Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters

Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO₂ in 6% H₂SO₄ in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K₂CO₃ and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.     

Synthesis of 2([Methyl-5-[(E)-2-aryl-1-ethenyl]-4-isoxazolyl]imino)-1,3-thiazolan-4-ones and Their Mannich Bases

Isoxazolyl chloroacetamides (2) were obtained from 4-amino-3-methyl-5-styrylisoxazoles (1) on reaction with chloroacetyl chloride. Cyclocondensation of 2 with NH₄SCN yielded 2([-methyl-5-(E)-2-aryl-1-ethenyl]-4-isoxazolylimino)-1,3-thiazolan-4-ones(3). Mannich reaction of 3 with formaldehyde and secondary amines gave isoxazolyl thiazolidinone Mannich bases (4 and 5).     

2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4- 噻唑啉酮的合成

以2-氨基-5-取代苯氧甲基-1,3,4-噻二唑(1)为起始原料, 合成了中间体2-氯乙酰氨基-5-取代苯氧甲基-1,3,4-噻二唑)-2-乙酰亚胺(2)和2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-4-噻唑啉酮(3), 化合物3进一步与取代苯甲醛发生类Knoevenagle缩合反应, 得到了一系列2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4-噻唑啉酮类化合物4a～4p. 目标化合物4a～4p的结构经IR, ¹H NMR和元素分析确证.     

Synthesis of Novel 2-(4-Oxo-3,4- Dihydroquinazolin-2-Ylsulfinylmethyl)-3H-Quinazolin-4-One

Abstract

Condensation of 2-mercapto-3H-quinazolin-4-one (1) with chloroacetic acid gave 4-oxo-3,4-dihydroquinazoline-2-yl-sulfanyl)-acetic acid (2) that with anthranilamide (3) gave 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-quinazolin-4-one (4). Oxidation of 4 with sodium hypochlorite in alkaline medium gave the novel product, 2-(4-oxo-3,4- dihydroquinazolin-2-ylsulfinyl methyl)-3H -quinazolin-4-one) (5). The entire sequences of reactions in this work have been carried out using eco-friendly solvents and green conditions.

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1,2-双[2-甲基-5-(3,4-二氟苯基)噻吩-3-基]全氟环戊烯的合成

在冰浴条件下, 2-甲基噻吩(1)与液溴反应生成3,5-二溴-2-甲基噻吩(2); 在－78 ℃条件下, 硼酸三丁酯加入2, 得到2-甲基-3-溴-5-硼酸基噻吩(3); 3,4-二氟溴苯与3反应得到2-甲基-3-溴-5-(3,4-二氟苯基)噻吩(4); 在－78 ℃下全氟环戊烯与4反应, 得到一种新的二芳基乙烯类光致变色化合物1,2-双[2-甲基-5-(3,4-二氟苯基)噻吩-3-基]全氟环戊烯(DT-1). 用IR, NMR, MS和元素分析确定了化合物DT-1的结构, 并对该化合物的光致变色特性进行了初步研究.     

A New Synthetic Approach Towards the Synthesis of 2-(3-Aryl-2H-1,4-benzthiazin-2-yl)-3-aryl-2H-1,4-benzothiazines

Synthesis of 2-(3-Aryl-2H-1,4-benzthiazin-2-yl)-3-aryl-2H-1,4-benzothiazines (3 a-e) from 3-aryl-5(4H)-isoxazolones (1 a-e) and 2-aminothiophenol (2).     

Preparation and Structure of (E)-1-(3′-Hydroxy-2-Furanyl)-3-(3″-Hydroxy-4″-Methoxyphenyl)-2-Propen-1-One

Abstract

A facile procedure is presented for the synthesis of (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2- propen-1-one (6). Galactosylisomaltol (1) was condensed with isovanillin (2) under strong alkaline conditions at 25 [ddot]C to form (E)-1-(3′-O-β-D-galactopyranosyloxy-2′-furanyl)-3-(3″- hydroxy-4″-methoxyphenyl)-2-propen-1-one (4). (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2-propen-1-one (6) was obtained by acid hydrolysis of 4 in a 53.9% yield. This hetero-cyclic 2-propen-1-one was characterized on the basis of spectral data (IR and ¹H NMR), physicochemical properties, and conversion to a mono-O-acetyl derivative.     

