Action of Grignard reagents on thiophthalic anhydride, 3-benzal-2-thiophthalide, 3-p-chloro- and 3-p-methoxybenzalphthalides

Thiophthalic anhydride 1 reacts with the GRIGNARD reagents 2a – e (1:1 mol.) to give the corresponding 3-aryl(alkyl)-3-hydroxy-2-thiophthalides 3a – e . The interaction of 1 with 2c and f (1:2 mol.) yields the corresponding 1,2-diaroylbenzene derivatives 4 . On the other hand, 1 reacts with 2b (1:2 and 1:3 mol.) to give 5 and 6 , respectively. When 3-benzal-2-thiophthalide 7a and 3-p-chlorobenzalphthalide 7b are allowed to react with the GRIGNARD reagents 2c – f , the corresponding indenone derivatives 8 are obtained. On the other hand, the reaction of 7a and b with 2b (1:2 mol.) yields 6 and 9 , respectively. 7a and p-methoxybenzalphthalide 7c react with 2b (1:1 mol.) to give 5 and 10 ( a and b ). The constitution of the products has been investigated by means of IR and UV spectra.     

Synthesis and some reactions of 1-(4.6-dimethoxybenzo-furanyl)- and 1-(4.6.7-trimethoxybenzofuranyl)butane-1.2.3-trione-2-arylhydrazones

Both 4.6-dimethoxy-( 1c ) and 4.6.7-trimethoxy-5-acetoacetylbenzofuran 1d are obtained from visnaginone ( 1a ) and khellinone methyl ethers 1b , respectively, by a CLAISEN condensation. The β-diketones 1c and 1d couple with aromatic diazonium compounds to form the hydrazones 2a – i . 1-(4.6-Dimethoxybenzofuranyl)- and 1-(4.6.7-trimethoxybenzofuranyl)butane-1.2.3-trione-2-arylhydrazones 2 a–i react with hydrazine hydrate in acetic acid to yield the corresponding pyrazole derivatives 3a–i or 4a–i . The monohydrazones 5a–b are isolated when 2e or 2i are treated with hydrazine hydrate in ethanol. The hydrazones are converted to the respective pyrazoles by the action of glacial acetic acid. Hydroxylamine hydrochloride reacts with 1.2.3-trione-2-arylhydrazones 2a, c, e, f and i to yield the corresponding isoxazole derivatives 6a–e or 7a–e . The 2-arylhydrazones 2a, c, d, e, h and i form the corresponding pyrazole derivatives 8a–f when treated with semicarbazide hydrochloride.     

Synthese von 6-(pyrid-4-yl)-substituierten Pyrido[: 3-d]pyrimidinen und 1,8-Naphthyridinen

Synthesis of 6-(4-pyridinyI)-substituted Pyrido[2,3-d]pyrimidines and 1,8-Naphthyridinms A series of new 6-(4-pyridinyl)-substituted pyrido-[2,3-d]pyrimidines 2 – 4 and 1,8-naphthyridines 6 , respectively, is described. Cyclisation of 2-amino-5-(4-pyridinyl)-pyridinm-3-carboxamide 1a with diethyl oxalate gives the pyrido-[2,3-d]pyrimidinm 2a . Alkylation of( 2a ) yields the 3-ethylaminoxyrido[2,3-d]pyrimidine derivative 2b . Saponification of 2a , b gives the corresponding carboxylic acids 3a , b , which are decarboxylated by heating above the melting point to give 4a , b . The 2-amino-5-(4-pyridinyl)-pyridinm carboxylic acid derivatives 1 b – e react with ethylmalonylchloridm and diethyl malonate to afford the 1,8-naphthyridines 6b – e . The 1-oxide 7 in a similar reaction gives 8 and the oxdiazole( 9 ) which is converted by ring transformation to the 1,8-naphthyridine 10 .     

