Synthesis and biological activity of novel 1‐(2,3,4‐trimethoxyphenyl)‐2‐{[5‐(3,4,5‐trimethoxyphenyl)‐1,3,4‐thiadiazol‐2‐yl]thio}ethanone oxime ester derivatives

In a search for new fungicide and anticancer agent with improved biological properties and different bioactivity spectrum, we designed and synthesized a series of novel oxime esters containing 1,3,4‐thiadiazole group in moderate yield starting from gallic acid. The title compounds were identified by IR, ¹H NMR, ¹³C NMR and elemental analysis. The bioassay tests showed that these title compounds exhibit weak to moderate anticancer activity in vitro by MTT method.     

1‐(Thiophen‐3‐yl)ethanone

The structure of the title compound, C₆H₆OS, exhibits a flip‐type disorder of the thiophene ring [occupancy ratio = 0.848 (3):0.152 (3)], which is typical for many thiophene derivatives. The puckered thiophene ring is essentially coplanar with the plane formed by the non‐H atoms of the acetyl substituent, similar to its simple analogues, i.e. 3‐acetyl‐2‐carboxythiophene, 4‐acetyl‐3‐carboxythiophene and 3,5‐diacetyl‐2‐ethylamino‐4‐methylthiophene. In the crystal structure, molecules are connected by C—H...π hydrogen bonds, forming a sheet parallel to the (001) plane. Moreover, an inspection of the crystal lattice reveals that there are short S...O contacts connecting the molecules of adjacent sheets. Comparison of the title crystal structure with its simple 3‐methoxythiophene analogue shows a close similarity in the herringbone arrangement of molecules and in the presence of C—H...π interactions and S...O contacts.     

1‐(2‐Hydroxy‐4,6‐di­methyl­phenyl)­ethanone

In the crystal of the title compound, C₁₀H₁₂O₂, there are two symmetry‐independent mol­ecules, which are essentially superimposable. Each mol­ecule exhibits an intramolecular O—H?O hydrogen bond, with O?O separations of 2.483 (4) and 2.468 (4) Å.     

1‐(1,3‐Di­thian‐2‐yl)‐2‐phenyl­ethanone

The title mol­ecule, C₁₂H₁₄OS₂, has approximate C_s symmetry. The di­thia­ne ring adopts a chair conformation with the acetyl substituent in an axial orientation. Weak intermolecular C—H?O hydrogen bonds link mol­ecules into a chain along the y axis.     

Synthesis and reactions of 2‐chloro‐2‐(hydroximino)‐1‐(4‐methyl‐2‐phenylthiazol‐5‐yl)ethanone

3‐Nitrosoimidazo[1,2‐a]pyridine, 3‐nitrosoimidazo[1,2‐a]pyrimidine, 3‐nitrosoquinoxaline, 2‐nitroso‐4H‐benzo[b]thiazine, 2‐nitroso‐4H‐benzo[b]oxazine, isoxazoles, isoxazolo[3,4‐d]pyridazines and pyrrolo[3,4‐d]isoxazole‐4,6‐dione were synthesized from 2‐chloro‐2‐(hydroximino)‐1‐(4‐methyl‐2‐phenylthiazol‐5‐yl)ethanone and different reagents. Structures of the newly synthesized compounds were confirmed by elemental analysis and spectral data.     

N‐(X‐Methylphenyl)‐2‐{(Z)‐[(2,3,4‐trimethoxyphenyl)methylidene]amino}‐4,5,6,7‐tetrahydro‐1‐benzothiophene‐3‐carboxamide,where X = 2 and 3

The title isomers, viz. the N‐(3‐methylphenyl)‐, (I), and N‐(2‐methylphenyl)‐, (II), derivatives, both C₂₆H₂₈N₂O₄S, adopt an E configuration that places the thiophene and trimethoxyphenyl groups on opposite sides of the C=N double bond, providing a suitable orientation for formation of an intramolecular N—H...N hydrogen bond. However, while the molecule in (I) is close to being planar, the N‐methylphenyl group in (II) is twisted significantly from the plane of the remainder of the molecule. Both crystal structures are essentially layered and there are no intermolecular N—H...O hydrogen bonds. Compound (I) has a significantly higher calculated density than (II) (1.340 cf 1.305 Mg m⁻³), indicating that the molecular packing in the meta isomer is overall more efficient than that in the ortho isomer.     

