Amines Favorskii rearrangement

In the reaction of 2-chlorocyclohexanone with a secondary amine (632) one encounters an intramolecular enamine alkylation analogous to the internal alkylations which constitute the critical step of some Favorskii rearrangements. 

Aliphatic c a -dibromo ketones, such as 2,4-dibromopentan-3-one (262), react with primary amines RNH2 (R = Me, Et, Pr, /-Pr or t-Bu) to give mixtures of imines 263 and lesser amounts of diimines 264. l,3-Dibromo-l-phenylpropan-2-one yields only the amide 265, the product of a Favorskii rearrangement. The nature of the products from aliphatic amines and cyclic a,a -dibromo ketones depends on ring size the cyclohexanone derivative 266 gave Favorskii amides 267 (R = Pr, /-Pr or t-Bu), while trans-2,5-dibromocyclopentanone afforded the enamines 268 (R = /-Pr or t-Bu) (equation 95)296. 

The reaction of a-halo ketones (chloro, bromo, or iodo) with alkoxide ions143 to give rearranged esters is called the Favorskii rearrangement.144 The use of hydroxide ions or amines... 

Addition of alcohols or other car-bocation sources to nitriles (Ritter) 6-65 Addition of water to isocyanides 8-7 Rearrangement of ot-halo ketones in the presence of amines (Favorskii) 8-8 Rearrangement of diazo ketones in the presence of amines (Arndt-Eis-tert)... 

The best base turned out to be the tertiary amine Et3N and the reaction had to be performed in alcoholic solution as alcohols were the only solvents able to keep the organic and ionic materials in solution. However, a substantial amount of a by-product was formed in ethanol—evidently the product of a Favorskii rearrangement. 

Sterically crowded a-haloketones and a-haloketimines cyclize to cyclopropanones and ketiinines, respectively, upon treatment with bases. The reaction of a series of a-haloketones with dialkyl sodiomalonate has been found to give the adducts of the malonate anion to incipient cyclopropanones, i.e. (l-hydroxycyclopropyl)malonic esters, instead of the products of the Favorskii rearrangement . Cyclopropanone aminals and l-alkoxycyclopropylamines have been obtained in the reactions of cyclic a-chloroketones (equation 16) with secondary amines and of a-chloroketimines with... 

This reaction is called the Favorskii rearrangement. Again, there are many variations for example, instead of an alkoxide anion, a hydroxide anion or even an amine may be used, in which case the salt of the carboxylic acid or the amide will be formed, respectively. This reaction may also be used so as to result in a ring contraction. Write down the mechanism for the reaction between an alkoxide anion and 2-chlorocyclohexanone. 

The whole process comprising the conversion of an a-halo ketone into a cyclopropanone, the adduct formation, and subsequent ring opening into carboxylic acid derivatives (carboxylic esters, carboxylic acids or carboxylic amides by using alkoxides in alcohols, hydroxides in water or amines in various solvents, respectively) is known as the Favorskii rearrangement. 

This reaction was initially reported by Favorskii in 1894. It is a base-induced rearrangement of a-halo ketones to the corresponding carboxylic acid derivatives (e.g., acids, esters, and amides) with the same number of carbon atoms in the skeletons and the bases can be hydroxide, alkoxide, or amines. Therefore, it is generally known as the Favorskii rearrangement. Occasionally, it is also referred to as the Favorskii reaction. ... 

In order to carry out the Favorskii rearrangement, the a-haloketone is generally added to a solution or a suspension of the base. Many bases have been used alkali and alkali earth hydroxides, alcoholates, neutral and acidic alkali carbonates, ammonia and amines. The reaction can be carried out either in protic solvents (water, alcohols) or aprotic solvents (ether, dioxane, dimethoxyethane,...). 

The Favorskii rearrangement can also be promoted using amines as base, giving thus amides as products. An example related to the ring contraction was described for the functionalized tncjo-dichloroketone 33 (Scheme 18.8). ... 

SCHEME 18.8. Favorskii rearrangement using amine as base. 

De Kimpe N, D Hondt L, Moens L. Formation of a-imi-noketones and a-diimines versus Favorskii rearrangement products from the reaction of a,a -dibromoketones and primary amines. Tetrahedron 1992 48 3183-3208. 

The rearrangement of a-halo ketones under the influence of base was first described by Favorskii in 1892, and the general scope of the reaction and the mechanistic implications have been the subject of a number of reviews. In its most generally useful form, a-halo ketones undergo skeletal rearrangement when treated with a nucleophilic base (hydroxide, alkoxide or amine) to produce salts, esters and amides respectively (Scheme 1). With polyhalogenated ketones unsaturated acid derivatives are prcxluced, as shown in Scheme 2. 

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