Grant MacEwan University Fall 2012 CHEM 362 (AS 40) Advanced Organic Chemistry. Organic Chemistry by Clayden, Greeves, Warren and Wothers

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1 1 Instructor: Office: Grant MacEwan University Fall 2012 CHEM 362 (AS 40) Advanced Organic Chemistry Dr. Manzar Saberi G, City Center Campus Phone: Lectures: Monday, Wednesday, Friday 11:00-12:00 CCC Room Office Hours: Monday, Wednesday, Friday 9:00-10:30. Web address: Textbook: Organic Chemistry by Clayden, Greeves, Warren and Wothers Grade Distribution: 1 st Midterm- Friday, September 28 (50 min) 10 % 2 nd Midterm- Friday, October 19 (50 min) 15% 3 rd Midterm-Friday, November 9(50 min) 15% Final Examination- December 14, AM (3.0 hours) 30 % Laboratory 30% (Note: Students are responsible for verifying the date of the final examination when the final examination schedule is posted later in the term.) Description: This course is designed to build upon the concepts introduced in Chemistry 261 and Chemistry 263, offering a more advanced and sophisticated insight into the physical properties and chemical reactions of organic compounds. A focal point is the chemistry of carbonyl compounds. Mechanistic and multistep synthesis approaches are emphasized. Prerequisite: Minimum grade of C- in CHEM 263. Laboratory: Laboratory classes begin the second week of the term. The laboratory component is compulsory for credit in CHEM 362; attendance is mandatory and no make-up labs are available. If you know that you will be unable to attend a scheduled laboratory period, it is your responsibility to inform your laboratory instructor at least one week prior so that you can complete the experiment in another laboratory session. If a laboratory period is missed for a valid reason, the experiment may not be counted towards the final laboratory grade. In all other cases, a mark of zero will be assigned. Students who miss more than two labs will not receive credit for the laboratory component. Students must pass the laboratory component (minimum 50 %) in order to pass the course. College Information Grading: Grant MacEwan College adheres to the Alberta Common Grading Scheme, which is a letter grade system. While instructors may use percentages to aid in their grade development, only the letter grade will appear on transcripts. A+ 100 > 95 B 80 > 75 C 60 > 55 A 95 > 90 B 75 > 70 D+ 55 > 50 A 90 > 85 C+ 70 > 65 D 50 > 45 B+ 85 > 80 C 65 > 60 F 45 > Unofficial FINAL grades (lecture and laboratory) will be posted on my website approximately one week after each respective final exam at

2 2 Important Dates: Sept. 4 Sept. 10 Sept. 11 Oct. 8 Nov.9 Nov. 12 Dec st First day of classes Laboratories begin Last day for program changes (drop/add courses) Thanksgiving day; College closed Last day to withdraw without academic penalty Remembrance Day; College closed Final examination period Student Responsibilities Students are expected to be aware of their academic responsibilities as outlined in the Students Rights and Responsibilities section in the College Calendar. ACADEMIC INTEGRITY: All forms of student dishonesty are considered unacceptable. MacEwan s Academic Integrity policy (C1000) promotes honesty, fairness, respect, trust, and responsibility in all academic work. According to the policy, Academic dishonesty involves participating in acts by which a person fraudulently gains or intentionally attempts to gain an unfair academic advantage thereby compromising the integrity of the academic process. All incidents of academic dishonesty are reported and recorded by the Office of Academic Integrity. The penalties and sanctions for academic dishonesty can include the following: a mark reduction up to zero on a piece of academic work, a grade reduction up to an F in the course, and suspension or expulsion (with transcript notation) from the College. Please see the academic policy at for more details. You are responsible for understanding what constitutes academic dishonesty. Registration Status: You are responsible for your registration status at the College. Program Advisors may assist you with the process of registration, including adding or dropping of courses, but it is your responsibility to verify that these changes have been officially completed. This verification can be done at any time using Web Advisor. You should check your official registration status before the last date to officially withdraw from the course. WITHDRAWING FROM THE COURSE: Students who stop attending class must officially withdraw from the course. This must be done by the official withdrawal deadline for the course, which can be determined from the Academic Schedule in the College Calendar. Failure to withdraw properly will result in a grade, based on completed course work, being assigned. EXAMS: Your student photo I.D. is required at exams. It is at the discretion of the instructor whether you will be allowed to write the exam if you arrive over 15 minutes after the exam has begun. You must remain in the exam room for at least 20 minutes from the time it commenced. Permission to use the washroom during exams is at the discretion of the instructor and may require accompaniment. MISSED TERM EXAMS: If you miss a term exam you must provide the instructor with an explanation within 24 hours or a grade of zero may be given. Notification may be provided through , voice mail, or direct contact with the instructor. Official documentation as to why the exam was missed will be needed to assess whether pro-rating of the course grade will be allowed. Medical excuses must include the date you were examined, the specific dates for the period of the illness, a clear statement indicating that the severity of the illness prevented you from attending school or work, and the signature of the examining physician (a signature by office staff on behalf of the physician is not acceptable). Medical notes obtained subsequent to the date of the exam are generally not accepted. A grade of zero will be given if the instructor considers the excuse inappropriate or inadequately substantiated. DEFERRED FINAL EXAM: A deferred exam will be granted if you miss the final lecture exam for reasons considered by the Science Department to be unavoidable (deferred exams do not apply to term or lab

