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Organic Chemistry
322a/325a Lab
Manual
Fall 2023
Name _______________________
Group # _____________________
TA’s email ____________________
University of Southern California
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CHEM 322 Quick Access Information:
TAs names & emails:
__________________________________________________________________________________
University of Southern California
Organic Chemistry Laboratory Syllabus
Chemistry 322/325aL
Laboratory Director: Dr. Jennifer Moore
E-mail: mooreJL@usc.edu
Laboratory Location: SGM 204 & 209
Schedule: Changes to the schedule will be posted on blackboard.
Course: Chem 322aL is the laboratory portion that accompanies the first semester lecture of a twosemester sequence in organic chemistry. The points from the lab portion of the course are combined with
the points from the lecture portion into one letter grade.
Required Course Materials:
► Lab Manual: The “Organic Chemistry 322a Lab Manual” may be purchased & downloaded
from the USC Bookstore, for the current semester. Be aware the lab manual changes each semester.
Welcome to Chem 322a Lab
Welcome!! Our goal is to provide you with the hands-on experience that goes with the lecture portion
of the course. See the Blackboard Announcements page for the lab experiment calendar. Here are a
few notes to get you started this semester:
Week 1 – Lab Orientation – ONLINE, you will receive an email when Blackboard & Lab
Orientation are available for accessing and completing. Labs do NOT meet in-person this week.
Week 2 – Check-In & Molecular Modeling – Found in this lab manual, bring your laptop to lab this
week. TA office hours will begin. Labs meet IN-PERSON. More information will be provided on BB
about this week of lab. Arrive to your lab section in FULL PPE and USCID ready for checking as you
enter. No pre-lab or lab notebook required this week. However, you should start working on the first
pre-lab for Solubility and ask your TAs any questions you have about preparing.
Week 3 –Lab Safety & Chemical Literature Assignment – Labs do NOT meet in-person this week.
Online Assignment will be posted to BB.
Any change to this plan will be posted on Blackboard.
Your TAs and I look forward to working with you this semester!
Dr. Moore
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Chemistry 322a – Organic Chemistry Laboratory Manual
Lab Director: Dr. Jennifer Moore
Table of Contents
Course Overview & Laboratory Objectives
Laboratory Policy
Attendance and Grading
Laboratory Notebook Guidelines
Your Laboratory Grade
Sample Rubric
Safety
Chemical Waste Disposal
Experiment
1.
3
4
5
5
7
8
9
10
Title
Page
Chemical Information Literacy for Organic Chemistry –
13
Summary: Exploration of chemical resources and research tools
Keywords: MSDS, Merck Index, CHEMnetBASE, SDBS, Reaxys, PubMed, Web of Science,
SciFInder, ChemBioDraw
2.
Solubility of Organic Compounds
19
3.
Recrystallization
26
4.
Chromatography
30
5.
Extraction
36
Summary: Experiments of Solubility, Miscibility, Acid/Base Chemistry & Critical Analysis
Keywords: Solid Solubility, Miscible and Immiscible Pairs, Organic Acids & Bases, Data Analysis
Summary: Determine good recrystallization solvents and recrystallize crude compound
Keywords: Temperature/Solubility Relationship, Vacuum Filtration, Percent Recovery
Summary: Analyze solvent choice in TLC, develop TLC plates, run column chromatography Separation of
mixture via acid/base chemistry & liquid-liquid extraction
Keywords: Chromatography, Thin-Layer Chromatography (TLC), Column Chromatography, Solubility,
Miscibility, Extraction, Separation Scheme
Summary: Separation of mixture via acid/base chemistry & liquid-liquid extraction
Keywords: Partition coefficients, Solubility, Miscibility, Extraction, Separation Scheme
6.
Distillation
39
Summary: Perform simple and fractional distillation, analyze via gas chromatography
Keywords: Distillation (Simple, Fractional), Data Analysis, GC Analysis, Vapor Pressure, Boiling Point
7.
Synthesis of Methylbutenes
41
Summary: Acid-catalyzed dehydration and critical analysis of isomers via IR, GC, NMR
Keywords: Formal Report, Dehydration, Hickman Distillation, Characterization (GC, IR, NMR)
8.
Predicting Organic Substitution Reactions
44
9.
Reduction of Vanillin_________________
56
Summary: Studio-based exploration and experiments featuring substitution-reactions
Keywords: Substitution Reactions, Intermediates, Mechanism, Solubility, Energy Diagrams
Summary: Performa a reduction reaction and follow the reaction by TLC.
Keywords: Reduction Reaction, TLC, Solubility
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Course Overview and Laboratory Objectives
Objectives of the laboratory course include:
1. To recognize that chemistry is an experimental science and develop competencies in the handson aspect of chemistry, including common organic techniques, characterization, and instruments
associated with organic laboratory.
2. To understand that success depends on preparation, understanding of chemical reactions, the
ability to adapt to unforeseeable circumstances, and to utilize techniques, instruments, and
chemical intuition safely, accurately, and precisely.
3. To develop critical problem-solving skills that are valuable regardless of the career you pursue.
4. To develop competencies in analysis, reasoning, critical observation skills, and develop your
scientific writing.
Associated with these objectives are the following learning outcomes:
1. To recognize the importance of safety and proper handling of chemicals during experiments.
2. To gain experience running reactions that you have learned in the lecture part of this course.
3. To build or expand your competency with techniques to execute laboratory procedures.
4. To continue to build your chemical intuition.
Regulatory Notice Warning: Any student under the care of a physician for a continuing medical
problem and/or may be pregnant should advise his/her physician that s/he is taking organic chemistry
lab. It is the student’s responsibility to bring any such condition to the attention of the lab director.
Students with Disabilities: Any students requesting academic accommodations based on a disability
is required to register with DSP, Disability Services and Programs, each semester. A letter of
verification for approved accommodations can be obtained from DSP. DSP is located in GFS 120 and
is open 8:30 a.m. -5:00 p.m., Monday through Friday. The phone number for DSP is (213) 740-0776.
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Laboratory Policy
Drop Deadline: If you drop Chem 322, then you must also drop the Chem 322 Lab and Chem 322
Discussion sections.
Plagiarism is NOT TOLERATED. We expect that each student will write all parts of his or her
laboratory reports. Plagiarism of part of another student's laboratory report will result in a ZERO for
all students involved and a case filed with SJACS. Plagiarism on a lab quiz/exam will result in an F for
the course.
Preparedness and Lab Reports: You have 2 hours and 50 minutes to complete each experiment
and clean up. Each lab report will be written in three parts. The first part, the pre-lab report, includes
a set of instructions you write before lab for yourself in order to carry out the experiment. You will
not be allowed to use your lab manual during the lab, so your pre-lab report needs to be as complete as
is necessary for you to do each experiment. All pre-labs are to be handwritten, scanned and
uploaded to Gradescope by 10am the Monday before your lab section. The second part includes
the in-lab observations that are turned in to Gradescope at the end of lab. ZERO points for the in-lab
if it is missing the TA signature. The duplicate copy will also be turned into your TA at the end of
lab. The third part includes the post-lab report. Instructions for the post-lab report will be available on
Blackboard and the post-lab assignment will be uploaded to Gradescope unless otherwise specified.
Post-labs are due the following THURSDAY by 9pm.
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Attendance and Grading
ALL LAB ASSIGNMENTS MUST BE COMPLETED IN ORDER TO PASS THE LAB.
Satisfactory completion of the laboratory component of 322 is required to pass the course.
Absences: ALL assignments/experiments must be completed to pass the course. All labs must be
completed in your scheduled lab period.
►Lab reports will not be graded if they are not legible by the TA.
►Regrades are due by the deadline give on the BB schedule.
A lab report containing inappropriate material will receive a zero.
Laboratory Notebook Guidelines
Most lab reports will be written in three parts.
1. Pre-Lab:
•
No pre-lab report, no lab.
•
Use duplicate style notebook
•
All pre-labs are to be handwritten – see page 8 for what to include
•
Uploaded to Gradescope by 10am the Monday before your lab section
2. In-Laboratory Account:
•
Uploaded to Gradescope immediately following lab
•
Physical copy turned in at the end of lab, directly to your TA – see page 8 for what to
include
•
Use a duplicate style notebook
•
2-point deduction will be taken if the TA sends you a copy of the in-lab assignment
3. Post-Lab:
•
You will have the next lab period to ask questions and the post-lab will be due by 9pm
on that Thursday. Exceptions will be communicated via Blackboard announcements.
•
Typed and Uploaded, Chem-Draw required for structures
•
See page 8 for what to include
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Pre-Lab - No pre-lab report, no lab.
Hand written in a duplicate style notebook. Errors are crossed out with a single line allowing the
original notation to be read.
Include the following components in this order:
ü Date you will carry out the experiment
ü Title of Experiment
ü Your name & your Group #
ü Objective
ü Reaction scheme, if appropriate
ü Data Table – include reactants, products and solvents but not drying agents along the left-hand
side. Physical constants - MW, mp, bp, d, mass -should be written in columns across the page.
Include safety considerations (toxicity, flammability and any danger of skin contact, i.e.
corrosive) as the last column.
ü Sketch of apparatus if two or more parts are assembled and a list of other glassware.
ü Separation Scheme for any compound you isolate. Use actual structures NOT generic structures.
ü Calculation of Limiting reagent and estimated theoretical yield, if appropriate
ü Pre-lab questions
ü Procedure – DO NOT copy from the lab book! Remember that the reader has at minimum a
college degree in chemistry, so save time by using the highest level of technical vocabulary to
describe the procedure. For example, it is sufficient to say that the solid product was “collected
by vacuum filtration” instead of writing “a Buchner funnel will be attached to a suction
filtration flask that is then connected to a vacuum line. Then, I will place a piece of filter paper
in the funnel and moisten it with a little bit of solvent…etc.”
ü Late Pre-Lab assignments result in one point off per day.
ü Submit to Gradescope by the due date listed on BB.
In-Laboratory Account
ü Observations - During lab, a running account of what you do and what you observe, e.g., color
changes, accidents, and changes to the procedures after you get to lab. You should also write
down in your notebook, as you take the measurements, weights/volumes of reagents and
solvents used, and melting points and boiling points, which should be reported as temperature
ranges.
ü Submit all in-lab materials to your TA before leaving lab and upload to Gradescope before
leaving lab.
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Post-Laboratory Report
ü This portion should be completed on your own. Once you start working on the post-lab, stop
talking with your peers.
ü Any modifications to the procedure
ü Calculations/Data analysis - of theoretical yield and actual % yield. Calculations of actual %
yield should be to the nearest whole number.
ü Additional data - e.g., IR, MS, NMR spectral data.
ü Critical Thinking & Analysis Inquiries
ü Citations - If you use any material that is not your own (article, another student’s data, etc.), you
must properly cite the source. All citations should be in ACS format. See
http://www.lib.berkeley.edu/CHEM/acsstyle.html for a quick guide.
ü Conclusion - one to two sentences connecting the purpose of the lab and what was accomplished.
ü Submit to Gradescope by the due date. Late assignments will result in one point off per day late.
