Synthesis of Some Benzoquinolines and Benzacridines

2-Arylidene-3,4-dihydro-1(2H)-naphthalenones 1 react with ethyl cyanoacetate in presence of ammonium acetate to give 4-aryl-7:8-benzo-3-cyano-1,2,3,4,5,6-hexahydro-2-oxoquinoline 2 , 4-aryl-7:8-benzo-3-cyano-2-oxo-1,2,5,6-tetrahydroquinoline 3 and an oily product 4 . Hydrolysis and decarboxylation of 4 gave β-aryl-β-(2-α-tetralonyl)propanoic acid 5 . Thermolysis of 4 gave 2 and 3 . Compounds 2 and 3 were also obtained by treatment of 1 with cyanoacetamide using piperidine as a catalyst. Condensation of 1 with diethyl malonate, cyclohexanone, and α-tetralone in presence of ammonium acetate afforded 4-aryl-7:8-benzo-1,2,3,4,5,6-hexahydro-2-oxoquinoline 8 , 9-aryl-3:4-benzo-1,2,6,7,8,10-hexahydroacridine 9 , and 9-aryl-3:4,5:6-dibenzo-1,2,7,8-tetrahydroacridine 10 , respectively.     

Action of Grignard Reagents on 6-Arylpyridazin-3(2H)-thiones

6-Arylpyridazin-3(2H)-thiones ( 1a—c ) react with Grignard reagents by 1,4-addition to give either 4-substituted 6-aryl-4,5-dihydropyridazin-3(2H)-thiones ( 2a—c ) or their dehydrogenated products, namely 4-substituted 6-arylpyridazin-3(2H)-thiones ( 3d—k ). The reaction of Grignard reagents with 6-aryl-4-methylpyridazin-3(2H)-thiones ( 3d—f ) proceeds also by 1,4-addition yielding 4,4-disubstituted 6-aryl-4,5-dihydropyridazin-3(2H)-thiones ( 5 ). Structural assignments are based on analytical and spectral data and also on the synthesis of authentic samples in some cases.     

Synthesen mit 1, 3-Dithietanen. XIII. Synthesen von kondensierten Heterocyclen aus substituierten 5-Thioxo-Δ3-pyrazolin-4-carbonsäureestern

Syntheses with 1, 3-Dithietanes. XIII. Syntheses of Condensed Heterocycles from 5-Thioxo-3-pyrazoline-4-carboxylates 3-Amino-2-aroyl-5-thioxo-3-pyrazoline-4-carboxylates 1d – f react with bromoacetal-dehydediethylacetale, phenacyl bromides, ethyl bromopyruvate, ethyl α-chloro-acetate or chloro-acetylacetone to give ethyl dihydropyrazolo[5,1-b]thiazolecarboxylates 2 , 4 , 5 or 7 . The derivatives of ethyl tetrahydropyrazolo [5,1-b]thiazolecarboxylates 8 or 9 are obtained by reaction of 1d – f with ethyl β-anilino-α-chloro-crotonate and oxalylchloride, respectively. The ethyl methylthiopyrazoline-carboxylate 10d and an excess of hydrazine hydrate afford pyrazolo[3,4-c]pyrazole 11 . Compounds 10 react with phenyl isocyanate to give pyrazolo[3,4-d][1,3]oxazin-6-ones 13 . The dithietanes 12 and cinnamohydrazide yield pyrazolo[1,2-a]pyrazolecarboxylates 15 .     

