Heterocycles: 2—Regiospecific addition of methylhydrazine to acetylenic ketones

The reaction of 1-p-methoxyphenyl-3-phenyl-2-propen-1-one and 3-p-methoxyphenyl-1-phenyl-2-propen-1-one with methylhydrazine gave 1-methyl-3-p-methoxyphenyl-5-phenylpyrazoline and 1-methyl-3-phenyl-5-p-methoxyphenylpyrazoline, respectively. These compounds, on oxidation, gave 1-methyl-3-p-methoxyphenyl-5-phenylpyrazole(2) and 1-methyl-3-phenyl-5-p-methoxyphenylpyrazole, respectively. When methyl-hydrazine was made to react with 1-p-methoxyphenyl-3-phenyl-2-propyn-1-one, a pyrazole was obtained which proved to be identical with 2. Confirmatory evidence for this identity was obtained from their spectral data.     

Physicochemical studies on solid products of reactions of chromyl chloride and chromyl acetate with alkylaromatics. Part I. Infrared spectra and magnetic measurements

Summary Reaction of chromyl chloride, CrO₂Cl₂, with various alkylaromatics leads to solid products of composition 2CrO₂Cl₂ · HR (where HR is an alkylaromatic); however, they are not the simple adducts as the oxidation state of chromium appears to be reduced from VI to IV. The products of chromyl acetate reactions with the same hydrocarbons are monochromo(IV)- and dichromo(IV)-hydroxyacetates depending on the method of preparation. Infrared spectra and magnetic measurements were interpreted as showing that none of these compounds are the adducts of chromyl chloride or chromyl acetate but that all contain chromium(IV).     

A one-pot reaction of (chlorocarbonyl) phenyl ketene with β-ketoamides and thiochromen-2-one

Readily available (chlorocarbonyl)phenyl ketene and a varied set of β-ketoamides were reacted in a one-step procedure to produce 2-pyrone derivatives. β-Ketoamide derivatives are versatile intermediates for the synthesis of heterocyclic compounds. For instance, 1-morpholino-3-phenyl-1,3-propanedione, 1-phenyl-3-piperidino-1,3-propanedione, 1-phenyl-3-pyrrolidino-1,3-propanedione, 1-piperidino-1,3-butanedione, 1-morpholino-2-phenyl ethanone were used in these reactions to produce 2-pyrone derivatives. In addition, the preparation of 4-hydroxy-3-phenylthiochromeno[4,3-b]pyran-2,5-dione derivatives and 4-hydroxy-7-methyl-3-phenyl pyrano[3,2-c]chromeno-2,5-dione were described. For the synthesis of these compounds 4-hydroxy-2H-thiochromen-2-ones and 4-hydroxy-8-methyl-2H-chromen-2-one were reacted with (chlorocarbonyl)phenyl ketene and the final products were isolated in good yields.     

Flüssig-Flüssig-Extraktion von Vanadium mit ausgewählten zweizähnigen Chelatbildnern

Liquid-Liquid Extraction of Vanadium with Bidentate Ligands The extraction of vanadium(V) as well as vanadium(IV) with thenoyltrifluoracetone, 1-phenyl-3-methyl-4-benzoylpyrazol-5-one, N-benzoyl-N-phenylhydroxylamine, maltol, di-2-ethylhexylphosphoric acid, and selected 8-quinolinols was studied in comparison with corresponding thioanalogue compounds. In the reaction of vanadium(IV) with 7-methyl-8-quinolinol vanadium(IV) and vanadium(V) compounds were isolated side by side.     

水中3-甲基-6-氨基-5-氰基-4-芳基-1-苯基-1，4-二氢吡喃[2，3-c]吡唑的洁净合成

在水溶剂中并有三乙基苄基氯化铵（TEBA）存在下，取代芳亚甲基丙二腈与3- 甲基-1-苯基-2-吡唑啉-5-酮缩合成为3-甲基-6-氨基-5-氰基-4-芳基-1-苯基-1， 4-二氢吡喃[2,3-c]吡唑，此法为相应化合物的合成提供了一种快速、方便、高效 和洁净的方法。     

Studies on the synthesis of heterocyclic compounds. Part IV. Further investigation of the pschorr reaction with some pyrazole derivatives

