STUDIES ON THIAZOLOPYRIDINES. PART 5: SYNTHESIS OF HITHERTO UNKNOWN THIAZOLINONE AND THIAZOLO[3,2-a]PYRIDINE DERIVATIVES HAVING IN THEIR STRUCTURE THE MORPHOLIN-4-YL MOIETY

Condensation of thiazolinone 1 with benzaldehydes 2a, b in ethanolic piperidine afforded the methylidene derivatives 3a, b. Cyclocondensation of compound 3b with malononitrile furnished the novel thiazolo[3,2-a]-pyridine 5. Also, compound 3b was condensed with dimethylformamide-dimethylacetal (DMF-DMA) and triethylortho-formate to yield N,N-dimethylamino 6 and ethoxymethylene 7 derivatives respectively. The novel thiazolo[3,2-a]pyridines 10a, b were obtained by cyclocondensation of compounds 3a, b with benzylidene-malononitriles 8a, b. Similarly, cyclocondensation of compound 3b with benzylidenemalononitrile 11 afforded the thiazolopyridines 12a–c. Ternary condensation of compound (12), 4-morpholinobenzaldehyde 2b and malononitrile (1:1:1 molar ratio) produced the thiazolopyridines 14a–c. When compound 10b was subjected to react with malononitrile in dioxane/piperidine under reflux the novel condensed heterocyclic system 18 was obtained. Treatment of ortho-aminocarbonitrile 10b with formic acid, aromatic aldehyde and triethylorthoformate furnished the thiazolo[2′,3′:1,6] pyrido[2,3-d] pyrimidine 20, azomethine 21a, b and ethoxymethylene 22 derivatives respectively. The structure of the synthesized compounds was established by analytical and spectral data.     

One-Pot Synthesis of Novel Spiro Pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine Derivatives

In a one-pot synthesis, 1′-methyl-2,3″-dioxo-5″-aryl-1,2,5a″,7″,8″,9a″-hexahydro-5″H,6″H-dispiro[indole-3,2′-pyrrolidine-3′,2″-pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine]-4′-carboxylic acid methyl ester was prepared via the sequential reaction of 4-aryl-octahydro-pyrano[2,3-d]pyrimidine-2-thione, dimethyl acetylenedicarboxylate (DMAD), and a mixture of isatin and sarcosine. All the novel spiro compounds, in moderate yields, were characterized thoroughly by infrared, NMR, mass spectromentry, and elemental analysis together with x-ray crystallographic analysis.     

HETEROCYCLES SYNTHESIS THROUGH REACTIONS OF INDOLIN-2-ONE DERIVATIVES WITH ACTIVE METHYLENE AND AMINO REAGENTS,PART 3, NOVEL AND FACILE ONE-STEP SYNTHESIS OF SPIROTHIOPYRAN-4- YL INDOLIDENE DERIVATIVES

Abstract

New spirothiopyran-4-yl indolidene derivatives have been synthesised via a facile one-step method. Structures and reaction mechanisms are also reported and supported by another synthetic route.     

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.     

NOVEL AND FACILE SYNTHESIS OF THIOPHENE,THIAZOLE, 2H-PYRAN-2-ONE BENZIMIDAZO[1,2-a]PYRIDINE AND PYRIDINE DERIVATIVES CONTAINING ANTIPYRINE MOIETY

Several new thiophene, thiazole, 2H-pyran-2-one, benzimidazo[1,2-a]pyridine and pyridine derivatives were synthesised from active methylene reagents, 4-chloroacetylantipyrine and enaminones as starting materials.     

