CHEM-313 Instructor: Office: Phone: Office Hours: SYLLABUS Dr. J. L. Lyle NSM D-323 (310)243-3388;243-3376 Will be announced in class; open-door policy Required Texts: Introduction to Organic Laboratory Techniques Pavia, Kriz, Lampman & Engel. CRC Handbook of Chemistry and Physics (highly recommended) Lab notebook Safety goggles 1. Grading: Traditional letter grades will be assigned on the same basis as in CHE-312. Lab reports 75%, Notebook 10%, Evaluation 15% 2. Lab reports and prelabs. A pre-lab is to be turned in 24 hours before the scheduled lab (see father below for format). A typed lab report will be required for each experiment. The report is due one week after the scheduled completion of the lab. These reports are due at the scheduled start time for the lab. Late reports will be penalized one letter grade for the first 24 hours. Lab reports that are submitted more than 24 hours late will not be accepted! Please note that lab reports are not written in the lab notebook, but are separate requirements. You will be given explicit instructions about what each lab report is to contain. Lab reports are to be your own work and not plagiarized from some other student or lab report. Academic dishonesty will not be tolerated! 3. Notebook. A written record of what you are doing in the lab will be kept in your notebook. You are expected to have your notebook with you in the lab. Failure to do so can affect your grade. The notebook entries will be written in ink. The carbon copies that you make will be submitted with your lab reports. 4. Evaluation. Part of your grade will be an evaluation of your lab technique, preparedness, punctuality, etc. by the instructor. 5. Safety. You must wear approved eye protection at all times in the lab. Failure to do so will result in expulsion from the lab. 6. Prerequisite. You must have completed CHE-310 and CHE-311. Co-requisite is enrolment in CHE-310. 8. Attendance. You are expected to attend all laboratory sessions. Make-ups will only be allowed if arrangements are made prior to the missed lab and for good reason. 9. Course goals, objectives, and requirements are covered elsewhere in this syllabus. CHE-313 TENTATIVE SCHEDULE section topic reference 313-01 313-02 1. 2. 3. 1/26 1/28 2/2 1/27 1/29 2/3 check-in oxidation/IR & nmr cont. 4. 2/4 2/5 cont. 5. 6. 2/9 2/11 2/16 2/18 2/23 2/25 3/1 3/3 3/8 3/12 3/15 3/17 3/22 3/24 3/29,3/31 4/5 4/7 4/12 4/14 4/19 4/22 4/26 4/28 5/3 5/5 5/10 5/12 2/10 2/12 2/17 2/19 2/24 2/26 3/2 3/4 3/11 3/11 3/16 3/19 3/23 3/25 3/30,4/1 4/6 4/8 4/13 4/15 4/20 4/23 4/27 4/29 5/4 5/6 5/11 5/13 7. 8. 9. 10. 11. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. Spring '04 supplement p. 842-845 Appendix 3 p. 855-858 Appendix 4 supplement p. 888-889 ID of unknown ketone cont. no lab Reduct. of acetophenone supplement cont. Grignard synthesis supplement of toluic acids supplement Esterification p. 96-99 cont. Aldol condensation p. 409-411 cont. Diels Alder supplement cont. α,β-unsaturated ketone p. 413-417 no lab Spring Break cont. Lidocaine supplement cont. cont. Qualitative analysis p. 485-533 Pre-labs: For each preparative lab you are required to submit at least 24 hours before the lab a pre-lab write-up. The pre-lab is to be written in your lab notebook and the carbon copies submitted for review. These carbon copies will later be attached to your lab report. 1. Title (be specific, eg. "Reduction of Acetophenone with Sodium Borohydride"), name & date. 2. Balanced chemical equation(s) for the reaction(s) that you are going to carry out. 3. Table of Physical Properties summarizing the physical properties of the reactants, solvents, and products. Make photocopies of the sample provided, or make up your own. 4. A step-by-step procedure for the reaction, separation, and purification. Be specific as to amounts (moles & weight or volume). 5. For multi-step syntheses prepare a separate Table of Physical Properties for each reaction in the sequence. You may turn in pre-labs directly to the instructor or they may be placed in his mailbox in the Chemistry Office (NSM B-302). If you have not submitted a pre-lab before the lab you will not be allowed to begin the experiment until the pre-lab has been completed and okayed. Failure to submit pre-labs on time can severely affect your grade. Lab Reports A typed lab report is required for each experiment. Reports are due one week after the scheduled completion of the experiment at 1:00 pm for section 01 and 9:00 am for section 02. Labs turned in after these times will be penalized 10% per day late. Follow the following format for preparative reports: 1. Title, name & date (unknown #) 2. Balanced equation(s) for the reaction(s) you carried out. 3. Step-wise mechanism(s) for the reaction(s). 