number of classes of organic functional groups for the past century. Although Grignard reagents are unstable and decompose in air and moisture, they can be prepared and used immediately with moderate difficulty in the undergraduate organic chemistry laboratory. Care will need to be exercised and the equipment must be thoroughly dried before use to insure success. No water may enter the reaction mixture until the final product has been synthesized. Group IA metals (Li, Na, and K) form very basic organometallic compounds which are very hazardous to handle. They can be spontaneously flammable in air and react explosively with water to release hydrogen gas. In these cases, the C-M bond is very polar and the carbon group is highly basic, especially in sodium and potassium compounds. With the Group IIA metal magnesium, the C-Mg bond is not as polar and the compound is not as difficult to handle. Yet they are reactive enough to be very useful in synthesis. The exact 17 nature of the bonding in Grignard reagents has been extensively studied in the past century and is beyond the scope of this discussion. For the purposes of this experiment, one can consider the bonding to be R-MgBr, where R is an alkyl or aryl group. Organometallic compounds with transition metals (such as, iron, mercury, lead, tin, cadmium, and many others) have an even more covalent carbon metal bond. Many of these compounds are stable and often very toxic. Organic mercury compounds are often mentioned as environmental hazards in the New Jersey area. One reason for the extreme toxicity of some organometallic compounds is the volatility that the organic group imparts on the molecule which makes it easier for entry into the body. Returning to the chemistry of the organomagnesium (Grignard) compounds, they are generally prepared by the reaction of an alkyl or aryl halide with magnesium metal turnings. The magnesium turnings are crushed in a mortar and pestle just before use to expose a fresh surface on the metal. Of the halides used, iodides are best, fluorides are the least reactive and bromides are usually preferred for their good reactivity and reasonable cost. Grignard reagents are usually prepared in anhydrous ether as the volatile ether solvent helps keep air away from the reaction. It cannot be stressed enough that the ether must be very dry and kept that way if the reaction is to be successful. Small traces of water will destroy the reagent or keep the reaction from starting. Once formed, the Grignard reagent must be used immediately. One can combine this reagent with a large number of different functional group compounds to give a wide variety of possible products. The Grignard reagent can react with: 1. 2. 3. 4. 5. 6. 7. Any active hydrogen (such as water, alcohols, carboxylic acids, etc.) to produce and alkane or arene (usually this is not a desirable reaction). Formaldehyde to form a primary alcohol. An aldehyde (other than formaldehyde) to form a secondary alcohol. A ketone to form a tertiary alcohol (which will be done in this experiment). An ester to form a tertiary alcohol. Carbon dioxide (as solid dry ice) to form a carboxylic acid. Many other classes of compounds to form other useful products. Due to the great reactivity of Grignard reagents, the alkyl or aryl halide starting material cannot have any reactive function group as part of its molecule. This generally limits the halide to be alkyl, alkenyl, alkynyl, or aryl. An ether group is also compatible and unreactive with the Grignard reagent. In today’s experiment, bromobenzene will react with magnesium turnings to form phenyl magnesium bromide (the Grignard reagent). This intermediate will then be immediately treated with benzophenone to prepare triphenylmethanol (a solid tertiary alcohol). 18 EXPERIMENTAL PROCEDURE: In order to minimize the exposure of the Grignard reagent to water, the equipment and reagents used in this experiment must be absolutely dry. All glassware (reaction glassware, two sample vials and a stirring rod) must be pre-dried in an oven at 110°C for at least 30 minutes prior to use. The anhydrous diethyl ether solvent and the bromobenzene will be stored over molecular sieves to absorb any moisture they are exposed to and the magnesium metal will be pre-dried in an oven and crushed in a mortar and pestle to give a fresh magnesium surface. The above preparation work will be completed by the staff before you arrive at the laboratory. PART 1: Generation of Grignard Reagent The procedure for this experiment is still being developed and your Instructor may give directions that are different from what follows. Remove the first reaction vessel or test tube from the oven and cap it with a rubber septum. Add magnesium powder or turnings (50 mg, 2 mmol) to the tube, minimizing the time that the tube is un-capped. Carefully add anhydrous diethyl ether (0.5 mL) to the tube using a dry syringe, injecting the needle through the rubber septum. If a glass syringe is not available a dried disposable glass pipette can be used instead. Remove a sample vial from the oven and cap it with a rubber septum. To this vial add bromobenzene (330 mg, 2.1 mmol) and diethyl ether (0.7 mL) via the syringe as you did for the first tube. After addition of the ether solvent, do not remove the needle from the septum. As soon as the ether has been added to the vial, swirl the mixture and immediately remove the entire bromobenzene-ether mixture by carefully sucking it up into the syringe. Once this has been done, inject approximately one third of the bromobenzene-ether mixture into the first reaction tube containing the magnesium metal in ether. Mix the contents and add a pressure release needle to the septum. If the reaction does not appear to start at this point, first remove the syringe (if used) containing the remaining bromobenzene-ether mixture. Carefully remove the septum and the pressure release needle and quickly grind the magnesium metal using the oven dried glass stirrer rod. Replace the septum and pressure release needle as soon as possible to minimize air-water exposure. Once the reaction starts, the clear solution will become cloudy and the ether may begin to boil. At this point, reattach the syringe containing the remaining bromobenzene-ether mixture and add the rest of the solution drop wise at such a rate that the reaction does no get out of control. Once the entire contents of the syringe has been added, continue to agitate the reaction vessel until the reaction is complete, which will be visible when very little, if any, magnesium metal remains. The synthesized phenylmagnesium bromide is not isolated, but will be used in situ for part 2. PART 2: Synthesis of Triphenylmethanol Remove the second oven dried vial and cap it with a rubber septum. Add benzophenone (0.364 g, 2.0 mmol) and diethyl ether (1.0 mL) in the same manner and using the same precautions as you did in part 1. Shake the vial to dissolve the benzophenone and remove the resulting solution by sucking it up into the dry syringe. Carefully remove the syringe containing the benzophenone-ether solution and inject it drop wise into the reaction tube containing the phenylmagnesium bromide. A red color should be 19 observed at this point. After all the benzophenone solution has been added, rinse the vial with a few drops of ether and inject these washings into the reaction tube. The reaction is complete when the red color disappears. On completion, cool the reaction tube in ice, and very carefully add 3 M hydrochloric acid (2 mL) drop wise with stirring. If there is any un-reacted magnesium metal in your reaction tube be especially careful as acids react with metals to release hydrogen gas. This could lead to your reaction solution bubbling out of your tube. On addition of the acid, a two-phase system should result. Add more ether solvent if the white triphenylmethanol product begins to crystallize out. Carefully remove the lower aqueous layer using a Pasteur pipette. To the remaining ether layer add an equal volume of saturated aqueous sodium chloride solution, shake the tube, allow the layers to settle and remove the lower aqueous layer as before. Dry the ether layer over calcium chloride pellets for 5-10 minutes. Then carefully transfer the ether layer via pipette into a pre-weighed beaker. Wash the solid drying agent with a small amount of ether and combine the washings with the solution in the beaker. Remove the ether solvent by carefully blowing a stream of air over the solution in the beaker. When it appears to be dry, re-weigh the beaker to record the mass of triphenylmethanol produced. Then add ice-cold petroleum-ether (1 mL) to the white residue and grind (triturate) the product with a glass rod. Filter the product using a Hirsch funnel and air dry the solid. Weigh the solid to record the mass of purified triphenylmethanol obtained. Calculate the percent yield of the final triphenylmethanol product and determine the melting point. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will follow the usual format. Be sure the percent yield calculation is carefully done. Also, record the melting point range of the final product and compare that melting point to the reported melting point of triphenylmethanol. Using these data, discuss the relative success of the experiment. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 20 LAB 7: DIELS-ALDER REACTION PURPOSE: This experiment will introduce the student to an important cycloaddition reaction. The Diels-Alder reaction is reversible and the student will need to consider methods to increase the yield, if possible. IMPORTANT REACTIONS: [4 + 2] cycloaddition Diene Dienophile O O O -Phellandrene MW 136.23 g/mol bp 175-176°C Maleic anhydride MW 98.06 g/mol mp 51-57°C Adduct H H O H O O endo-7-isopropyl-4-methylbicyclo[2.2.2] oct-4-ene-1,2-dioic anhydride MW 234.29 g/mol mp 126-127°C BACKGROUND INFORMATION: The Diels-Alder reaction is an example of a cycloaddition reaction discovered by two German chemists (Otto Diels and Kurt Alder) in the 1950’s. This reaction is an example of a concerted reaction in which bonds are being made as other bonds are being broken. Effective overlap of all bonding orbitals is essential for the reaction to occur which leads to a specific stereochemistry in the products. In this reaction, the endo isomer is formed. The Diels-Alder reaction is an example of a [4+ 2] cycloaddition reaction in which an alkene adds in a 1,4 addition to a diene. Neither Diels nor Alder fully understood the generality or significance of cycloaddition reactions. This was left for Roald Hofmann (now at Cornell University) and R. B. Woodward from Harvard University to discover in the late 1960’s. The Woodward Hofmann rules for cycloaddition reactions (which are beyond the scope of this discussion) were perhaps one of the major discoveries in organic synthesis in the 20th century. In early work with this reaction, results were mixed and yields varied quite a bit. Later it was found that this reaction is reversible. If one considers LeChatelier’s rule, it might be possible to shift the equilibrium in the desired direction. In the experiment that will be done here, alpha-phellandrene will react with maleic anhydride. The alpha-phellandrene is a natural product derived from cedar wood and has a characteristic cedar wood odor. It is not 100% pure so the directions call for an added amount to be used to compensate for the impurity. Maleic anhydride is a white solid. It can hydrolyze with water to give maleic acid so water should be avoided if possible. With prolonged exposure to 21 moisture, the anhydride group in the product may convert to the diacid which will have different properties. The final bicyclic product is usually obtained without difficulty. EXPERIMENTAL PROCEDURE: This reaction must be done in a fume cupboard. Place maleic anhydride (0.527 g, 5.4 mmoles) and -phellandrene (1 mL, 85 % pure, 5.4 mmoles) into a 25 mL round bottomed flask and attach a water-cooled condenser. Add anhydrous acetone (3 mL) through the top of the condenser and swirl the reaction mixture. The reaction is exothermic and a yellow color should appear at this point. Heat the reaction under reflux for 1 hour using a steam bath or hot water bath. After this time, carefully remove the condenser, pour the reaction mixture into a 20 mL beaker and allow the acetone solvent to evaporate to approximately half of its original volume. Allow the reaction to cool to room temperature, then cool the reaction vessel in an ice bath to induce crystallization of the Diels-Alder adduct (scratching with a glass rod may be required). Filter off your product using a Hirsch funnel, washing the flask with a small amount of ice-cold acetone. Dry and weigh the final product, record the melting point and determine the percent yield. If required, (i.e. if the melting point of the product is much lower than expected) recrystallize the product using the minimum amount of warm methanol (be very careful to not overheat as methanolysis of the anhydride group could occur). IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will follow the usual format. Discuss the mechanism of the reaction and the stereochemistry of the product. Be sure the percent yield calculation is carefully done. Also, record the melting point range of the final product and compare that melting point to the reported melting point of the product given above. Using these data, discuss the relative success of the experiment. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 22 LAB 8: NITRATION OF METHYL BENZOATE PURPOSE: This experiment will introduce the student to one of the important electrophilic aromatic substitution reactions. The experiment uses concentrated nitric acid and concentrated sulfuric acid so the student will need to use great care in handling these reagents. IMPORTANT REACTIONS: HNO3 2 H2SO4 O N O 2 HSO4 H3O Nitronium ion CO2Me CO2Me HNO3 H2SO4 Methyl Benzoate MW 136.15 g/mol bp 198-199°C NO2 Methyl-3-nitrobenzoate MW 181.15 g/mol mp 78-80°C BACKGROUND INFORMATION: This experiment and the one next week are examples of electrophilic aromatic substitution reactions. Aromatic systems such as the benzene ring have enhanced resistance toward reactions due to the stability that resonance gives to the aromatic ring. Addition reactions are highly unlikely as they would destroy the conjugated aromatic system. Substitutions can occur and the best reagent to use should have electrophilic properties as the aromatic ring is rich in electrons. The class of reactions known as electrophilic aromatic substitution reactions is studied extensively in the lecture part of the course. These two experiments will show how they can be performed in the laboratory. There are five reactions that are normally presented when discussing electrophilic aromatic substitution reactions. They include: 1. Nitration using concentrated nitric acid and concentrated sulfuric acid to generate the nitronium ion electrophile (which will be done in this experiment). 2. Halogenation using a halogen and a Lewis acid to generate the halonium ion electrophile. 3. Sulfonation using sulfur trioxide as the electrophile. This is the only neutral electrophile in this series of reactions and this reaction is reversible. 4. Friedel-Crafts alkylation using some source of a carbocation as the electrophile. This reaction will be done next week and will use an alcohol and concentrated sulfuric acid to generate the carbocation. 5. Friedel-Crafts acylation using an acyl halide and a Lewis acid to generate the acylium ion electrophile. In the experiment that will be done today, a substituted aromatic ring is used which will lead to meta nitration of the ring. The substituent chosen will moderate the reaction to avoid di- and tri23 substitution of the ring which could lead to explosive products. Trinitrobenzene is explosive. It is best not to heat the reaction too high or too long to avoid further undesired substitution. Also note that this reaction often shows a delayed start. It is best to be patient. If the mixture is heated highly or longer than directed, an uncontrolled reaction may ensue. And, if the reaction is quickly quenched in an ice bath, it may be permanently stopped. If brown fumes start to form, the reaction may be proceeding too quickly and should be moderated. Concentrated nitric acid and concentrated sulfuric acid pose a hazard when being handled. Gloves must be worn and care must be used. If any of the acid mixture gets on the skin, it must be immediately washed with large amounts of cold water. Immediately wash the affected area with water if you suspect that acid may be on your skin. Nitric acid destroys proteins and if some of it (either as liquid or vapors) gets on the skin, the skin cells will die over a few hours to days leaving an orange patch on the surface. This generally wears off in a few days. This reaction usually goes well if care is exercised. The final product is a crystalline solid with a low melting point. EXPERIMENTAL PROCEDURE: Carefully combine concentrated sulfuric acid (0.4 mL) and concentrated nitric acid (0.4 mL) in a suitable test tube or vial and place it in an ice bath. To a second test tube or vial, add methyl benzoate (0.6 g, 4.4 mmoles) and concentrated sulfuric acid (1.2 mL), flick the container to mix the components of this viscous mixture, and then cool it in an ice bath as well. Using a glass Pasteur pipette, carefully add the sulfuric-nitric acid mixture drop wise to the methyl benzoate solution, using a glass stirring rod to mix the reaction. On complete addition of the acid mixture, remove the reaction from the ice bath, allow it to warm up to room temperature, and let is stand for 15 minutes. After this time, in order to crystallize the product, pour the mixture into a small beaker that contains approximately 5g of ice. Filter the resulting solid using a Hirsch funnel and wash out the reaction tube with ice-cold water. When all the product has been transferred to the filtration funnel, wash the product with ice-cold methanol (0.5 mL). Record the mass and melting point of this crude product and calculate the percent yield. Recrystallize the product using an equal mass of methanol and re-record the mass, melting point and percent yield of the pure product. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will follow the usual format. Be sure the percent yield calculation is carefully done. Also, record the melting point range of the final product and compare that melting point to the reported melting point of methyl 3-nitrobenzoate. Using these data, discuss the relative success of the experiment and discuss whether there is any evidence polysubstitution occurred. Draw a mechanism for the conversion of methyl benzoate to methyl 3nitrobenzoate using the curved arrow formalism. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 24 LAB 9: FRIEDEL-CRAFTS ALKYLATION PURPOSE: This experiment will introduce the student to a Friedel-Crafts alkylation reaction, another one of the important electrophilic aromatic substitution reactions. The experiment uses concentrated sulfuric acid to generate an unstable carbocation. IMPORTANT REACTION: OMe OMe H2SO4 OH MeO 1,4-dimethoxybenzoate MW 138.16 g/mol bp 54-56°C MeO 2-methyl-2-propanol MW 74.12 g/mol bp 83°C 1,4-di-tert-butyl-2,5-dimethoxybenzene MW 250.38 g/mol mp 104-105°C BACKGROUND INFORMATION: The Friedel Crafts reaction, named in honor of its two founders, is another example of an electrophilic aromatic substitution reaction. Two variations exist - an alkylation using a carbocation and an acylation using an acylium ion. In this experiment, an alkylation will be performed. Any source of a carbocation can be used in a Friedel Crafts alkylation reaction. Historically, alkyl halides were treated with the Lewis acid, aluminum trichloride. The current experiment will use an alcohol in concentrated sulfuric acid. One could also use an alkene with sulfuric acid. The Friedel Crafts alkylation reaction has many problems that make the acylation reaction (followed by a Clemmensen or Wolff-Kishner reduction) a better choice. However, by carefully choosing the reagents in this experiment the problems were minimized. The three main difficulties involve the activity of the ring, the possibilities of carbocation rearrangement, and further activation of the ring by the adding alkyl groups. By choosing tertbutyl alcohol in this experiment, rearrangement of the carbocation is not a factor as the tertiary carbocation that is generated will not rearrange. The activity of the benzene ring is enhanced by the addition of two methoxy groups. The bulky tert-butyl groups stop the polyaddition at disubstitution. You may want to further ponder the choice of reagents in this reaction which gives a good yield of only one isomer compared to many possible isomers in normal alkylation reactions. EXPERIMENTAL PROCEDURE: Place 1,4-dimethoxybenzene (0.300 g, 2.2 mmoles) and acetic acid (1 mL) in a suitable test tube or vial (not micro-scale) and, if needed, gently warm to dissolve. Add pre-melted t-butyl alcohol (0.5 mL) to this tube and cool the entire mixture in an ice bath. Carefully add concentrated sulfuric acid (1 mL) drop wise via a glass pipette, mixing the solution with a glass rod after each drop. A solid product may be visible at this point, but in order to complete the reaction, remove the reaction vessel from the ice-bath, allow it to warm to room temperature, and 25 let it stand for 10 minutes. After this time, re-cool the tube in ice in order to induce complete crystallization. At this point, very carefully add water (5 mL) drop wise to the mixture in the reaction vessel, stirring after the addition of each drop. Filter off the product using a Hirsch funnel and wash the solid with ice-cold water. You could also further wash the crystals in the Hirsch funnel with cold methanol to purify it. After drying, record the mass and melting point of the crude product and determine the percentage yield. If needed, recrystallize the product in the minimum amount of hot methanol, and determine the mass, melting point and percent yield of the purified product. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will follow the usual format. Discuss the mechanism of this reaction. Be sure the percent yield calculation is carefully done. Also, record the melting point range of the final product and compare that melting point to the reported melting point of 1,4-di-tert-butyl-2,5-dimethoxybenzene. Using these data, discuss the relative success of the experiment. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 26 LAB 10: QUALITATIVE ORGANIC ANALYSIS AND SIM-ORG PURPOSE: This experiment will introduce the student to qualitative organic analysis. A number of test tube reactions will be done to identify an aldehyde and/or a ketone unknown in Part A and a computer simulation program called Sim-Org will be used as a homework assignment in Part B. IMPORTANT REACTIONS AND DATA: Part 1: Tollen’s Test O R O 2 Ag(NH3)2OH H O R NH4 2 Ag H2O 3 NH3 Silver Mirror Aldehyde Part 2: Iodoform Test O R O Me 4 HO 3 I2 O R Methylketone 3 I CHI3 3 H2O Iodoform Part 3: 2,4-Dinitrophenylhydrazones O2N O R R' N O2N R H H2N N R' NO2 N H NO2 H 2,4-dinitrophenylhydrazone 2,4-dinitrophenylhydrazine Part 4: Semicarbozones Cl R N R R' H NH2 O N O H3N O N R' N H NH2 -H2O Semicarbazide hydrochloride N H Cl Semicarbazone 27 LAB 10: Table of Unknown Aldehydes and Ketones Compound 2-heptanone 3-heptanone n-heptanal n-butanal Acetone 3-pentanone Benzaldehyde Acetophenone Cinnamaldehyde Hexane-2,5-dione mp (°C) of 2,4-DNP 89 81 108 123 126 156 237 238 255 257 mp (°C) of Semicarbazone 123 101 109 95106 187 138 222 198 215 224 BACKGROUND INFORMATION: This experiment will be the first of a few experiments that will explore qualitative organic analysis. Analysis of unknown compounds is routinely done by chemists and occupies much of the time expended by scientists. Analytical chemistry is an entire separate study which, by its very nature, crosses into other branches such as organic chemistry. Analytical chemistry can be qualitative (interested only in the identification of an unknown) or quantitative (interested in the nature and percentage composition of unknowns). Of the two, qualitative is less demanding. Qualitative analysis may use instruments or classical wet chemical test tube reactions. Instrumental analysis was introduced last semester in the discussions on infrared and proton magnetic resonance spectroscopy. Wet chemical analysis was also presented in the experiment that studied SN1 and SN2 reactions. This experiment will expand on that brief introduction last semester. Wet chemical analysis usually involves using simple and quick test tube reactions that have clear observations. However, since many factors can affect the result, the observer must look beyond the observation and carefully interpret the data in making a decision about the identity of an unknown. Reactions that quickly give a precipitate, color change or gas evolution are ideally suited for qualitative tests. Usually, in organic chemistry a qualitative test only identifies the functional group class to which the unknown belongs. Further work must be done to fully determine the exact identity of the unknown compound. This later aspect of qualitative organic analysis is called ‘making a derivative’. In today’s experiment there are four tests. The first two (Tollen’s test and iodoform reaction) are used to get a general class of possibilities. The last two (2,4dinitrophenylhydrazone formation and semicarbazone formation) are used to make derivatives. Actually, in the broader scheme of qualitative organic analysis, the 2,4-dinitrophenylhydrazone reaction identifies the class and makes a derivative. However, since we know that today’s unknowns are aldehydes or ketones, this test does not supply any useful differentiation as it is positive for both these classes. The Tollens test gives a precipitate of silver metal (either as a beautiful silver mirror on the inside of the test tube or a black precipitate of colloidal silver) if the unknown is an aldehyde. This mild oxidizing agent can also give a positive test for any very easily oxidized organic 28 compound such as some carbohydrates. Further note that an insoluble unknown aldehyde may give a false negative test if the reagents are not mixed thoroughly. The iodoform test gives a light yellow precipitate of iodoform if the unknown has a methyl carbonyl group as part of the molecule. Since the reagent is also mildly oxidizing, a methyl group next to a secondary alcohol group will give a positive test. The test is positive for 2-pentanone, acetone, 2-butanone, ethanol, 2-propanol and like compounds. The test is negative for 3-pentanone, for example. The iodoform that forms has a melting point of 117°C but cannot be used as a derivative as it is the same product no matter what the unknown is. The formation of a 2,4-dinitrophenylhydrazone is a messy reaction. Sulfuric acid is one of the ingredients in the test reagent. The precipitate is difficult to filter and dry. Some success in cleaning the product can be achieved by washing the solid with cold ethanol. Since percent yields of derivatives are never an issue, loss of material is acceptable if a purer solid results. Sometimes, the color of the 2,4dinitrophenylhydrazone (2,4-DNP for short) can give some information about the unknown. Highly conjugated carbonyl groups give deep red 2,4-DNP derivatives while non conjugated carbonyl groups give yellow 2,4-DNP compounds. The formation of a semicarbazone derivative is a nice second choice in identifying an unknown. Since precipitation can be difficult it is usually not a first choice. Considering the table of data above, if the unknown were 3-pentanone and a successful 2,4-DNP was prepared with a melting point of, say, 153°C, there would be no need to make a second derivative as this melting point would uniquely identify the unknown from this list of possibilities. However, if the unknown were acetone, the 2,4-DNP would not clearly rule out nbutanal as their 2,4-DNP derivatives have similar melting points. A semicarbazone would clearly identify what the unknown would be in this case. However, other data would help distinguish acetone from n-butanal. A Tollen’s test would be positive for n-butanal and the iodoform test would be positive for acetone. So, the final