3 3 exams). Advise your instructor within 24 hours of your absence and intent to apply for a deferred exam. Application forms are available from the Science Department Office. Completed applications and supporting documentation must be submitted to the Science Department within 48 hours from the date of the missed final exam or a grade of zero will be given on the final exam. You should advise the instructor prior to the exam if you know beforehand that you will be unable to attend the scheduled exam time. Deferred exams are granted by the Science Department, not by the course instructor. LATE ASSIGNMENTS (INCLUDING LABORATORY ASSIGNMENTS): As due dates for assignments are known well in advance, medical and other excuses are generally not accepted as a reason for submitting late assignments. ELECTRONICS: All electronic equipment (cell phones, pagers, walkmans, A/V recorders, etc., except calculators approved by the instructor) are to be turned off during class and exam periods (except with written approval of the instructor). STUDENTS WITH DISABILITIES: Students with disabilities who may have special requirements in this course are advised to discuss their needs with Services to Students with Disabilities located in the Student Resource Centre. The course instructor(s) should be advised of any special needs that are identified. See Policy E3400 Students with Disabilities. MYMAIL MACEWAN All students are given a <name>@mymail.macewan.ca address. ISCLAIMER: The information in this Course Outline is subject to change. Any changes will be announced in class or, if applicable, in the laboratory. Chemistry 362 Course Outline 5. Organic Reactions Charge attraction bring molecules together Orbital overlap bring molecules together Electron flow is the key to reactivity Nucleophiles donate high-energy electrons to electrophiles Electrophiles have a low energy vacant orbital Interaction between HOMO and LUMO leads to reaction Use of curly arrows to represent reaction mechanisms Charge is conserved in each step of a reaction The decomposition of molecules Drawing your own mechanisms with curly arrows Decide on a push or a pull mechanism Guidelines for writing your own mechanism Assigned Chapter 5 problems: 1,2,3,4,5,6,7. 6. Nucleophilic Addition to the Carbonyl Group Molecular orbitals explain the reactivity of the carbonyl group Cyanohydrins from the attack of cyanide on aldehydes and ketones The Burgi-Dunitz angle Nucleophilic attack by hydride on aldehydes and ketones Addition of organometallic reagents to aldehydes and ketones Addition of water to aldehydes and ketones Hemiacetals from reaction of alcohols with aldehydes and ketones Acid and base catalysis of hemiacetal and hydrate formation Bisulfate addition compounds Assigned Chapter 6 problems: 1, 2, 3, 4, 6, 7, 10, 11.

4 4 10. Conjugate Addition Conjugation changes the reactivity of carbonyl groups. Alkenes conjugated with carbonyl groups are polarized. Polarization is detectable spectroscopically. Molecular orbitals control conjugate additions Ammonia and amines undergo conjugate addition. Conjugate addition of alcohols can be catalyzed by acid or base. Conjugate addition or direct addition to the carbonyl group. - reaction conditions - kinetic or thermodynamic control - structural factors - the nature of nucleophile: Hard and soft. Reactivity of hard and soft nucleophiles on conjugate addition. Copper (I) salts have a remarkable effect on organometallic reagents. Organocopper reagents undergo conjugate addition. Assigned Chapter 10 problems: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, Nucleophilic Substitution at the Carbonyl group The product of nucleophilic addition to a carbonyl group is not always a stable compound Carboxylic acid derivatives How do we know that the tetrahedral intermediate exist Why are tetrahedral intermediate unstable? pkah is a useful guide to leaving group ability. Amines react with acyl chloride to give amides. Using pkah to predict the outcome of substitution reactions of carboxylic acid derivatives Factors other than leaving group ability can be important. Guide to nucleophilicity. Reactivity of carboxylic acid derivatives Carboxylic acids do not undergo substitution reactions under basic conditions Acid-catalyzed substitution reactions of carboxylic acids Acid-catalyzed ester hydrolysis and transesterification Acid-base catalyzed hydrolysis of esters amides, and nitriles Synthesis of acid chloride using SOCl 2, PCl 5, and oxalyl chloride Synthesis of alcohols, ketones, by substitution reactions of acid derivatives Making ketones from esters; the problem - Making the starting materials more reactive - Making the product less reactive. Assigned Chapter 12 problems: 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, Formation and Reactions of Enols and Enolates Tautomerism: Formation of enols by proton transfer. Why don t simple aldehydes and ketones exist as enols? Evidence for equilibration of carbonyl compounds with enols Acid-base catalyzed enolization The intermediate in the base-catalyzed is the enolate ion. Summery of types of enol and enolate Kinetically stable enols Thermodynamically stable enols; Enols of 1,3-dicarbonyl compounds. Consequences of enolization Reaction with enols or enolates as intermediates Acid-base catalyzed halogenation of carbonyl compounds Stable enolate equivalents Assigned Chapter 21 problems: 1, 2, 3, 4, 5, 7, 8, 9, 10.

