Isocyanates reaction with hydrazoic acid

Schmidt reaction (see review ). This reaction provides a method for the conversion of a carboxylic acid into an amine in one step. On reaction with hydrazoic acid in benzene in the presence of sulfuric acid, an acid is converted beyond the stage of the acyl azide (a) into the conjugate acid (b), which loses nitrogen more easily than the azide itself, with rearrangement to the isocyanate (d). The one-step... 

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. 

Ketene also appears to react with hydrazoic acid according to the general mechanism outlined in equation (88). Carbamoyl azides are produced and it is thought that the reaction proceeds by initial protonation and subsequent attack by azide ion to afford an acyl azide further reaction of the derived isocyanate would then lead to the observed product (equation 90). 

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 with hydrazoic acid has the advantage over Curtius rearrangement that it is only one step from the acid to the amine, but the conditions are more drastic (usually sulphuric acid plus sodium azide). Under these harsh conditions, the isocyanate intermediate is rarely isolated. For these reasons, the Curtius rearrangement is frequently employed to convert acids to amines. The Schmidt reaction of ketones with hydrazoic acid is a powerful method for the synthesis of amides and lactams. TTiis process is somewhat related to the Beckmann rearrangement of oximes however, the Schmidt reaction is more succinct, allowing the conversion of ketones to amides in a single operation. Considering its widespread... 

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." ... 

A few studies have appeared dealing with substitutions brought about by oxidation and reduction of co-ordinated ligands. Mention has already been made in this section of the reactions of co-ordinated azides, amides, and isocyanates with NO+. The reverse process (attack at co-ordinated NO+) is postulated to have a reactivity pattern which correlates with the i.r. N—O stretching frequencies. Co-ordinated NO+ behaves as an electrophile if the N—O stretching frequency is less than 1886 cm and the force constant is less than 13.8 mdyn A . A study of the rate of reaction of cis- and /ra -[Co(en)2(N02)2]+ ions with hydrazoic acid has also appeared ... 

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. 

Significantly, trimethylsilyl azide is an excellent substitute for hydrazoic acid in many reactions-such as curtius rearrangement of acid chlorides to isocyanates which proceeds with Me3SiN3 in one pot process and in higher yields. 

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. 

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