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.     

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.     

Junjappa–Ila (JI) Heteroaromatic Annulation: A New General α‐Oxoketene Dithioacetals Mediated Inverse Method for Synthesis of Substituted Benzothiazoles

3‐(Methylthio)‐5‐oxo‐2‐(2‐phenyl‐1,3‐thiazol‐4‐yl)‐4,5‐substituted‐pent‐2‐enenitriles 3a–j were obtained in good yields by condensation of (2‐phenyl‐1,3‐thiazol‐4‐yl)‐acetonitrile (1) with various α‐oxoketene dithioacetals 2a–j in the presence of sodium hydride. The intermediates 3a–j underwent smooth cyclization in the presence of PTSA to afford the corresponding benzothiazoles 4a–j in moderate yields.     

3-(4-吡啶基)-4-(6-取代色酮-3-基-亚甲氨基)-5-芳氨基-1,2,4-三唑的合成

N-芳基-N'-[(4-吡啶基)羰基]氨基硫脲用85%的水合肼环化, 得到3-(4-吡啶基)-4-氨基-5-芳氨基-1,2,4-三唑(2a～2c). 然后再与3-甲酰基色酮(3a～3d)反应, 制备得到了一系列新化合物: 3-(4-吡啶基)-4-(6-取代色酮-3-基亚甲氨基)-5-芳氨基-1,2,4-三唑(4a～4c, 5a～5c, 6a～6c, 7a～7c). 化合物的结构经元素分析, IR, ¹H NMR和MS确证.     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Silyl- and germylpropynals in the synthesis of azolyl-substituted 2-imidazoline 3-oxide 1-oxyls

Azolyl-substituted nitronylnitroxyls were synthesized using Me 3Si- and Et 3Ge-substituted propynals. When synthesizing 2-[3-(triethylgermyl)-l H-pyrazol-4-yl]-4,4,5,5-tetramethyl-4,5-dihydro-1 H-imidazole 3-oxide 1-oxyl ( 3b), the cycle was assembled by the reaction of CH2N2 with the corresponding triethylgermylethynyl-substituted nitronylnitroxyl. In the case of 2-[4-(trimethylsilyl)-l H-1,2,3-triazol-5yl]- (8a) and 2-[4-(triethylgermyl)-1 H-1,2,3-triazol-5-yl]-4,4,5,5-tetramethyl-4,5-dihydro-l H-imidazole 3-oxide l-oxyls (8b), the corresponding heterocyclic aldehydes were synthesized first and then were used for the preparation of compounds 8a and 8b. According to the X-ray diffraction study, the presence of the bulky substituent Me3Si or Et3Ge in the heterocycle causes its turn by 40.9(2)° in 8a and 33.6(6)° in 3b relative to the plane of the paramagnetic fragment ONCNO.     

N-Methylpyridinium Tosylate Catalysed Green Synthesis,X-Ray Studies and Antimicrobial Activities of Novel (E)-3-Amino-2-(e)-(3, 4-Dihydronaphthalen-1(2H)-Ylidene)Hydrazono)Thiazolidin-4-Ones

Abstract

3,4-Dihydro-2H-naphthalen-1-ones 1,on reaction with thiocarbohydrazide, afforded monothiocarbohydrazones 2, which, on condensation with chloroacetic acid in the presence of an ionic liquid and bromotrimethylsilane furnish (E)-3-amino-2-(E)-(3,4-dihydronaphthalen-1-(2H)-ylidene)hydrazono)thiazolidin-4-ones 3 in quantitative yields. Acetyl derivatives 5 were obtained from 3 with acetic anhydride. Monothiocarbohydrazones 2 on condensation with benzaldehyde yield azomethines 4. The structure of compounds 2–5 has been established by elemental analysis, IR, ¹H NMR, and mass spectral data. The structure of compound 3a has been further confirmed by X-ray crystallographic data. The compounds 2–5 were screened for antimicrobial activity. The thiazolidinones 3a and 3b showed maximum antimicrobial activities.     

New Approach to 4‐ and 5‐Aminopyrazole Derivatives

3‐Oxo‐3‐(pyrrol‐2‐yl)‐propanenitrile 1 coupled with aromatic diazonium salts to yield the corresponding 2‐arylhydrazones 2a–c. The latter products reacted with chloroacetonitrile and ethyl chloroacetate to yield 4‐aminopyrazole derivatives 5a–f. Reaction of 2 with hydrazine hydrate led to formation of 5‐amino‐4‐arylazopyrazole 6a–c. Compound 1 reacted also with trichloroacetonitrile to yield enamine 7, which in turn reacted with hydrazine hydrate to yield 5‐amino‐3‐(pyrrol‐2‐yl)‐pyrazole‐4‐carbonitrile 8.     

