von Braun-Rudolf synthesis

What is von Braun-Rudolf synthesis?

The origins of the von Braun-Rudolf tetrazole synthesis can be traced back to 1909, when Forster and Schroeter independently prepared 1-hydroxy-5-phenyltetrazole and 1,5-diphenyltetrazole by reacting corresponding imidyl chlorides (or imide chlorides) with sodium azide. In 1941, von Braun and Rudolf extended this method to the preparation of substituted tetrazoles by treating imidyl chlorides with anhydrous hydrazoic acid in benzene or chloroform, a process now known as the von Braun-Rudolf reaction or von Braun-Rudolf tetrazole synthesis.

von Braun-Rudolf synthesis - general reaction scheme - von Braun-Rudolf reaction - von Braun-Rudolf tetrazole synthesis
von Braun-Rudolf synthesis

R, R’ = alkyl, aryl

However, most imide chlorides, except those with two aryl groups at the imidyl moiety, are very labile and easily undergo thermal decomposition. Therefore, the von Braun-Rudolf synthesis allows the cyclization to proceed at room temperature or slightly above, broadening the scope for the preparation of tetrazoles to include many thermal labile imide chlorides or those that only cyclize with sodium azide at very high temperatures.

Despite its advantages, the von Braun-Rudolf synthesis under a strongly proton-donating environment promotes side reactions that lead to ureas (via carbodiimides) and anilinotetrazoles. To overcome this, the reaction can be carried out with sodium azide in an aqueous phosphate buffer together with a water-miscible organic solvent, such as acetone.

Although the tetrazole ring system is relatively stable in the absence of a heat-sensitive group, tetrazoles can decompose to give various molecules. For example, 5-diazotetrazole decomposes to cyanogen and nitrogen, while 5-phenyltetrazole and 5-p-anisyltetrazole yield 3,5-diaryl-1,2,4-triazole and diaryl-sym-tetrazine, respectively. In the presence of a strong acid at temperatures above 160 ºC, 1,5-diaryltetrazole completely decomposes to amines.

References

  • Forster, M. O., J. Chem. Soc., Trans., 1909, 95, 184
  • Schroeter, G., Ber., 1909, 42, 2336
  • von Braun, J. and Rudolf, W., Ber., 1941, 74, 264
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