1. Chemistry 125: Lecture 70 April 19, 2010 Acyl Compounds (Ch. 18) -H Reactivity (Ch. 19) This For copyright notice see final page of this file

2. OH RC O Fischer Esterification (sec. 17.7a) H + H + + RO H + Tetrahedral Intermediate (A/D, not pentavalent transition state) substitution at C OR starts with addition

3. Victor Meyer 9/8/48 - 8/8/97 Geliebte Frau! Geliebte Kinder! Lebt wohl! Meine Nerven sind zerstört; ich kann nicht mehr. Victor Meyer (1848 - 1897) introduced the idea of Steric Hindrance (1894) …the source of this behavior is stereochemical…the space filling of the neighboring groups vant Hoff (1874) Sachse (1891) Configuration Conformation

4. Tetrahedral Intermediate Fischer Esterification Didnt Work with 2,6-Dimethylbenzoic Acid STRAIN! Carboxylic Acid

5. Tetrahedral Intermediate (A/D) R Linear Acylium Intermediate (D/A, like S N 1) OH R C O substitution at C Fischer Esterification (sec. 20.8, p. 965) H + H + O + OR H + 100% H 2 SO 4 Pour into ROH Melvin Newmans Method (1941) (attaching second H + inhibits reversal) H+H+ + O H H H+H+ + sometimes

6. Acyl Derivatives from Ketene sec. 18.11, p. 907 H 2 C=C=O Nu:

7. Remember PhCHO + O 2 Baeyer-Villiger Reaction (insert O) pp. 907-909 H - migration R - migration

8. Migration from Acyl Carbon L R X C O + R inserts X between R and C=O

9. Beckmann Rearrangement (insert N) pp. 909-911 inserts in anti bond

10. Beckmann Rearrangement (insert N) pp. 909-911 R - migration in cation

11. elongates acid by one carbon Arndt-Eistert Reaction (insert C) pp. 915-917 Wolff Rearrangement R - migration

12. Acidity Tables 19.1 (p. 933), 19.2 (p. 943), 19.3 (p. 958) pK a ~ 18 H

13. complete formation of enolate not just a little at equilibrium LDA hindered strong base (pK a = 36) (p. 944) pK a ~ 25 K ~ 10 11 (slow attack on C=O, none on enolate)

14. Acid & Base H/D Exchange via enol and enolate (sec. 19.2a)

15. Racemization via enol and enolate (sec. 19.3)

16. -Halogenation ketones/aldehydes (19.4a) + Iodoform with base

17. -Halogenation carboxylic acids (19.4b) Hell-Volhard-Zelinsky

18. End of Lecture 70 April 19, 2010 Copyright © J. M. McBride 2010. Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0).Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0) Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol. Third party materials may be subject to additional intellectual property notices, information, or restrictions. The following attribution may be used when reusing material that is not identified as third-party content: J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0