Reduction of 4-arylidene-1,3-(2H,4H)isoquinolinediones

Catalytic hydrogenation of some 4-arylidene-1,3-(2H,4H)isoquinolinediones (1) afforded the corresponding 4-arylmethyl-1,3-(2H,4H)isoquinolinediones (2) , but reduction of 1 by sodium borohydride gave 4-arylmethyl-1(2H)isoquinolones (isocarbostyrils, 3). Compounds of type 1 studied had aryl substituents phenyl, 3,4-dimethoxyphenyl, 3,4-methyleneoxyphenyl and 2-furyl. In one example of sodium borohydride reduction of an N-methylisoquinolinedione derivative (1) the heterocylic ring was opened, and 2-(1-hydroxymethyl-2-phenylethenyl)-N-methylbenzamide (4) was obtained from 4-benzylidene-2-methyl-1,3-(2H,4H)isoquinolinedione.     

Bildung von 5,6-Dihydro-1,3(4H)-thiazin-4-carbonsäure-estern aus 4-Allyl-1,3-thiazol-5(4H)-onen

Formation of Methyl 5,6-Dihydro-l, 3(4H)-thiazine-4-carboxyiates from 4-Allyl-l, 3-thiazol-5(4H)-ones . The reaction of N-[1-(N, N-dimethylthiocarbamoyl)-1-methyl-3-butenyl]benzamid ( 1 ) with HCl or TsOH in MeCN or toluene yields a mixture of 4-allyl-4-methyl-2-phenyl-1,3-thiazol-5(4H)-one ( 5a ) and allyl 4-methyl-2-phenyl-1,3-thiazol-2-yl sulfide ( 11 ; Scheme 3). Most probably, the corresponding 1,3-oxazol-5(4H)-thiones B are intermediates in this reaction. With HCl in MeOH, 1 is transformed into methyl 5,6-dihydro-4,6-dimethyl-2-phenyl-1,3(4H)-thiazine-4-carboxylate ( 12a ). The same product 12a is formed on treatment of the 1,3-thiazol-5(4H)-one 5a with HCl in MeOH (Scheme 4). It is shown that the latter reaction type is common for 4-allyl-substituted 1,3-thiazol-5(4H)-ones.     

2H-1,2,4,6-thiatriazin-3(4H)-one 1-oxides and their regioselective N4-methylation and -amination

The syntheses of 2H-1,2,4,6-thiatriazin-3(4H)-one 1-oxides and 1,1-dioxides is described. The reaction of 1-carbamoyl-2-methylisothioureas 2 with thionyl chloride gave 2H-1,2,4,6-thiatriazin-3(4H)-one 1-oxides 3 in high yields. The treatment of 3 with either diazomethane or O-(2,4-dinitrophenyl)hydroxylamine furnished regioselectively N⁴-methylated and N⁴-aminated 2H-1,2,4,6-thiatriazin-3(4H)-one 1-oxides, respectively. Subsequent dimethylamination of 4 followed by oxidation with m-chloroperoxybenzoic acid led to 2H-1,2,4,6-thiatriazin-3(4H)-one 1,1-dioxides 6a-c .     

N-(1,3-Thiazol-5(4H)-yliden)amine aus 1,3-dipolaren Cycloadditionen von Aziden mit 1,3-Thiazol-5(4H)-thionen

N-(1,3-Thiazol-5(4H)-ylidene)amines via 1,3-Dipolar Cycloaddition of Azides and 1,3-Thiazol-5(4H)-thiones Organic azides 5 and 4,4-dimethyl-2-phenyl-1,3-thiazol-5(4H)-thione ( 2 ) in toluene at 90° react to give the corresponding N-(1,3-thiazol-5(4H)-ylidene)amines (= 1,3-thiazol-5(4H)-imines) 6 in good yield (Table). A reaction mechanism for the formation of these scarcely investigated thiazole derivatives is formulated in Scheme 3: 1,3-Dipolar azide cycloaddition onto the C?S group of 2 leads to the 1:1 adduct C . Successive elimination of N₂ and S yields 6 , probably via an intermediate thiaziridine E .     

