Synthesis of 4(pyrazol-3-yl)[1,2,4]triazolo[4,3-a]quinoxalines and tetrazolo analog

The transformation of 2-chloro-3-[5-(acetoxymethyl)-1-phenylpyrazol-3-yl]quinoxaline 3 to 1-aryl-4-[5-(hydroxymethyl-1-phenylpyrazol-3-yl][1,2,4]triazolo[4,3-a]quinoxalines 4a-c has been achieved upon treatment with aroylhydrazines in boiling butanol. Compounds 4a-c were smoothly acetylated by acetic anhydride to give their acetyl derivatives 5a-c in good yield. 4-[5-(Acetoxymethyl)-1-phenylpyrazol-3-yl]-1-methyl[1,2,4]triazolo[4,3-a]quinoxaline was prepared by ring closure of 2-hydrazino-3-[5-(hydroxymethyl)-1-phenylpyrazol-3-yl]quinoxaline 6 by the action of acetic anhydride. The reaction of 6 with acetylacetone afforded 3-[5-(hydroxymethyl)-1-phenylpyrazol-3-yl]-2-(3,5-dimethylpyrazol-1-yl)quinoxaline 8 . In addition, the reaction of 3 with sodium azide in boiling N, N-dimethylformamide yielded the fused tetrazolo[1,5-a]quinoxaline 9 .     

Synthesis and Dehydration of endo-2-(3-R-Isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ols

endo-2-Ethynyl-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ol reacts with nitrile oxides, yielding endo-2-(3-R-isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ols. Treatment of the latter with methanesulfonyl chloride in pyridine leads to dehydration and formation of mixtures of the corresponding 1-(3-R-isoxazol-5-yl)-3,3-dimethyl-2-methylenebicyclo[2.2.1]heptanes and 2-(3-R-isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]hept-2-enes at a ratio of 2:1.     

A new method for the synthesis of novel 6-quinoxalinylpyrazolo[5,1-c][1,2,4]triazines

The reaction of the quinoxaline 1 with 4-ethoxycarbonyl-1H-pyrazole-5-diazonium chloride 7 at room temperature gave 3-[α-(4-ethoxycarbonyl-1H-pyrazol-5-ylhydrazono)methoxycarbonylmethyl]-2-oxo-1,2-dihydroquinoxaline 8. The pmr spectrum of 8 in deuteriodimethylsulfoxide supported the presence of two tautomers 8-I and 8-II. Refluxing of 8 in N,N-dimethylformamide or acetic acid resulted in cyclization to afford 8-ethoxycarbonyl-4-oxo-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-1,4-dihydropyrazolo[5,1-c][1,2,4]triazine 9. Compound 9 was also obtained directly by the reaction of 1 with 7 under reflux in better yield. The reaction of 9 with hydrazine hydrate provided the hydrazinium salt 10 , while the reactions of 9 with triethyl and trimethyl orthoformates in the presence of 1,8-diazabicyclo[5,4,0]-7-undecene produced 8-ethoxycarbonyl-4-ethoxyl-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)pyrazolo[5,1-c][1,2,4]triazine 11a and 8-ethoxycarbonyl-4-methoxyl-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)pyrazolo[5,1-c][1,2,4]triazine 11b , respectively. The chlorination of 11a with phosphoryl chloride gave 3-(3-chloroquinoxalin-2-yl)-8-ethoxycarbonyl-4-ethoxylpyrazolo[5,1-c]-[1,2,4]triazine 12 , whose reaction with morpholine afforded 8-ethoxycarbonyl-4-ethoxyl-3-[3-(morpholin-4-yl)-quinoxalin-2-yl]pyrazolo[5,1-c][1,2,4]triazine 13.     

