Synthesis of 4H-pyrazolo- and 4H-pyrrolophenothiazin-4-one derivatives

5-Methyl- and 6-methyl-2-phenyl-2H-indazole-4,7-diones were condensed with 2-aminobenzenethiol or 6-substituted-3-aminopyridine-2(1H)thiones 4 to produce a new type of 5-methyl-2-phenyl-4H-pyrazolophenothiazin-4-ones or 8-substituted-7-aza-5-methyl-2-phenyl-4H-pyrazolophenothiazin-4-one derivatives. From 6-bromo-2,5-dimethyl-1,3-diphenyl-2H-isoindole-4,7-dione and 4 8-substituted-7-aza-2,5-dimethyl-1,3-diphenyl-4H-pyrrolophenothiazin-4-one derivatives were also prepared.     

Relative reactivity in the condensation of 2H-isoindole- and 2H-indazole-4,7-dione derivatives with o-aminobenzenethiol and its derivatives

The effects of substituents on the condensation of o-aminobenzenethiol derivatives with 2H-isoindole- and 2H-indazole-4,7-dione derivatives were studied by competitive reactions.     

Synthese und polarographisches Verhalten von 2H-Isoindol-4,7-dionen

Summary 2-Phenylthio-1,4-benzoquinone (1 a) reacts with azomethine ylide AY-A to give 2-methyl-5-phenylthio-2H-isoindole-4,7-dione (4 f). With 2-(N-methylanilino)-5-methyl-1,4-benzoquinone (1 b), the azomethine ylide AY-B undergoes cycloaddition to yield an inseparable mixture of 5a-methyl-8-(N-methylanilino)-2,3,5,5a,9a,9b-hexahydro-pyrrolo[2,1-a]1H-isoindole-6,9-dione (5 bI) and 9a-methyl-7-(N-methylanilino)-2,3,5,5a,9a,9b-hexahydropyrrolo[2,1-a]1H-isoindole-6,9-dione (5 bII). The structures of5 bI and5 bII were established on basis of two-dimensional-NMR-techniques. The mechanism of the cycloaddition of azomethine ylides to 1,4-quinones was studied on basis of cyclovoltammetric investigations. To determine the electron affinity of the isoindoledione derivatives4 a–f and5 a–b the peak potentials were measured by differential pulse polarography (DPP).

     

Condensation of 2H-indazole-4,7-dione derivatives with 2-aminophenol derivatives

A new type of 9-substituted-5-methyl-2-phenyl-4H-pyrazolophenoxazin-4-one derivatives was prepared by the condensation of 5-methyl- and 6-methyl-2-phenyl-2H-indazole-4,7-diones with 4-substituted-2-aminophenols in pyridine. Relative reactivity of 2-aminophenol derivatives in the condensation was studied.     

Synthesis of 2H-indazole-4,7-dione derivatives from 3-phenylsydnone and p-toluquinone. The crystal and molecular structure of 6-bromo-5-methyl-2-phenyl-2H-indazole-4,7-dione

The 1,3-dipolar cycloaddition of 3-phenylsydnone with p-toluquinone afforded 5-methyl- and 6-methyl-2-phenyl-2H-indazole-4,7-diones 3a and 3b. No regioselectivity was observed in this cycloaddition yielding an equimolar amount of the regioisomers. Reactions of 3a and 3b with bromine gave the corresponding mono- 4a and 4b and dibromo derivatives 5a and 5b , respectively. The crystal structure of 6-bromo-5-methyl-2-phenyl-2H-indazole-4,7-dione ( 4a ) has been determined by the single crystal X-ray method. The crystals are monoclinic, space group PI with two molecules in a unit cell of dimensions a = 8.029(1), b = 14.309(1), c = 5.895(1)Å, β = 90.24(1)° and V = 621 ų. The structure has been solved by the direct method using 1827 reflections and refined by full-matrix least-squares calculations to R = 0.0739.     