Synthese und Reaktionen von N-Phthalimido-keten-S,S-acetalen

Synthesis and Reactions of N-Phthalimido-ketene-S,S-acetals N-substituted phthalimido derivatives 1a – f react in the presence of bases (NaH, t-BuONa) with carbon disulfide to the N-phthalimido-ketene-S,S-acetals 3 , 4 , 5 and 6 , respectively. 2-Amino-ketene-S,S-acetals 7a – c are formed by reaction of 3a , b or 5a with hydrazine hydrate. 3c produces with phenylhydrazine the pyrazole 8 , and with piperidine and pyrrolidine the E/Z mixture of the corresponding ketene-S, N-acetals 9a , b . 1c is transformed into 10a – c (E/Z-mixture)by treatment with phenylisothiocyanate under basic condition followed by alkylation.     

The Behaviour of Some 4-Hydroxy-1-thiocoumarins toward amines and phenylhydrazine

Acetylation of 4-hydroxy-1-thiocoumarin 1 b in the presence of phosphorus oxychloride yields the 3-acetyl derivative 2 , which condenses with aromatic aldehydes to give the corresponding 3-cinnamoyl derivatives 3 a – e , and yields 3-arylazo-4-hydroxy-1-thiocoumarins 4 a – d upon treatment with aromatic diazonium salts. Whereas treatment of 1 b with primary amines results in the formation of 4-substituted amino derivatives 5 a – c , 3-acetyl-4-hydroxy-1-thiocoumarin 2 reacts with the same reagents to yield the 3-α-alkyliminoethyl derivatives 7 a – c . Treatment of 1 b with phenylhydrazine affords the 4-phenylhydrazine derivative 5 d . On the other hand, 2 reacts with the same reagent to yield a mixture of the phenylhydrazone 9 and the pyrazolo-1-thiocoumarin 10 .     

Zur Umkupplung von 4-Arylazo-2-pyrazolin-5-onen mit p-Chinondiiminkationen

Recoupling of 4-Arylazo-2-pyrazoline-5-ones with p-Quinonediimine Cations 4-Arylazo-2-pyrazoline-5-ones ( 1a – j ) readily undergo coupling reaction with p-quinonediimine cations ( 2a , b ) to form azomethin dyes ( 3a , b ). The dependence of the rate constants k_K of the dye formation on the substituents of 1a – j as well as on the ionic strength show that the rate-determining step of the coupling reaction is the formation of the intermediate 4 in a bimolecular reaction between the carbanions of 1a – j and p-quinonediimine ( 2a , b ). It became evident that the benzenediazoniumion ( 5a – j ) is eliminated in the reaction of 4 to 3a , b . Under the coupling conditions used, substituted benzene is formed in the reduction reaction of 5a , b by the p-phenylendiamine ( 7a , b ) or by the leuco dye ( 6a , b ).     

Zur Synthese von 6-nitrosubstituierten 2H-Benzo[b]thiopyran-Derivaten aus 2-Mercapto-5-nitro-benzaldehyd

About the Synthesis of 6-nitro-substituted 2H-Benzo[b]thiopyran Derivatives Starting from 2-Mercapto-5-nitro-benzaldehyde Benzene derivatives useful as C₃S-building blocks for the synthesis of 2H-benzo[b]thiopyrans are not easily available. The synthesis starting with 2-chloro-benzaldehyde via 2-chloro-5-nitrobenzalde-hyde to 2-mercapto-5-nitro-benzaldehyde-tert-butylimin 1b and its cyclisation to 2H-benzo[b]thiopyrans ( 2a – h ) and ( 3a – d ) is described. By reaction with acceptor substituted alkenes, e.g. acroleine or ω-nitrostyrene respectively 2-chloro-propenes, e.g. substituted ß-chloroacroleines or 2-chloro-propene-1,3-dicarboxylates the compounds 2a – h and 3a – d are obtained. Vilsmeier's reaction of the diester 3d with DMF/POCl₃ yields the formyl compound 4 .     

