Chemistry 20: Organic Chemistry I Spring 2016 MWF 9-10am, Science Center D Website: https://canvas.harvard.edu/courses/9181 Instructor:

Dr. Logan McCarty ([email protected]; 496-9009; Science Ctr 108) • A schedule of office hours will be posted on the course website.

Head TFs:

Eddie Schiffman (section), [email protected] David Rose (lab), [email protected]

Sectioning:

You must section for this course using the sectioning survey on our course website. You must section by Thursday, Jan. 28 at 5:00pm. Sections and labs begin the following week, Feb. 1. Sectioning questions should be sent to the Head TF ([email protected])

Course Texts:

Required: Chemistry 20 Organic Laboratory Procedures Purchase at FlashPrint, 99 Mount Auburn St. (Telephone: 617-492-7767) Recommended: The Organic Chem Lab Survival Manual, 8th ed. James Zubrick Wiley, 2010 (ISBN: 0470494379) Organic Chemistry, by Clayden, Greeves, Warren, and Wothers, Oxford University Press, 2001 (ISBN: 9780199270293) Supplementary: Organic Chemistry as a Second Language, David Klein Wiley, 2007 (ISBN: 0470129298) Organic Chemistry II as a Second Language, David Klein Wiley, 2005 (ISBN: 0471738085) Advanced Organic Chemistry, Parts A and B, 5th ed., Carey and Sundberg Springer, 2007 (ISBN: 0387683461 and 0387683542) (for students desiring further depth and more advanced treatment)

Course Description:

An introduction to structure and bonding in organic molecules; mechanisms of organic reactions; chemical transformations of the functional groups of organic chemistry; synthesis; determination of chemical structures by infrared and NMR spectroscopy.

Placement Information:

Chemistry 20/30 is an integrated two-semester sequence that prepares students to study chemistry and other physical sciences, whereas the Chemistry 17/27 sequence focuses on application of organic chemistry concepts to the life sciences. Either sequence satisfies the organic chemistry requirement for medical school and the chemistry concentration. The content of Chemistry 17 is accelerated and overlaps with topics from both Chemistry 20 and 30. Students may not count both Chemistry 17 and 20 toward the degree. However, Chemistry 27 and Chemistry 20/30 cover different material, so students may take Chemistry 27 after completing the 20/30 sequence.

Examination Dates:

Wednesday, Feb. 24 Wednesday, March 30 Wednesday, April 27

Course Grading:

Three hour exams Final Exam Best of all 4 exams Problem Sets Laboratory

Exam 1 Exam 2 Exam 3 30% 30% 10% 15% 15%

8:00–10:00am 8:00–10:00am 8:00–10:00am

*Exams start early to give enough time for group exams.

Note: There will be no makeup exams. If you miss one exam for a valid reason, your final exam score will be used in place of the missed exam. Note: Your lowest problem set score will be dropped. Note: You must complete all labs to pass the course.

Graded exams will be returned in discussion sections. Any concerns about grading errors must be noted in writing and submitted to your TF in person before leaving the classroom. Once an exam has left the classroom its grade will be considered final.

Prerequisites:

Open to students who scored 4 or 5 on the Chemistry Advanced Placement Examination, or who successfully completed Life Sciences 1A or Life and Physical Sciences A. Others should contact the instructor to discuss their preparation.

Accessible Education:

Any student receiving accommodations through the Accessible Education Office should present their AEO letter to the Head Section TF by Friday, Feb. 11. Failure to do so may prevent us from making appropriate arrangements for the first exam.

Molecular Models:

The department has arranged for each of you to be provided with a high-quality molecular model kit that will help you improve your visualization and 3-D spatial reasoning. You can check out a model kit at the Chemistry Library starting on Monday, February 1. The library is open Monday through Friday, 9:30 AM to 5:00 PM. You will need your HUID# to check out a kit. You should acquire your kit prior to working on the second problem set, as it will be instrumental to problem-solving. You may purchase a kit for your own use if you like (please contact the Head TF directly if you would like to arrange this). Please note that while these model kits will be invaluable to your learning and comprehension of the subject matter, they are extremely expensive to replace; failure to return the kit to the CCB library on or before Monday, May 16, or any other damage to the kit that renders it unusable will result in the full replacement cost ($150) being applied as a fine to your termbill. We recommend that you bring your model kits with you to the final exam, and return it to course staff when you have completed the exam.

