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.     

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.     

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 .     

Organophosphorus chemistry. 16. The Reaction of Furfurylidenemalonitrile with Alkyl Phosphites

Dialkyl phosphites ( 2a – c ) react with furfurylidenemalonitrile ( 1 ) to give the corresponding 1:1 phosphonate adducts 3a – c . On the other hand, trialkyl phosphites ( 6a , b ) affected C -alkylation of the exocyclic ethylenic linkage in compound ( 1 ) to give the respective phosphonate 7a , b .     

Reactions with 5,6-Diphenyl-2,3-dihydro-imidazo[2,1-b]thiazol-3-ones and 6,7-Diphenyl-2,3-dihydro-4H-imidazo[2,1-b]1,3-thiazin-4-one

2-Methyl-5,6-diphenyl-2,3-dihydro-imidazo[2,1-b]thiazol-3-one 5 and 6,7-diphenyl-2,3-dihydro-4H-imidazo[2,1-b]1,3-thiazin-4-one 6 are prepared from 4,5-diphenyl-2-mercapto-imidazole 1 . Compounds 5 and 6 react with amines or hydrazines to give the 2-(4,5-diphenyl-imidazol-2-ylthio)acet(or propan) amides (hydrazides) 7a – g and the 3-(4,5-diphenyl-imidazol-2 ylthio) propanamides(hydrazides) 8a – e , respectively. The hydrazides 7a, 7b and 8a are condensed with aromatic aldehydes to the hydrazones 9a – h and 10a – d . Compound 5 couples with aryldiazonium salts to give 2-arylazo-2-methyl-5,6-diphenyl-2,3-dihydro-imidazo[2,1-b]thiazol-3-ones 11a – d .     

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 .     

Cyclisierungsreaktionen β,γ-ungesättigter Kohlensäurederivate. IX. Regiochemie der elektrophilen Cyclofunktionalisierung β,γ-ungesättigter Carbamidsäureester mit Brom – Synthese von Oxazolidin-2-onen und Tetrahydro-2H-1,3-oxazin-2-onen

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. IX. Regiochemistry of Electrophilic Cyclofunctionalization of β,γ-Unsaturated Carbamic Acid Esters with Bromine – Synthesis of Oxazolidine-2-ones and Tetrahydro-2H-1,3-oxazine-2-ones N,N-Disubstituted β,γ-unsaturated urethanes ( 1 ) and bromine react in methylene chloride at room temperature. The crotyl urethanes ( 1a – 1c and 1e ) and bromine give mixtures of corresponding saturated urethanes (dibromine adducts) ( 2a – 2c and 2e ), the oxazolidine-2-ones ( 3a – 3c and 3e ), and the tetrahydro-2H-1,3-oxazine-2-ones ( 4a – 4c and 4e ). The reaction of γ,γ-dimethylallyl urethanes ( 1f – 1h ) with bromine gives similar results. A useful synthetic route to N-substituted tetrahydro-2H-1,3-oxazine-2-ones ( 4l – 4q ) is demonstrated by the reaction of cinnamyl urethanes ( 1l – 1q ) with bromine.     

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 .     

Diastereo‐ and Enantioselective Synthesis of Chiral Pyrrolidine‐Fused Spirooxindoles via Organocatalytic [3+2] 1,3‐Dipolar Cycloaddition of Azomethine Ylides with Maleimides

In the presence of a Cinchona alkaloid‐based squaramide organocatalyst, the [3+2] cycloaddition of isatin‐derived azomethine ylides with maleimides proceeded readily, thus delivering the desired pyrrolidine‐fused spirooxindoles in 61–89% yields with >20:1 dr and 12 to >99 % ee. The absolute configuration of 5‐chloro‐1,5′‐dimethyl‐3′‐phenyl‐3′,3a′‐dihydro‐2′H‐spiro[indoline‐3,1′‐pyrrolo[3,4‐c]pyrrole]‐2,4′,6′(5′H,6a′H)‐trione was unambiguously determined by means of X‐ray single crystal structure analysis. The reaction mechanism was hypothesized to account for the enantioselective formation of 5‐chloro‐1,5′‐dimethyl‐3′‐phenyl‐3′,3a′‐dihydro‐2′H‐spiro[indoline‐3,1′‐pyrrolo[3,4‐c]pyrrole]‐2,4′,6′(5′H,6a′H)‐trione.

