Structure and Conformational Analysis of 5,5-Bis(bromomethyl)-2-(4-methoxyphenyl)-1,3-dioxane

The structure of 5,5-bis(bromomethyl)-2-(4-methoxyphenyl)-1,3-dioxane has been studied by ¹H and ¹³C NMR and X-ray diffraction. Molecules of the title compound exist in the chair conformation with equatorial orientation of the methoxyphenyl substituent. The dioxane ring inversion path, free conformational energy, and optimal conformation of the aryl group have been determined by computer simulation in terms of the DFT PBE/3ζ method. The calculation results are consistent with the X-ray diffraction data.     

Chemistry of 1,5-diketones: I. Halogenation of aryl-substituted pent-2-ene-1,5-diones,pentane-1,5-diones,and their fused analogs

Halogenation of 3-(4-methoxyphenyl)-1,5-diphenylpent-2-ene-1,5-dione, 3-(4-methoxyphenyl)-1,5-diphenylpentane-1,5-dione, and 2-[1-(4-methoxyphenyl)-3-oxo-3-phenylpropyl)-1,2,3,4-tetrahydroaphthalen-one with bromine, chlorine, and dichloro(phenyl)-λ³-iodane leads to formation of the corresponding monobromo-, dichloro-, or trichloro-substituted 1,5-diketones, depending on the conditions. Halogenation of the aliphatic chain and methoxyphenyl substituent can be accompanied by heterocyclization to give pyrylium salts.     

Synthesis and pharmacological evaluation of some 3-(4-methoxyphenyl)-2-substitutedamino-quinazolin-4(3H)-ones as analgesic and anti-inflammatory agents

A variety of novel 3-(4-methoxyphenyl)-2-substitutedamino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one with a variety of alkyl and aryl ketones. The starting material 2-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one was synthesized from 4-methoxyaniline. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. While the test compounds exhibited significant activity, compounds 2-(1-methylpropylidene)-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one (A1), 2-(1-ethylpropylidene)-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one (A2) and 2-(1-methylbutylidene)-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one (A3) showed moderately more potent analgesic activity and the compound 2-(1-methylbutylidene)-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one (A3) showed moderately more potent anti-inflammatory activity when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.     

Synthesis and spectral properties of 3,3′-bis(dipyrrolylmethene)

Bis(2,4,7,8,9-pentamethyldipyrrolylmethene-3-yl)(4′-methoxyphenyl)methane dihydrobromide was synthesized and its spectral properties were studied. It was found that the basicity of the ligand 3,3′-bis-(dipyrrolylmethene) decreases upon insertion of the methoxyphenyl group in the 3,3′-spacer.     

Stereoselective synthesis of Z-3-alkoxy-2-[(4′-methoxyphenyl)methylidene]-1(3H)-isobenzofuranones

Photoreorganisation of 2-alkoxy-2-(4′-methoxyphenyl)-1H-indene-1,3(2H)-diones in anhydrous acetone affords exclusively Z-3-alkoxy-3-[(4′-methoxyphenyl)methylidene]-1(3H)-isobenzofuranones. The products were identified by X-ray crystallography of one of them.     

1-(1-Phthalazinyl)- and 1-(4methoxyphenyl)-6,6dimethyl-4oxo-4,5,6,7-tetrahydroindazole

2-(1-Phthalazinylhydrazino)methylene-(IIIa) or 2-(1-phthalazinylhydrazino)ethylidene-5,5-dimethyl-1,3-cyclohexanediones (IIIb) were prepared from 1-hydrazinophthalazine and 2 formyl- or 2-acetyldimedone. Cyclization of IIIb in the presence ofp- TsOH gave 1-(1-phthalazinyl)3, 6, 6-trimethyl-4-oxo-4, 5, 6, 7-tetrahydroindazole. Reaction of 4-methoxyphenylhydrazine with 2 formyl- and 2-acetyidimedone gave the corresponding 1-(4methoxyphenyl)-4-oxo-4, 5, 6, 7-tetrahydroindazole. In the case of 2 -formyldimedone the intermediate 2-(4methoxyphenylhydrazinomethylene)-5, 5-dimethyl-1,3-cyclohexanedione was isolated.Riga Technological University, Riga LV-1658. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 708–710, May, 1996. Original article submitted December 31, 1995.     

