H. Nagarajaiah

Synthesis, characterization and biological evaluation of thiazolopyrimidine derivatives

AbstractDifferent substituted diesters of thiazolopyrimidine were prepared by the treatment of 3,4 dihydropyrimidine2-thione with α-haloesters using ethanol under reflux condition affording 71–85% yield. IR, 1HNMR, 13CNMR and elemental analyses were used for the characterization of these compounds. The crystal and molecular structure of one of the product, 5-phenyl-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidine-2,6-dicarboxylic acid diethyl ester (3e) was verified by single crystal X-ray diffraction method. The antimicrobial activity was evaluated against four bacterial strains and one fungal species. Few of the derivatives exhibited antibacterial and antifungal activities. Graphical AbstractWe have reported the synthesis of some thiazolopyrimidine derivatives by cyclo-condensation of dihydropyrimidine with halo esters. Crystal structure analysis of one of the derivatives has been carried out. Some of the derivatives exhibited antibacterial and antifungal activities.

Methyl 5-(4-hy­droxy-3-meth­oxy­phen­yl)-2-(4-meth­oxy­benzyl­idene)-7-methyl-3-oxo-2,3-dihydro-5H-thia­zolo[3,2-a]pyrimidine-6-carboxyl­ate

In the title compound, C24H22N2O6S, a pyrimidine ring substituted with 4-hydroxy-3-methoxyphenyl is fused with a thiazole ring. The 4-hydroxy-3-methoxyphenyl group is positioned axially to the pyrimidine ring, making a dihedral angle 85.36 (7)°. The pyrimidine ring adopts a twist boat conformation. In the crystal, O—H⋯N interactions result in a chain running along the b axis. The carbonyl O atom bonded to the thiazole ring is involved in two C—H⋯O hydrogen-bond interactions forming centrosymmetric dimers; the ten- and six-membered rings resulting from these interactions have R 2 2(10) and R 1 2(6) motifs, respectively.

Structural modifications leading to changes in supramolecular aggregation of thiazolo(3, 2-a)pyrimidines: Insights into their conformational features

AbstractThe compounds, 7-methyl-3,5-diphenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (1), 3-amino-2-cyano-7-methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl ester (2), 2-dimethylaminomethylene-7-methyl-3-oxo-5-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (3), 2-(3-cyano-benzylidene)-5-(4-hydroxy-phenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl ester; with N,N-dimethyl-formamide (4) and 3-ethoxycarbonylmethyl-5-(4-hydroxy-3-methoxy-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl ester (5) have been synthesized and their structures evaluated crystallographically. Compound 1 crystallizes in the space group Pı̄ with Z=8, with four molecules in the asymmetric unit. Compound 2 also crystallizes in the space group Pı̄ with Z=4 wherein asymmetric unit accommodates two molecules. Compound 3 belongs to P21/c with Z=4, compound 4 crystallizes in Pbc2 1 with Z=4 and compound 5 belongs to Pı̄ with Z=2. In all the above compounds, the aryl ring positioned at C5 of thiazolopyrimidine ring is almost perpendicular. In the case of compounds with substituted phenyl ring, aryl group-up conformation predominates. However, for compounds with unsubstituted phenyl ring, aryl group-down conformation is adopted. By varying the substituents at positions C2, C3, C6 and on the aryl at C5 in the main molecular scaffold of (1-5), we have observed significant differences in the intermolecular interaction patterns. The packing features of the compounds are controlled by C-H…O, C-H…N, N-H…N O-H…N, C-H…π and π…π weak interactions. Graphical AbstractConformational features of some thiazolopyrimidines are described. In addition, by varying the substituents at positions C2, C3, C6 and on the aryl at C5 in the main molecular scaffold of (1-5), resulted in significant differences in the intermolecular interaction patterns. The packing features of the compounds are controlled by C-H…O, C-H…N, N-H…N O-H…N, C-H…π and π…π weak interactions.

2-(3,4-Di­fluoro­phen­yl)-1H-benzimidazole

In the title molecule, C13H8F2N2, the dihedral angle between the benzimidazole ring system and the difluoro-substituted benzene ring is 30.0 (1)°. In the crystal, molecules are linked by N—H⋯N hydrogen bonds, forming chains along [010]. In addition, weak C—H⋯F hydrogen bonds connect chains into a two-dimensional network parallel to (001). A weak C—H⋯π interaction is observed between an H atom of the benzimidazole ring sytem and the π system of the difluoro-substituted benzene ring.

Crystal structure of ethyl 5-(3-fluoro-phen-yl)-2-[(4-fluoro-phen-yl)methyl-idene]-7-methyl-3-oxo-2H,3H,5H-[1,3]thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.