L-Proline-Catalyzed Knoevenagel Condensation: A Facile,Green Synthesis of (E)-Ethyl 2-Cyano-3-(1H-indol-3-yl)acrylates and (E)-3-(1H-Indol-3-yl)acrylonitriles

L-Proline has been utilized as a novel and ecofriendly catalyst in ethanol medium for the Knoevenagel condensation of indole-3-carboxyaldehydes and their N-methyl derivatives 1(a–e) and 4(a–e) with the active methylene compound, ethyl cyanoacetate (2) to afford substituted (E)-ethyl 2-cyano-3-(1H-indol-3-yl)acrylates 3(a–e) and 5(a–e) respectively. These products were reacted with dimethyl sulfate in the presence of PEG-600 as an efficient and green solvent to afford the corresponding N-mthylated derivatives 5(a–e). These Knoevenagel products react with 5% NaOH, yielding (E)-3-(1H-indol-3-yl)acrylonitriles 6(a–e) and 7(a–e).     

Efficient Synthesis of N‐Oxide Derivatives: Substituted 2‐(2‐(Pyridyl‐N‐oxide)methylsulphinyl)benzimidazoles

Different substituted 2‐chloromethylpyridyl derivatives (6a–d) were oxidized with mCPBA to give the respective 2‐chloromethylpyridine‐N‐oxide derivatives (7a–d) at low temperature, which on condensation with 2‐mercapto‐1H‐benzimidazole (8a–c) in the presence of aprotic solvents give the 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfanyl]‐1H‐benzimidazole (9a–d) in good yield. Finally, 9a–d oxidized with mCPBA in chlorinated solvent gives a mixture of 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfonyl]‐1H‐benzimidazole (3a–d, 10%) and 2‐[[(pyridin‐2‐yl‐1‐oxide) methyl]sulfinyl]‐1H‐benzimidazole (4a–d, 90%) derivatives.     

New Heterocyclic Phosphorus Ylides: Synthesis,Crystal Structure,and Theoretical Calculation of Alkyl Substituted 3-(4-Benzoyl-1,5-diphenyl-2,3-dihydro-1H-pyrazol-3-yl)-3-oxo-2-(triphenylphosphoranylidene) Propanoates

Novel alkyl substituted 3-(4-benzoyl-1,5-diphenyl-2,3-dihydro-1H-pyrazol-3-yl)-3-oxo-2-(triphenylphosphoranylidene) propanoates (3) were synthesized from 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carbonylchloride (1) and alkyl (triphenylphosphoranylidene) acetates (2a–b). The synthesized compounds were characterized by elemental analysis, spectroscopic studies (3a–b), and single crystal X-ray diffraction (3a). The mechanism of the reaction between (1) and (2a) was studied by AM1, and the geometrical parameters of the studied molecules were also carried out in B3LYP methods with the standard 6–31G (d,p) basis set. NBO analysis were studied for 1 and 2a B3LYP methods with the standard 6–31G (d,p) basis set.     

Unexpected Synthesis of Novel 3-Allyl-5-(arylidene)-2-thioxo-thiazolidin-4-ones in Reactions of 3-Allylrhodanine with 2-Arylidene-4-methyl-5-oxopyrazolidinium Ylides

Abstract

The reaction of 3-allylrhodanine with 2-arylidene-4-methyl-5-oxopyrazolidinium ylides proceeded unexpectedly to form novel 3-allyl-5-(arylidene)-2-thioxo-thiazolidin-4-ones 6a–k in good yields. All structures have been formulated on the basis of their spectral (IR, NMR, MS) data and elemental analyses. In addition, the structure of compound 6a was confirmed by means of x-ray crystallographic analysis.     

Reactions of 3-alkylsulfanyl-2-arylazo-3-(1-azacycloalk-1-yl)acrylonitriles with maleimide

Reactions of 2-arylazo-3-(1-azacycloalk-1-yl)-3-methylsulfanylacrylonitriles with male-imide in benzene gave octahydropyrrolo[3,4-a]pyrrolizines 2a–c, decahydro-2,7a-diaza-cyclopenta[a]indene 2e, and decahydro-5-oxa-2,7a-diazacyclopenta[a]indene 2f as a result of 1,3-dipolar cycloaddition. In a similar reaction with 3-allylsulfanyl-2-arylazo-3-(1-azacycloalk-1-yl)acrylonitriles 3, dipolar cycloaddition and intramolecular cyclization competed to give a mixture of compounds 2 (major products) and 1,4,6,7,8,8a-hexahydropyrrolo[2,1-c]-1,2,4-triazines 4b–d, 1,6,7,8,9,9a-hexahydro-4H-pyrido[2,1-c]-1,2,4-triazine 4e, and 1,4,6,7,9,9a-hexahydro-1,4-oxazino[3,4-c]-1,2,4-triazine 4f (minor products).     

