Synthesis of N-Substituted Methyl 4<Emphasis Type="Italic">H</Emphasis>-Thieno[3,2-<Emphasis Type="Italic">b</Emphasis>]pyrrole-5-carboxylates

The alkylation of methyl 4H-thieno[3,2-b]pyrrole-5-carboxylate with methyl iodide and allyl, propargyl, and benzyl bromides in the presence of sodium hydride in THF afforded the corresponding N-substituted derivatives. Some reactions of the alkylation products were studied.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 2-amino-1,3-thiazole and 2-amino-1,3-benzothiazole

N-Aryl-3-oxobutanethioamides react with 2-amino-1,3-thiazole (2-amino-1,3-benzothiazole) in acetic acid to give mixtures of 7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-5-thione (2-methyl-4H-pyrimido-[2,1-b][1,3]benzothiazole-4-thione) and 5-arylimino-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidines (4-arylimino-2-methyl-4H-pyrimido[2,1-b][1,3]benzothiazoles), whose ratio depends on the nature of the aryl substituent in the initial butanethioamide.     

Electrophilic intramolecular cyclization of functional derivatives of unsaturated compounds: VIII. Cyclization of 4-aryl-<Emphasis Type="Italic">N</Emphasis>-(thiophen-3-yl)but-3-enamides by the action of polyphosphoric acid and chlorosulfanylarenes

Intramolecular cyclization of 4-aryl-N-(thiophen-3-yl)but-3-enamides on heating in polyphosphoric acid afforded 8-aryl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones and 5-aryl-1-(thiophen-3-yl)pyrrolidin-2-ones. Cyclofunctionalization of the title compounds with (chlorosulfanyl)benzene and 4-(chlorosulfanyl)-toluene led to the formation of 8-aryl-7-arylsulfanyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones or their mixtures with 5-aryl-4-arylsulfanyltetrahydrofuran-2-ones. 1-(Chlorosulfanyl)-4-nitrobenzene reacted with 4-(4-methylphenyl)-N-(thiophen-3-yl)but-3-enamide and 4-(4-fluorophenyl)-N-(thiophen-3-yl)but-3-enamide to give 5-(4-methylphenyl)-4-(4-nitrophenylsulfanyl)-1-(thiophen-3-yl)pyrrolidin-2-one and 5-(4-fluorophenyl)-4-(4-nitrophenylsulfanyl)tetrahydrofuran-2-one, respectively.     

Synthesis of 5,8-Diamino-Substituted Pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidines and Pyrimido[4′,5′:4,5]thieno[2,3-<Emphasis Type="Italic">c</Emphasis>]isoquinolines

Ethyl 1-amino-8,8-dimethyl-5-(piperidin-1-yl)-8,9-dihydro-6H-pyrano[4,3-d]thieno[2,3-b]pyridine-2-carboxylate and ethyl 1-amino-5-(piperidin-1-yl)-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxylate reacted with benzoyl isothiocyanate to give the corresponding 1-thioureido derivatives which underwent cyclization to 2,2-dimethyl-5-(piperidin-1-yl)-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4″,3″:4′,5′]pyrido-[3′,2′:4,5]thieno[3,2-d]pyrimidin-8(9H)-one and 5-(piperidin-1-yl)-10-thioxo-1,2,3,4,10,11-hexahydropyrimido-[4′,5′:4,5]thieno[2,3-c]isoquinolin-8(9H)-one. The cyclization products were converted into 8-chloro derivatives, and the chlorine atom therein was replaced by various amines.     