Synthesis of Urinary Metabolites of Retinoic Acid

Urinary metabolites 5-methyl-5-[2-(2,6,6-trimethyl -3-oxo-1-cyclohexen-1-yl)-vinyl]-2-tetrahydrofuranone (1) and 5-[2-(6-hydroxymethyl-2, 6-dimethyl-3-oxo-1- cyclohexen-1-yl)vinyl]-5-methyl-2-tetrahydrofuranone (2) of retinoic acid have been synthesized from 4-[2,2,6-trimethyl-3-(tetrahydro-2 H -pyran-2-yl)oxy-1-cyclohexen-1-yl]-3-buten-2-one (4) and methyl 2-(3,3-ethylenedioxy-1-butenyl)-1, 3-dimethyl-4-oxo-2-cyclohexene-1-carboxylate (5) .     

Synthesis of some new pyrimidine selanyl derivatives

The targeted synthesis of 2-(methylsulfanyl)-6-(furan-2-yl)-4(3H)-selenoxo -pyrimidine-5-carbonitrile failed due to the formation 1-methyl-2-methylsulfanyl-6-oxo -4-(furan-2-yl)-1,6-dihydropyrimidine-5-carbonitrile. A new series of 5,6,7,8-tetrahydro-1-benzo thieno[2,3-d]pyrimidine-4-yl substituted selanyl derivatives were prepared by the reaction of sodium diselenide with 4-chloro-5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine followed by the reaction with chloroacetic acid derivatives such as ethyl chloroacetate, chloroacetamide or chloroacetonitrile. Hydrazinolysis of ethyl (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine- 4-ylselanyl)acetate with hydrazine hydrate gave the corresponding hydrazino derivative. The latter reacted with ethyl acetoacetate, acetylacetone, diethyl malonate, ethoxymethylenemalononitrile or ethyl 2-cyano-3-ethoxyacetate to afford 5-methyl-2-[2-(5,6,7,8-tetrahydro-1-benzothieno [2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazol-3-one, 1-(3,5-dimethylpyrazol-1-yl)-2- (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)ethanone, 1-[2-(5,6,7,8-tetrahydro -1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazolidine-3,5-dione and 5-Amino-1-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)acetyl]-1H-pyrazol -4-yl substituted carbonitrile or ethyl carboxylate, respectively. The structure of the novel compounds was confirmed by spectroscopic tools (IR, ¹H NMR ¹³C NMR and mass spectra) and elemental analysis.     

Design and synthesis of novel quinoline derivatives bearing oxadiazole,isoxazoline, triazolothiadiazole,triazolothiadiazine, and piperazine moieties

A new series of 2,3-disubstituted quinoline derivatives were synthesized from 2-chloroquinoline-3-carbaldehyde. In the reaction sequence, acetanilide was cyclized to give 2-chloroquinoline-3-carbaldehyde 1 , which was transformed to 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 by reaction with 4-phenylpiperazine in DMF-containing anhydrous K₂CO₃; then, compound 2 was oxidized by iodine in methanol, and methyl 2-(4-phenylpiperazin-1-yl)quinoline-3-carboxylate 3 was synthesized. The key intermediate 4 , 4-amino-5-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-4H-1,2,4-triazole-3-thiol, was prepared using the ester 3 by a series of step. Reaction of 5 with various aromatic carboxylic acids or phenacyl bromides yielded 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 5a-c and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 6a-c , respectively. Moreover, compound 2 condensed with o-phenylenediamine to give 2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-1H-benzimidazole 7 . Interaction of 7 and 2-chloromethyl-5-aryl-1,3,4-oxadiazoles in the presence of K₂CO₃ led to the title compounds 8a-c . Furthermore, 4,5-dihydroisoxazoline derivatives 9a-c were obtained by the reaction of readily accessible starting materials including 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 , 1-phenyl-2-(triphenylphosphoranylidene)ethanone and hydroximoyl chlorides under mild conditions in the presence of Et₃N. The hydrazone intermediates 10a-c were obtained by the condensation of 2 with aroylhydrazides in ethanol, then, refluxing in acetic anhydride yielded 3-acetyl-5-aryl-2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-2,3-dihydro-1,3,4-oxadiazoles 11a-c . Structures of these compounds were established by their elemental analysis, IR, ¹H NMR, and mass spectral data.     