4. Physical data for your product(s) (weight, mp or bp, %yield, & literature mp or bp for comparison). 5. Tabulation of spectral data. (Tables summarizing the IR and nmr spectra and your interpretation). see attached. 6. Conclusions, comments, deviations, etc. Discuss your results. 7. Answers to the questions at the end of each preparation. 8. Attach to the end of the report: a) the pre-lab including table of physical properties b) any additional carbon copies from your lab notebook c) IR & nmr spectra, glc's, etc. Products With your lab reports you are to turn in the products that you have synthesized in the laboratory. Note, the labels must contain your name, the date, the identity of the contents, the net weight, and the mp or bp. Solid products should be in wide-mouth bottles and liquids in narrowmouth containers. TABLE OF PHYSICAL PROPERTIES (This table must be completed before coming to lab!) Reactants and solvents Product(s) fw Moles (g) weight (mL) volume (g/mL) density bp mp solubility TABLE OF PHYSICAL PROPERTIES (This table must be completed before coming to lab!) Reactants and solvents Product(s) fw Moles (g) weight (mL) volume (g/mL) density bp mp solubility CHE-313 Reporting IR and nmr spectra Report the results of infrared and nmr spectroscopy in tabular form. See example below: For the nmr: 1. Draw the structure of the compound and label the groups of hydrogens that give rise to each signal using a, b, c ... (let a = most up-field). 2. Make a table showing the chemical shift, integration and splitting pattern for each group of hydrogens assigned to the structure. example: ethoxybenzene Ph-O-CH2CH3 c b a 3H triplet a 1.3 ppm b 3.9 ppm 2H quartet c 6.6-7.2 ppm 5H complex For the IR: Make a table listing in decreasing order all of the absorbances and identify those that are important. example: ethoxybenzene frequency (cm-) interpretation 3040 3000 2940 1600 1580 1500 1480 1390 1300 1240 1170 1120 1050 880 800 750 690 C-H stretch unsaturation, Ar-H C-H stretch saturation C=C stretch, aromatic ring C=C stretch, aromatic ring C-H bend, saturated " " " C-O stretch, ether C-H out of plane bend mono-substitution Oxidation of a side chain & introduction to IR and nmr You will oxidize an unknown arene with KmnO4 to a benzoic acid. See the procedure in this supplement. Because the starting material is an unknown, the table of physical properties is a little different from the ones you have previously prepared. You will be given (on the unknown bottle) the molecular formula of your unknown. Calculate the gram formula weight and the number of moles contained in 1.0 grams. The amount of KMnO4 you will use is based on the formula of your unknown. You will identify the unknown arene from the melting point of the acid product and the IR and nmr spectra of the unknown. Be sure to balance your chemical equations correctly. No mechanism is required for this report. Include the answers to the following questions in your report. Answer the following questions: 1. Write a balanced chemical equation for the permanganate oxidation of p-xylene under basic conditions. See your general chem text for review of balancing oxidation-reduction equations. 2. Write a balanced chemical equation for the permanganate oxidation of tolune. 3. Write chemical equations to show how you would oxidize toluene to benzaldehyde rather than benzoic acid. see M&B 4. Why is benzoic acid more soluble in base than in aced? What is this difference in solubility used for? 5. Tert-butylbenzene is not oxidized by permanganate to benzoic acid. Why not? 6. a) Draw all of the arenes with formula C7H7Br and show the products of oxidation for each one. b) Look up the mp of each product. c) Can you identify every isomer based on the melting point of the carboxylic acid derivative? Explain. 7. Write a balanced equation for the reaction of potassium permanganate with sodium bisulfite. Identification of an unknown arene by oxidation to the carboxylic acid; introduction to IR and nmr spectroscopy. A classical approach to the identification of some aromatic compounds is the oxidation of side chains to carboxylic acid groups. Measurement of the derivative's melting point and comparison with the known melting points of different benzoic acids provided a means of identifying or eliminating certain possible structures. For example: if a compound was found to have the formula C8H10, it could be four different compounds: ethyl benzene, o-xylene, m-xylene, or p-xylene. If you look up the boiling points of these four compounds, they are very close to each other. On the other hand, the melting points of the