Synthesis,Crystal Structure,and Flame Retardance of 2-(3-Silatranyl-Propylamino)-4-(2,4-Dichlorophenyl)-5,5-Dimethyl-1,3,2-Dioxaphosphinane-2-Sulfide

Abstract

2-(3-Silatranylpropylamino)-4-(2,4-dichlorophenyl)-5,5-dimethyl-1,3,2-dioxa phosphinane-2-sulfide 4 was synthesized by a nucleophilic substitution reaction of 2-chloro-1,3,2-dioxaphosphinane-2-sulfide 2 with γ-aminopropylsilatrane 3, which was prepared by the cyclization reaction of triethanolamine and γ-aminopropyltriethoxysilane. The structure of the title compound was confirmed by IR, ¹H NMR, ³¹P NMR, EI-MS, and elemental analysis as well as by single crystal X-ray diffraction and its thermal properties were studied by thermogravimetry (TG) and differential scanning calorimetry (DSC). Thermal analysis and preliminary fire retardance testing suggest that compound 4 should function as a good flame retardant.     

Synthesis of 2-(2-methoxyethyl)- and 2-(2-thiomethoxyethyl)-aniline and related compounds

Summary 2-(2-Nitrophenyl)-ethanol (2) was methylated with dimethyl sulfate to give 2-(2-methoxyethyl)-1-nitrobenzene (3a) which then was reduced with hydrazine hydrate in the presence ofRaney nickel to 2-(2-methoxyethyl)-aniline (1a). Compound1a can be transformed into the N-monosilylated derivative4 by lithiation withn-butyllithium and subsequent reaction with chlorotrimethylsilane. Reaction of2 withp-toluenesulfonyl chloride yields 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-thiomethoxyethyl)-1-nitrobenzene (3b).3b was reduced with hydrazine hydrate in the presence ofRaney nickel to yield 2-(2-thiomethoxyethyl)-aniline (1b). Ethyl (2-nitrophenyl)-acetate (6) could be dimethylated with methyl iodide in the presence of potassiumtert-butoxide and 18-crown-6 to give ethyl 2-methyl-2-(2-nitrophenyl)-propionate (7). Reduction of7 with lithium borohydride yields 2,3-dihydro-3,3-dimethyl-1H-indole (9) and 2-[(1-hydroxy-2-methyl)-2-propyl]-aniline (10).

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Synthese von 2-(2-Methoxyethyl)- und 2-(2-Thiomethoxyethyl)-anilin und verwandten Verbindungen

Zusammenfassung 2-(2-Nitrophenyl)-ethanol (2) wurde mit Dimethylsulfat zu 2-(2-Methoxyethyl)-1-nitrobenzol (3a) methyliert, das sich mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Methoxyethyl)-anilin (1a) reduzieren läßt. Verbindung1a kann durch Metallierung mitn-Butyllithium und anschließende Reaktion mit Chlortrimethylsilan in dasN-monosilylierte Derivat4 umgewandelt werden. Reaktion von2 mitp-Toluolsulfonylchlorid ergab 2-(2-Nitrophenyl)-ethyl-p-Toluolsulfonat (5), das mit Natriumthiomethanolat zu 1-Nitro-2-(2-thiomethoxyethyl)-benzol (3b) reagiert.3b wurde mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Thiomethoxyethyl)-anilin (1b) reduziert. Ethyl-2-(nitrophenyl)-acetat (6) kann mit Methyliodid in Gegenwart von Kalium-tert-butoxid und 18-Krone-6 zu Ethyl-2-methyl-2-(2-nitrophenyl)-propionat (7) dimethyliert werden. Reduktion von7 mit Lithiumborhydrid lieferte 2,3-Dihydro-3,3-dimethyl-1H-indol (9) und 2-[(1-Hydroxy-2-methyl)-2-propyl]-anilin (10).