Synthesis and characterization of mono- and bicyclic heterocyclic derivatives containing 1,2,4-triazole, 1,3,4-thia-, and -oxadiazole rings

A series of new N- and S-substituted 1,3,4-oxadiazole derivatives were synthesized. 5-Pyridin-3-yl-3-[2-(5-thioxo-4,5-dihydro-l,3,4-thiadiazol-2-yl)ethyl]-1,3,4-oxadiazole-2(3H)-thione and 5-[(5-(pyridin-3-yl)-1,3,4-oxadiazol-2-ylthio)methyl]-N-phenyl-1,3,4-thiadiazol-2-amine were formed by cyclization of 3-(5-pyridin-3-yl-2-thioxo-1,3,4-oxadiazol-3(2H)-ylpropanimidohydrazide and 2-[(5-pyridin-3-yl-1,3,4-oxadiazol-2-yl)thio]thiosemicarbazide with CS₂ and H₂SO₄. On the other hand, a number of new bicyclic 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives were synthesized. 6-Pyridin-3-ylbis[1,2,4]‐triazolo[3,4-b:4′,3′-d][1,3,4]thiadiazole-3(2H)-thione was synthesized by reaction of 6-(hydrazino)-3-pyridine-3-yl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole with CS₂/KOH/EtOH. The structures of the newly synthesized compounds were elucidated by the spectral and analytical data IR, Mass, and ¹H NMR spectra. Correspondence: Adel A.-H. Abdel-Rahman, Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt; Wael A. El-Sayed, National Research Centre, Department of Photochemistry, Cairo, Egypt.     

Syntheses of 4-(benzo[b]furan-2 or 3-yl)- and 4-(benzo[b]-thiophen-3-yl)piperidines with 5-HT2 antagonist activity

The syntheses of 4-(benzo[b]furan-3-yl)piperidines, 4-(benzo[b]furan-2-yl)piperidines and 4-(benzo[b]thiophen-3-yl)piperidines with 5-HT₂ antagonist activity are described. Reaction of 1-acetyl-4-(2,4-difluorobenzo-yl)piperidine 2 with methyl glycolate gave methyl 6-fluoro-3-(1-acetylpiperidin-4-yl)benzo[b]furan-2-carboxylate 3 , which was converted to 2-[2-[4-(benzo[b]furan-3-yi)piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyridin-3(2H)-one hydrochloride 9 . Analogous benzo[b]furans 17a-d and benzo[b]thiophenes 10a,b and 18a were prepared by a similar method. Cyclization of 4-fluoro-2-(4-pyridinylmethoxy)acetophenones 20a,b afforded 4-(benzo[b]furan-2-yl)pyridines 21a,b , which were converted to 2-[2-[4-(benzo[b]furan-2-yl)-piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one hydrochlorides 24a,b. Among them, benzo[b]furans 9 and 17a,d and benzo[b]thiophenes 10 and 18a showed potent 5-HT₂ antagonist activity in vitro.     

Synthesis of isonipecotinoyl analogues of aminopterin and folic acid

The preparation of isonipecotinoyl analogues of aminopterin and methotrexate is described. Condensation of diethyl N-isonipecotinoyl-L-glutamate 4 with 2-amino-5-bromomethyl-3-cyanopyrazine 5 afforded diethyl N-(N-[(2-amino-3-cyanopyrazin-5-yl)methyl]isonipecotinoyl)-L-glutamate 6 . Cyclisation of 6 with guanidine followed by blocking group hydrolysis afforded N-([N-(2,4-diaminopteridin-6-yl)methyl]isonipecotinoyl)-L-glutamic acid 8 . Coupling of N-(2-amino-4(3H)ioxopteridin-6-yl]methyl)isonipecotinic acid 11 with diethyl L-glutamate gave diethyl N-[(N-[2-amino-4(3H)-oxopteridin-6-yl]methyl)isonipecotinoyl]-L-glutamate 12 . Blocking group hydrolysis afforded N-[(N-[2-amino-4(3H)-oxopteridin-6-yl]methyl)isonipecotinoyl]-L-glutamic acid 13 .     

