Synthesis of nitrogen‐containing heterocycles 10. Reaction of 2‐amino‐1h‐imidazole derivatives with ethoxymethylene compounds

Abstract

The direct annelation reaction of 4-substituted 2-amino-1-benzylideneamino-1H-imidazoles (1) or 2-amino-1-isopropylideneamino-1H-imidazole (8) with ethoxymethylenemalononitrile (I) gave successfully bicyclic imidazo[1,2-a]pyrimidine compounds 2 and 9 in high yields. The reactions of other ethoxymethylene compounds of lower reactivity, i.e., ethyl ethoxymethylenecyanoacetate (II) and diethyl ethoxymethylenemalonate (III), with 2-amino-1H-imidazoles under similar conditions afforded the corresponding enamines 3, 4 and 10, which, upon heating in the presence of an acid or a base, could readily be cyclized to form imidazopyrimidines except for 1-isopropylideneamino compound 10. In general, the 3-phenyl compounds (3b and 4b) did not cyclize to the type 2 compound resulting in a full recovery of the starting enamines.

EMCA and DEEM as Michael Reagents Used in Organic Synthesis

“…Synthesis of some novel imidazo[1,2-a]pyrimidines (33) (Fig. 31) has been also reported recently by Miyamoto [151].…”

“…Miyamoto [151] obtained derivatives of imidazole (67) (Fig. 64), wh`ich were then cyclized to two types of imidazo [1,2-a]pyrimidine.…”

Interaction of 1,2-Diaminoimidazoles with Ethoxymythelene-Containing Compounds

“…As a polynucleophilic agent (1,3-C,N and 1,4-N,N) diaminoimidazole can form six-and seven-membered systems in the reaction with dielectrophilic agents. The determinative factor in the reaction direction are electrophile nature and conditions in which synthesis was performed [12][13][14][15][16].…”

“…Among the majority of condensed systems based on imidazole, special attention is paid to imidazopyridazine. These compounds have proven to be good anti-viral, anti-epileptic and anti-cancer drugs [2][3][4][5][6][7][8][9][10][11][12]. Imidazo [1,2-b]pyridazine and imodazo [1,5-b]pyridazine have a special place among possible variants of the system existence.…”

“…Previously it was described interaction ethoxymethylene-containing compounds with 4-substituted 2-amino-1-benzaliden (isopropylidene) of aminoimidazoles leading to imidazo[1,2-a]pyrimidines formation. The reaction was performed in acetonitrile with acid or basis catalyst [12]. However this reaction was not extended to 1,2-diaminoimidazoles unsubstituted on carbon in the fifth position.…”