     

Synthesis of 3-[4-(1-Benzofuran-2-yl)-1,3-thiazol-2-yl]-2-(4-aryl)-1,3-thiazolidin-4-one Derivatives as Biological Agents

A protocol for the synthesis of 3-[4-(1-benzofuran-2-yl)-1,3-thiazol-2-yl]-2-(4-aryl)-1,3-thiazolidin-4-one derivatives (5a–e) has been developed from 1-(1-benzofuran-2-yl)-2-bromoethanone (2),which served as a key intermediate for the synthesis of the title compounds. The reaction of compound 2 with thiourea furnished 4-(1-benzofuran-2-yl)-1,3-thiazol-2-amine 3, which upon further reaction with various aromatic aldehydes, gave Schiff bases 4a–e. These Schiff bases, when treated with thioacetic acid in the presence of catalytic amount of anhydrous ZnCl₂, yielded thiazolidinone derivatives 5a–e. All the newly synthesized compounds have been characterized by analytical and spectral data and screened for their antimicrobial and analgesic activity.

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Synthesis, spectroscopic properties and crystal structure determination of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives

Substituted 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives 2, 3 and 6 were synthesized. 2-(2-Pyridin-4-yl-vinyl)-1H-benzimidazole 2 and 6-methyl-2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 3 were prepared by condensation reaction from 3-pyridin-4-yl-acrylic acid and corresponding 1,2-phenylenediamines in polyphosporic acid (PPA). 2,7,11-b-Triaza-benzo[c]fluorene 4 was prepared by photochemical dehydrocyclization reaction of ethanolic solution of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2. 2-(2-Pyridin-4-yl-vinyl)-3H-benzimidazole-6-carbonitrile 6 was prepared by condensation reaction from 3-pyridin-4-yl-propenal and 4-cyano-1,2-phenylenediamine using p-benzoquinone as oxidants. The structure of novel benzimidazole derivatives has been studied by ¹H and ¹³C NMR, IR, MS, UV/Vis and fluorescence spectroscopy. The structure of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2 was confirmed by X-ray single crystal structure analysis. The conformation of the molecule is E in regard to substituents position around vinyl double C=C bond. The non-planar molecules are mutually connected via the N–H···N and C–H···N type of intermolecular hydrogen bonds into infinite chains spreading along y axis.     

Convenient synthesis of 4H-chromenyl-tetrahydro-2H-pyrancarboxylates and cleavage of chromone and pyran rings leading to 5-(2-hydroxybenzoyl)-2-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylates

4H-Chromenyl-tetrahydro-2H-pyrancarboxylates 3a–k have been conveniently prepared by the reaction of 3-formylchromones 1a–k and ethyl 4,4,4-trifluoro-3-oxobutanoate 2a with good yields. Thus obtained 4H-chromenyl-tetrahydro-2H-pyrancarboxylates 3a–k were reacted with amines 4a–e to provide series of 5-(2-hydroxybenzoyl)-2-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylates 5a–o. The reaction proceeded via Michael addition (C-N bond formation) and followed by cleavage of chromone and pyran rings (C-O bond cleavage) in one pot.     

Efficient Synthesis of Novel 3-[5-(1H-Benzimidazol-2-Ylmethanesulfonyl)-4-Phenyl-4H-(1,2,4)Triazol-3-Yl]-1H-(1,8)Naphthyridin-4-One Derivatives

Abstract

of 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbohydrazide (4) with substituted phenyl isothiocyanates (5) in ethanol under reflux for 30 min gave thiosemicarbazide derivatives 6, which on cyclization in 2N NaOH under refluxing conditions for 1 h resulted in 3-(5-mercapto- 4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (7). Alternatively, 7 could also be prepared from following sequence of reactions, i.e., 4 → 8 → 7. In another sequence of reactions, condensation of 7 with chloroacetic acid in dimethylformamide (DMF) and K₂CO₃ as a mild base at 120 °C for 2 h resulted in 2-((5-(1,4-dihydro-4-oxo-1,8-naphthyridin-3-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetic acid (10). The latter, on reaction with substituted o-phenylenediamine (11) in 6N HCl for 4 h yielded 3-(5-((1H-benzo[d]imidazol-2-yl)methylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (12). Alternatively, 12 could also be prepared by reacting 7 with 13 in DMF and K₂CO₃ as a mild base at 120 °C for 2 h, followed by oxidation with H₂O₂ resulting in the corresponding sulfonyl derivatives 14.     

