Neighbouring Group Participation.pptx

NGP,SYNTHESIS

1. Neighboring Group Participation Dr.Gurumeet C Wadhawa , Assistant Professor, Department of Chemistry. Rayat Shikshan sansthas Veer Wajekar ASC College,Phunde,Uran

2. Rearrangement

3. NH 2 HO 2 N + HO 2 HO CH + HN O 2 - N 2 OH OH O

4. III. Non-classical Carbocations 非经典碳正离 子 Non-classical ions are a special type of carbonium ions displaying delocalization of sigma bonds in 3-center-2-electron bonds of bridged systems. S. Winstein (1949): Acylation (solvoysis) of norbornyl brosylate endo- exo- A key observation is that in this nucleophilic displacement both isomers give the same reaction product an exo-acetate 2. Also the reaction rate for the exo-reaction is 350 times the reaction rate for the endo reaction.

5. In a related experiment both enantiomers 1 and 2 of the exo-brosylate on solvolysis give the same racemic reaction product. The optical activity of the reaction disappears at the same reaction rate as that of the solvolysis.

6. Sigma electrons in the C1-C6 bond assist by neighbouring group participation with the expulsion of the leaving group 1 2 7 4 6 exo- 1 2 6 end o - 3. A non-classical ion: pentavalent, symmetrical In a non-classical carbocations, the positive charge is delocalized by a double or triple bond that is not in the allylic position or by a single bond.

7. George A Olah (1964): direct evidence for the norbornyl cation by NMR analysis Olah, G.A., J. Am.Chem.Soc . 104 , 7105(1982)

8. IV. Neighbouring group participation (NGP) Neighbouring group participation or NGP has been defined by IUPAC as the interaction of a reaction centre with a lone pair of electrons in an atom or the electrons present in a  bond or  bond. When NGP is in operation it is normal for the reaction rate to be increased. It is also possible for the stereochemistry of the reaction to be abnormal (or unexpected) when compared with a normal reaction. A. NGP by heteroatom lone pairs The rate of reaction is much higher for the sulfur mustard and a nucleophile than it would be for a primary alkyl chloride without a heteroatom.

9. B. NGP by an alkene (C=C as a neighboring group) H Ts O H T s O The rate of acetolysis 1 1 O Configuration retention retention Ts = H 3 C S O

10. Even if the double bond is more remote from the reacting center the alkene can still act in this way. H OB s H OB s O S O O Br BsO : -(syn-7-no r bo r nenyl) ethyl brosylate (A): Relative rate of acetolysis (A) 140,000 (B ) 1

11. DISCUSSION Evidence for the non-classical cations. A neighboring group lends anchimeric assistance only when there is sufficient demand for it. The ability of C=C to serve as a neighboring group can depend on its electron density. H SO 2 Mo s O R 1 Mos = MeO R 2 Relative rates of the solvolysis R 1 = R 2 = H R 1 = H, R 2 = CF 3 R 1 = R 2 = CF 3 1.4x10 12 1.5x10 6 1

12. C. NGP by an aromatic ring A n aromati c rin g ca n a ssis t i n th e f ormatio n o f a c arbocationic intermediate called a phenonium i on by delocali s i ng the positive charge . the tosylate reacts with acetic acid in solvolysis then rather than a simple SN2 reaction forming B ,a 48:48:4 mixture of A , B and ( C + D ) was obtained. QUESION: please give a mechanism which forms A and B.

13. D. Cyclopropyl as a neighboring group Where cyclopropyl lends considerable anchimeric assistance, the developing p orbital of the carbocation is orthogonal to the participating bond of the cyclopropane ring.

14. E. The C-C single bond as a neighboring group i. The 2-norbornyl system +

15. ii The Cyclopropylmethyl System 2 CH Cl EtOH/H 2 O 2 CH OH 48 % 17 % OH + CH OH + 2 homoally alcohol 5% CH 2 X o r 2 H C H 2 C CH 2 CH + H 2 C CH CH 2 CH 2 H 2 C CH CH 2 CH 2 OH or CH 2 =CHCH 2 CH 2 Cl The c arbocationi c i ntermidat e i s delocalise d ont o m an y different carbons through a reversible ring opening.

16. 3 3 iii. Methyl or Hydrogen as Neighboring Group 3 3 3 3 3

17. CH 3 CH 2 CDCD 3 CH 3 CHDCHCD 3 CH 3 CHCDHCD 3 CH 3 CDCH 2 CD 3 open cations in equilibrium no NGP by hydrogen H OTs C CD 3 H 3 C C H D O S - O Ts= H 3 C CD 3 NGP by hydrogen H CH 3 CH CD (e)

18. Pinacol-pinacolone rearrangements

19. Conversion of an alcohol having two adjacent OH groups (pinacol) to a ketone (pinacolone) by the action of acid P i n ac o l - p i n ac o l one Rearrangements

20. H C 3 C H 3 OH OH CH 3 + C H 3 O H C H 3 CH 3 H 3 C H O CH 3 CH 3 CH 3 CH 3 CH 3 H C CH H C 3 3 3 OH OH 2 C H 3 CH 3 CH 3 O H 3 C 2 H SO 4 + _ H _ OH 2 p i na c ol p i na c o l one + + C H 3 CH 3 CH 3 CH 3 + H 3 C .. H O M ec h a n i s m Mechanism of the pinacol rearrangement of a symmetrical glycol 1. Protonation of a hydroxyl group 2. Loss of water Resonance-stablized carbocation 3. Methyl migration 4. Deprotonation

21. F a cts 1, 2 shift takes place in carbonium ion which is already a tertiary carbonium ion It is probably due to stabilization of rearranged ion that can be affected by delocalization involving the electron pair on the oxygen atom, and ready loss of proton from the oxygen to produce a stable end product

22. The stable cation formed superior for stabilization H + P h C C H 2 2 O H O H P h C C H 2 + 2 O H Ph 2 CH CH + OH H + Ph 2 CH C H O + Ph 2 CH CH O H

23. Bromohydrin to pinacolone

24. Hydroxyamine to pinacolone

25. F a c ts It seems that migration of alkyl group is extremely fast on the loss of leaving group, taking place simultaneously That migrating group is from the opposite side of the leaving group – Because rearrangement is much more easy in compounds having trans configuration than that having cis configuration

26. Pinacol rearrangement of an asymmetrical glycol H O O H H O M e P h M e M e M e O P h H SO 2 4 O H P h M e B P h C P h D Me Ph A Me + Me P h + P h H O O H E t P h E t P h H O E t E t E t E t O P h P h H SO 2 4 H + _ F E P h + P h

27. Which group migrates? Phenyl group move first because of greater chances of stabilization due to delocalization PhHC CHPh H + P h H C C H P h OH + Ph 2 CH C H O H + Ph 2 CH CH + OH Ph 2 CH C H O H O H O H +

28. Which group migrates?

29. The steric chemistry of Pinacol Rearrangements It is found that o -MeOPh migrate more than a 1000 time less readily that p -substituent and even much less than phenyl. This is due to interference in the transition state with non-migrating group

30. Solved problem Explain the following experimental facts ： R R R O R O R C R H 2 SO 4 + OH OH ( A ) (B) ( C ) When R=CH 3 , （ B ） and （ C ） are formed ； When R=Ph, only （ C ） is formed .

31. - H + + R R : O H ( 6) + C R R : OH (3) C + R R O H ( 5) + C R R OH (2) R C R OH + OH 2 (4) - H + C R R O H + OH 2 ( 1) (B) + H + R C R O O R ( C) R O H O H (A) R C R When R=Me

32. When R=Ph