Tetrazolverbindungen. 4 [1]. Alkylierung von 1-Aryl-5-(2-dimethylamino-vinyl)-1 H-tetrazolen

Tetrazole Compounds. 4. Alkylation of 1-Aryl-5-(2-dimethylamino-vinyl)-1 H-tetrazoles Alkylation of 1-aryl-5-(2-dimethylamino-vinyl)-1 H-tetrazoles 1 with dialkyl sulfates or alkyl iodides yields mainly 4-alkyl-1-aryl-5-(2-dimethylamino-vinyl)-1 H-tetrazolium salts which can be isolated free from isomers by separation as perchlorates 2 . The reaction proceeds with retention of the E configuration of the vinyl group. In contrast to 1 the methyl groups of the dimethylamino substituent in 2 are magnetically non-equivalent indicating restricted rotation of this residue. On heating 2 with aqueous mineral acids the dimethylaminovinyl moiety undergoes degradation to a methyl group affording 4-alkyl-1-aryl-5-methyl-1 H-tetrazolium salts 4 , the structure of which was confirmed by independent synthesis. With hot aqueous alkali hydroxide 2 reacts under ring cleavage to give aryl azide. — ¹H n.m.r. and u.v. spectroscopic data of the tetrazolium salts 2 and 4 are reported.     

Tetrazolverbindungen. 1. 1-Aryl-5-(2-dialkylamino-vinyl)-1H-tetrazole aus 3-Chlor-propen-iminiumsalzen

Tetrazole Compounds. 1. 1-Aryl-5-(2-dialkylamino-vinyl)-1H-tetrazoles from 3-Chloropropeniminium Salts 3-Chloropropeniminium salts 1 react with excess sodium azide in refluxing alcohols to give mainly 1-aryl-5-(2-dialkylamino-vinyl)-1H-tetrazoles 3 ; in minor quantities isomeric 5-aryl-1-(2-dialkylamino-vinyl)-1H-tetrazoles 4 are formed. The reaction involves splitting off N₂ and C → N migration of the aryl and dialkylaminovinyl group, respectively. A cross-over experiment indicated that the rearrangement step proceeds intramolecularly. — The i.r., u.v., and n.m.r. spectroscopic data of the novel 1H-tetrazoles 3 as well as the u.v. spectra of some new starting products 1k—v are reported.     

Preparation of 4-(2-Aryl-2-oxo-ethylidene)-5,7-dinitrobenzofurazan derivatives

Upon treatment with KF in acetonitrile the zwitterionic Meisenheimer complexes 3 undergo β-elimination leading to potassium 7-(2-aryl-2-oxo-ethylidene)-4,6-dinitro-7,x-dihydrobenzofurazanide 1-oxides 4 in 72–87% yield. Compounds 4 give 7-(2-aryl-2-oxo-ethyl)-4,6-dinitrobenzofuroxans 6 when treated with hydrochloric acid. 4-(2-Aryl-1-dimethylsulfonio-2-oxo-ethylidene)-5,7-dinitro-4,x-dihydrobenzofurazanides 5 are obtained by reaction of 3 with sodium methoxide. The structure of 5e is confirmed by X-ray structure analysis. The reaction of complexes 8 with acetic acid/potassium acetate at 80°C affords 4-(2-aryl-2-oxo-1-pyridinio-ethylidene)-5,7-dinitro-4,x-dihydrobenzofurazanides 9 in moderate yields.     

1,2,3-Triazabutadiene. XIII. UV-vis-spektroskopische Untersuchungen zur Protonierung Z-E-isomerer 1-Aryl-3-[3-methylbenzthiazolinyliden-(2)]- und 1-Aryl-3-[1,3-dimethylbenzimidazolinyliden-(2)]-triazene

1,2,3-Triazabutadienes. XIII. U.V.-vis-Spectroscopic Investigations of the Protonation of Z-E-Isomeric 1-Aryl-3-[3-methylbenzthiazolinyliden-(2)]- and 1-Aryl-3-[1,3-dimethylbenzimidazolinyliden-(2)]-triazenes The u.v.-vis absorption spectra of Z-E-isomeric 1-aryl-3-[3-methylbenzthiazolinyliden-(2)]- and 1-aryl-3-[1,3-dimethyl-benzimidazolinyliden-(2)]-triazenes 1–3 resp. 4 show a pronounced halochromic effect in the presence of acids. The reason is the protonation of the N¹-atom of the triazabutadiene chain whereby the energetically favourable structure of a diazatrimethine is formed. The magnitude of the halochromic effect depends on the substituents in the aryl and benzo residue and on the Z-E-structure of the compounds.     