corresponding carboxylic acids produced from the oxidation of the side chains are distinctly different. When combined with additional information, such as the IR and nmr spectra, the melting point of the derivative will usually be sufficient to determine the structure of the unknown. You will be given a small sample of an unknown arene for which the only information provided is the molecular formula. You are to carry out the permanganate oxidation in alkalai solution and isolate the carboxylic acid. You will measure the melting point of the acid and compare it to the melting points of the possible derivatives from your molecular formula. In addition, you will obtain the IR spectrum of your original uknown and the nmr spectrum. procedure: 1. The apparatus consists of a 250 mL round-bottom flask fitted with a reflux condenser. 2. Place about 1 gram (40 drops) of the unknown into the flask. 3. Add approx. 80 mL of water and 1-2 mL of 6M NaOH to the flask. 4. Using the powder funnel, introduce the required amount of potassium permanganate (see table below) into the flask and add a couple of boiling chips. compound formula C7H8 C8H10 C9H12 g KMnO4/g unknown 4g 6g 8g 5. Attach the reflux condenser and begin heating the mixture with a heating mantle. Be careful when the mixture first starts to boil as it has a tendency to "bump". 6. Continue the reflux for 2-3 hours. At the end of the first period, cool the flask, label it, cork it, and place it in one of the hoods until next lab. 7. Suction filter the contents of the round-bottom flask to remove the solid MnO2. 8. Transfer the filtrate to a 250 mL beaker. Place the beaker in a ice bath, and after the solution has cooled for 10 minutes, acidify with 10 mL of 6 M H2SO4, while stirring. (If the solution is still purple due to excess permanganate, destroy it by adding no more than about 2 mL of 20% sodium bisulfite. 9. Test the solution with litmus to verify that it is acidic; if not add more sulfuric acid. 10. Filter the precipitated acid with suction through a small buchner funnel and wash with a few mL of cold water. (If no acid has precipitated, consult with the instructor). 11. Recrystallize the acid from a suitable solvent (try water first). 12. Let the product air dry, weigh it, package it, and obtain its melting point. Identification of an unknown carbonyl In this experiment you will be given an unknown aldehyde or ketone. You will obtain the IR and nmr spectra, do the Tollen's test, and prepare two solid derivatives. In the report, identify the unknown and compare the experimental values with the ones given in the text; make a TABLE for comparison. Be sure to include balanced equations for the Tollen's test, the preparations of the derivatives, as well as appropriate mechanisms. Do not weigh derivatives or calculate % yield. Prepare the 2,4-dinitrophenylhydrazone derivative of your unknown. The reagent is already prepared. Mix 10 drops (0.5 mL) of your unknown in 20 mL of 95% ethanol. To this solution, add 15 mL of the 2,4-DNPH reagent. Shake the mixture vigorously. If a precipitate does not form immediately, let it stand for 15 minutes. Suction filter the solid derivative and recrystallize from 95% ethanol. After air drying, obtain the mp. Make an additional derivative, the semicarbazone, according to the directions on page 888 and obtain the mp. Test the unknown with Tollen's Reagent (p 511) to see if it is a ketone or an aldehyde. Page 878879 lists possible aldehydes in increasing order of boiling point and the melting points of easily prepared derivatives. Ketones are listed in the table on pages 879-880. Do a simple distillation to measure the boiling point of your unknown carbonyl compound. Obtain the IR and nmr spectra of your unknown carbonyl compound. Answer the following questions: 1) An unknown organic compound (b. 212-216 oC) gives a positive 2,4-DNPH test and is positive with Tollen's reagent. A semicarbazone derivative is made that melts at 228-232 oC. What is the identity of the unknown? What would you do next? 2) Predict the products of the reaction of the following with silver nitrate in ammonium hydroxide: cylcohexanone formaldehyde acetone acetophenone butyraldehyde 3) In the reaction of an aldehyde or ketone with derivatives of ammonia, the reaction can be catalyzed by sulfuric acid. However, it is important that the pH not be too low since the reaction will slow down at very high acid concentrations. Explain. 