A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Ethylenediamine diacetate-catalyzed three-component reaction for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones and their spirooxindole derivatives

Ethylenediamine diacetate (EDDA)-catalyzed one-pot syntheses of biologically interesting 2,3-dihydroquinazolin-4(1H)-ones and their spirooxindole derivatives from isatoic anhydride, amines, and benzaldehydes or isatins via a three-component condensation in aqueous media have been described. This method is of great value because of high yields and ease of handling.     

Synthesis of 2,3-dihydroquinazolin-4(1H)-ones catalyzed by zirconium (IV) chloride as a mild and efficient catalyst

2, 3-Dihydroquinazolin-4 (1H)-ones have been synthesized in the high to excellent yields via condensation of 2-aminobenzamide with aldehydes and ketones in the presence of catalytic amount of ZrCl₄ in EtOH at room temperature. Mild reaction conditions, clean reaction media, simple workup and easy purification are advantages of this methodology.     

Efficient Synthesis of 3,5,6,7-Tetrahydro-4H-cyclopenta[4,5] thieno[2,3-d]Pyrimidin-4-ones

The title compounds 3,5,6,7-tetrahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-ones（6） were synthesized by base catalytic reactions of secondary amines with carbodiimides 4, which were obtained from the aza-Wittig reaction of iminophosphoranes（3） with aromatic isocyanates.     

Palladium-mediated synthesis of 5-substituted 4-alkynylthieno[2,3-c]pyran-7-ones

We describe here, the first palladium-mediated tandem C-C bond forming reaction between 3-iodothiophene-2-carboxylic acid and terminal alkynes to afford the unexpected 5-substituted 4-alkynylthieno[2,3-c]pyran-7-ones in good yields.     

Oxidation of styrene by 2,3-dichloro-5,6-dicyano-p-benzoquinone

Styrene is oxidized by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), affording hydroquinone mono(2-phenylethyl) ether. Kinetic studies (50°C in CHCl₃) show that the reaction is faster under N₂ than under air and takes placevia intramolecular H-atom transfer within the 1:1 and 1:2 DDQ-styrene charge-transfer complexes. The semiquinone radical intermediate is reoxidized to DDQ by O₂ when the latter is present, therefore, the apparent rate of DDQ reduction is lower. Stability constants of the CT-complexes and kinetic parameters for the oxidation are reported.     

An efficient synthesis of benzylidene-2-alkoxy-4-aryl-2,3-cycloalkenopyridine-3-carbonitrile derivatives

An efficient procedure for the synthesis of a novel class of benzylidene-2-alkoxy-4-aryl-6,7-dihydro-5H-cyclopenta[b]pyridine-, -5,6,7,8-tetrahydroquinoline and/or -6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-carbonitrile was introduced through the one-pot multi-component reaction of cyclopentanone, cyclohexanone, and/or cycloheptanone with different aromatic aldehydes and malononitrile. The same products were also produced by classical route by the two-component reaction of dibenzylidine cyclopentanone, cyclohexanone, and/or cycloheptanone derivatives with malononitrile. The reactions were achieved using sodium alkoxide solution as catalyst and reagent.     

Urea/Thiourea as Ammonia Surrogate: A Catalyst-Free Synthesis of 2-Substituted 2,3-Dihydroquinazolin-4(1H)-ones/Quinazoline-4(3H)-ones

Urea/thiourea have been identified as an effective ammonia surrogate in the construction of quinazolin-4(3H)-one ring. This strategy afforded a simple and catalyst-free synthesis of 2-substituted 2,3-dihydroquinazolin-4(1H)-ones and quinazolin-4(3H)-ones via the reaction of isatoic anhydride and aryl aldehydes in the presence of urea or thiourea in ethanol. The reaction proceeded well to afford the quinazolin-4(3H)-one or its dihydro derivative, depending on the nature of carbonyl compounds employed.     

Synthesis of substituted 2-amino-5,6-dihydropyrimidin-4-ones using an aza-Wittig reaction

An aza-Wittig reaction has been used for the first time in the synthesis of substituted 2-amino-5,6-dihydropyrimidin-4-ones via condensation of triphenyliminophosphoranes with aromatic heterocumulenes (arylisocyanates and thiocyanates). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1037–1041, July, 2006.     

Intramolecular [2+2]-cycloaddition of propargylic 2,3-allenoates for the efficient synthesis of 3-oxabicyclo[4.2.0]octa-1(8),5-dien-4-ones: a dramatic substituent effect

[2+2]-Cycloaddition reactions of propargylic 2,3-allenoates under conventional heating conditions afforded 3-oxabicyclo[4.2.0]octa-1(8),5-dien-4-ones, which contain both the biologically important 5,6-dihydropyran-2-one and cyclobutene units.     

