Tandem Cycloaddition of Azides to 3,3-Diaminoacrylonitriles (2-Cyanoacetamidines) and Cornforth-Type Rearrangement as an Approach to 5-Amino-1,2,3-triazole-4-N-substituted Imidamides

Abstract

An efficient base-catalyzed, metal-free method for the synthesis of 5-amino-1,2,3-triazole-4-N-sulfonyl-and arylimidamides, directed by the structure of the amidine group, has been developed. It is based on a previously unknown tandem process involving cycloaddition reaction to 3,3diaminoacrylonitriles (2-cyanoacetamidines) with aryl(alkyl)sulfonyl or aryl azides and Cornforth-type rearrangement. During the reaction optimization, different factors were found to facilitate the title reaction, which include the use of a strong base and N-mono-or N,N′-disubstituted 3,3-diaminoacrylonitriles. The reaction is tolerant to variously N-monosubstituted and N,N′-disubstituted 3,3-diaminoacrylonitriles and to various aryland aryl/alkyl sulfonyl azides. The developed method has a broad scope and can be applied to obtain a variety of 5-amino-1,2,3triazole-4-carbimidamides bearing at the N 1 position alkyl, allyl, propargyl, benzyl, cycloalkyl, and heteroaryl substituents and sulfonyl and aryl substituents at the amidine group. Post-cyclization reactions of prepared 5-amino-1,2,3-triazoles with DMF-DMA DMA-DMF leads to 1,2,3-triazolo [4,5-d]pyrimidines, 8-aza purine analogues demonstrating the applicability of the prepared compounds in organic synthesis.

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

“…To our surprise we obtained (Z) -5-amino-1-benzyl- N' -(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-1 H- 1,2,3-triazole-4-carboximidamide ( 3a ) in 93% yield as the major product with 5-amino-1-benzyl-1 H -1,2,3-triazole-4-carbonitrile ( 4 ) in 5% yield when the reaction was carried out at room temperature in 1,4-dioxane in the presence of an equivalent amount of TEA ( Table 1 , entry 1). This result is in contrast to our previous findings where the reaction of compound 1a with sulfonyl azides led to 5-amino-1,2,3-triazole-4- N -sulfonylamidines selectively [ 17 ].…”

“…Some of the prepared compounds exhibited a mild toxic effect on tumor cells in comparison with normal human embryonic cells. [17] and compounds 1a,c-e,h-j are commercially available. Azides 2a-d,f,g were synthesized according to the literature procedures [18][19][20][21][22][23], and azide 2e is commercially available.…”

“…3,3-Diaminoacrylonitriles 1b and 1f were synthesized from ethyl 2-cyanoacetimidate and corresponding amines according to the literature procedure [ 17 ] and compounds 1a , c – e , h – j are commercially available. Azides 2a – d , f , g were synthesized according to the literature procedures [ 18 – 23 ], and azide 2e is commercially available.…”

“…Method A. In a manner similar to [ 17 ], DBU (0.5 mmol) was added to the solution of amidine 1 (0.5 mmol) in 1,4-dioxane (2 mL) at room temperature and azide 2 (0.5 mmol) was added to the resulting solution 5 min later. The reaction mixture was stirred for 30 min at room temperature, then water (6 mL) was added and the resulting solution was stirred for additional 5 min.…”

Synthesis of Non-Aromatic Pyrroles Based on the Reaction of Carbonyl Derivatives of Acetylene with 3,3-Diaminoacrylonitriles

“…Synthesis 3.1.1. Preparation of 3,3-Diaminoacrylonitriles 3 3,3-Diaminoacrylonitriles 3a-f, h, l were synthesized from ethyl 2-cyanoacetimidate and corresponding amines according to the literature procedures [20][21][22][23]; the compounds 3g, i-k, m are commercially available.…”