5- tetrazole, Finnegan

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. 

In a modification to the Finnegan reaction, preparation of 5-amino-tetrazoles has been accomplished via preparation of intermediate 12 from cyano-azide 11. Reaction of 11 with a variety of amines 10 at room... 

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. 

Use of mesopourous ZnS nanospheres (MZnSS) has been reported to promote the Finnegan reaction to prepare tetrazoles. The reactions still required high temperature (120 °C) and used catalytic amounts of MZnSS... 

Other solid supports have been reported to promote the Finnegan tetrazole reaction, like catalytic FeCl3-Si02- The procedure was shown to be general and the catalyst could be re-used. 

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. 

Generation of the nitrile or a nitrile equivalent has been successfully utilized for tetrazole formation. For example, reaction of an amine 70 with an orthoformate in the presence of NaNa and ln(OTf)3 was proposed to provide the azido-imine (Finnegan intermediate 22), which cyclized to the tetrazole 71. These conditions also proved general for a range of amines and provided the 1 -substituted-5//-tetrazole. ... 

Glycosyltetrazoles were prepared as inhibitors dehydroquinate, which would potentially be used as antibacterial or herbicidal agents. The traditional Finnegan tetrazole method was used and enabled preparation of these substrates. 

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