1. Chemistry 125: Lecture 66 April 6, 2011 Carbonyl Chemistry: Imines & Enamines Oxidation/Reduction & Electron Transfer This For copyright notice see final page of this file

2. Ketone to Imine + Iminium Ion Imine Unfavorable Equilibrium Constant R R H R H - OHH (e.g. J&F Sec. 16.11) Allylic : 2,4-DNP (dinitrophenylhydrazone) Oxime : Overlap ?

3. Ketone to Imine + Cl - Girard’s Reagent makes steroidal ketones soluble in water (cortisone) as cationic imines (hydrazones)

4. : n-*n-* R n-  * Transitions of Organic “Chromophores” : CX + +- - Oscillating electric field wags electrons up and down by mixing n with  *. With sufficient “conjugation” the  * LUMO energy shifts close enough to n that the transition is at visible wavelength. e.g. the retinaldehyde imine of rhodopsin, which is the visual pigment in our eyes. + +- - + +- -  * mix approaches energy of 2p orbital Imine Holds Retinaldehyde to the Protein Opsin Ketone to Imine

5.  NH 4 Cl + K + CN - Imine in Synthesis of Alanine (1854) by Adolph Strecker (1822-1871) alanine + CN -  HCl + OH 2  OH 2 + H+H+ 50-60% yield Often cited in discussing the “Origin of Life” Note: RCN gives RCOOH

6.  -ketoglutaric acid  NH 3 + NAD H An Imine in the Amino Acid Synthesis Catalyzed by L-Glutamate Dehydrogenase + + H-H- H Not an “essential” amino acid for mammals H+H+ glutamic acid

7. Transamination  -ketoglutaric acid H Not an “essential” amino acid glutamic acid Alanine H H

8. H C C C C C O O O N NH2NH2 O N C C C C H H H H O What functional group does this hemiaminal remind you of? OROR Ketal C C C DNA chain sugar base Protecting Group for Sugar

9.  -Substitution via Enamine + Iminium Ion can’t lose H + from N to give imine Enamine (nucleophilic carbon) O +  -diketone but can lose this  H + (Stork Enamine Acylation) Gilbert Stork (Columbia Univ.) O + (Stork Enamine Alkylation) - - H+H+ with permission F. E. Ziegler + - R R R 65-70% for R = C 5 H 11 55% for R = PhCH 2 R Cl R OH H 85-90% yield by distilling H 2 O H2OH2O H2OH2O

10. Enamine Enamine Lore (nucleophilic carbon)  -diketone (Stork Enamine Acylation) + - R + R 65-70% for R = C 5 H 11 H + H R (acidic) H+H+ O Requires 2 moles of Enamine! or add Et 3 N: to soak up H + (also Basic!)

11. Enamine Lore + (Stork Enamine Alkylation) - O 71% yield Actually : enolate - H +

12. Oxidation/Reduction as e - Transfer CH 3 -Br ** Mg CH 3 -Br Mg + CH 3 Br CH 3 -Mg Br + Mg Grignard Reagent (like CH 3 - sec. 16.13 ) Nobel Prize (1912) ** (CH 3 ) 2 C=O Mg (CH 3 ) 2 C=O (CH 3 ) 2 C O “reduction” Mg +2 “reduction” (CH 3 ) 2 C O H 2 O ~50% (CH 3 ) 2 C OH “Pinacol” “Pinacolone” (CH 3 ) 3 C C CH 3 O H+H+

13. Oxidation/Reduction as Bookkeeping Arbitrarily assign shared electron pairs to the more electronegative element

14. (CH 3 ) 3 C C CH 3 OH H 0 Oxidation/Reduction as Bookkeeping (for purposes of reagent selection) (CH 3 ) 3 C C CH 3 O “reduction” +2 C C -3 0 0 Need a “reducing agent” ?

15. Oxidation/Reduction as Bookkeeping (for purposes of reagent selection) (CH 3 ) 3 C C CH 3 O “reduction” (CH 3 ) 3 C C CH 3 OH H +2 C C 0 Need a “reducing agent” Oxidizing:Reducing : Neither : H-Cl +1 H-Cl Br-Br 0 0 CH 4 -4 1 CH 4 Li + AlH 4 - +1 +3 LiAlH 4 NaH +1 NaH K 0 K KCl +1 KCl RS-SR RS-SR CrO 3 +6 -2 CrO 3 ? HOCrO 2 - is a stable ion +4 Not all reducing agents would work satisfactorily, but it is usually futile to try a reagent from the wrong redox class. H 2 C CH 2 Br -2 (oxidizes RS-H H-SR to RS-SR) Certainly reduces O 2, and Fe 2 O 3 at great heat; Br 2 in free-radical halogenation; but not generally reactive. +1-2 H2OH2O H2OH2O But photosynthesis changes H 2 O into O 2 and “H - ” (NAD +  NADH) RSH H 2 C CH 2 H OH -2 -3

16. End of Lecture 66 April 6, 2011 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