Synthesis and some reactions of 1-(4.6-dimethoxybenzo-furanyl)- and 1-(4.6.7-trimethoxybenzofuranyl)butane-1.2.3-trione-2-arylhydrazones

Both 4.6-dimethoxy-( 1c ) and 4.6.7-trimethoxy-5-acetoacetylbenzofuran 1d are obtained from visnaginone ( 1a ) and khellinone methyl ethers 1b , respectively, by a CLAISEN condensation. The β-diketones 1c and 1d couple with aromatic diazonium compounds to form the hydrazones 2a – i . 1-(4.6-Dimethoxybenzofuranyl)- and 1-(4.6.7-trimethoxybenzofuranyl)butane-1.2.3-trione-2-arylhydrazones 2 a–i react with hydrazine hydrate in acetic acid to yield the corresponding pyrazole derivatives 3a–i or 4a–i . The monohydrazones 5a–b are isolated when 2e or 2i are treated with hydrazine hydrate in ethanol. The hydrazones are converted to the respective pyrazoles by the action of glacial acetic acid. Hydroxylamine hydrochloride reacts with 1.2.3-trione-2-arylhydrazones 2a, c, e, f and i to yield the corresponding isoxazole derivatives 6a–e or 7a–e . The 2-arylhydrazones 2a, c, d, e, h and i form the corresponding pyrazole derivatives 8a–f when treated with semicarbazide hydrochloride.     

Nitriles in Organic Synthesis: Synthesis of aromatic amines,aminopyridines, pyrido[2,3-b] pyridine and pyrido[2,3-d]pyrimidine derivatives

The reaction of the α-arylethylidenemalononitrile derivatives 1a , c with piperonylidenemalononitrile ( 2a ) and with ethyl piperonylidenecyanoacetate ( 2b ) yield 1-amino-3,5-diaryl-2,6-benzenedicarbonitrile ( 3a , c ). Phenylaminopyridines 5a , b were obtained from the reaction of 1a , b with phenyl isocyanate and pyridopyridine 6 from the reaction of 5b with benzylidenemalononitrile. Pyridopyrimidines 7b , c was formed from the reaction of 1b , c with phenyl isothiocyanate.     

Synthese und Reaktionen von N-Phthalimido-keten-S,S-acetalen

Synthesis and Reactions of N-Phthalimido-ketene-S,S-acetals N-substituted phthalimido derivatives 1a – f react in the presence of bases (NaH, t-BuONa) with carbon disulfide to the N-phthalimido-ketene-S,S-acetals 3 , 4 , 5 and 6 , respectively. 2-Amino-ketene-S,S-acetals 7a – c are formed by reaction of 3a , b or 5a with hydrazine hydrate. 3c produces with phenylhydrazine the pyrazole 8 , and with piperidine and pyrrolidine the E/Z mixture of the corresponding ketene-S, N-acetals 9a , b . 1c is transformed into 10a – c (E/Z-mixture)by treatment with phenylisothiocyanate under basic condition followed by alkylation.     

1,2,3-三氮唑的合成工艺研究

以对甲苯磺酰肼为原料合成 1,2 ,3 三氮唑。研究了各种工艺条件对收率的影响 ,获得了较佳合成工艺 :用苯作溶剂 ,对甲苯磺酰氯与水合肼配比为 1∶2 (mol) ,在 60～ 70℃下进行缩合反应制得对甲苯磺酰肼 ,收率为 80 6% ;对甲苯磺酰肼与乙二醛以配比 1∶2 7(mol)反应后 ,通入定量的氨气进行环合反应生成 1,2 ,3 三氮唑 ,收率达 66 8%     

Nitriles in organic synthesis: The Reaction of Cinnamonitriles with cyclohexanone and acetylacetone

The reaction of 1 a , b with cyclohexanone afforded hexahydronaphthalene derivatives ( 3 a , b ). In contrast to the behaviour of 1 a , b , cyclohexanone reacts with 4a – c to yield the propenylidenecyclohexanone derivatives ( 5a – c ). The reaction of 1a with acetylacetone gives 4H-pyran 6 and a 1:2-adduct 8 a . On treatment of 8 a with sodium metal in the presence of dioxane, the pyrano [2, 3-b]pyridine ( 9a ) was obtained. When 1 b , c reacted with acetylacetone, the only isolable products were 8 b , c . Reaction of 4a with acetylacetone gives acyclic compound 10 . This on treatment with basic reagents, gives the pyran derivative ( 13 ).     