Synthesis and selected transformations of 1-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)ethanones and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl]ethanones

By cycloaddition of arylazides to acetylacetone are obtained derivatives of 1,2,3-triazole. In the reaction of 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] ethanones (VIIa-VIIe) with isatin are obtained 2-[1-(R-phenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-4-quinolinecarboxylic acids (IIIa–IIIe) and 2-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] -4-quinolinecarboxylic acids (IXa, IXb), respectively. We found that 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) readily transform into [5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] acetic acids (IVa–IVc) by the method of Wilgerodt-Kindler. The (5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)acetic acid reacts with 5-phenyl-4-amino-4H-1,2,4-triazol-3-thiol affording 6-[(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl) methyl]-3-phenyl[1,2,4] triazolo[3,4-b] [1,3,4] thiadiazole (VI). Original Russian Text ? N.T. Pokhodylo, R.D. Savka, V.S. Matiichuk, N.D. Obushak, 2009, published in Zhurnal Obshchei Khimii, 2009, vol. 79, no. 2, pp. 320–325.     

Synthesis of New 2-[(Substituted-pyrazol-1-yl)carbonyl]-thieno[2,3b]pyridine Derivatives Using 1,3-Diketones,Alkylethoxymethylenes and Ketene Dithioacetals

The reaction of 3-amino-4,6-dimethyl-2-thieno[2,3-b]pyridine carbohydrazide ( 1 ) with appropriate 1,3-diketones 2a-2d in glacial acetic acid afforded 3-amino-2-[(3,5-disubstituted-pyrazo)-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 3a-3d. 3-Amino-2-[(5-amino-3,4-disubstituted-pyrazol-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 5a-5h were also prepared by treatment of carbohydrazide 1 with appropriate alkylethoxymethylenes and ketene dithioacetals 4a-4h , respectively.     

Studies on the synthesis of heterocyclic compounds. Part IV. Further investigation of the pschorr reaction with some pyrazole derivatives

Thermal decomposition of the diazonium sulfate derived from N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-aminobenzamide afforded products formulated as 1-phenyl-3-methyl[2]benzopyrano[4,3-c]pyrazol-5-one (yield 10%), 1,4-dimethyl-3-phenylpyrazolo[3,4-c]isoquinolin-5-one (yield 10%), N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-hydroxybenzamide (yield 8%) and 4′-hydroxy-2,3′-dimethyl-1′-phenylspiro[isoindoline-1,5′-[2]-pyrazolin]-3-one (yield 20%). Decomposition of the diazonium sulfate derived from N-methyl-(1,3-diphenylpyrazol-5-yl)-2-aminobenzamide gave products formulated as 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]-diazocin-10-(9H)one (yield 8%), 4-methyl-1,3-diphenylpyrazolo[3,4-c]isoquinolin-5-one (yield 7%) and 4′-hydroxy-2-methyl-1′,3′-diphenylspiro[isoindoline-1,5′-[2]pyrazolin]3-one (yield 10%). The spiro compounds 6a,b underwent thermal and acid-catalysed conversion into the hitherto unknown 2-benzopyrano[4,3-c]pyrazole ring system 7a,b in good yield. Analytical and spectral data are presented which supported the structures proposed.     

Studies on the Synthesis of New 3-(3,5-Diamino-1-substituted-pyrazol-4-yl)azo-thieno[2,3-b]pyridines and 3-(2-Amino-5,7-disubstituted-pyrazolo[1,5-a]pyrimidine-3-yl)azothieno[2,3-b]pyridines

Coupling the diazonium salt of 3-amino-2-cyano-4,6-dimethylthieno[2,3-b]pyridine 1 with malononitrile 2 gave 2-cyano-3-(hydrazonomalononitrile)-4,6-dimethylthieno[2,3-b]pyridine 3 which then reacted with hydrazine compounds 4a-4h to yield corresponding 2-cyano-3-(3,5-diamino-1-substituted-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 5a-5h. The 2-cyano-3-(2-amino-5,7-disubstituted-pyrazolo-[1,5-a]pyrimidine-3-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 7a-7f were obtained in good yield by the cyclocondensation reaction of 2-cyano-3-(3,5-diamino-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridine 5a with the appropriate 1,3-diketones 6a-6f under acidic condition.     