Cycloadditions-Eliminierungsreaktionen mit 4-Aryl-5-arylimino-1,2,4-dithiazolidin-3-onen (Senföloxiden)

Cycloaddition Elimination Reactions of 4-Aryl-5-arylimino-1,2,4-dithiazolidin-3-ones (Mustard Oil Oxides) 4-Aryl-5-arylimino-1,2,4-dithiazolidin-3-ones ( 1 ) react with isocyanates, isothiocyanates, and cyanic acid esters by exchange of the COS-part from 1 affording thiadiazole and dithiazole derivatives 4 , 5 , 6 or 12 . The reaction products are able to give further exchange reactions. Ring opening of 2-substituted 4-aryl-5-arylimino-1,2,4-thiadiazolin-3-ones ( 4 ) and -3-thiones ( 6 ) yields thio- and dithiobiurets ( 7 , 8 ) with aryl substituent in 3-position. Oxidation of dithiobiurets, generated from 6 , affords dithiazolidines 9 , which are Dimroth-isomers of 6 .     

Push-pull-Butadiene. II [1]. Reaktionen von 2-Aryl-4,4-bis(methylthio)buta-1,3-dien-1,1-dicarbonitrilen mit Malononitril und Cyanessigsäure-ethylester

Push-pull-Butadienes. II. Reactions of 2-Aryl-4,4-bis(methylthio)-1,3-butadiene-1,1-dicarbonitriles with Malononitrile and Ethyl Cyanoacetate 2-Aryl-4,4-bis(methylthio)-1,3-butadiene-1,1-dicarbonitriles 1 react with sodium salts of malononitrile or ethyl cyanoacetate 3 to give 4-aryl-2-methylthio-1,4-pentadiene-1,1,5,5-tetracarbonitriles and ethyl-4-aryl-1,5,5-tricyano-2-methylthio-1,4-pentadienecarboxylates 4 , respectively. Also, arylethylidenemalononitriles 5 and bis(methylthio)methylenemalononitrile or ethyl bis(methylthio)methylenecyanoacetate 6 afford 4 . Substituted dihydropyridines 8 are prepared by treating 4 with aromatic amines. Compounds 4 d, e can be converted to 2-amino-6-aryl-4-methylthio-benzene-1,3-dicarbonitriles 11 a, b .     

Synthese und Polymerisation von 2-Aryl-5-methylen-1,3-dioxolan-4-onen und Arylbis(5-methylen-1,3-dioxolan-2-yl-4-on)en

Synthesis and Polymerization Behaviour of 2-Aryl-5-methylene-1,3-dioxolan-4-ones and Arylbis(5-methylene-1,3-dioxolan-2-yl-4-on)es Starting from 2,6-di(hydroxymethyl)-4-methylphen-ol-Na-salt-1-hydrate ( 1 ) a synthesis of 2-alkoxy-5-methyliso-phthaldialdehydes ( 3a,b ) is described via alkylation and oxidation. Condensation of aromatic aldehydes with 3-bromo-2-hydroxypropanoic acid (β-bromolactic acid) affords diastereoisomeric mixtures of new 2-aryl-5-bromomethyl-1,3-dioxolan-4-ones ( 6a–h ) as well as the corresponding bisdioxolanones ( 6i–l ). Dehydrobromination of 2-aryl-5-bromomethyl-1,3-dioxolan-4-ones ( 6a–d,i ) with DBU leads to 2-aryl-5-methylene-1,3-dioxolan-4-ones ( 8a–e ). Polymerization of compounds 8a , b , d and e proceed via opening of the dioxolanone ring.     

Umsetzung von (Z/E)-1-Aryl-4-arylmethylen-pyrrolidin-2,3,5-trionen mit Enaminocarbonylverbindungen

Reaction of (Z/E)-1-Aryl-4-arylmethylene-pyrrolidine-2,3,5-triones with Enaminocarbonyl Compounds Treatment of the α, β-unsaturated ketones (Z/E)- 1a–e with alicyclic or aliphatic enamines afforded cyclic Michael adducts 2 and 3a–e , respectively. By dehydration of the N,O-hemiacetals 3b–d the corresponding 1,4-dihydropyridines 4a–c were obtained. The acid-catalyzed reaction of aminosubstituted maleimides with (Z/E)- 1e , aldehydes or indan-1,2,3-trione led to 5a–c , 6a–c , 7a–c and 8 . O-Methylation of the aryl-bis(maleinimidyl)methanes 5c , 6c by using diazomethane gave 5d , 6d , whereas 5a cyclized spontaneously to the 1,4-dihydropyridine 9a . Further 1,4-dihydropyridines were prepared by cyclocondensation of 6a , b in the presence of ammonium acetate and oxidized to the pyridine derivative 10 .     