Thermal decomposition of the diazonium sulfate derived from N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-aminobenzamide afforded products formulated as 1-phenyl-3-methyl[2]benzopyrano[4,3-c]pyrazol-5-one (yield 10%), 1,4-dimethyl-3-phenylpyrazolo[3,4-c]isoquinolin-5-one (yield 10%), N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-hydroxybenzamide (yield 8%) and 4′-hydroxy-2,3′-dimethyl-1′-phenylspiro[isoindoline-1,5′-[2]-pyrazolin]-3-one (yield 20%). Decomposition of the diazonium sulfate derived from N-methyl-(1,3-diphenylpyrazol-5-yl)-2-aminobenzamide gave products formulated as 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]-diazocin-10-(9H)one (yield 8%), 4-methyl-1,3-diphenylpyrazolo[3,4-c]isoquinolin-5-one (yield 7%) and 4′-hydroxy-2-methyl-1′,3′-diphenylspiro[isoindoline-1,5′-[2]pyrazolin]3-one (yield 10%). The spiro compounds 6a,b underwent thermal and acid-catalysed conversion into the hitherto unknown 2-benzopyrano[4,3-c]pyrazole ring system 7a,b in good yield. Analytical and spectral data are presented which supported the structures proposed.     

Cyclic acylimines and cyclic carbinolamides 1. 2-azaphenaiones.

2-Azaphenalone hydrochloride (VI), 2-methyl-1-azaphenalonium chloride (XIV), 3-phenyl-2-azaphenalone (XVIII) and 3-phenyl-2-methyl-2-azaphenalonium chloride (XXI) were synthesized and their chemical and physical properties were studied. At room temperature they add weak nucleophiles (e.g., alcohols, amides) as well as compounds possessing active methylene groups. The methanol addition products (e.g., V) reacted thermally or in the presence of an acid catalyst with nucleophiles to give products identical with those obtained from the azaphenalone hydrochlorides.     

Tautomerism of Aza heterocycles: V. Structure of the spontaneous transformation products of 5-methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo-[4,3-c]pyridin-3-one in crystal and solution

5-Methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one exists as zwitterion with a proton localized on the nitrogen atom of the piperidine ring and negative charge delocalized over the pyrazololate fragment. The compound is stable in crystal but ustable in solution. Its chromatographic purification and attempts to recrystallize or synthesize by condensation of phenylhydrazine with alkyl 1-methyl-4-oxopiperidin-3-carboxylate on heating in alcohols or benzene lead to the formation of a complex mixture of products. Among these products, we isolated and identified 3a,3a′-methylenebis(5-methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one), 1-methyl-3-(2-phenylhydrazinylidene)pyrrolidin-2-one, and 5-methyl-2-phenyl-3,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine. The structure of methyl 3-(2-phenylhydrazinylidene)-4,5-dihydro-3H-pyrrole-2-carboxylate and 3a,5-dimethyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one was proved by NMR spectroscopy. 3a,5-Dimethyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one was isolated as hydrochloride hydrate whose structure was determined by X-ray analysis.     

The preparation and aqueous basic oxidation of diethyl 1-methyl-3-hydroxy-5-phenylpyrrole-2,4-dicarboxylate

Diethyl 1-methyl-3-hydroxy-5-phenylpyrrole-2,4-dicarboxylate has been synthesized in good yield from readily available materials, diethyl benzylidenemalonate and ethyl sarcosinate. It was found to react with oxygen in aqueous base to give two oxidation products, ethyl 1-methyl-2-oxo-3-hydroxy-5-phenyl-3-pyrroline-4-carboxylate ( 9 ) and ethyl 1-methyl-2,3-dioxo-5-phenyl-4-pyrroline-4-carboxylate ( 10 ). These two oxidation products are postulated to arise from the decomposition of a common intermediate, diethyl 1-methyl-2-hydroperoxy-3-oxo-5-phenyl-4-pyrroline-2,4-dicarboxylate. Reaction of the title compound with oxygen in pyridine containing Triton B again produced two products, the dioxo compound ( 10 ) and diethyl 1-methyl-2-hydroxy-3-oxo-5-phenyl-4-pyrroline-2,4-dicarboxylate ( 12 ). Compound 12 was shown to react in aqueous base to give exclusively 9 . The hydration of 10 in acidic and basic media is also discussed.     