Addition of arylureas to aroyl isothiocyanates and the synthesis of 1-aroyl-5-aryl-2-thiobiurets and 2-aryl-5-aroylamino-2,3-dihydro-1,2,4-thiadiazol-3-ones

The hitherto unknown 1-aroyl-5-aryl-2-thiobiurets ( 5a – h ) were synthesized by addition of mono arylureas ( 4 ) to aroyl isothiocyanates ( 3 ). Treatment of 1-aroyl-5-aryl-2-thiobiurets ( 5a – h ) with alkali gave 5-aryl-2-thiobiurets ( 6a – e ). Oxidation of 1-aroyl-5-aryl-2-thiobiurets ( 5d , f , h ) with hydrogen peroxide in the presence of hydrochloric acid or bromine in chloroform gave 2-aryl-5-aroylamino-2,3-dihydro-1,2,4-thiadiazol-3-ones ( 7a – c ).     

Furylvinylhalogenide. IX. Reaktionen von β-Fur-2-yl-β-chlor-α-cyanacrylsäureestern mit Aminen

Furylvinylhalides. IX. Reactions of β-fur-2-yl-β-chloro-α-cyanoacrylates with amines β-Fur-2-yl-β-chloro-α-cyanoacrylates 4 react with amines to yield β-Fur-2-yl-β-amino-α-cyanoacrylates 5 . The ¹H-n.m.r. spectra of 5 are discussed.     

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.     

Furylvinylhalogenide. X [1]. Reaktionen von β-Fur-2-yl-β-chlor-α-cyanacrylsäurederivaten mit Hydrazinen

Furylvinylhalides. X. Reactions of β-Fur-2-yl-β-chloro-α-cyanoacrylic Acid Derivatives with Hydrazines β-Fur-2-yl-β-chloro-α-cyanoacrylic acid derivatives 3 react with hydrazines yielding 3-fur-2-yl-5-aminopyrazoles 5 or 3-fur-2-yl-4-cyanpyrazolin-5-ones 6 . In some cases the β-hydrazino-α-cyanoacrylic acid derivatives 4 , could be isolated.     

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 .     

Microwave-assisted reactions of α-diazoketones with hetaryl and ferrocenyl thioketones*

Differently substituted hetaryl thioketones react with less reactive diazoketones under microwave (MW) irradiation in toluene solution. After only 2?min, the reactions were complete and, depending on the type of the used diazoketone, α,β-unsaturated ketones, acyl substituted thiiranes or 1,3-oxathioles were obtained as final products. In the case of azibenzil and di(thiophen-2-yl) thioketone, a new type of 1,5-dipolar electrocyclization of the intermediate thiocarbonyl ylide involving a thiophene ring led to a fused sulfur heterocycle. In contrast to hetaryl thioketones, the ferrocenyl analogues decompose under MW irradiation. Alternatively, they react with diazopropanone and 2-diazo-1-phenylethanone in boiling THF in the presence of LiClO₄ to give α,β-unsaturated ketones as sole products. In these cases, the reactions require long reaction times.     

微波促进碳酸钾催化一锅法合成2-氨基-3氰基-4-芳基-4H-苯并色烯衍生物

微波辐射下,乙醇溶剂中K₂CO₃催化芳甲醛、丙二腈和α-萘酚（或β-萘酚）三组分一锅法快速合成了一系列2-氨基-3-氰基-4-芳基-4H-苯并[h]色烯或苯并[f]色烯衍生物。以苯甲醛、丙二氰与α-萘酚的反应为模板反应,通过单因素实验方案优化了反应的工艺条件。结果表明：反应物各10 mmol,催化剂K₂CO₃ 1 mmol,溶剂无水乙醇15 ml,采用微波功率500 W,80℃回流反应 5 min,2-氨基-3-氰基-4-苯基-4H-苯并[h]色烯（4a）的收率83.6%。在上述最佳条件下,利用取代苯甲醛代替苯甲醛,4H-苯并[h]色烯衍生物(4)产率为65.8%~89.4%。 利用β-萘酚代替α-萘酚,4H-苯并[f]色烯衍生物(6)产率为67.5%~82.9%,合成产物通过熔点和红外光谱表征其结构。     