identification of an unknown is achieved by an analysis of the data available rather than following a rigid set of rules or procedures. EXPERIMENTAL PROCEDURE: Your goal is to identify the unknown aldehyde or ketone sample assigned to you from the table. The tests in parts 1 & 2 will enable you to narrow your search to a particular type of compound, and measuring the melting points of the derivatives you synthesize in parts 3 & 4 will give the identity of a particular aldehyde or ketone. PART 1: Tollen’s Test This test must be performed on three samples: a known aldehyde (positive test), a known ketone (negative test) and your unknown sample. Clean three test tubes by adding sodium hydroxide solution (2 mL) to them and heating them in a water bath. To prepare the Tollens reagent, place a 0.03 M solution of silver nitrate solution (2 mL) into a 10 mL volumetric flask and add a 3 M of sodium hydroxide solution (1 mL) to produce a grayish suspension of silver oxide. To this, add a 2.8 % solution of ammonia (0.5 mL) dropwise with shaking. If the precipitate does not dissolve, add more ammonia dropwise until it does to a maximum of 3 mL. Then dilute the entire mixture to 10 mL total by addition of water. The Tollens reagent can form explosive compounds on standing and should not be stored. Remove the sodium hydroxide solution from your three test tubes, rinse them with water, and add your freshly prepared Tollens reagent (1 mL) to each of the tubes. To the first tube add 29 one drop of your known aldehyde, to the second tube add one drop of your known ketone and to the third tube add one drop of your unknown. Allow the tubes to stand for several minutes and look for the appearance of a silver mirror coating on the inside of the tube. If no precipitate has formed, heat the test tube in a warm water bath for a few minutes. PART 2: Iodoform Test This test must be performed on three samples: a known methyl ketone (positive test), a non-methyl ketone (negative test) and your unknown sample. Place the sample to be tested (approximately 50 mg or three drops) in a test tube and dissolve it in water (2 mL). (If it does not dissolve in water, repeat the procedure and dissolve it in 2 mL of 1,2-dimethoxyethane instead). Add 3 M sodium hydroxide solution (2 mL) followed by the careful addition of the iodoform solution (3 mL). For a positive test with a known methyl ketone, the iodoform reagent’s color should disappear and the yellow iodoform product separates. Repeat the procedure for a known non-methyl ketone and your unknown. PART 3: 2,4-Dinitrophenylhydrazone Place the 2,4-Dinitrophenylhydrazine solution (5 mL) in a test tube and add approximately 50 mg (or three drops) of your unknown sample. Heat the sample tube in a water bath for several minutes until the presence of a precipitate is observed. Then cool the reaction tube in an ice bath and filter off the product using a Hirsch (or perhaps a Buchner funnel would be better) funnel. Wash the product and the test tube with ice-cold water, and then wash the product with ice-cold ethanol and allow the solid to dry thoroughly. Record the melting point range of your product. PART 4: Semicarbazone Place the semicarbazide hydrochloride solution (0.5 mL) in a test tube and add approximately 100 mg of your unknown sample. To this add methanol (1 mL) and pyridine (10 drops, use in a fume hood), then heat the sample tube in a water bath for 10 minutes. Cool the reaction tube in an ice bath and allow the product to crystallize (you may need to scratch the tube with a glass rod to induce crystallization). Filter off the product using a Hirsch funnel and wash the product and the reaction tube with ice-cold water. Finally, wash the product with ice-cold methanol and allow it to dry thoroughly. Record the melting point range of your product. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will be different from the usual format of the past few experiments. No percent yield calculation will be done. Melting point ranges of any derivatives must be recorded and compared to the melting points given in the table to determine the identity of any unknown. The identity of any unknown and its unknown number should be given along with conclusive evidence that supports the claim that is made. END OF LABORATORY EXPERIMENT PART A (SEE PART B ON NEXT PAGE) © 2010 Anderson, Shine, Carberry, and Carreon 30 LAB 10: PART B: SIM-ORG SOFTWARE HOMEWORK ASSIGNMENT PURPOSE: The student will use a computer simulation program called Sim-Org developed at Ramapo College to learn a great deal about qualitative organic chemistry. After some practice with the software, the student will be asked to do a number of unknown analyses. This assignment will be done on your own time in the next few weeks. The program may be run on any computer on campus. It is not available on the internet. Exact instructions about this assignment and how to run the program will be given to you. Also, see Appendix A at this time to see a longer, more informative version of the Program Help section which appears below. BACKGROUND INFORMATION: QUALITATIVE ORGANIC ANALYSIS SIM-ORG PROGRAM HELP SECTION SHORT VERSION SEE APPENDIX A FOR LONG VERSION Dr. Scott Frees and Dr. Robert Shine and Jeffrey Ludwig Ramapo College of New Jersey Mahwah, NJ 07430 CONTENTS: Introduction Solubility Classification Functional Group Classification Tests Derivative Formation and Use Final Identification of an Unknown Substance INTRODUCTION There are two methods for identifying the structure of an unknown organic compound. The first and older method is to run classification tests to identify the functional group of the compound followed by the production of one or more derivative compounds to confirm the exact nature of the unknown. The second method is to determine the spectral properties of the unknown using mainly infrared and proton magnetic resonance spectroscopy. The first method will be covered in this simulation program. This program has 12 different functional group classes and 500 different unknowns. There are 22 different classification tests to determine the functional group of the unknown. There are 21 different derivatives to help identify the exact name for the unknown. Since this program is still under development as this manual is being printed, special instructions for the use of Sim-Org will be given as a handout when the assignment is presented. The general method to determine the identity of an unknown substance by classical methods is to gather some introductory information about the compound. Note the odor, color, and melting or boiling point of the material. Then find its solubility characteristics by doing a 31 solubility classification as described below. From the information obtained from the solubility classification run appropriate functional group classification tests to identify the group to which the unknown belongs. Then the unknown is converted into one or more different solids called derivatives. Consulting tables of derivative melting points one can then identify the exact identity of the unknown compound. In order to intelligently conduct the functional group classification tests a solubility classification is usually done first to narrow down the possible functional group possibilities. A problem may arise when an unknown substance has two or more functional groups in the molecule. This may lead to confusion when interpreting the functional group and could lead one to the wrong table of derivatives. Such unknowns are more difficult to identify. There are a few such compounds in this simulation program. SOLUBILITY CLASSIFICATION The solubility of an organic compound in various solvents can give valuable information about the unknown. The general rule of 'like dissolves like' or 'polar compounds dissolve more readily in polar solvents' is useful. Also, organic acids (such as carboxylic acids and phenols) react with bases to form water soluble salts and organic bases (such as amines) react with acids to form water soluble salts. It should be noted that the polarity of an organic compound is increased by the kind and number of polar functional groups in the molecule and that the polarity decreases as the size of the non polar aliphatic group in the molecule increases. With this background, one begins the solubility classification by adding 3 drops or 3 mg of the unknown to 3 mL of water and shaking the mixture. If the unknown dissolves, it is a polar compound and is placed in solubility group S1. An unknown in class S1 is then tested as above using ether as the solvent. If it dissolved in both water and ether it is then placed in class S2. For unknowns that do not fall into either class S1 or S2, the unknown’s solubility in 5% sodium bicarbonate is determined. If it is soluble, the unknown is placed in class A1. If it is not soluble, the solubility in 5% sodium hydroxide is studied. If it is soluble at this point, the unknown belongs in class A2. If an unknown is insoluble to this point it is next tested for solubility in 5% hydrochloric acid. Compounds soluble in 5% hydrochloric acid are placed in solubility class B1. For compounds insoluble to this point the next solvent to try is concentrated sulfuric acid. Unknowns soluble in only this acid are placed in solubility class N1. A further distinction can be made for compounds soluble in concentrated sulfuric acid by testing their solubility in 85% phosphoric acid. Such compounds that are soluble in 85% phosphoric acid are placed in class N2. Finally, for compounds insoluble to this point are paced in class IN. These solubility classes and their consequences can be summarized below: S1 These are very polar compounds which consist of salts of carboxylic acids or amines. It is also possible the compound is of low molecular weight and has many polar functional groups such as a carbohydrate. S2 These compounds are low molecular weight (generally less than 5 carbons) with a polar functional group such as carboxylic acid, amine, alcohol, aldehyde, or ketone. A1 Higher molecular weight carboxylic acids fall into this class. A2 Phenols show this kind of solubility. B1 Primary, secondary and tertiary amines fall into this class. However, if there are two or more phenyl groups on the nitrogen, the amine will probably not be basic enough to form the salt and will, then, be insoluble. 32 N1 These are higher molecular weight compounds (generally more than 9 carbons) containing an oxygen atom. N2 These are medium size molecules (generally containing from 5 to 9 carbons) containing an oxygen atom. IN These are neutral compounds. Alkyl halides and alkanes fall into this class. The results of a solubility classification should not be strictly interpreted as there are many overlaps. Use the results of this classification only as a focus into which classification tests should be done first. FUNCTIONAL GROUP CLASSIFICATION TESTS Below are listed 22 chemical tests that could be used to help identify an unknown. The tests are listed in numerical/alphabetical order. 1. 2,4-dinitrophenylhydrazone 2. Acetyl chloride 3. Basic hydrolysis 4. Beilstein 5. Benedict 6. Bromine in carbon tetrachloride 7. Ceric nitrate 8. Chromic acid 9. Combustion 10. Ferric chloride 11. Ferric hydroxamate 12. Ferrous hydroxide 13. Hinsberg 14. Hydroxylamine hydrochloride 15. Iodoform 16. Lucas 17. Nitrous acid 18. pH in ethanol/water 19. Potassium permanganate 20. Silver nitrate in ethanol 21. Sodium fusion 22. Tollens DERIVATIVE FORMATION AND USE Below are listed 21 derivatives that could be prepared from various unknowns to help in a final determination of the unknown. The derivatives are listed in numerical/alphabetical order. 1. alpha-naphthylurethane 2. 2,4-dinitrophenylhydrazone 3. 3,5-dinitrobenzoate 4. Acetamide 5. Acid from hydrolysis 6. Amide 7. Anilide 33 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. Benzamide Benzenesulfonyl chloride Bromo derivative Methiodide Neutralization equivalent Oxime Phenylhydrazone Phenylurethan Picrate p-Nitrobenzyl ester p-Nitrophenylhydrazone p-Toluenesulfonamide p-Toluidide Semicarbazone FINAL IDENTIFICATION OF AN UNKNOWN SUBSTANCE Tables of organic substances can be used to identify the unknown based on the results of the classification tests and the derivative melting point results that you obtained. TABLES OF UNKNOWNS - Once the derivative melting point data have been recorded enter the Tables of Unknowns by selecting the suspected functional group class. Here a list of organic compounds separated by type will appear. Select the family that the unknown belongs to. A list of all the compounds of that type, presented in order of increasing boiling/melting point will appear. Also listed are the melting points of any derivatives that can be synthesized from the class of the unknown compound. By matching the table data with the unknown compound data obtained above, one can identify the unknown. ANSWER TRIAL - Based on all the melting point data in the Tables of Unknowns, one will now have an idea of what the unknown sample is. To see if you are correct, you can enter it into the program by selecting Answer Trial. Make sure that you select the compound correctly, exactly as it appears in the table of unknowns. If you are correct, a congratulation message will appear. If you are wrong, first re-check your data for the unknown. If it is still incorrect, then you will need to go back into the program in order to correctly identify the unknown sample. IMPORTANT INFORMATION ABOUT THE REPORT FOR THIS ASSIGNMENT: You will be assigned a number of unknowns to determine using the Sim-Org software. For your report, be sure to identify the unknown number and compound name for each unknown. After you give the name of the unknown, be sure to carefully and completely describe how you reached your decision. Tell the tests you did to determine the identity of the compound and how you eliminated other possibilities. END OF SIM-ORG ASSIGNMENT © 2010 Scott Frees and Robert Shine 34 LAB 11: PART A: ALDOL CONDENSATION REACTION PURPOSE: These experiments will introduce the student to one of the many condensation reactions in Organic Chemistry. These two syntheses (Part A and Part B) usually give good yields with