(E)‐3‐(Benzo[b]thiophen‐2‐yl)‐2‐(3,4,5‐trimethoxyphenyl)acrylonitrile and (Z)‐3‐(benzo[b]thiophen‐2‐yl)‐2‐(3,4‐dimethoxyphenyl)acrylonitrile

The title compounds, C₂₀H₁₇NO₃S, (I), and C₁₉H₁₅NO₂S, (II), were prepared by the reaction of benzo[b]thiophene‐2‐carbaldehyde with (3,4,5‐trimethoxyphenyl)acetonitrile and (3,4‐dimethoxyphenyl)acetonitrile, respectively, in the presence of methanolic potassium hydroxide. In (I), the C=C bond linking the benzo[b]thiophene and the 3,4,5‐trimethoxyphenyl units has E geometry, with dihedral angles between the plane of the bridging unit and the planes of the two adjacent ring systems of 5.2 (3) and 13.1 (2)°, respectively. However, in (II), the C=C bond has Z geometry, with dihedral angles between the plane of the bridging unit and the planes of the adjacent benzo[b]thiophene and 3,4‐dimethoxyphenyl units of 4.84 (17) and 76.09 (7)°, respectively. There are no significant intermolecular hydrogen‐bonding interactions in the packing of (I) and (II). The packing is essentially stabilized via van der Waals forces.     

4,6‐Di­chloro‐2‐(methyl­thio)­pyrimidine

The structure of the title compound, C₃₀H₂₄Cl₁₂N₁₂S₆, (I), comprises six symmetry unique mol­ecules that vary only slightly in their N—C—S—C torsion angle. All the mol­ecules are planar to within less than 3.1°.     

1‐(2‐Hydro­xy‐4‐methoxy­phenyl)‐3‐(2,3,4‐tri­methoxy­phenyl)­prop‐2‐en‐1‐one

The title compound, C₁₉H₂₀O₆, crystallizes in the centrosymmetric space group P2₁/c with one mol­ecule in the asymmetric unit. The mol­ecule is approximately planar and the dihedral angle between the phenyl rings is 11.0 (1)°. The H atoms of the central propenone group are trans. There is an intramolecular O—H⃛O hydrogen bond and the mol­ecules are crosslinked by four intermolecular C—H⃛O hydrogen bonds, producing a three‐dimensional network.     

Hydrogen‐bonding patterns in enaminones: (2Z)‐1‐(4‐bromophenyl)‐2‐(pyrrolidin‐2‐ylidene)ethanone and its piperidin‐2‐ylidene and azepan‐2‐ylidene analogues

The title compounds, namely (2Z)‐1‐(4‐bromophenyl)‐2‐(pyrrolidin‐2‐ylidene)ethanone, C₁₂H₁₂BrNO, (I), (2Z)‐1‐(4‐bromophenyl)‐2‐(piperidin‐2‐ylidene)ethanone, C₁₃H₁₄BrNO, (II), and (2Z)‐2‐(azepan‐2‐ylidene)‐1‐(4‐bromophenyl)ethanone, C₁₄H₁₆BrNO, (III), are characterized by bifurcated intra‐ and intermolecular hydrogen bonding between the secondary amine and carbonyl groups. The former establishes a six‐membered hydrogen‐bonded ring, while the latter leads to the formation of centrosymmetric dimers. Weak C—H...Br interactions link the individual molecules into chains that run along the [011], [101] and [101] directions in (I)–(III), respectively. Additional weak Br...O, C—H...π and C—H...O interactions further stabilize the crystal structures.     

Molecular dynamics of cis‐1‐(2‐hydroxy‐5‐ methylphenyl)ethanone oxime and N‐(2‐hydroxy‐4‐methylphenyl)acetamide in solution studied by NMR spectroscopy

The formation of hydrogen bonds and molecular dynamics for the molecules cis‐1‐(2‐hydroxy‐5‐methylphenyl)ethanone oxime ( I ) and N‐(2‐hydroxy‐4‐methylphenyl)acetamide ( II ) have been investigated in solution using NMR. The results confirm the formation of O? H···O, O? H···N and O···H? N type inter‐ and intramolecular hydrogen bonds. Spin‐lattice relaxation times (T₁), activation energy of molecular dynamics and energy of intramolecular hydrogen bonds have been determined. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis of n‐(thio)phosphoryl‐n′‐2‐benzoxazolyl semicarbazides

We prepared the benzoxazole derivatives bearing the (thio) phosphoryl moiety by addition reactions of 2‐hydrazionbenzoxazole with isothiocyanato (thio) phosphates and characterized their structures by elementary analysis and ¹H NMR and IR spectral data. From the results of biological activity screening, we found that these compounds possess some herbicidal, and plant growth regulator activities, and especially good fungicidal activity against Puccinia recondita. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:151–155, 2001     

Synthesis of novel N1‐(2‐furanidyl)‐5‐fluorouracil derivatives of α‐hydroxy(thio)phosphonates