4) Ketones do not oxidize readily. However, cyclohexanone will react with powerful oxidizing agents at high heat to adipic acid (HO2C-(CH2)4-CO2H). The reaction is not really one of the ketone, but the enol. Write equations to show how this is possible. Reduction of acetophenone to 1-phenylethanol - 1.2 g NaBH4 + 25 mL EtOH (95%) - dropwise (controlled addition; keep temperature < 50o ) of 12 mL of acetophenone - let stand 15 minutes - acidify with 10 mL (3M) HCl - boil down on hot plate until you have two layers - extract with (1) 20 mL Et2O (2) 10 mL Et2O -dry combined ether extracts over anh. MgSO4 TWICE! -distill off Et2O ( waste bottle ) -residue = crude product (bp 102.5 – 103.5 @ 19 Torr), do not distill IR, nmr of product AND acetophenone We will not purify the product with vacuum distillation. After the removal of the diethyl ether, package, weigh and label the crude product. Obtain IR and nmr on both the acetophenone and the product. Answer the following questions: 1. What was the molar ratio of NaBH4 to acetophenone that you used in the experiment. What is the theoretical ratio? Why did you use more than the theoretical ratio? 2. After the reaction of the carbonyl with sodium borohydride, the mixture is treated with water and acid to produce the desired alcohol. Indicate the source of the alcoholic hydrogen in the product. 3. Although sodium borohydride reacts slowly with methanol, when mineral acid was added, it rapidly decomposed with the evolution of hydrogen. Explain. 4. Why is 1-phenylethanol more prone to dehydration than 2-phenylethanol? 5. What is the structure of the white precipitate that forms in the reaction of acetophenone with NaBH4? 6. Write an equation for the reaction of the white ppt with water and HCl. 7. Draw the structure of the products of the reduction of each of the following with NaBH4: a) cyclohexanone b) 3-cyclohexen-1-one c) 1,4-butanedial d) 4-oxohexanal 8. Draw the structure of the products for the reduction of each of the compounds in question 7 with excess hydrogen gas over Nickel. 9. Why does the concentration of the ethanolic reaction mixture, followed by the addition of HCl, result in the formation of two layers? Organometallics You will be running a Grignard synthesis of a carboxylic acid from the reaction of a Grignard Reagent and carbon dioxide. See your lab text: p. 280-283 & p. 285-288. You will modify the procedure to make either p-tolyl or o-tolyl magnesium bromide from p-bromotoluene (section 01) or o-bromotoluene (section 02) and react it with carbon dioxide in the form of dry ice. Modify the procedure in your text for the synthesis of phenyl magnesium bromide as follows: Take one-fifth of the required amounts of the bromotoluene and diethyl ether and place the mixture in a dry test tube. Add some of the magnesium metal. Scratch and break up the metal with a stirring rod to begin the reaction. Once the reaction has started, add the mixture to the ether and remaining magnesium in the round bottom flask with 10 mL of diethyl ether. Begin the slow addition of the bromotoluene/ether mixture as detailed in the lab text. Answer the following questions: 1) Where in the nmr spectrum would you see the carboxylic acid hydrogen? 2) Why must all equipment be dry when reacting tolyl magnesium bromide with carbon dioxide? (show equations) 3) a) Explain the difference between "inverse" and "normal" addition of organometallics and substrates. b) Which was done in this experiment? Why? 4) Write chemical equations to show all of the different methods that can be used to synthesize tertiary alcohols with Grignard reagents. 4) Write all steps in the mechanism for the reaction of an ester with a Grignard reagent. 5) What side reactions are possible during the formation of a Grignard reagent? Write structures. How were these separated from the product? 6) p-Toluic acid cannot be made from p-xylene by oxidation. Explain. Answer questions 1, 2, 5 on page 288. Esterification You will make isopentyl acetate (banana oil) according to the instructions in your lab text on page 96. Obtain the IR and nmr spectra of the product. Answer the following questions as part of your report: 1) a) If the Keq for the esterification of acetic acid with isopentyl alcohol is 3.0, what is the maximum amount of isopentyl acetate that can be recovered at equilibrium if a 1:1 mole ratio of acid:alcohol is used? b) If a 1:5 mole ratio is used? c) 5:1 mole ratio? 2) What role does sulfuric acid play in this reaction? Explain; show equations. 3) Tell what effect doubling the concentration of sulfuric acid would have on the yield of the ester. 4) Why were the contents of the round bottom flask after reflux poured into 10 mL of water? 5) Why do we wash the ester with sodium carbonate solution? 6) Why would solid NaOH not be a good drying agent for the ester? 