little difficulty. Both can be completed within one lab period. IMPORTANT REACTION: O O O 2 NaOH H Benzaldehyde MW 106.12 g/mol bp 178-179°C Me Me Acetone MW 58.08 g/mol bp 56°C Dibenzalacetone MW 234.29 g/mol mp 110.5-112°C BACKGROUND INFORMATION: The aldol addition reaction is one in which two aldehyde molecules react with one another to give a product which contains both an aldehyde and alcohol function group, hence the name ‘aldol’. A molecule of water can easily be lost from this product giving a conjugated alphabeta unsaturated aldehyde. If this dehydration occurs, the reaction is called a condensation reaction. The overall reaction in that case would be called an aldol condensation. There are very many variations of reactions that seem to have an aldol flavor and such reactions are often called aldol reactions even though they are technically different. The reaction in this experiment is really a Claisen-Schmidt reaction because it is a reaction of an aldehyde with a ketone. Aldol type reactions will be thoroughly presented in the lecture part of this course. This broad class of reactions has a common mechanism. One of the molecules has a mildly acidic hydrogen which can be removed by a strong base to give a carbanion. The resulting carbanion acts like a nucleophile and attacks a partially positively charged carbon in a second molecule. The negative charge on this addition product is removed in some way depending on the nature of the starting molecules. One way would be to add a proton. Another would be to eliminate an anion. Aldol and related reactions are extremely important in organic synthesis as they allow the chemist to construct larger molecules from smaller ones. In these reactions, a carbon-carbon bond is formed. Also of great importance is that the product molecule can have many different useful functional groups which can be transformed in subsequent reactions to other useful products. The strength of the base that is used is determined by the acidity of the active hydrogen compound. Often the base of choice is sodium hydroxide or sodium ethoxide which are effective in removing a hydrogen that has a pKa in the 1720 range. The alpha hydrogen to a carbonyl or ester group often has such a pKa due, in part, to the resonance stabilization of the resulting anion. In the first experiment to be done today, the alpha hydrogen on an acetone molecule is removed by the hydroxide ion giving a carbanion which attacks the carbonyl of a benzaldehyde molecule. A hydrogen ion then adds to neutralize the adduct. A water molecule is lost from this adduct to extend the conjugated system. Remember that conjugated systems increase the stability of a compound. An alpha hydrogen on the other methyl group of the acetone molecule repeats 35 the process described above with a second benzaldehyde molecule giving the final product, dibenzalacetone. Two molecules of water are formed as products in this reaction. The final product is a nicely crystalline yellow solid. EXPERIMENTAL PROCEDURE: Place sodium hydroxide (2.5 g) in a 100 mL Erlenmeyer flask and add water (25 mL) and ethanol (20 mL). Add a magnetic stirrer bar and stir until all the NaOH has dissolved. To a second reaction vessel, add benzaldehyde (2.65 g, 0.025 mol) and acetone (0.725 g, 0.0125 mol). Add approximately half of the aldehyde-ketone solution to the sodium hydroxide solution, and stir for 10 minutes with a watch glass covering the top of the flask. After this time, add the remainder and stir for a further 10 minutes. Filter off the product using a Buchner funnel and wash the product with water until the washings no longer appear to be basic (test using pH paper). The best way to do this is to remove the vacuum tube from the filter flask, fill the Buchner funnel with water, carefully stir the product with a glass rod and re-apply the vacuum. Each time the funnel is filled with water, add some litmus paper to the solution to test the pH. When all traces of NaOH have been removed via water washing, dry the product and record the mass and melting point of the crude product. Then calculate the percent yield. Recrystallize the product from the minimum amount of hot ethanol, recording the mass, melting point and percent yield of the pure product. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will follow the usual format for synthesis experiments. Be sure the percent yield calculation is carefully done. Be sure to pay attention to the coefficients in the balanced equation when determining which starting material is the limiting reagent. Record the melting point range of the final product and compare that melting point to the reported melting point of dibenzalacetone. Using these data, discuss the relative success of the experiment. END OF PART A EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 36 LAB 11: PART B: A SOLVENT-FREE ALDOL REACTION PURPOSE: This experiment is yet another example of a condensation reaction. Avoiding the use of a solvent is one of the techniques used by the Green Chemistry method. IMPORTANT REACTION: O O Me O NaOH H Me Acetophenone MW 120.15 g/mol bp 202°C 4-Methylbenzaldehyde MW 120.15 g/mol bp 204-205°C Me 4-Methylbenzylideneacetophenone MW 222.3 g/mol mp 93-94.5°C BACKGROUND INFORMATION: This experiment is a condensation reaction similar to the one done above. The synthesis of the unsaturated ketone will be achieved by the reaction of a ketone with an aldehyde using sodium hydroxide as the base. The difference will be that no solvent will be used in this reaction. The reduction in the amount of hazardous waste that is generated in a given process is one of the methods used in Green Chemistry. Elimination of the solvent should reduce the quantity of hazardous waste. Usually, solvents are needed to give mobility to the reagents so that the reacting molecules can collide and then react with one another. Reactions between solid materials go slowly if at all. Normally the solvent used in a reaction must be removed when the desired product is being purified. This generally results in the generation of more hazardous waste than is necessary. The choice of reagents in this reaction provides some mobility on their own. The two reacting molecules are both liquids. However, the necessary base, sodium hydroxide, is a solid and must touch the acetophenone molecule to remove the alpha hydrogen on the methyl group. This will be achieved by grinding all three reagents together in a mortar and pestle. The generation of an equimolar amount of water as a product of the reaction will give some added mobility to the reactants. The product is a solid material which makes its isolation from the reaction mixture easier. One thing to note in the work up procedure of this experiment is that water is added to the solid product until the solution does not have a basic pH. Be sure to record the approximate amount of water you will need to reach a neutral pH. If much water is used the Green Chemistry aspect will be lessened. In your report, comment on how successful this reaction is from a Green Chemistry perspective. How much waste was generated and how hazardous was that waste? What could be done to treat the waste to reduce its volume or make it less hazardous? EXPERIMENTAL PROCEDURE: Place para-methylbenzaldehyde (0.5 g, 4.2 mmol), acetophenone (0.5 g, 4.2 mmol) and sodium hydroxide (0.18 g, 4.5 mmol) into a mortar and grind the components together for 5 37 minutes. After this time, add a small amount of water to the mortar to aid in the transfer of the yellow product to a Hirsch funnel. Wash the product with as little water as possible until the washings no longer appear to be basic. The best way to do this is to remove the vacuum tube from the filter flask, fill the Hirsch funnel with water, carefully stir the product with a glass rod and re-apply the vacuum. Each time the funnel is filled with water, dip the end of a piece of litmus paper to the solution to test the pH. When all traces of NaOH have been removed via water washing, dry the product and record the mass and melting point of the product. Then calculate the percent yield. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will simply be a separate results and discussion section. Discuss each reaction along with the mechanism and be sure to point out the important differences between the two reactions. Be sure the percent yield calculation is carefully done. Record the melting point range of the final product and compare that melting point to the reported melting point of 4-methylbenzylideneacetophenone. Using these data, discuss the relative success of the experiment in your discussion section. END OF PART B EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 38 LAB 12: HYDROLYSIS OF METHYL BENZOATE-GREEN METRICS PURPOSE: This experiment will use microwave energy to cause a hydrolysis of the ester methyl benzoate to benzoic acid using a 5% aqueous sodium hydroxide solution. After the reaction mixture cools, the solution will need to be acidified to cause the precipitation of benzoic acid. This experiment will also introduce the concept of Green Metrics. Please read Appendix F (Green Metrics). IMPORTANT REACTIONS: O O OMe 1. 5% NaOH OH 2. conc. HCl Methyl Benzoate MW 136.16 g/mol bp 198-199°C Benzoic Acid MW 122.12 g/mol mp 121-123°C BACKGROUND INFORMATION: The hydrolysis of an ester is an easy and important reaction in organic chemistry. One can use an acid or a base to shorten the time needed for the reaction to occur. The acid catalyzed hydrolysis of an ester gives the product in the free acid form without further pH adjustment. While this may seem preferable, it is seldom done as this reaction is reversible and the equilibrium process significantly lowers the yield. The base promoted reaction forms the sodium salt of the carboxylic acid which cannot enter into an equilibrium reaction so the reaction can proceed to completion giving a high yield of product. Note that the base, sodium hydroxide, is not a catalyst in this reaction as it is consumed in forming the sodium salt. The free acid form is recovered from the sodium salt quite easily by a simple pH adjustment. In this reaction, concentrated hydrochloric acid will be used to acidify the basic reaction product. Since benzoic acid is moderately water soluble, it is necessary to limit the amount of water in the solution. Microwave heating will be used in this experiment. As mentioned in an earlier experiment, the use of microwave energy for heating dates back to the 1960’s and became widespread in the 1980’s. Since microwave energy can penetrate deep within a molecule, the entire molecule can be heated at the same time. Conventional heating is generally done by conduction and heats from the outside to the inside of the sample. Therefore, microwave heating can be faster than conventional heating. However, for heating to occur, the microwave energy needs to be absorbed by the bonds in the molecule. Absorption of energy is better in polar bonds and poor in nonpolar bonds. Hence, water heats rapidly in a microwave oven. It is said that alkanes do not heat well with microwave energy. The design of a microwave oven presents some challenges to the designer. It is hard to have a uniform distribution of microwave energy in the cabinet. Further, if no absorption of microwave energy occurs a reflection of energy in the unit can destroy to apparatus. Some manufacturers warn that operating a microwave oven when empty can ruin the oven. 39 Microwave ovens can also cause fires. Many people who have made popcorn in a microwave oven have seen burnt popcorn kernels at one time or another. It is important to remember that three things are needed for a fire to start: a source of ignition such as microwave energy, a combustible substance such as many organic compounds, and a source of oxygen such as air. It is important that one follows the experimental details carefully to work in a safe manner. Microwave energy can penetrate the human body and can interfere with certain electronic devices that may be implanted for health reasons (such a cardiac pacemakers). If you have implanted electronic devices, let the Instructor know and avoid the lab while the microwave unit is turned on. Please make careful observations during this experiment and comment on any success or failure in your report. EXPERIMENTAL PROCEDURE: You will use the laboratory microwave in this experiment. Be especially careful when handling the microwave reaction tubes as they are delicate and expensive to replace. Place methyl benzoate (1.00 mL) in a microwave reaction tube and add 5% aqueous sodium hydroxide (10 mL). Add a magnetic stirrer bar, then screw on the cap and place your tube in the microwave turntable. Record the position number of your reaction tube on the turntable. When all of the tubes have been added, your instructor will place the turntable into the microwave unit, close the door and select the correct file-setting for your reaction (Ester.rot). The program will take 12 minutes to run, followed by a 5 min. vent and cool down program. On completion, your instructor will open the microwave door and remove the turntable. Carefully remove your reaction tube, and empty the contents into a beaker. Cool the contents to room temperature, and acidify the solution with about 2 mL of concentrated HCl. As acidification proceeds, solid benzoic acid will precipitate. Be sure to check that the final solution is acidic by using pH paper. Cool the mixture in an ice bath and suction filter the benzoic acid. After the benzoic acid has dried sufficiently, weigh the solid, take its melting point and calculate the percent yield. IMPORTANT INFORMATION ABOUT THE REPORT: The report for this experiment will follow the usual format for synthesis reactions. Be sure the percent yield calculation is carefully done. Also, record the melting point range of the final product and compare that melting point to the reported melting point of benzoic acid. Using these data, discuss the relative success of the experiment. Also, be sure to critique the effectiveness of using microwave heating to cause the reaction to occur. Draw a mechanism for the conversion of the methyl ester to the corresponding carboxylic acid using the curved arrow formalism. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 40 LAB 13: ANALYSIS OF CARBOHYDRATES PURPOSE: Continuing with the techniques of qualitative organic analysis, the student will do test tube experiments to learn about the different classes of carbohydrates and natural sweeteners. IMPORTANT STRUCTURES: Monosaccharides Aldohexose: CHO CHO CHO HO H H HO H HO H OH H OH H OH H HO H H OH HO H H OH H CH2OH CH2OH D-Mannose OH OH CH2OH D-Galactose D-Glucose Aldopentose: Ketohexose: CH2OH CHO O H HO OH H H OH H OH CH2OH D-Fructose HO H H OH CH2OH D-Xylose 41 Disaccharides Lactose (from galactose and glucose, shown in aldehyde form) OH CH2OH OH O HO CHO O HO CH2OH OH OH Maltose (from 2 glucose units, shown in aldehyde form) CH2OH O HO CH2OH HO OH O OH CHO HO OH Sucrose (from glucose and fructose) CH2OH O CH2OH HO HO O OH OH O CH2OH OH BACKGROUND INFORMATION: Sweetening the foods and drink humans consume is very important to the food chemist. Natural caloric sweeteners have been known for many centuries. Within the last century there has been a growing importance to reduce the calories humans consume to control weight. A few successful non-caloric sweeteners have been developed and reached commercial importance. The first of these to be introduced around the 1950’s was calcium cyclamate. This product was 42 abruptly taken off the market in the late 1960’s when a connection between its use and bladder cancer was shown. Another artificial sweetener developed around that time and still in use is saccharin. This successful sweetener leaves an unpleasant after taste in some people so it is not an ideal substitute. During the 1980’s aspartame (NutraSweet) was introduced. This sweetener is a methyl ester of an amino acid dimer. It has been very successful. The latest artificial sweeter is a chlorinated sucrose molecule which is found in sucralose (Splenda).The above mentioned compounds are not carbohydrates. They are artificial sweeteners. Carbohydrates are polyhydroxy aldehydes or ketones or compounds that can be hydrolyzed to polyhydroxy aldehyles or ketones. Carbohydrates which contain one carbonyl group or potential carbonyl group (which would result from the hydrolysis of a hemiacetal linkage) are called monosaccharides. Monosaccharides generally contain 4 to 7 carbon atoms. When two monosaccharide molecules bond together via an acetal or hemiacetal linkage, a disaccharide is formed. Three monosaccharide molecules would give a trisaccharide, etc. If a very large number of monosaccharide molecules join together, a polysaccharide (such as: cellulose, starch or glycogen) is formed. These larger molecules can be split apart into the simpler units via acid hydrolysis or enzymatic action. The lower molecular weight carbohydrates (mono, di and trisaccharides) are often sweet to varying degrees and are often called sugars. Monosaccharides can be further classified by the number of carbon atoms in the molecule. The nomenclature ending suffix for carbohydrates is -ose. A five carbon monosaccharide would be a pentose; a six carbon one would be a hexose, etc. If the carbonyl group is an aldehyde, the monosaccharide is a aldose. The ketone containing monosaccharides are ketoses. The six carbon aldehyde sugar known as glucose is an example of an aldohexose. With 4 chiral centers in this molecule, glucose has 16 stereoisomers. This number rises to 32 when glucose forms an intramolecular hemiacetal ring. Carbohydrates can also be classified as reducing or nonreducing. If the carbohydrate can be easily oxidized, it is a reducing carbohydrate. If not, it is a nonreducing carbohydrate. Reducing carbohydrates have an aldehyde group or a hemiacetal linkage. Since carbohydrate molecules contain a large number of polar alcohol groups, the lower carbohydrates are mostly water soluble. As the molecular weight increases, water insolubility can arise. Carbohydrates are often difficult to crystallize. The tests described below will give information about the class of carbohydrate to which the test substance belongs. Perform the tests as described below and draw conclusions about the unknowns that were assigned. It is possible that you may not be able to fully identify a given unknown but clearly state the conclusions that can be made. EXPERIMENTAL PROCEDURE: Perform the following identification tests on each of the six sugars to be tested: glucose, fructose, xylose, sucrose, lactose, and maltose. For your classification tests, you will be using 1 % solutions of each of the sugars. 1) Red Tetrazolium Test This test distinguishes between reducing and non-reducing sugars. In clearly labeled test tubes, place one drop of the sugar to be tested, and add the red tetrazolium solution (1 mL) and 3 M sodium hydroxide solution (1 drop). Put the tube in a hot water bath and estimate the time that it takes for a color to appear. 43 2) Barfoed’s Test This test distinguishes between mono and disaccharides that are reducing sugars. In clearly labeled test tubes, place the sugar to be tested (1 mL) and add the Barfoed’s reagent (0.5 mL). Put the tube in a hot water bath and estimate the time that it takes for a red precipitate to form. 3) Bial’s Test This test distinguishes between pentoses and hexoses. In clearly labeled test tubes, place the sugar to be tested (1 mL), add the Bial’s reagent (1 mL) and a boiling chip. Heat the tubes in a sand bath and estimate the time that it takes for a color to form. Also note the intensity of the color that develops. As a standard of reference, add the Bial’s reagent (1 mL) to water (1 mL) and heat that along with your samples for comparison. 4) Seliwanov’s Test This test distinguishes between aldohexoses and ketohexoses. Place Seliwanov’s reagent (1 mL) in each clearly labeled test tubes. Add the sugar to be tested (5 drops), agitate to mix, then heat in a water bath for 5 minutes. Note the color and its intensity. IMPORTANT INFORMATION ABOUT THE REPORT: You will be assigned a number of unknowns to determine using the tests described above. For your report, be sure to identify by unknown number and class name for each unknown, if possible. After you give this information, be sure to carefully and completely describe how you reached your decision. Tell the tests you did to determine what the compound was and how you eliminated other possibilities. END OF EXPERIMENT © 2010 Anderson, Shine, Carberry, and Carreon 44 APPENDIX A: QUALITATIVE ORGANIC ANALYSIS QUALITATIVE ORGANIC ANALYSIS SIM-ORG PROGRAM HELP SECTION LONG VERSION Dr. Scott Frees and Dr. Robert Shine Ramapo College of New Jersey Mahwah, NJ 07430 CONTENTS: Introduction Strategy for Identifying and Unknown Solubility Classification Functional Group Classification Tests Derivative Formation and Use Final Identification of an Unknown Substance This simulation program includes: 12 organic chemistry functional groups 24 classification tests 21 derivative tests 500 unknowns GENERAL INTRODUCTION TO QUALITATIVE ORGANIC ANALYSIS There are two methods for identifying the structure of an unknown organic compound. The first and older method is to run classification tests to identify the functional group of the compound followed by the production of one or more derivative compounds to confirm the exact nature of the unknown. The second method is to determine the spectral properties of the unknown using mainly infrared and proton magnetic resonance spectroscopy. The first method will be covered in this simulation program. This program has 12 different functional group classes and 500 different unknowns. It is planned that the second method will be covered in a later revision of this program. The general method to determine the identity of an unknown substance by classical methods is to gather some introductory information about the compound. Note the odor, color, and melting or boiling point of the material. Then find its solubility characteristics by doing a solubility classification as described below. From the information obtained from the solubility classification run appropriate functional group tests to identify the group to which the unknown belongs. Then the unknown is converted into one or more different solids called derivatives. Consulting tables of derivative melting points one can then identify the exact identity of the unknown compound. In order to intelligently conduct the functional group classification tests a solubility classification is usually done first to narrow down the possible functional group possibilities. A problem may arise when an unknown substance has two or more functional groups in the molecule. This may lead to confusion when interpreting the functional group and could lead 45 one to the wrong table of derivatives. Such unknowns are more difficult to identify. There are a few such compounds in this simulation program. STRATEGY FOR IDENTIFYING AN UNKNOWN The following steps should be taken to identify an unknown compound: 1. Perform a solubility classification test to determine the possible functional group classes to which the unknown may belong. 2. Narrow the choices of possible functional groups to one group by performing appropriate functional group tests. 3. Make one or more derivatives to finally determine the exact identity of the unknown. The above approach should lead to a successful identification of an unknown about 80 % of the time. In other cases, the unknown may pose difficulties that would require imagination and careful analysis of the data to be successful in its identification. SOLUBILITY TEST ANALYSIS: Obtain the solubility class for the assigned unknown. Shown below is a list of possible functional groups for each solubility class. This classification method is not exact and may need further thought and imagination in certain cases. These solubility classes and their consequences can be summarized below: S1 These are very polar compounds which consist of salts of carboxylic acids or amines. It is also possible the compound is of low molecular weight and has many polar functional groups such as a carbohydrate. S2 These compounds are low molecular weight (generally less than 5 carbons) with a polar functional group such as carboxylic acid, amine, alcohol, aldehyde, or ketone. A1 Higher molecular weight carboxylic acids fall into this class. A2 Phenols show this kind of solubility. B1 Primary, secondary and tertiary amines fall into this class. However, if there are two or more phenyl groups on the nitrogen, the amine will probably not be basic enough to form the salt and will, then, be insoluble. N1 These are higher molecular weight compounds (generally more than 9 carbons) containing an oxygen atom. N2 These are medium size molecules (generally containing from 5 to 9 carbons) containing an oxygen atom. IN These are neutral compounds. Alkyl halides and alkanes fall into this class. FUNCTIONAL GROUP ANALYSIS: Below are listed 24 chemical tests that could be used to help identify an unknown. The tests are listed in numerical/alphabetical order. 23. Introduction to qualitative tests 24. 2,4-dinitrophenylhydrazone 25. Acetyl chloride 26. Basic hydrolysis 27. Beilstein 28. Benedict 29. Bromine in carbon tetrachloride 30. Ceric nitrate 46 31. Chromic acid 32. Combustion 33. Ferric chloride 34. Ferric hydroxamate 35. Ferrous hydroxide 36. Hinsberg 37. Hydroxylamine hydrochloride 38. Iodoform 39. Lucas 40. Nitrous acid 41. pH in ethanol/water 42. Potassium permanganate 43. Silver nitrate in ethanol 44. Sodium fusion 45. Sodium iodide in acetone 46. Solubility 47. Tollens DERIVATIVE USAGE: Below are listed 21 derivatives that could be prepared from various unknowns to help in a final determination of the unknown. The derivatives are listed in numerical/alphabetical order. 22. Introduction to derivative use 23. 1-naphthylurethane 24. 2,4-dinitrophenylhydrazone 25. 3,5-dinitrobenzoate 26. Acetamide 27. Acid from hydrolysis 28. Amide 29. Anilide 30. Benzamide 31. Benzenesulfonamide 32. Bromo derivative 33. Methiodide 34. Neutralization equivalent 35. Oxime 36. Phenylhydrazone 37. Phenylurethan 38. Picrate 39. p-Nitrobenzyl ester 40. p-Nitrophenylhydrazone 41. p-Toluenesulfonamide 42. p-Toluidide 43. Semicarbazone 47 SOLUBILITY CLASSIFICATION The solubility of an organic compound in various solvents can give valuable information about the unknown. The general rule of 'like dissolves like' or 'polar compounds dissolve more readily in polar solvents' is useful. Also, organic acids (such as carboxylic acids and phenols) react with bases to form water soluble salts and organic bases (such as amines) react with acids to form water soluble salts. It should be noted that the polarity of an organic compound is increased by the kind and number of polar functional groups in the molecule and that the polarity decreases as the size of the non polar aliphatic group in the molecule increases. With this background, one begins the solubility classification by adding 3 drops or 3 mg of the unknown to 3 mL of water and shaking the mixture. If the unknown dissolves, it is a polar compound and in placed in solubility group S1. An unknown in class S1 is then tested as above using ether as the solvent. If it dissolved in both water and ether it is then placed in class S2. For unknowns that do not fall into either class S1 or S2, the unknown’s solubility in 5% sodium bicarbonate is determined. If it is soluble, the unknown is placed in class A1. If it is not soluble, the solubility in 5% sodium hydroxide is studied. If it is soluble at this point, the unknown belongs in class A2. If an unknown is insoluble to this point it is next tested for solubility in 5% hydrochloric acid. Compounds soluble in 5% hydrochloric acid are placed in solubility class B1. For compounds insoluble to this point the next solvent to try is concentrated sulfuric acid. Unknowns soluble in only this acid are placed in solubility class N1. A further distinction can be made for compounds soluble in concentrated sulfuric acid by testing their solubility in 85% phosphoric acid. Such compounds that are soluble in 85% phosphoric acid are placed in class N2. Finally, compounds insoluble to this point are placed in class IN. These solubility classes and their