Activated nitriles in heterocyclic synthesis: Novel Synthesis of Pyrimidine and of Pyridine Derivatives

α-Cyanochalcone reacted with thiourea and guanidine to yield the corresponding pyrimidine derivatives 2 and 4 . On the other hand, urea reacted with the same reagent under the same experimental conditions to yield the known urea derivatives 3 . A new synthesis of polyfunction pyridine via reaction of 1a with malononitrile in presence of aniline could be developed. Similar to the behaviour of 1a , Compounds 1b , c reacted with malononitrile in presence of aniline to yield compounds 8 and 9 . In contrast to the behaviour of compounds 1a – c , 1d reacted with malononitrile to yield the malononitrile derivatives 10 or 11 based on the reaction conditions. Mechanisms to account for formation of the reaction products were suggested.     

6-氯烟酸酰肼的合成工艺研究

以6-氯烟酸(Ⅰ)为原料,在N-甲基吗啉的催化下,与氯甲酸乙酯反应成酸酐活化羧基,再与干肼缩合,合成6-氯烟酸酰肼,考察了物料配比、反应温度、反应时间对收率的影响。结果表明,合成6-氯烟酸酰肼的最佳工艺条件为:n(Ⅰ)∶n(氯甲酸乙酯)∶n(N-甲基吗啉)∶n(肼)=1∶1.2∶1.5∶5,反应温度为-5℃,两步反应的反应时间均为2 h,收率可达83%。     

Darstellung und Reaktionen von 2-Mercapto-6-thioxo-thiopyran-3-carbonsäure-Derivaten

Synthesis and Reactions of 2-Mercapto-6-thioxo-thiopyran-3-carboxylate derivatives 6-Amino-thiopyran-2-thiones ( 1 ) react with dihydrogen sulfide in the presence of pyridine and triethyl amine to yield 6-thioxo-thiopyran-2-thiolates ( 2 ). Methylation of 2 gives the methylthio compounds 3 and 4 . Further methylation of 3a and 4a yields the thiapyrylium salt ( 7 ). The reaction of 2-imino-thiopyran ( 6 ) with carbon disulfide represents another route to the 6-methylthio-thiopyran-2-thione ( 4a ). The 2-methylthio-thiopyran-6-thione ( 3a ) undergoes substitution of the methylthio group with amines to 8 or reacts with phenylhydrazine to phenylhydrazono-thiopyrane ( 9c ). 6-Thioxo-thiophen-2-thiolates ( 2a , b ) react with hydrazine hydrate to give hydrazono-thiopyranes ( 10a , b ) which can be S-methylated. On the contrary 2c gives with hydrazine hydrate under ring transformation the pyridine-2-thiolate ( 11 ). N,S-Acetals ( 12 ) and 1,3,4-thiadiazoles ( 15 ), which give rise to new pyridine derivatives ( 14 ) and ( 17 ), can be obtained from 1-Amino-pyridin-2-thiolate ( 11 ).     

Studies on alkylheterocycles. I. A convenient Synthesis of Phthalazines

Ethyl-2-arylhydrazono-2,3-dioxobutyrate 1a, b reacted with ethylcyanoacetate to yield the pyridazino derivatives 2a, b . Similarly, the pyridazine 2c was obtained via reaction of 3-arylhydrazonopentan-2,3,4-trione with the same reagent. The phthalazines 6 were obtained upon reaction of 2a–c with ylidenemalonitrile 3a, b . The styrene derivatives 7a–d were isolated from the reaction of 2a–c with the appropriate aromatic aldehyde. Compounds 7a–d were subsequently utilized for the synthesis of 6a, d–f respectively via reaction with malononitrile. On the other hand, the phthalazine derivative 8 was formed upon reaction of 2a with either ethylcyanoacetate or malononitrile.     

6-氯哒嗪-3-羧酸甲酯的合成研究

文章介绍了目标化合物6-氯哒嗪-3-羧酸甲酯方便的、高产率的合成方法.本方法以α-酮戊二酸,水合肼作为起始原料,经环合反应、与溴素反应、酯化反应、氯代反应4步,合成了目标化合物,并经IR和1HNMR等对其结构进行了表征.该合成路线原料易得,操作简便,且反应条件温和,适合工业化生产,反应总收率为64.8%.     