Thermal Rearrangements of 3<Emphasis Type="Italic">H</Emphasis>- and 4<Emphasis Type="Italic">H</Emphasis>-Pyrazoles Prepared by Reactions of 9-Diazofluoren with Methyl Tetrolate and Methyl 3-Phenylpropiolate

9-Diazofluoren adds in Et₂O at 20°C to methyltetrolate in keeping with Auwers rule and nonregioselectively adds to methyl-3-phenylpropiolate with the formation of spirocyclic 3H-pyrazoles. The methyltetrolate adduct at boiling in toluene converts into methyl 3a-methyl-3aH-dibenzo[e,g]indazole-3-carboxylate, at 190°C in benzene, into methyl 3-methyl-2H-dibenzo[e,g]indazole-2-carboxylate, and at 160°C in methanol, into 3-methyl-2H-dibenzo[e,g]indazole. Auwers adduct of methyl 3-phenylpropiolate at boiling in benzene gives cyclopropene derivative and at boiling in methanol isomerizes into methyl 3a-phenyl-3aHdibenzo[e,g]indazole-3-carboxylate. Anti-Auwers adduct at boiling in benzene isomerizes into methyl 2-phenylpyrazolo[1,5-f]phenanthridine-3-carboxylate.     

Iodocyclization of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

Iodination of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3H)-ones was accompanied by cyclization to 2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodides. 3-(Iodomethyl)-3-methyl- 7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodide was reduced with sodium iodide to 3,3-dimethyl-7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium iodide.     

Functionalization of methyl 3-acetyl-5-[(methoxycarbonyl)amino]-2-methyl-1<Emphasis Type="Italic">H</Emphasis>-indole-1-carboxylate

Oxidative heterocyclization of methyl 3-{1-[2-(carbamoylhydrazinylidene)]ethyl}-2-methyl-5-[(methoxycarbonyl)amino]-1H-indole-1-carboxylate by the action of selenium dioxide in acetic acid and heating of the corresponding thiosemicarbazone in boiling acetic anhydride gave 1,2,3-selenadiazole and 2,3-dihydro-1,3,4-thiadiazole derivatives, respectively. Methyl 3-acetyl-2-methyl-5-[(methoxycarbonyl)amino]-1H-indole-1-carboxylate reacted with selenium dioxide in dioxane–water (30: 1) at 80?90°C to form methyl 5-[(methoxycarbonyl)amino]-2-methyl-3-(2-oxoacetyl)-1H-indole-1-carboxylate whose condensation with o-phenylenediamine afforded methyl 2-methyl-5-[(methoxycarbonyl)amino]-3-(quinoxalin-2-yl)-1H-indole-1-carboxylate.     

Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.     

Synthesis of new functionally substituted hetarylcarbamates from methyl {4-[(2<Emphasis Type="Italic">E</Emphasis>)-3-(4-methoxyphenyl)-prop-2-enoyl]phenyl}carbamate

Three-component condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}- carbamate with ninhydrin and L-proline in methanol–water (10: 1) afforded methyl {4-[1,3-dioxo-1′- (4-methoxyphenyl)-1,1′,2′,3,5′,6′,7′,7a′-octahydrospiro[indene-2,3′-pyrrolizin]-2′-ylcarbonyl]phenyl}carbamate. Heating of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}carbamate with isatin and benzylamine in methanol gave methyl {4-[4′-(4-methoxyphenyl)-2-oxo-5′-phenyl-1,2-dihydrospiro[indole-3,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate. The condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2- enoyl]phenyl}carbamate with sarcosine and 11H-indeno[1,2-b]quinoxalin-11-one generated in situ from ninhydrin and o-phenylenediamine in boiling ethanol led to the formation of methyl {4-[4′-(4-methoxyphenyl)-1′-methyl-11,11a-dihydro-5aH-spiro[benzo[b]phenazine-6,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate.     

