Chem 360, Special Topics: Modern Organic Synthesis, Spring 2008

Transcription

1 Chem 360, Special Topics: Modern Organic Synthesis, Spring 2008 Instructor Office: HS-446 Course Web Page Office Hours Lecture oratory Dr. Brant Kedrowski Phone: or (Chem. Office) Tues. and Fri. 9:10-11:30 (HS-446), or by appointment M W 10:20-11:20 (HS-456) T 1:50-5:10 (HS-452), lab will also be open at other times Required Materials - Modern Organic Synthesis, An Introduction 1 st Ed., 2007, W. H. Freeman, by G. S. Zweifel and M. H. Nantz - A Bound Notebook Not Spiral. (you can use one from a previous lab if it s in good condition) - An acceptable pair of goggles for lab (Required) Recommended Materials - Advanced Practical Organic Chemsitry 2 nd Ed., 1994, CRC by J. Leonard, B. Lygo, and G. Proctor - Your old text books and model kit from introductory organic chemistry (chem 235 & 335) Introduction to Chem 360 Welcome to Modern Organic Synthesis! This course is a continuation of your education in organic chemistry at an intermediate level, and will focus on organic synthesis. This is the process of building organic target molecules from simpler starting materials through chemical reactions. This is an important subject since organic molecules form the basic fabric of life, and they frequently play a pivotal role in human health, in agriculture, and in biology. Virtually all drugs, vitamins, hormones, food additives, pesticides, herbicides and plastics are organic molecules. We ll learn a variety of new reagents and reactions, synthetic strategies, and laboratory techniques used in modern organic synthesis. The concepts from beginning organic chemistry (chem 235 & 335) will serve as a foundation for this course. From time to time we will review concepts from these previous courses, but the focus of chem 360 this semester will be on new material. Goals for the Course 1. Understand fundamental reactions, mechanisms, and strategies of organic synthesis. 2. Become profecient at reading organic chemistry literature, and learn how to search for this information using modern information resources. 3. Learn standard laboratory techniques in synthetic organic chemistry for carrying out reactions, purifying products, and analyzing these compounds using modern instrumental methods. 4. Develop skills in chemical communication including scientific writing, use of structure drawing programs, and use of presentation software. 1

2 Lecture, and Exam Schedule We ll be covering selected sections in the Zweifel and Nantz text. Sections we ll be covering are listed below. Week Date Chapter - concepts Sec. 1 2/4 2/6 Synthetic Design Exp 1: Intro to chemical literature, information seraching, and drawing software Protecting functional groups: N-H, O-H, diols 1.1, /11 2/13 Protecting functional groups: aldehydes, ketones, carboxylic acids Exp 2: Synthesis of the insect pheromone frontilin, part 1, tosylate formation Enolate chemistry: 1,3-dicarbonyl enolates /18 2/20 Enolate chemistry: ester and ketone enolates Exp 2: Synthesis of frontilin part 2, acetoacetic ester alkylation Imines, hydrazones and enamines /25 2/27 Aldol reaction, part 1 Exp 2: Synthesis of frontilin part 3, ester hydrolysis/decarboxylation Aldol reaction, part /3 3/5 3/6 Mannich reaction, Michael addition, Robinson Annulation Exp 2: Synthesis of frontilin part 4, alkene epoxidation Review Exam 1: Thursday Evening, 6-8 PM, March 6 th (Chapters 1, 3, and 6) /10 3/12 Reactions of C=C bonds: epoxidation Exp 2: Synthesis of frontilin part 5, epoxide rearrangement to form frontilin Reactions of C=C bonds: dihydroxylation and oxidative cleavage of C=C /17 3/19 Reactions of C=C bonds: hydrogenation and dissolving metal reductions Exp 3: Synthesis of the natural product carpanone part 1, allylation of sesamol Synthesis of carbocyclic systems: ring-closing metathesis (RCM) /22-30 Spring Break 8 3/31 4/2 Claisen rearrangement Exp 3: Synthesis carpanone part 2, Claisen rearrangement Formation of C=C bonds: elminations, reduction of alkynes; carbometallation /7 4/9 Wittig and related olefination reactions Exp 3: Synthesis carpanone part 3, alkene isomerization Synthesis of carbocyclic systems: cation-p cyclizations, Diels-Alder reaction /14 4/16 4/17 Synthesis of carbocyclic systems: Diels-Alder reaction continued Exp 3: Synthesis carpanone part 4, oxidative coupling and hetero Diels-Alder Review Exam 2: Thursday Evening, 6-8 PM, April 17 th (Chapters 5, 8, and 9) 9.3 2