consequences can be summarized below: S1 These are very polar compounds which consist of salts of carboxylic acids or amines. It is also possible the compound is of low molecular weight and has many polar functional groups such as a carbohydrate. S2 These compounds are low molecular weight (generally less than 5 carbons) with a polar functional group such as carboxylic acid, amine, alcohol, aldehyde, or ketone. A1 Higher molecular weight carboxylic acids fall into this class. A2 Phenols show this kind of solubility. B1 Primary, secondary and tertiary amines fall into this class. However, if there are two or more phenyl groups on the nitrogen, the amine will probably not be basic enough to form the salt and will, then, be insoluble. N1 These are higher molecular weight compounds (generally more than 9 carbons) containing an oxygen atom. N2 These are medium size molecules (generally containing from 5 to 9 carbons) containing an oxygen atom. IN These are neutral compounds. Alkyl halides and alkanes fall into this class. The results of a solubility classification should not be strictly interpreted as there are many overlaps. Use the results of this classification only as a focus into which classification tests should be done first. FUNCTIONAL GROUP CLASSIFICATION TESTS INTRODUCTION TO QUALITATIVE TESTS - The first test that should be done is a solubility test to determine the class or classes to which the unknown belongs. From the results 48 of the solubility tests, some idea of the type of organic compound should be evident. If the solubility test results put the unknown substance in the ‘Neutral’ section, it is recommended that the classification tests be done in this order: aldehydes, ketones, alcohols, esters, amides, nitriles, ethers, alkenes and alkynes. Select a test from the list of tests that would help confirm the presence or absence of the suspected functional group class. Do as many tests that may be necessary to absolutely confirm the functional group to which the unknown belongs. Be careful to interpret correctly the test results for those unknowns that may contain two or more functional groups. At that point, proceed to the preparation of derivatives to identity the exact identity of the unknown. 2,4-DINITROPHENYLHYDRAZINE TEST (for aldehydes and ketones) - This test will be positive for an aldehyde or ketone as indicated by the formation of a yellow, orange or red precipitate which is called a 2,4-dinitrophenylhydrazone. This precipitate can also be used as a derivative for the unknown if its melting point is determined (see below for derivative use). The color of the precipitate can help further identify the extent of conjugation for the carbonyl group. Highly conjugated aromatic aldehydes or ketones generally give red solids whereas non conjugated carbonyl compounds give yellow products. ACETYL CHLORIDE (for acidic hydrogen compounds) - This test will help identify carboxylic acids, phenols and alcohols. A positive test will be noted by the evolution of heat which may be hard to detect. So, this test may give false positive or negative tests depending on the expertise of the person doing the test. In some cases, a solid (usually white) may form. If this happens, the solid, if isolated and its melting point is determined, could be used as a derivative for the unknown. If water is present in the unknown, the test will probably give a false positive test as acetyl chloride reacts vigorously with water. BASIC HYDROLYSIS (for amides, esters and nitriles) - Amides and esters can be hydrolyzed by heating in a sodium hydroxide solution. This reaction pH gives the acid as a water soluble carboxylate salt. Acidifying this solution with concentrated hydrochloric acid would result in a precipitate if the carboxylic acid is water insoluble. If this precipitate is formed, it should be filtered and used as a derivative for the unknown. BEILSTEIN TEST (for halogenated compounds) - Placing a small amount of an organic compound on the end of a copper wire and heating it in the open flame of a Bunsen burner results in a transient green color in the flame if the compound contains a halogen atom. If the unknown is volatile, it may evaporate before it burns resulting in a negative test. BENEDICT TEST (for aldehydes and sugars) - When easily oxidized organic compound (such as aldehydes and reducing sugars) is heated in Benedict’s solution (which is a blue solution containing a complexed copper (II) ion) a brick red precipitate of cuprous oxide forms. If the unknown is not soluble in the reagent a negative test may be observed due to the lack of a reaction. BROMINE IN CARBON TETRACHLORIDE (for alkenes and alkynes) - When a solution bromine in carbon tetrachloride is added drop wise to an colorless unknown compound, the 49 brownish color of elemental bromine disappears as the bromine adds to the unsaturated organic compound. CERIC NITRATE (for alcohols and phenols) - Alcohols with 10 carbons or less will give a red color with ceric nitrate solution whereas phenols will give a green-brown to brown precipitate. Easily oxidized compounds may destroy the ceric nitrate solution before the test results may be observed. CHROMIC ACID (for aldehydes, primary and secondary alcohols) - Easily oxidized compounds convert the red chromium (VI) ion to a green chromium (III) precipitate. COMBUSTION (for flammable or combustible organic compounds) - When a few milligrams of an organic liquid or solid are placed directly into a Bunsen burner flame they often burn. Note that highly halogenated organic compounds may not burn. Very volatile compounds may evaporate before burning or burn very rapidly. The manner in which a compound burns can give some information about its nature. Highly oxygenated compounds burn with a blue flame, aliphatic compounds give a yellow flame and aromatic compounds give a sooty flame. FERRIC CHLORIDE (for phenols) - Some (but not all) phenols give a color when ferric chloride solution is added. This test is not a definitive one and the results should be carefully evaluated. FERRIC HYDROXAMATE (for esters, acid chloride and anhydrides) - Esters of carboxylic acids give a magenta color with this reagent. Acid chloride and anhydrides give a magenta or burgundy color with the test reagent. FERROUS HYDROXIDE (for nitro compounds) - Most compounds that contain a nitro group will give a brown to red-brown precipitate of ferric hydroxide by oxidation of ferrous hydroxide. HINSBERG TEST (to distinguish primary, secondary and tertiary amines) - Benzenesulfonyl chloride can be used to distinguish primary, secondary and tertiary amines. The amine functional group must be confirmed before this test can be performed as the test will give very confusing results with any other functional group. Primary amines give a solid benzenesulfonamide product that is soluble in 5% sodium hydroxide. Secondary amines give a solid benzenesulfonamide product that is insoluble in 5% sodium hydroxide. Tertiary amines do not react with benzenesulfonyl chloride. HYDROXYLAMINE HYDROCHLORIDE (for aldehydes and ketones) - Aldehydes and most ketones give a red color when added to a solution of hydroxylamine hydrochloride in ethanolwater that has a universal indicator added. IODOFORM TEST (for methyl carbonyl compounds) - This test is mainly used to identify methyl ketones. The iodoform regent iodinates the methyl group which then cleaves in the basic solution. One should confirm the presence of a carbonyl group in the unknown before this test is done as misleading results could occur with other compounds. For example, acetaldehyde and 50 alcohols that have a methyl group bonded to the C-OH group can also give a positive test since such an alcohol can be oxidized to a methyl ketone by the iodoform reagent. LUCAS TEST (to distinguish primary, secondary and tertiary alcohols of six carbons or less) - A solution of zinc chloride in aqueous hydrochloric acid can be used to distinguish primary, secondary and tertiary alcohols. The unknown compound must be soluble in the reagent in order for the test to be valid. When a tertiary alcohol is added drop wise to the reagent, an immediate second layer of a liquid alkyl chloride is formed. Secondary alcohols form a second layer of the insoluble alkyl chloride in three to 5 minutes. Primary alcohols are unreactive with the Lucas reagent. NITROUS ACID (to distinguish primary, secondary and tertiary amines) - Primary aromatic amines give nitrogen gas evolution with the nitrous acid reagent. Other aromatic amines can undergo coupling reactions to form colored products. pH IN ETHANOL (to distinguish low molecular weight acidic or basic compounds) - The pH of compounds that are soluble in water or aqueous alcohol can be measured. If the pH is in the acid range the compound can be a carboxylic acid, acid chloride or anhydride. If the pH is in the basic range, the compound may be an amine. Organic salts may hydrolyze in water which can lead to acidic or basic solutions. POTASSIUM PERMANGANATE (for compounds that can be oxidized) - Organic compounds that can be readily oxidized will convert the purple permanganate ion to a brown precipitate of manganese dioxide. Such organic compounds include: aldehydes, reducing sugars, primary or secondary alcohols and some alkenes and alkynes. SILVER NITRATE IN ETHANOL (for alkyl halides that can undergo S N1 reactions) - Tertiary alkyl halides will give a white to yellow silver halide precipitate with this reagent. Some secondary halides will react more slowly. Aryl and vinyl halides do not react. SODIUM FUSION (for compounds that contain halogen, nitrogen or sulfur) - When an organic compound is placed in molten elemental sodium the molecules are violently destroyed. Any halogen, nitrogen or sulfur in the original molecule is converted to ionic materials which are then identified. The halide is identified by precipitation with silver ions. The sulfide ion is identified by precipitation with lead ions. The cyanide ion formed from the nitrogen in the molecule is converted into Prussian blue by ferrous sulfate. SODIUM IODIDE IN ACETONE (for alkyl halides that can undergo SN2 reactions) - Primary and some secondary alkyl chlorides or bromides will give a precipitate of sodium iodide in the reagent. Alkyl iodides will not give a precipitate. Aryl or vinyl halides do not react. SOLUBILITY (for general classification of organic compounds) See SOLUBILITY CLASSIFICATION section above. TOLLENS TEST (for aldehydes and reducing sugars) - Water soluble aldehydes and reducing sugars give a silver mirror or black precipitate of elemental silver with the Tollens reagent. 51 DERIVATIVE FORMATION AND USE INTRODUCTION TO DERIVATIVE USE - Derivative Tests - Once the classification tests have indicated an organic family of compounds (i.e. an aldehyde), one can see if derivatives of the unknown can be synthesized to help in its identification. Based on the results of the classification tests, the correct derivative tests to use can be determined. On selecting the relevant test, the results will be illustrated. If the derivative test is positive, it is evidence that the correct family of compound has been chosen, and the melting point of the derivative should be recorded on a data sheet. Order all the derivative tests relevant to the search (i.e. for an aldehyde, obtain the melting points of both the semicarbazone and 2,4-dinitrophenylhydrazine derivatives) and then proceed to the final identification of the unknown substance. 1-NAPHTHYLURETHANE DERIVATIVE - (for alcohols and phenols) 2,4-DINITROPHENYLHYDRAZONE - (for aldehydes and ketones) 3,5-DINITROBENZOATE - (for alcohols) ACETAMIDE - (for primary and secondary amines) ACID FROM HYDROLYSIS - (for acid chloride, anhydride, ester, amides, and nitriles) AMIDE - (for carboxylic acids, acid chlorides, and anhydrides) ANILIDE - (for carboxylic acids, acid chlorides, and anhydrides) BENZAMIDE - (for primary and secondary amines) BENZENESULFONAMIDE - (for primary and secondary amines) BROMO DERIVATIVE - (for phenols) METHIODIDE - (for tertiary amines) NEUTRALIZATION EQUIVALENT - (for acids, amides, esters and nitriles) OXIME - (for aldehydes and ketones) PHENYLHYDRAZONE - (for aldehydes and ketones) PHENYLURETHAN - (for alcohols and amines) PICRATE - (for tertiary amines) p-NITROBENZYL ESTER - (for carboxylic acids) p-NITROPHENYLHYDRAZONE - (for aldehydes and ketones) 52 p-TOLUENESULFONAMIDE - (for primary and secondary amines) p-TOLUIDIDE - (for primary and secondary amines) SEMICARBAZONE - (for aldehydes and ketones) FINAL IDENTIFICATION OF AN UNKNOWN SUBSTANCE Tables of organic substances can be used to identify the unknown based on the results of the classification tests and the derivative melting point results. TABLES OF UNKNOWNS - Once the derivative melting point data have been recorded, enter the Tables of Unknowns by selecting the suspected functional group class. Here a list of organic compounds separated by type will appear. Select the family to which the unknown belongs. A list of all the compounds of that type, presented in order of increasing boiling/melting point will appear. Also listed are the melting points of any derivatives that can be synthesized from the class of the unknown compound. By matching the table data with the unknown compound data obtained above, one can identify the unknown. ANSWER TRIAL - Based on all the melting point data in the Tables of Unknowns, one will now have an idea of what the unknown sample is. To see if you are correct, you can enter it into the program by selecting Answer Trial. Make sure that you select the compound correctly, exactly as it appears in the table of unknowns. If you are correct, a congratulation message will appear. If you are wrong, first re-check your data for the unknown. If it is still incorrect, then you will need to go back into the program in order to correctly identify the unknown sample. © 2010 Scott Frees and Robert Shine 53 APPENDIX B: SAFETY ISSUES INTRODUCTION: A very important aspect of laboratory work is working safely. It is your responsibility to yourself and the other people in the laboratory to work in a serious and careful manner. If you are not sure about the dangers involved