Hydrazoic acid, reaction with ketones

When the Schmidt reaction is applied to a,/3-unsaturated carboxylic acids, the product of the rearrangement is an enamine, which hydrolyzes to the corresponding ketone. Reaction with hydrazoic acid converts ketones to amides, and is thus an alternative method for effecting the same transformation as the Beckmann rearrangement. A drawback of this method is that the features that determine which... 

The mechanism is similar to those of the analogous reactions with hydrazoic acid (18-16 with ketones) and diazomethane (18-8) ... 

The reaction with hydrazoic acid converts ketones to amides. 

An aryl cyclopropyl ketone reacted with hydroxylamine followed by a mixture of tosyl chloride and pyridine to give the corresponding 7V-arylcyclopropanecarboxamide as the sole product in fair yield.Alkyl cyclopropyl ketones, on the other hand, afforded mixtures of the corresponding A-alkylcyclopropanecarboxamide and A7-cyclopropylalkanamide in excellent total yield on reaction with hydrazoic acid (Schmidt reaction) in the presence of sulfuric acid or trichloroacetic acid, an example is the formation of 3. When sulfuric acid was used, the amide ratio was sensitive to the acid strength of the reaction mixture. ... 

Use of the Beckmann reaction in the quinuclidon-3 series and interaction of the bicyclic ketone (VI) with hydrazoic acid under Schmidt conditions gave rise to a new type of 1-azabicyclic system derivatives of 1,4-diazabicyclo-(3,2,2)-nonane (XLIV) [117-119]. 

Reaction of carboxylic acids, aldehydes or ketones with hydrazoic acid... 

The reaction of carboxylic acids, aldehydes or ketones with hydrazoic acid in the presence of a strong acid is known as the Schmidt reaction A common application is the conversion of a carboxylic acid 1 into an amine 2 with concomitant chain degradation by one carbon atom. The reaction of hydrazoic acid with a ketone 3 does not lead to chain degradation, but rather to formation of an amide 4 by formal insertion of an NH-group. 

There are actually three reactions called by the name Schmidt reaction, involving the addition of hydrazoic acid to carboxylic acids, aldehydes and ketones, and alcohols and alkenes. The most common is the reaction with carboxylic acids, illustrated above.Sulfuric acid is the most common catalyst, but Lewis acids have also been used. Good results are obtained for aliphatic R, especially for long chains. When R is aryl, the yields are variable, being best for sterically hindered compounds like mesi-toic acid. This method has the advantage over 18-13 and 18-14 that it is just one laboratory step from the acid to the amine, but conditions are more drastic. Under the acid conditions employed, the isocyanate is virtually never isolated. 

The Schmidt reaction of ketones with hydrazoic acid is believed to be a similar rearrangement, again with concerted trans migration and elimination of nitrogen. 

The Schmidt reaction of cyclic ketones with hydrazoic acid affords convenient access to ring-expanded N-unsub-stituted lactams but extension of this process to alkyl azides to provide Aralkyl lactams is capricious in nature. A protocol... 

The tetrazole analogue (341) of 7-oxocholest-5-en-3/3-yl acetate has been prepared 82 by reaction of the afi-unsaturated ketone with hydrazoic acid and boron trifluoride etherate hydrolysis of the 3)3-acetate and oxidation of the resultant alcohol furnished 7a-aza-B-homocholest-4-eno[7a,7-d]tetrazol-3-one. Cycloaddition of ethylenediamine to 2a-bromo-5a-cholestan-3-one has furnished a simple one-step route to 5 -cholestane[2,3-e]dihydro-2,3-pyrazine (342).183 Analogous cycloaddition has been achieved using 16a-bromoandrostan-17-ones. 

Hexafluoroacetone imine has been prepared by the reaction of hexafluoroacetone with triphenyl phosphine imine,2 by the pyrolysis of N-phenyl-2,2-diaminohexafluoropropane,23 by the reaction of hexafluorothioacetone with hydrazoic acid,4 and by the reaction of ammonia and phosphorus oxychloride with hexafluoroacetone.4,5 The latter method, which is described here, is the most convenient for it does not require preparation of several intermediates or use of pressure equipment. This method has also been used to prepare the imines of other Huoroketones, including the imines of chloropentafluoroacetone, dichlorotetrafluoroacetone, and perfluorodiethyl ketone.5 Substitution of methylamine for ammonia in this procedure gives the N-methyl imine.5... 

Reaction of ketones with hydrazoic acid proceeds similarly to the Beckmann rearrangement to give amides, while aldehydes yield nitriles and formamides under analogous reaction conditions (equations 4 and 5). 

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