Tautomerism-dependent ring construction of N-heterocyclic compounds from the reactions of 1-alkynyl Fischer carbene complexes and substituted pyrazolinones

Four types of N-heterocyclic ring systems were successfully constructed from the reactions of 1-alkynyl Fischer carbene complexes (OC)5M=C(OEt)C[triple bond]CPh (1) (M = Cr, W) and substituted pyrazolinones (2). Reactions of 1 with 3-methyl-2-pyrazolin-5-one (2a), 3-n-propyl-2-pyrazolin-5-one (2b), 3,4-dimethyl-2-pyrazolin-5-one (2c), 3,4-trimethylene-2-pyrazolin-5-one (2d), or 3,4-tetramethylene-2-pyrazolin-5-one (2e) generated three kinds of Fischer aminocarbene complexes (3-5), and reactions of 1 with phenyl-substituted pyrazolinones, i.e., 3-phenyl-2-pyrazolin-5-one (2f) and its tautomer 3-phenyl-3-pyrazolin-5-one (2g), gave Fischer alkoxycarbene complexes (6) as the major products and aminocarbene complexes of types 3-5 as the minor products. Multiple tautomerism of pyrazolinones is attributed to the versatile formation of N-heterocyclic Fischer carbene complexes. Oxidative demetalation of complexes 3-6 with pyridine N-oxide or m-chloroperoxybenzoic acid efficiently afforded organic carbonyl products, and thus, strongly fluorescent syn-mixed-bimanes were prepared. The present findings constitute an alternative new method to synthesize mixed bimanes and other novel N-heterocyclic compounds.     

Flavonoids isolated from Draconis Resina

One new chalcone, 4,6-dihydroxy-2-methoxy-3-methyldihydrochalcone (4), together with four known compounds, dammaradienol (1), (-)-5-methoxyflavan-7-ol (2), 5-methoxy-6-methyl-2-phenyl-7H-chromen-7-one (3), and dracorhodin (5), were isolated from Draconis Resina. The structures of these compounds were determined by spectral methods. Among these five compounds, compounds 1, 2, and 3 exhibited cytotoxicity against KB and HepG2 cells.     

Formation of 3-phenylhydrazono-3-aroylpropionamides from the reaction of 5-aroyl-3(2H)-isothiazolones with phenylhydrazine

Reaction of 2-substituted-5-aroyl-3(2H)-isothiazolones 1 with phenylhydrazine in refluxing ethanol was found to give sulfur-free products, which were characterized as 3-phenylhydrazono-3-aroyl-N-substituted-pro-pionamides 4. Acid hydrolysis of the 3-benzoyl compounds 4 was shown to yield 1-phenyl-3-benzoyl-2-pyrazolin-5-one ( 7 ), whose structure was confirmed by an independent synthesis starting with the chloride of 1-phenyl-5-methoxypyrazole-3-carboxylic acid ( 10 ).     

Design, synthesis and hypoglycemic activity of 3-methyl-1-phenyl-4-{4-[(5-methyl-2-phenyloxazol-4-yl)methoxy]benzylene(benzyl)}-2-pyrazol-5-one

Based on the SAR (structure activity relationship) of TZDs (thiazolidinediones), 3-methyl-1-phenyl-2-pyrazoline-5-one was selected as a substitute for TZD. Compounds of 3-methyl-1-phenyl-4-{4-[(5-methyl-2-phenyloxazol-4-yl)methoxy]benzylene(benzyl)}-2-pyrazol-5-one were designed and synthesized to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds. Butanedione monoxime reacted with (substituted) benzaldehyde via cyclization and chlorination to give 4-(chloromethyl)-5-methyl-2-phenyloxazole derivatives, which condensed with 4-hydroxybenzaldehyde or vanillin, and was followed by the Knoevenagel reaction with 3-methyl-1-phenyl-2-pyrazol-5-one to give compounds Ia-Ih. Compounds Ia-Ih were hydrogenated with Pd-C to give IIa-IIh, and their hypoglycemic activity was evaluated with a glucose oxidase kit and insulin load test on normal mice. Sixteen new target compounds were synthesized. All the compounds were characterized by ¹H NMR, IR, MS and elemental analysis. The preliminary pharmacological tests show that the compounds have good hypoglycemic activity and can enhance the action of insulin, especially Ib, Id and If. __________ Translated from Chemical Journal of Chinese Universities, 2007, 28(4): 672–677 [译自: 高等学校化学学报]     