Die Reaktion von E-ß-Nitro-styrolen mit Pyrazolidon-(3)-azomethiniminen – eine nicht-cisoide 1,3-dipolare Cycloaddition

The Reaction of E-ß-Nitro-styrenes with 3-Pyrazolidone-azomethinimines – a Non-cisoid 1,3-Dipolar Cycloaddition Normal flipping at both ring-N-atoms postulated, the thermal addition of E-β-nitro- 5a or E-(4-chloro-β-nitro)-styrene 5b to 3-pyrazolidone-azomethinimine-1,3-dipoles 4a or 4b formally can yield 8 isomeric pairs of enantiomers, 4 of which are “permitted”(cisoid) and 4 of which are “forbidden” according to the concerted [_π4_s + _π2_s]-mechanism. If the addition of 5 to 4 is regiospecific, 2 “permitted”(cisoid) ( 1 and 6 ) and 2 “forbidden”( 3 and 10 ) isomers are conceivable. From pure 5a and 4a we regiospecifically got 1ref,3trans-diphenyl-2cis-nitro- 6a (75%) and 1ref,3trans-diphenyl-2trans-nitro-5-oxo-perhydropyrazolo[1,2-a]pyrazol 10a (25%), from 5b and 4b the corresponding bis(4-chloro-phenyl)-isomers 6b and 10b . The sodium salts 8a, b , gained from 6a, b and 10a, b , are identical. With H⊕ (D⊕) in water (D₂O) 8a, b give 6a, b (2-deutero- 6a, b = 7 a, b ). The ¹H-n.m.r. spectra of 6a, b, 7a, b, 8a, b, 10a, b , and of the 2-amino-isomers 11a/12a , corresponding to 6a/10a , are discussed. For the first time products of a non-cisoid 1,3-dipolar cycloaddition ( 10a, b ) were isolated. In the discussion (E ⇌ Z)-isomerization of 5a , and conceivable mechanisms of isomerizations 6a → 10a are excluded. Theoretical consequences are suggested.     

Reactivity of the Methylene Group and cleavage of S-alkyl groups in 1-alkylmercapto-3(4H)-isoquinolone derivatives

Treatment of 2a-thiohomophthalimide 1a and 4-phenylthiohomophthalimide 1b with alkyl halides gave the products 2a – e . By further alkylation of 2a, d the corresponding ethers 3a – h were obtained. When 2a, c were treated with aryl diazonium chloride, the red azo compounds 4a – f were separated. Also 2a – c were found to react with aliphatic and aromatic aldehydes to give the bis-compounds 8a – c and 9a – f respectively. The S-alkyl group present in the aryl azo derivatives 4 was found to be cleaved by treating them independently with phenyl hydrazine, hydroxylamine and primary aromatic amines to give compounds 10, 11 and 12 respectively.     

Folgeprodukte halogenierter Aldehyde. XVII. Reaktionen des N-(1,2,2,2-Tetrachlorethyl)-trichloracetaldimins mit Alkoholen und Mercaptanen

Derivatives of Halogenated Aldehydes. XVII. Reactions of N-(1,2,2,2-Tetrachloroethyl)trichloroacetaldimine with Alcohols and Thioalcohols Reactions of N-(1,2,2,2-tetrachloroethyl)trichloroacetaldimine 1 with methanol lead to 1,2,2,2-tetrachloroethyl-(2,2,2-trichloro-1-methoxyethyl)amine 2a , N-(2,2,2-trichloro-1-methoxyethyl)trichloroacetaldimine 3a and bis-(2,2,2-trichloro-1-methoxyethyl)amine 5 . After the reaction of the aldimine 1 with ethanol or propanol only the N-(1-alkoxy-2,2,2,-trichloroethyl)trichloroacetaldimines 3b, c are isolated; with thioalcohols only the N-(1-alkylthio-2,2,2-trichloroethyl)-trichloroacetaldimines 4a–c are obtained. The aldimines 3a–c and 4b, c are decomposed on treatment with hydrochloric acid and an excess of an alcohol or thioalcohol to yield the amine hydrochlorides 6a–c, 7b, c , which are transformed into the amines 8a–c and 9b, c . From these amines the derivatives 10–15 are prepared.     

Nitriles in organic synthesis: The Reaction of Cinnamonitriles with cyclohexanone and acetylacetone

The reaction of 1 a , b with cyclohexanone afforded hexahydronaphthalene derivatives ( 3 a , b ). In contrast to the behaviour of 1 a , b , cyclohexanone reacts with 4a – c to yield the propenylidenecyclohexanone derivatives ( 5a – c ). The reaction of 1a with acetylacetone gives 4H-pyran 6 and a 1:2-adduct 8 a . On treatment of 8 a with sodium metal in the presence of dioxane, the pyrano [2, 3-b]pyridine ( 9a ) was obtained. When 1 b , c reacted with acetylacetone, the only isolable products were 8 b , c . Reaction of 4a with acetylacetone gives acyclic compound 10 . This on treatment with basic reagents, gives the pyran derivative ( 13 ).     