Discussion Sections:

Discussion sections (1 hour) meet on Wed. and Thu. starting Feb. 3; you will choose your section with the online sectioning program. For questions about sectioning, contact the Head Section TF ([email protected]).

Weekly Reviews:

The Head TF will hold comprehensive weekly reviews on Mondays from 3:30–5pm. Attendance is strongly encouraged; these reviews will also be available online.

Problem Sets:

Problem sets will be posted on the course website each Wednesday and will be due the following Wednesday in class (by 9:05am). Late problem sets will not be accepted, but we will drop your lowest problem set grade. Collaboration on problem sets is allowed, but you must acknowledge your collaborators, and you may not simply copy answers: the final write-up must be your own work. Collaboration on examinations is not allowed.

Help Room:

Teaching Fellows will be available to help with problem sets. The Help Room is open on Tuesdays at times and locations to be announced.

Laboratory:

Laboratory experiments are an integral part of the course. Lab sessions meet in Sci Ctr 210 on Mondays and Tuesdays from 1–6pm. You should sign up for a lab time using the online sectioning program. Attendance and participation is required.

How to Succeed:

Do as many practice problems as you can get your hands on. We will post extra practice problems for each major topic on the course website, as well as practice exams. Doing practice problems is far more important than poring over the textbook trying to understand the meaning of every sentence! Our lectures will help you with conceptual understanding of the course material, and your TF can assist you with some aspects of problem-solving, but most of the learning in this course will come as you work on problems on your own. This is the only way to learn organic chemistry.

Welcome to Chemistry 20!

Chemistry 20 — Spring 2016 — Lecture Schedule Module/ Lecture 1a 1b 2a 2b 2c 3a 3b 3c 4a

Date Mon 1/25 Wed 1/27 Fri 1/29 Mon 2/1 Wed 2/3 Fri 2/5 Mon 2/8 Wed 2/10 Fri 2/12 Mon 2/15 Wed 2/17 4b Fri 2/19 4c Mon 2/22 4d Wed 2/24 Fri 2/26 5a Mon 2/29 5b Wed 3/2 5c Fri 3/4 6a Mon 3/7 6b Wed 3/9 6c Fri 3/11 7a 3/14–3/18 Mon 3/21 7b Wed 3/23 7c Fri 3/25 7d Mon 3/28 7e Wed 3/30 Fri 4/1 8a Mon 4/4 8b Wed 4/6 8c Fri 4/8 9a Mon 4/11 9b Wed 4/13 9c Fri 4/15 10a Mon 4/18 10b Wed 4/20 10c Fri 4/22 10d Mon 4/25 10e Wed 4/27 Fri 4/29 Mon 5/2 Wed 5/4 Thu 5/5

Topics Introduction; Bonding, structure, and hybridization Skeletal structures, functional groups, conformations of alkanes Atomic and molecular orbitals Frontier orbitals, curved arrows, electrophiles, and nucleophiles Acids and bases; HW#1#due Carbonyls: Irreversible additions; Oxidation, Reduction Carbonyls: Reversible additions Carbonyls: Conjugate addition; Organic synthesis; HW#2#due Stereochemistry: Chirality, Enantiomers, and Diastereomers President's*Day*(no*lecture) Alkyl halides; Substitution: SN2; HW#3#due Substitution and Elimination: E2 vs SN2 SN1 and E1; Carbocations: Structure, stability, and rearrangement Exam#1#(8:00am)#covers#modules#1–3 Stereochemistry and conformations of cyclic compounds Ethers and epoxides Alkenes: Nomenclature, acid-catalyzed addition; HW#4#due Alkenes: Halogenation, halohydrins, haloethers, epoxidation Alkenes: Oxymercuration, Hydroboration, Cyclopropanation Alkenes: Dihydroxylation, Ozonolysis; Thiols and sulfides; HW#5#due Stereochemistry: Diastereoselective and enantioselective reactions Spring*break Introduction to radical reactions Reactions of alcohols; HW#6#due Reactions of alkynes Putting it together: Organic synthesis Exam#2#(8:00am)#covers#modules#1–6 Cumulated and conjugated pi-systems Allylic and benzylic reactivity Diels-Alder reaction; HW#7#due Introdution to aromaticity; electrophilic substitution Synthesis using electrophilic aromatic substitution Nucleophilic aromatic substitution; HW#8#due Spectroscopy: UV and Infrared Spectroscopy: NMR Chemical shifts Spectroscopy: NMR Spin-spin splitting; HW#9#due Spectroscopy: Chemical and stereochemical equivalence Putting it together: Organic synthesis and spectroscopy Exam#3#(8:00am)#covers#modules#1–9 Reading period (review) Reading period (review) HW#10#due Examination*period*begins