Green synthesis of novel (E)-2-(1,4-dioxo-1,2,3,4-tetrahydrophthalazine-2-carbonyl)-3-(1H-indol-3-yl)acrylonitriles

Green synthesis of novel title compounds (6) has been developed from 3-(1,4-dioxo-3,4-dihydrophthalazin-(1H)-yl)-3-oxopropanenitrile (3) and indole-3-aldehyde (4) using Knoevenagel condensation followed by alkylation with alkylating agents. Compound 6 could also be synthesised by alkylation of 4 followed by condensation with 3. In an alternate sequence of reactions, 6 could be synthesised either from treatment of 3 with N,N-dimethylformamide dimethyl acetal to form (E)-3-(dimethlamino)-2-(1,4-dioxo-1,2,3,4-tetrahydrophthalazine-2-carbonyl)acrylonitrile 8 followed by reaction with 10 or by the reaction 8 with 9 followed by alkylation.     

A CONVENIENT SYNTHESIS OF 1,3-DISUBSTITUTED-4-(1′,3′-DITHIOLANE/DITHIANE-2′-YLIDENE)-2-PYRAZOLIN-5-ONES

1, 3 - Disubstituted- 4 - (1′, 3′- dithiolane /dithiane - 2′- ylidene) - 2 -pyrazolin-5-one derivatives like (1a–c), (2a–c), (3a–c) have been obtained by condensation of 2-pyrazolin-5-ones (1), (2) and (3) with carbon disulfide in presence of triethylamine followed by the reaction with 1,2-dibromoethane (4a), 1,3-dibromopropane (4b) and 1,3-dibromobutane (4c) respectively.     

Facile Synthesis of Some 3-(Benzimidazol-2-yl)- and 3,6-Di(Benzimidazol-2-yl)-9-ethyl-9H-carbazoles

A simple and efficient synthesis of novel 3-(benzimidazol-2-yl)- and 3,6-di(benzimidazol-2-yl)-9-ethyl-9H-carbazoles is described. The synthetic approach for the preparation of 2-substituted benzimidazoles 4–8 and bis-benzimidazoles 9–12 was achieved by the condensation of carbazole-3-carbaldehyde 2 and carbazole-3,6-dicarbaldehyde 3 with o-phenyldiamines in dimethylformamide or dimethylsulfoxide in moderate to excellent yield. The identities of synthesized compounds were confirmed using ¹H NMR, ¹³C NMR, infrared (IR), and high-resolution mass spectrometry (HRMS).     

Transformations of 1-(2-chloropyridyl-3)-4-ethoxycarbonyl-and 1-(2-chloropyridyl-3)-4-ethoxycarbonylmethyl thiosemicarbazides. Attempts to prepare pyrido[3,2-e]-1,2,4-thiadiazine

2-Chloro-3-hydrazinopyridine (2) was converted with ethoxycarbonyl and ethoxycarbonylmethyl isothiocyanates into 1,4-disubstituted thiosemicarbazides3 and4, while with phenyl isothiocyanate directly 1H-pyrido[3,2-e]-1,3,4-thiadiazine7 was formed. Attempts to cyclize the thiosemicarbazides3 and4 into pyridothiadiazine derivatives5 and6 failed. In the reaction of3 with hydrazine 2-aminothiazolo[5,4-b]pyridine (9) was formed, while4 gave only the corresponding hydrazide10. The cyclization of the side chain occurred in compound4 by heating in aqueous hydrochloric acid to give11, which was further transformed with N,N-dimethylformamide dimethyl acetal (DMFDMA) into12, while with diethyl acetylene dicarboxylate the thiazolidone derivative13 was produced.