Synthese von 5-Hetaryl-1,3-dithiol-Derivaten durch Reaktion von Hetarylmethyl-dithiokohlensäurediestern mit Schwefelkohlenstoff

Synthesis of 5-Hetaryl-1,3-dithiole Derivatives by Reaction of Hetarylmethyl-dithiocarbonates with Carbon Disulfide (Pyrid-2-yl)- and (quinol-2-yl)-dithiocarbonates 4 and 7 cyclocondense with carbon disulfide to yield 4,5-disubstituted 1,3-dithiole-2-thiones 5 and 8a – d after alkylation reaction. 8 is transformed into the 2-oxo-derivatives 9 by reaction with mercuric acetate. A series of heterocyclic substituted dithiocarbonates 10a , 10b , 12a , 12b , and dithiocarbamates 12c – g , respectively, is synthesized by reactions of halomethylheterocycles with the corresponding salts of xanthates or dithiocarbamates.     

Heterocyclic synthesis with nitriles: Syntheses of some novel pyrazolo[1,5-a]pyrimidine and Pyrrolo[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine Derivatives

3,5-Diamino-4-phenacylpyrazoles 1a , b react with the cinnamonitriles 2a , b to afford the novel 7-phenacylpyrazolo[1,5-a]pyrimidine derivatives 4a – d , respectively. Compounds 4c , d undergo cyclization with trichloroacetonitrile to afford the novel tricyclic system pyrrolo-[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine derivatives 5e , f , respectively.     

Umsetzungen des Pentamethylcyclopentadienyl‐Halbsandwichkomplexes Cp*Ta(CO)4 mit Chlor,Brom und Iod

The reaction of Cp*Ta(CO)₄ ( 1 ) (Cp* = η⁵‐pentamethylcyclopentadienyl, η⁵‐C₅Me₅) with chlorine leads to Cp*TaCl₄ ( 2a ), whereas the corresponding reactions with bromine or iodine give the oxo‐bridged complexes [Cp*TaX₃]₂(μ‐O) (X = Br ( 3b ), I ( 3c )). The oxygen atom apparently stems from a carbonyl ligand. In the presence of air, the binuclear complexes 3a , b are converted into mononuclear Cp*Ta(O)X₂ ( 4b , c ). The X‐ray structural determination of [Cp*TaBr₃]₂(μ‐O) ( 3b ) confirms a linear Ta–O–Ta bridge with a Ta–O distance of 190,4(1) pm.     

Alkylaminomethylation and Chloromethylation of 2,3-Diphenyl Hydroxybenzofurans

The application of the Mannich reaction to 2,3-diphenyl-5-hydroxybenzofuran 1 a and 2,3-diphenyl-6-hydroxybenzofuran 2 a , which gives rise to the corresponding aminomethyl derivatives 1 b – i and 2 b – i is described. Chemical, analytical and spectroscopic results are in a accord with the assigned structures. Attempted chloromethylation of compounds 1 a and 2 a afforded only the methylene-bis-compounds 3 and 4 , respectively.     

Reactions with 2-thiazolin-5-ones. III. The behaviour of 4-Arylazo-2-alkoxy-2-thiazolin-5-ones toward amines and Grignard reagents

Treatment of 4-arylazo-2-alkoxy-2-thiazolin-5-ones 4a – f with glycine or phenylhydrazine effects their conversion into 1-aryl-5-alkoxy-1 H-1,2,4-triazole-3-carboxylic acid derivatives 5a – j , with the loss of hydrogen sulfide. On the other hand, the reaction of the 2-ethoxy ( 4a – c ) and the 2-isopropyloxy ( 4g – i ) derivatives with strong basic amines involves the loss of an alkyl mercaptan to yield the N-substituted amines 7d – j of 1-aryl-Δ²-1,2,4-triazolin-5-one-3-carboxylic acids. The 2-benzyloxy derivatives 4d – f react with the same reagents to give the N-substituted amides 2a – g of 1-aryl-Δ²-1,2,4-triazolin-5-thione-3-carboxylic acids, with the loss of benzyl alcohol. Hetero-ring opening of 4 , followed by recyclisation, occurs upon treatment with ethyl or phenyl magnesium halides to yield the triazolinethione derivatives 13 a – c .     