in what you are assigned to do, be sure to ask the Instructor before you begin. You should consult the material safety data sheets (MSDS) for those chemicals you will be working with before coming to the lab. You can find MSDS data by typing the chemical name followed by MSDS in a Google search box. For example msds data for acetone could be found by typing acetone msds in the search box. If you have allergies, you should consult your Allergist for advice in working with organic chemicals. If you are pregnant or become pregnant, you should consult your doctor for advice in working with organic chemicals. There are risks involved with all activities you do. By knowing what those risks are and taking prudent actions, you can lessen the dangers you face and thereby lead a relatively safe life. The dangers you are likely to face in the organic chemistry laboratory are due to: 1. Equipment 2. Toxic chemicals 3. Flammable chemicals EQUIPMENT: You will use glassware, plastic ware, and electrical heating equipment in the lab. As you know, glass items can break and cause cuts that can be minor or severe. You should exercise care when handling glassware to minimize breakage. If a glass item breaks, notify the Instructor who will then use a broom and dustpan to clean up the area. Broken or discarded glassware must be placed in the separate container that is marked for broken glass. No other items other than glassware should be placed in that container. Plastic ware generally has no safety concerns and is safe to use. Heating in the lab will generally be done using electrical heating equipment such as hot plates and heating mantles. We will not use Bunsen burners in the laboratory. We may use steam baths on occasion. Steam can cause a bad scalding burn. Hotplates and heating mantles do not change appearance when they are hot so you should always assume they are hot until proven otherwise. There can also be an electrical shock hazard with any electrical equipment. Electrical outlets in the organic chemistry laboratory are protected by ground fault interrupter circuit breakers. Also be aware that heating equipment can be hot enough to exceed the flash point of a chemical and can start a fire. Chemicals that have a low flash point can be ignited by a warm hot plate. Evaporating diethyl ether from a beaker on a hotplate caused a fire in our organic chemistry laboratory many years ago. TOXIC CHEMICALS: Eye protection must be worn in the laboratory whenever anyone in the lab is working with chemicals. Only department approved eye goggles can be used. If, at any time, you suspect that a chemical got onto your skin or eyes, immediately wash the affected area with plenty of cold water for a significant period of time. Be sure to notify the Instructor after you begin the 54 washing process. Chemicals that are immediately washed from the skin will cause less damage than those that are allowed to remain on the skin until you feel pain. So, even if you feel no pain, wash the affected area immediately. Many chemicals have toxic properties which vary from compound to compound. The best source of information about the toxic properties of chemicals you will use is the material safety data sheet (msds) for that chemical. Be aware that chemicals can enter the body by inhalation, ingestion, absorption or injection through the skin. You should use gloves to protect the skin and should rinse your hands after handling chemicals. When you leave the lab you should thoroughly wash your hands. Ingestion of chemicals can be avoided by not putting anything in your mouth during the laboratory period. Never pipette by mouth; use approved suctioning devices. Never eat or drink any food in the lab, including chewing gum, as it could have been contaminated. Inhalation of volatile chemicals can be avoided by working in the fume hood. Try to minimize the time a volatile chemical will be exposed to the air outside the hood. Weigh such substances quickly and move them immediately to the hood. Some chemicals used in the lab are corrosive. Generally these include acids and bases. The more concentrated the acid or base, the more corrosive it will be. So use extreme care with concentrated sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, and sodium hydroxide solutions. Nitric acid will cause orange patches to appear on the affected skin in one to three days. This orange patch will slowly wear off. Silver nitrate will cause black stains to appear in the affected area within a few hours after exposure and will wear off in a few days. Volatile organic solvents that enter the body can cause systemic poisoning. Often, the liver or kidneys are affected. Be sure to read the material safety data sheet for specific information about the chemicals with which you are working. FLAMMABLE CHEMICALS: Many organic chemicals can burn. Halogenated organic compounds are usually less flammable than others but they tend to be more toxic, especially to the liver. Compounds with a high percentage of carbon (such as aromatic hydrocarbons) burn with a very black sooty flame. Other hydrocarbons burn with a yellow flame and as the oxygen content of the compound increases, the flame becomes more bluish. In order to have a fire start, three things are needed. You must have a compound that can burn, an oxidizing material such as air, and an ignition source that will raise the temperature of the flammable substance above its flash point. Of real concern is whether or not a compound can cause a fire. There are terms whose meaning you need to know. These terms are: nonflammable, inflammable, flammable, and combustible. Nonflammable means the compound will not burn under reasonable conditions. They pose no fire hazard. Water is such a substance. Inflammable is a very bad choice for a word. The dictionary defines inflammable as "capable of being set on fire; combustible." Inflammable does not mean "not flammable." The word inflammable should not be used. A flammable substance is "one that is easily set on fire" and a combustible substance is "capable of being set on fire." Flammable substances, with their lower flash points, pose a more serious fire hazard than combustible substances. Gasoline would be considered flammable and wood would be considered combustible. So, use care when working with flammable and combustible substances, especially with flammable substances. © 2010 Anderson, Shine, Carberry, and Carreon 55 APPENDIX C: COMMENTS ABOUT WRITING STYLE Before you begin writing lab reports for this course, you should carefully study the following statements, which are presented to help you achieve good grades. Failure to use this advice could result in a lower lab grade. 1. On all written work you submit, place your name, the full descriptive name of the experiment, and the day of the week (that is, Monday, Tuesday, Wednesday, or Thursday) that you have lab. 2. Reports are due at the beginning of the next class meeting. If you computer dies, submit the report on time, neatly handwritten. Reports cannot be submitted electronically unless allowed by your Instructor. 3. Use correct grammar and spelling. Use adjectives, nouns and verbs correctly. Use scientific terms correctly. Proofread your report and check all spelling as spell checkers do not recognize the misuse of words (such as to, too and two). 4. Use terms (especially scientific terms) correctly. Do not misspell the name of a chemical. Failure to use technical terms correctly will have a definite negative impact on your report grade. For example, do not report the boiling point of a solid; report its melting point. 5. Do not be vague or overly explicit. Give only the important data, observations and conclusions. 6. Your report should have a correct, logical flow. For example, give the data before the conclusions that are made. 7. When giving a measurement, be sure to include both the number (with the correct number of significant figures) and correct units. 8. Pay attention to the correct use of significant figures. See Appendix D for more information about the correct use of significant figures. 9. Do not start a sentence with a digit. Spell out any numbers that start a sentence. 10. Use the third person, passive voice in science report writing. 11. The data page that you submit when you leave the lab is part of your lab grade. The data page must be clearly presented, as neat as possible, and must give all the critical measurements (numbers and units) you made in the lab. Computations of results may be left until the final report is written if they are difficult to do. Simple computations may be included with the data sheet. 12. Be sure that each section in the report has an introductory sentence. 13. Cite all references used and be exact in giving each reference. 14. The introduction section must have structures of important compounds or a chemical equation drawn early in the section. 15. The introduction section should deal with the theory of the experiment and not give experimental details. 16. The experimental section can be brief with a reference to the lab manual. You need add only the changes you made that differed from the lab manual. 17. As much as possible, tabulate data and place them near the text that describe it. Be sure the table has a meaningful title and that the data are presented in a clear manner. 18. Do not describe a math formula in text. Draw the formula and separate it from the text by at least one line. 19. For results that are computed from lab data, be sure to show how the computation was done. That is, show the math used. When doing computations in the lab report, show the general 56 formula and then show the formula with your actual data to show how you obtained your result. Set the mathematics away from text so it stands out. 20. Fully explain the data. Do not leave any critical data out of the report. If you calculated the amount of a substance by measuring the weight of a container empty and then again with the sample in it, both weights must be in the report along with the final weight. 21. Be sure data, calculations and conclusions are tied together. If these items are in different parts of the report, be sure to tell the reader where they can be found. 22. All data in the lab report should be able to be traced back to the experimental data you recorded on the data sheet you submitted. Do not take any shortcuts in data handling. You must show all relationships in a logical, orderly manner, and you must show how results were calculated. 23. When giving melting point or boiling point data, be sure to report these data as a range, and be sure to give the accepted literature values in parentheses immediately after your experimental data. 24. The conclusion section may be brief but should tell what the objectives of the experiment were and if they were achieved. 25. Do not report a percent error unless told to do so. We measure percent recovery or percent yield. Be sure you know the difference between these terms. 26. Repeating errors, such as the misspelling of a chemical, will be noted only once when reports are graded. 27. Do not capitalize a chemical name unless it is the first word in the sentence. 28. Mass is not used as a verb in this course. A chemical can be weighed but not massed. Also, precipitates are filtered, not funneled. 29. Two words are often misused in this course. The first is 'separate' which is often misspelled with an 'e' after the 'p'. Fortunately, spell checkers fix this error. The other misused word is 'vial' which many students write as 'vile'. A spell checker does not repair this mistake. The dictionary defines 'vile' as: "mean, worthless, unclean, repulsive, bad." The same dictionary defines the homonym 'vial' as: "a small vessel." Be sure to use these two terms correctly. 30. Do not use the first or second person in scientific writing. Do not use I, we, or you. 31. A rewrite of a previously graded lab report will not be accepted unless it was authorized and agreed upon by the Instructor before it was done. 32. More information about good report writing style for chemists can be found on the Web by doing a Google search on ‘writing style for chemists’. © 2010 Anderson, Shine, Carberry, and Carreon 57 APPENDIX D: MEASUREMENTS AND SIGNIFICANT FIGURES INTRODUCTION: A very important aspect of laboratory work is making and reporting measurements carefully. A significant part of your grade will be based on how you gather and report data. You will need to know which measurements will need to be made carefully and which are less important and can be made quickly with less accuracy. There are three terms that you will need to know and understand: precision, accuracy, and significant figures. These terms have similar meaning and are often confused. Precision: The ability of repeated measurements to have the same value. If you weigh an item three different times, the number of grams should be exact or very close for all the measurements. Accuracy: The agreement of a measurement with the accepted value reported for that value. If you measure the density of water at 4 degrees Celsius, it should be 1.00 g/mL. Significant figures: The number of digits that can be reported for a measurement. If you weigh some item on the top loading balance in our laboratory, it can be recorded to the third decimal place if using units of grams, such as, 1.234 g. In this laboratory course, the correct use of significant figures will be the most important of the three. Accuracy will be the next most important and precision will generally be disregarded as you will usually not make repeated measurements of the same data item. SIGNIFICANT FIGURES: The number of significant figures you give in your lab report is governed by the limits of the measuring devices you use and the care you exercise in making a measurement. Mathematical manipulation of data can never increase the number of significant figures in your result. You will need to know what measurements are important and which are not. Do not waste time in making a very careful measurement on some less significant piece of data. For example, the exact amount of a reagent is needed but the precise volume of solvent in which it is dissolved is often not needed. Be