7) How would you distinguish between the nmr spectra of methyl benzoate and phenyl acetate? Aldol condensation You are to prepare anisalacetophenone (AKA 4-methoxychalcone) via an aldol condensation according to the directions on page 411 of your lab text. You will recrystallize the crude product from 95% ethanol. Run the nmr and IR (CCl4) spectra of your product. answer the following questions: 1) In the aldol condensation you ran: a) Why doesn't the ketone undergo a self-condensation? b) Why doesn't the aldehyde undergo the Cannizzaro reaction? c) Write equations for both of the above reactions. 2) Are there geometric isomers of the product of this synthesis? Draw them. Is the reaction stereoselective or stereospecific? Which product is actually formed and why. 3) Predict the products of the following: a) b) c) d) e) butyraldehyde, dil. NaOH formaldehyde, conc. NaOH acetone, p-tolualdehyde(2 mol), dil NaOH 2,2-dimethylpropanal, formaldehyde, conc. NaOH benzaldehyde, methyl acetate, sodium methoxide 4) Why does the intermediate in the synthesis undergo spontaneous dehydration? 5) Show the stereochemistry of the hydroxylation with potassium permanganate of transanisalacetophenone using Fischer projections. Answer question 4 on page 412 of your lab text. Diels Alder Read pages 427-433. Run the Diels Alder condensation reaction between alpha-phellandrene and maleic anhydride according to the directions below. Obtain IR (KBr pellet) spectrum of the product. Write up a pre-lab for the condensation of α-phellandrene (2-methyl-5-isopropyl-1,3cyclohexadiene) and maleic anhydride. You won't find the product in the CRC. The α-phellandrene that we have is not pure, it only contains 70% α-phellandrene by weight. You will need to figure how much of the impure compound to weigh out that will contain 0.050 mole of the α-phellandrene. In a 100-mL round-bottom flask put 0.050 mole of maleic anhydride and the weight of impure α-phellandrene that contains 0.050 mole. Add 25 mL of ethyl acetate, attach a reflux condenser, and heat on a hot water wath for one hour. Cool in an ice-water bath and then suction filter. Recrystallize the product from ethyl acetate, vacuum filter, let air dry, weigh, package, and obtain the IR spectrum (KBr method). answer the following questions: 1) Why is the endo product usually preferred in Diels-Alder condensations? 2) In your product, which way is the isopropyl group pointed? Explain. 3) The product of your synthesis has three chiral centers. Draw the product and label each chiral center with and asterisk (*). How many stereosiomers are theoretically possible? Only one stereoisomer is actually formed in this reaction, explain. 4) Predict the products of the following: a) b) c) d) e) 1,3-butadiene + 2-butyne 1,3-cyclopentadiene + cis-2-butene 1,3-butadiene + dimethyl maleate(methyl ester of maleic acid) (2 mol)1,3-cyclopentadiene + p-benzoquinone dicylopentadiene + heat (retro Diels-Alder) 5) Explain why the diene must be in the sigma-cis conformation in order to undergo a Diels-Alder reaction. Preparation of an α,β-unsaturated ketone via Michael Addition combined with an aldol condensation. The procedure for this experiment is in your text: p. 413-416. You will obtain the IR spectrum of the product. Answer questions 1-4 on page 416. Lidocaine You will synthesize lidocaine via a series of synthetic reactions according to the instructions below. A single report is required with IR and nmr spectra of the final product. Be sure to calculate % yield for each step of your synthesis as well as the overall % yield. multistep synthesis of lidocaine first lab: Reduction of 1,3-dimethyl-2-nitrobenzene to 2,6-dimethylaniline Ar-NO2 + SnCl2.2H2O, HCl ---> Ar-NH3+,Cl- + SnCl4 -make up the following two solutions: solution 1: 0.10 mole (22.6 g) SnCl2.2H2O in 40 mL of conc. HCl (warm to dissolve) solution 2: 0.033 mole (5 g, 4.5 mL) 1,3-dimethyl-2-nitrobenzene in 50 mL acetic acid -mix the two solutions and let stand for 15 minutes -after fifteen minutes, cool in ice bath and vacuum filter Ar-NH3+,Cl- + KOH ---> Ar-NH2 -tranfer solid to a flask and add 25 mL of water, make strongly basic with 40-50 mL of 8M KOH (caution!) -cool to room temperature with ice bath -extract with (1) 25 mL diethyl ether (2) 10 mL diethyl ether -wash combined ether extracts with 10 mL water; repeat -dry over anh. K2CO3 -filter into pre-weighed RB flask and remove diethyl ether by distillation (ether --> waste bottle) -reweigh flask α-chloro-2,6-dimethylacetanilide Ar-NH2 + Cl-CH2COCl ---> Ar-NHCOCH2-Cl -residue from above + 25 mL acetic acid -add (3.7 g, 2.6 mL) α-chloroacetyl chloride (caution!) -warm to 40-50oC -add solution: (5 g NaO2CCH3.3H2O in 100 mL water) -cool, vacuum filter, air dry, weigh, mp second lab: lidocaine Ar-NHCOCH2-Cl + NH(CH2CH3)2 Ar-NHCOCH2-N(CH2CH3)2 -note: all reagents and apparatus must be dry! -in a 250 mL RB flask, combine the α-chloro-2,6-dimethylacetanilide from above with 45 mL toluene -calculate the number of moles of α-chloro-2,6-dimethylacetanilide and add three times that number of moles of diethylamine to the RB. -attach a water cooled condenser and reflux for 90 minutes. -cool in an water bath and vacuum filter off the solid that forms. (this is not your product!) -transfer the filtrate to a separatory funnel and extract with two 25 mL portions of 3M HCl. -combine the aqueous layers in a 250 mL Erlenmeyer flask and add 50 mL of 8 M KOH to make the solution stronly basic. -warm the mixture and blow across the surface to remove any excess diethylamine -cool in an ice bath, continuing to blow and scratch until crystals form. -vacuum filter the crude lidocain, wash the crystals with cold water and remove from the filter paper immediately. -let dry on a watch glass, package, weigh, mp, IR & nmr spectra. Answer the following questions: 1) Write a balanced chemical equation for the reduction of nitrobenzene with Fe in HCl to form aniline. (Fe --> FeCl3) 2) Draw the structures of at least two by-products produced in the reaction in 1). 3) Why does 2,6-dimethylaniline react with chloroacetyl chloride to produce an amide rather than a secondary amine? 4) Lidocaine is commercially sold in the form of the hydrogen chloride salt. Why? 5) In the reduction of 2,6-dimethylnitrobenzene with stannous chloride, what is the structure of the ppt that is collected by suction filtration? 6) What is the precipitate collected by filtration after the reaction with diethylamine? 7) Why do we use three moles of diethylamine for every mole of the anilide? Qualitative analysis You will receive three unknown organic compounds which you are to identify by a traditional qualitative analysis scheme. The report will consist of a form that you will fill out. Read p 485-490 in your text. Qualitative Organic Analysis The analysis experiment is equivalent to identifying a substance about which you have absolutely no information: the contents of an unlabeled bottle; a natural product isolated from the leaf of a tropical plant; a component of a competitor's formulated product; etc. Such an analysis requires a systematic approach, as is described in in your text. 1. Prior to receiving your unknown sample, a practice sodium fusion (analysis for constituent elements) must be done. Read: page 500-502 A solid "known" mixture of organic compounds that contains nitrogen, sulfur, and halogen (N, S, X) is to be used. After you have observed the demonstration of the sodium fusion technique, you are to perform the sodium fusion with the "known" mixture, and then test the resulting aqueous solution for the constituent ions. NOTE: Do not carry out the procedures to determine the identity of the halogen (or halogens) in the known or in your unknown. If you do get a positive test for halogen with Ag+, you will be able to determine if the X is F, Cl, Br, or I (or a combination) from subsequent tests and/or clever reasoning. 2. When you have completed the practice sodium fusion and ion tests, obtain a numbered vial containing your unknown from the instructor. Record the unknown number in your notebook immediately! 3. Perform the analysis according to the list on page 485, including the indicator tests according to the attached handout. 4. If you wish to carry out any classification or functional group tests with known compounds, ask the instructor who will cheerfully fulfill your request. 5. Consult the Handbook of Tables for Organic Compound Identification and the tables in your text (p. 878-888). Qualitative Analysis -- preliminary classification Solubility tests: To carry out the solubility tests, approximately 0.1 g or 0.1 mL of the substance is added to 3 mL of the solvent. If most of the material appears to dissolve, the compound is considered soluble. If there is no immediate change, especially with a solid unknown, the mixture should be thoroughly stirred with a glass rod and at least 2 minutes allowed to elapse before a decision is made. The solubility tests must be applied in the sequence given below to avoid misleading observations. a. Solubility in water. A compound that is soluble in water must be at least somewhat polar. b. Solubility in ether. A compound that dissolves in water is tested for solubility in diethyl ether. Organic compounds that contain more than one polar functional group are not likely to dissolve in ether. Only compounds that have one polar group and a relatively small number of carbon atoms are expected to dissolve in both polar and