The selective preparation of 1,4-diaryl-6-methyl- and 1,6-diaryl-4-methyl-2-(1H)pyrimidinones

N-Phenylurea reacted with benzoylacetone derivatives (I) to give 1,4-diaryl-6-methyl-2-(1H)pyrimidinones (II) in addition to low yields of 1,6-diaryl-4-methyl-2-(1H)pyrimidinones (IV), while N-phenylthiourea afforded only 1,6-diaryl-4-methyl-2-(1H)pyrimidinethiones (III) in good yields. Further 1,6-diaryl-4-methyl-2-(1H)- pyrimidinethiones (III) were successfully converted in satisfactory yields into the corresponding 2-(1H)-pyrimidinones (IV) by the treatment with methyl iodide in the presence of sodium methoxide in methanol at room temperature.     

Thioureas from 3-aminoquinazolin-4(3H)-one. 2. Unusual alkaline recyclization of 3-(N",N",S-trialkylisothioureido)quinazolin-4(3H)-ones into new 1,3,4-oxadiazoles

3-(N",N",S-trialkylisothioureido)quinazolin-4(3H)-ones obtained by the reactions of 3-(N",N"-dialkylthioureido)quinazolin-4(3H)-ones with alkyl halides undergo unusual recyclization into 5-(2-aminophenyl)-2-dialkylamino-1,3,4-oxadiazoles under the action of aqueous solutions of alkali, hydrazine, and primary aliphatic amines. A plausible mechanism of the recyclization was proposed.     

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     

Synthesis of 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

The reaction of methyl 2-bromo-6-(trifluoromethyl)-3-pyridinecarboxylate ( 1 ) with methanesulfonamide gave methyl 2-[(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridine-carboxylate ( 2 ). Alkylation of compound 2 with methyl iodide followed by cyclization of the resulting methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate ( 3 ) yielded 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 4 ). The reaction of compound 4 with α,2,4-trichlorotoluene, methyl bromopropionate, methyl iodide, 3-trifluoromethylphenyl isocyanate, phenyl isocyanate and 2,4-dichloro-5-(2-propynyloxy)phenyl isothiocyanate gave, respectively, 4-[(2,4-dichlorophenyl)methoxy]-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazine 2,2-dioxide ( 5 ), methyl 2-[[1-methyl-2,2-dioxido-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4-yl]oxy]propanoate ( 6 ), 1,3,3-trimethyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 7 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 8 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-phenyl-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 9 ) and N-[2,4-dichloro-5-(2-propynyloxy)phenyl]-4-hydroxy-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2] thiazine-3-carboxamide 2,2-dioxide ( 10 ).     

Synthesis of 1-[3-methyl-2(3H)-benzazolon-5- or 6-yl]-4-{4-[cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]methyleneoxyphenyl}piperazines

Reactions of 3-methyl-6-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzoxazolone, 3-methyl-6-[4-(4-hydroxy-phenyl)-1-piperazinyl]-2(3H)-benzothiazolone and 1,3-dimethyl-5-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzimidazolone with cis-{[2-(2,4-dichlorophenyl) -2-(1H-imidazol-1-ylmethyl)]-1,3-dioxolan-4-yl}methyl meth-anesulfonate in the presence of sodium hydride furnish the title compounds.     

Synthese von 4-Benzylthio- und 4-(Arylthio)-1,3-oxazol-5(2H)-onen

Synthesis of 4-(Benzylthio)-and 4-(Arylthio)-1,3-oxazole-5(2H)-ones Following a known procedure, 4-(benzylthio)-1,3-oxazol-5(2H)-one ( 4a ) was synthesized starting from sodium cyanodithioformate ( 1 ) and cyclohexanone (Scheme 1). The structure of the intermediate 4-(benzylthio)-1,3-thiazol-5(2H)-one ( 3a ) was established by X-ray crystallography. An alternative route was developed for the synthesis of 4-(arylthio)-1,3-oxazol-5(2H)-ones which are not accessible by the former reaction. Treatment of ethyl cyanoformate ( 5 ) with a thiophenol in the presence of catalytic amounts of Et₂NH and TiCl₄, followed by addition of a ketone and BF₃.Et₂O in a one-pot-reaction, gave 4f–i in low-to-fair yields (Scheme 3). Both synthetic pathways-complementary as for benzyl–S and aryl-S derivatives–seem to be limited with respect to variation of substituents of the ketone.     