1,2,3-Triazabutadiene. VI. Untersuchungen zur cis-trans-Isomerie von 1-Aryl-1-äthyl-3-[3-methyl-benzthiazolinyliden-(2)]-triazeniumtetrafluoroboraten

1,2,3-Triazabutadiene. VI. Studies on the Cis-trans-Isomerisation of 1-Aryl-1-äthyl-3-(3-methylbenzthiazolin-2-ylidene) -triazeniumtetrafluoroborates Cis-trans-isomeric 1-aryl-3-[3-methylbenzthiazolinylidene-(2)]-triazenes will be alkylated under kinetic control stereospecifically to the corresponding cis-trans-isomeric 1-aryl-1-ethyltriazenium-tetraflouroborates 2 . By their n.m.r.(¹H and ¹³C)- and u.v.-vis.-spectroscopical as well as by their thermical and photochemical behavior the pairs of isomers are characterized as cis-trans-isomers about the N-1-N-2-bond. The rate of the thermal cis-trans-isomerisation depends from the substituents in 2 and from the solvent. Electron withdrawing substituents in para-position of the arylresidue and electron donors in the heterocycle increases the rate of the isomerisation. Morever it increases with an increasing DN-value of the solvent. The isomers can be changed into each other photochemically. The quantum yield of the cis-trans-isomerisation is evidently higher than of the trans-cis-transformation.     

Tetrazolverbindungen. 5. Synthese und Umaminierung von Enaminoketonen der Tetrazolreihe

Tetrazole Compounds. 5. Synthesis and Transamination of Enamino Ketones of the Tetrazole Series Tetrazole-5-acetaldehyde enamines 5 react with aliphatic and aromatic carboxylic acid chlorides in the presence of an auxiliary base (e.g. pyridine or triethylamine) to give tetrazolylsubstituted enamino ketones 6 . The latter can be modified by acid-catalyzed transamination with secondary aliphatic amines (e.g. diethylamine, pyrrolidine, piperidine, morpholine, hexamethylene imine) yielding 5-(1-acyl-2-dialkylamino-vinyl)-1-aryl-1 H-tetrazoles 7 . The analogue transamination of 6 with primary alkyl, aralkyl, and aryl amines results in corresponding secondary enamino ketones 8 , which exist in solution as an equilibrium mixture of the Z and E form. Acylation of secondary tetrazole-5-acetaldehyde enamines 9 does not lead to 8 , but to the isomeric N-acyl derivatives 10 . – Characteristic ¹H-n.m.r., u.v., and i.r. spectroscopic data of the novel products are reported.     

Die Reaktion von α,β-Dihalogen-propionitrilen mit monosubstituierten Hydrazinen - einfache Synthese 1-substituierter 3- bzw. 5-Amino-pyrazole

The Reaction of α,β-Dihalogeno-propionitriles with Monosubstituted Hydrazines — A Simple Synthesis of 1-Substituted 3- or 5-Amino-pyrazoles In methanol hydrazines 3 , and α,β-dihalogeno-propionitriles 1, 2 even at 0°C irreversibly yield 3 · HX, and α-halogenoacrylonitriles 4, 5 (A₁). Fast addition of alkyl- and aralkyl- hydrazines 3 to 4, 5 (C) gives 1-substituted 1-(2′-halogeno-2′-cyan-ethyl)-hydrazines 6 , the addition of arylhydrazines 3 to 4, 5 (D) 1-aryl-2-(2′-halogeno-2′-cyan-ethyl)-hydrazines 8 . In methanol 6 spontaneously cyclise (E) to hydrogen halides 7 · HX of 1-alkyl- and 1-aralkyl-3-amino-pyrazoles, 8 with 2 moles of acids (F) to salts 10 · 2HY of 1-aryl-4-halogeno-5-imino-pyrazolidines, and the free 10 spontaneously (G) to hydrogen halides 9 · HX of 1-aryl-5-amino-pyrazoles. Mechanisms (A₁), (C), (D), (E), (F), and (G) are proved by t.l.c., ¹H-n.m.r., and isolation of intermediates, the structures of 7 resp. 9 , using the significant ¹H-n.m.r.-parameter Δ. Simple general syntheses are described for 3-amino-pyrazoles 7 (R = H, alkyl, aralkyl) or 5-amino-pyrazoles 9 (R = aryl) starting with α,β-dihalogeno-propionitriles 1, 2 , and for α-bromo-acrylonitrile 5 .     

