Two-stage threecomponent synthesis of 6,11-diaza-1,5(2,5)-dioxazole- 3(1,2)-benzenecycloundecapha ne-14,54- dicarbonitrile

Abstract

The possibilities of 2-amino-3,3-dichloroacrylonitrile (ADAN) used for the construction of macrocyclic structures such as cyclophanes with two oxazole fragments are investigated. For this purpose, bifunctional reagents were used in the classic ADAN transformation into 5-amino-4-cyanooxazoles (sequential treatment of ADAN with acyl chloride and a primary or secondary amine). As a result of the reaction of 2,2'‎-(1,2-phenylene)-diacetyl chloride with 2 eq of ADAN, a compound with two acrylonitrile fragments, 2,2' ‎- (1,2-phenylene)bis(N- (2,2-dichloro-1-cyanovinyl)acetamide), was obtained. In this substance, both ADAN residues can interact with amines and form oxazole cycles: for example, the treatment with an excess of dimethylamine produces 2,2'‎ - (1,2-phenylenebis(methylene))bis(5-(dimethylamino)oxazole-4-carbonitrile). The target macrocyclic structure was obtained by the interaction of 2,2'‎ - (1,2-phenylene)bis(N-(2,2-dichloro-1-cyanovinyl)acetamide) with butane-1,4-diamine, as a result the simultaneous forming of both oxazole rings and an aliphatic bridge connected with them was happened. At this stage, it was used a procedure, that is typical of the creation of macrocyclic structures based on polyfunctional reagents, — strong dilution (about 0.04 M). The molecule of the synthesized 6,11-diaza-1,5(2,5)-dioxazole-3(1,2)-benzenecycloundecaphan-14,54-dicarbonitrile has high spatial symmetry, which is confirmed by the presence of only one series of peaks in the 1H and 13C NMR spectra (for example, the butane-1,4-diamine fragment in the aliphatic part of the spectrum looks likes two triplets). The formation of a macrocyclic structure is evidenced by HPLC-MS data, as well as homo- and heteronuclear correlations in the NMR spectra. The proposed procedure for the synthesis of 6,11-diaza-1,5(2,5)-dioxazole-3(1,2)-benzenecycloundecaphan- 14,54-dicarbonitrile is based on the use of simple and inexpensive reagents, and the total yield of the target substance in two stages starting with the 2,2'‎ - (1,2-phenylene)diacetyl chloride, is 51 %.