Regio- and stereoselectivity of 1-(Pyridazin-3-yl)-3-oxidopyridinium Betaines towards 2π- and 4π-conjugated olefins

1-(6-Phenyl) and 1-(6-(4-tolyl)-3-oxidopyridinium betaines ( 1a , b ) react as 1,3-dipoles with conjugated olefines, namely 4-vinylpyridine, ethyl cinnamate and styrene as 2π-1,3-dipolarophiles to give 2,6-cycloadducts [6-substituted-8-azabicyclo[3,2,1]oct-3-en-2-ones ( 3a , b , 4a , b and 5b )] and with butadiene and furan as 4π-dipolarophiles to give 2,4-cycloadducts [7-substituted-7-azabicyclo[4,3,1]deca-3,8-diene-10-one] and 3-6-phenylpyridazin-3-yl)-3-aza-10-oxatricyclo-[5,2,1,1^2,6]undeca-4,8-diene-11-one ( 9a ). Structural and configurational assignments were based on H.n.m.r. spectral analysis.     

(S/R)-2-(2-(5-氟-2,4-二氧-3,4-二氢嘧啶-1(2H)-基)乙酰氨基)-3-(4-羟苯基)丙酸的合成及抗肿瘤活性

以1-乙基-3-(3-二甲胺丙基)碳二亚胺盐酸盐(EDCI)/1-羟基苯并三氮唑(HOBt)为缩合剂,5-氟尿嘧啶-1-基乙酸为中间体,分别与L-酪氨酸甲酯和D-酪氨酸乙酯通过液相偶联合成了(S)-2-(2-(5-氟-2,4-二氧-3,4-二氢嘧啶-1(2H)-基)乙酰氨基)-3-(4-羟苯基)丙酸甲酯和(R)-2-(2-(5-氟-2,4-二氧-3,4-二氢嘧啶-1(2H)-基)乙酰氨基)-3-(4-羟苯基)丙酸乙酯,水解后得到相应的酸对映体。所合成的化合物结构经1H NMR1、3C NMRI、R、MS及比旋光度等测试得以确证。四种化合物的体外抗肿瘤活性测试结果,说明该化合物的抗肿瘤具有一定的选择性,且R构型对抗肿瘤也起到了一定的作用。     

Anodic oxidation of 3-amino-5-(pyrid-4-yl)-1, 2-dihydropyrid-2-one (amrinone)

The anodic behavior of the cardiotonic drug 3-amino-5-(pyrid-4-yl)-1,2-dihydropyrid-2-one 1 and of 6 compounds with similar structure was investigated at platinum and vitreous carbon electrodes in acetonitrile and in aqueous medium. Caused by the 3-amino group 1 is oxidized at a relatively small oxidation potential in an irreversible two-electron process. Depending on the addition of a strong base or a strong acid the oxidation potential vs. SCE in acetonitrile is −0.08 V (anion), +0.66 V (neutral compound), +0.93 V (monocation) or +1.15 V (dication). In H₂O a strong decrease of the oxidation potential with increasing pH was found as a reason for the sensitivity of 1 against oxygen in alkaline solution. The anodic oxidation of 3-dimethylamino-5-(pyrid-4-yl)-1, 2-dihydro-pyrid-2-one 3 in 0.1 m H₂SO₄ leads to 5-(pyrid-4-yl)-piperidine-2,3,6-trione 9a or 5-(pyrid-4-yl)-piperidine-2,3,4-trione 9b , which is also the oxidation product of 1 at small concentration. At high concentration of 1 coupling reactions at the 3-amino-group lead to dimeric products, which could not be identified.     

The synthesis of fused and pendant pyrazole heterocyclic compounds from 5-amino-3-methyl-1-phenylpyrazole and their evaluation as fluorescent brightening agents

5-Amino-3-methyl-1-phenylpyrazole ( 1 ) has been condensed with EMME ( 2 a) and EMCA ( 2 b) and the resulting ethyl 5-aminoacrylates ( 3 a–b) cyclized to pyrazolo[3,4,-b]pyridines ( 4 a–b). 3-Methyl-1-phenylpyrazol-5-yl diazonium salt ( 7 ), prepared from ( 1 ) was coupled with tobias acid ( 8 ) and 2-methoxy-6-aminoquinoxaline ( 9 ) to get the corresponding O-aminoarylazo and heterylazo dyes ( 10 ) which were oxidatively cyclized to 2-N-(3-methyl-1-N-phenylpyrazol-5-yl)-1,2,3-triazolo[4,5-a] naphthalene and [4,5-f] quinoxaline derivative ( 11 ). The spectral properties of the compounds ( 4 a–b, 5 , 6 , 11 a–b) were studied.     