     

Vergleichende Untersuchungen zur Arylaminierung von Benzofuroxan-Derivaten

Comparative Studies on Arylamination of Benzofuroxan Derivatives The amination of benzofuroxan 2a and monosubstituted benzofuroxans 2b – e with alkali metal salts of formanilides 1 and sodium acetanilides 6 is described. Thus, the reaction of 2a with 6a – d gives the benzotriazole 1-oxides 3a – d . The benzofuroxans 2b and 2c react with sodium formanilides to give the isomeric mixtures 3f / 3g and 3h / 3i . Potassium 4-nitroformanilide reduces 2a furnishing benzofurazan 7 . Nitrobubstituted benzofuroxans such as 2d and 2e undergo a carbocyclic amination leading to the benzofurazans 8 and 9 .     

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.     

Some reactions with 3-Methyl-1H-naphtho[2,1-b]pyran-1-one

3-Methyl-1H-naphtho[2,1-b]pyran-1-one 1 has been shown to react with various aldehydes to give the styryl derivatives 2 . Reaction of 1 with P₂S₅ gave the thio-derivative 3 which reacted with aldehydes giving the thiostyryl-derivatives 4 . Hydroxylamine reacted with 1 giving the isoxazole derivative 5 . Hydrazine reacted with 2 giving the pyrazole derivative 6 . Compounds 2 have been shown to undergo DIELS -ALDER reaction to give the adducts 7, 8 and 9 . When 1 was allowed to react with different dicarboxylic acid anhydrides, the phthalide derivatives 10 were obtained, which on reaction with phenol, gave the dihydroxyphthalophenones 11 .     

Darstellung und Charakterisierung N-Disubstituierter 2-Amino-4-chlor-thiazol-5-aldehyde und ihrer Dicyanmethylen-Derivate

Preparation and Characterisation of N-Disubstituted 2-Amino-4-chloro-5-formyl-thiazoles and Their Dicyanmethylene Derivatives In contrast to N-disubstituted 3-hydroxy-anilines 5 which react with the Vilsmeier reagent to N-substituted 4-amino-salicylaldehydes 7 their heteroanalogous N-disubstituted 2-amino-4-hydroxy-thiazoles 6 react with the same reagent to N-substituted 2-amino-4-chloro-thiazole-5-aldehydes 12 via their corresponding iminium salts precursors 11 . Both types of compounds can be transformed, in analogy to other 2-amino-thiazole-5-aldehydes, by reaction with malodinitrile 13 into stable N-substituted 2-amino-4-chloro-5-(2,2-dicyano-ethenyl)-thiazoles 14 .     

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 und spektroskopische Eigenschaften chiraler 1,3-Oxazolidine

Synthesis and Spectroscopic Properties of Chiral 1,3-Oxazolidines (1S,2S)-2-Amino-1-(p-nitrophenyl)-propan-1,3-diol 2a and the (1R,2R)-configurated isomer 2b react with N-substituted dithiocarbimidic acid diesters and ketenedithioacetals, respectively, to give the 2-substituted chiral 4-hydroxymethyl-5-phenyl-1,3-oxazolidines 4 and 7 . N-Carbmethoxy-dithiocarbimidic acid dimethylester yields under the same conditions the isomeric 1,3-oxazolidine 5 . On treatment of 4 and 7 with isocynantes crystalline urethanes 9 are formed.     

Biologically polyactive compounds. Nitrovinylfurans,Dihydro-furo[2,3-b]benzo[e]dioxins,and hydroxyphenyl esters of 2-furoic acid of inhibiting properties towards bacteria,fungi, yeast,and aquatic snails

Tetrachloro- and tetrabromo-o-benzoquinone react with furfurylidene-( 2a ) and 5-chlorofurfurylidene- ( 2b ) nitromethane in boiling benzene to give the dihydrofurobenzodioxin adducts 3a – d , respectively, through a DIELS -ALDER type of reaction. In contrast, under similar conditions, tetrachloro-o-benzoquinone reacts with furfural and 5-chlorofurfural to give, in both cases, the ether 10 without incorporation of the furyl residue into the molecule. However, when the reaction is light catalysed, the polyhalohydroxyphenyl esters 11a and b are obtained. The thiophene analogue 11c is obtained in a similar manner. The reaction mechanism is discussed. The nitrovinylfurans, dihydrofurobenzodioxins and hydroxyphenyl esters showed well expressed growth inhibiting properties towards bacteria, fungi, and yeast. The activity of the products towards Biomphalaria boissi snails, the intermediate host of Schistosoma mansoni in Egypt, is discussed.     