The Photocycloaddition of Olefins to Unsaturated 3-Ketosteroids

Photoadditions of ethylene and of cyclopentene to Δ⁴ - and Δ^4,6-3-ketosteroids gave mixtures of cis -4α,5α and trans -4α. 5β adducts. In the case of cyclopentene and Δ^4,6-androstadiene-3-one-17β-ol propionate, only the trans adduct was observed. Cis -4β,5β adducts were obtained by base-catalyzed isomerization of the trans adducts. The ratio of cis:trans adducts varied considerably with solvent, temperature, and olefin concentration in steroid reactions but not in reactions with cyclohexenone. The different types of adducts exhibited markedly different ORD curves in agreement with the structures assigned. Carbonyl maxima of trans adducts appeared at shorter wavelengths than maxima of cis adducts in both infrared and ultraviolet spectra. The infrared shifts provide a convenient method for differentiating between cis and trans fused isomers.     

Action of grignard reagents on 6-(α-styryl)pyridazin-3(2H)-ones; synthesis of some 4-Substituted 6-(α-Styryl)-pyridazin-3(2H)-ones

6(α-Styryl)pyridazin-3(2H)-ones ( 1a – e ) reacted with phenylmagnesium bromide and/or methylmagnesium iodide to give the 1,4-addition products, 4-phenyl and/or 4-methyl-6-(α-styryl)pyridazin-3(2H)-ones ( 3a–e ). The structures assigned to the products are established by electronic and infrared spectroscopy and by synthesis of authentic samples in most cases.     

Azoic dyes derived from 1-aryl-5-methyl-3-hydroxypyrazoles

The potentialities for 1-aryl-5-methyl-3-hydroxypyrazoles as intermediates in the field of dyes have been analysed. Some azoic derivatives have been synthesized and both electronic spectra and tinctorial properties on various substrates (wool, nylon, polyester, plasticized PVC) examined. The effect of substituents on the position of the long wavelength absorption maxima is discussed in terms of Hammett σ constants and interesting relationships are obtained. For each application the most important technical properties are assessed and significant fastness to various agents is evaluated.Finally a comparison with properties of similar pyrazol-5-one derivatives is made.     

β-Fur-2-yl-α-halogenacrylonitrile. I. Darstellung von β-Fur-2-yl-ß-aminoacrylonitrilen und β-Fur-2-yl-α-aminoacrylonitrilen

β-Fur-2-yl-α-halogenacrylonitriles. I. Preparation of β-Fur-2-yl-ß-aminoacrylonitriles and β-Fur-2-yl-α-aminoacrylonitriles β-Fur-2-yl-α-halogenacrylonitriles 1 react with secondary amines to yield β-fur-2-yl-ß-aminonitriles 2 and β-fur-2-yl-α-aminoacrylonitriles 3 . The ¹ H-n.m.r. spectra of the E/Z isomers are discussed.     

Ringtransformationen heterocyclischer Verbindungen. XII. Neuartige Spiroindoline via Ringtransformation von 2,4,6-Triaryl-pyryliumsalzen mit 2-Methylen-indolinen

Ring Transformations of Heterocyclic Compounds. XII. Novel Spiroindolines via Ring Transformation of 2,4,6-Triarylpyrylium Salts with 2-Methyleneindolines 2,4,6-Triarylpyrylium salts 1 react with 2-methyleneindolines 2 or their salts 2 HX in the presence of triethylamine/acetic acid in ethanol by a 2,5-[C₄ + C₂] pyrylium ring transformation to give diastereomerically pure 6-aroyl-3,5-diaryl-spiro[cyclohexa-2,4-diene-1,2′-indolines] 3 , which represent a novel type of spiroindoline compounds. When the 1′-phenyl substituted spiroindolines 3 (RPh, R′H) are treated with p-toluenesulfonic acid in chloroform the 4,6-diaryl-2-[1-methyl-1-(2-phenylaminophenyl)methyl]benzophenones 4 are obtained as the result of an intramolecular amine elimination. Structural elucidation of the reaction products 3/4 is based on spectroscopic data and on an X-ray determination of the bis(4-bromophenyl) substituted spiroindoline 3i.     