The Synthesis and Absolute Configuration of Enantiomeric Pure (R)- and (S)-3-(piperidin-3-yl)-1H-Indole Derivatives

This article describes the synthesis of new chiral 3-(piperidin-3-yl)-1H-indole derivatives (R)-10a-c and (S)-11a-c from the corresponding diastereomers: (3R, 2R) and (3S, 2R)-2-[3-(1H-indol-3-yl)-1-piperidyl]-2-phenyl-acetamides (3R, 2R)-4a, (3R, 2R)-6b, (3R, 2R)-8c and (3S, 2R)-5a, (3S, 2R)-7b, (3S, 2R)-9c. Diastereomers were obtained by N-alkylation of derivatives of racemic 3-(piperidin-3-yl)-1H-indoles 1a-c using (S)-2-(4-toluenesulfonyloxy)-phenylacetic amide (S)–II. The same method was applied to obtain (3R, 2S)-methyl-2-[3-(1H-indole-3-yl)-1-piperidyl]-2-phenylacetate (3R, 2S)-2a and (3S, 2S)-methyl-2-[3-(1H-indole-3-yl)-1-piperidyl]-2-phenylacetate (3S, 2S)-3a diastereomers by treating amine 1a with (R)-2-(4-toluenesulfonyloxy)-phenylacetic acid methylester (R)-I. Systematic studies via single crystal X-ray crystallography were used to determine the molecular structure of the racemates 1a-c and the absolute configuration of the enantiomers. The solid racemates 1b and 1c were “true racemates” crystallizing in a centrosymmetric space group, while 1a formed a racemic conglomerate of homoenantiomeric crystals. The absolute configuration was determined for the enantiomeric pairs (R)-10a/(S)-11a, (R)-10b/(S)-11b, and (R)-12c/(S)-13c, as well as for (3S,2S)-3a. Spectra of ¹H, ¹³CNMR, HPLC, and HRMS for diastereomers and enantiomers were consistent with the determined structures.     

1-(5,7-二羟基-2,2-二甲基苯并吡喃)-3-(2,2-二甲基苯并吡喃)双氢查尔酮的首次全合成

标题化合物是从Metrodorea stipularis树枝中提取出来的,此化合物具有抗南美洲锥虫病、抗疟疾、抗肿瘤等药理作用。以廉价的2,4,6-三羟基苯乙酮、4-羟基苯甲醛为原料,经吡喃环化、苄基保护酚羟基、羟醛缩合和Pd-C/H2还原不饱和双键及脱保护基,完成天然产物1-(5,7-二羟基-2,2-二甲基苯并吡喃)-3-(2,2-二甲基苯并吡喃)双氢查尔酮的全合成。所有新化合物的结构均经过NMR、IR、HR-MS确认。初步生物活性实验结果表明,1-(5,7-二羟基-2,2-二甲基苯并吡喃)-3-(2,2-二甲基苯并吡喃)双氢查尔酮对大肠杆菌的最小抑菌浓度为32μg/mL。     

Reactions with 2-thiazolin 5-ones. IV. Action of amines on 4-substituted 2-alkoxy- and 2-benzylmercapto-2-thiazolin-5-ones

Whereas treatment of 2-butyloxy-, 2-pentyloxy- and 2-β-phenylethyloxy-4-arylazo-2-thiazolin-5-ones 1d–h with strong basic amines results in their rearrangement into 1-aryl- Δ²-1,2,4-triazolin-5-one-3-carboxylic acid derivatives 2 , the 2-isobutyloxy, 2-(2-octyloxy)- and the 2-cyclohexyloxy-4-arylazo-2-thiazoline-5-ones 1i–n rearrange upon treatment with the same reagents into Δ²- 1,2,4-triazoline-5-thione-3-carboxylic acid derivatives 3 . On the other hand, 1d–h,1 react with aromatic amines to give 1-aryl-2-alkoxy-1,2,4-triazole-3-carboxylic acid anilides 4a–i , via the loss of hydrogen sulphide. The phenylhydrazides 4j–l are obtained upon treatment of 1g, h,l with phenylhadrazine. Treatment of 4-arylidene-2-benzylmercapto-2-thiazolin-5-ones 6a–c with ammonia results in the formation of the thiohydantoin derivatives 7e, g . However, 6b, c react with phenylhydrazine to yield the phenylhydrazides 8b, c . The reaction of 6a–e with piperidine or morpholine involves to molecules of the reagent to yield 10a–d which are thermally cyclised to the thiazolone derivatives 11a–d .     