Synthesis of bifunctional thieno[3,2-c]pyrazole,pyrazolothieno[2,3-d]pyrimidin derivatives and their antimicrobial activities

A simple and convenient route was performed for the synthesis of some new heterocyclic compounds based on thieno[3,2-c]pyrazole derivative for antimicrobial evaluation. The key intermediate, 5-amino-3-methyl-1-phenyl-1H-thieno[3,2-c]pyrazole-6-carbohydrazide 3, was prepared by Gewald’s synthesis of Ethyl 5-amino-3-methyl-1-phenyl-1H-thieno[3,2-c]pyrazole-6-carboxylate 2. This intermediate reacted with various reagents to afford different fused and polyfunctional substituted. The structures of these compounds were confirmed by elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectral data. All the new synthesized compounds were screened for various microorganisms such as Aspergillus fumigatus; Geotrichum candidum; Syncephalastrum racemosum (Fungus); Candida albicans (Yeast fungus); Staphylococcus aureus; Bacillus subtilis (as Gram-positive bacteria); Pseudomonas aeruginosa and Escherichia coli (as Gram-negative bacteria) by the disc diffusion method. In general, the novel synthesized compounds possessed moderate to high antimicrobial activity against the previously mentioned microorganisms.     

Reactions of 1,3-Dialkyl-5-amino-1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-ones with acetylacetone and ethyl acetoacetate

1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones reacted with acetylacetone to give the corresponding 4-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)pent-3-en-2-ones which underwent intramolecular cyclization to 1,3-dialkyl-5,7-dimethyl-1,3-dihydro-2H-imidazo[4,5-b]-[1,8]naphthyridin-2-ones on heating in polyphosphoric acid or diphenyl ether. Analogous reaction of 1,3-dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones with ethyl acetoacetate led to the formation of ethyl 3-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)but-2-enoates whose cyclization afforded 1,3-dialkyl-8-hydroxy-7-methyl-1,3-dihydro-2H-imidazo[5,4-b][1,8]naphthyridin-2-ones.     

Reactions of 2-(2-propynylsulfanyl)-5,6,7,8-tetrahydrobenzo[<Emphasis Type="Italic">b</Emphasis>]thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(<Emphasis Type="Italic">3H</Emphasis>)-one with arylsulfenyl chlorides

2-(2-propynylsulfanyl)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-4(3H)-one with arylsulfenyl chlorides in chloroform gave products of anti-Markownikoff Ad _E-addition. The use of nitromethane as solvent in the presence of lithium perchlorate additives favored intramolecular electrophilic cyclization into 1-arylsulfanyl-1,2,6,7,8,9-hexahydro-4H-benzo[4,5]thieno[3,2-e][1,3]thiazolo[3,2-a]-pyrimidin-5-one.     

Cross-recyclization of 4-aryl-2,6-diamino-4<Emphasis Type="Italic">H</Emphasis>-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene: New route to 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-[1]pyrindine-3-carbonitriles and their derivatives

Reaction of 4-aryl-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene led to the formation of 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1H-[1]pyrindine-3-carbonitriles used in the synthesis of substituted 2-alkylsulfanyl-4-aryl-6,7-dihydro-5H-[1]pyrindine-3-carbonitriles and 3-amino-4-aryl-6,7-dihydro-5H-cyclopenta[bthieno[3,2-e]pyridines.     

Synthesis of novel 4<Emphasis Type="Italic">H</Emphasis>-furo[3,2-c]pyran-4-ones and 4<Emphasis Type="Italic">H</Emphasis>-furo[3,2-<Emphasis Type="Italic">c</Emphasis>]chromen-4-ones

It was found that the condensation of two equivalents of 4-hydroxy-6-methyl-2H-pyran-2-one or 4-hydroxycoumarin with arylglyoxals in boiling formic acid leads to 4H-furo[3,2-c]-pyran-4-ones or 4H-furo[3,2-c]chromen-4-ones, respectively.     

Synthesis of 6-Acyl-7-aryl-4,7-dihydrotetrazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-5-carboxylic acids and their methyl esters

6-Acyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylic acids and methyl 6-acyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylates were synthesized by fusion of 4-aryl-2,4-dioxobutanoic acids and their methyl esters, respectively, with 1H-tetrazol-5-amine and aromatic aldehydes. The reaction of methyl 2,4-dioxopentanoate with 1H-tetrazol-5-amine and 2-fluorobenzaldehyde in boiling acetic acid gave methyl 6-acetyl-5-hydroxy-7-(2-fluorophenyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine-5-carboxylate.     