SYNTHESIS AND REACTIONS OF SOME NEW THIENO[2,3-b]-PYRIDINES AND THE ANTIMICROBIAL EFFECTS

Abstract

3,5-Dicyano-6-mercapto-4-phenylpyridin-2(1H)-one (1) was reacted with ethyl chloroacetate to give compound (II) which on reaction with hydrazine hydrate gave the corresponding hydrazide derivative (III). Acylation of (III) with acetic acid, phenylisocyanate, or phenylisothiocyanate gave different monoacyl derivatives (IV-VI). Condensation of III with aromatic aldehydes and acetylacetone gave compounds VII_a-c, VIII respectively. Compound I was reacted with chloroanilides, bromoacetone and phenacyl bromide to yield the IX-XI; these and compound II gave thieno[2,3-b]-pyridines (XU-XV) on treatment with sodium ethoxide solution. Reaction of XII with acetic anhydride gave the diacetyl derivative XVI. Hydrolysis of compound XII with sodium hydroxide gave the corresponding acid (XVII) which on treatment with acetic anhydride gave the oxazine derivative (XVIII). Reaction of oxazine compound XVIII with ammonium acetate and hydrazine hydrate gave pyrido[3′,2′:4,5] thieno[3,2-d]pyrimidin-4.7-dione derivative (XIX) and (XX) respectively. The N-amino derivative (XX) was reacted with 4-nitrobenzaldehyde to give the corresponding azomethine (XXI).

Significant in vitro gram-positive and gram negative antibacterial activities as well as anti-fungal effect were observed for some members of the series.     

REACTIONS OF HYDRAZONOYL HALIDES 371: SYNTHESIS OF TRIAZOLO[4,3-a]PYRIMIDINES, 1,3,4-THIADIAZOLES AND 1,3,4-SELENADIAZOLES

1,2,4-Triazolo[4,3-a]pyrimidines, thiadiazolines and selenadiazolines synthesized via reactions of hydrazonoyl halides with each of ethyl 4-(3,4-dimethoxyphenyl)-6-methyl-2-methylthio-3,4-dihydropyrimidine-5-carboxylate (or ethyl 6-(3,4-dimethylphenyl)-4-methyl-2-thio1,3,6-trihydropyrimidine-5-carboxylate), ethyl 4-(2,3-dimethoxyphenyl)- 6-methyl-2-methylthio-3,4-dihydropyrimidine-5-carboxylate, potassium thiocyanate, potassium selenocyanate, and carbodithioates respectively.     

SYNTHESIS AND ABSORPTION PROPERTIES OF SOME NEW 4-THIO-1,8-NAPHTHYLIMIDES AND 4-(THIO)-7H-BENZIMIDAZO [2,1-A] BENZ [D,E] ISOQUINOLIN-7-ONE DERIVATIVES

A series of new 1,8-naphthylimide and 4-(thio)-7H-benzimidazo[2,1-a]benz[d,e]isoquinolin-7-one derivatives has been synthesized, and the UV/Vis absorptioin characteristics discussed. Substituents' effect on the UV/Vis absorption characteristics have been investigated.     

Ultrasound-assisted synthesis and preliminary bioactivity of novel 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivatives containing fluorine

Eight novel 5,7-disubstituted-2-{5-methyl-3-(4-trifluoromethylphenyl)isoxazol-4-ylcarbonylimino}-2H-1,2,4-thiadiazolo[2,3- a]pyrimidines were synthesized by multi-step reactions in yields 68-85%.Reactions were carried out either by ultrasound irradiation or conventional method,and found it was faster and more efficient under ultrasonic irradiation.Preliminary herbicidal activities against Echinochloa crus-galli,Digitaria sanguinalis and Chenopodium serotinum were also evaluated by flat-utensil method,and the results indicated that the target compounds exhibited significant activities,some were even higher than the control herbicide.     

Some chemical properties of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones

We have studied the reaction of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones with amines, alkylating reagents, and hydrogen peroxide. We have shown that the presence of an aryl substituent at the 2 position of [1,3-thiazino[3,2-a]benzimidazol-4-ones has a substantial effect on the direction of the reactions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 445–452, March, 2006.     

SYNTHESIS AND REACTIONS OF SOME NEW HETEROCYCLIC COMPOUNDS CONTAINING THE THIENYLTHIENO[2,3-B]PYRIDINE MOIETY

(4-Aryl-3-cyano-6-(2-thienyl)pyridin-2-ylthio)acethydrazides (5a–c), 3-amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbohydrazides (6a–c) and 3-amino-4-phenyl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxylic acid (30) were prepared and employed as key intermediates in the synthesis of the title compounds.     