Reactions with the Arylhydrazones of some α-cyanoketones

Ethereal diazomethane reacts with the arylhydrazones of mesoxalic acid dinitrile 1a–c and of ethyl α-cyanoglyoxalate 2b, d–g to yield the methylarylhydrazones 3a–c and 4a–e respectively. Treatment of 4b–e with phenylmagnesium bromide results in the formation of the imino derivatives 5a–d . Whereas 2a–g react with phenylhydrazine to yield the aminopyrazoles 8a–g , the hydrazides 10a, b are formed on treatment of 4c, e with hydrazine hydrate. 1a–c react with hydrazine hydrate and with phenylhydrazine to yield 3-amino-4-arylhydrazono-5-imino-2-pyrazoline derivatives 11a–f 11a, b react with acrylonitrile to yield 3-amino-1(β-cyanoethyl)-4-arylhydrazono-5-imino-2-pyrazoline derivatives 12a, b which can be readily cyclised to the pyrazolo[3,2-b]pyrimidine derivatives 13a, b by the action of hot acetic acid.     

2-甲基氨基硫脲的合成

以水合肼和亚磷酸二甲酯为起始原料合成甲基肼,再直接和硫氰酸铵反应两步制取2-甲基氨基硫脲。详细研究并得到两步反应的优化条件:甲基化反应以四丁基溴化铵为催化剂,反应温度为110-120℃,反应时间为2h;后一步反应原料配比n(甲基肼)∶n(硫氰酸铵)=1∶1.2,热重排温度为120℃左右,热重排时间为2h。在此条件下总收率达45.5%(以水合肼计)。     

Rapid Synthesis of Flavor Compound 4-Ethyloctanoic Acid under Microwave Irradiation

Rapid synthesis of 4-ethyloctanoic acid by means of microwave irradiation is described. Diethyl malonate reacted with 2-ethyl-1-bromohexane in the presence of sodium ethoxide to give diethyl (2-ethylhexyl)malonate (1b). 1b was saponified in the solution of ethanol and potassium hydroxide and then acidified to form (2-ethylhexyl)propanedioic acid (1c), and 1c was heated and decarboxylized to give 4-ethyloctanoic acid (1d). The influence of reaction temperature and reaction time on the yield of 1b and the effect of reaction time on the yield of 1c and 1d were investigated in order to optimize the synthetic conditions. The relative optimal conditions for the synthesis of 1b were a mole ratio of sodium to diethyl malonate to 2-ethylhexyl bromide of 0.1:0.11:0.11, a reaction temperature of 80-85 °C, and a reaction time of 2-2.5 h. The yield of 1b was about 79%. 1b was saponified for 30 min and then acidified to form 1c, and the yield of 1c was 96%. 1c was heated for 16 min at 180°C to give 1d, and the yield of 1d was about 90%. The overall yield of 1d is 70% under microwave irradiation. The reaction time was reduced greatly. In order to compare the result of microwave irradiation with that of an oil bath, the reactions were also performed in an oil bath. The structures of intermediates, product and by-product were confirmed by HRMS, (1)H NMR, (13)C-NMR and IR.     

Reactivity of the Methylene Group and cleavage of S-alkyl groups in 1-alkylmercapto-3(4H)-isoquinolone derivatives

Treatment of 2a-thiohomophthalimide 1a and 4-phenylthiohomophthalimide 1b with alkyl halides gave the products 2a – e . By further alkylation of 2a, d the corresponding ethers 3a – h were obtained. When 2a, c were treated with aryl diazonium chloride, the red azo compounds 4a – f were separated. Also 2a – c were found to react with aliphatic and aromatic aldehydes to give the bis-compounds 8a – c and 9a – f respectively. The S-alkyl group present in the aryl azo derivatives 4 was found to be cleaved by treating them independently with phenyl hydrazine, hydroxylamine and primary aromatic amines to give compounds 10, 11 and 12 respectively.     

Heterocyclic Synthesis with Nitriles: Synthesis of some novel pyrrolo [2,1-b]thiadiazoline,pyrrolo[2,1-b]thiadiazolo[3,2-a]pyrimidine and pyridine derivatives

α-(Bromothiocyanatomethyl)benzylidenemalononitrile ( 1 ) reacts with the hydrazides 2a – c , cyanoacethoydrazide ( 2d ,) cyanoacetamide ( 3a ) and cyanoacetanilides 3b – d to afford pyrrolo[2,1-b]thiadiazolines 5a – c , pyrrolo[2,1-b]thia-diazolo[3,2-a]pyrimidine ( 8 ) and the pyridone derivatives 11a – d . Structures and conceivable mechanisms are discussed.     

