Cyanide-Free Synthesis of Air Stable N-Substituted Li and K Cyanamide Salts from Tetrazoles. Applications toward the Synthesis of Primary and Secondary Cyanamides as Precursors to Amidines

Abstract

A practical two-step synthesis of N,N′-disubstituted cyanamides consists in the low-temperature metalation of Nsubstituted 5H-tetrazoles that undergo spontaneous cycloreversion at 0 °C releasing dinitrogen, and forming N-metalated cyanamides that can be reacted in situ with a variety of electrophiles. Remarkably, the N-substituted Li and K cyanamides are air stable white solids at room temperature. Addition of lithium organometallics to the N,N′-disubstituted cyanamides provides a new method for accessing N,N′-disubstituted amidines.

Photoredox- and piezo-catalysed access to complex trifluoromethylated polycyclic structures from ynamides

“…Despite the versatility of these methods, limitations remained for the preparation of some functionalized ynamide derivatives, which prompted us to explore a new synthetic route. Inspired by Hanessian's work on the synthesis of N , N ′-disubstituted cyanamides from tetrazoles, 24 we hypothesized that easily reachable N -aryl-4-(trimethylsilyl)-5 H -triazoles could serve as synthons for ynamide synthesis (Scheme 2, method C ). Conveniently, treatment of the triazole substrate with a strong base such as n -BuLi leads to a N -metalated ynamide intermediate formed through the cycloreversion of the triazole releasing dinitrogen.…”

Advances in Tetrazole Synthesis – An Overview

“…The potential hazards of side products such as HBr and HCN formed during the synthesis of cyanamides using cyanide reagents can be avoided. [40] Tetrazoles can be used as an isosteric substituent of several functional groups in forming biologically active substances. Tetrazole motifs are used in drug pharmacophores to replace carboxylic acid moiety because they are more stable than carboxylic derivatives.…”

“…The process is a cyanide‐free scalable method for primary and secondary cyanamides. The potential hazards of side products such as HBr and HCN formed during the synthesis of cyanamides using cyanide reagents can be avoided [40] …”

Green and efficient synthesis of dibenzyl cyanamides and ureas with cyanamide as a block

“…(2) Further techniques involve thiourea dehydrosulfurization, hydration of urea, and the transformations from isocyanates, isocyanides, or isothiocyanates. 4 (3) Cyanogenic metals to introduce cyanide, such as lithium cyanide. 5 (4) Substitution of secondary amines react with cyanide reagents.…”