Your Laboratory Grade
► In the lab this semester, you will perform ~10 experiments.
► 8 min pre-lab quizzes will be given at the start time of the lab period – e.g. if you have a 12pm lab,
quizzes will start at 12pm.
• If you are late, you miss the quiz – no extra time for late students
► One Lab Practical will be given in the semester. More information can be found on BB as we get
closer to the Lab Practical.
► In addition to experiments, multiple assignments will be graded and must be completed to pass the
course.
► Completion of all assignments by the late due date are required to pass the class.
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CHEM 322: Master Rubric Overview
Pre-Laboratory Report (XX):
(X)
Each Missing: Name, Title, Purpose, Date
(X)
Reaction Scheme
(X)
Table of Chemical Data
(X)
Apparatus Sketch; List of Glassware
(X)
Separation Scheme
(X)
Limiting Reagent Calculations, Theoretical
Yield
(X)
(X)
Pre-Laboratory Questions / Case Studies
Procedure (Utilizing the Left-Half of the
Page) – No Procedure, No Lab.
The Procedure must be completed
before arriving to lab.
In Laboratory Account (XX):
Procedural Observations (Utilizing Right(X)
Half of the Page)
(X)
Visual Observations
(X)
Data Observations
(X)
Characterization
Post-Laboratory Report (XX):
(X)
Calculations
(X)
Critical Thinking & Analysis
(X)
Conclusion
Total: ___________ (XX)
Point Deductions (From Adjusted Lab Score):
(-2)
Safety Violations
(-1)
Laboratory Etiquette
(X)
Other point deductions
Final Lab Score: ________ (XX)
Requirements for Pre-Laboratory Report:
Pre-Laboratory Report should be ready to turn in prior to lab (stapled,
has your name, etc.) with the rubric stapled to the front.
Name: Full Name as it appears on Student Roster
Title: Experiment # and Title
Date: Date Experiment was performed
TA: Group #
Purpose: 2-3 sentences about the goals and objectives of the
experiments
Reaction Scheme: Structures with reactants on left and products on
right; reagents denoted on an arrow.
Table of Chemical Data: Structures, name, and all relevant physical
constants, including but not limited to density, molecular weight,
boiling point, melting point; also safety considerations for chemicals.
Apparatus Sketch; List of Glassware: If 2 or more pieces are
assembled, must draw a sketch of the apparatus. Also list the other
glassware/equipment utilized in the experiment.
Separation Scheme: A flow chart of the route toward isolating the
desired compound, including extraction and all washing steps,
evaporation, drying agents, filtration, decanting, column
chromatography, or any technique that purifies a compound in some
way.
Limiting Reagent: Calculations toward determining the limiting
reagent with the quantities provided in the lab manual.
Theoretical Yield: Estimated yield given complete conversion based
on the quantities provided in the lab manual.
Requirements for In-Laboratory Account
Procedure: Left-hand side of the page; must be written prior to lab to
be allowed to run the lab.
Procedural Observations: A running account on the right side of the
page. It is essentially confirmation that the procedure was followed as
written but also includes accidents, quantities, techniques, or detailed
procedures that would allow a qualified individual to replicate your
results.
Visual Observations: The colors, consistency, quality of the reagents,
intermediates, and products you are handling. Include descriptions of
accidents and visual cues as well as obstacles.
Data Observations: Things you measured. Tared vials or
watchglasses. Exact masses of materials, reagents, etc.
Characterization: Techniques used for characterization beyond
visual or data indicators. These include melting point, pH, TLC,
distillation temperature, NMRs, GCs, etc. Any analyzed spectra
should be submitted with Post-Laboratory Report
Requirements for Post-Laboratory Report:
Calculations: Calculations such as limiting reagent and theoretical
yield given your actual quantities in lab, Rf values, percent recovery.
Work must always be shown.
Critical Thinking & Analysis/Conclusion: Questions or assignments
from the Lab Manual or assigned by TA/handed out. Should include
an analysis of all the results, an analysis of your observations, a
critique of your technique or the experimental protocol, suggestions or
strategies for improving the laboratory. Include photo/image of
analyzed spectra.
Conclusion: A couple of sentences that ties together the experiment
objective.
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Safety
Eye Safety: All students, teaching assistants, professors and visitors must wear safety eyewear at all
times in the laboratory. THIS IS CALIFORNIA STATE LAW. We follow the safety model of the
industrial laboratory. Safety eyewear is donned prior to entering the lab and is not to be removed
until outside of the lab. Students without safety eyewear will not be permitted to attend the lab.
Contact Lenses: You should consult with your health professional regarding the wearing
of contact lenses while performing lab work.
Accidents in the Laboratory:
For minor cuts and scrapes, flush with water and then call the TA.
In the event of an eye injury involving chemicals, flush immediately with water at the eyewash station
for at least 15 minutes (you may require assistance holding your eyes open) and you must go to the
Student Health Center.
Report all accidents to your TA IMMEDIATELY (no matter how minor they may seem).
For all injuries, it is your prerogative and you are encouraged to seek professional medical advice or
treatment. For minor injuries, you may choose to decline to go to the Student Health Center. We
require that you sign an acknowledgement of this decision on the departmental Incident Report Form.
Declining is an option only for minor injuries, as determined by the TA not the student.
Building Evacuation When the alarm sounds, leave the building immediately by the nearest exit and
meet your TA on the North steps of GFS (Grace Ford Salvatori). No one is authorized to interrupt
your evacuation. You are required to stay with your TA until it is safe to re-enter the building and roll
has been called. Keep your keys in your pocket in case it is not possible to return to the laboratory
that day.
Chemical Waste Disposal
Chemical Supply Etiquette: Chemical waste is a major concern in chemistry because it is
expensive and potentially bad for the environment. As a result, it is our collective responsibility to
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THINK GREEN! Always take only the amount of solvent required by the lab manual. Always read
the label on the reagent bottle at least twice, when reaching for the chemical bottle and again when
drawing the reagent up with your pipette. Never remove large chemical bottles from the chemical
hood, these can be slippery and easy to drop! In general, you should always collect your reagent in a
secondary container and bring it to your hood with a covered top. Always make sure the pipette you
are using to collect reagents is associated with the bottle!—if you are not sure, get a fresh pipette to
avoid cross contamination. Never place a used pipette or stopper on the bench top, they can be
easily contaminated, use a clean Erlenmeyer or graduated cylinder to store pipettes. Always secure
caps on reagent bottles to prevent evaporation, decomposition, or accidentally spillage. Be vigilant
and careful!
Do not pour chemicals into the sinks. Most of the chemicals that you will use in your experiments
must be safely disposed of according to California State Law. In addition, many of these chemicals
can be harmful to the environment. Since you are unaware of the state regulations and possible
adverse effects of these chemicals, do NOT take a chance. Always dispose of chemicals in the
designated waste container, unless your TA or Dr. Moore specifically tells you not to. When in
doubt, ask the TA.
****Only soap and water go down the drain****
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Laboratory Housekeeping: Store your belongings in the cubbyholes provided. Work areas must
be left clean and dry before leaving the lab. Turn off ALL gas outlets and water taps before leaving
lab. Paper, broken glass, etc. must be removed from the sink before leaving. Your TA may have you
clean the following:
• Shared benchtops
• Sinks
• Balances
• Hoods
• Ovens
• Drying racks
• Acetone wash collection beakers
• Locations with debris, such as weigh paper or paper towels in hoods
Good Laboratory Habits: Traces of chemicals may remain on the laboratory bench surface.
• Never lay pens down on the lab bench top and then place them in your mouth
• Never rub your eye or scratch your head during the lab
• Always wash your forearms and your hands before leaving the lab
• Keep your safety eyewear clean
• Never bring food or drink into the lab
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1 Critical Analysis of Chemical Literature
Links and tutorials for this assignment can be found on the Chem 322a/325a Course Guide:
http://libguides.usc.edu/chem322a
For questions contact Shalini Ramachandran, shalinir@usc.edu
Introduction
Technology plays a major role in today’s understanding of chemistry. Chemists utilize different
electronic and online resources for research and laboratory work. It is important to be aware of
these tools and keep up-to-date on the most recent and relevant research, databases, and data.
In this lab you will explore chemical resources important for future lab assignments and research.
Answer the questions in each section. There is no specific format. By the end of this lab, you should
be able to determine what resource is best suited to answer a question and how to use that specific
resource to determine a viable answer.
Ø Combine all of the requested spectra/responses/structures in one PDF.
Ø Upload a single PDF on Gradescope
Ø Make sure the final version is submitted. There is a 1pt penalty for having the TA clear
your report.
Materials Needed
Computer/Laptop*
v This assignment will not work on a tablet. If you do not have a personal computer, please use
the
software provided in one of the ITS managed computer labs
(https://itservices.usc.edu/spaces). If you use a personal computer, access ChemDraw
through USC’s virtual lab (https://lab.usc.edu).
Part I: Chemical Data and Laboratory Safety
Before stepping into a lab, it is imperative to know physical data, safety information, and other
guidelines regarding any of the chemical or procedures you will be carrying out. In a teaching lab,
most of the information is provided to you by a teaching assistant or by your instructor. In research
labs, this is the responsibility of the researcher. There are many different places to find this
information, but what is important is to use a reputable, accurate, and well-respected resource.
Chemical dictionaries and databases will provide a great deal of reputable and reliable information.
On the Chem 322a course guide, go to the tab labeled Reference Tools. Click on The Merck Index.
1. Perform a Quick Search for acetaminophen (the generic name for Tylenol). Include the
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following information: drawn structure (using ChemDraw), CAS registry number, CAS name
(formal chemical name), molecular formula, molecular weight (assume g/mol), and percent
composition.
2. Scroll to the bottom of the page and enter a chemical, medication, or drug you are interested
in finding more information about in the Quick Search box. Using The Merck Index provide the
following information: name, drawn structure, CAS number, CAS name (formal chemical name),
molecular formula, molecular weight (assume g/mol), and percent composition.
Other resources are available to find chemical information including the CHEMnetBASE suite.
Some chemical dictionaries provide safety and hazard information, but they are not complete or
thorough. One of the most reliable places to look for this information is a chemical manufacturer’s
website. By law, a company must provide a Material Safety Data Sheet (or MSDS or SDS) for every
chemical that company produces and sells. Most companies have made this information free and open
on their respective websites.
Sigma-Aldrich is one of the largest chemical manufactures in the world. Click on the link for SigmaAldrich and answer the following questions.
3. In the top right corner, search for acetone. You will see multiple results appear. Often
chemicals/compounds/substances are sold as derivatives or with some type of stabilizer or
counter ion. Select the first entry. You will note that the first item is HPLC Plus and includes the link
for the SDS. Click the link and scroll through it. You will see a lot of available information including
first aid information and handling instructions. Find the section labeled Exposure
Control/Personal Protection. What is the recommendation for eye/face protection when
handling acetone?
4. Look through your MSDS and note down anything interesting, new, or confusing.
Part II: Finding Spectra
When performing laboratory experiments, characterizing your compounds is extremely important.