相转移催化合成1-羟基苯并三氮唑

研究了在相转移催化剂聚乙二醇(PEG)800存在下,邻硝基氯苯和水合肼反应生成1-羟基苯并三氮唑的工艺过程。讨论了催化剂种类、原料摩尔比、反应温度、反应时间、搅拌速度等因素对目的产品收率的影响,得出适合的操作条件为:n(邻硝基氯苯)∶n(水合肼)∶n(PEG-800)=1∶4∶0.03、反应温度110℃、反应时间5h、搅拌速度500r/min,产品收率达98.1%。该合成方法具有工艺原料摩尔比小、反应时间短、操作简便、能耗小等优点。     

Synthesis of 1,1,1-Tris(2-hydroxyethyl)amine-2-acylimide

1,1,1-Tris(2-hydroxyethyl)amine-2-acylimide (I) was prepared by the reaction of hydrazine hydrate, ethylene oxide, and fatty acid methyl ester. Reaction conditions such as solvent, reaction temperature, and molar ratio of reactants were investigated, and (I) was obtained in 73% yield by heating an isopropanol solution of hydrazine hydrate, methyl palmitate, and ethylene oxide in molar ratio of 1:6:6 at 80 C for 2 hr.     

2-氨基-6-烷氧基嘌呤的合成

2-氨基-6-烷氧基嘌呤是重要的核苷类药物的中间体。以鸟嘌呤为原料,通过酰化制得N2.9-二乙酰鸟嘌呤(Ⅰ),收率95.8%。氯化水解得到2-氨基-6-氯嘌呤(Ⅱ),收率75.8%。通过2-氨基-6-氯嘌呤(Ⅱ)与醇钠反应得到2-氨基-6-甲氧基嘌呤(Ⅲa),收率96.5%;2-氨基-6-乙氧基嘌呤(Ⅲb),收率79.6%;2-氨基-6-异丙氧基嘌呤(Ⅲc),收率73.2%;2-氨基-6-三氟乙氧基嘌呤(Ⅲd),收率49.8%。用元素分析,核磁共振,质谱,红外光谱对所得产品进行了分析,证明所得产品为目标产品。重点研究了2-氨基-6-三氟乙氧基嘌呤(Ⅲd)的合成,其合成的最佳工艺条件为:n(Ⅱ)∶n(NaOCH2CF3)=1∶5,用二甲亚砜(DMSO)作为反应溶剂,其用量为m(DMSO)∶m(Ⅱ)=13∶1,用碘化亚铜(CuI)为催化剂,其用量为n(CuI)∶n(Ⅱ)=2∶1,反应温度为160℃。     

6-氨基喹啉合成研究

以4-硝基苯胺和甘油为起始原料,经Skraup反应、80%水合肼和10%Pd/C还原,合成了AQC的重要中间体6-氨基喹啉。产品含量达99%(HPLC),总收率为53%。其结构经ESI-MS、1H NMR确证。     

Pyryliumverbindungen. 42. Benzocycloalkenone und Dihydro-2H,7H-1-benzopyranone aus 2,4,6-Triaryl-pyryliumsalzen und Cycloalkan-1,2-dionen

Pyrylium Compounds. 42. Benzocycloalkenones and Dihydro-2H,7H-1-benzopyranones from 2,4,6-Triarylpyrylium Salts and Cycloalkane-1,2-diones 2,4,6-Triarylpyrylium salts 1 react with cycloalkane-1,2-diones 2 in the presence of an appropriate condensing agent to yield benzocycloalkenones 3 . Thus, sodium acetate and cyclo-hexane-1,2-dione ( 2a ) lead to the dihydro-2H-naphthalenones 3a – i , whereas with cycloheptane-1,2-dione ( 2b ) and piperidine acetate, triethylamine or sodium acetate the tetrahydro-5H-benzo-cyclohepten-5-ones 3j – r are formed. As shown for the example 3a, j → 4a, b , benzocycloalkenones of type 3 can be converted into phthalazines 4 on heating with hydrazine in ethanol. By reaction of the dione 2a and an equimolar mixture of triethylamine and acetic acid or morpholine acetate with the salts 1 5,6-dihydro-2H,7H-1-benzopyran-8-ones 5 are obtained as a result of a new type of ring transformation. The pyrans 5 can be cleaved with perchloric acid in ethanol to 5,6,7,8-tetrahydro-8-oxo-1-benzopyrylium perchlorates 6 . If the pyrans 5 are heated with sodium acetate in ethanol, a conversion to benzocycloalkenones 3 is achieved (cf. 5a → 3a ). The structure of the new compounds was established by spectroscopic methods.