Pyryliumverbindungen. 44 [1]. 2-(2-Hydroxy-3-oxo-cycloalk-1-enyl)-2H-thiopyrane aus 2,4,6-Triaryl-thiopyryliumsalzen und Cycloalkan-1,2-dionen

Pyrylium Compounds. 44. 2-(2-Hydroxy-3-oxo-cycloalk-1-enyl)-2H-thiopyranes from 2,4,6-Triarylthiopyrylium Salts and Cycloalkane-1,2-diones 2,4,6-Triarylthiopyrylium salts 5 react with cyclopentane-1,2-dione ( 2a ) or cyclo-hexane-1,2-dione ( 2b ) in the presence of an appropriate acid binding agent (e.g. sodium acetate, piperidine acetate, triethylamine/acetic acid, triethylamine) to give the hitherto unknown 2-(2-hydroxy-3-oxo-cycloalk-1-enyl)-2H-thiopyranes 6 . – The structure of the novel compounds was established by n.m.r., i.r. and u.v. spectroscopic methods.     

4-(1-Methyl-2-sulfamoylvinyl)pyrazoles by Ring Transformation of 1,1-dioxo-2H-1,2-thiazine-4-carbaldehydes with hydrazines

As masked 1,3-dicarbonyl compounds, 1,1-dioxo-2H-1,2-thiazine-4-carbaldehydes ( 2a–e, 7 ) undergo ring transformations with nucleophilic hydrazines to produce 4-[1-methyl-2-(arylsulfamoyl)vinyl]pyrazoles ( 9a–i ). For 9h , an X-ray structural analysis is reported. With less nucleophilic semicarbazide and p-nitrophenylhydrazine the hydrazones ( 11a, b ) were isolated. The carbaldehydes 2a–e , 7 and 8a, b were synthesized by formylation of the 1,1-dioxo-2H-1,2-thiazines 1a–e, 5 and 6a, b with dichloromethyl methyl ether/TiCl₄. In the case of 1a–e mixtures of 4- and 6-carbaldehydes ( 2a–e/3a–e ) were obtained, which, however, could be used for the synthesis of pyrazoles.     

β-Fur-2-yl-α-halogenacrylonitrile. VII. Reaktionen von β-(5-Brom-fur-2-yl)-α-bromacrylonitril mit Mercaptan,Thioharnstoff und Thioharnstoffderivaten

β-Fur-2-yl-α-halogenacrylonitriles. VII. Reactions of β-(5-Bromo-fur-2-yl)-α-bromoacrylonitriles with Mercaptans, Thiourea and Thiourea Derivatives β-(5-Bromo-fur-2-yl)-α-bromoacrylonitrile 1 reacts with ethylmercaptan to yield β-(5-bromo-fur-2-yl) β-ethylthioacrylonitrile 3 . With thiourea β,β′-thio-bis[β-(5-bromo-fur-2-yl)]-acrylonitrile 2 is formed. The pyrimidines 4 and 5 have been prepared by the reaction of 1 with s-methylthiourea and 2-aminothiazole, respectively. The structure of the new compounds were determined by means of x-ray analysis, ¹H-n.m.r., ¹³C-n.m.r. and mass-spectroscopy.     

1-[2-(2,4-二氯苯基)-4-酰氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑的合成及生物活性

