A concise synthesis of a highly substituted 6-(1H-benzimidazol-1-yl)-5-nitrosopyrimidin-2-amine: synthetic sequence and the molecular and supramolecular structures of one product and two intermediates

Abstract

A concise and efficient synthesis of 6-benzimidazolyl-5-nitrosopyrimidines has been developed using Schiff base-type intermediates derived from N-(2-aminophenyl)-6-methoxy-5-nitrosopyrimidine-2,4-diamine. 6-Methoxy-N-{2-[(4-methylbenzylidene)amino]phenyl}-5-nitrosopyrimidine-2,4-diamine, (I), and N-{2-[(ethoxymethylidene)amino]phenyl}-6-methoxy-5-nitrosopyrimidine-2,4-diamine, (III), both crystallize from dimethyl sulfoxide solution as the 1:1 solvates CHNO·CHOS, (Ia), and CHNO·CHOS, (IIIa), respectively. The interatomic distances in these intermediates indicate significant electronic polarization within the substituted pyrimidine system. In each of (Ia) and (IIIa), intermolecular N-H...O hydrogen bonds generate centrosymmetric four-molecule aggregates. Oxidative ring closure of intermediate (I), effected using ammonium hexanitratocerate(IV), produced 4-methoxy-6-[2-(4-methylphenyl-1H-benzimidazol-1-yl]-5-nitrosopyrimidin-2-amine, CHNO, (II) [Cobo et al. (2018). Private communication (CCDC 1830889). CCDC, Cambridge, England], where the extent of electronic polarization is much less than in (Ia) and (IIIa). A combination of N-H...N and C-H...O hydrogen bonds links the molecules of (II) into complex sheets.

A concise and efficient synthesis of amino-substituted (1H-benzo[d]imidazol-1-yl)pyrimidine hybrids: synthetic sequence and the molecular and supramolecular structures of six examples

“…The starting pyrimidine (A) (see Scheme 1) was prepared as described previously (Cobo et al, 2018). In a typical procedure for the synthesis of intermediate (B), sodium dithionite (2.872 g, 16.5 mmol) was added to a suspension of (A) (1.00 g, 3.8 mmol) in methanol/water (3:1 v/v, 65 ml) at 323 K, and the resulting mixture was stirred for 30 min.…”

“…In addition to the structure of compound (VIIb) (Vicentes et al, 2019), it is of interest briefly to compare the structure of the hydrate (V) with that of the closely related nitroso compound (VIII) (see Scheme 2), whose constitution differs from that of the benzimidazole-pyrimidine component of (V) only in the replacement of one amino group in (V) with a nitroso group (Cobo et al, 2019). The supramolecular assembly of (VIII), like that of (V), is 2D but it is built from a combination of two independent N-HÁ Á ÁO hydrogen bonds and one C-HÁ Á ÁO hydrogen bond to form sheets in which rings of the R 2 2 (8), R 2 2 (20) and R 4 4 (16) types can be identified (Cobo et al, 2018).…”

“…In addition, benzimidazole has been shown to be an important heterocyclic fragment present in a large number of compounds with broad biological activity, including antimicrobial and antitumour activity (El-Gohary & Shaaban, 2017). With these considerations in mind, we have synthesized a new series of aminopyrimidine-benzimidazole hybrids, which can be regarded as a development of the nitrosopyrimidinebenzimidazole hybrids which we reported recently (Cobo et al, 2018). We report here the synthesis and characterization of a series of such hybrids, together with the structures of six of them.…”

“…We report here the synthesis and characterization of a series of such hybrids, together with the structures of six of them. The synthetic approach adopted here utilizes the recently reported (Cobo et al, 2018) N 4 -(2-aminophenyl)-6methoxy-5-nitrosopyrimidine-2,4-diamine (A) (see Scheme 1), which was readily reduced to the corresponding triamine (B) using sodium dithionite as the reducing agent. Whereas reaction of nitroso compound (A) with an aryl aldehyde produces a Schiff base intermediate which requires oxidation to form a benzimidazole unit (Cobo et al, 2018), the reaction of (B) with two molar equivalents of an aryl aldehyde produces the benzimidazole-pyrimidine hybrids (I)-(IV) directly, in a reaction which involves both a cyclocondensation and a double H-atom transfer to reduce the N-benzylidene substituent to an N-benzyl unit.…”

A self-penetrated three-dimensional zinc(II) coordination framework based on 4,4′,4′′-(1,3,5-triazine-2,4,6-triyl)tribenzoic acid and 1,3-bis[(imidazol-1-yl)methyl]benzene ligands: synthesis, structure and properties

“…A number of novel complexes are formed by nitrogen-containing ligands through noncovalent forces involving hydrogen bonds andstacking interactions (Jian et al, 2016). Recently, imidazole derivatives have been used to design intricate MOFs utilizing their excellent bridging functions (Arıcı et al, 2016;Cobo et al, 2018). Considering the superiority of these two types of organic ligands, novel high-dimensional MOFs with interesting topological frameworks and splendid performances can be synthesized on account of their plentiful coordination sites and flexible coordination modes.…”