Konfigurative Zuordnung über sterisch definierte Epoxidringe. VIII. Glycidonitrile. I. Synthese von 4-Aryl-1-oxaspiro(2,5)octan-2-nitrilen und 4-Aryl-1-oxaspiro(2,5)octan-2-carbonsäureestern

Determination of Configurations by the Aid of Sterically Corresponding Epoxides. VIII. Glycidic Nitriles. I. Synthesis of 4-Aryl-1-oxaspiro(2,5)octane-2-nitriles and 4-Aryl-1-oxaspiro(2,5)octane-2-carboxylic Acid Methyl Esters The condensation of 2-aryl-cyclohexan-1-ones ( 1–5 ) with ClCH₂CN or ClCH₂CO₂CH₃ at 80°C in the presence of NaH and in dimethoxyethane yields the corresponding glycidic nitriles and the glycidic esters, respectively. The configuration and the preferred conformation of the two isomeric 1-oxaspiro-[2,5]octane derivatives ( 12 A and 12 B ) formed have been determined by ¹H-n.m.r. spectroscopy. Some earlier results from BOEKELHEIDE and SCHILLING and from SCHWARTZMAN and WOODS have been corrected.     

Synthese und Reaktionsverhalten von 2-Aryl-3-chlormaleinimiden

Synthesis and Reaction Behaviour of 2-Aryl-3-chloro-maleimides 2-Aryl-3-chloro-maleimides 2 are prepared by the chlorination of aryl-maleicanhydrides and aminolysis of the resulting 1-aryl-2-chloro-maleicanhydrides 1 . The imide 2a is reacted with N , S , O and C nucleophiles and inorganic salts to give 2, 3-disubstituted maleimides 3–6 , 9 , 10 , 12 , condensed heterocycles 7 and maleimide dimeres 8 , 13 , 14 .     

Thiation of new 5-(2-aryl-2-oxoethyl)-2,4-dioxo-1, 3-thiazolidines

Abstract

The hitherto unknown 5-(2-aryl-2-oxoethyl)-3-substituted-2,4-dioxo-1,3-thiazolidines 2 and 5-(2-aryl-2-oxoethylidene)-3-aryl-2,4-dioxo-1,3-thiazolidines 4 have been prepared from their 2-thioxo- homologues 1 and 3, respectively, via treatment with CrO₃. Compound 4 has also been obtained by treating 1 and/or 2 with bromine at different experimental conditions. Thiation of 2 and/or 4, gave a mixture of 3,5-di-substituted-2,3-dihydro-2-oxothieno[2,3-d]thiazoles 5 and the respective 2-thioxo derivatives 6. Reactions of hydrazine hydrate with 1c, d, were carried out at room temperature as well as under reflux, affording di-(3-oxo-6-aryl-4,5-dihydropyridazin)disulfides 7c, d and di-(3-oxo-6-arylpyridazin)disulfides 8c, d, respectively, together with 4-arylthiosemi carbazides 9c, d, under both conditions. Structures of the above products have been elucidated based on their microanalytical and spectroscopic data. Compound 2e exhibited pronounced antischistosomal activity.     

6,7-二氢-6-甲基-3-甲硫基吡喃[4,3-c]吡唑-4-(2H)-酮衍生物的合成及生物活性

6-甲基-5,6-二氢吡喃-2,4-二酮和二硫化碳、碘甲烷缩合得到5,6-二氢吡喃-2,4-二酮的二硫缩醛化合物,然后和取代肼反应得到1位取代和2位取代6,7-二氢-6-甲基-3-甲硫基吡喃[4,3-c]吡唑-4-(2H)-酮衍生物。其化学结构通过单晶X衍射、1HNMR、13CNMR、元素分析证实。生物活性测试结果初步表明,该类化合物表现出一定的杀菌和对前列腺癌细胞PC3的抑制活性。     

1-(2-三甲基硅氧乙基)-5-巯基四氮唑的合成研究

以乙醇胺为起始原料,经三甲基氯硅烷保护制得2-(三甲基硅氧基)乙胺,再经与二硫化碳反应,再与溴乙烷缩合得到N-(2-三甲基硅氧乙基)二硫代氨基甲酸乙酯、然后再与叠氮化钠成环反应合成了1-(2-三甲基硅氧乙基)-5-巯基四氮唑.用三甲基氯硅烷作为乙醇胺的羟基保护试剂,保护和脱保护具有反应条件温和、收率高等 优点,反应总收...     