The process of characterizing proves the compound you created is the compound you intended to
create. One way to determine if you have created the correct compound is through spectra. The
spectra from NMR, IR, UV-Vis, Raman, MS, etc. can be compared to a reference spectra (a spectra
that is verified as correct).
Find spectra for compounds can be extremely challenging. For organic compounds, the first place to
look is SDBS, or the Spectral Database for Organic Compounds. This database is managed by the
National Institute of Advanced Industrial Science and Technology, or AIST, in Japan. Go to the
Databases and Spectra tab in the course guide.
5. Click on SDBS and agree to the disclaimer. Search for N-methylphthalimide in SDBS. Are any
derivatives listed? What spectra is available for this compound? Include with the assignment. Label
this spectra as “spectra #1.”
For more complex organic compounds or non-organic, SDBS will not have any spectra. The next
best place to look is Reaxys. On the course guide, click on Reaxys.
Read the section below before first before answering question 8. Follow these instructions to find
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spectra in Reaxys:
To find details regarding a compound, when you have the name or CAS number, click on “Substance,
Names, Formulas”. Enter your search. On the results page, find the compound that matches your
search and find the link to Spectra (it should be in the right hand column). The page will load with
available spectra, a citation to where the article the spectra is from, and a link to the full-text article.
6. Search for N-methylphthalimide. What spectra types are available? Are there more or less than
listed in SDBS? You will select one of the article references to obtain the spectra. Select “Spectra”
under the “Available Data” column. Select a reference. Include one spectra from this article. Label
this spectra as “spectra #2.”
Part III: Topic and Article Searching
Topic searching is an important tool in discovering articles and research materials. The most
effective way to do a topic search is to use a database. Databases allow you to search across
multiple disciplines, journals, and years. USC Libraries subscribes to thousands of databases. You
will try out two different databases: PubMed and Web of Science.
A note about searching for articles: articles are only as good as your ability to find the full-text of an
article. Without the full-text, you do not get the graphs, tables, references, and supplemental
information. Usually the full-text article is not available in the database, but on a different website.
USC Libraries has provided the “Find it @ USC” link to directly link to the full-text article, if available.
Occasionally, USC Libraries does not have a subscription to the journal the article appears in. When
clicking the “Find it @ USC” link, you will be told to request the article via interlibrary loan (ILL).
PubMed is a service provided by the National Institutes of Health and contains millions of citations
of medically related research. All NIH funded research must ultimately be available through
PubMed for free.
7. Click on PubMed in the course guide and search for “acetaminophen”. Then start over and
search for “acetaminophen delivery systems.” What happens when you submit the
aforementioned phrase? How many articles appeared in each search?
8. On the left side, you will see a filter tool. Using the second search results, try limiting the number
of results by only selecting articles less than five years old. Now how many articles appear?
9. Perform a PubMed search for the compound you chose in question 2. Find an article about it and
write down the citation in ACS format and a brief description of the research. It is important to
provide the citation for the work of others that you include in your analyses or summaries. For
review, see the citation tab for videos on avoiding plagiarism and citing sources in the sciences. If
you need help formatting a citation, see the course guide for a sample citation.
10. Citation check. Locate the following article on PubMed:
“The Effect of Time, Roasting Temperature, and Grind Size on Caffeine and Chlorogenic Acid
Concentrations in Cold Brew Coffee”
Is this citation formatted correctly for ACS? If not, write it correctly. Hint: This is an online article.
Click through to the pdf version of the article to see more details.
Fuller M, Rao NZ. The Effect of Time, Roasting Temperature, and Grind Size on Caffeine and
Chlorogenic Acid Concentrations in Cold Brew Coffee. Scientific Reports. 2017, 7, 17979.
Web of Science is one of the most broad science databases we have here at USC. This database
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covers resources from all fields of physical sciences, life sciences, and engineering, in addition to
the social sciences and humanities.
11. Click on Web of Science and do a topic search on the “formation of peroxides” (quotes are not
required). Like PubMed, you will see a filter tool on the left side. Experiment by selecting and
deselecting various filters. Pick an article that seems interesting to you and find the full-text. Save
the cover page to PDF and attached it onto your assignment. If you cannot find the full-text choose a
different article.
Part IV: Chemical Drawing Software Adapted from Experiment 1: Molecular Modeling, ChemDraw & Excel (U.
Colorado Boulder)
Chemical drawing software assists chemists in representing both simple and complex chemical
structures in 2D form. All professional correspondences, articles, and presentations use compounds
drawn on this type of software. These drawings will be required for any formal lab report in future
classes. This part of the assignment will allow you to become comfortable with ChemDraw
Professional and test your ability to draw organic compounds.
ChemDraw Professional (PC and Mac) is available for download to personal computers for all
current USC students, faculty, and staff. The download link and instructions are available on the
course libguide under the tab Chemical Drawing Software. If you do not want to download this
software to your computer or do not have a computer, the software is available in the ITS computer
labs. A demonstration of the software will be given during the lab lecture period.
After drawing your structures in ChemDraw Professional, you will be exporting them to Microsoft
Word to print and submit. Depending on your operating system and version of Word, you might
encounter compatibility issues with inserting the drawing directly into Word. In these cases, the
best workaround is to save your ChemDraw Professional file as an image file (.gif, .jpg, .png, .tif,
or .emf should all work) then insert them into Word as a picture.
A quick warning, if you open your Microsoft Word document on a computer without ChemDraw
Professional, your structures will appear as gray boxes. Please make sure to print your document
before you leave the computer lab.
When you launch ChemDraw Professional, you will see various toolbars and a blank document. On
the left side you will see the main toolbar including single, double, and triple bonds, hash marks,
wedges, pre-drawn rings, and a text editor.
12.
Draw the structure shown below. It does not have to be tidy. Copy the structure
into a blank Word document. Label the structure as #1.
13. Draw the following molecule and copy it into your Word document. Label the structure as #2.
16
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NH
14. Draw the structures shown below and copy them into your document. Label the rings #3 and #4
respectively.
Br
OH
OCH3
HN
R
ChemDraw also allows drawing a reaction mechanism so you can visually show someone how you
got from reactant A to product B. On the left side you will see a tool that looks like an arrow.
15.
Can you duplicate the reaction drawing below? It does not have to be tidy. Hint:
draw the reactant and copy and paste it as the product and make the change to the double
bonded oxygen. Copy and paste the completed reaction into your Word document labeled as
#5.
Br
O
Br
HO
H2N
H2N
Br
Br
O
O
Sometimes the drawings can get messy. The bond lengths are different, the angles can look funny,
and the proportions are off. ChemDraw Professional has several tools to help clean up your
drawings.
Structure à Clean Up Structure (Ctrl+Shift+K): when your structure highlighted, this feature will
align bonds, adjust angles, and make the drawing neater. You may need to repeat this several times.
Object à Align: when multiple drawings are selected, this tool aligns the highlighted drawings one
of six different ways. Most often you will use align T/B (top/bottom) centers.
Object à Distribute: when multiple drawings are selected, this tool evenly spaces out the drawings
either horizontally or vertically.
16. Take the drawings from questions 12-15 and use the cleanup tools on them. Then copy and
paste these cleaned up drawings into your Word document. Label the set of drawings as #6.
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The grouping features allows you combine multiple drawings into one. This makes copying and
pasting the drawing much easier. Usually you will use grouping only after you have used the
cleanup tools on your drawings.
17. Draw the reaction scheme below. Make sure to clean up each individual drawing first, then align,
and finally group the drawings together. Copy and paste into your Word document and label the
drawing #7.
HBr
Br
ChemDraw Professional has the ability to analyze certain properties of a drawn molecule. Go to View
à Show Analysis Window.
18. Draw the following molecule and open the analysis window. Copy and paste the drawing into your
Word document and include the information provided on the analysis window. Label your drawing as
#8.
O
O
18
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2
Solubility
Introduction
Solubility is a fundamental topic in organic chemistry that can best be understood with a hands on
experience. Solubility is really controlled by intermolecular forces. However a simple, empirical rule is
very useful. That simple rule is “like dissolves like” and it is based on the polarity of the system, i.e.
polar molecules dissolve in polar solvents, e.g. water and alcohols. This is why ionic compounds like
table salt, sodium chloride, or compounds like sugar, dissolve in water but not most organic solvents.
The polarity of molecules is determined by polar bonds due to the presence of electronegative atoms,
e.g. nitrogen and oxygen, in polar functional groups such as amines (-NH2) and alcohols (-OH).
The solubility of a solute, dissolved substance, in a solvent, the dissolving medium, is the most important
chemical principle underlying three major techniques you will study in the organic chemistry laboratory:
crystallization, extraction and chromatography.
You will determine whether a solid organic compound is soluble or insoluble in a given solvent. You
may notice that some solids may be partially soluble in a given solvent. If the organic compound being
dissolved in a solvent is a liquid, then we refer to the compound and the solvent as miscible, mix
homogeneously in all proportions. Likewise, if the liquid organic compound is insoluble in the solvent,
then they are immiscible, do not mix and form two phases.
Objectives
•
•
Make predictions about solubility and build your chemical intuition
Understand how structure affects solubility
Safety Hazards
•
•
•
•
WEAR GLOVES, GOGGLES, AND PROTECTIVE CLOTHING AT ALL TIMES
MANY organic compounds are flammable and potentially carcinogenic. Work in the fume
hoods at all times. Dispose of all excess organic solvents in the organic waste containers.
HYDROCHLORIC ACID (HCl), an aqueous solution, is corrosive and causes chemical burns.
Wash affected area with water for 15 minutes.
SODIUM HYDROXIDE (NaOH) aqueous solution is corrosive and causes chemical burns. Use
caution when transferring solutions.
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Procedure
For each of the following pairs of liquid
compounds, predict if the pairs will be miscible or
immiscible. It is best to make your prediction for
each pair after you have complete B. Then add 1
mL of both liquids to the same test tube. Use a
different test tube for each pair.
You will work in GROUPS of 2.
WASTE REMINDER: Dispose of all waste in the
designated waste container. No waste from this lab
should be poured down the sink
A. Solubility of Solid Compounds
Mix the contents of the test tube, using a pipet and
pipet bulb to push air through the mixture. Continue
for 10-20 seconds to determine if the two liquids are
miscible, form one layer, or immiscible, form two
layers. Record your results in your table.
Place about 40 mg of biphenyl into each of two dry
test tubes. Don’t worry about exact measurements,
you can be off by 1-2 mg and the experiment will
still work. Label the test tubes and then add 1 mL of
water to the first tube and 1 mL of hexane to the
second tube.
Mixtures:
Determine the solubility of each sample in the
following way; using the rounded end of a spatula,
stir each sample continuously for 60 seconds by
twirling the spatula rapidly.
•
•
•
•
•
After 60 seconds, note whether the compound is
soluble, dissolves completely, or insoluble, none of
it dissolves. If all but a couple granules have
dissolved, then you should state that the sample is
soluble.
water and ethanol
water and diethyl ether
water and methylene chloride
water and hexane
hexane and methylene chloride
D. Solubility of Organic Acids and Bases
Place about 30 mg of benzoic acid into each of three
dry test tubes. The mass and volumes are
approximate in this experiment. Do not spend too
much time try to get exact amounts. We will save
that for future experiments.