Chemistry 20 Laboratory General Information Head TF Dave Rose

[email protected]

Laboratory TFs Ethan Magno Jim Tucker

[email protected] [email protected]

Location The organic chemistry laboratory is located in Science Center 210 (across from the elevator). A Teaching Fellow (TF) must be present for you to enter the laboratory. Overview This laboratory course is designed to introduce you to the basic analytical and synthetic techniques employed in the practice of organic chemistry. A passing grade for all experiments is required to pass the course. Any announcements related to lab will be posted on the Chem 20 website (https://canvas.harvard.edu/courses/9181) on the Lab page. Here you will also find lab lecture videos and the lab calendar. Scheduling Laboratory sessions are scheduled for five consecutive hours (tentatively 1 pm – 6 pm), on an approximately biweekly basis. Before the first lab, there will be a required one-hour lab orientation that will cover important safety information as well as introduce you to the lab space. Any student who is late to lab (arrives more than 15 minutes past the hour) for any reason will receive a zero for the quiz and will not be allowed to complete the lab, as these experiments often take the whole lab period. You will section for the laboratory using the FAS Online Sectioning tool (you must section separately for lab and section). Lab exemptions will be granted exclusively to those students who have completed the labs associated with Chemistry 27, 20/30, E-2a, or S-20ab here at Harvard. There will be no exceptions. Contact the Head TF before labs begin if you have previously completed the lab component of any of these courses. You will work with one other person to complete each experiment, but must submit all written work individually. Each student pair will be assigned their own chemical fume hood during the first laboratory session, and all chemical work must be performed in this hood.

Important Lab Safety Rules The primary goal for the instructors of this laboratory is for each and every person (both students and TFs) to safely make it through the semester. Never endanger the safety of yourself or others for any reason. Detailed safety policies are outlined in the lab manual. However, the following items are so important that they will be stressed from the outset: • Safety goggles (available for purchase at the Harvard COOP) must be worn in the lab at all times. They must be worn from the second you walk in until the second you leave, even if you are not doing chemistry. The correct type of goggles will be shown at the first lecture. Although we may have extra goggles on hand from time to time, failure to show up to lab with your own goggles will automatically incur a safety/clean-up point penalty. Furthermore, any student who arrives at lab without goggles is at risk of being barred from that lab session altogether if there are no extra pairs to wear – always bring your goggles! • You must wear proper attire to lab. This means no shorts or shoes that expose ANY part of the foot or leg are permitted in the laboratory. You will be immediately sent home to change if you attempt to enter the lab wearing shorts, capri pants, short dresses or skirts, sandals, flip-flops, flats, “Toms”, boat shoes, high-heeled footwear, etc. – you will also receive a safety/clean-up point penalty to your grade for that lab. You will not receive a warning before incurring this penalty. The best way to comply with policy and protect yourself from exposure is to ALWAYS wear long pants (a sturdy pair of jeans is best) and sneakers that cover the entire foot and ankle. If you wear tall boots, you must be sure that your pants can fit over the top of them. • You must wear one of the provided lab coats over your clothing at all times while working in the lab. Neither gloves nor lab coats should ever be worn outside the laboratory – they are contaminated! • A Teaching Fellow (TF) must be present for you to enter the laboratory. • Make-up labs will NOT be arranged for any students who miss a lab due to failure to adhere to our proper laboratory attire policies. • There will be no exceptions to any of these policies. Preparation Nothing less than complete preparation prior to arriving in the organic chemistry laboratory is acceptable. Lack of preparation will retard your progress through the experiments, and will also result in danger to yourself, your TF, and your labmates. Contact your TF or the Head Lab TF if you have any questions about an experiment. See the lab manual for extensive details on preparation for each lab.