In the title molecule, C23H18F2N2O3S, the pyrimidine ring is in a half-chair conformation and the 3-fluorophenyl group is in the axial position. The thiazole ring (r.m.s. deviation = 0.0252 Å) forms dihedral angles of 84.8 (7) and 9.6 (7)° with the 3-fluoro-substituted and 4-fluoro-substituted benzene rings, respectively. In the crystal, weak C—H⋯F and C—H⋯O hydrogen bonds connect molecules, forming zigzag chains along the b axis. In addition π–π stacking interactions with a centroid–centroid distance of 3.7633 (9) Å connect these chains into ladders via inversion-related 4-fluorophenyl groups.

Crystal structure of 2-acetyl-5-(3-methoxyphenyl)-3,7-dimethyl-5H-1,3-thiazolo[3,2-a]pyrimidine-6-carboxylate.

In the title molecule, C20H22N2O4S, the pyrimidine ring is in a flattened half-chair conformation and the 3-methoxyphenyl substituent is in an axial arrangement. The thiazole ring forms a dihedral angle of 81.3 (1)° with the benzene ring. In the crystal, weak C—H⋯S interactions link molecules into chains along [001]. In addition, there are π–π interactions between inversion-related thiazole rings with a centroid–centroid distance of 3.529 (2) Å. The ethyl group was refined as disordered over two sets of sites with an occupancy ratio of 0.52 (3):0.48 (2).

4-Bromo-methyl-6-tert-butyl-2H-chromen-2-one.

In the crystal structure of the title compound, C14H15BrO2, weak C—H⋯O interactions link the molecules into zigzag chains extending along the c-axis direction. These chains are further assembled into (100) layers via π–π stacking interactions between inversion-related chromenone fragments [interplanar distance = 3.376 (2) Å].

Ultrasonic synthesis and crystal structure analysis of two trimethylsilyloxy-substituted bicyclo[2.2.2]octene derivatives

AbstractThe compounds: 11-trimethylsilyloxy-1,2,3,4,4a,9a-hexahydro-1,4-etheno-anthraquinone and 4-benzyl-8-trimethylsilyloxy-4-aza-tricyclo[5.2.2.0]undec-8-ene-3,5-dione were synthesized by the Diels–Alder [4πs + 2πs] cycloaddition reaction of 2-(trimethylsilyloxy)-1,3-cyclohexadiene with naphthaquinone and N-benzylmaleimide under ultrasonic conditions. The crystal structure analysis was done using single crystal X-ray diffraction method. In both the compounds, the trimethylsilyloxy- and naphthaquinone/ N-benzylmaleimide moieties are endo- to the bicyclic ring. Graphical AbstractThe synthesis of two novel trimethylsilyloxy- substituted bicyclo[2.2.2]octene derivatives by employing ultrasonic reaction conditions is reported. The compounds have been characterized by single crystal X-ray studies.

Methyl 5-(4-acet­oxy­phen­yl)-2-(2-bromo­benzyl­idine)-7-methyl-3-oxo-2,3-di­hydro-5H-1,3-thia­zolo[3,2-a]pyrimidine-6-carboxyl­ate

In the title molecule, C24H19BrN2O5S, the pyrimidine ring is in a flattened half-chair conformation and the 4-acetoxyphenyl group is substituted axially to this ring. The thiazole ring is essentially planar [with a maximum deviation of 0.012 (2) Å for the N atom] and forms dihedral angles of 17.65 (13) and 88.95 (11)° with the bromo- and acetoxy-substituted benzene rings, respectively. The dihedral angle between the benzene rings is 81.84 (13) Å. In the crystal, pairs of weak C—H⋯O hydrogen bonds lead to the formation of inversion dimers. A weak C—H⋯π interaction and π–π stacking interactions with centroid–centroid distances of 3.5903 (14) Å are observed.

Methyl 2-(2-bromo-benzyl-idene)-5-(4-hy-droxy-phen-yl)-7-methyl-3-oxo-2,3-dihydro-5H-1,3-thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.

In the title compound, C22H17BrN2O4S, the central dihydropyrimidine ring, with a chiral C atom, is significantly puckered and adopts a half-chair conformation with the chiral C atom displaced from the mean plane of the remaining ring atoms by 0.305 (6) Å. The hydroxy-phenyl ring is positioned axially to the pyrimidine ring and almost bisects it, the dihedral angle between the mean-planes of the two rings being 89.78 (12)°. The methoxycarbonyl group is disordered over two sites with an occupancy ratio of 0.568 (5):0.432 (5), resulting in a major and a minor conformer. In the crystal, O—H⋯N and C—H⋯S interactions result in sheets along the c axis. The supramolecular assembly is stabilized by π–π stacking interactions between the 2-bromobenzylidene and thiazolopyrimidine rings [centroid–centroid distance = 3.632 (1) Å]. In addition, C—H⋯π interactions are also observed in the crystal structure.