The kinetics and mechanisms of the gas phase elimination of 4-(methylthio)-1-butyl acetate and 1-chloro-4-(methylthio)-butane

The gas phase elimination of 4-(methylthio)-1-butyl acetate and 1-chloro-4-(methylthio)-butane has been investigated in a seasoned, static reaction vessel over the temperature range of 310–410°C and the pressure range of 46–193 Torr. The presence of the inhibitors propene, cyclohexene, and/or toluene had no effect on the rates. The reactions are homogeneous, unimolecular, and obey a first-order rate law. The rate coefficients are given by the following Arrhenius equations: for 4-(methylthio)-1-butyl acetate, log k₁(s^?1) = (12.32 ± 0.29) ? (192.1 ± 3.6) kJ/mol/2.303RT; for 1-chloro-4-(methylthio)-butane, log k₁(s^?1) = (12.23 ± 0.59) ? (175.7 ± 6.8) kJ/mol/2.303RT. The CH₃S substituent in 1-chloro-4-(methylthio)-butane has been found to participate in the elimination reaction, where tetrahydrothiophene and methyl chloride formation may result from an intimate ion-pair type of mechanism. The yield of a cyclic product in gas phase reactions provides additional evidence of an intimate ion pair mechanism through neighboring group participation in gas phase elimination of special types of organic halides.     

7种中位—四取代苯基卟啉化合物的合成

卟啉是一类结构与生命物质(如血红素和维生素B_(12))相似的化合物,近年来曾被用于人体肿瘤的光动力学治疗;此外,在电化学、光物理学和光化学、放射医学、微量元素测定、纺织品漂洗等领域中的应用也相当广泛,已受到科技工作者的普遍关注和重视。本文按Rothemond法将相应的取代苯甲醛与新蒸吡咯在丙酸中缩合,制得具有酸性、中性和碱     

Synthesis of carba-analogues of myoseverin by regioselective cross-coupling reactions of 2,6-dichloro-9-isopropylpurine

A series of 9-isopropylpurine derivatives bearing 4-methoxyphenyl, 4-methoxybenzyl, (4-methoxyphenyl)ethynyl and 2-(4-methoxyphenyl)ethyl groups in positions 2 and 6 were prepared as carba-analogues of antimitotic myoseverin. Cross-coupling reactions of 2,6-dichloro-9-isopropylpurine (1) with one equivalent of (4-methoxyphenyl)boronic acid or (4-methoxybenzyl)zinc chloride gave regioselectively the 6-substituted 2-chloropurines which were used for another cross-coupling reaction with a second equivalent of the organometallic reagent. The Sonogashira reaction of 1 with 4-(methoxyphenyl)ethyne gave 2,6-bis[(4-methoxyphenyl)ethynyl]-9-isopropylpurine that was hydrogenated to 2,6-bis[2-(4-methoxyphenyl)ethyl]-9-isopropylpurine. Regioselectivity of the couplings was proved by means of ¹H-¹⁵N HMBC experiments. 2,6-Bis[(4-methoxyphenyl)ethynyl]-9-isopropylpurine showed considerable cytostatic activity, while the other compounds were inactive.     

Crystal structure and quantum chemical calculations of (E)1-benzyl-3-((4-methoxyphenyl)imino)-5-methylindolin-2-one

The known Schiff base compound, (E)1-benzyl-3-((4-methoxyphenyl)imino)-5-methylindolin-2-one, was prepared as before by reacting 1-benzyl-5-methylindoline-2,3-dione with 4-methoxyaniline. The product was unambiguously characterized using elemental analysis, ¹H and ¹³C-NMR spectroscopy, and its new single-crystal X-ray structural analysis. Molecular orbital calculations were conducted in order to investigate the structures and relative stabilities of the (E) and (Z) isomers of 1-benzyl-3-([4 methoxyphenyl]-imino)-5-methylindolin-2-one. Specific attention was paid to the (E) isomer. The available crystallographic experimental data for the latter ensured also validation of the model structures computationally derived at the theoretical B3LYP/6-31G(d,p) level.     