3 Week Date Chapter - concepts Sec. 11 4/21 4/23 Organolithium reagents Exp 4: Synthesis (E)- and (Z)-anethole part 1, boronic acid formation Grignard reagents /28 4/30 Palladium catalyzed coupling reactions Exp 4: Synthesis (E)- and (Z)-anethole part 2, Suzuki reaction Organocopper reagents /5 5/7 Carbonyl reduction, part 1: Exp 5: Synthesis of rasagiline mesylate, a drug for treating Parkinson s disease Carbonyl reduction part 2: distereoselective and enantioselective reductions /12 5/14 5/15 Oxidation of alcohols: to aldehydes and ketones, to carboxylic acids Literature Presentations Review Exam 3: Thursday Evening, 6-8 PM, May 15 th (Chapters 4 and 7) 4.1-3, 6 Evaluation of Performance (1000 points total) Three Exams Graded Homework Assignments 600 points (200 points each) 150 points 250 points In calculating grades, I look for logical breaks in score distributions to set A, AB, B, BC, C, and D cut-offs. Clumps of students that have similar scores are assigned similar grades. As an approximate guide, I use the following percentages: A 90%, B 80%, C 65%, D 50%, with intermediate grades of AB, BC, and CD assigned to people near the boarders. The class will be kept updated on exam performance. Exams There will be three exams throughout the semester worth 200 points each for a total of 600 points. Exams will cover material discussed in lecture, listed in the assigned reading in the textbook, and material from the laboratory portion of the course. The exams will be given in the evening. If you can t attend the evening exams for a valid reason see me (ahead of time) and an early exam will be scheduled for you. Graded Homework I ll be assigning, collecting, and grading homework throughout the semester. The homework will cover material from lecture, the textbook, and the lab. There will be ten homework assignments total, each worth 15 points, for a total of 150 points. Assignments There will be a number of graded assignments associated with the laboratory portion of the course. All written laboratory assignments need to be word-processed and have structures created using an computer drawing program (like ISIS Draw, which is free to download). Also, proper use of written English is required. When you work with a lab partner on an experiment, the two of you should complete lab assignments together and turn them in jointly. A schedule with due dates and specific guidelines for completing each type of assignment are provided on the next page. 3

4 Due date Assignment Points 2/11 Experiment 1 Informal Report 15 2/25 Experiment 2 Progress Report /3 Experiment 2 Progress Report /17 Experiment 2 Full Formal Report 50 4/7 Experiment 3 Progress Report 10 4/21 Experiment 3 Full Formal Report 50 5/5 Experiment 4 Full Formal Report 40 5/12 Experiment 5 Informal Report 15 5/12 Synthesis Article Presentation 50 Total 250 Informal Reports: These reports are similar to those from Chem 235/335. You ll be given a sheet listing the data that you need to report, the questions that you need to answer, and any experimental attachments that need to be provided such as spectra, chromatograms, etc Although the format of these reports is informal, you still need to word process them, computer-generate any sturctures, and use proper written English. Progress Reports: For experiments that span more than two weeks you ll need to turn in progress reports on the dates listed above. These reports will allow me to gauge the progress you have made toward the target molecule, including yields and purity of intermediates. It will also serve to help you catalog your data in preparation for the formal lab report to follow. The information from these progress reports can be cut and pasted into the formal lab report when it comes time to write it. Use the following format: I. Names, Title of Experiment, Date II. For each experimental step report the following: a. Name of the reaction b. Structural equation, in the style of the American Chemical Society (ACS) c. Experimental details of the reaction performed, in the style of the ACS d. Spectral data condensed into text form, in the style of the ACS III. Attach copies of any spectra you were asked to aquire such as NMR, GCMS, IR. Neatly draw structures on each spectrum and assign peaks. 4

5 Full Formal Reports: A formal lab report will be required after each large multi-week experiment is completed. There are three total, and they are worth a signifcant number of points. These will help develop your technical writing abilities. We will be emulating the style used in ACS journals, so you ll be learning to communicate as professional chemists communicate. For good examples of papers written in this style, see any recent issue of the Journal of Organic Chemistry (J. Org. Chem.). A guide to formating formal lab reports is listed on the next page. Grading of the formal reports will be based on technical chemistry-related details, quality of the writing, following ACS conventions, and purity of the final product. Yields will not be graded. However, they do need to be good enough so that you can finish the multi-step synthesis and have a final product to characterize and turn in at the end. (Formal report formatting) Report Title First Author Name and Second Author Name Department of Chemistry, University of Wisconsin, Oshkosh, Oshkosh, WI Graphical abstract In this space place a small 3.5 wide by 1.5 high structural diagram that describes the chemical essence of the report. You have to be very efficeint in your use of this space. Text abstract In 150 words or less, summarize the report. It is intended to present an overview of the experiment and should be as concise as possible. You should explain what was done and why you did it, and summarize your results. Do not include experimental procedures, raw data, spectral information, and/or conclusions in the abstract. Introduction The introduction should include a small amount of background on the molecule you have synthesized. If it was isolated from a plant or animal, report the species and reference literature reports on its isolation and characterization. Use superscript numbers 1 to reference literature. Number references sequentially in the order that they appear in the paper. Include a references section at the end of the report. If there is any known activity associated with the molecule the introduction section is a good place to discuss this. Keep this section brief, including just enough information to give the reader a sense of the nature and significance of the project. Provide a short, simple description of the experiment and describe the synthetic strategy briefly. Results and Discussion In the results and discussion section you present, analyze, and interpret your experimental results. Describe what reactions were run and what functional groups changed during the reaction. Include schemes with structures, and reaction arrows with reagents to graphically show how molecules change structurally. Place a boldface number below each structure in the paper, numbering them sequentially in the order that they appear in the paper, starting with 1. The first time a molecule is referred to in the text, use its chemical name followed by its boldface number in parentheses. Thereafter 5

