Curtius reaction Schmidt reactions

The Curtius and Schmidt reactions both involve N2 as the leaving group from the azide intermediate (67), and here again the migration of R occurs in a concerted process. The azide may be obtained either by nitrosation of an acid hydrazide (65)—Curtius reaction—or by the reaction of hydrazoic acid, HN3, on a carboxylic acid (66)—the Schmidt reaction. 

Hofmann, Curtius, and Schmidt reactions yield primary amines free of secondary or tertiary amines. The three reactions are closely related but differ in reaction conditions. They apply to alkyl, allyl, and aryl derivatives. See Section 23-12E. 

The reaction sequence - including subsequent reaction with water which leads to amines - is named the Curtius Reaction. This reaction is similar to the Schmidt Reaction with acids, differing in that the acyl azide in the present case is prepared from the acyl halide and an azide salt. 

Into this group fall the named oxidation rearrangement reactions which proceed with carbon-carbon bond cleavage and 1,2-transfer of an alkyl group to a heteroatom, such as the Baeyer-Villiger reaction (discussed in Chapter 5.1, this volume) and the Beckmann reaction (found in Chapter 5.2, this volume) of ketones, as well as the Hofmann reaction/Schmidt reaction/Curtius reanangement of carboxylic acid derivatives. The two examples discussed here involve related reactions of alcohols. 

Amino-quinuclidine derivatives are interesting as starting materials for the synthesis of compounds of potential biological activity. Along with the above synthesis of 2-acylaminoquinuclidines [97] routes to 4-aminoquinuclidine (XXXVII) involving Curtius and Schmidt reactions [116] and to 3-amino-quinuclidine (XXXVIII), 3-alkyl(aryl)-3-aminoquinuclidines (XXXIX) and their derivatives [100] have been devised. 

The Curtius and Schmidt reactions can be run in completely anhy-droxylic environment, in the Schmidt reaction by use of such catalysts as stannic chloride instead of the customary sulfuric acid. All three reactions can be carried out under anhydrous conditions, but only in the Curtius and Hofmann reactions can an anhydrous alcohol be used as a solvent. Since the Curtius reaction is successful under conditions ranging from neutral to strongly acid, compounds may be d raded without exposure to strong acid or alkali. In the Hofmann reaction it is difficult to avoid a certain amount of exposure to strong alkali in the Schmidt reaction all the required catalysts are strong acids in the Lewis sense and act as catalysts for a variety of other reactions. 

The Curtius and Schmidt reactions are inapplicable to sugar acids. The Hofmann degradation has been applied successfully in this field. 

By application of the Schmidt reaction, the conversion of a carboxylic acid into an amine that has one carbon atom less than the carboxylic acid, can be achieved in one step. This may be of advantage when compared to the Curtius reaction or the Hofmann rearrangement, however the reaction conditions are more drastic. With long-chain, aliphatic carboxylic acids yields are generally good, while with aryl derivatives yields are often low. 

Carboxylic acids and esters can also be converted to amines with loss of the carbonyl group by reaction with hydrazoic acid, HN3, which is known as the Schmidt reaction,278 The mechanism is related to that of the Curtius reaction. An azido intermediate is generated by addition of hydrazoic acid to the carbonyl group. The migrating group retains its stereochemical configuration. 

An extensive review of the chemistry of aliphatic and aromatic azides is given by Boyer and Canter [167] and Gray [168]. Organic azides are subject to various reactions such as the Bergmann degradation and the synthesis of peptides, the well known Curtius rearrangement, the Darapsky synthesis of a-aminoacids [169], for synthesis of triazoles [170], tetrazoles ( Schmidt reaction ) [169] and [171] etc. These reactions lie beyond the scope of the present book. 

For example, 2-bromoquinuclidine (80) does not form Grignard reagents and 2-aminoquinuclidine is so unstable that on hydrolysis of its urethans (81) under mild conditions ammonia is lost and polymers of dehydroquinuclidine are formed. The synthesis of 2-bromoquinuclidine (80) was achieved by the Borodin reaction,90 and the urethans (81) were obtained from quinuclidine-2-carboxhydrazide (82) by the Curtius reactions.142 The Curtius reaction with quinucli-dine-4-carboxylic acid derivatives gave 4-aminoquinuclidine (83).143 This compound (83) was also synthesized directly from quinuclidine-4-carboxylic acid by the Schmidt reaction. However, the first method is better, in spite of having more steps. 

A closely related reaction of general applicability is the Curtius rearrangement222 of acyl azides. The rearranging species in the Schmidt reaction (see p. 898) is in fact also a protonated acyl azide these azides are readily prepared by the action of nitrous acid on acyl hydrazides which are themselves formed from esters and hydrazine (Section 9.6.17, p. 1269). On heating in aprotic solvents the acyl azides decompose to yield the corresponding isocyanates in good yield. 

This reaction is related to the Hofmann and Schmidt Reactions and the Curtius Rearrangement, in that an electropositive nitrogen is formed that initiates an alkyl migration. 

Phthalein type dyes have been prepared from 2,3-dicarboxypyrazine by heating with phenols or aromatic amines and zinc chloride. For example, compound (25) was obtained with resorcinol (1353). Efforts to prepare 2,6-diaminopyrazine through a Curtius-Schmidt reaction on 2-acetamido-6-carboxypyrazine (with sodium azide, sulfuric acid, and trichloroacetic acid) proved unsuccessful (434). The preparation of bicyclic heterocyles from 2-amino-3-carboxypyrazines has been described in Section VIII. 1D(6). 

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. 

Although the rearrangement of alkyl and aryl azides on treatment with acids, reaction (39), was discovered by Curtius , it is sometimes called a Schmidt reaction, although Schmidt did not work with these... 

Smith, The Curtius Reaction 111-8, H. Wolff, The Schmidt Reaction. ... 

Degradation reactions of carboxylic acids and their derivatives to amines and their derivatives with one less carbon unit involve rearrangements of a carbon to an electron deficient nitrogen atom as key steps, namely the Hofmann Curtius (C), - Schmidt and Lessen rearrangements, as... 

Related reactions Curtius rearrangement. Lessen rearrangement, Schmidt reaction ... 

In several ways this reaction resembles the molecular rearrangements involving transitory carbonium ions. The reaction is acid-catalyzed60 (see the Schmidt reaction). In the presence of triphenylmethyl free radicals no mixed products are formed.61 The migrating group never leaves the field of the electronically deficient atoms concerned since the Curtius reaction with (—)o-(2-methyl-6-nitrophenyl)-benzoic acid (LXXV) produces an optically active amine62 (LXXVI). 

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