含肟醚的新型四唑啉酮衍生物的合成及除草活性研究

1-(4-氯苯基)-1,4-二氢-四唑-5-酮(1)与氯丙酮反应生成1-(4-氯苯基)-4-(2-氧代丙基)-1,4-二氢-四唑-5-酮(2). 中间体2、盐酸羟胺和卤化物通过三组分一锅法合成了目标化合物3. 初步生物活性测试结果表明: 目标化合物3具有较好的除草活性.     

Synthesis of some 1-methyl-3-alkoxy-5-arylpyrrolecarboxylic acids and derivatives

By a combination of hydrolysis, decarboxylation, and methylation diethyl 1-methyl-3-hydroxy-5-phenylpyrrole-2,4-dicarboxylate was converted into 1-methyl-3-methoxy-5-phenyl-pyrrole-2,4-dicarboxylic acid (5) and into the isomeric compounds ethyl 1-methyl-2-phenyl-4-methoxypyrrole-3-carboxylate (4a) and ethyl 1-methyl-3-methoxy-5-phenylpyrrole-2-carboxylate (9a). 1-Methyl-2-phenyl-4-methoxypyrrole-3-carboxylic acid was synthesized both by the selective decarboxylation of 5 and by the hydrolysis of 4a. Hydrolysis of 9a, however, did not give the corresponding acid, but rather an oxidation product, 1-methyl-3-methoxy-5-hydroxy-5-phenyl-3-pyrrolin-2-onc (10a). Compound 10a was shown to arise from the air oxidation of the completely decarboxylated product, 1-methyl-2-phenyl-4-methoxypyrrole. Reduction of 9a with lithium aluminum hydride gave 1-methyl-3-methoxy-5-phenylpyrrole-2-methanol, which yielded 10a upon oxidation with silver oxide.     

Synthesis of 1,8- and 2,8-dihydrocycloheptapyrazol-8-one derivatives by the reactions of 3-acetyltropolone and its methyl ethers with phenylhydrazine

3-Acetyltropolone ( 1 ) reacted with phenylhydrazine to give 3-acetyltropolone phenylhydrazone ( 3 ) and 3-methyl-1-phenyl-1,8-dihydrocycloheptapyrazol-8-one ( 4 ). The former ( 3 ) cyclized to afford the latter ( 4 ). The reaction of 3-acetyl-2-methoxytropone ( 2a ) with phenylhydrazine gave 4 , 3-methyl-2-phenyl-2,8-dihydrocyclo-heptapyrazol-8-one ( 5 ), and 3-methyl-2-phenyl-2,8-dihydrocycloheptapyrazol-8-one phenylhydrazone ( 6 ). The compound ( 5 ) reacted with phenylhydrazine to afford 6 . The reaction of 7-acetyl-2-methoxytropone ( 2b ) with phenylhydrazone gave 7-acetyl-2-methoxytropone phenylhydrazone ( 7 ), 7-acetyl-2-(N′-phenylhydrazino)-tropone phenylhydrazone ( 8 ), 3-methyl-1-phenyl-1,8-dihydrocycloheptapyrazol-8-one phenylhydrazone ( 9 ), and 6 . The compound ( 7 ) was heated to afford 4 and reacted with phenylhydrazine to afford 8 and 9 . The compound ( 8 ) was also refluxed to give 9 .     