Record the results, in the table on the results page.
Now repeat the directions given above with succinic
acid. Record the results.
For each solubility test, add 1 mL of solvent, water
or hexane, to a test tube. Then add one of the
alcohols, methanol or 1-octanol, dropwise. Shake
the tube after adding each drop.
Ø Label Test Tube 1 – add 1 mL of water
Ø Label Test Tube 2 – add 1 mL of 1.0 M
NaOH
Ø Label Test Tube 3 – add 1mL DCM (also
known as dichloromethane or methylene
chloride)
Continue adding the alcohol until you have added
10 drops. If you see one layer, the liquids are
miscible, soluble. If you see two layers, they are
immiscible.
The flow chart should be written in your lab
notebook as part of the pre-lab assignment, fill it
out as you go! This is part of your in-lab
observations.
Record your results, miscible or immiscible, in the
table on the results page.
Take Test Tube 1 and swirl for 10-20 seconds, note
whether the compound is soluble or is insoluble.
Record your results in the table/flow chart.
B. Solubility of Different Alcohols
C. Miscible and Immiscible Pairs
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Ø Recap all reagents after use
Ø Dispose of organic solvents in Organic
Waste container
Ø Dispose of aqueous mixtures in the
Aqueous Waste container
Ø Decant immiscible mixtures and dispose of
them properly
Ø In the fume hood, RINSE any pipet
containing acid or base into a wash beaker,
using acetone, before placing the pipet into
the glass waste container
Now take Test Tube 2 (the tube containing benzoic
acid and 1.0 M NaOH) and add 0.5 mL of 6 M HCl
to the mixture. Swirl the tube for 10-20 seconds.
Record this result in the table/flow chart.
Now take Test Tube 3 and add 1 mL of water.
Swirl the tube for 10-20 seconds. Fill in the flow
chart, where do you think benzoic acid is soluble?
Clean-up
Critical Thinking & Analysis
•
•
•
•
•
•
Go through the solubility tests that you ran today and discuss your results in terms of polarity. Hint:
polarity of the solvent vs. polarity of the solute.
In Part A and Part C, is hydrogen bonding possible? If so, draw the interactions to illustrate hydrogen
bonding.
Discuss your predictions and results. Were any of your predictions wrong? Explain.
Discuss the results for the in which 1.0 M NaOH (aq) was added to benzoic acid. Write an equation for
this reaction in the space provided under Part D.
o Include an explanation and an equation
Did you see a similar result with 6.0 M HCl (aq)?
o Include an explanation and an equation
If a student dissolved benzoic acid in DCM and then added aqueous sodium hydroxide, how many
layers would form? Would benzoic acid still be present? In which layer? Use a flow chart or equations
to accompany your explanation.
21
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Tables & Flow Charts – DRAW IN PRE-LAB
Part A:
Compound
Water Prediction
Water Result
Hexane
Prediction
Hexane Result
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
Observations
O
HO
OH
O
Part B:
HO
Compound
Water Prediction
Water Result
Hexane
Prediction
Hexane Result
HO
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
soluble / insoluble
22
Observations
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Part C:
Mixture
Prediction
Result
water/ethanol
miscible / immiscible
miscible / immiscible
water/diethyl ether
miscible / immiscible
miscible / immiscible
water/hexane
miscible / immiscible
miscible / immiscible
water/dichloromethane (DCM)
miscible / immiscible
miscible / immiscible
hexane/dichloromethane (DCM)
miscible / immiscible
miscible / immiscible
Part D:
Equation 1:
Equation 2:
23
How many
layers are
formed?
Observation
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test tube 1
test tube 2
O
O
OH
OH
what did you add?
what did you add?
chemical rxn?
yes / no (circle one)
draw structure
chemical rxn?
yes / no (circle one)
draw structure
1. soluble / insoluble ? (circle one)
2. How many phases? ____
3. Draw what makes up each
phase, cross out one if not used.
phase 1
1. soluble / insoluble ? (circle one)
2. How many phases? ____
3. Draw what makes up each
phase, cross out one if not used.
phase 1
phase 2
phase 2
what did you add?
chemical rxn?
yes / no (circle one)
draw structure
1. soluble / insoluble ? (circle one)
2. How many phases? ____
3. Draw what makes up each
phase, cross out one if not used.
phase 1
phase 2
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test tube 3
O
OH
what did you add?
chemical rxn?
yes / no (circle one)
draw structure
1. soluble / insoluble ? (circle one)
2. How many phases? ____
3. Draw what makes up each
phase, cross out one if not used.
phase 1
phase 2
H2O
chemical rxn?
yes / no (circle one)
draw structure
1. miscible / immiscible ? (circle
one)
2. How many phases? ____
3. Draw what makes up each
phase, cross out one if not used.
phase 1
phase 2
What would you add to
move benzoic acid from
one phase to the other?
Add to the flow chart to
show phases. Label one
"organic phase" and one
"aqueous phase."
25
Introduction
Recrystallization is the go-to method of choice when purifying organic solids. An impure solid is dissolved
in a hot solvent followed by solute precipitation. Ideally, impurities remain in solution and the pure desired
product crashes out of solution.
There are three main types of impurities which are likely to present in a crude organic solid:
(1) insoluble material in the solvent
(2) soluble, colored, high molecular weight material
(3) soluble material in the solvent
If a crude sample does not dissolve completely, it may be that some of the impurities are insoluble in the
solvent being used. Insoluble impurities are straightforward to remove by performing a hot filtration.
Carry out a hot filtration by quickly filtering the mixture while close to the boiling point of the
recrystallization solvent. This step allows the desired compound to remain in solution while insoluble
impurities are removed. Gravity filtration is the method of choice since vacuum filtration will cool the
solvent and crystallization of the product may occur.
Soluble, colored and high molecular weight compounds are removed by adsorption onto an added
insoluble material and filtration. Fine charcoal, decolorizing carbon, itself insoluble in common organic
solvents, often strongly adsorbs such colored impurities. Thus, addition of decolorizing carbon to the hot
solution and hot filtration removes colored impurities with charcoal.
Organic chemists view picking a recrystallization solvent more as an art than a science and as you build
your chemical intuition you will gain an understanding of this art. Recrystallization relies on the fact that
solubility increases with temperature. In general, soluble impurities can be eliminated if they have high
solubility in the cold solvent relative to the amount of this impurity in the sample. If the impurity dissolves
to an appreciable extent in hot solvent, one would like it to be quite soluble in cold solvent. In this case,
the impurity will remain in solution when the desired material recrystallizes.
solubility in grams
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3
Recrystallizaiton
high solubility at low temperature
high solubitlity at high temperature
low solubility at low temperature
high solubility at high temperature
low solubility at low temperature
low solubility at high temperature
temperature
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In order to separate the crystalline product from excess solvent quickly, a vacuum filtration is required.
Apply vacuum long enough to remove the solvent. The objective here is to produce a wet cake of
recrystallized solid of uniform thickness. Next, gently add a shallow layer of ice cold solvent to the wet
cake, apply vacuum and draw the wash through the wet cake. Repeat washing step if necessary.
Any purification step leads to some loss of product. After collecting the pure solid, some of the compound
remains in solution in the filtrate. The filtrate is everything that goes through the filter paper. Using
solubility data, the amount of solid lost to the filtrate can be estimated. Solubility is often reported as
grams of solute per 100 mL of solvent (g/100g) at some temperature.
Sample Calculations:
Consider the solubility of phthalic acid in 100 mL water:
18 g/100 mL H2O at 100 oC
0.54 g/ 100 mL @ 15 oC
A student obtained 3.2 g of crude phthalic acid. After recrystallization and drying, 2.5 g of pure
acid was isolated. The percent recovery is determined by dividing the isolated mass by the crude mass of
the compound:
2.5/3.2 x 100% = 78% recovery
A 3.2 g sample of crude requires approximately 20 mL of water for recrystallization:
3.2 g acid x (100 mL/18 g) = 17.7 mL (at the boiling point of the solvent)
In this example, a student heated about 25-28 mL of solvent to boiling and then added the solvent
to the crude acid. After recrystallization and vacuum filtration, the volume of the filtrate was about
20 mL. The amount of product lost to the filtrate can be estimated:
20 mL x (0.54 g/100 mL) = 0.108 g = 0.11 g (at low temperature of the solvent)
Prepare yourself for the laboratory: Question #1
A student performed a recrystallization of phthalic acid and used 15 mL of water as the solvent. Assuming no loss
of solvent to evaporation, calculate the loss of product in the filtrate based on the solubility of phthalic acid.
If desired, or if you do not isolate much product, a second round of crystallization may be performed by
partially evaporating the filtrate to induce more solid to precipitate. Successive amounts of product
obtained in this manner are often less pure than first round since concentrating the filtrate solution may
induce some impurities to precipitate with the product.
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The most common mistake during a recrystallization is to add too much solvent! In order to circumvent
this problem:
1. Heat the solvent to boiling
2. Add solvent in small portions
3. Swirl after each addition
Prepare yourself for the laboratory: Question #2
A student performed a recrystallization and after the solid dissolved, the solution was immediately placed in an
ice bath. Within a few seconds, a large amount of solid formed and was collected by vacuum filtration. The
percent recovery was high but the melting point of the dried solid showed that the solid was contaminated with
impurities. Explain.
In this experiment, you will be given approximately 1 gram each of acetanilide. Draw the structure of the
compound and describe the properties that make the solvent a good recrystallization solvent.
•
acetanilide
EtOH
Objectives
• Perform a recrystallization
• Understand the concept of crystallization
• Understand the concept of temperature and solubility
Safety Hazards!!
• ORGANIC SOLVENTS are highly flammable and potentially carcinogenic. Work in the fume
hoods at all times. Dispose of all excess organic solvents in the organic waste containers.
• WEAR GLOVES at all times. Some solvents are toxic and absorb easily on the skin.
• CHECK GLASSWARE for cracks and chips. Heating chipped or cracked glassware is a safety
hazard.
Procedure
Everyone will work in breakout groups or on
your own.
Once the solvent has started to boil, begin
adding a minimum amount of hot solvent,
dropwise, to start dissolving the assigned
compound. Note: At this point, your flask is still
on the benchtop.
WASTE REMINDER: Dispose of all waste in
the designated waste container.
Since you are starting with 1 gram of material,
a minimum amount may still end up being
around 2-5 mL. So start off dropwise trying to
cover the solid and swirl. Then continue to add
dropwise. Place the flask on the hotplate once
the crystals are covered in solvent.
Start by heating approximately 10 mL of
solvent, in an Erlenmeyer flask containing a
boiling chip, on a hotplate. In a separate
Erlenmeyer flask, weigh out approximately 1 g
acetanilide and add a wooden boiling stick.
Record the mass before moving forward.
Keep the both flasks on the hotplate to ensure
that the solvent stays HOT! Once the solid is
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dissolved turn off the hotplate and set the flask
on the benchtop.
successfully isolated crystals. Leave the flask in
the ice bath for a minimum of 5 minutes. During
this time, start to clean up.