Synthesis of some isomeric 4-ethoxycarbonyl-3-and 5-(1- and 2-hydroxyalkyl)-1,3- and 1,5-dimethylpyrazoles from 3-(2H)furanones and 2,3-dihydro-4-pyrones

The title compounds were prepared by reaction of 3-(2H)furanones and 2,3-dihydro-4-pyrones with methylhydrazine or alternatively by methylation of the corresponding N-unsubstituted pyrazoles. ¹³C and ¹H nmr were used to assign the isomeric 3-methyl or 5-methyl structures.     

Synthesis of 2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentan)-2(1H)-one and 2-amino-2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentane) from 6-(cyclopent-1-enyl)-2-methylaniline

The reaction of 6-(cyclopent-1-enyl)-N-ethoxycarbonyl-2-methylaniline with Br₂ or its reaction with NH₃ followed by the reaction with Br₂ afforded 2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentan)-2(1H)-one and 2-amino-2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentane), respectively.     

Synthesis of novel 6-(substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones via azo coupling

Abstract  

6-(Substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones were prepared from β-aryl glutaconic acid, which, on fusion with aniline, results in 4-(4-ethoxyphenyl)-1-phenylpyridine-2,6(1H,5H)-dione. This, on further treatment with phosphorus oxychloride gave 6-chloro-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinone, and further treatment with secondary amines yielded 6-(substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones. These were subjected to azo coupling with different aryldiazonium chlorides furnishing two isomers, which were separated by column chromatography. All compounds were characterized by elemental analysis, and use of IR and NMR spectral data, and were evaluated for antimicrobial activity.     

Diels-alder reaction of (E)-4-(2-nitroethenyl)-1H-imidazoles and methyl (E)-3-(1-imidazol-4-yl)propenoates

Diels-Alder reaction of methyl (E)-3-(1H-imidazol-4-yl)propenoates 2, 3a-c and (E)4-(2-nitroethenyl)-1H-imidazoles 3d,e with 2,3-dimethyl-1,3-butadiene, cyclopentadiene, and cyclohexa-1,3-diene gave the corresponding cycloadducts 6–9 .     

Products from furans. VI. Synthesis of dihydro-2-disubstituted-2H-pyran-3(4H)-ones,tetrahydro-3-(aminomethyl)-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3-ol derivatives and 6-(p-methoxyphenyl -6-methyl-7-oxa-1,3-diazaspiro[4,5]decane-2,4-dione

Hydrogenolysis of 5,6-dihydro-6-(p-methoxyphenyl)-6-methyl-5-oxo-2H-pyran-2-yl ethyl carbonate yielded dihydro-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3(4H)-one, 3 . Subsequently cyanohydrin 4 , derived from 3 , on reduction afforded 3-(aminomethyl)tetrahydro-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3-ol, 5 . The synthesis of N-dimethyl,N-isopropyl,N-imidazolyl as well as N-oxazolinyl derivatives of 5 is presented. The synthesis of 6-(p-methoxyphenyl)-6-methyl-7-oxa-1,3-diazaspiro[4,5]decane-2,4-dione 10 , a spiro hydantoin prepared from ketone 3 is also reported.     

Darstellung und Kristallstruktur von [P(C6H5)4][2,9-{N,N′-(2-NH?(C5H4N))}B10H8]

Synthesis and Crystal Structure of [P(C₆H₅)₄][2,9-{N,N′-(2-NH? (C₅H₄N))}B₁₀H₈] [N(C₄H₉)₄]₂[B₁₀H₁₀] reacts with 2-aminopyridine forming a product mixture from which [2,9-{N,N′-(2-NH? (C₅H₄N))}B₁₀H₈]^? can be isolated by ion exchange chromatography on diethylaminoethyl(DEAE) cellulose. The crystal structure of [P(C₆H₅)₄][2,9-{N,N′-(2-NH? (C₅H₄N))}B₁₀H₈] (triclinic, space group P1 , a = 10.1103(9), b = 11.5665(9), c = 14.877(2) Å, α = 102.600(8), β = 107.567(8) und γ = 96.487(7)°, Z = 2) reveals the bonding of 2-NH₂-(C₅H₄N) via both N atoms to vicinal B atoms of the two square planes of the B₁₀ cluster (B2? N1 = 1,541(7) und B9? N2 = 1.505(7) Å) forming a five-membered ring.     

