Freshman Organic Chemistry 2

J. Michael McBride
  • 3.4 (15)
  • SCIENCE

This is a continuation of Freshman Organic Chemistry I (CHEM 125a), the introductory course on current theories of structure and mechanism in organic chemistry for students with excellent preparation in chemistry and physics. This semester treats simple and complex reaction mechanisms, spectroscopy, organic synthesis, and some molecules of nature.

  1. 04/02/2012

    34. Acids and Acid Derivatives

    Reactions of carboxylic acids and their salts include nucleophilic substitution and decarboxylation to leave enols, free radicals, or alkyl halides. A review of the IR spectroscopy of acid derivatives includes the use of vibrational coupling in the structure determination of anhydrides and imides. Many acid derivatives can be interconverted by substitution through a tetrahedral intermediate, and differences in acidity can be used to drive such reactions toward completion. Reduction of acid derivatives illustrates the challenge of designing selective reactions. Acidic and basic mechanisms allow conversion of nitriles to carboxylic acids. Ketenes provide routes to several acid derivatives. The Baeyer-Villiger oxidation of ketones to esters illustrates atom insertion into acyl-R bonds. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

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  2. 04/02/2012

    27. Triphenylmethyl and an Introduction to Carbonyl Chemistry

    Painstaking studies of his “hexaphenylethane” and its reactivity convinced Gomberg that he had prepared the first trivalent carbon compound, triphenylmethyl radical, the discovery of which marked the emergence of fundamental organic chemistry in America. Isotopic labeling could decide whether protonated cyclopropane plays a role in Friedel-Crafts alkylation. C-13 NMR spectra of aldehydes and ketones show how characteristic chemical shifts are established empirically. The carbonyl group is thermodynamically stable but kinetically reactive. Its acid- and base-catalyzed reactions often involve loss of an [gr]α-proton to form an enol or enolate intermediate. Carboxylic acids display four fundamentally different reaction patterns. Acid-catalyzed hydrolysis of acetals illustrates a multistep reaction mechanism involving the carbonyl group. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

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  3. 04/02/2012

    6. Brønsted Acidity and the Generality of Nucleophilic Substitution

    The coincidentally substantial extent of ionic dissociation of water provides an example of Brønsted acidity, or nucleophilic substitution at hydrogen. Relative pKa values are insensitive enough to solvent that they provide insight on the role of energy-match, overlap, and resonance in ionic dissociation. The titration of alanine in water illustrates the experimental determination of pKa values and the phenomenon of buffering. The limited pKa scale in water can be extended dramatically by titration in other solvents, providing one of the best ways to measure many “effects” in organic chemistry. A wide range of important organic reactions discovered in the 19th century and many biochemical reactions can be understood under the rubric of nucleophilic substitution. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

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  4. 04/02/2012

    38. Review: Synthesis of Cortisone

    Discoverers of the structure and biological activity of steroid hormones won seven Nobel Prizes between 1927 and 1975. Studying the steps involved in Woodward’s 1951 “total” synthesis of cortisone provides a review of the organic reactions covered this semester. Many steps involved novel insights, others were based on lore from previous work In the area. The overall yield of such sequential syntheses is typically much lower than that of convergent syntheses. Practical syntheses of cortisone were based on modification of related steroids readily available from nature. Milestones in total synthesis include both purely intellectual work with natural products and commercially important synthesis of designed pharmaceuticals. The course ends with thanks to those, young and old, who have taught us all. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

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  5. 04/02/2012

    37. Proving the Configuration of Glucose and Synthesizing Two Unnatural Products

    Modern spectroscopic tools show not only the constitution, configuration, and conformation of glucose but also how it interconverts between isomeric hemiketal pyranose rings. One of mankind’s great accomplishments was determinining its constitution and especially its configuration before such spectroscopy. By 1887 Heinrich Kiliani had established the constitution of glucose as an aldohexose, and with help from Emil Fischer, he developed a method for homologating aldoses. Fisher assembled a great deal of experimental evidence on interconversion of natural and artificial aldoses, and their derivatives, especially their crystalline osazones. In 1892 he used this evidence to prove logically which of eight aldohexose configurations corresponds to glucose and to provide definitive support for van’t Hoff’s stereochemical theory. In 1991 Cram, Tanner, and Thomas reported the NMR spectrum of antiaromatic cyclobutadiene, which they prepared by photolysis inside a clamshell molecule that they designed and constructed in order to isolate this highly reactive molecule. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

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  6. 04/02/2012

    36. [gr]α-Reactivity and Condensation Reactions

    As in many synthetic procedures, an important challenge in ketone alkylation is choosing reagents and conditions that allow control of isomerism and of single vs. multiple substitution. [gr]β-Dicarbonyl compounds allow convenient alkylation and preparation of ketones and carboxylic acids. The aldol condensation, in which an [gr]a-position adds to a carbonyl group to generate a [gr]β-hydroxy- or an [gr]α,β-unsaturated carbonyl compound, can be driven to completion by removal of water. The Robinson annulation reaction is an important example of conjugate addition to [gr]α,β-unsaturated carbonyl compounds. [gr]α-Acylation of esters as in the Claisen condensation is a key step in the biosynthesis of fatty acids. Determining the constitutional structure of sugars posed a daunting challenge to early carbohydrate chemists. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

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  7. 04/02/2012

    33. Green Chemistry. Acids and Acid Derivatives

    Green chemistry needs new asymmetric reactions and safer, more environmental Mitsunobu reactions. The Mitsunobu mechanism is general and reliable, but atom inefficient, generating almost 30 times as much weight of by-products as of the water it is designed to eliminate. Admirably green processes include autoxidation of aldehydes to carboxylic acids using only O2, and oxidation of alcohols by loss of H2 using a ruthenium catalyst. Relative pKa values of carboxylic acids provide insight into the role of inductive and resonance effects in organic transformations. One analysis suggests that the special acidity of carboxylic acids owes four times as much to inductive as to resonance effects. Carboxylic acids can be prepared both by oxidation and by reduction. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

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  8. 04/02/2012

    35. Acyl Insertions and [gr]α-Reactivity

    When a nucleophilic atom bearing a good leaving group attacks a carbonyl group, an adjacent R group can migrate to the new atom, inserting it into the R-acyl bond. This mechanism can insert O, NH, or CH2 groups into the acyl bond with informative stereospecificity in the case of the Beckmann rearrangement of oximes. Although the migrating groups are formally anionic, relative migratory aptitudes show that they give up electron density during rearrangement. Acid dissociation of protons [gr]α to a carbonyl group to form enolates, and the ease of forming enols, gives [gr]α-carbons nucleophilic reactivity under both basic and acidic conditions. This explains H/D exchange and racemization as well as halogenation and alkylation of [gr]α-carbons. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

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This is a continuation of Freshman Organic Chemistry I (CHEM 125a), the introductory course on current theories of structure and mechanism in organic chemistry for students with excellent preparation in chemistry and physics. This semester treats simple and complex reaction mechanisms, spectroscopy, organic synthesis, and some molecules of nature.

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