sure to record important data to the level of precision the measuring instrument allows. If the directions tell you to measure out exactly 0.500 g of a compound, then you will have to spend some time to carefully get 0.500 g. However, often the directions will say to measure about 0.500 g of a compound. Here, you can quickly weigh out an amount that is approximately 0.500 g but you must record your exact weight. For example, you may have weighed 0.476 g. You would then use that figure (0.476 g) in your report and further calculations. It is important that you know the difference between 0.05 and 0.050. The first of these (0.05) has one significant figure while the second (0.050) has two significant figures. A zero used to place the decimal point is not a significant figure. So, if you carefully weighed out 0.500 g and wrote it as 0.5 g or 0.50 g, you would be wrong. You must show all the significant figures 58 allowed by the measurement you made along with the correct units such as grams (g), milligrams (mg), milliliters (mL), etc. In any measurement, the last significant figure has an uncertainty associated with it. Often you will see the balance going up and down over time in the last decimal place. So a measurement such as 0.476 g really is 0.476 0.001 g. In using conversion factors such as 1 pound/453.6 g, the number 1 is exact and can be assumed to have the same number of significant figures as the other value. So here, the conversion factor is 1.000 pound/453.6 g. Also note that every conversion factor equals one so the reciprocal also is true. That is, 453.6 g/1 pound is also true. In all your calculations, be sure to show the numerical data and the correct units. Both are required. It is important to consider how to use significant figures when doing mathematical operations. Using a calculator, which can report 8 digits, does not make your result more accurate. You must report your calculated result to the correct number of significant figures allowed by the laboratory measurements and not the calculator. If the mathematical operation is addition or subtraction, your result can only be reported to the decimal place of the least accurate measurement. The following examples may clarify this. If you add 123.4 g to 0.123 g, the result is 123.5 g. If you add 1.2 g to 0.123 g, the result is 1.3 g. If you subtract 1.234 g from 1.236 g, the result is 0.002 g. Note that in addition and especially subtraction, you can appear to lose significant figures. So, in such cases, if one measurement can only be made to the first decimal place, it is a waste of time to make the other measurement carefully to the third decimal place. If the mathematical operation involves multiplication and division, the result will have the number of significant figures equal to that of the least significant piece of data. If you multiply 123 by 12, the result is 1500 which has 2 significant figures and 2 zeros to place the decimal point. Such results are better written in scientific notation (1.5 103) to avoid confusion. Be sure you fully understand the meaning and use of significant figures as a major part of your laboratory grade will be based on your lab measurements and data manipulation in your lab reports. © 2010 Anderson, Shine, Carberry, and Carreon 59 APPENDIX E: PERCENT YIELD CALCULATION METHOD The calculation of a percent yield is a very important part of those labs where a chemical synthesis has been done. In your report be sure to correctly do the percent yield calculation (showing the correct significant figures and units) and present it in a very clear manner. Do not forget the show the correct units with each measurement as you perform the calculation. A percent yield calculation is an application of a weight-weight problem, which you learned in Fundamentals of Chemistry. You must show how the calculations are done in an area that is separated from text. Do not put data details in paragraph text. Present data details in tabular form and be sure this data is near the text that makes reference to it for clarity of presentation or, if the calculations have been attached to the end of your report as an appendix, give a clear sentence that refers the reader to this page. Calculations should be close to where the final data are presented in your report. Briefly, a percent yield calculation is an application of a weight-weight problem in General Chemistry. You calculate the number of moles (or millimoles) of each reagent. Determine which reagent is the limiting reagent from the balanced equation. Catalysts are not usually limiting reagents. Then, determine from the balanced equation the maximum number of moles of the desired product that could be obtained and this is your theoretical yield in moles. Convert this number of moles of product to a theoretical weight of product. Then, divide the weight of product that you obtained by the theoretical weight of product you calculated and multiply by 100%. Alternatively, you could determine the actual moles of product obtained by taking the mass of the product isolated and dividing by its molecular weight. The percent yield in that case would be the actual moles divided by the theoretical moles times 100%. Be sure to identify which method you use by showing numerical and unit values for all data in your calculations. Percent yield calculations will be a major part of your report grade in those labs where percent yield data needs to be reported. SAMPLE CALCULATION: Below is just a guide to show you how the calculations are done, presented in a manner to help you understand the process. This is not an acceptable percent yield calculation for your lab report. The method below was adapted from a reaction of a diamine with an acid to give a salt, which appeared in the Organic Chemistry I laboratory manual. The balanced equation showed that 1 mole of diamine reacts with 1 mole of acid to give 1 mole of salt. You started with 1.20 mL of diamine. 1.20 mL .951 g/mL gives 1.14 g of diamine 1.14 g of diamine/114 g/mole of diamine gives 0.0100 mole of diamine used. You also weighed some tartaric acid that varied from group to group. Say your group weighed 0.732 g. The number of moles of acid in the 0.732 g is 0.732 g/ 150 g/mole of tartaric acid or 0.00488 mole of tartaric acid. 60 From the balanced equation, the acid is the limiting reagent and the theoretical yield of the product would be 0.00488 moles of salt. From the molecular weight of the product, the theoretical weight of the product is 0.00488 mole 264 g/mole of salt or 1.29 g. If you obtained .847 g of product, your percent yield is (0.847 g /1.29 g) 100% or 65.7 %. © 2010 Anderson, Shine, Carberry, and Carreon 61 APPENDIX F: GREEN METRICS For most of this laboratory course, percent yield was used to measure the efficiency of a synthetic reaction. However, the percent yield does not consider the fate of other reagents, solvents or catalysts. It does not consider the costs involved in handling byproducts and hazardous waste. As we have seen, green chemistry focuses on finding methods for the development of new, less polluting processes. Green metrics is a branch of green chemistry, which attempts to quantify the total environmental cost of a process. Green metric calculations keep track of the amount of material that goes into and comes out of a chemical reaction. Common green metric terms include: percent yield, E-factor, atom economy, atom efficiency, effective mass yield and reaction mass efficiency. Each of these terms will be described below. The percent yield has been used throughout this course to give a crude measure of the success of a synthetic reaction. It is: (actual yield theoretical yield) 100% Percent yield could be increased by using better processes or reaction conditions, minimizing competing reactions, and minimizing mechanical loss. The E-factor (efficiency factor) is a number that correlates with the amount of organic and aqueous waste produced in a chemical process. It is: total waste in g/product weight in g The smaller the E-factor, the better the process since less waste is produced. The E-factor has a range of 0 to infinity. Atom economy (or percent atom economy) is a theoretical number that shows the amount of reactants that remain in the final product. It is: (MW of product/sum of MW of all reactants) 100% The bigger the number for atom economy, the higher the percent of all reactants that remain in the final product. The range is 0% to 100%. Atom economy is dictated by the chemical reaction. The Diels-Alder reaction is an example of a reaction that has a good atom economy. Atom efficiency is a practical number that attempts to join the concept of percent yield and atom economy. This metric gives a good indication of the greenness on the process. Atom efficiency is: Percent yield atom economy Atom efficiency has a range of 0% to 100% and the closer the atom efficiency is to 100%, the greener the process. Effective mass yield is the percentage of the mass of the desired product relative to the mass of all hazardous materials used in the synthesis. It is: (product mass g/hazardous reagents mass g) 100% 62 This metric evaluates the amount of hazardous reagents used in making the final product. It may be difficult in determining what is hazardous or not. Reaction mass efficiency is the percentage of the mass of reagents that remain in the final desired product. It takes into account the stoichiometry, yield, and atom economy. It is: (product mass in g/mass of reagents in g) 100% The larger the number for reaction mass efficiency, the better the process. The range is 0% to 100%. Reaction mass efficiency is similar to effective mass yield. The only difference is that the effective mass yield takes into consideration the hazardous reagents whereas the reaction mass efficiency uses the total mass of all reagents. It would be a worthwhile exercise for the student to apply the above principles to an evaluation of the greenness of the hydrolysis of methyl benzoate experiment or, indeed, any other experiment performed this semester. © 2010 Anderson, Shine, Carberry, and Carreon 63 APPENDIX G: CHEMICAL DATA INTRODUCTION: This appendix will present physical data and safety data about chemical substances that are mentioned in the experiments described in this manual. The data are presented in an Excel spreadsheet format. Table 1 gives all the data in one location but the printing is small and may be difficult to read. Table 2 gives safety information while Table 3 gives the physical properties of the chemicals. Data were obtained from chemical handbooks, supplier catalogs, and material safety data sheets. In many cases, the value for a given piece of data such as a melting point varied from source to source within a narrow range. Therefore, you may find a data value from some source you check that does not agree with what is reported in this appendix. However, if you find any serious error in the data tables, please send an e-mail to Robert Shine (bshine@ramapo.edu) informing him of the nature of the error. A blank cell in the data tables indicate the value for that data point was not found or does not apply. For example, the boiling point of an inorganic solid is generally not useful in this course. Also, the density for a solid substance could be meaningless for us. Remember that you can obtain more complete information from the Material Safety Data Sheet (MSDS) for a given substance. You can obtain a material safety data sheet for a compound by doing a Google search. For example, an MSDS for acetone can be obtained by typing "acetone MSDS" (don't include the quote marks) in the search box. Usually this search will result in many hits so you can just link to one of the sources. If you do not get any results from a Google search, try to search using an alternate name for the chemical. With practice, you will find your favorite source for an MSDS. EXPLANATION OF COLUMN HEADINGS: The Chemical Name column gives the usual name for the substance listed. All tables are arranged alphabetically according to the Chemical Name. The Alternate Name column gives another name for a given substance. The Formula column gives the general chemical formula for that substance. If you compute the molecular weight for that chemical formula, you would obtain the data value in the Mol.Wt. column. The units for these data are grams/mole. The next column, Melt.Pt., gives the melting point in degrees Centigrade (Celsius). After this, comes the column Boil.Pt. which gives the boiling point for the substance in degrees Centigrade (Celsius). The Density column gives the density for the substance is grams/mL. The density for a solid is not useful in this course but the density for a liquid could give a useful method when measuring liquid reagents. One can accurately measure a liquid by volume. The weight of that sample would then be equal to the volume times the density. If you know the weight you wish to measure, the volume would be equal to the desired weight divided by the density. Expressed in mathematical terms, the formulae are: Volume = Weight Density Weight = Volume Density The remaining three columns give some safety data. The CAS # is the Chemical Abstract Service number for the substance. The CAS# is a unique identifier for a chemical assigned by the American Chemical Society. The FlashPt gives the temperature at which a 64 substance can be readily ignited. Substances with a flash point below 100 degrees Centigrade are classified as flammable while those above 100 degrees are called combustible. Be especially cautious with chemicals with a flash point below 0 degrees. The final column gives the NFPA Rating of the substance. NFPA stands for the National Fire Protection Association and their web site can be found at www.nfpa.org (not .com) which is a 'for profit' organization. You can find more information about this rating system by doing a Google search on “nfpa diamond”. The rating assigns values from 0 to 4 for each of three categories Health, Fire, and instability (which is sometimes called reactive). A value of 0 indicates little or no hazard whereas a value of 4 indicates an extreme hazard. © 2010 Anderson, Shine, Carberry, and Carreon 65