An Unexpected Isomerization of N-Aryl-3-amino-4-nitroisothiazol-5(2H)-imines to 2-(Benzothiazol-2-yl)-2-nitroethene-l,l-diamines

The syntheses of several N-aryl-3-amino-4-nitroisothiazol-5(2H)-imines 12 from 3, 3-diamino-2-nitro-thioacrylamides 11 are reported (Scheme 3). In polar solvents, a spontaneous isomerization of some of the prepared isothiazol-5(2H)-imines 12 yielded benzothiazoles 13 (Scheme 4). In the case of 2-alkyl-substituted derivatives of type 12 , the isomerization occurred only at higher temperatures. Electronic influences of different substituents on the rate of the isomerization were studied, and a polar reaction mechanism is proposed in Scheme 6. The structures of 12e and 13e were established by X-ray crystallography. Conformational analyses of 3-(methylamino)-2-nitro-N-phenyl-3-(pyrrolidin-1-yl)thioacrylamide (111) by NMR and X-ray methods were performed with the aim of explaining the distinct behavior of this amide towards Br₂ or diethyl azodicarboxylate.     

The First Hexa-coordinated Tetranuclear Nickel Complex {[Ni(en)2]4[H4L]}(ClO4)4·7H2O with Tetrakis-bidentate Oxamato Bridge

The first tetranuclear nickel complex with the oxamato ligand, {[Ni(en)₂]₄[H₄L]}(ClO₄)₄·7H₂O ( 1 ) (L = N, N′, N″, N‴-methanetetrayltetrakismethylenetetrakis (oxamato)), has been prepared and determined by single-crystal X-ray analysis. 1 crystallizes in the tetragonal space group I4₁/a, with a = 15.2744(9), c = 31.3748(2) Å and Z = 4. Each nickel (II) ion is in a distorted octahedral donor atom environment, which comprises four nitrogen atoms of two en molecules and two oxygen atoms of oxamato bridge. The shape of the entity looks like a propeller. The temperature-dependent magnetic susceptibilities were analyzed by the Curie-Weiss law; the following values were found C = 4.36 cm³ K mol^-1, θ = -24.7 K, respectively.     

Herstellung der 1H-Indazole durch Photolyse von 2-Aminophenylketon-O-(äthoxycarbonyl)oximen und von 3,1,4-Benzoxadiazepin-2 (1H)-onen

1H-Indazoles Obtained by Photolysis of 2-Aminophenylketon-O-(ethoxycarbonyl)oximes and of 3, 1, 4-Benzoxadiazepine-2(1 H)-ones Irradiation of (E)- and (Z)-O-(ethoxycarbonyl)oximes 1 of 2-aminophenyl ketones in solution with UV, and/or visible light gives 1 H-indazole derivatives 2 in high yields (Scheme 1). For this reaction the amino group must be un- or mono substituted. With the N, N-disubstituted (E)- 1d (Scheme 2) no 1 H-indazole formation is observed, because the radicals formed by its photolysis react in an unspecific manner with each other and with the solvent. From the behaviour of (E)- 1d and from the lack of any E/Z-isomerization of 1 we conclude that the photoreaction starts with a splitting of the N, O-bond in two separate radicals, whereas the radical pair produced by the also studied photolysis of 3,1,4-benzoxadiazepine-2(1 H)-one derivatives 3 is fixed in the parent molecule, and therefore tends to recombine. This makes a prolonged irradiation necessary to convert the benzoxadiazepinones 3 into the 1 H-indazoles 2 . The different reaction rates of the (E) and (Z)-isomers of 1 (provided R⁴ = H) are understood by means of different intramolecular H-bridges.     

Synthesis of 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones and their conversion into 2-aryl-1,2,4-triazine-3,5-(2H,4H)odiones. A new synthesis of 1-aryl-6-azauracils

Treatment of 6-amino-5-arylazo-1,3-dimethyluracils with urea or N,N′-carbonyldiimidazole gave the respective 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones, which were hydrolyzed with alkali to afford 2-aryl-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carboxylic acids (1-aryl-6-azauracil-5-carboxylic acids). Thermal decomposition of these carboxylic acids gave the corresponding 2-aryl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-6-azauracils). Methylation of the latter with methyl iodide gave the corresponding 2-aryl-4-methyl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-3-methyl-6-azauracils).