Directed regiospecificity of 1,3-dipolar cycloaddition of 2-diazopropane to 4- and 5-substituted pyridazin-3(2H)-ones

6-Methoxy-2-methylpyridazin-3(2H)-one ( 1 ) gave with 2-diazopropane ( 8 ) a mixture of 3H-pyrazolo[3,4-d]-pyridazin-4(5H)-one derivative 12 , as the main product, and -7(6H)-one derivative 10 , as the minor product. On the other hand, 4-substituted pyridazin-3(2H)-ones 2, 3 , and 4 gave 3H-pyrazolo[3,4-d]pyridazin-7(6H)-one 10 , exclusively, while 5-substituted pyridazin-3(2H)-ones 5, 6 , and 7 produced only the isomeric 3H-pyrazolo[3,4-H]pyridazin-4(5H)-one 12 . The 5-phenylsulfonyl derivative 13 gave with 8 by elimination of a molecule of nitrogen, followed by rearrangement, 1,2-diazepine derivative 15 and with an excess of 8 3H-pyrazolo[3,4-d][1,2]diazepine derivative 16. 1 ,2-Dimethylpyridazine-3,6-(1H,2H)-dione and its derivatives 18 and 19 produced 3H-pyrazolo[3,4-d]pyridazine-4,7(5H,6H)-dione derivative 23 , while from 17 and 1-diazoindane ( 24 ) the spiro compound 27 was obtained. The 1,2-dihydro and 3a,7a-dihydro intermediates 21 and 25 were isolated.     

Reactivity of 4-azido- and 4-amino-6-methyl-2H-pyran-2-one. Preparation of 1-(6-methyl-2-oxopyran-4-yl)-1,2,3-triazoles and 5-oxopyrano[4,3-b]pyridines

1,3-Dipolar cycloadditions of stable 4-azido-6-methyl-2H-pyran-2-one 1 with electron-rich alkenes and alkynes lead to 4,5-substituted 1-(6-methyl-2-oxopyran-4-yl)-1,2,3-triazoles. Iminophosphoranes derived from 1 have also been synthesized. 5-Oxopyrano[4,3-b]pyridines are prepared by reaction of 4-amino-6-methyl-2H-pyran-2-one 2 with β-dicarbonyl compounds.     

Chemical and X-Ray crystallographic characterization of the reaction products in the 1,3-dipolar cycloaddition of diazomethane to p-toluquinone

The product 2 in the 1,3-dipolar cycloaddition of one equivalent of diazomethane to p-toluquinone (1) was determined by 250 MHz nmr spectra to be approximately 85% 6-methyl-1-H-indazole-4,7-dione (2b). X-ray crystallographic analysis was employed in the characterization of 1,6-dimethyl-1-H-indazole-4,7-dione (4a), which was the major 1-N-methyl regioisomer in the methylation of the cycloaddition mixture 2 with diazomethane. Methylation of the cycloaddition product 2 with diazomethane also provided a regioisomeric mixture of the 2-N-methyl derivatives 5. This mixture was synthesized for characterization by an independent method which utilized the cycloaddition of 3-methylsydnone (10) to toluquinone (1). 1,5,6-Trimethyl-1-H-ind-azole-4,7-dione (9) was found to be a minor product in the reaction of diazomethane with the cycloaddition product 2.     

The interaction of 2-(5-methyl-2-phenyl-2h-1,2,3-diazaphosphol-4-yl)-4h-benzo[e]-1,3,2-dioxaphosphinin-4-one with activated carbonyl compounds. Synthesis of bis-heterocyclic systems containing di- and tetracoordinated phosphorus

The interaction of 2-(5-methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-4H-benzo[e]-1,3,2-dioxaphosphinin-4-one with mesoxalic and trifluoropyruvic acids ethyl and diethyl esters, hexafluoroacetone and chloral proceeds with an exclusive participation of P(III) atom and allows to obtain 2-(5-methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-derivatives of 1,4,2- and 1,3,2-dioxaphosphepines as well as dichlorovinylphosphonate, being the product of Perkow reaction in the case of chloral.     

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.     