2, 4 二氯苯乙酮经溴化得ω 溴 2, 4 二氯苯乙酮,该化合物与丙三醇反应并脱水得 2 (2, 4 二氯苯基 ) 2 溴甲基 4 羟甲基 1, 3 二氧戊环,再在常温下与苯甲酰氯反应合成 2 (2, 4 二氯苯基) 2 溴甲基 4 苯甲酰氧基甲基 1, 3 二氧戊环,然后在 130℃与 1H 1, 2, 4 三唑钠反应 36h,所得产物经水解得 1 [2 (2, 4 二氯苯基 ) 4 羟甲基 1, 3 二氧戊环 2 基]甲基 1H 1, 2, 4 三氮唑,再在室温以吡啶作缚酸剂,与甲磺酰氯反应 20h,合成 1 [2 (2, 4 二氯苯基) 4 甲磺酰氧基甲基 1, 3 二氧戊环 2 基]甲基 1H 1, 2, 4 三氮唑,最后与各类羧酸的钾盐反应,合成了 10种 1 [2 (2, 4 二氯苯基 ) 4 酰氧基甲基 1, 3 二氧戊环 2 基 ]甲基 1H 1, 2, 4 三氮唑类化合物。产物的结构经GC MS、IR证实。对目标产物进行了杀菌活性测定,结果表明,各化合物均具有不同程度的生物活性,其中: 1 [2 (2, 4 二氯苯基) 4 (α 甲基苯乙酰氧基)甲基 1, 3 二氧戊环 2 基]甲基 1H 1, 2, 4 三氮唑对水稻稻瘟病菌和油菜菌核病菌的抑制率,分别达到 92 1%与 95 6%,对小麦赤霉病菌和瓜类灰霉病菌的抑制率达到 80%以上;1 [2 (2, 4 二氯苯基) 4 对氟苯甲酰氧基甲基 1, 3 二氧戊环 2 基 ]甲基 1H 1, 2, 4 三氮唑对水稻稻瘟病菌和油菜菌核病菌的抑制率分别为 9     

Synthesis of some new heterocyclic systems derived from 2-acetylbenzimidazole

The named compound was reacted with thiosemicarbazide and/or semicarbazide to produce the corresponding condensation products II and V respectively. Reaction of II with chloroacetic acid in ethanol containing anhydrous sodium acetate yielded III. Condensation of III with aromatic aldehydes yielded the corresponding arylidene derivatives (IV). Oxidation of the semicarbazone V with selenium dioxide gave 2-(1,2,3-selenadiazole-4-yl)benzimidazole (VIa, b) while with thionyl chloride it gave 2-(1,2,3-thiadiazole-4-yl)benzimidazole (VIIa, b). The chalcones of 2-acetyl and/or 1-methyl-2-acetylbenzimidazole were condensed with hydrazine hydrate, phenylhydrazine and/or hydroxylamine to produce 2-(5-aryl-1(H)-pyrazolin-3-yl)-, 2-(5-aryl-1-phenyl-2-pyrazolin-3-yl)- and 2-(5-aryl-2-isoxazolin-3-yl)benzimidazole (IX, X, XI) respectively.     

Reactions with β-ketodianilides. I. New synthesis of Pyrido[3,4-c]pyridine Derivatives

Acetonedicarboxylic acid dianiline reacted with malononitrile, ethyl cyanoacetate or benzoylacetonitrile to give (6-amino-5-cyano-1,2-dihydro-2-oxo-1-phenylpyrid-4-yl)-acetanilide ( 3 ), (3-cyano-2,6-dioxo-1-phenyl-1,2,5,6-tetrahydropyrid-4-yl)acetanilide ( 8 ) or (3-cyano-1,6-dihydro-1,2-diphenyl-6-oxopyrid-4-yl)acetanilide ( 9 ). Compounds 3 and 8 could be cyclised into 8-amino-1,6-diphenyl-1,2,4,5,6,7-hexahydro-7-iminopyrido[3,4-c]pyridine-2,5-dione ( 4 ) and 7-amino-1,2,3,5,6,8-hexahydro-1,6-diphenylpyrido[3,4-c]pyridine-2,5,8-trione ( 10 ) respectively by heating their solutions in dimethylformamide in the presence of triethylamine. Each of 3 and 4 coupled with arenediazonium chlorides to give the corresponding arylhydrazone derivatives ( 5a–d ) and ( 6a–c ), respectively. Condensation of 4 with p-nitrosodimethylaniline yielded 8-amino-4- (p-dimethylaminophenylimino)-1,6-diphenyl-1,2,4,5,6,7-hexahydro-7-iminopyrido[3,4-c]pyridine2,5-dione ( 7 ).     