In some cases you may have an insoluble
impurity and guess what? It will not dissolve. A
good rule of thumb is watch for the solution to
stop changing. If you add a few more drops and
nothing changes, most likely you have an
insoluble impurity. While the solution is still
hot, decant the liquid into a dry flask
Next, set up the vacuum filtration apparatus. Wet
the filter paper with cold solvent and filter the
crystals. Use a small amount of ice-cold solvent
to rinse any remaining crystals out of the flask.
Remember: Your product is somewhat soluble in
the recrystallization solvent, therefore the more
you add, even cold, may result in loss. Rinse
sparingly.
Do not disrupt the solution in any way.
Disrupting the solution at this point may cause
premature crystallization and trapping of
impurities. Allow the flask to cool to room
temperature. Once the solution is at room
temperature, place in an ice water bath. At this
point crystals should start to form. If you do not
see crystals, try scratching the inside of the flask
with a stir rod or spatula. As a last resort you
may add a seed crystal from a neighbor that has
Allow the crystals to dry with the vacuum on for
5 minutes. Note: a low melting point will result if
the crystals are not dry. Transfer crystals to a
tared watch glass to continue drying while you
finish cleaning up.
Obtain a melting point for the compound and
calculate the percent recovery.
29
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4
Chromatography
Introduction
Chromatography by definition is the separation of a mixture by passing it through a medium in which the
components move at different rates. Over the course of this year, you will be introduced to TLC, column
chromatography and gas chromatography. The mixtures are in the form of a solution, suspension or vapor.
In gas chromatography, the mobile phase is an inert gas, usually helium, and the stationary phase is a high
boiling liquid coating absorbed on the surface of a granular solid in a column. In thin layer chromatography
(TLC) and column chromatography, the mobile phase is a liquid and the stationary phase is a solid
adsorbent.
Part A - Thin Layer Chromatography
O
OH
benzophenone
diphenylmethanol
biphenyl
Advantages of TLC:
1.
2.
3.
4.
The process from sample preparation to visualization is relatively fast.
TLC plates are cheap and disposable.
Multiple samples can be run simultaneously under identical conditions.
TLC is reproducible.
In thin layer chromatography, the stationary phase is a sheet of glass, plastic or aluminum coated with an
adsorbent. The most common adsorbent is silica (SiO2), however alumina and cellulose plates are
available for TLC. The most important characteristic of a stationary phase is its polarity. Most synthetic
organic chemists rely on TLC to determine if a reaction is complete and if any byproducts were formed
during the reaction. Column chromatography is a purification technique in a large scale, which leads to
isolation of separated compounds. TLC is used to find the proper solvent system to perform a column
separation.
The mixture for analysis starts as a small spot near the bottom of the plate. The mobile phases, in this case
organic solvent carries the compounds up the plate as it moves up the plate by capillary action. Ideally,
each compound in the mixture will move at a different rate up the stationary phase. Since the stationary
phase is very polar, more polar compounds tend to stick to the silica gel while the less polar molecules
migrate up the plate with the mobile phase. There is an equilibrium that occurs between the interactions
of a compound and each phase (stationary/mobile). Separation occurs because some things spend more
time adsorbed on the stationary phase than others.
The variable that you can control in this laboratory is the solvent system. The solvent system refers to
either a single solvent or mixture of solvents that are used as the mobile phase. Adjusting the polarity of
the solvent system can alter the migration of compounds. As you can see in the list provided below, there
are many choices for solvents and solvent mixtures. The substances being separated are adsorbed onto the
30
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stationary phase, but polar solvent molecules are also adsorbed by the stationary phase. Molecules that
are already adsorbed are displaced and “pushed along” by polar solvent molecules. Thus, everything
moves up the plate faster in more polar solvent systems. The eluting power of a solvent is largely a measure
of how well it is adsorbed on the stationary phase, displacing other molecules.
Common Eluting Solvents for Chromatography
Least Eluting Power
Hexane or Pentane
Cyclohexane
Benzene
Chloroform
Ether (anhydrous)
Dichloromethane
Ethyl acetate (anhydrous)
Acetone (anhydrous)
Ethanol
Methanol
Water
Pyridine
Greatest Eluting Power
Acetic acid
The non-polar solvents at the top are often used as a base and a few percent of a stronger eluting more
polar solvent is added. As the eluting power of the added solvent increases, the amount that is generally
added decreases. Solvent such as diethyl ether and ethyl acetate are somewhere in the middle and may be
used in 1-50% combination with hexane. Hexane mixtures are common and easily tunable. Stronger
eluting solvents like methanol cannot be used in more than 10% of the solution or the silica gel will
dissolve in them causing problems with separation. More than 1% of pyridine or acetic acid is not often
necessary, a drop or two is most common. While these two additives are next to each other on the list,
they can have very different effects on a separation depending on the functional groups in the molecules
being separated. Water is very strongly eluting and it’s presence as an impurity in your solvent can be
problematic.
The functional groups of the molecules in your mixture effect how strongly they are adsorbed by the
stationary phase. Very “greasy” non-polar compounds usually made entirely of carbon and hydrogen,
hardly adsorbed by silica gel at all. Polar groups, with oxygen and especially nitrogen are more strongly
adsorbed. The ability to hydrogen bond with the silica gel creates a strong adsorbing interaction in
alcohols, carboxylic acids and amines.
Adsorbability of organic compounds by functional group
Least Strongly Adsorbed
Saturated hydrocarbons; alkyl halides
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Unsaturated hydrocarbons; alkenyl halides
Aromatic hydrocarbons; aryl halides
Polyhalogenated hydrocarbons
Ethers
Esters
Aldehydes and ketones
Alcohols
Most Strongly Adsorbed
Acids and bases (amines)
TLC can be reproduced as long as you know the solvent system that was used to run the plate. The ratio
of the distance the compound travels to the distance the solvent travels remains constant. This ratio is
called the retention factor, Rf value.
!"#$%&'( *+,(! -. $/( #0+$
Rf = !"#$%&'( *+,(! -. $/( #+1,(&$
While having the same Rf value does not prove that two compounds are the same, having different Rf
values demonstrates that they are different.
Objectives
• Perform a separation with TLC
• Understand the concept of polarity and movement between mobile and stationary phases
Safety Hazard!!
• ORGANIC SOLVENTS are highly flammable and potentially carcinogenic. Work in the fume
hoods at all times. Dispose of all excess organic solvents in the organic waste containers.
• WEAR GLOVES at all times. Some solvents are toxic and absorb easily on the skin.
• SILICA GEL is a fine powder that, inhaled over time, causes a disease called “white lung” or
silicosis. All operations with this powder should be performed in the fume hood.
32
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Procedure
Prepare two TLC plates as follows:
WASTE REMINDER: Dispose of all waste in
the designated waste container.
Ø Using pencil, lightly draw a line across the
bottom of the TLC plate
Ø Draw a tick mark perpendicular to the line –
this is the point of origin
Ø Spot the sample on the tick mark
Ø Allow solvent to evaporate
Ø Place into the TLC chamber taking care that
the point of origin is above the mobile phase
(solvent)
Ø Allow sample to elute
Ø Remove from chamber and draw solvent
front
Solvents at your disposal
Least Eluting Power
hexanes
toluene
dichloromethane
diethyl ether
ethyl acetate
methanol
water
Greatest Eluting
Power acetic acid
Prepare yourself for the laboratory: Question #1 From
the solvents listed above, select a single solvent that you
think would give you the best chance of separating
benzophenone, diphenylmethanol and biphenyl using TLC
on silica gel. Explain your reasoning behind your choice.
Keep in mind that phenyl groups are fairly “greasy” and
non-polar
Based on your answers to Question #1, choose
two solvents to start with. Prepare a TLC
chamber with each solvent.
tick mark
spot mixture
elute TLC plate
Spot two TLC plates using the stock solution of
the mixture (benzophenone, biphenyl,
diphenylmethanol) that is dissolved in
dichloromethane. After spotting, allow
dichloromethane to evaporate.
The TLC chamber consists of following pieces:
Ø Beaker – acts as the
chamber
Ø Filter paper – saturates
the environment inside
the chamber to
promote capillary
action
Ø Watch glass – keeps
solvent vapor from escaping and TLC plate
from drying
Ø Solvent – acts as the mobile phase
Ø TLC plate – thin layer of silica (stationary
phase) on a surface
At this point you should have two TLC plates
and two TLC chambers. Each chamber contains
a different solvent. Develop the plates
simultaneously.
After developing the plates, remove them from
the chamber, indicate the position of the solvent
front with a pencil mark, and allow the plates to
dry for a few minutes. Examine them under UV
light, gently circle the spots that you see with
your pencil and make a sketch in your lab
notebook of the appearance of each plate
showing the positions of all spots.
Calculate Rf values for each spot, measuring in
millimeters to the center of the spots.
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Depending on your results from the first TLC
experiment, design and conduct a second TLC
experiment using two other solvents:
the standards. The plate you prepare will then be
spotted four times, once with the mixture and
once with each of the three standards. Be sure to
label the spots. Then develop this final plate
using the best solvent from your earlier
experiments and compare Rf values to confirm
the identity of the three spots in the mixture.
1. If neither of the first two solvents
separated all three compounds on the
TLC plate, then based on the appearance
of each plate, decide if the solvent used
was too polar or not polar enough. Then
select two new solvents that you believe
will change the polarity in the right
direction to achieve separation. Test the
new solvents by preparing and
developing two additional plates
If you were not able to achieve a very good
separation of the compounds in the first or second
experiment, conduct additional experiments (as
time permits) until you achieve a good separation
of all three compounds. Be sure to carefully
consider the results of all previous experiments
to make the best choice of solvents, and make
sketches of all plates in your lab notebook.
2. If one of the first two solvents separated
the three compounds on the TLC plate,
but the other didn’t, then, based on the
appearance of each plate and the relative
polarity of the two solvents, consider how
the polarity might be changed from the
solvent that worked to improve
separation. Test two new solvents to see
if you can improve the separation. There
is more than one solvent which will
achieve this separation.
3. If both the solvents you tested in the first
place provided separation of all three
compounds, conduct a second experiment
to determine if the separation can be
improved by increasing or decreasing the
polarity of the solvent from the two
solvents that worked.
In the second experiment, as with the first, make
sketches of each TLC plate showing the positions
of the spots, and calculate Rf values.
After conducting at least two pairs of TLC
experiments (developing four plates) as
described above and finding one or more solvents
that can be used to separate the three compounds
in the mixture, prepare one final TLC plate in
which you spot the mixture of three compounds
side-by-side with each of the three standards. The
standards are separate, identified solutions of
each compound. Be careful not to contaminate
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fractions of ~1 mL. Note: if you allow the column
to go dry, the separation will be compromised.
Part B: Column Chromatography
Procedure
A yellow band will move down the column. Once
all of the yellow-colored material is collected,
start eluting with diethyl ether. A new band of a
colored material will move down the column.
Continuing adding solvent to the column until
you have collected all of the second compound.
Everyone will work in GROUPS OF 2.