Required Materials Text The Organic Chem Lab Survival Manual: A Student’s Guide to Techniques, 8th ed. by James W. Zubrick. This book is available at the Harvard COOP. You may come across other editions, which are acceptable, but you are responsible for figuring out the appropriate pages to read in any other editions, and some older editions may actually lack entire chapters assigned for reading, so be careful if you decide to purchase them. Notebook Your lab notebook must be the kind that makes carbon copies, so that a copy of your notes can be submitted to your TF at the end of each lab session. These research lab notebooks are available for purchase at the Harvard COOP, but you can buy them anywhere you wish. Students who arrive to lab without the proper laboratory notebook will be provided with a temporary replacement notebook on a one-time basis, but will incur a penalty to their grade for that lab, and will be refused participation in subsequent labs unless a satisfactory lab notebook has been procured. Students who arrive at lab without having completed the pre-lab write-up in its entirety present a danger to themselves and others and will be barred from participating in that lab. There will be no exceptions made for any student under any circumstances. Always come to lab prepared!! Lab Manual Available for purchase from FlashPrint, 99 Mount Auburn Street. Copies of the lab manual should be available for purchase starting on Wednesday, January 27. Lab Safety Goggles Available from the Harvard COOP. You must purchase your own and bring them to every scheduled laboratory session. Any student who shows up to lab without goggles will be dismissed from lab (presumably to fetch their goggles) and will earn a score of zero on that week’s quiz. Attendance You must attend every one of your assigned laboratory sessions. The number of students enrolled in the course and our unwavering commitment to safety in the laboratory make it impossible for us to permit attendance of non-assigned laboratory sections without explicit permission from the Head TF. Should a serious illness or family emergency arise, please notify the Head TF and your own Lab TF as soon as possible, so that we can work with you to help you complete all of the experiments. If you have a religious conflict during the semester, please notify the Head TF at least two weeks prior.

Grading Your lab score will be calculated as follows: 5 Lab Reports (10 points each) 50 points 5 Labs (2 Individual Clean-Up points each) 10 points 5 Labs (2 Group Clean-Up points each) 10 points 5 Pre-Lab Quizzes (6 points each) 30 points __________________________________________________ Total

100 points

Lab Reports Lab reports consist of two parts: a prelab and a postlab. The prelab must include the experiment, title and purpose, safety specifics, reagent table (when applicable), and reaction mechanism. Each of these “sections” is worth one point of your lab. You may also find it helpful to map out an abbreviated procedure to add context to your observations. Your postlab consists of your observations along with your results and conclusions. As you aren’t required to write a complete procedure, we expect a thorough observation section that allows your TF to follow along with your experiment. At a minimum, the observations section should include qualitative observations about filtrates or reaction mixtures in addition to quantitative observations (i.e., yield and melting point). The results and conclusions should sum up your findings succinctly, using observations as evidence. See the lab manual for a description of how to write good lab reports. Appendix 4 also shows an example of a report that would receive full credit. Your TF will let you know any specific expectations beyond the ones mentioned above. You will turn in your completed lab report by the end of the lab period. Late lab reports will not be accepted except under extenuating circumstances. Failure to complete all of the lab experiments and all of the write-ups will result in a failing grade for the course. Pre-lab Quizzes The pre-lab quizzes are designed to test practical understanding of the procedures, safety considerations, and fundamental chemical concepts as explained in lab lectures, your lab manual, your textbook/lecture notes, and in Zubrick. The possible pre-lab quiz questions can be found at the end of each experiment in the lab manual. Pre-lab quizzes will be administered promptly at 15 minutes past the start of each lab period. Any student who is late to lab (arrives more than 15 minutes past the hour) for any reason will receive a zero for the quiz. The quizzes may require that you watch lab lectures, do all required reading, and think about the lab in advance. Your TF is always available by e-mail to help you with the quiz material, although if you expect to have all of your answers “checked over” by your TF, you will be sorely disappointed. If you have any questions about the quiz material for Lab 1, please e-mail the Head TF.