Kinetics and mechanism of ring transformation of S-[1-(4-methoxyphenyl)pyrrolidin-2-on-3-yl]isothiuronium bromide to 2-methylimino-5-[2-(4-methoxyphenylamino)ethyl]thiazolidin-4-one

The kinetics and mechanism of transformation reaction of S-[1-(4- methoxyphenyl)pyrrolidin-2-one-3-yl]-N-methyl-isothiuronium bromide into 2-methylimino-5-[2-(4-methoxyphenylamino) ethyl)]thiazolidin-4-one have been studied in aqueous solutions of amine buffers (pH 8.1-11.5) and sodium hydroxide solutions (0.005-0.5 mol l-1) at 25 degrees C and at I = 1 mol l-1 at pseudo-first-order reaction conditions. The kinetics observed shows that the transformation reaction is subject to general base, general acid, and hydroxide-ion catalyses. The rate-limiting step of transformation is the splitting-off a proton from the tetrahedral intermediate In. The value of pKa for S-[1-(4-methoxyphenyl)- pyrrolidin-2-one-3-yl]-N-methylisothiuronium bromide has been determined from the kinetic data (pKa = 8.75 +/- 0.10) and by potentiometric titration (pKa = 8.90 +/- 0.05). With increasing pKa value of the acid buffer component, the value of Br?nsted coefficient beta gradually decreases from about 0.7 to almost zero. The value of pKa approximately 10 for the intermediate to base-catalysed transformation has been found from this dependence. In the N-methylpyrrolidine and triethylamine buffers, the rate-limiting step of transformation is changed into ring opening of In-, and the general-base-catalysed reaction changes into a specific-base-catalysed one.     

Synthesis of 5-substituted 2-(4- or 3-methoxyphenyl)-4(1H)-quinolones

5-Substituted 7-methoxy-2-(4- or 3-methoxyphenyl)-4(1H)-quinolones 8-17 have been synthesised in good yields from the corresponding 7-methoxy-2-(4- or 3-methoxyphenyl)-5-trifluoromethanesulfonate-4(1H)-quinolones 7 via palladium-mediated cross-coupling reactions or aromatic nucleophilic substitution (SN_Ar) reactions.     

Synthesis of optically active 4,4,4-trifluoro-3-{4-(4-methoxyphenyl)phenyl}butanoic acid and its application to chiral dopant for nematic liquid crystals

We synthesized an optically active 4,4,4-trifluoro-3-{4-(4-methoxyphenyl)phenyl}butanoic acid (5^*). New chiral dopants for nematic liquid crystals were derived from (R)-(−)-5^*, and their helical twisting power (HTP) values were measured. Their HTP values were largely influenced by the linkage between the asymmetric frame and the core moiety. The chiral dopant, (R)-(+)-4,4,4-trifluoro-1-(4-hexyloxyphenyl)-3-{4-(4-methoxyphenyl)phenyl}-1-butanone ((R)-(+)-7^*) showed the largest HTP value (−21.7 μm⁻¹).     

Crystal and molecular structure of 7,7-dimethyl-2,3-di(4-methoxyphenyl)-5-oxo-5,6,7,8-tetrahydroquinoline

An x-ray crystallographic investigation of 7,7-dimethyl-2,3-di(4-methoxyphenyl)-5-oxo-5,6,7,8-tetrahydroquinoline, obtained by the hydrolysis of its oxime, was undertaken. The oxime, together with the isomeric oxime of 7,7-dimethyl-2,4-di(4-methoxyphenyl)-5-oxo-5,6,7,8-tetrahydroquinoline, is formed in the reaction of 5,5-dimethyl-2-[1,3-di(4-methoxyphenyl)-3-oxopropyl]cyclohexane-1,3-dione with hydroxylamine hydrochloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1085–1088, August, 1987.     

Design,synthesis and preclinical evaluations of (s)-2-((s)-1-benzyl-2,5-dioxopyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (succ-5) as cardioprotective,hepatoprotective and lipid lowering molecule. in-vivo and in-silico approaches

In this study, the newly synthesized compound (Succ-5) was analyzed through spectral methods, seen for potential receptor targets via molecular docking, and pre-clinically evaluated for therapeutic effects and safety profile using biochemical and histopathological techniques. The biochemical analysis included assessment of cardiac biomarkers, hepatic enzymes, and lipid profiles, while histopathology included evaluation of cardiac and liver tissues. The toxic dose was determined pre-clinically, followed by dividing albino rats into five treatment groups (each having n = 6). The control group received oral saline for eight days. The 5-FU (5-Fluorouracil) group received oral saline for 8 days and 5-FU (150 mg/kg I.P.) on day 5. The atenolol group was administered with atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5. Two groups of rats were administered with the test compound (Succ-5) at doses of 5 mg/kg I.P and 10 mg/kg I.P (for 8-days), followed by 5-FU (150 mg/kg I.P.) on day 5. Elevated serum levels of CK-MB (creatinine kinase myocardial band), cTnI (troponin I), LDH (lactate dehydrogenase), lipid profile, and selected liver enzymes including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total) and BD (direct bilirubin) were associated with 5-FU toxicity. After administration of the test compound at the mentioned doses, these biomarkers significantly decreased. Likewise, histological examination revealed 5-FU damaged the heart and hepatic tissues, which were also considerably recovered following administration of the test compound. Immunohistochemistry of heart tissue also revealed the low expression of COX-2 and TNF-α in Succ-5 treated groups compared to toxic group. Dose-response evaluation showed that a dose of 10 mg/kg provided better results than 5 mg/kg. The analysis of binding energy values computed via docking simulations showed that Succ-5 interacts with the human beta2-adrenergic G protein-coupled receptor with a slightly stronger affinity than calcium channel T-type. In conclusion, the histological and biochemical findings revealed that the test compound had significant cardioprotective, hepatoprotective, and lipolytic effects in the 5-FU-induced toxicity.     