On the Reaction of Nitrilium Salts with Heterocyclic Nitrones

Nitrilium hexachloroantimonates 1a – c react with pyridine N-oxides 2a , d , f , j , m , o to afford bicyclic 2,3-dihydropyridinium salts 5a – p . The constitution of 5f was secured by an X-ray crystallographic analysis. Compounds 5 proved to be thermally labile (23–82°C) rearranging to 2-acylamino- pyridinium salts 6a , f – i or decomposing to tars. The benzimidazole-3-oxide 7 reacts with nitrilium salts 1a , b to 2-acylaminobenzimidazoles 9a , b . The experimental results as well as AM1 calculations support a mechanism for the reaction of nitrilium cations with heterocyclic nitrones, which has originally been suggested by Abramovitch [25, 26].     

P/B Ketene Adduct Formation from Acyl Chlorides at a Vicinal Phosphane/Borane Frustrated Lewis Pair

The intramolecular frustrated phosphane/borane Lewis pair Mes₂PCH₂CH₂B(C₆F₅)₂ ( 3 ) reacts with acetyl chloride to give a 1 : 1 mixture of the FLP-ketene adduct, 6a , and the FLP-HCl addition product, 7 . Similarly, the acyl chlorides phenylacetyl chloride and isobutyryl chloride react with 3 to give the respective substituted FLP ketene adducts, 6b and 6c , with HCl elimination. A series of aroyl chlorides reacts with 3 by formation of the respective aroyl-phosphonium/chloroborate zwitterions, 11a – d . The hetero-aromatic furoyl chloride reacts with 3 in a more complicated, but mechanistically probably closely related pathway, to form the 2 : 1 reaction product, 14 . Most of the products were characterized by X-ray diffraction.     

Pyryliumverbindungen. 42. Benzocycloalkenone und Dihydro-2H,7H-1-benzopyranone aus 2,4,6-Triaryl-pyryliumsalzen und Cycloalkan-1,2-dionen

Pyrylium Compounds. 42. Benzocycloalkenones and Dihydro-2H,7H-1-benzopyranones from 2,4,6-Triarylpyrylium Salts and Cycloalkane-1,2-diones 2,4,6-Triarylpyrylium salts 1 react with cycloalkane-1,2-diones 2 in the presence of an appropriate condensing agent to yield benzocycloalkenones 3 . Thus, sodium acetate and cyclo-hexane-1,2-dione ( 2a ) lead to the dihydro-2H-naphthalenones 3a – i , whereas with cycloheptane-1,2-dione ( 2b ) and piperidine acetate, triethylamine or sodium acetate the tetrahydro-5H-benzo-cyclohepten-5-ones 3j – r are formed. As shown for the example 3a, j → 4a, b , benzocycloalkenones of type 3 can be converted into phthalazines 4 on heating with hydrazine in ethanol. By reaction of the dione 2a and an equimolar mixture of triethylamine and acetic acid or morpholine acetate with the salts 1 5,6-dihydro-2H,7H-1-benzopyran-8-ones 5 are obtained as a result of a new type of ring transformation. The pyrans 5 can be cleaved with perchloric acid in ethanol to 5,6,7,8-tetrahydro-8-oxo-1-benzopyrylium perchlorates 6 . If the pyrans 5 are heated with sodium acetate in ethanol, a conversion to benzocycloalkenones 3 is achieved (cf. 5a → 3a ). The structure of the new compounds was established by spectroscopic methods.     

Synthese von Benzo[b]thioxanthenen

Synthesis of Benzo[b]thioxanthenes Benzo[b]thioxanthenes, heterocyclic compounds related to tetracenes and tetracyclines can be obtained by the reaction of 2H-benzo[b]thiete ( 1 ) and 1,4-naphthoquinones ( 3a–g ). The primary cycloadducts 4a–g undergo an autoxidation process leading to the quinones 6a–g . The dihydroxy compound 4e shows an additional isomerization by a tetrafold H transfer ( 4e → 5e ′). Another preparative route to benzo[b]thioxanthenes makes use of the cycloadditon reaction of 1 and 1,4-epoxynaphthalenes ( 7a–d ). The primary adducts can be transformed to the title compounds by catalytic dehydration processes ( 8a–d → 9a-d ). An alternate regioselective opening of the oxygen bridge can be performed by the action of trimethyliodosilane ( 8a → 10a ). Methylation of 9a furnishes the sulfonium salt 14a which rearranges in a strongly alkaline medium to 16a ; in the presence of oxygen ketone 17a is generated.