WASTE REMINDER: Dispose of all waste in
the designated waste container.
Prepare
a
microscale
column
for
chromatography. Take a 5” Pasteur pipette and
gently push a small amount of cotton loosely
down into the stem using a wooden stick. Note:
Packing the column too tightly will result in very
slow elution. Place the pipette through a one-hole
rubber stopper and clamp. Fill the pipette 2/3 full
with silica gel.
Prepare yourself for the laboratory: Question #1 Why
is the solvent changed in the middle of the chromatography
procedure?
TLC each of the collected fractions in a 9:1
hexanes/acetone solvent system. Run
no more than four fractions on one
plate.
Run another TLC plate to compare
the isolated fractions with a
standard. Determine the identity of
the isolated compounds. Which
compound is acetyl
Fractions: 1 2 3 4
ferrocene?
Prepare yourself for the laboratory: Question #2 Predict
which compound will come off the column first. Explain.
Fill the column with hexanes and allow the
solvent to saturate the silica and drip into the
Erlenmeyer flask.
As the column becomes saturated, dissolve 25
mg of a 1:1 mixture ferrocene/acetylferrocene in
1 mL of hexanes. Once the hexanes level has
reached the top of the silica gel, transfer the
hexanes solution to the pipette column.
Keep the column wet by adding more solvent
once the ferrocene mixture has reached the top of
the silica. Continue to elute with hexanes. Collect
35
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5
Extraction
Introduction
Extraction is a separation technique that is used in the organic laboratory to isolate one or more
compounds from a mixture. Unlike other separation techniques, extraction does not lead to purified
products. The technique is based on solubility and equilibrium distribution of a substance between two
immiscible phases. For our purposes, the extraction solvent is usually a volatile organic liquid that can
be removed by evaporation after the desired component has been extracted. The desired substance is
usually extracted from an aqueous solution.
A substance is transferred from one immiscible liquid to another based on the extent of solubility in
each liquid; it can be transferred from one liquid to another by shacking or mixing the two liquids
together. Two liquid layers are formed, and the layer that has most of the desired product in it can be
separated from the other. Sometimes not the entire product is extracted in a single operation and the
process must be repeated once or twice more to assure a clean separation. It has been found that
when two immiscible solvents are shaken together, the solute distributes itself between them in a
ratio roughly proportional to its solubility in each. The ratio of the concentration of the solute in each
solvent at equilibrium is a constant called the distribution ratio(d) or partition coefficient (Kd).
The larger the value of Kd, the more solute will be transferred to the ether with each extraction, and the
fewer portions of ether will be required for essentially complete removal of the solute.
Wo/
[solute]o
Co
Vo
Kd =
=
=
Waq/
[solute]aq
Caq
Vaq
Where o and aq refer to organic and aqueous layers, respectively, and Wo and Waq are the weights in
grams of material dissolved in each respective layer. Co is the concentration of the organic solution and
Caq is the concentration of the aqueous solution.
Desirable properties of extractions solvents are listed below:
•
•
•
•
•
It must readily dissolve the substance being extracted but must not dissolve to any appreciable
extent in the solvent from which desired substance is being extracted.
It should extract neither the impurities nor other substances present in the original mixture.
It should not react with the substance being extracted.
It should be readily separated from desired solute after extraction.
It should be reasonably safe to work with and inexpensive
An ideal solvent may be difficult to come by, therefore one will need to find a solvent that satisfies as
many of these criteria as possible.
Some of the solvents commonly used for extracting aqueous solutions or mixtures include diethyl ether,
methylene chloride, hexanes and various mixtures of saturated hydrocarbons from petroleum (petroleum
36
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ether, ligroin, etc.). Each of these has a relatively low boiling point so that it may be fairly easily
separated from the solute by evaporation or distillation. Methanol and ethanol are not good solvents for
extracting aqueous solutions or mixtures because of their solubility in water; however, if an aqueous
solution can be saturated with potassium carbonate without affecting the solute, ethanol can be used to
extract polar solutes from the solution.
This is where you will get introduced to separation schemes. A separation scheme is a flowchart to
identify where a particular compound is at any point in a work-up or purification. Students tend to
struggle with this part of the pre-lab. Read MTC and attend lab lecture for further discussion on
separation schemes.
Objectives
• Perform a separation of a liquid-liquid extraction
• Understand how solubility is a major component of extraction
• Understand acid/base chemistry
• Understand how to use a separation scheme
Safety Hazards!!
• HYDROCHLORIC ACID (HCl) aqueous solution is corrosive and causes chemical burns.
Wash affected area with water for 15 minutes.
• SODIUM BICARBONATE (NaHCO3) aqueous solution is corrosive and causes chemical
burns. Use caution when transferring solutions.
• DIETHYL ETHER is highly flammable and volatile. Work in the fume hoods at all times.
Dispose of all excess organic solvents in the organic waste containers.
• WEAR GLOVES at all times. Some solvents are toxic and absorb easily on the skin.
Procedure
Repeat. Now shake the separatory funnel
vigorously with frequent venting.
Work in pairs.
WASTE REMINDER: Dispose of all waste in
the designated waste container.
Remove the stopper from the top of the funnel
and allow the mixture to separate into two
sharply defined layers. Drain off the lower layer
in a 125 mL Erlenmeyer flask, labeled as A.
Which layer is this? Aqueous or organic?
In a 125 mL Erlenmeyer flask, dissolve 1 g of a
mixture containing biphenyl and benzoic acid in
15 mL diethyl ether.
Transfer the mixture to a 125 mL separatory
funnel that is held on a ring stand. Use a small
quantity of ether to complete the transfer by
washing any remaining mixture from the
Erlenmeyer flask. Add 20 mL saturated aqueous
sodium bicarbonate to the separatory funnel.
Repeat extraction two more times by adding
another portion of sodium bicarbonate.
Slowly and cautiously add 6 M HCl dropwise, at
first, to flask A until precipitate begins to form.
At that point check the pH using pH paper for
confirmation. Continue adding 6 M HCl until pH
3, ~7 mL. To spot the pH paper, use a glass stir
rod and spot the pH paper.
Stopper the funnel, invert the funnel and open the
stopcock to vent the liberated carbon dioxide.
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Once acidified, cool the Erlenmeyer flask in an
ice water bath. Isolate A by vacuum filtration.
Note: turn the vacuum on slowly or you may have
to redo the filtration. Wash the collected
precipitate with a small amount of cold water.
Determine the mass of the crystals A and B in
mixture and obtain a melting point. Predict which
compound is which. Compare the observed
melting point with the literature value.
Calculate the percent recovery of the original
mixture. The percent recovery will be equal to
the mass of two compounds divided by the
amount of the original mixture that you started
with, multiplied by 100%. What does this tell you
about your extraction technique?
Allow crystals to dry in the oven while you
continue on with the isolation of B. This solution
contains B.
Take B and dry it by adding anhydrous sodium
sulfate. Decant the solid drying agent and collect
the dry ether filtrate in a separate tared 8-dram
vial. Cover and take the flask to the nitrogen
evaporate (NEVAP) where a TA will add the vial
to the queue.
Calculate the mass percent of each of the two
compounds. Take the mass of one compound and
divide it by the total mass of the compounds
isolated, multiply by 100%.
What is the ratio of benzoic acid to biphenyl?
38
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6
Distillation
Introduction
Everyone has had experience with the boiling point of water at some point, whether boiling water to make
pasta or brew coffee. At the boiling point liquid water is converted to gaseous water, or steam. A substance
will boil only when the vapor pressure of the liquid is equal to the external pressure being applied by the
surroundings. In this experiment, you will heat a mixture of organic liquids to their boiling points. We can
take advantage of this physical property and separate liquids with different boiling points. The process of
heating a substance until it vaporizes followed by cooling the vapors and collecting the condensed liquid
is the basis for the purification technique of distillation.
Distillations can be used to efficiently purify volatile, low boiling, compounds. The general concept of
distillation involves the boiling of a mixture, resulting in the lower boiling compound boiling off and
being collected first.
Objectives
• Perform a separation of a liquid mixture by distillation
• Understand the concept vapor pressure and boiling point
• Understand the difference between simple and fractional distillation
• Use gas chromatography to observe the efficiency of simple versus fractional distillation
Safety Hazards!!
• ORGANIC SOLVENTS are highly flammable and potentially carcinogenic. Work in the fume
hoods at all times. Dispose of all excess organic solvents in the organic waste containers.
• WEAR GLOVES at all times. Some solvents are toxic and absorb easily on the skin.
• CHECK GLASSWARE for cracks and chips. Heating chipped or cracked glassware is a safety
hazard.
Procedure
You will be given a mixture that contains a 1:1
ratio of hexane & toluene.
Method 1. Simple Distillation
One group member
You will be assigned either simple or fractional
distillation, by your TA when you arrive in lab,
prepare for both. You will collect data from the
other student in your hood.
Before coming to lab, draw a table of temperature
and volume. This is the data you will need in
order to plot the curve of distillation in your postlab.
WASTE REMINDER: Dispose of all waste in
the designated waste container.
Measure out 20 mL of the 1:1 mixture of
hexane:toluene into a graduated cylinder.
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Transfer the mixture to a 25 ml round bottom
flask containing a boiling chip.
to your TA for GC analysis.
Now, adjust the heat input to get a moderate,
steady distillation rate; ~15-20 drops per minute
is reasonable, half of that will give a sharper
breaking distillation curve.
Connect the flask directly to the simple
distillation still head. Place the flask onto the
aluminum block sitting on a hotplate. Using a
clamp, secure the apparatus by clamping the
flask.
In a table in your notebook, prepared in advance,
record total distillate vs. boiling temperature.
Record data for every 0.5 mL collected. Note: Do
not write your table on the same page as your prelab since you will have to turn that in upon arrival
to lab.
Make sure the apparatus is vertical and straight.
Carefully insert the thermometer into the
distillation still head, so that the bulb of the
thermometer rests just below the opening of the
side arm of the still head.
Collect distillate in your 10 mL graduated
cylinder. Continue collecting until you have
collected ~10 mL. Comment on what you
observe.
Begin heating the mixture using a setting of ~5.
Record the initial temperature at which the
distillate first starts to collect. Allow the mixture
to boil until at least 0.5 mL of distillate has been
collected.
Method 2. Fractional Distillation
Second group member
Record the maximum temperature at which the
distillate was collected. Transfer 0.5 mL of
distillate to a GC vial using a glass pipet.
Same as Method 1 with the exception of a
fractioning column placed between the round
bottom flask and the simple distillation still head.
The fractioning column is simply an air
condenser loosely packed with a portion of
copper sponge
Give the clearly labeled GC vial:
•
Name, TA, section number, expt #
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7
Synthesis of Methylbutenes
Acid Catalyzed Dehydration of 2-Methyl-2-Butanol
HO
H2SO4
H3PO4
2-methyl-2-butanol
Δ
2-methyl-1-butene
2-methyl-2-butene
Introduction
There are three distinct steps in most organic preparative reactions:
1. the reaction itself
2. isolation of the final product
3. final product purification
In some instances, as in the dehydration of an alcohol, it is necessary to combine the first two steps so that
the product can be removed from the reaction mixture as it is formed. This serves to drive the equilibrium
toward alkene formation and to minimize the possibility of oxidation or polymerization of the alkene.
