reaction mechanism ii: molecular rearrangement

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Reaction mechanism II: Molecular Rearrangement Continuation Lecture-5 By Dr. Mahender Khatravath Central University of South Bihar, Gaya MSCHE2002C04 21-04-2020 1

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Page 1: Reaction mechanism II: Molecular Rearrangement

Reaction mechanism II: Molecular Rearrangement Continuation

Lecture-5By

Dr. Mahender KhatravathCentral University of South Bihar, Gaya

MSCHE2002C04

21-04-2020 1

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The base-induced rearrangement ofO-acylated ketoximes to the correspondingα-amino ketones is known as theNeberrearrangement.

The rearrangement has become an important synthetic tool in the synthesis of heterocycles in which amino ketones are

used as key intermediates

Neber rearrangement

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Neber rearrangement: Mechanism

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The general features of the reaction are: 1.) Acylated ketoximes derived from both acyclic and cyclic ketones can be used; 2) the required oximes are readily prepared

from the ketones by reacting them with hydroxylamine under acidic conditions; 3)O-acylation of the oximes is conducted

using acyl halides or anhydrides in the presence of a mild base (e.g., pyridine); 4) the rearrangement is usually carried out in

an alcohol solution containing equimolar quantities of an alkali alkoxide.

when two methylene groups are available at theα- andα'positions, the rearrangement mainly gives rise to a product in which

the amino group is located on the more electrophilic carbon.

the rearrangement is not stereospecific, since the stereochemistry of the substrate (syn or anti) usually does not influence the

outcome of the reaction, and this is in sharp contrast with the stereospecificity of theBeckmann rearrangement; and

The product amino ketones have a tendency to dimerize, so they often needto be prepared in a protected form as their amino

acetals or hydrochloride salts (e.g., the amino acetals are preparedfrom the 2H-azirine intermediates by treatment with acidic

alcohols). There are a few limitations to the Neber rearrangement: 1) O-acylated aldoximes do not yield a-amino ketones

upon treatment with base, but rather undergo E2 elimination to afford the corresponding nitriles or isonitriles.

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Baker-Venkatraman rearrangement The base-catalyzed rearrangement of aromatic ortho-acyloxyketones to the corresponding aromatic β-

diketones is known as the Baker-Venkataraman rearrangement. β-Diketones are important syntheticintermediates, and they are widely used for the synthesis of chromones, flavones, isoflavones, and coumarins.The most commonly used bases are the following: KOH, potassium tert-butoxide in DMSO, Na metal intoluene, sodium or potassium hydride, pyridine, and triphenylmethylsodium.

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Mechanism

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Stevens Rearrangement The base-promoted transformation of sulfonium or quaternary ammonium salts to the corresponding sulfides or

tertiary amines involving the [1,2]-migration of one of the groups on the nitrogen or sulfur atom is known as theStevens rearrangement.

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Alternative Mechanism for the same reaction

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The general features of this reaction are: 1) The quaternary ammonium salts are readily available by the alkylation ofthe corresponding tertiary amines; 2) the

sulfonium salts are usually prepared by the direct alkylation of the corresponding sulfides; 3) the key intermediate of therearrangement is the nitrogen- or sulfur ylide; 3) the R1 group has to be able to stabilize carbanions, so it is often anelectron-withdrawing group; 4) depending on the nature of R1 , the acidity of the adjacent C-H bond varies so the typeof base used for the deprotonation must be chosen accordingly; 5) when R1 =aryl or heteroaryl, theSommelet-Hauserrearrangement becomes competitive.

6) R2 and R3 groups of ammonium salts cannot contain a hydrogen at their ß-position, since theHofmann eliminationmay compete; 7) the migrating group (R4 ) is usually capable of stabilizing a carbon-centered radical; 8) the migratoryaptitude of benzyl groups depends on the substituents on the phenyl ring and decrease in the following order:pNO2>p-halogen>p-Me>p-OMe.

when the migrating group has a stereocenter, it is transferred with retention of configuration at the migratingterminus; 10) the degree of the retention of configuration is influenced by the natureof substituents present on themigrating group; 11) in the case of sulfonium salts, the retention of configuration at the migrating terminus occurs to alesser extent than in the case of quaternary ammonium salts; and 12) in addition to nitrogen to carbon migrations, thereare nitrogen to heteroatom migrations as well (when Y=NH).

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