Studies in Quinazoline Chemistry. 3. Synthesis of 2-(2-Pyridon-3-yl)- and 2-[Thieno[2,3-b]pyridin-2(3)-yl]-3,4-dihydroquinazolines

Abstract

We have studied the reaction of o-aminophenyldiphenylcarbinol with substituted cyanothienopyridine, cyanopyridines, cyanopyridones, and cyanopyridinethiones. We have shown that in the case of pyridine derivatives, the reaction occurs with formation of 3,4-dihydroquinazolines, which exist in solution in two tautomeric forms. We have determined the general characteristics of initial fragmentation of the indicated products under electron impact.Continuing our work on synthesis of 3,4-dihydroquinazolines [2], in this report we describe the reactionThe reaction of nitriles 1a-h with carbinol 1 was carried out according to the procedure previously developed in [2], in the presence of equimolar amounts of HClO 4 . We established that the direction of the reaction and the product yields are mainly determined by the structure of the nitrile (see Scheme 1).Thus in the case of cyanothienopyridine 2a, cyanopyridines 2b,c, and N-unsubstituted cyano-2-pyridones 2d-e, the corresponding dihydroquinazolinium perchlorates 3a-e are formed; and from N-ethyl-3-cyano-6-methyl-4-methoxymethyl-2-pyridone (2f) and 3-cyano-2-pyridinethiones 2g-h, instead of products of type 3, the 9-phenylacridinium perchlorate (4) is formed according to a competing reaction [3].We have established that in the conversions under consideration, the solvent plays an important role. In nitromethane, we obtain salts 3 in good yields (Table 1). In chloroform, the yields of the latter decrease as a result of a secondary reaction to form the acridinium salt 4. In DMSO, no products of type 3 or 4 are formed. Thus we determined the optimal conditions for synthesis of salts 3: boiling nitromethane as the solvent, equimolar ratios of carbinol 1, nitrile 2, and HClO 4 . Under these conditions, the perchlorates 3a-e were obtained in 50%-85% yields (see Table 1). When treated with an aqueous solution of base, salts 3 are converted to the corresponding free bases 5a-e.

Synthesis, crystal and molecular structure of 2-(3-chloropropyl)-6-methyl-4-phenylquinazoline 3-oxide

“…The mass spectrometry of quinazolines has been examined by a number of workers [5][6][7][8][9][10]. In previous work [5], we showed that the initial pathways for the decomposition of the molecular ions of quinazoline 3-oxides are accompanied by the elimination of the methyl substituent or oxygen atom, followed only then by opening of the heteroaryl ring.…”

“…3b demonstrates the different displacement of molecules A and B relative to the central molecule. The shortest interatomic distances in the "dimer" are N (1) ...C (6B) (3.460) and N (2) ...C (2B) (3.457 Å) and the shortest distances between the "dimers" are C (1) ...C (5A) (3.649) and C (7) ...C (3A) (3.565 Å).…”