Tetrazoles Finnegan synthesis

Finnegan Tetrazole Synthesis Timothy T. Curran 5.3.7 Description... 

The Finnegan tetrazole synthesis is the reaction of a functionalized nitrile 1 with hydrazoic acid or an alkyl, aryl, or inorganic azide 2 to generate tetrazole 3 and/or 4. Typically, the 1,5-disubstituted tetrazole or l//-5-substituted tetrazole 3 is the predominant or exclusive product. The reaction can be promoted thermally or by use of mild organic, inorganic, or Lewis acids. The substituents allowed on both the nitrile and azide span a wide variety of functionality however, electron poor nitriles react more smoothly than electron-rich nitriles using standard protocol. 

The use of tetrazoles in the pharmaceutical industry has improved quality of life in a key therapeutic area. The tetrazole moiety is a key structural component of compounds known as angiotensin II receptor blockers used in the treatment of hypertension. Materials known as sartans exemplified by 14 through 18 contain the tetrazole moiety. In part, the need for robust chemistry to prepare sartans has encouraged development of modified Finnegan tetrazole syntheses and tetrazole synthesis as a whole. 

The Finnegan tetrazole synthesis has also provided an opportunity to showcase fluorous chemistry. In this instance, a polyfluorinated tin azide 64 was used in excess and reacted with electron-rich nitrile 63 to provide excellent yield of the tetrazole 65. This procedure was quite general, providing yields of tetrazoles in modest to excellent yield. 

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