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Transformationen von 1-(2-Chlorpyridyl-3)-4-ethoxycarbonyl- und 1-(2-Chlorpyridyl-3)-4-ethoxycarbonylmethylthiosemicarbaziden. Versuche zur Synthese von Pyrido[3,2-e]-1,2,4-thiadiazinen

Zusammenfassung 2-Chlor-3-hydrazinopyridin (2) wurde mit Ethoxycarbonyl- und Ethoxycarbonylmethylisothiocyanaten zu 1,4-disubstituierten Thiosemicarbaziden3 und4 umgesetzt, mit Phenylisothiocyanaten wurden direkt die 1H-Pyrido[3,2-e]-1,3,4-thiadiazine7 erhalten. Versuche zur Cyclisierung der Thiosemicarbazide3 und4 zu den Pyridothiadiazinderivaten5 und6 gelangen nicht. Bei der Reaktion von3 mit Hydrazin entstand 2-Aminothiazolo[5,4-b]pyridin (9),4 gab nur das entsprechende Hydrazid10. Die Cyclisierung der Seitenkette von4 gelang durch Erhitzen in wäßriger HCl unter Bildung von11, das seinerseits mit N,N-Dimethylformamiddimethylacetal (DMFDMA) weiter zu12 umgesetzt wurde, währenddessen mit Diethylacetylendicarboxylat die Thiazolidonderivate13 entstanden.

     

2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤的合成

报道了2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤(1)的合成, 通过对起始原料2-氨基-6-氯-9-(4-乙酰氧基-3-乙酰氧甲基丁基)嘌呤(2)水解脱去乙酰基, 得到2-氨基-6-氯-9-(4-羟基-3-羟甲基丁基)嘌呤(3). 化合物3与三甲胺乙醇溶液在混合溶剂[V(THF)∶V(DMF)＝3∶1]中反应得到相应的氯化铵盐4, 然后与KF在DMF溶剂中反应, 得到化合物1. 产品经UV-vis, IR, ¹H NMR, ¹⁹F NMR和MS表征. 考察了反应温度、氟化试剂等因素对氟化反应的影响, 为6位含氟的嘌呤核苷类化合物的合成提供了一种直接、简易的新方法.     

Novel Synthesis of 2-(2-(3-Hydroxy-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic Acid Analogues and Their Anti-Inflammatory Properties

This article describes the reaction of 3,6-diphenyl-thieno[3,2-b]furan-2,5-dione 1 with different amino acids 2a–j in glacial acetic acid which afforded the 2-(2-(3-hydroxy-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic acid analogues 3a–j and also describes the reaction of 3,6-diphenyl-thieno[3,2-b]thiophene-2,5-dione 4 with different amino acids 5a–e in acidic medium to give 2-(2-(3-mercapto-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic acid analogues 6a–e. All the compounds have been screened for their anti-inflammatory activity against the carrageenan induced rat paw edema in albino rats. In the primary screening, some of the compounds exhibited appreciable activity.

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Facile and Green Syntheses of 2-(N-Methylindole-3-carbonyl)-3-(N-methylpyrrol-2-yl)acrylonitriles and a Study of Their Antimicrobial Activities

Facile and green syntheses of substituted-2-(N-methylindole-3-carbonyl)-3-(N-methyl pyrrol-2-yl) acrylonitriles 6a–d are being reported. L-Proline has been utilized as an efficient and ecofriendly catalyst in aqueous medium for Knoevenagel condensation of pyrrole-2-carboxyaldehyde (1) and its N-methyl derivative (2) with the active methylene compounds 3-cyanoacetylindoles 3a–d at room temperature to afford substituted-2-(1H-indole-3-carbonyl)-3-(1H-pyrrol-2-yl)acrylonitriles 4a–d and substituted-2-(1H-indole-3-carbonyl)-3-(N-methylpyrrol-2-yl) acrylonitriles 5a–d respectively. Subsequently these products were treated with dimethyl sulfate (DMS) in polythylene glycol (PEG)–600 as an efficient and green solvent to afford the corresponding substituted-2-(N-methylindole-3-carbonyl)-3-(N-methylpyrrol-2-yl)acrylonitriles 6a–d. The antibacterial and antifungal activities of 4a–d, 5a–d, and 6a–d have been studied.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]