nonpolar solvents. c. Solubility in aqueous acid or base. A water-insoluble organic acid should dissolve in an aqueous base; an organic base that is not soluble in water should dissolve in aqueous acid. The observed solubility in each case is the result of the formation of an ionic salt which remains dissolved in the aqueous medium. It should be obvious that these tests are applied only if the original compound does not dissolve in water. If the substance is found to be soluble in 5% NaOH, indicating that it is an acid, it is tested further with 5% sodium hydrogen carbonate. Only acids stronger than carbonic acid will dissolve. A compound may therefore be classified as a strong or weak acid on the basis of these two solubility tests. An organic base can be identified by its solubility in 5% hydrochloric acid. No further classification is possible. If a compound is found to be an acid, it should also be tested with hydrochloric acid on the chance that it may contain both acidic and basic functional groups (e.g., an amino acid). d. Solubility in sulfuric acid. A compound that is insoluble in water, hydrochloric acid, and sodium hydroxide is considered to be neutral. Those substances that contain nitrogen or sulfur are not tested further and are classed as nitrogen-sulfur neutrals (class M). Other compounds are tested for solubility in concentrated sulfuric acid. In this test, a solution in the sense of an ordinary aqueous solution is not necessarily formed. If heat is evolved, a color develops, or any other change indicative of a reaction is seen, it is concluded that the substance is "soluble" in H2SO4. Solubility classification of some organic compounds: S : soluble in water and soluble in diethyl ether 1 oxygen and nitrogen compounds having less than five carbon atoms: monofunctional alcohols, aldehydes, amines, carboxylic acids, ketones. S2 : soluble in water and insoluble in diethyl ether polyfunctional oxygen and nitrogen compounds: diols, triols, etc.; polyamines; dicarboxylic acids. A1 (weak acids) : soluble in dilute sodium hydroxide phenols, beta-diketones. A2 (strong acids) : soluble in dilute sodium bicarbonate carboxylic acids, polynitrophenols, polyhalophenols, acyl halides. B (bases) : soluble in dilute hydrochloric acid amines (except diaryl and triarylamines) N1 (neutrals) : soluble in conc. sulfuric acid alkenes, some arenes, ethers, water-insoluble: alcohols, aldehydes, esters, ketones. N (neutrals) : insoluble in conc. sulfuric acid 2 alkanes, halides, diarylethers. M (nitrogen-containing neutrals) amides, nitrocompounds, diaryl- and triarylamines, nitroarylamines. Indicator Classification Method: The solubility method suffers from several shortcomings. One is that it is difficult to estimate solubility in borderline cases. There are also some instances in which a solid substance dissolves, only to react with the solvent to form an insoluble product. The indicator method overcomes these difficulties and also provides a more specific classification. That is, it is possible to classify an acid as weak, intermediate, or strong, rather than just weak or strong as in the solubility system. Bases can also be classified as weak, intermediate, or strong. A set of four indicators, A-I, A-II, B-I, and B-II is required. To carry out the test, 1 mL of the indicator is placed in a small test tube and one drop of a liquid or about 30 mg or a solid (about as much as can be carried on the tip of a small spatula) is added to the indicator. The effect on each indicator solution is described below: A-I Indicator (original color: purple) If the color changes from purple to yellow, the compound is an intermediate acid (Ai) or a strong acid (As). If the color change is from purple to green, the unknown is a weak acid (Aw). To distinguish between Ai and As, you must use the A-II indicator. A-II Indicator (original color: blue-violet) A change from blue-violet to yellow occurs if the unknown is an intermediate acid. A strong acid causes a change from blue-violet to a shade of red. B-I Indicator (original color: Purple) Any base changes the color from purple to yellow. B-II Indicator (original color: Yellow) A weak base (Bw) has no effect (color remains yellow), while an intermediate base (Bi) produces a change from yellow to blue-violet. (There are relatively few strong organic bases. Although it is possible to detect strong organic bases by special treatment of the indicators, they will not be considered here. Caution: The indicators are made up in nonaqueous solvents. The addition of water to any of the indicators may cause a color change. It is imperative therefore that a clean, dry test tube be used for each test, and