The phenomenon of steam distillation is observed in this experiment. Any water initially present in the
mixture, and additional water formed as a result of the reaction, is immiscible with the alkene product. In
the distillation experiment we learned that in a mixture, of two miscible liquids, the total vapor pressure
is the sum of the partial pressures of each component. There is a different situation in the distillation of a
mixture of two compounds that are not mutually soluble. In this case, each liquid exerts its own vapor
pressure independently of the other.
As long as separate phases are present in the liquid, the mixture will have a constant boiling point that is
lower than the boiling point of either component. In addition, the distillate will have a constant
composition, which is determined by the ratio of the vapor pressures.
Objectives
• Perform a dehydration reaction
• Analyze the final product ratio by GC and NMR
• Qualitatively analyze by IR
• Understand the concept of steam distillation
Safety Hazards!!
• PHOSPHORIC ACID (H3PO4) and SULFURIC ACID (H2SO4) are corrosive and cause
chemical burns and should be handled with great care. Wash affected area with water for 15
minutes.
• WEAR GLOVES at all times. Some solvents are toxic and absorb easily on the skin.
• CHECK GLASSWARE for cracks and chips. Heating chipped or cracked glassware is a safety
hazard.
Chemical Data Table:
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Compound
MW
(g/mol)
BP
(°C)
MP °C
d (g/mL)
Safety
88.15
101 to
103
-9
0.805
Flammable, Harmful
70.13
39
−134
0.662
Flammable
70.13
31
-137
0.650
Flammable
H2SO4
98.08
337
10
1.84
Highly Corrosive and
irritant
H3PO4
98
158
42.35
1.88
Highly Corrosive and
irritant
•
Procedure
Tare a 5 mL conical vial and add 3 mL of 2methyl-2-butanol. Reweigh the vial to determine
an accurate weight of the alcohol. Add 4 drops
of 85% phosphoric acid and 6 drops of
concentrated sulfuric acid.
the Hickman head and transferring it to a 3 mL
conical vial with a cap. Immediately cap the vial
after the transfer is complete.
Note: The cap on the side-arm and the 3 mL
conical vial should be capped at all times except
when liquid is being added or removed.
Caution! Phosphoric acid and sulfuric acids are
strong and corrosive chemicals and should be
handles with great care.
Continue collecting until ~0.5 mL remains in the
5 mL conical vial. Caution! Never let a vessel
boil to dryness.
Place a spin vane in the vial and assemble the
distillation apparatus as shown in lab slides and
MTC2.
Slowly stir and slowly heat the reaction mixture
in the beginning. The distillation should take
~30-45 minutes. Note: If you distill too quickly
the product will be contaminated with acid.
When the distillation is complete, remove as
much distillate as possible from the Hickman
head and transfer to the 3 mL conical vial. Then,
using a Pasteur pipet, rinse the sides of the inside
wall of the Hickman head with 1.0 mL of brine.
Do this thoroughly so that as much liquid as
possible is washed down into the well of the
Hickman head. Transfer this to the 3 mL conical
vial.
As distillate starts collecting in the Hickman head
well, remove using a Pasteur pipet. Distillate is
removed by removing the cap on the side-arm of
Allow the layers to separate and remove the
bottom aqueous layer. Dry the organic phase
over anhydrous sodium sulfate. Cap the 3 mL
Prepare yourself for the laboratory: Which olefin should
predominate in the dehydration of 2-methyl-2-butanol?
Explain.
42
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conical vial and set aside for 10-15 min to
remove the last traces of water. Use this time to
clean up!
Critical Thinking & Analysis
• Briefly discuss the theory behind
chromatography (why is it used?). What
information can one obtain from it etc.
• Discuss how you identified the isomers
• Were the two alkenes products formed in
equal amounts? in a ratio that equals the
statistical probability of forming each
alkene? Hint: Think of the number of protons
on a particular carbon that can be removed.
• What controls the observed ratio of the
product formation?
• Include the mechanism for the formation of
both products using ChemBioDraw
• Analyze the GC and NMR spectra and
include in your online submission.
• Find an IR for the starting material and
product. Analyze, compare and include in
your report.
Carefully transfer as much distillate as possible
to a tared GC vial with a cap. Weigh the product
and calculate the percent yield.
Analyze the product by making a GC and NMR
sample.
Clean Up
Cautiously, neutralize the pot residue with
sodium bicarbonate solution and discard in the
aqueous waste container. Flush the distillation
apparatus with water and acetone. Discard
washings into the aqueous waste.
43
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8
Predicting Organic Reactions
A studio-based organic experience designed by:Dr. Jeremy Cody and Dr. Tina Collison
Part I.
1. A bond is made up of ___________________________________________________.
Arrow pushing is a way organic chemists show the movement of electrons. Thus we use arrows to indicate
bond making and bond breaking.
2. The molecule drawn below has a chlorine attached. Halogens are great leaving groups.
a. Indicate the partial charges for the alkyl chloride species below (use δ+ and δ-.)
b. Will the nucleophile (Nu:─) attack the δ+ or the δ-?
c. If a nucleophile (Nu:─) attacks AT THE SAME TIME that the chlorine leaves,
i. Use an arrow to show the bond being formed and WHERE the new bond will be formed
ii. Use an arrow to show the bond that’s breaking and WHERE those electrons will go
iii. Draw the organic product (A) and give the by-product (B) (Don’t forget your charges)
Nu:
solvent
+
A
+
B
C
Cl
3. The following reaction is an example of a precipitation reaction you have seen in general chemistry. BaCl2
and Na2SO4 have an (aq) after them meaning they are soluble in water….they are IN solution.
BaCl2 (aq) + Na2SO4(aq)
BaSO4 (
)
+
2NaCl(
)
a. Using the solubility chart given, fill in the parentheses for BaSO4 as either aq (soluble in water), or s
(precipitates/not soluble in water)
b. Using the solubility chart in Appendix I of this worksheet, fill in the parentheses for NaCl as either
aq (soluble in water), or s (precipitates/not soluble in water)
4. Given the exercise in #3, how might you design an experiment to test that a reaction shown in #2 is
occurring in your test tube?
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Experiment I:_________________________________________
1-chlorobutane will undergo a reaction with all three of the following nucleophiles. Only one
nucleophile has a solubility trend that will allow for the reaction to be VISUALLY observed.
Nucleophile
NaCl
Soluble in:
Water, glycerol, ethylene
glycol, formic acid
NaBr
NaI
Water, methanol
Water, ethanol. acetone
Electrophile
1-chlorobutane
Soluble in:
diethyl ether, hexanes,
acetone, tetrahydrofuran
Given the information above, write a balanced equation using 1-chlorobutane as the electrophile
that would VISUALLY demonstrate a reaction such as the one described in question #2.
Equation: (use structures and not names)
Once your equation has been approved by the instructor, go to your hood use the general
procedure handout to perform the experiment.
IN YOUR NOTEBOOK: (title and date)
•
•
•
Record the Balanced Equation you tested
Record the Procedure you followed using actual reagents.
Record the observations you made in a Data Section
Discuss the following questions in your group and then answer the questions on this worksheet.
a) What did you expect to observe?
b) What did you observe?
c) How would one determine that the experiment was successful?
d) Was your experiment successful?
5. (15 minutes) Let’s take a look at the GENERAL reaction below:
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Nu:
R
solvent
+
C
Nu
R
+
X
R
R = alkyl groups or hydrogens
C
R
R
X
R
Given your proposed electron pushing mechanism, list as many factors that could play a role in the
success or failure of the reaction:
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
Add any of your NOVEL suggestions from above to list being generated on the board.
Class Assessment: (Save this section for after class discussion)
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
46
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Experiment II:_________________________________________________________________
In order to test some of your hypotheses from the previous page, the following compounds will be made available to you. Design a minimum of
FOUR experiments that would test some of the concepts from your list in question #5. For each experiment you will use an 18% NaI solution in
acetone.
Cl
Cl
Br
Cl
Br
In your notebook:
Briefly describe the experimental procedure for the substrates you tested. You can allude to the procedure that you already wrote
up for Expt. I if it is the same. Be sure to indicate any changes made to the procedure and to indicate which substrates you tested.
Set up a chart like the one below and fill it in
Experimental Equations to Test
What do I expect to see?
Once you are done, report your findings to the TA.
47
What did I observe?
Cold
/
Hot
Conclusions
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Bringing it all together
The reactions we have just studied are called nucleophilic substitution reactions.
There are two types of nucleophilc substitution reactions: SN1 and SN2
What we just looked at was called SN2:
______________________________________________________________________________
Example: (R = alkyl or H group)
R
+
Nu
R
R
X
Nu
R
R
+
X
R
Given that in the name it’s a second order reaction, let’s write a rate equation that describes this
reaction:
6. Now tell me what would happen to the rate if the concentration of Nu─ was doubled?
_______________
7. Now tell me what would happen to the rate if the concentration of the alkyl halide was
doubled?_______
8. Given the mechanism on page 3, is there
an intermediate? (Y/N)_______
9. Given the mechanism on page 3, is there a
transition state? (Y/N) _______
10. Are transition states maxima or minima?
_____________________
11. Draw an Energy diagram that illustrates
an SN2 reaction using the space to the left.
Energy
R
+ Nu:
R
R
X
Rxn Coordinate
Stereochemical Considerations
Let’s consider the SN2 reaction below:
48
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H3C
CH3
H
I
C
Br
C
I
H3CH2C
+ Br
H
CH2CH3
12. What is the hybridization (sp, sp2 or sp3) the carbon that the Br is attached to in the starting
material?_________
13. Is this carbon a 1˚, 2˚ or 3˚ bromide? ______
14. Was the absolute stereochemistry of the starting material R or S? _______
15. Is the absolute stereochemistry of the product R or S? _________
16. Is this called inversion or retention of stereochemical
configuration?______________________
17. In order for the carbon to change its configuration, the transition state must be planar. In the
brackets above, draw the transition state for the SN2 reaction.
• Remember that when drawing a transition state, bonds being formed are drawn as dotted
lines and bonds being broken are drawn as dotted lines.
•
Note that the Nu and Br dotted lines should be 180˚ relative to one another.
Part II.
Given the SN2 reaction (A) we just took a look at:
(A)
H
+
I
H3C
H
C
Br
I
C
H3CH2C
+
CH3
Br
CH2CH3
S
R
100%
100%
Examine the following SN1 experimental observation from reaction (B): (This is NOT an SN2 reaction)
(B)
I
+
H3C
C
Br
I
C
CH3
+
H3C
C
S
R
S
100%
50%
50%
49
I
+ Br
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18. What is (are) the major difference(s) between the reactions (A) and (B)?
19. What must happen mechanistically before the Nucleophile can attack if we are to see the S
product?
20. This transformation goes through a planar reactive intermediate. As such, what is formed on
the electrophile if what you propose in question #19 above occurs?
