Trimerization of nitriles in the synthesis of multipyrimidinophanes

Abstract

Multimacrocycles, i.e., compounds in which several macrorings are covalently linked by intermolecular bridges, are promising subjects for studies due to their potential unique aggregation and complexing properties. Multicalixarenes [1], multicyclodextrins [2, 3], multiporphyrins [4–6], and combinations of different covalently linked macrocycles [7, 8] have been synthesized and are extensively studied. In the present communication we describe the synthesis of macrocyclic compounds containing uracil fragments, pyrimidinophanes, and a new method for their covalent binding with each other to obtain a multimacroring, multipyrimidinophane. At present, multipyrimidinophanes are known, in which two “monomeric” pyrimidinophane units are linked through intermolecular paraand meta-phenylenedimaleimide [9], 4,4′-diphenol [10], and methylene [11] bridges. We now report on the synthesis of multipyrimidinophane consisting of three macrocyclic units attached to the carbon atoms of 1,3,5-triazine ring via trimerization of CN groups to 1,3,5-triazine structure. Successful cyclotrimerization of nitriles to 1,3,5-triazines requires quite severe conditions (high temperature and pressure) [12]. Cyanamide derivatives undergo cyclotrimerization more readily than nitriles [13–15]. For example, dialkylcyanamides react with trifluoromethanesulfonic anhydride under mild conditions to give the corresponding 1,3,5-triazines in almost quantitative yield [16, 17]. Both sterically hindered cyanamides and those containing various heteroatoms (N, O, S) in the substituents can be involved in this reaction. By reaction of 1,3-bis(5-bromopentyl)-6-methyluracil (I) with disodium cyanamide in acetonitrile we obtained 22% of pyrimidinophane II containing a cyanamide fragment in the decamethylene linker (Scheme 1). The H NMR spectrum of II was typical of other pyrimidinophanes consisting of one uracil fragment and 10 methylene group in the bridge; namely, protons in the methylene groups on the uracil nitrogen atoms (CH2 and CH2) were magnetically nonequivalent [18], and they resonated as four multiplets in the region δ 4.45–3.62 ppm. Pyrimidinophane II was treated with trifluoromethanesulfonic anhydride in methylene chloride. The reaction was accompanied by heat evolution, and the product was assigned the structure of multipyrimidinophane III formed as a result of trimerization of the ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 7, pp. 1096–1098. © Pleiades Publishing, Ltd., 2013. Original Russian Text © A.E. Nikolaev, V.E. Semenov, I.V. Galyametdinova, L.F. Saifina, D.R. Sharafutdinova, V.S. Reznik, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 7, pp. 1110–1112.