Personal Clean-Up/Safety Points You will earn up to two points in each lab session for obeying all safety regulations and leaving your fume hood, bench-top, sink, and drying rack in immaculate condition at the end of each lab. In order to earn these points, it is your responsibility to have your TF initial your notebook at the end of each lab period to verify that you did in fact leave your work area clean. For a description of exactly what is expected of you, refer to Appendix 3 of the lab manual. Failure to adhere to ANY rules and regulations of the laboratory could result in losing your personal safety/clean-up points for that session, at your TF’s discretion and as mentioned above. Please note that your TF may assign groups to handle additional clean-up tasks, and failure to complete these tasks could also result in personal safety/clean-up point deductions. Group Clean-Up/Safety Points Each lab section will earn up to two points as a group each week for properly following waste disposal rules, handling reagents responsibly, and keeping all common areas in the lab clean. These include the waste disposal hoods, center bench reagent dispensing areas, balances and melting point apparatus areas, glassware room and bins, white shelves, and the instrument room. Failure to keep these areas spotless will result in the entire laboratory section loosing up to two points for that lab session, at the Head Lab TF’s discretion. The easiest way to avoid this is to always be sure to clean up after yourself!

Chemistry 20 Laboratory Spring 2016 Syllabus Lab Description

Lab Date

Lab Number

Feb 1 – Feb 9

1

Separation of an Unknown Mixture

Feb 22 – Mar 1

2

Purification of Organic Compounds

Mar 7 – Mar 22

3

Mar 28 – Apr 5

4

Apr 11 – Apr 19

5

Skills and Topics

Acid-Base Extraction

Recrystallization and Distillation

The Grignard Reaction

Preparation of a Grignard Reagent Synthesis of Triphenylmethanol

Electrophilic Addition and E2 Elimination Synthesis of Diphenylacetylene Reactivity of α-Pinene

Friedel-Crafts Acylation

Fridel-Crafts Acylation of Ferrocene Thin-Layer and Flash Chromatography

Note: Unexcused absences from lab are not permitted. Contact Dave Rose, Head Lab TF ([email protected]) in case of a medical emergency. The attendance policy is detailed in the lab manual.

Lecture 1a

Chemistry 20 Chemistry E-2a: Lecture 1

September 18, 2008

Chemistry 20: Introduction Course Content An introduction to structure and bonding in organic molecules; mechanisms of organic reactions; chemical transformations of the functional groups of organic chemistry; synthesis; determination of chemical structures by infrared and NMR spectroscopy.

Course Organization Lectures give overview of each topic, conceptual background, and demonstrations Laboratory gives hands-on experience and reinforces chemical concepts Discussion Sections show how to solve problems and give you practice Review Lectures (Mon. 3:30–5pm) give extra help in problem solving Problem sets and practice problems give you practice in problem-solving Practice examinations give you more practice in solving problems Examinations evaluate your ability to solve organic chemistry problems

Course Philosophy The Chemistry Team:

Our Coaching Staff:

Background We expect that you have taken Life Sciences 1a or Life and Physical Sciences A, or that you have comparable preparation in general chemistry (e.g. 4 or 5 in AP Chem). 1 1

Chemistry 20

Lecture 1a

The Organic Chemist’s Periodic Table

•

As of January 21, 2016: chemists have identified over 105 million organic and inorganic substances, of which over 32 million are available commercially!

•

“Learning organic chemistry is hard work. The amount of information out there is as close to infinite as makes no difference... The best solution is to make sure that we understand what we learn... develop a feel for the way molecules behave.” —A.J. Kirby, Cambridge UK 2

