Isocyanates, addition hydrazoic acids

The intermediates in making amines are isocyanates (0==C==N) just like the Hofmann Rearrangement. The isocyanates are decomposed with water, just like the Hofmann. In fact, there is a lot of similarity between the Hofmann and the Schmidt reactions. Before I detail the synthesis steps, I should note that if you wish to generate the Hydrazoic Acid in the flask by adding Sodium Azide, you might need a powder addition funnel. This bit of equipment is quite pricey and it s likely you won t have one, so the first part of the synthesis details how to make the Hydrazoic Acid separately. 

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 addition products of hydrazoic acid and isocyanates have been used as intermediates in the synthesis of monophosphazenes ... 

Addition of ketenes to imines addition of enamines to isocyanates 8-17 Reaction between cyclic ketones and hydrazoic acid (Schmidt)... 

The addition of hydrazoic acid to a carbodiimide [156] was used by Hiibich in the synthesis of analogues 238 of 3 -azido-3 -deoxythymidine (AZT, 234). AZT (234) is an important drug for the treatment of AIDS that belongs to the class of nucleoside reverse transcriptase inhibitors. AZT (234) was transformed to the carbodiimide 237 through Staudinger reaction with tri-phenylphosphane, followed by reaction of 235 with an alkyl or aryl isocyanate 236. The carbodiimide 237 was then treated with hydrazoic acid in toluene at room temperature for 6 horns to give the desired 5-aminotetrazole 238 in 43-90% yield (Scheme 45) [ 170). 

The Schmidt reaction of carboxylic acids proceeds via acylium ion, which undergoes addition with hydrazoic acid to generate acyl azide. This azide rearranges with loss of nitrogen to give isocyanate, which leads to an amine upon hydrolysis." ... 

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