Gold-catalyzed consecutive [1,2] alkyl migration-oxygen transfer reaction of 2-alkynyl-1-tetralones

Gold-catalyzed isomerization of 2-alkynyl-1-tetralones afforded the corresponding 2-naphthylmethyl ketones in good to high yields. For example, the reaction of 2-{4-(methoxyphenyl)methyl}-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)-one and 2-benzyl-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)-one in the presence of 5 mol % of (Ph₃P)AuCl and 5 mol % of AgOTf in THF at 50 °C gave 2-{1-(4-methoxyphenylmethyl)naphthalen-2-yl}-1-(4-methoxyphenyl)ethanone and 2-(1-benzylnaphthalen-2-yl)-1-phenylethanone in 85% and 96% yields, respectively. The present reaction proceeds through [1,2] alkyl migration followed by oxygen transfer.     

Solvent-free reaction of 3-aryl-6-(3-nitrophenyl)-1,2,4-triazines with 4-(cyclohex-1-en-1-yl)morpholine

The aza-Diels–Alder reaction of 3-aryl-6-(3-nitrophenyl)-1,2,4-triazines with 4-(cyclohex-1-en-1-yl)morpholine as dienophile was accompanied by reduction of the nitro group to amino. In the reaction of 3-(4-methoxyphenyl)-6-(3-nitrophenyl)-1,2,4-triazine with 4-(cyclohex-1-en-1-yl)morpholine, 3-[3-(4-methoxyphenyl)-1,2,4-triazin-6-yl)aniline was formed together with the cycloaddition product.     

Formation of metal-lustrous organic crystals from 2-aryl-1-(4-methoxyphenyl)-5-(5-tricyanoethenyl-2-thienyl)pyrroles

Various 2-aryl-1-(4-methoxyphenyl)-5-(5-tricyanoethenyl-2-thienyl)pyrroles (3) were synthesized. When the 2-aryl group of 3 is phenyl, 4-tolyl, and 4-methoxyphenyl, organic crystals with greenish yellow metallic luster are formed. In contrast, a 2-(4-fluorophenyl) derivative of 3 gives gold-like lustrous crystals. The relation of their crystal structures with the appearance of metallic color is mentioned.     

Semiconductor-catalyzed photocycloreversion,valence isomerization and [1,3]-sigmatropic rearrangement

The semiconductor-catalyzed photochemical [2+2]cycloreversion of n-methylquinolone dimer, valence isomerization of hexamethyl(Dewar)benzene, and [1,3]-sigmatropic rearrangement of 2,2-bis(4-methoxyphenyl)-1-dideuteriomethylenecyclopropane gave N-methylquinolone, hexamethylbenzene, and 2,2-bis(4- methoxyphenyl)-3,3-dideuterio-1-methylenecyclopropane, respectively.     

The base-promoted dehydration of rac.-trans-tetrahydro-6-hydroxy-4-[(2-(dimethylamino)ethyl]-7-(4-methoxyphenyl)-1,4-thiazepin-5(2H)-one

The base-catalyzed alkylation of rac.-trans-tetrahydro-6-hydroxy-7-(4-methoxyphenyl)-1,4-thiazepin-5(2H)-one ( 1 ) with dimethylaminoethyl chloride in dimethyl sulfoxide provided predominantly rac.-trans-tetrahydro-6-hydroxy-4-[(2-dimethylamino)ethyl]-7-(4-methoxyphenyl)-1,4-thiazepin-5(2H)-one ( 2 ) and in addition, 2,3-dihydro-4-[2-(dimethylamino)-ethyl]-7-(4-methoxyphenyl)-1,4-thiazepin-5(4H)-one ( 3 ). A plausible mechanism is postulated for the dehydration of the rac.-trans-amide 2 .