Chemistry 20

Lecture 1a

Chemistry E-2a: Lecture 1

September 18, 2008

Lewis Structures: Rules These rules are helpful guidelines. Practice using them until they become second-nature. 1. Count the total number of valence electrons that must appear in the structure. •Be sure to account for the extra or fewer electrons in a polyatomic ion! 2. Arrange the atoms in the correct arrangement for the molecule or ion. •A few guidelines: •Molecules are often written in the order that the atoms are connected. •The least electronegative atom is usually the central atom. •Hydrogen and fluorine are always terminal atoms. •In oxyacids (H2SO4, HNO3, etc.), the oxygen atoms are bonded to the central atom, and the hydrogen atoms are bonded to the oxygens. 3. Connect each pair of adjacent atoms with a single bond. (Use lines for bonds.) 4. Complete the octets of terminal atoms by filling in lone pairs of electrons. (Use dots!) •Remember that hydrogen should only have two electrons. 5. Add leftover electrons to the central atom (even if that gives it more than an octet). 6. Try multiple bonds if the central atom lacks an octet. •As a guide for where to place multiple bonds in order to minimize formal charges, the total number of bonds to any uncharged atom is usually given by its position on the periodic table. This is a guideline, not a hard-and-fast rule! Group #: Example: # of bonds:

1A H 1

2A Be 2

3A B 3

4A C 4

5A N 3

6A O 2

7A F 1

6. Check formal charges on each atom, and write in any non-zero formal charges. •Formal charge = (# of valence e in free atom) – (# of dots and lines around atom) •The sum of the formal charges on all atoms will equal zero for a neutral molecule, and will equal the charge on the ion for a polyatomic ion. •Lewis strucutres should be drawn to minimize formal charges. •In general, negative formal charge should go on the most electronegative atoms.

7. Check for resonance, and indicate it if necessary. 8. Check your Lewis structure. •Have you drawn the correct number of valence electrons? •Do all atoms have octets? (Except for examples of reduced or expanded octets.) •Have you minimized formal charges?

7 3

Chemistry 20

Lecture 1a

Chemistry E-2a: Lecture 1

September 18, 2008

Lewis Structures •

Using the rules for Lewis structures, provide Lewis structures for each of the following. Be sure to include any non-zero formal charges, and resonance (if appropriate).

NH3 (ammonia)

(CH3)3C+ (the tert-butyl carbocation)

H2CO (formaldehyde)

CH3CO2– (the acetate ion)

CH3NC (methyl isonitrile)

8 4

Chemistry 20

Lecture 1a

Chemistry E-2a: Lecture 1

September 18, 2008

Molecular Shapes: The VSEPR Model

•

Note the “wedge and dash” notation that chemists use to represent three-dimensional structures on a flat page.

9 5

Chemistry 20

Lecture 1a

Chemistry E-2a: Lecture 1

September 18, 2008

Electronegativity and Polarity •

Linus Pauling invented the tremendously useful concept of electronegativity to describe the distribution of electron density in covalent compounds. The electronegativity of an atom is a measure of its tendency to attract electron density in covalent bonds. Here are the electronegativities of the main-group elements:

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A bond can be polar if there is a difference in electronegativity between the atoms in the bond. However, even if a molecule contains polar bonds, it is possible for the entire molecule to be nonpolar. Let's look at some examples:

10 6

Chemistry 20

Lecture 1a

Chemistry E-2a: Lecture 1

September 18, 2008

Hybridization and Multiple Bonds •

A dirty secret: Hybridization is simply a code for electron domain geometry. Let's take a look:

•

Consider ethylene (also called ethene): C2H4. Draw a Lewis structure, and use it to determine the geometry and hybridization of each of the carbon atoms. How can we describe a double bond in terms of the overlap of orbitals?

11 7

Chemistry 20

Lecture 1a

Chemistry E-2a: Lecture 1

September 18, 2008

The Master Table of Bonding and Hybridization •

Let's fill out the following table of bonding and hybridization:

Number of Electron Domains

•

Electron Domain Geometry

Hybridization

Number of Hybridized Orbitals

Number of “Leftover” p-orbitals

Now let's use this table to describe the bonding in acetonitrile (CH3CN):

12 8

Reading: Section 1.9

Chemistry 20

Lecture 1a

Chemistry E-2a: Lecture 1

September 18, 2008

Resonance and Hybridization: The Wrong View •

Note: From here on, the material is new; we are finished with our review of topics from general chemistry!

•

Draw the Lewis structure of formamide, HCONH2.

•

What is the hybridization of the nitrogen atom?

•

The bond angles around the nitrogen atom in formamide are 120°. Is this consistent with the hybridization that you determined?

14 9