RESUMO
The solvent-free elimination of sulfinic acid and aromatization of 1,6-trans-substituted bis(arylsulfone) trienes is reported. It is shown that sublimation can be used as a 'green' method to combine the thermal transformation of six trienes and the crystal growth of the resulting 4-(phenylsulfonyl)biphenyls. When the sublimation conditions are carefully controlled, high quality single crystals of the 4-(phenylsulfonyl)biphenyls are obtained. Theoretical modelling of the reaction using the simplified triene Ph-(CH)6-SO2H showed that the cyclization is energetically feasible and that the complete conversion is possible during the timescale of the sublimation. At temperatures slightly higher than the optimum sublimation temperature two of the trienes transformed into 1,4-cyclohexadienes that did not eliminate phenylsulfinic acid. A reaction mechanism involving a 1,3-hydrogen shift induced by free PhS⢠radicals is proposed for the formation of the 1,4-cyclohexadienes.
RESUMO
The identification and study of supramolecular synthons is a fundamental task in the design of pharmaceutical cocrystals. The malaria drug pyrimethamine (pyr) and the antibiotic trimethoprim (tmp) are both 2,4-diaminopyrimidine derivatives, providing the same C-NH2/N=C/C-NH2 and C-NH2/N=C interaction sites. In this article, we analyze and compare the synthons observed in the crystal structures of tmp and pyr cocrystals and molecular salts with sulfamethazine (smz), α-ketoglutaric acid (keto), oxalic acid (ox), sebacic acid (seb), and azeliac acid (az). We show that the same coformer interacts with different binding sites of the 2,4-diaminopyrimidine ring in the respective tmp and pyr cocrystals or binds at the same site but gives H bonding patterns with different graph set notions. Pyr·smz·CH3OH is the first crystal structure in which the interaction of the sulfa drug at the C-NH2/N=C/C-NH2 site with three parallel NH2···N, N···NHsulfonamide, and NH2···O=S H bonds is observed. The main synthon in (tmp+)(keto-).0.5H2O and (tmp+)2(ox2-)·2CH3OH is the motif of fused R 2 1(6) and R 1 2(5) rings instead of the R 2 2(8) motif typically observed in tmp+ and pyr+ carboxylates. Tmp/az is a rare example of cocrystal-salt polymorphism where the two solid-state forms have the same composition, stoichiometry, and main synthon. Theoretical calculations were performed to understand the order of stability, which is tmp·az cocrystal > (tmp+)(az-) salt. Finally, two three-component tmp/sulfa drug/carboxylate cocrystals with a unique ternary synthon are described.