7-羟基-4′-(β-D-吡喃葡萄糖苷基)葛根素的合成

先将葡萄糖经酰化和溴化反应制备α-溴代四乙酰葡萄糖;再与葛根素在丙酮溶液中碳酸钾作用下醚化得到7-羟基-4-′(2,3,4,6-四乙酰基-β-D-吡喃葡萄糖苷基)葛根素,收率61.4%(以葛根素计);最后,将其进一步在甲醇溶液中与碳酸钠作用得到目标产物7-羟基-4-′(β-D-吡喃葡萄糖苷基)葛根素,收率90.5%。中间体和产物结构经1HNMR、MS确证。7-羟基-4-′(β-D-吡喃葡萄糖苷基)葛根素的水溶性与葛根素相比,提高了14.2倍。     

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 .     

Pyryliumverbindungen. 36. Substituierte Benzoesäureester aus 2,4,6-Triaryl-pyryliumsalzen und α-Ketocarbonsäureestern

Pyrylium Compounds. 36. Substituted Benzoic Acid Esters from 2,4,6-Triarylpyrylium Salts and α-Ketocarboxylic Acid Esters 2,4,6-Triarylpyrylium salts 1 react with α-ketocarboxylic acid esters 2 in the presence of two equivalents of an appropriate condensing agent (e.g. dialkylamine salts of weak acids, triethylamine/acetic acid, or sodium acetate) to give 2-aroyl-3,5-diarylbenzoic acid esters 3 . However, using only one equivalent of the condensing agent, the formation of 3,5-diarylbenzoic acid esters 5 predominates. Alkaline saponification of the new esters 3 and 5 yields the corresponding substituted benzoic acids 4 and 6 , respectively. – I.r., u.v., n.m.r. and mass spectroscopic data of the novel products 3 – 6 are reported.     

Studies on 4-thiazolidinones. VIII. The role of substituents at position-3 on the mode of cleavage of 5-Arylmethylene-2,4-dioxothiazolidines

Hydrazine hydrate, morpholine and benzylamine react with 3-aryl-5-arylmethylene-2,4-dioxothiazolidines 1a – d to give mixtures of thiolopropenamides 2 , ethylideneamino-biuret 3 and/or 4-arylaminocarboxamides 4 in varying proportions. However, 3-benzyl-5-arylmethylene 2,4-dioxothiazolidines 1e – f afford mixtures of pyrazolinones 5 and 4-benzyl-hydrazinocarboxamide 6 upon treatment with hydrazine hydrate. The formation of these products is rationalized and discussed on the basis of the role of the substituent at the 3-position. Structures 2 – 6 have been established.     

New bile alcohols II: Synthesis and mass spectra of C26 bile alcohols

The synthesis of (23α-) and (23β-)24-nor-5β-cholestane-3α,7α,23,25-tetrols (VII-a and VII-b) and 24-nor-5β-cholestane-3α,7α,25,26-tetrol (VIII) is described. Dehydration of 24-nor-5β-cholestane-3α,7α,25-triol (II) (synthesized from methyl chenodeoxycholate via a Grignard reaction) with acetic anhydride and acetic acid yielded two unsaturated compounds. These were oxidized with osmium tetroxide to produce a mixture of 24-nor-5β-cholestane-3α,7α-diacetoxy-23ξ,25-diol (V) and 24-nor-5β-cholestane-3α,7α-diacetoxy-25,26-diol (VI). After separating these diols (V and VI) by column chromatography, each compound was hydrolyzed with KOH to give 24-nor-5β-cholestane-3α,7α,23ξ,25-tetrol (VII) and 24-nor-5β-cholestane-3α,7α,25,26-tetrol (VIII), respectively. Two isomers of the tetrol (VII) were separated using alumina column chromatography (VII-a and VII-b).