Schmidt rearrangement mechanism

The rearrangement has a mechanism similar to those of the Hofmann rearrangement of amides, the Lossen rearrangement of acylhydroxamic esters, the Schmidt rearrangement of carbonyl compounds and the Wolff rearrangement of diazoketones. Evidence concerning the mechanism of one can often be applied to the others, and the whole family has been reviewed briefly . Sometimes the distinction is made that the conversion of an acyl azide into an isocyanate or urethane is the Curtius rearrangement whereas the overall sequence is the Curtius reaction, but usually the former name is used for both processes. 

In the Schmidt rearrangement, the treatment of a carboxylic acid with hydrogen azide (hydrazoic acid) also gives the amine, via the isocyanate, when catalysed by an acid, such as sulphuric acid. The first step is the same as the AAC1 mechanism to form the acylium cation, and so is favoured by hindered substrates. The protonated azide undergoes the rearrangement reaction. Illustrate this mechanism as well. 

When the two groups of the ketone are para-substituted phenyls, the product of the Schmidt reaction is usually a nearly equimolecular mixture of the two isomeric amides.806 This result, obtained instead of a preferential migration of the more electron-releasing group, is consistent with a mechanism in which the formation of the intermediate rather than its rearrangement is rate determining. 

A variation of the Schmidt type reaction is the rearrangement of an azidocyc-loalkane, which is formed from the addition of hydrazoic acid to an cycloalkene. This reaction was used in the synthesis of muscopyridine (II/U4), a base isolated from the perfume gland of the musk deer [85]. In this context the reaction of II/115 as a model compound under the conditions of the Schmidt reaction gave a mixture of two compounds which after dehydrogenation yielded 11/116 and 11/117. The mechanism can be explained in terms of the migration of different bonds in the precursor. 

The reaction is a Schmidt reaction and its mechanism closely resembles that of the Beckman and Wolff rearrangements. The final step is deprotonation, followed by tautomerization to the lactam. Note that the alternate lactam formed by migration of the secondary carbon was not found. 

After consideration of the mechanism of the Schmidt reaction of carboxylic acids (cf. section III.A)the prediction was made and verified that the Curtins rearrangement would be subject to acid catalysis The charge and bond distribution in the substrate can almost certainly be best represented by 1 and protonation (reaction 7) was believed to form 2 in which the positive charge on the nitrogen of the... 

Schmidt Reaction.54 Closely related to the Curtins reaction in its mechanism is the Schmidt reaction, whereby carbonyl compounds react with hydrazoic acid in acid solution to give rearranged products. Amines, amides, nitriles, and tetrazoles are the most common substances obtained from the reaction. 

The present chapter is not intended to be a catalogue of all aspects of azepine chemistry which have been published since CHEC-I. Thus, for example, many established areas such as the Beckmann and Schmidt reactions for the preparation of reduced azepines are discussed only in respect to newer developments. The Beckmann rearrangement has been reviewed <870R(35)i>. The emphasis is to take forward the knowledge of azepine chemistry, to describe new chemistry and to develop earlier aspects which were just emerging when CHEC-I was being prepared. Such aspects include the synthesis and properties of azepine-3(2//) Ones, the formation of bicyclic and tricyclic azepines by the cyclization of diene-conjugated nitrile ylides and those results since 1984, theoretical and experimental, on the mechanism and synthetic applications of aryl azide chemistry. 

The mechanism of the Schmidt reaction has not been established with certainty. Schmidt proposed a mechanism in which the hydrazoic acid is cleaved by the strong mineral acid to nitrogen and the imide radical (NH). This radical is supposed to add to the carbonyl group, followed by a rearrangement either directly or by a Beckmann transformation of an intermediate oxime to the amide. ... 

Treatment of ketones with azide derivatives affords amides by a Schmidt reaction [389]. Its mechanism is similar to that of the Beckmann rearrangement The key intermediate is an iminodiazonium ion [390]. In transformations of bridged bicycHc ketones both the Schmidt and the Beckmann reaction are complementary [391] since inverse selectivities have been observed [392]. 

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