Reactions with 2-thiazolin 5-ones. IV. Action of amines on 4-substituted 2-alkoxy- and 2-benzylmercapto-2-thiazolin-5-ones

Whereas treatment of 2-butyloxy-, 2-pentyloxy- and 2-β-phenylethyloxy-4-arylazo-2-thiazolin-5-ones 1d–h with strong basic amines results in their rearrangement into 1-aryl- Δ²-1,2,4-triazolin-5-one-3-carboxylic acid derivatives 2 , the 2-isobutyloxy, 2-(2-octyloxy)- and the 2-cyclohexyloxy-4-arylazo-2-thiazoline-5-ones 1i–n rearrange upon treatment with the same reagents into Δ²- 1,2,4-triazoline-5-thione-3-carboxylic acid derivatives 3 . On the other hand, 1d–h,1 react with aromatic amines to give 1-aryl-2-alkoxy-1,2,4-triazole-3-carboxylic acid anilides 4a–i , via the loss of hydrogen sulphide. The phenylhydrazides 4j–l are obtained upon treatment of 1g, h,l with phenylhadrazine. Treatment of 4-arylidene-2-benzylmercapto-2-thiazolin-5-ones 6a–c with ammonia results in the formation of the thiohydantoin derivatives 7e, g . However, 6b, c react with phenylhydrazine to yield the phenylhydrazides 8b, c . The reaction of 6a–e with piperidine or morpholine involves to molecules of the reagent to yield 10a–d which are thermally cyclised to the thiazolone derivatives 11a–d .     

Preparation and crystal structure determination of adducts of copper(II) chloride with 3-aryl-1-(imino-pyridin-2-yl-methyl)-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-pyrazoles

1,1,1-Trifluoro-4-methoxy-4-aryl-but-3-en-2-ones react with 2-pyridylcarboxamidrazone to produce the corresponding 1,1,1-trifluoro-4-aryl-4-(N¹-pyridine-2-carboxamidrazone)-3-buten-2-ones. The butenones react with copper(II) chloride to give 1:1 adducts, in which the donor molecules were shown to isomerize to their cyclic pyrazolic forms. The crystal structure of the 4-fluoro-phenyl derivative, dichloro-[3-(4-fluorophenyl)-1-(imino-pyridin-2-yl-methyl)-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-pyrazole]-copper(II), was solved by X-ray crystallography. The structural results are compared with those of other copper(II) chloride adducts of similar ligands containing the amidrazone pharmacophore, which have been tested as anticancer drugs.     

1,2,3-Triazabutadiene. XI. Untersuchungen zur iod-sensibilisierten Fotoisomerisierung von 1-Aryl-3-(3-methyl-benzthiazolin-2-yliden) triazenen

1,2,3-Triazabutadienes. XI. Investigation of the Iodine-induced Photoisomerization of 1-Aryl-3-(3-methyl-benzthiazolin-2-yliden) triazenes cis-1-Aryl-3-(3-methyl-benzthiazolin-2-yliden)triazenes isomerize induced photo-chemically by iodine to the trans-isomer. The wavelength of the used irradiation light was 546 nm so that only I₂ absorb. The dependence of the quantum yields on the concentration of the cis-isomer and on the intensity of the irradiation light was investigated. The influence of the light intensity on the quantum yields shows, that the primary step is the dissoziation of I₂-molecules to I·- radicals, which induce the isomerization.     

r-5-(α-Halogenbenzyl)-3, t-4-diaryl-c-4-hydroxy-oxazolidin-2-one als Ringtautomere von α-(Arylaminocarbonyloxy)-β-halogen-dihydrochalkonen

r-5-(α-Halogenobenzyl)-3, t-4-diaryl-c-4-hydroxy-oxazolidin-2-ones as Ring Tautomers of α-(N-Arylaminocarbonyloxy)-β-halogeno-dihydrochalcones The reaction of chalcone halogenohydrins ( 1–3 ) with arylisocyanates does not stop at the stage of the α-arylaminocarbonyloxy-β-halogeno-dihydrochalcones ( 7 ), but the cyclic urethanes 4–6 are formed. Compound 7h was synthesized independently. The structure and stereochemistry of 4–6 and 7h were determined by ¹³C n.m.r. spectroscopy.