Reaction of 4-Aryl-1-(4-oxo-3,4-dihydrothieno-[2,3-d]pyrimidin-2-yl)thiosemicarbazides with Dimethyl Acetylenedicarboxylate

4-Aryl-1-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)thiosemicarbazides react with dimethyl acetylenedicarboxylate in methanol to give the corresponding methyl {3-aryl-4-oxo-2-[(4-oxo-3,4-dihydro-thieno[2,3-d]pyrimidin-2-yl)hydrazono]-1,3-thiazolidin-5-ylidene}acetates, whereas in dioxane methyl 5-aryl-amino-2-methoxycarbonylmethyl-3-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)-2,3-dihydro-1,3,4-thiadiazole-2-carboxylates are mainly formed.     

4-Aminofurazan-3-carboxylic Acid Iminoester in Reactions with N,O-Nucleophiles

Reactions of 4-aminofurazan-3-carboxylic acid iminoester with o-aminophenol and ethylenediamine give rise respectively to 4-(1,3-benzoxazol-2-yl)- and 1-(4,5-dihydro-1H-imidazol-2-yl)-1,2,5-oxadiazol-3-amines, with aminoethanol arises 2-[(Z)-1-amino-1-(4-amino-1,2,5-oxadiazol-3-yl)methylideneamino]-1-ethanol. Treating of 3-amino-4-(1H-benzo[d]imidazol-2-yl)-1,2,5-oxadiazole with triethyl orthoformate in acetic anhydride yielded benzo[4,5]imidazo[1,2-c][1,2,5]oxadiazolo[3,4-e]pyrimidine, and alkylation with haloalkanes furnished 3-amino-4-(1-R-benzo[d]imidazol-2-yl)-1,2,5-oxadiazoles.     

Synthesis of Some New Thiazoles and Pyrazolo[1,5-a]pyrimidines Containing an Antipyrine Moiety

Ethyl 2-{2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-(pyrazolin-4-yl)]-2-cyano-1-(phenylamino)vinylthio}-acetate, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]2-(4-oxo-3-phenyl-(1,3-thiazoilidin-2-ylidene))ethanenitrile, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]-2-(4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))ethanenitrile, 2-(5-acetyl-4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))-2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]ethanenitrile, and ethyl 2-(cyano(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)methylene)-2,3-dihydro-4-methyl-3-phenylthiazole-5-carboxylate were synthesized by treatment of 2-(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)-3-mercapto-3-(phenylamino)-acrylonitrile with appropriate halo ketones or halo esters. Also, 4-{2-[5,7-dimethyl-2-(phenylamino)(7a-hydropyrazolo[1,5-a]pyrimidin-3-yl](1,-thiazol-4-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one derivatives were synthesized via reaction of 4-{2-[5-amino-3-(phenylamino)pyrazolin-4-yl](1,3-thiazol-2-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one with β-diketone or β-keto ester. All synthesized compound were established by elemental analysis, spectral data, and alternative synthesis whenever possible.     

Fused polycyclic nitrogen-containing heterocycles: IX. Synthesis and molecular structure of methyl 3-(2-R-5-phenylthiazol-4-yl)-7-phenyl-7<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazolo-[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazine-6-carboxylates

4-Amino-3-(2-R-5-phenylthiazol-4-yl)-1,2,4-triazole-5-thiones react with methyl 3-chloro-2-oxo-3-phenylpropionate to give methyl 3-(2-R-5-phenylthiazol-4-yl)-7-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-6-carboxylates. According to the X-ray diffraction data, the thiazole ring in the products is planar, while the thiadiazine ring has a distorted unsymmetrical boat conformation. Depending on the substituent in the thiazole ring, methyl 3-(2-R-5-phenylthiazol-4-yl)-7-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-6-carboxylates in crystal give rise to different supramolecular structures, lamellar and cylindrical.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 9, 2004, pp. 1358–1365.Original Russian Text Copyright © 2004 by Mamedov, Mustakimova, Gubaidullin, Litvinov, Levin.     

Halocyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">de</Emphasis>]isoquinoline-1,3(2<Emphasis Type="Italic">H</Emphasis>)-dione

Cyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione by the action of iodine, bromine, or sulfuryl chloride gave 2-(2-{4-[4,5-dihydro-5-(halomethyl)-thiazol-2-yl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione hydrohalides which were converted into 2-{2-[4-(5-methylthiazol-2-yl)piperazin-1-yl]ethyl}-1H-benzo[de]isoquinoline-1,3(2H)-dione.     

Synthesis and anticonvulsant activity of 3-[3-[(dimethylamino)-methyl]-5-methyl-4H-1,2,4-triazol-4-yl]-4-(o-chlorobenzoyl)pyridine

Wolff-Kishner reduction of 3-amino-4-(o-chlorobenzoyl)pyridine ( 3 ) afforded 3-amino-4-(o-chlorobenzyl)pyridine ( 5 ), which on subsequent reaction with triethyl orthoformate and then acetyl hydrazide yielded 1-acetyl-2-[N-[4-(o-chlorobenzyl)pyridin-3-yl]formimidoyl]hydrazone ( 7 ). Cyclization of hydrazone 7 gave 3-(3-methyl-4H-1,2,4-triazol-4-yl)-4-(o-chlorobenzyl)pyridine ( 8 ), which on Jones oxidation yielded 3-(3-methyl-4H-1,2,4-triazol-4-yl)-4-(o-chlorobenzyl)pyridine ( 9 ). The Mannick reaction of 3-(3-methyl-4H-l,2,4-triazol-4-yl)-4-(o-chlorobenzyl)pyridine ( 9 ) with aqueous formalin and dimethylamine hydrochloride afforded 3-[3-[(dimethylamino)methyl]-5-methyl-4H-1,2,4-triazol-4-yl]-4-(o-chlorobenzoyl)-pyridine ( 10 ). 3-[3-[(Dimethylamino)methyl]-5-methyl-4H-1,2,4-triazol-4-yl]-4-(o-chlorobenzoyl)pyridine ( 10 ) exhibited good anticonvulsant activity in the subcutaneous pentylenetetrazole anticonvulsant screen indi cating that an appropriately substituted-pyridine ring moiety can serve as a bioisostere of a chlorobenzene ring with respect to anticonvulsant activity.     

Structures and photochromic properties of fulgides based on naphtho[1,2-<Emphasis Type="Italic">b</Emphasis>]furan and benzo[<Emphasis Type="Italic">g</Emphasis>]indole

The novel heterocyclic fulgides, i.e. 3-isopropylidene-4-{1-[5-methoxy-1-(4-methoxy-phenyl)-2-methyl-1H-benzo[g]indol-3-yl]ethylidene}dihydrofuran-2,5-dione and 3-isopropylidene-4-[1-(1-benzyl-5-methoxy-2-methyl-1H-benzo[g]indol-3-yl)ethylidene]dihydrofuran-2,5-dione, were prepared and isolated as E-isomers. Photochromism, E-configuration, and high resistance to photocoloration—photobleaching of solutions of these fulgides as well as 3-isopropylidene-4-[1-(5-methoxy-2-methylnaphtho[1,2-b]furan-3-yl)ethylidene]dihydro-furan-2,5-dione and 3-isopropylidene-4-[1-(5-methoxy-2-methyl-1-phenyl-1H-benzo[g]indol-3-yl)ethylidene]dihydrofuran-2,5-dione synthesized previously were shown by X-ray diffraction analysis, ¹H NMR spectroscopy and electronic absorption spectroscopy. The novel fulgides show fluorescence and high thermal stability of photogenerated cyclic form. Repeated photo-coloration—photobleaching is accompanied by reversible photoinduced E—Z isomerization. Benzo[g]indolyl fulgides are characterized by the longer wavelength absorption of both original (E) and photoisomeric cyclic (C) forms as compared to naphthofuran fulgide.