Synthesis and Properties of Substituted Isoxazolo[3',4':4,5]thieno[2,3-b]pyridines

We synthesized derivatives of a novel heterocyclic system, isoxazolo[3',4':4,5]thieno[2,3-b]pyridine by sequential conversions in three steps: isomerization of 2-(2-R-ethylthio-2-oxo)-3-pyridyl cyanides obtained by alkylation from substituted 3-cyano-2(1H)-pyridinethiones by -halomethyl ketones in alkaline medium, to form 3-aminothieno[2,3-b]pyridines; diazotization of the amino group followed by nucleophilic substitution of the diazonium group by an azido group, bypassing the step of isolating the diazonium salts; and thermolysis of the azides formed.     

Studies with Polyfunctionally Substituted Heterocycles: New Synthesis of Pyrido[5′, 4′:2,3][1,3,4]oxadiazolo[3,2-a]pyridine; Pyridazine; 1,3,4-Oxadiazote; and Pyrazolo[1,5-a]Pyrimidine Derivatives

Cyanoacetohydrazide 1a reacts with 2-arylhydrazoketons 2a,b and 3a,b in refluxing ethanol to yield pyrido[5′,4′:2,3][1,3,4]oxadiazolo[3,2-a]pyridine and pyridazine derivatives; in the absence of solvent pyrazolo[1,5-a]pyrimidine derivatives were obtained. The reaction of 2a,b and 3a,b will) benzoylhydrazine afforded 1,3,4-oxadiazole and pyrazole derivatives.     

Reactions of Hydrazonoyl Halides 41: 1 Synthesis of 1,2,4-Triazoles, 2,3-Dihydro-1,3,4-thiadiazoles,and Triazolo[4, 3-a]pyrimidines

Triazoles, thiadiazoles, and triazolo[4, 3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of 3-methyl-4-(methylthiothioxomethyl)-2-pyrazolin-5-one, 3-methyl-4-[methylthio(phenylamino)methyl]-2-pyrazolin-5-one, and pyrimidine-2-thiones. Structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative-methods synthesis whenever possible.     

REACTIONS OF PHENYL ISOTHIOCYANATE AND SULFUR WITH DIMERIC ADDUCTS: NOVEL SYNTHESIS OF THIAZOLES,THIAZOLO-[4,5-d]PYRIMIDINE AND THIAZOLO[4,5-d]-PYRIDINE DERIVATIVES

Abstract

Dimeric adducts 1–3 react with phenyl isothiocyanate and sulfur to afford the thiazole derivatives 4, 12 and 14. The latter products react with different chemical reagents to afford new thiazoles and their fused derivatives which show high fungicidal and bactericidal activities.     

Green synthesis of naphtho[2,3-f]quinolin-13-one and naphtho[2,3-a]acridin-1(2H)-one derivatives catalyzed by heteropoly acid supported montmorillonite K-10 clay

Herein, synthesis of a series of naphtho[2,3-f]quinolin-13-one and naphtho[2,3-a]acridin-1(2H)-one derivatives directly by one-pot multi-component reaction of 1,3-dicarbonyl compounds (1,3-indanedione/1,3-cyclohexanedione), 2-aminoantharacene/2-naphthylamine and various substituted aldehydes under solvent-free conditions using heteropoly-11-molybdo-1-vanadophosphoric acid supported on montmorillonite K-10 clay catalyst (10% PVMoK-10) is reported. The successful formation of naphtho[2,3-f]quinolin-13-one and naphtho[2,3-a]acridin-1(2H)-one derivatives was confirmed by various spectroscopic techniques. This study offers a green approach for the synthesis of novel quinolinone derivatives.     

四氢咪唑并[2',1':2,3]噻吩并[5,4-c]哌啶衍生物的合成及抗肿瘤活性

以4-哌啶酮为原料,经过胺基保护、缩合、环合、脱保护等步骤,设计合成了一系列新型的5,6,7,8-四氢咪唑并[2',1':2-3]噻吩并[5,4-c]哌啶类化合物。通过核磁共振波谱仪(~1H NMR、~(13)C NMR)、质谱(MS)和元素分析确证了其结构。对其体外活性研究发现,该类化合物对乳腺癌细胞MCF-7具有一定的抑制活性,其中化合物5a的抑制活性最为显著,半数抑制浓度(IC_(50))值达到了8.6μmol/L。为此类化合物的抗肿瘤活性研究提供了参考。