Synthesis of biologically active 4-benzyl-1(2H)-phthalazinones and 2-aryl-3(2H)-1-benzal-isoindolinones

4-Benzyl-2-1(2H) phthalazonyl derivatives of type 2, 3, 5a, b were synthesized by Mannich reaction of 4-benzylphthalazinone 1 which by the reaction with diazomethane yielded O-methylated derivative 4 . Various 1-benzal-2-substituted aryl-3(2H) isoindolinones 7a–f, 8a–e were also prepared. Its i.r., ¹H-n.m.r. and mass spectra were discussed. Some of them exhibit pronounced antimicrobial activities. A number of phthalazinones have found application in clinical medicine [1–3] due to the their pronounced antipyretic, analgesic and tuberculostatic activity and the importance of some benzylidenephthalimidines as stabilisers for halogen containing high polymers [4] and the local anesthetic activity superior to that of procaine [5], tempted us to procure some new phthalazinones and isoindolinones with biological interest.     

A SERS investigation of Cu electrodeposition in the presence of the model leveller 4-{2-[1-(2-cyanoethyl)-1,2,3,4-tetrahydroquinolin-6-yl]diazenyl} benzonitrile

In situ SERS measurements were performed during the potentiostatic electrodeposition of Cu from an acidic cupric sulphate solution containing 4-{2-[1-(2-cyanoethyl)-1,2,3,4-tetrahydroquinolin-6-yl]diazenyl} benzonitrile (CTDB). CTDB is a model leveller for Cu electroplating in ULSI semiconductor fabrication. The cathodic reactivity of CTDB at the diazo bridge was highlighted, leading to the formation of 3-cyan aniline and 6-amino-1-(2-cyanoethyl)-2,3,4-trihydro-quinoline and to denitrilation.     

(2R)-2-{(2S,3S)-3-[(1R)-1-叔丁基二甲基硅氧乙基]氮杂环丁-2-酮-4-基}丙酸的合成

从水杨酰胺和环己酮出发,经过亲核反应,丙酰氯取代反应,与4-AA缩合,最后水解合成(2R)-2-[(2S 3S)-3-[(1R)-1-叔丁基二甲基硅氧乙基]氮杂环丁-2-酮-4-基]丙酸,并通过红外,核磁确证其化学结构。该反应条件温和不苛刻,操作简便,适于工业化生产。     

2-(1-H-四唑)-4’-甲基联苯的合成

以2-氰基-4'-甲基联苯(Ⅱ)为原料,与氨基钠反应得到2-脒基-4'-甲基联苯(Ⅲ),该化合物与水合肼发生取代反应得到4'-甲基-[1,1'-联苯]-2-甲酰胺酰肼(Ⅳ),最后在酸性条件下与亚硝酸钠发生闭环反应得到2-(1-H-四唑)-4'-甲基联苯(Ⅰ),总收率达到81%,其结构经1HNMR和MS确证。     

Cyclisierungsreaktionen von 1-[2-Amino-1-cyan-2-thio-]ethylen-pyridiniumbetainen

Cyclization Reactions of 1-[2-amino-1-cyano-2-thio-]ethenepyridinium Ylides 1-[2-Amino-1-cyano-2-thio-]ethene-pyridinium ylides 1 can be alkylated with methyliodide or α-haloesters and α-haloketones, respectively, to form 1-[2-alkyl(aryl)amino-1-cyano-2-methylthio-ethene-1]pyridinium iodides 2a-–e or 1-[2-alkyl(aryl)-amino-1-cyano-2-alkoxy(aryl)-carbonylmethylthio-ethene-1] pyridinium salts 3a–f . With the exception of 3a–b the compounds 3 or 1 react with haloketones to yield 1-[4-amino-2-alkyl-(aryl)amino-5-benzoyl-thiene-3]pyridinium salts 4a–m or 3-alkyl-4-aryl-2-(1-cyano-1-pyridinium)methylene-Δ⁴-thiazoline salts 5a–f .     

3-(5,5-二甲基-1,3-二(口恶)烷-2-基)-2-丁烯醛合成研究

以4-乙酰氧基-2-甲基-2-丁烯醛为原料,经醛基保护、酯交换、氧化合成3-(5,5-二甲基-1,3-二(口恶)烷-2-基)-2-丁烯醛.首次采用氯化亚铜协同TEMPO催化氧化2-(3-羟基-1-甲基-1-丙烯基)-5,5-二(口恶)甲基-1,3-二(口恶)烷,合成3-(5,5-二甲基-1,3-二(口恶)烷-2-基)-2-丁烯醛.初步研究了催化氧化反应机理,指明了催化氧化反应研究的方向.氯化亚铜协同TEMPO催化氧化α-烯醇合成α-烯醛,对于现代类胡萝卜素类药物和其他新药开发研究具有重要意义.     

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.