Several N¹‐(2‐furanidyl)‐5‐fluorouracil derivatives of α‐hydroxythiophosphonates were synthesized via oxidation by Moffatt's method of N¹‐(2‐furanidyl)‐N³‐(hydroxyalkyl)‐5‐fluorouracil, followed by the addition of diethyl thiophosphite. The phosphonate products were obtained by the oxidation of the corresponding thiophosphonates with m‐chloroperoxybenzoic acid. The crystal structure of compound 6a was determined by X‐ray diffraction. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:211–215, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10021     

2‐[2‐(Pyrrolidin‐2‐yl)propan‐2‐yl]‐1H‐pyrrole and its amide derivative 1‐{2‐[2‐(1H‐pyrrol‐2‐yl)propan‐2‐yl]pyrrolidin‐1‐yl}ethanone

In the title compounds, C₁₁H₁₈N₂, (II), and C₁₃H₂₀N₂O, (III), the pyrrolidine rings have twist conformations. Compound (II) crystallizes with two independent molecules (A and B) in the asymmetric unit. The mean planes of the pyrrole and pyrrolidine rings are inclined to one another by 89.99 (11) and 89.35 (10)° in molecules A and B, respectively. In (III), the amide derivative of (II), the same dihedral angle is much smaller, at only 13.42 (10)°. In the crystal structure of (II), the individual molecules are linked via N—H...N hydrogen bonds to form inversion dimers, each with an R²₂(12) graph‐set motif. In the crystal structure of (III), the molecules are linked via N—H...O hydrogen bonds to form inversion dimers with an R²₂(16) graph‐set motif.     

(E)‐2‐(2‐Adamantylidene)‐3‐(1‐ferrocenylethylidene)succinic anhydride

The title compound, [Fe(C₅H₅)(C₂₁H₂₁O₃)], was obtained from successive Stobbe condensations between ketones and di­methyl succinate. The succinic anhydride five‐membered ring is distorted significantly from planarity, with the buta­diene moiety being twisted by 49.3 (2)° from planarity and the C atoms at the succinic anhydride end of the alkene bonds showing significant pyramidalization. The cyclo­penta­diene rings of the ferrocenyl moiety adopt an almost eclipsed conformation.     

‘Click Synthesis’ of 1H‐1,2,3‐Triazolyl‐Based Oxiconazole (=(1Z)‐1‐(2,4‐Dichlorophenyl)‐2‐(1H‐imidazol‐1‐yl)ethanone O‐[(2,4‐Dichlorophenyl)methyl]oxime) Analogs

The ‘click synthesis’ of some oxiconazole analogs 5a – 5v having 1H‐1,2,3‐triazolyl residues by Huisgen cycloaddition was achieved in four steps (Scheme 1). Oximation of phenacyl chloride ( 1 ) followed by azidation of 2‐chloro‐1‐phenylethanone oxime ( 2 ) provided azido ketoxime 3 . The CuI‐catalyzed Huisgen cycloaddition of 3 with terminal alkynes gave the 4‐substituted (at the triazole) 2‐(1H‐1,2,3‐triazol‐1‐yl)‐1‐phenylethanone oximes 4a – 4i . The O‐alkylation of 4a – 4i with various alkyl halides resulted in the formation of the target molecules 5a – 5v in good yields.     

Synthesis of 5‐(Arylselanyl)‐2‐(arylsulfanyl)benzoates by [3+3] Cyclocondensation of 3‐(Arylsulfanyl)‐1‐(silyloxy)buta‐1,3‐dienes with 2‐(Arylselanyl)‐3‐(silyloxy)alk‐2‐en‐1‐ones

Functionalized 5‐(arylselanyl)‐2‐(arylsulfanyl)benzoates were prepared by [3+3] cyclocondensation of 3‐(arylsulfanyl)‐1‐(silyloxy)buta‐1,3‐dienes with 2‐(arylselanyl)‐3‐(silyloxy)‐alk‐2‐en‐1‐ones.     

1‐[5‐(4,5‐Dimethyl‐1,3,2‐dioxaborolan‐2‐yl)thiophen‐2‐yl]ethanone and 4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)benzaldehyde

In both title compounds, C₁₀H₁₃BO₃S, (I), and C₁₃H₁₇BO₃, (II), the molecules adopt nearly planar conformations. The crystal packing of (I) consists of a supramolecular two‐dimensional network with a herringbone‐like topology formed by self assembly of centrosymmetric pairs of molecules linked via dipole–dipole interactions. The crystal structure of (II) consists of a supramolecular two‐dimensional network built up from centrosymmetric pairs of molecules viaπ–π interactions. These pairs of molecules are self‐organized in an offset fashion related by a symmetry centre, generating supramolecular ribbons running along the [101] direction. Neighbouring ribbons are stacked via complementary van der Waals and hydrophobic methyl–methyl interactions.