Reaction of nitrilimines with alkoxycarbonyl-hydrazines: Synthesis of 6-Acetyl-4-aryl-2-ethoxycarbonyl-1,2,3,4-tetrahydro-s-tetrazines

Nitrilimines 2 are found to react with alkoxycarbonylhydrazines 3 – 5 to afford the acyclic adducts 6 – 8. 6c is oxidized upon heating with charcoal in refluxing toluene to the corresponding formazan 9c . Compounds 8 cyclize upon heating with charcoal in refluxing toluene to the corresponding 6-acetyl-4-aryl-2-ethoxycarbonyl-1,2,3,4-tetrahydro-s-tetrazines ( 10 ) rather than to the expected corresponding tetrazinones 11 . NMR study of compounds 10 showed that these compounds exist in a tautomeric equilibrium.     

Synthesis of Diuloses by Chain Elongation of Aldonoyl Chlorides

2,3,4,5,6-Penta-O-acetyl-D -galactonic acid chloride ( 1a ) and D -gluconic acid chloride ( 1b ), respectively, react with alkyl acetoacetates and benzoylacetates 2 , respectively, to yield derivatives 3 of diuloses with an alkoxycarbonyl group in the branch. Decarboalkoxylation of these compounds gives 1,3-didesoxy-nono-2,4-diuloses 4a,b and 2-deoxy-octo-1,3-diuloses 4c , respectively. Compound 4a and diazomethane react to furnish the corresponding methyl enol ether 5a and 5b .     

Syntheses of 4-aroyl and 4-Disubstituted Hydroxymethyl-pyridazin-3(2H)-ones and Their 3-Mercapto Derivatives: Synthesis of 1,3-Dithiano[4,5-c]pyridazine as a New Ring System

A number of 4-aroylpyridazin-3(2H)-ones ( 2a – c ), 4-disubstituted hydroxymethyl-pyridazin-3(2H)-ones ( 3a – c ) and their thio derivatives ( 3d – f ) have been prepared from different Grignard reagents and 5,6-diphenyl-4-cyano( 1a ), 4-carbethoxy ( 1b )pyridazin-3(2H)-ones and 3-mercapto derivatives ( 1c and d ). The structures of the compounds prepared were inferred from their elemental analysis, spectral data and from the identity of some of them with authentic samples.     

Synthesis and characterisation of carboxylic acid and diphenylphosphine derivatives in the 1,3-diyne series: Spectral properties of polydiacetylene carboxylates

Symmetrically substituted 1,3-diynes containing hydroxyalkyl ( 1a-d ), bromoalkyl ( 1e-h ) (diphenylphosphinyl) ( 1i-k ) and carboxyalkyl ( 2a-d ) substituents have been prepared and characterised; the phosphine derivative ( 1k ) has been converted with alkyl iodides ( RI ; R = Me, Et) into bis(phosphonium) salts ( 1l and m ). During preparation of the diynedioic acid. ( 2a ), the non-centrosymmetrical diyne, HO₂CCH₂C?C—C?C(CH₂)₂OH ( 3 ), was also isolated. ⁶⁰Co γ-Irradiation of diacetylene monomers ( 2a – d ) and 10,12-tricosadiyn-1-oic acid gave the corresponding polydiacetylene derivatives ( 4a – d and 5 ), respectively. Rubidium salts of ( 4c ) and ( 4d ), a barium salt of ( 4c ), and a potassium salt of ( 5 ) were prepared and isolated; soluble potassium salts of the carboxylic acid polymers ( 4 ) were generated in aqueous solution. The effects of changes in pH on the UV/visible absorption spectra of aqueous solutions of selected carboxylic acid polydiacetylenes have been recorded, and are discussed.