MANY PARAMETERS INFLUENCE NUCLEOPHILIC SUBSTITUTION

1. MANY PARAMETERS INFLUENCE NUCLEOPHILIC SUBSTITUTION

2. NUCLEOPHILIC SUBSTITUTION MANY FACTORS INFLUENCE SN1 AND SN2 REACTIONS SOME PARAMETERS : a) solvent b) temp. c) pH d) DH a) structure a) structure of R, stereochemistry a) bond strength a) nature of X b) atom used b) atom used b) concentration c) concentration c) base strength c) bond strength d) base strength e) solubility f) size

3. STRUCTURE OF THE SUBSTRATE SN1

4. SN1 - SUBSTRATE AND CARBOCATION slow R-X R+ X- + R+ Nu- R-Nu + fast The energy of the carbocation intermediate is an important factor for an SN1 reaction. The better ion will have the lower energy pathway. 3o < 2o < 1o

5. SOLVOLYSIS OF tert-BUTYL BROMIDE acetone SN1

6. SOLVOLYSIS OF t-BUTYL BROMIDE tertiary + H3O+ + Br- 1935: Hughes & Ingold

7. 108 EFFECT OF INCREASING SUBSTITUTION - SN1 100% RBr + H2O ROH + HBr HCOOH methyl primary secondary tertiary 1.0 1.7 45 Guess ? relative rate increasing rate rate rel rate = rate CH3Br EFFECT OF SUBSTRATE ON RATE

8. HYPERCONJUGATION CARBOCATION STABILITY

9. CARBOCATION STABILITY HYPERCONJUGATION REVIEW H electrons in an adjacent C-H s bond help to stabilize the positive charge of the carbocation by proximity (overlap) .. + R C C H R H lowest energy highest energy << < tertiary secondary primary

10. BENZYL AND ALLYL CARBOCATIONS THESE ARE GOOD CARBOCATIONS

11. BENZYL AND ALLYL CARBOCATIONS RESONANCE STABILIZATION BENZYL ALLYL Systems that are similar in form to benzyl and allyl are called benzylic and allylic. isoelectronic with allylic (benzylic) (allylic)

12. SOLVOLYSIS RATES 80% Ethanol-water at 50° both reactions take place k rel Ethyl chloride very small good but not as good as tertiary 1 Isopropyl chloride 74 Allyl chloride 140 Benzyl chloride 12,000 tert-Butyl chloride

13. SOME CARBOCATIONS CANNOT FORM

14. WILL NOT REACT - SN1 X cannot become planar + + “steric rigidity”

15. STRUCTURE OF THE SUBSTRATE SN2

16. .. : H O .. SN2 - SUBSTRATE .. R : H O large groups introduce steric hindrance .. : C Br R R H easy access no steric hindrance : C Br H H

17. 150 1 0.01 0.001 rate rel rate = rate EtBr EFFECT OF DEGREE OF SUBSTITUTION - SN2 methyl primary secondary tertiary decreasing rate EFFECT OF SUBSTRATE ON RATE

18. a a a a 17 1 0.03 3 x 10-6 rate rel rate = rate EtBr EFFECT OF BULKY SUBSTITUENTS - SN2 ( substitution on the a carbon ) NEOPENTYL slower than t -butyl decreasing rate ALL ARE PRIMARY !

19. STERIC HINDRANCE

20. COMPARATIVE STERIC HINDRANCE isopropyl t-butyl neopentyl

21. Steric Hindrance WILL NOT REACT - SN2 backside attack is difficult

22. BENZYL SUBSTRATES

23. BENZYL ( GOOD FOR SN1 ) IS ALSO A GOOD SN2 SUBSTRATE primary, but faster than other primary I overlap in the activated complex lowers the activation energy H H Br critical overlap

24. rate rel rate = rate EtBr SN2 increasing rate

25. SUMMARY

26. SUMMARY Notice that benzyl and allyl are good for both SN1 and SN2 SN1 SN2 (fastest) (fastest) tertiary methyl** BEST BEST benzyl benzyl allyl allyl ** In SN2 reactions benzyl is actually better than methyl, but allyl is not. For illustration purposes benzyl and allyl were grouped in the yellow box. secondary primary primary secondary WORST bridgehead tertiary (slowest) (bicyclic) neopentyl APPROXIMATE RATE ORDERS bridgehead WORST (bicyclic) (slowest)

27. acetone no reaction + NaCN no reaction CH3CH2-C=CH-Br + H2O AND DON’T FORGET: SN1 and SN2 reactions occur only at sp3 (tetrahedral) carbon atoms. sp3 sp2 sp yes no (attempted SN2 reaction) (attempted SN1 solvolysis)

28. SOME EXTRA DATA FOLLOWS

29. SOLVOLYSIS RATES 80% EtOH 80% EtOH R-Cl R-Cl 50oC Relative Rate 25oC Relative Rate “nil” 1 1 74 1.7 SN1 140 2.6 1.2 x 104 3 2.4 x 105 13.6 6.4 x 106 Brown and Fletcher, JACS 71 1845 (1949)