Three Synthetic Routes to a Sterically Hindered Tetrazole. A New One-Step Mild Conversion of an Amide into a Tetrazole

Article abstract of DOI:10.1021/jo00007a027

5-<4'-Methyl-1,1'-biphenyl-2-yl>-1H-tetrazole (6), which contains a sterically hindered o-tetrazole group, was synthesized by three different routes, one of them employing a new tetrazole synthesis.The first involved the reaction of trialkyltin azides with 4'-methyl-1,1'-biphenyl-2-carbonitrile (3).The resultant trimethyltin-tetrazole adduct could be hydrolyzed with acid to yield biphenylyltetrazole 6.The tri-n-butyltin-tetrazole adduct, however, was transformed into the corresponding N-trityl-protected tetrazole 5 to permit removal of the organic soluble tri-n-butyltin byproducts.The trityl group also permits 5 to be brominated at the benzylic position and then alkylated by imidazole derivatives.Subsequent acid hydrolysis of the trityl protecting group of 5 yielded biphenylyltetrazole 6.The second synthesis involved the nitrosation of an N-(2-cyanoethyl)-protected biphenylamidrazone 10 using N2O4 (g) to yield N-(2-cyanoethyl)-protected tetrazole 12.Aqueous base removes the cyanoethyl protecting group to yield biphenylyltetrazole 6.The third method involves the novel transformation of an N-(2-cyanoethyl)-substituted amide into the corresponding N-(2-cyanoethyl)-protected tetrazole in one step using triphenylphosphine, diethyl azodicarboxylate (DEAD), and azidotrimethylsilane.Subsequent base hydrolysis of the cyanoethyl group yielded 6 as before.Examples are also provided of the application of this new reaction to other N-(2-cyanoethyl)-protected carboxamides.