21. If the intermediate you propose in question #20 is formed, it must be stabilized. What about the
structure of the electrophile would stabilize this intermediate?
22. Using the reasoning from questions 18-21, explain why experimental observation A did not
undergo the same mechanistic transformation that was observed in B.
50
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Experiment III:________________________________________________________________
Ethanolic silver nitrate allows the following to occur: R
d+
d+
Ag+
R
X
X
R
Ag
+ AgX (s)
In order to test some of your hypotheses about SN1 from the previous page, the following compounds will be made available to you. Design a
minimum of FOUR experiments that would test your hypothesis from page 7. For each experiment you will use a 1% AgNO3 solution in EtOH.
Cl
Br
Cl
Cl
Br
I
In your notebook:
Briefly describe the experimental procedure for the substrates you tested. You can allude to the procedure that you already wrote up for
Expt. I and II but using the correct nucleophilic solution. Be sure to indicate any changes made to the procedure and to indicate which
substrates you tested.
Set up a chart like the one below and fill it in
Experimental Equations to Test
What do I expect to see?
Once you are done, report your findings to the TA.
51
What did I observe?
Cold
/
Hot
Conclusions
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Bringing it all together
23. Compare a reaction you ran from experiment II (NaI in acetone) with an experiment run in
experiment III (AgNO3 in ethanol) using the same substrate.
Now let’s discuss SN1: __________________________________________________
SN1 Overall Reaction:
R
+
Nu:
R'
C
R
X
Nu
R
C
R'
R"
"R
+
R'
C
"R
Nu
Given that in the name, this is a first order reaction, let’s write a rate equation that describes this
reaction:
24. Now tell me what would happen to the rate if the concentration of the alkyl halide was
tripled?_______
25. What would happen to the rate if the Nu was doubled? _________
26. Draw an Energy diagram that illustrates this reaction:
Energy
X
Rxn Coordinate
SN1 Overall Reaction:
52
+
X
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R
C
Nu
R
R'
R"
+
Nu:
C
R'
+
X
+
R
"R
C
R'
Nu
"R
Explain what effect the factors below have during an SN1 reaction:
1. Strength of Nucleophile?
2. Steric effects on Nucleophile?
3. Leaving Group effects?
4. Substituent effects of electrophile?
Stereochemistry:
I
+
H3C
C
Br
I
C
100%
CH3
+
H3C
50%
C
I
+ Br
50%
27. Was the absolute stereochemistry of the starting material R or S? _______
28. Is the absolute stereochemistry of the product(s) R or S? _________Explain___________
________________________________________________________________________
________________________________________________________________________
29. Thus, SN1 mechanisms will give us a _______________mixture.
Let’s Sum up!
SN 1
Nucleophile
Substrate (R-X)
Leaving group
Stereochemistry
Rearrangements*
Solvent*
53
SN 2
X
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*Topics will be discussed in more detail during the lecture
Here’s a handy checklist for assessing whether a reaction will most likely proceed
via an SN1 or SN2 process:
In this order assess:
1. The electrophilic substrate 1°, 2°,3°
2. The stability of a potential carbocation
3. The strength of the nucleophile (neutral or negatively charged?)
Solubility Rules for Ionic Compounds in Water
A. SOLUBLE COMPOUNDS
1. Group 1 Elements
Compounds containing Na+, K+, and Li+ are generally soluble.
2. Ammonium Ions
Compounds containing NH4+ are usually soluble.
3. Nitrates
Compounds containing NO3-are usually soluble.
4. Acetates
Compounds containing C2H3O2- are usually soluble.
5. Chlorates and Perchlorates
Compounds containing ClO3- and ClO4- are usually soluble.
6. Halogens
Compounds containing chlorides (Cl-), bromides (Br-), and iodides (I-) are usually soluble.
• Exceptions: Combinations with Ag+, Hg 2+ , or Pb 2+ .
7. Sulfates
Compounds containing SO42- are usually soluble.
• Exceptions: Combinations with Ca 2+ , Sr 2+ , Ba 2+ , Pb 2+ , Hg+ , and Ag+ .
B. INSOLUBLE COMPOUNDS
1. Carbonates
Compounds containing CO32- are generally NOT soluble.
• Exceptions: Combinations with Group 1 Metals or NH4+
2. Phosphates
54
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Compounds containing PO43- are generally NOT soluble.
• Exceptions: Combinations with Group 1 Metals or NH4+
3. Sulfides
Compounds containing S2- are generally NOT soluble.
• Exceptions: Combinations with Group 1 Metals, Group 2 Metals or NH4+
4. Hydroxides
Compounds containing OH- are generally NOT soluble.
• Exceptions: Combinations with Group 1 Metals or Group 2 Metals.
55
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9
Sodium Borohydride Reduction of Vanillin
Adapted from Sodium Borohydride Reduction of Vanillin –C.S. Lecher
Introduction
Vanillin is a pleasant smelling aromatic compound that occurs naturally in the pods of the vanilla plant
(Vanilla planifolia). As with most natural products, vanilla from the source is the best quality, however
synthetic vanilla is far less expensive to isolate. Vanilla is used as an aromatic additive for candles,
incense, potpourri and fragrances. It is also used as a starting material for the synthesis of such drugs as
L-dopa, which is used for treating Parkinson’s disease.
Vanillin will be reduced in this experiment to vanillyl alcohol. In chemistry, reduction refers to the gain
of electrons. Generally, the addition of hydrogen atoms or a loss of oxygen atoms, or both, signifies a
reduction has occurred. In this experiment, a carbonyl group is being reduced to an alcohol.
When lithium aluminum hydride (LiAlH4 or LAH) was introduced as a reducing agent in the late
1940’s, it brought about a revolution in the preparation of alcohols by reduction. At the time, the most
popular reducing agents for carbonyl compounds were sodium metal and gaseous hydrogen under
pressure. The greater simplicity and convenience of hydride soon made it the preferred method for a
broad range of chemical reductions. Lithium aluminum hydride is a powerful reducing agent which is a
disadvantage when there are multiple functional groups present in a molecule that are susceptible to
reduction. Since it violently reaction with water, alcohols and phenols to produce hydrogen gas, it can be
used only in aprotic solvents, such as anhydrous ether.
On the other hand, sodium borohydride (NaBH4) is a milder reducing agent, so much so that you can
easily handle it in the solid form. Unlike LAH, it can be used in aqueous or alcoholic solutions.
The overall stoichiometry of sodium borohydride reduction of vanillin is given by the following
equation:
O
OH
H
4
+
NaBH4
+
4 H2O
+
4
HO
HO
O
H3BO3
NaOH
O
In practice, it is best to use an excess of 50-100% to compensate for any reactions with the solvent or
decomposition from sitting on the shelf. Please be courteous to your lab mates and keep the lid on
sodium borohydride to prevent decomposition.
Reductions like the one carried out in this experiment are generally run in a dilute (~1 M) aqueous
NaOH solution or an alcohol solvent. The reagent is not stable at low pH or in neutral aqueous solutions.
Sodium borohydride reacts slowly with alcohols, but methanol and ethanol are usually suitable solvents
when there are no acidic functional groups and the reaction time is no more than 30 minutes at room
temperature.
56
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The course of the reaction will be monitored by TLC and followed by reaction work up. The product can
be purified by any method based on its physical state and properties. Vanillyl alcohol is soluble in hot
water, hot and cold methanol, and hot and cold ether. It is relatively insoluble in cold water and tends to
form supersaturated solutions in water.
Caution!
Hydrochloric acid is corrosive and a chemical burn hazard. Avoid contact. If contact is made with skin,
wash the affected area with cold water for 15 minutes.
Sodium borohydride is caustic and will decompose violently with acid. Handle with care.
Objectives
• Perform a reduction reaction
• Follow the reaction in real-time by TLC
• Compare the IR of the starting material to the product formed
Safety Hazards!!
• SODIUM HYDROXIDE (NaOH) aqueous solution is corrosive and causes chemical burns. Use
caution when transferring solutions.
• ORGANIC SOLVENTS are highly flammable and potentially carcinogenic. Work in the fume
hoods at all times. Dispose of all excess organic solvents in the organic waste containers.
• WEAR GLOVES at all times. Some solvents are toxic and absorb easily on the skin.
Chemical Data Table
Compound
MW
(g/mol)
BP (°C)
MP
(°C)
d (g/mL)
Safety
152
170
81-83
1.056
Eye and skin irritation
O
H
HO
O
vanillin
NaBH4
sodium
borohydride
methanol
37.83
500
400
-
32.04
64.7
-97.6
0.792
Caustic
Decompose violently
with acid
Flammable, eye and
skin irritation
OH
154.17
HO
293
113
O
vanillyl alcohol
57
-
Caustic
Decompose violently
with acid
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HCl (aq)
Hydrochloric acid
36.47
109
-26
1.017
Corrosive, skin burn
hexanes
86.18
69.1
-94
0.655
Flammable, irritant
ethyl acetate
88.11
77
-84
0.902
Flammable
Reaction Scheme
O
OH
H
HO
1. NaBH4
2. H3O+ workup
O
HO
O
25 mg of sodium borohydride and immediately
add it to the reaction vessel. Begin timing the
reaction mixture and spot samples at the
following intervals: 15, 30 60 and 120 seconds.
Clean the capillary tube with acetone between
each sample.
Procedure
Everyone will work in a group of 2.
WASTE REMINDER: Dispose of all waste in
the designated waste container.
Prepare two TLC plates. Mark them with a pencil
to spot the reaction mixture over time. Make 3
marks on each plate, one for reference and two
others for different reaction time. During the
reaction you will monitor the reaction by taking
samples of the reaction mixture at 15, 30, 60 and
120 seconds.
Prepare your TLC chamber with 2:3
EtOAc/Hexane. Develop each plate and visualize
under UV lamp. Sketch a diagram of the plates in
your lab notebook.
If the reaction is not complete, you may add
another 50 mg of sodium borohydride to the
reaction mixture and prepare another TLC plate.
How would you know if the reaction is not
complete? This time spot the plate at 0, 30, 60
and 120. Check to the TLC plate to see if the
reaction went to completion. If the reaction is not
complete, add another 25 mg and follow by TLC.
Ø Plate 1 – 0, 15, 30
Ø Plate 2 – 0, 60, 120
Spot the reference sample now before
continuing. Take a 25 mL Erlenmeyer flask and
add ~5mL of acetone. Use this acetone to wash
the capillary tube in between sample collection.
Practice cleaning the capillary tube because once
the reaction begins, you will need to be quick to
collect the samples at the specific times.
Neutralize the reaction mixture. Cool the reaction
mixture in an ice water bath. Add 6 M HCl
dropwise with stirring until hydrogen gas is no
longer evolved. Check the pH to verify the
solution is neutralized.
Place spin vane in a 5 mL conical vial and add
200 mg of p-vanillin and 2 mL of methanol.
Clamp the vial and begin stirring. Continue
stirring until all the solid is dissolved. Now take
the first sample, the 0 second sample. Weigh out
WASTE REMINDER: Neutralize the filtrate
with aqueous sodium hydroxide solution and
dispose of it in the aqueous waste container.
58