the sample tested must be free of water. Indicator Classification of Some Organic Compounds: Strong acids (As): acyl halides, some carboxylic aicds, nitrophenols. Intermediate acids (Ai): carboxylic acids, o- and p-hydroxyaromatic aldehydes and ketones, polyhalophenols. Weak acids (Aw): phenols, beta-diketones, some aryl esters. Intermediate bases (Bi): aliphatic amines, heterocyclic amines. Weak bases (Bw): primary arylamines, arylalkylamines, heterocyclic amines. Neutrals (do not contain nitrogen): hydrocarbons, halides, alcohols, aldehydes, ketones, esters, ethers. Neutrals (contain nitrogen): diarylamines, triarylamines, nitriles, nitrocompounds, amides, polynitroarylamines, polyhaloarylamines. Chemistry 313 QUALITATIVE ORGANIC ANALYSIS REPORT Name Date Unkn. No. 1. Identity of Compound Physical properties of purified material: physical state b.p. color m.p. refractive index (liq. only) 2. other Elemental Analysis: elements in addition to C, H, O 3. Preliminary Classification a) Solubility tests (write "s" if soluble; "i" if insoluble). H2O Et2O HCl NaOH NaHCO3 H2SO4 Classification b) Indicator tests (note the color change, if any) A-I A-II B-I B-II Classification: 4. Functional Group Tests On a separate sheet of paper, prepare a table with the column headings: Reagent, Result, and Inference. In the appropriate spaces, list the actual reagent and observed result of every functional group test applied to the unknown, and the inference drawn in each case. (See sample below.) Reagent Result Inference 2,4-DNPH orange ppt; red color with alc.KOH carbonyl group Tollens no silver mirror or ppt ketone(no aldehyde) NH2OH, KOH no purple color no ester group 5. Probable Compounds: List all compounds with m.p. or b.p. within 5o of that of the unknown, which could be identical to the unknown. Also list the useful derivatives and their m.p.'s. 6. 7. Derivatives made: List the derivatives of the unknown that were actually prepared and their observed m.p.'s. Spectroscopic Data: Tabulate ir and nmr data, if obtained. Chemistry 313 QUALITATIVE ORGANIC ANALYSIS REPORT Name Date Unkn. No. 1. Identity of Compound Physical properties of purified material: physical state b.p. color m.p. refractive index (liq. only) 2. other Elemental Analysis: elements in addition to C, H, O 3. Preliminary Classification a) Solubility tests (write "s" if soluble; "i" if insoluble). H2O Et2O HCl NaOH NaHCO3 H2SO4 Classification b) Indicator tests (note the color change, if any) A-I A-II B-I B-II Classification: 4. Functional Group Tests On a separate sheet of paper, prepare a table with the column headings: Reagent, Result, and Inference. In the appropriate spaces, list the actual reagent and observed result of every functional group test applied to the unknown, and the inference drawn in each case. (See sample below.) Reagent Result Inference 2,4-DNPH orange ppt; red color with alc.KOH carbonyl group Tollens no silver mirror or ppt ketone(no aldehyde) NH2OH, KOH no purple color no ester group 5. Probable Compounds: List all compounds with m.p. or b.p. within 5o of that of the unknown, which could be identical to the unknown. Also list the useful derivatives and their m.p.'s. 6. Derivatives made: List the derivatives of the unknown that were actually prepared and their observed m.p.'s. 7. Spectroscopic Data: Tabulate ir and nmr data, if obtained. Chemistry 313 QUALITATIVE ORGANIC ANALYSIS REPORT Name Date Unkn. No. 1. Identity of Compound Physical properties of purified material: physical state b.p. color m.p. refractive index (liq. only) 2. other Elemental Analysis: elements in addition to C, H, O 3. Preliminary Classification a) Solubility tests (write "s" if soluble; "i" if insoluble). H2O Et2O HCl NaOH NaHCO3 H2SO4 Classification b) Indicator tests (note the color change, if any) A-I A-II B-I B-II Classification: 4. Functional Group Tests On a separate sheet of paper, prepare a table with the column headings: Reagent, Result, and Inference. In the appropriate spaces, list the actual reagent and observed result of every functional group test applied to the unknown, and the inference drawn in each case. (See sample below.) Reagent Result group Tollens no silver mirror or ppt NH2OH, KOH no purple color Inference 2,4-DNPH orange ppt; red color with alc.KOH carbonyl ketone(no aldehyde) no ester group 5. Probable Compounds: List all compounds with m.p. or b.p. within 5o of that of the unknown, which could be identical to the unknown. Also list the useful derivatives and their m.p.'s. 6. Derivatives made: List the derivatives of the unknown that were actually prepared and their observed m.p.'s. 7. Spectroscopic Data: Tabulate ir and nmr data, if obtained.