Intermolecular decomposition of N-acylcyanamides

Unprecedented Aromatic Homolytic Substitutions and Cyclization of AmideIminyl Radicals: Experimental and Theoretical Study

“…The preparation of N-acetylcyanamides, N-benzoylcyanamides, and some of their derivatives has been reported, but these molecules often show a lack of stability. [31][32][33][34] N-acylcyanamides display properties in different fields, for instance, as prodrugs of cyanamide, [32] enzymatic inhibitors, [35] or heteroanalogues of ethylenes, [36] so there was also interest in finding a practical way of preparing them. Although N-acylcyanamides and their parent compound, cyanamide, have been reported mainly as unstable compounds, the synthesis of a few of the N,N-diacyl and N,N-dialkyl analogues has been described under the experimental conditions that we decided to follow first.…”

“…[33][34]37] Therefore, our preliminary preparation installed the cyanamide moiety by nucleophilic displacement of the mesylate group of quinoline derivative 1 with the cyanamide salt (Scheme 3). [37] As the major product present in the crude material seemed to be the dialkylated cyanamide 2 and in order to prevent the dialkylation process, we treated the cyanamide sodium salt in a one-pot procedure successively with a carboxylic acid chloride [32] and with 2-iodobenzylmesylate. This latter procedure failed to produce the desired N-acyl-N-(2-iodobenzyl)cyanamides 3, except with the acetic acid chloride which gave compound 3 a (Scheme 3).…”

Chlorotrimethylsilane Activation of Acylcyanamides for the Synthesis of Mono-N-acylguanidines

“…18 To a solution of sodium hydroxide (46.9 g, 1.17 mol) in distilled water (750 mL) was added cyanamide (49.6 g, 1.17 mol) in portions over 15 min. The mixture was stirred for 30 min.…”

“…We first began examining the direct activation of the cyanamide 7 18 and its reaction with benzylamine (Table 1). As anticipated, there was no reaction in the absence of an activating agent or in the presence of an exogenous base (entries 1 and 2).…”

“…It has previously been observed that these acylcyanamides decompose to generate a variety of diacyl- and cyanoguanidine byproducts. 18 We anticipated that the alkali salts of the cyanamide might provide a convenient, shelf-stable version of this reagent. We developed an efficient scalable preparation of the potassium salt of 7 (Scheme 1).…”