Amines hydrazides, Curtius

Curtius transformation An alternative to the Hofmann transformation for obtaining an amine from an ester via the hydrazide, azide and isocyanate. Thus ethyl ethanoate is converted into melhylamine by the following series of reactions ... 

The methyl ester 2 can be converted into the trithiatriazepinamine 12 via the hydrazide 9. Nitrosation gives the azide 10. which undergoes a Curtius rearrangement to the isocyanate 11, which is not isolated but hydrolyzed in situ to the amine 12.418... 

Reactions of pyrimido[4,5-3] [l,4]thiazines were discussed in CHEC-II(1996) <1996CHEC-II(7)737> more recently, reported reactions of this system involve nucleophilic substitution in a number of guises. Hemiaminals at C-3 react with ammonium acetate to form aminals (Equation 166) <1999CHE97>. The formation of acyl hydrazides from pyrimido[4,5-3][l,4]thiazine-2-carboxylic acids, along with their subsequent conversion to acyl azides and Curtius... 

If primary or secondary amines are used, AT-substituted amides are formed. This reaction is called aminolysis. Hydrazines yield the corresponding hydrazides, which can then be treated with nitrous acid to form the azides used in the Curtius rearrangement. Hydroxyl amines give hydroxamic acids. 

For the conversion of hydrazides into amines by the Curtius reaction, see Section 27.3 other reported reactions are illustrated in the following examples. 

The Hofmann and Curtius reactions as applied to both the mono-and diamides and hydrazides have been reported. Marquardt found that a low yield of the amine can be obtained in the Hofmann reaction of l,2,5-thiadiazole-3-carboxamide. The main side reaction was hydrolysis of the electron-deficient amide to the carboxylic acid. Under the same conditions the dicarboxamide (78) formed the amino acid (16b). Attempts to prepare diaminothiadiazole via the Hofmann reaction of the amino amide (16a) resulted only in amide hydrolysis and the formation of the same amino acid. 

The ease of dehydration of pyridazine carboxamides, their hydrolysis, and Hofmann degradation to amines was outlined in CHEC-I <84CHEC-I(3B)1>. More recently, in the early 1990s, the Curtius rearrangement (Equation (19)) of the 4-carboxylic hydrazide of 6-(4-pyridyl)-3(2//)-pyridazinone to give an aza analogue of amrinone has been reported <90H(3i)2l63>. 

The synthesis of 4,5-difluoroimidazole has also been described by Kirk using a photochemical Schiemann reaction (Scheme 59) [74]. Curtius rearrangement of the acyl azide, prepared in two steps from ethyl 4-fluoroimidazole-5-carboxylate via hydrazide, afforded the key intermediate Boc-protected 5-fluoroimidazol-4-carboxylate. In situ Boc deprotection followed by diazotization of the amine and photolysis of the diazonium tetrafluoroborate afforded 4,5-difluoroimidazole. 

The structure of the acid or the presence of substituents may affect certain steps in the Curtius reaction. Although it is usually a matter of choice whether the hydrazide method or the sodium azide method is employed for the preparation of a given azide, for certain azides one of the methods may fail completely or may be preferable because of the structure of the acid or the presence of certain groups in the molecule. As a rule the rearrangement of azides to isocyanates proceeds without difficulty. The product obtained by hydrolysis of the isocyanate is not always an amine certain isocyanates yield aldehydes or ketones. 

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