Synthesis,characterization, and antioxidant activity of heterocyclic Schiff bases

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 1 ) with various aldehydes in methanol at reflux. In addition, diamine was reacted with an aldehyde to yield the corresponding Schiff bases. The structures of synthesized Schiff bases were elucidated by spectroscopic methods such as microanalysis, ¹H-NMR, ¹³C-NMR, and FTIR. Antioxidant activities of synthesized Schiff bases were carried out using different antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reducing power activity. (E)-4-((1H-indol-3-yl)methyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 3 ), (E)-1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one ( 5 ), (E)-1,5-dimethyl-2-phenyl-4-(thiophen-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 7 ), (E)-1,5-dimethyl-2-phenyl-4-(quinolin-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 9 ), (1S,2S,N1,N2)-N1,N2-bis((1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 11 ), and (1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 12 ) were synthesized in high yields. Compound 5 displayed a good ABTS^•+ activity. Compound 3 revealed the outstanding activity in all assays. Compound 7 has the best-reducing power ability in comparison to other synthesized compounds. Although compounds 5, 11, 12 are new, compounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the synthesized compounds ( 3, 5, 7 ) have the potential to be used as synthetic antioxidant agents.     

Crystal structure of phenylhydrazine with diacetyl substituted ketol of the cyclohexane series

The reaction of 2,4-diacetyl-5-hydroxy-5-methyl-3-phenylcyclohexanone-1 with phenylhydrazine is conducted, and the crystal structures of its products, 1-(6-hydroxy-3,6-dimethyl)-2,4-diphenyl-4,5,6,7-tetrahydro-2H-indazol-5-yl)ethane-1-one and 1-(2-hydroxy-2-methyl-6-phenyl-4-(2-phenylhydrazono)-5-(1-(2-henylhydrazono)ethyl)cyclohexyl)ethane-1-one, are determined by single crystal XRD.     

Synthesis and properties of enamine derivatives of 1-methyl-2-phenyl-5-pyrrolone and 5-thiopyrrolone

The corresponding dimethylaminomethylene derivative, from which a number of similar compounds were synthesized by reaction with amines, was obtained by the reaction of 1-methyl-2-phenyl-2-hydroxy-5-oxotetrahydropyrrole with dimethylformamide in the presence of phosphorous oxychloride. The formyl derivatives of 1-methyl-2-phenyl-5-pyrrolone and 5-thiopyrrolone were obtained, and the UV and IR spectra of the enamines of these compounds were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 791–793, June, 1972.     

Multiple pathways in the synthesis of new annelated analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (emivirine)

Condensation of 3-(3,5-dimethylphenyl)-2-oxocyclopentanecarboxamide (11) with oxalyl chloride and condensation of ethyl 2-benzylamino-5-methyl-3-phenylcyclopent-1-enecarboxylate (17a) with trimethylsilyl isothiocyanate gave 7-(3,5-dimethylphenyl)-6,7-dihydro-5H-cyclopenta[e][1,3]oxazine-2,4-dione (12) and 1-benzyl-5-methyl-7-phenyl-2-thioxo-1,2,3,5,6,7- hexahydrocyclopentapyrimidin-4-one (18a), respectively. Acid catalyzed ring-closure of 6-(4-methyl-1-phenylpent-3-enyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (26) and radical mediated ring-closure of 1,3-bis(benzyloxymethyl)-5-bromo-6-(1-phenylbut-3-enyl)-1H-pyrimidine-2,4- dione (32a) gave 5,5-dimethyl-8-phenyl-5,6,7,8-tetrahydro-1H-quinazoline-2,4- dione (28) and 1,3-bis(benzyloxymethyl)-5-methyl-7-phenyl-1,5,6,7- tetrahydrocyclopentapyrimidine-2,4-dione (33), respectively. Annelated emivirine analogues 7-(3,5-dimethylphenyl)-1- ethoxymethyl-1,5,6,7-tetrahydrocyclopentapyrimidine-2,4-dione (4), 1-ethoxymethyl-5,5-dimethyl-8-phenyl-5,6,7,8-tetrahydro-1H-quinazoline- 2,4-dione (5) and 1-ethoxymethyl-5-methyl-7-phenyl-1,5,6,7- tetrahydrocyclopentapyrimidine-2,4-dione (6) were obtained in few steps from 12, 28 and 18a/33, respectively. These new analogues can be considered as conformationally locaTed analogues of emivirine. However, the compounds 4 6 showed lower activities against HIV-1 than emivirine and it is concluded that the locked conformation disfavours activity against HIV-1.