Catalyst-free synthesis of novel 4H-indeno[1,2-b]furan-4-ones and furo[2,3-d]pyrimidines in water

An operationally simple, catalyst-free, and efficient protocol for the synthesis of novel 4H-indeno[1,2-b]furan-4-one and furo[2,3-d]pyrimidine derivatives by a one-pot reaction of 2-aminopyridines, 1,3-indandione, or barbituric acid and phenylglyoxal monohydrate in water at reflux, involving domino aldol condensation, Michael addition, and ring-closing reactions is described. This transformation has several advantages, including high yield, short reaction duration, simple workup, and simple purification.     

A new convenient synthesis of functionalized 2,3-dihydro-4-pyridones

A simple, efficient and diastereoselective route to 2,3,6-trisubstituted 2,3-dihydro-4-pyridones from methyl 3,5-dioxohexanoate, aryl aldehydes and ammonium acetate is described.     

An easy route for the synthesis of pyrazine-2,3-dicarbonitrile 5,6-bis-substituted derivatives using a palladium catalyst

An easy synthetic method for the preparation of pyrazine-2,3-dicarbonitrile 5,6-bis-substituted derivatives using Pd-catalyzed cross coupling reaction (Sonogashira, Suzuki, Heck) is described. The reaction conditions allow preparing symmetrical and unsymmetrical bis-substituted products in moderate to high yields, as precursors for the preparation of highly substituted symmetrical and non-symmetrical aza-phthalocyanines with well-defined spectral properties.     

选择性合成双[噻吩并[2,3-d]嘧啶-4(3H)-酮]

以2-氨基-4-三氟甲基-5-甲基-噻吩-3-羧酸乙酯(1)为起始原料制得膦亚胺2.在碳酸钾的催化下,膦亚胺2与芳基异氰酸酯和伯二胺的氮杂Wittig反应制得嘧啶环上2,2’取代的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]3;膦亚胺2与烷基异氰酸酯和伯二胺的氮杂Wittig反应制得嘧啶环上3,3’取代的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]4.化合物3的核磁共振氢谱表明关环反应在嘧啶环的2,2’位;化合物4的核磁共振氢谱表明关环反应在嘧啶环的3,3’位.对合成反应机理的推导及目标产物核磁共振氢谱数据的分析解释了此合成反应的选择性.     

Facile Synthesis of 2-Alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones

Isothiocyanate 2, obtained from aza-Wittig reaction of iminophosphorane 1 with CS₂, reacted with amine to give 2-thioxo-2,3,5,6,7,8-hexahydrobenzothieno[2,3-d]pyrimidin-4(1H)-ones 4 in the presence of sodium ethoxide. S-Alkylation of 4 produced 2-alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones 5 in good yields.     

2,3-Dihydro-5,6-tetramethylenespiro(cyclohexane-2-thieno[2,3-d]pyrimidine)-4(1H)-thione. A Novel Synthetic Route and Crystalline Structure

Self-condensation of cyclohexylidenecyanothioacetamide gave 2,3-dihydro-5,6-tetramethylenespiro(cyclohexane-2-thieno[2,3-d]pyrimidine)-4(1H)-thione, the structure of which was proved by X-ray analysis. A mechanism is proposed for its formation and its alkylation has been studied.     

2,3-二氢-3,5-二羟基-6-甲基-4(H)吡喃-4-酮的合成及热裂解行为

以葡萄糖和哌啶为原料，合成、分离并鉴定了2，3－二氢－3，5－二羟基－6－甲基－4－（H）吡喃－4－酮（1），以空气氛下直接热裂解，SPME吸附热裂解挥发生产物的方式，分析鉴定了20个裂解的挥发性化合物，讨论了热裂解的可能过程。     

左旋多巴与2,3-二氯-5,6-二氰-1,4-苯醌的荷移反应研究

研究了左旋多巴和2,3-二氯-5,6-二氰-1,4-苯醌(DDBQ)的反应条件,确定在硼砂溶液中,在60℃反应70 min可获得稳定的络合物,其λmax=346 nm,组成比为1∶1,表观摩尔吸收系数ε=1.1×104L.mol-1.cm-1,应用拟定的方法测定药物制剂测定结果与文献方法一致,回收率在97.25%~102.7%之间,相对标准偏差在0.7%以内。