2H-Isoindol-4,7-dione durch Addition von Azomethinyliden an 1,4-Benzochinone

Summary A new approach to the synthesis of 2H-isoindole-4,7-diones is described. Heating -amino acids with carbonyl compounds generates azomethine ylides through the elimination of water and carbon dioxide. The ylides were captured by quinones forming 2H-isoindole-4,7-diones, 2,3,3a,7a-tetrahydro-1H-isoindole-4,7-diones and 2,3-dihydro-1H-pyrrolo[2,1-a]isoindole-6,9-diones. The structures were established on the basis of spectroscopy (NMR, mass).

Herrn Univ.-Prof. Dr. G. Zigeuner zum 70. Geburtstag gewidmet     

Dichloromethylenation of substituted 1H-isoindole-1,3-(2H)-diones (phthalimides)

A number of substituted 1H-isoindole-1,3-(2H)-dione derivatives (phthalimides) underwent dichloro-methylenation when reacted with a mixture of triphenylphosphine and carbon tetrachloride.     

Unexpected photochemical transformation of imidazole derivatives containing the 5-hydroxy-2-methyl-4H-pyran-4-one moiety. Environmentally friendly method for the synthesis of substituted imidazo[1,5-a]pyridine-5,8-diones

An unexpected photochemical transformation of imidazole derivatives containing the 5-hydroxy-2-methyl-4H-pyran-4-one moiety was discovered, which led to the synthesis of previously unknown imidazo[1,5-a]pyridine-5,8-dione derivatives. The structures of imidazole and imidazo[1,5-a]pyridine-5,8-dione derivatives were unambiguously determined by X-ray diffraction analysis.     

Synthesis and Some Properties of 2-(5-Methyl-2-Phenyl-2H-1,2,3-Diazaphosphol-4-yl)-4H-Benzo[d]-1,3,2-Dioxaphosphorin-4-One

Abstract

2-(5-Methyl-2-phenyl-2Н-1,2,3-diazaphosphol-4-yl)-4H-benzo[d]-1,3,2-dioxaphosphorin-4-one 1 readily reacts with hexafluoroacetone, mesoxalic acid diethyl ester, trifluoropyruvic acid ethyl ester and chloral to give 2-(5-methyl-2-phenyl-2H-1,2,3-dizaphosphole-4-yl)-derivatives of 1,3,2- and 1,4,2-dioxaphosphepines.     

Elektrochemische Eigenschaften von 6-Methoxy-2,5-dimethyl-2H-isoindol-4,7-dion,einem antimikrobiell wirksamen Alkaloid ausReniera-Arten

Summary To determine the electronaffinity of 6-methoxy-2,5-dimethyl-2H-isoindole-4,7-dione — the first naturally-occurring isoindole alkaloid — the peak potential was measured by DPP.

Herrn Univ.-Prof. Dr. W. Fleischhacker mit besten Wünschen zum 60. Geburtstag gewidmet.     

Synthese von 2H-Isoindol-4,7 -dionen durch photochemische Cycloaddition von 2,3-Diphenyl-2H-azirin an 1,4-Chinone. 38. Mitteilung über Photoreaktionen

2, 3-Diphenyl-2H-azirine ( 1 ) reacts on irradiation with light of wavelength 290–350 nm with 1,4-benzoquinones 3–6 or with 1,4-naphthoquinones 7–9 forming the yellow to red coloured 1,3-diphenyl-2H-isoindole-4, 7-diones 10–13 (33–43% yield) resp. 1, 3-diphenyl-2H-benzo[f]isoindole-4,9-diones 14–16 (33–36% yield) (Scheme 1). The structures of these hitherto unknown products follow from the analytical and spectral data. The probable formation of the isoindole-diones is depicted in Scheme 2. The intermediate benzonitrile-benzylide ( 2 ), which most certainly arises, adds onto the unsubstituted C, C-double bond of the quinones and not onto the C,O-double bonds. On exclusion of atmospheric oxygen there results from 1 and 2-methyl-1, 4-benzoquinone ( 4 ) a product (probably b ) which hardly absorbs in the region 350–450 nm. The latter, with the agency of atmospheric oxygen (but not 4 ), is converted into 5-methyl-1, 3-diphenyl-2H-isoindole-4, 7-dione ( 11 ). The relative slowness of this oxidation (see Fig. 2) enables an almost complete photochemical transformation of the azirine 1 , which only weakly absorbs above 290 nm. Otherwise 11 , which strongly absorbs above 290 nm, would hinder the photolysis of 1 .     

