1. Chem 125 Lecture 72 4/24/08 Projected material This material is for the exclusive use of Chem 125 students at Yale and may not be copied or distributed further. It is not readily understood without reference to notes from the lecture.

2. Transition State Motion Li-CH 3 O=CH 2 Li CH 3 O CH 2 How can this work ,*,* ,*,* when this doesn’t? H 2 C=CH 2 ,*,* ,*,*

3. Transition State Orbital Mixing Li-CH 3 O=CH 2 HOMOLUMO+2  * LUMO  HOMO offset & asymmetry allow  -  * overlap use 2p Li (not  *) as vacant orbital

4. Enamines (sec. 19.11B, p. 929-930) 2° amine (2 R groups, no other H to lose to form C=N)

5. Enamines (sec. 19.11B, p. 929-930)

6. Carbonyl to Methylene (sec. 19.12, p. 931)

7. RCHO Oxidation / Making Mirrors (sec. 19.14, p. 937) OR

8. RCO 2 H Synthesis (sec. 20.6, p. 963)

9. RCOOH Reactions (sec. 20.7, pp. 964-965) OH RC O H substitution at  -C substitution at C R substitution at O R addition A Nu

10. OH RC O Fischer Esterification (sec. 20.8, p. 965) H + H + + RO H + Tetrahedral Intermediate (A/D, not pentavalent transition state) substitution at C OR starts with addition

11. Fischer Esterification (sec. 20.8, p. 965) Tetrahedral Intermediate

12. 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) Third Term Heidelberg with who had introduced Steric Hindrance 1894

13. Linear Intermediate Fischer Esterification Didn’t Work with 2,6-Dimethylbenzoic Acid STRAIN!

14. Linear Intermediate (D/A, like S N 1) Tetrahedral Intermediate (A/D) 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 H3O+H3O+ Melvin Newman’s Method (1941) (attaches 2 protons)

15. RCOOH Reactions (sec. 20.7, pp. 964-965) OH RC O substitution at O

16. Esters by Alkylation at O (sec. 20.8B, p. 969-970)

17. H PhCH 2 CH 3 CH O ClSO 2 CH 3 +33° H CH 3 O O C O PhCH 2 CH 3 CH PhCH 2 CH 3 CH OCH 3 C O OH -32° Inversion! (R)  (S) H nucleophilic substitution at S (A/D, A favored by vacant d orbital of S) PhCH 2 CH 3 CH O SO 2 CH 3 CO O PhCH 2 CH 3 CH OCH 3 C O OH H STEREOCHEMISTRY Kenyon and Phillips (1923) PhCH CH 3 CH - OH nucleophilic substitution at saturated C. nucleophilic substitution at C=O (A/D, A favored by  *) (alkylation at O - )

18. Making RCOX (sec. 20.9, pp. 971-974) Analogous to ROH  RCl

19. RCOOH to RCH 2 OH (sec. 20.10, p. 974-975) CH 3 (CH 2 ) 9 CH 2 CO 2 H

20. Decarboxylation (sec. 20.11, p. 976-977) HO malonic acid HO acetic acid

21. End of Lecture 72 April 24, 2009