1. Chemistry 125: Lecture 64 April 2, 2010 Carbonyl Compounds Overview This For copyright notice see final page of this file

2. Carbonyl Compounds This Chapters 16-19 (268 pages!)

3. Mechanism for Acid-Catalyzed Hydrolysis of Acetal RO CH 2 + H HOH : : RO CH 2 + HROH RO-CH 2 + HO RO CH 2 + H First remove RO, and replace it by HO. HO RO CH 2 Now remove second RO, then H (from HO) + H : HO RO CH 2 + H RO=CH 2 + cation unusually stable; thus easily formed ROH H-O-CH 2 + O=CH 2 ROH RO CH 2 O H H  : Overall Transformation: H 2 O + Acetal Carbonyl + 2 ROH H+H+ (pp. 785-787) (hemiacetal) Good News: Much of this is review! e.g. secs. 16.9-16.10

4. Chapter 16: Aldehydes & Ketones C=O Stable, but Reactive! Average Bond Energies (kcal/mole) C-C 83 C=C 146 C-O 86 C=O 176 (aldehyde) 179 (ketone) “second bond” 63 90 93 (more substituted sp 2 C )

5. PMR Spectrum R-C O H  9.5 Spectrometer Frequency? 1 ppm = 180 Hz  180 MHz

6. CMR Spectrum TMS CDCl 3

7. Carbonyl Reactivity O Nu 1)Nucleophilic Addition (B ü rgi-Dunitz Angle) Chapter 16 O Nu O Rare for C=C 2) Nucleophilic Substitution of “Acid Derivatives” (A/D, like Aromatic) Chapter 18 L L ** H+H+ especially interesting for alcohol synthesis Nu = “R - ” (e.g. CH 3 Li) Nu = “H - ” (e.g. LiAlH 4 ) Secs. 16.13,16.16

8. HO Hydrate (gem-diol) RO Hemiacetal (  Acetal) RNH Carbinolamine (  Imine) HOSO 2 Bisulfide addition product NC Cyanohydrin etc. Secs. 16.6-16.11 Carbonyl Reactivity O H A B 3) Electrophilic Addition n (acid catalysis) O H (Easier than for C=C) O H 4) Allylic Rearrangement Ketone to Enol O H A A O H A O 5)  Substitution (electrophilic)  -proton Nu Chapter 19 H then Nucleophile

9. Enols, Enolates and Enolization O >10 13 OH -3 O H O O 93 O O pK a 19 K enol formation 5  10 -9 O H (ketone ~11 kcal below enol) (ketone  enol help from conjugation, H-bonding) (ketone >17 kcal above enol help from aromaticity) pK a = 10 (anion only ~ 13 kcal/mol above phenol) H B (base catalysis) Chapter 19 pK a ~11!

10. RCOOH Reactions (Chapter 17) OH RC O H substitution at  -C substitution at C R substitution at O R addition A Nu

11. End of Lecture 64 April 2, 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