The Synthesis and Antimicrobial Screening of Some Novel AZA-Imidoxy Compounds as Potential Chemotherapeutic Agents

Some novel azaimidoxy compounds viz. 2-{[(4-chlorophenyl)diazenyl]oxy}-1H-isoindole-1,3-(2H)-dione (Va), and 1-{[1-naphthyldiazenyl]oxy}pyrrolidine-2,5-dione (IVc), etc. have been synthesized by a simple diazotization reaction followed by a coupling with 2-hydroxy-1H-isoindole-1,3(2H)-dione (III)/1-hydroxypyrrolidine-2,5-dione (II) of corresponding aromatic primary amine derivatives at a suitable pH. A similar reaction with a [1,3]thiazolo[4,5-b]pyridin-2-amine (VIII) lead us to some interesting results variable with a pH. The structure of all synthesized compounds has been established by IR, ¹H NMR, and mass studies. These compounds have been screened for antimicrobial activities in order to evaluate the possibility of the derivatives to be used as potential chemotherapeutic agents.     

Synthesis and Evaluation of 2-{[(2-Oxo-1H-quinolin-8-yl)oxy]methyl}-Substituted α-Methylidene-γ-butyrolactones

O-Alkylation of 8-hydroxy-1H-quinolin-2-one ( 1 ) afforded 8-(2-oxopropoxy)-1H-quinolin-2-one ( 2 ) which was immediately cyclized to form the tricyclic 2,3-dihydro-3-hydroxy-3-methyl-5H-pyrido[1,2,3-de][1,4]benzoxazine,-5-one ( 3). The Reformatsky-type condensation of 3 furnished antiplatelet 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylidene-5-oxofuran-2-yl)melhoxy]-1H-quinolin-2-one ( 4 ). Its counterparts 7a – f , Ph-substituted at C(2) of the furan ring, were obtained from 1 via alkylation and the Reformatsky-type condensation. Although compound 4 was less active against platelet aggregation than 7a – f , it was the only compound which exhibited significant inhibitory activity on high-K⁺ medium, Ca²⁺-induced vasoconstriction and was more active than most of its Ph-substituted counterparts against norepinephrine-induced vasoconstrictions.     

Permanganate Oxidation of Quinoxaline and Its Derivatives

The oxidation reactions of a series of quinoxaline derivatives, using KMnO₄ in the presence or absence of NaOH, are described. Neutral oxidation of 2-chloro- and 2, 3-dichloroquinoxalines 2 – 4 afforded the corresponding chloro- and dichloropyrazinedicarboxylic acids 13 and 14 in good yield. On the other hand, oxidation of quinoxalin-2(1H)-one and 1, 4-dihydroquinoxaline-2, 3-dione derivatives in alkaline medium gave different products, with the quinoxalin-2(1H)-one ( 5 ) forming 1, 4-dihydroquinoxaline-2, 3-dione ( 9 ), while various substituted quinoxalin-2, 3-dione derivatives (see 9 – 11 ) gave a new type of dimeric products. The structural assignments for the new compounds were based on spectroscopic data.     

A reinvestigation of the synthesis of 3H-[1,2]diazepino[5,6-b]indoles. The synthesis of pyrido[4,3-b]indoles

Recently reported [1] syntheses of 6-methyl-1,2,4,5-tetrahydro-1,4-dioxo-3H[1,2]diazepino[5,6-b]indole ( 5 ) and 4-hydroxy-6-methyl-3H[1,2]diazepino[5,6-b]indole ( 12 ) were reinvestigated and shown to be in error. The correct assignments for these respective structures are 3-amino-1,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2,4(3H)-dione ( 6 ) and 3-amino-3,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2-one ( 13 ). Condensation of 6 and 13 with p-nitrobenzaldehyde produced benzylidene derivatives, which confirmed the presence of the amino groups.