5 5 24. Chemoselectivity: Selective reactions and protection Selectivity Reducing agents Reduction of carbonyl groups - Esters - Amides - Carboxylic acids Catalytic hydrogenation How to reduce unsaturated carbonyl group Getting rid of functional groups Dissolving metal reductions How to react the less reactive functional group: protecting groups Chemoselectivity in the reaction of dianions Oxidizing agents Assigned Chapter 24 problems: 1, 2, 3, 4, 5, 6, 7, 9, 11, Alkylation of Enolates Diversity of carbonyl groups Some important considerations that affect all alkylations Alkylation of nitroalkanes and nitriles Choice of electrophile for alkylation Lithium enolates of carbonyl compounds Alkylation of lithium enolates - alkylation of ketones - alkylation of esters - alkylation of carboxylic acids Using specific enol equivalents to alkylate aldehydes and ketones - enamines - silyl enol ethers - aza-enolates derived from iminess Alkylation of β-dicarbonyl compounds A problem of regioselectivity for alkylation of ketone - thermodynamically controlled enolate formation - kinetically controlled enolate formation Enones provide a solution to regioselectivity problems Dissolving metal reduction of enones give enolates regiospecifically Conjugate addition to enones gives enolates regiospecifically Assigned Chapter 26 problems: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, Reactions of Enolates with Aldehydes and Ketones: The Aldol Reaction Introduction: The aldol reaction Aldol reactions of unsymmetrical ketones Cross-condensations Compounds that can enolize but that are not electrophilic Controlling aldol reactions with specific enol equivalents - Lithium enolates in aldol reactions - Silyl enol ether in aldol reactions - Specific enolequivalents from 1,3-dicarbonyl compounds Specific enol equivalents for carboxylic acids - Enols and enolates from acid anhydride - Enols and enolates from esters Specific enol equivalens for aldehydes and ketones

6 6 Making the less substituted enolate equivalent: Kinetic enolates Making the more substituted enolate equivalent: Thermodynamic enolates The Mannich reaction The Cannizzaro reaction Intramolecular aldol reactions Assigned Chapter 27 problems: 1, 2, 3, 4, 6, 8, 9, 10, 11, Alkylation at Carbon The Claisen ester condenasation compared to the aldol reaction Problem with acylation at carbon. Acylation of enolates by ester The claisen ester condensation and other self-condensation How do we know that deprotonation drives the reaction? Intramolecular acylation: The Dieckmann reaction Crossed ester condensations Reactive esters that cannot enolize Cross Claisen ester condensation between two different esters Claisen condensations between ketones and esters Preparation of keto-esters by the Claisen reaction Summary of preparation of keto-esters by the Claisen reaction Intramolecular crossed Claisen ester condensations Symmetry in intramolecular cross-claisen condensation Direct C-acylation of enols and enolates The acylation of enamines Assigned Chapter 28 problems: 1, 2, 3, 4, 7, 8, 9, 11, Pericyclic Reactions: Cycloadditions A new sort of reaction General description of the Diels-Alder reaction -the diene -the dieophile -the product Stereochemistry of the diene Stereochemistry of dieophile The endo rule for the Diels-Alder reaction The frontier orbital description of cycloaddition Dimerizations of dienes by cycloaddition reactions The Diels-Alder reaction in more detail The solvent in the Diels-Alder reaction Intramolecular Diels-Alder reactions Summary of regioselectivity in Diels-Alder reactions Lewis acid catalysis in Diels-Alder reactions Regioselectivity in intramolecular Diels-Alder reactions Clayden, Greeves, Warren and Wothers, Organic Chemistry.