Experimental and theoretical structural studies on 4-(2-phenylethyl)-5-(2-furyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione

The structural and conformational features of 4-(2-phenylethyl)-5-(2-furyl)-2, 4-dihydro-3H-1,2,4-triazole-3-thione (1a), which can be related to the biological activity, have been investigated by X-ray diffraction and molecular modeling techniques. Ab initio method (RHF/6-31G) and density functional theory (B3LYP/6-31G(D)) have been used to calculate structural parameters, conformations, and relative energy of two tautomeric specious (1a and 1b) of the title compound. The geometry and the conformation of the thione form, 1a, is well reproduced by the DFT (B3LYP/6-31G(D)) method as compared with X-ray structure in which this form is found. The thione form is also predicted to be 14.42 kcal/mol more stable than the thiol form in the gas-phase by the DFT method.     

7β-[2-(2-氨噻唑-4-基)-(Z)-2-甲氧亚胺乙酰胺基]-3-杂环硫亚甲基头孢菌素衍生物的半合成及抗菌活性

通过5-取代-1,3,4-噁二唑-2-硫醇(2a～2h), 5-芳胺基-1,3,4-噻二唑-2-硫醇(2i～2j)和头孢菌素母体7-氨基头孢烷酸(7-ACA)反应, 制得头孢菌素中间体3a～3j, 用氨噻唑肟活性酯4和头孢菌素中间体缩合, 合成了头孢菌素衍生物5a～5j. 体外抗菌结果表明头孢菌素衍生物对革兰氏阳性菌和阴性菌均有显著抑制活性, 对金黄色葡萄球菌尤为敏感     

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.]     

Synthese und Reaktionsverhalten von 3-(Bis(alkylthio)methylen)-3H-isobenzofuran-1-on-und 2-(Bis(alkylthio)methylen)-3(2H)-benzofuranon-Derivaten

Summary 3(Bis(alkylthio)methylene)-3H-isobenzofuran-1-ones2a–e and 2-(bis(alkylthio)methylene)-3(2H)-benzofuranone derivatives4a–c are obtained by reaction of phthalides1a–d or 3(2H)-benzofuranone (coumaranone3), respectively, with carbon disulfide under basic conditions followed by alkylation. The reaction behaviour of the new compounds2 and4 is investigated. 2-((2-Dimethylthio-1-oxo)ethyl)benzoic acid N,N-dimethylamide (7a) and 2-((2-dimethylthio-1-oxo)ethyl)-benzoic acid 2-methylpiperidide (7b) are surprisingly formed instead of the methylthio substitution products by treatment of2a with the corresponding amine in the presence of aluminum chloride.

Herrn Professor Dr. Dr. h. c.Waldemar Adam zum 60. Geburtstag gewidmet     

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.     

2-(1-苯基/取代苯基-3-甲基-5-氯-1H-4-吡唑基)-3-芳酰胺-4-噻唑啉酮的合成及生物活性

利用1-芳基-3-甲基-5-氯-1H-4-吡唑醛(2)分别与取代苯甲酰肼反应, 进一步与巯基乙酸关环, 合成了11个新的2-(1-芳基-3-甲基-5-氯-1H-4-吡唑基)-3-芳酰胺-4-噻唑啉酮类化合物 3a～3k, 并利用元素分析, IR, ¹H NMR和X-ray晶体衍射确定了其结构. 初步生物活性表明: 3e具有杀菌活性, 3e和3k具有除草活性.     

N-(6-色酮-3-基-亚甲氨基)-S-{[4-芳基-5-(吡啶-4-基)]-1,2,4-三唑-2-基}巯乙酰胺类化合物的合成

N-芳基-2-[(吡啶-4-基)羰基]氨基硫脲1a～1e用NaOH溶液环合, 得到3-巯基-4-芳基-5-(吡啶-4-基)-1,2,4-三唑(2a～2e), 经酯化, 肼解, 得S-{[4-芳基-5-(吡啶-4-基)]-1,2,4-三唑-3-基}巯乙酰肼(3a～3e), 再与3-甲酰基色酮(4a～4d)反应, 合成得到了一系列新化合物5a～5e, 6a～6e, 7a～7e, 8a～8e. 化合物的结构经元素分析, IR, ¹H NMR和MS谱确证.