6 in the paper, refer to the structure by its boldface number. Talk about the mechanism of the reaction, such as which species act as a nucleophiles and which act as electrophiles. Comment on the selectivity of reactions. Does the reaction take place at only one site on the molecule, and if so, explain why. Does the reaction produce stereoisomers such as a racemic mixture? Discuss the yield of each reaction, and mention if you detected or isolated any byproducts produced in the reaction. When reactions don t go perfectly it s helpful to know what s going wrong chemically. Report to what extent each intermediate was purified (by distillation, crystallization, chromatography or used crude in the next step, for example). Report what techniques were used to characterize each intermediate (IR, NMR, GC-MS, for example). Reference any literature reports that describe the synthesis of the same molecules as in your experiment. If other people have synthesized the same molecule before they need to be given credit. Did these syntheses use the same, or essentially the same reaction, or did they use a different synthetic strategy? Are there reports of characterization data for any of the intermediates in your experiment? If so, reference these articles as well. Discuss the key diagnostic features of your spectral results in words. Did your spectral data prove that you actually synthesized the molecule you were after? Comment on this by reporting any peaks that are especially diagnostic. For example, if you were synthesizing an aldehyde this functional group has a very distinctive peak for the H C=O proton at 9 ppm, which would be an important piece of data to discuss. Finally, include a conclusion statement here. Experimental Section Very carefully follow the format of the Journal of Organic Chemistry for reporting experimental details. Each compound gets a paragraph that lists in this order: 1) the chemical name and number you assigned to it, 2) a description of the reagent amounts used, the order of addition of the reagents, temperatures, reaction times, and work up methods, 3) purification methods, 4) actual and % yield, and 5) spectral data reported in tabular form. There are a number of formatting conventions in the way that these items are reported that you need to follow, especially in regards to the spectral data. Look at a few recent synthesis articles in J. Org. Chem. to get these details down. References Citations made in the body of the paper are to be listed in this section using the format found in a current issue of an ACS journal such as J. Org. Chem., or J. Am. Chem. Soc. Again, formatting is very specific and probably different from what you used in your composition courses. Spectra Attach spectra for your final purified product including IR, 1 H NMR, 13 C NMR, GC chromatogram, and mass spectrum. Guide to Writing Style: Scientific writing style makes frequent use of the passive voice and past tense although the active voice and present tense are acceptable at times. The imperative tense is not used. The following generalizations may be helpful to you. Also, remember to write in complete sentences, use proper punctuation and grammar, and spell words correctly. a) In the experimental section use the past tense, passive voice. Don t use the imperative tense. Correct: The reaction was stirred for I h. (Note past tense, passive voice). 6

7 Incorrect: Incorrect: I stirred the reaction for I h. (Note active voice). Stir the reaction for 1 h. (Note imperative voice). b) Be careful in your use of the word reacted Correct: Reagents A and B were mixed and they then reacted to form product C. Incorrect: I reacted reagent A with reagent B to give product C. c) Sentences are not to be started with a number written in numerical form. Correct: Correct: Incorrect: Five grams (0.064 mole) of benzene were placed in the flask. In the flask were placed 5 grams (0.064 mole) of benzene. 5 g (0.064 mole) of benzene were placed in the flask. (Note sentence started with a number written in numerical form). d) Sentences normally are not started with I or We in ACS Journals. Correct: Incorrect: Benzene was put in the flask. [(Use passive voice to avoid starting the sentence with I (We)]. I (we) put benzene in the flask. [(Note sentence started with I (we)]. e) Any current issue of the J. Org. Chem. or J. Am. Chem. Soc. should be reviewed to see how the above suggestions are implemented in a paper. Additionally the format for presenting equations and tables including numbering compounds should be reviewed and followed in your paper. f) The title and abstract pages should be two separate pages. The introductory, experimental, discussion, and reference sections are to follow each other rather than starting new pages for each section. Each section of the report should be headed with the appropriate title. (e.g. Abstract, Discussion, etc.) g) This paper is a formal report of your experimental work and, as such, should be written in a careful, concise, and professional manner. Word processed papers with computer generated structures are required. Synthesis Article Presentation Each pair of students will be given an organic synthesis article near the beginning of the semester. Throughout the semester you and your partner will study paper, learning the reactions, mechanisms, and the strategy employed in the synthesis. The two of you will prepare a minute PowerPoint presentation describing the synthesis in your own words. On the last lab meeting of the semester, 5/12, groups will present to the class, and answer questions for 5 minutes. More details will follow on this assignment. 7