Photochromic Dihetarylethenes: XVI. Synthesis of 1,2-Dihetarylethenes on the Basis of Thieno[3,2-b]pyrrole

The reaction of 3,4-dichlorocyclobutene-1,2-dione with methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate occurs at the thiophene ring of the latter, yielding a product in which the thienopyrrole fragments are linked through a dioxocyclobutene ring. Oxidation of this product with hydrogen peroxide gives previously unknown thermally stable photochromic system containing thienopyrrole groups linked through a 2,5-dioxofuran bridge.     

A New Approach to the Synthesis of Functional Derivatives of 3-(4-Pyridinyl)-1<Emphasis Type="Italic">H</Emphasis>-indole and 4-(1<Emphasis Type="Italic">H</Emphasis>-Indol-3-yl)thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine

Sequential reaction of indole-3-carbaldehyde with cyanothioacetamide and KOH led to the formation of potassium 6-amino-4-(1H-indol-3-yl)-3,5-dicyanopyridine-2-thiolate. S-Alkylation of the latter afforded new functional derivatives of 3-(pyridine-4-yl)-1H-indole and 4-(1H-indol-3-yl)-thieno[2,3-b]pyridine.     

Fused pyrimidine systems: XVI. Electrophilic intramolecular cyclization of 2-(alkenylsulfanyl)pteridin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

2-[Allyl(but-3-en-1-yl, pent-4-en-1-yl)sulfanyl]pteridin-4(3Н)-ones at heating in polyphosphoric acid undergo an intramolecular cyclization affording respectively 9-methyl-8,9-dihydro-5H-[1,3]thiazolo[3,2-a] pteridin-5-one and 10-methyl(ethyl)-9,10-dihydro-5Н,8Н-[1,3]thiazino[3,2-a]pteridin-5-ones of angular structure. The cyclization of 2-(alkenylsulfanyl)pteridin-4(3Н)-ones under the action of iodine or arylsulfenyl chlorides afforded iodo(arylsulfanyl) derivatives of angularly fuzed thiazolo- and thiazinopteridines.     

Nenitzescu synthesis of carbamate indole derivatives from <Emphasis Type="Italic">N,N′</Emphasis>-bis(methoxycarbonyl)-<Emphasis Type="Italic">p</Emphasis>-benzoquinone diimine

N,N′-Bis(methoxycarbonyl)-p-benzoquinone diimine reacted with 4-(cyclohex-1-en-1-yl)-and 4-(cyclopent-1-en-1-yl)morpholines in methylene chloride at room temperature to give morpholino-substituted cyclohexane-and cyclopentane-fused indole derivatives. Heating of the latter in boiling 10% hydrochloric acid led to the formation of methyl 6-(methoxycarbonylamino)-1,2,3,4,4a,9a-hexahydro-9H-carbazole-9-carboxylate and methyl 7-(methoxycarbonylamino)-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-4-carboxylate, respectively. The reaction of N,N′-bis(methoxycarbonyl)-p-benzoquinone diimine with 4-benzylaminopent-3-en-2-one in CH₂Cl₂ in the presence of BF₃·Et₂O on heating gave methyl 3-acetyl-2-methyl-(5-methoxy-carbonylamino)-1H-indole-1-carboxylate.     

Fotochromic Dihetarylethenes: XIX. Synthesis of 1,2-Dihetarylethenes with 2,5-Dihydrothiophene Bridge from Thieno[3,2-b]pyrroles

Reductive cyclization by McMurry method was performed with diketosulfide obtained by treating with Na₂S of compound prepared by regioselective acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate with chloroacetyl chloride. As a result was synthesized a photochromic 1,2-dihetarylethene where the fuzed rings are connected by a 2,5-dihydrothiophene ring. The oxidation of the latter provides 2,5-dihydrothiophene-1,1-dioxide bridge.