Synthesis of 1-(2-ethyl-3-indolyl)-1-(3-pyridyl)ethylene and related ellipticine analogues

Indole, 2-methylindole, and 3-etliylindole have been condensed with acetyl- and propionylpyridine, respectively. When propionylpyridine was used as the reactant, the product always was a 1-(pyridyl)-1-indoly[propylene. Condensation of 2-substituted indoles with 3-acetylpyridine gave similar products, whereas a similar condensation with 4-acetylpyridine gave 1,2-bis(3-indolyl)-1-(4-pyridyl)ethanes (e.g. 7a ). Condensation of unsubstituted indole with 3-or 4-acetylpyridine respectively, gave 1,1-bis(3-indolyl)-1-(pyridyl)ethanes (e.g. 6c ).     

Ozonolysis of ortho-alkenylanilines

Ozonolysis of N-acyl-2-(1-methylbut-2-enyl)- and N-acyl-2-(cyclopent-2-enyl)anilines followed by treatment with NaBH₄ afforded the corresponding 2-(2-hydroxyethyl-1-methyl) and 2-(1,5-dihydroxypent-2-yl) derivatives. The reaction can be directed to indole derivatives by varying the nature of both the acyl group and reducing reagent.     

The oxidative coupling of indole with some phenolic compounds,naphthols and catechols

The oxidative coupling of indole with three naphthols, 2-naphthol, 2,3-dihydroxynaphthalene and 2,7-dihydroxynaphthalene gave 1,1-bis(3′-indolyl)-2(1H)naphthalenone, 1,1-bis(3′-indolyl)-3-hydroxy-2(1H)naphthalenone and 1,1-bis(3′-indolyl)-7-hydroxy-2(1H)naphthalenone, respectively. The coupling of indole with protocatechuic aldehyde gave bis-(3-indolyl)-(3′,4′-di-hydroxyphenyl)methane and that of indole with homocatechol gave 3-(2′-methyl-3′,4′-di-hydroxyphenyl)indole.     

About the synthesis of [1,2]diazepinoindole derivatives from ethyl 2-(1-methylindole)acetate, 2-indole and 3-indoleacetohydrazones

The Vilsmeier-Haack reaction with ethyl 2-(1-methylindole)acetate and N,N-Dimethylamides/phosphorus oxychloride gave (65–85%) of ethyl 2-(3-acyl-1-methylindole)acetates 2 , which when boiled with hydrazine yielded about 90% of 4,5-dihydro-6-methyl-4-oxo-3H[1,2]diazepino[5,6-b]indoles 3. The attempted cyclization of 2-(1-methylindole)acetohydrazones 6 with acyl (acetyl and benzoyl) chlorides/triethylamine, to [1,2]diazepino[5,6-b]indole derivatives was fruitless and the bis(acyl)hydrazones 9 were obtained. Several transformations of 9 are reported. Similarly, the attempted cyclization of 3-indoleacetohydrazones 14 with acetyl chloride/triethylamine to [1,2]diazepino[4,5-b]indole derivatives was also fruitless and the bis(acyl)hydrazones 16 were again obtained.     

Change of mechanism with a change of substituents for a Zincke reaction

The reaction between N-(2,4-dinitrophenyl)-4-(4-pyridyl)pyridinium chloride and 4-aminothiophenol led to an unexpected displacement of the 2,4-dinitrophenyl group, in contrast with the normal Zincke product formed with other nucleophilic 4-substituted anilines. Evidence for a SET process was obtained from EPR spectra of the reaction mixture.     

Synthesis and reactions of some 3-(2-haloacyl)indoles

The reaction between indole and N-(2-haloacyl)pyridinium salts has been studied. With dioxan as solvent 1-(2-haloacyl)indole (2) was generally the product at low temperatures and 3-(2-haloacyl)indole (1) at high temperatures, as illustrated by the following α-bromopropionylation: Product ratio (1c/2a), 20° (0·01), 40° (0·8) and 60° (8·5). The fact that the a-bromobutyrylation at 60° gave 3-{N-(2-bromobutyryl)-1,4-dihydro-4-pyridyl}indole (6) as the main product, and 3-(2-bromobutyryl)indole (1d) only as a minor product, shows that the 3-acylation is affected by steric hindrance.At high reaction temperature (> 60°) the yield of1 decreased, owing to the formation of 3-indacylpyridinium salts (4).     

Synthesis of a 1,3,4,5-tetrahydrobenzindole β-ketoester

Pd(OAc)₂-catalyzed decomposition of ethyl 2-diazo-4-(4-indolyl)-3-oxobutanoate leads to a tricyclic tetrahydrobenzindole compound formed by a formal C-H insertion reaction. This tricyclic indole rearranges to a novel and thermodynamically more stable naphthalene derivative. Treatment of N-tosyl-protected ethyl 2-diazo-4-(4-indolyl)-3-oxobutanoate with a base induces facile pyrazole formation.     

Acid-base transformations of quaternary salts of pyridylindoles

It was established that the reaction of alkali with 4-(3-indolyl)pyridinium salts gives stable anhydronium bases, which are readily alkylated at the indole nitrogen atom. The p^K _a values of the anhydro bases were determined by spectrometry. The spectral data and reactivities are compared with the results of calculation by the self-consistent-field (SCF) MO LCAO method.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1477–1481, November, 1978.     

Synthesis of pyridyloxadiazoles 1. Characterization and thermal rearrangement of an unexpected 1,2,4-oxadiazol-5(4H)one

The synthesis of pyridyloxadiazoles by the reaction of acid chlorides with 5-(2-pyrklyl)-tetrazole or 2-pyridineamidoxime was studied. Reaction of 2-pyridineamidoxime with N,N-dimethylcarbamyl chloride produced 3-(2-pyridyl)-4-N,N-dimethylaminocarbony 1-1,2,4-oxadi-azol-5(4H)one instead of the expected oxadiazole. The oxadiazolone underwent thermal rearrangement with expulsion of carbon dioxide to yield the desired 3-(2-pyridyl)-5-N,N-dimethylamino-1,2,4-oxadiazole.     

Die Acylierung von 5-Amino-1 H-1, 2, 4-triazolen. Eine 13C-NMR.-Studie

The Acylation of 5-Amino-1 H-1,2,4-triazoles. A ¹³C-NMR. Study The acylation of 3-substituted-5-amino-1 H-1,2,4-triazoles (1) with methyl chloroformate or dimethylcarbamoyl chloride yielded mainly 1-acyl-5-amino-1,2,4-triazoles ( 2 and 3 ). Acylation of 3-methyl-, 3-methoxy- and 3-methylthio-5-amino-1 H-1,2,4-triazole ( 1b , 1c and 1d ) with methyl chloroformate gave up to 10% of the 1-acyl-3-amino-1,2,4-triazoles. For the unsubstituted 5-amino-1,2,4-triazole (1a) , a (1:1)-mixture of the 3- and 5-isomers 2a and 4 was obtained in dioxane in the presence of triethylamine. No 4-acylated product was detected in contrast to earlier reports. The structures of the reaction products were determined with the aid of proton coupled ¹³C-NMR. spectra using the corresponding N-methyl-1,2,4-triazoles as reference compounds.     

Benzomorphan related compounds. XIV. Synthesis of 2-(2-pyrrolylmethyl)- and 2-(2-indolylmethyl)tetrahydropyridines and cyclization to pyrrolo[3,2-f]morphans

The synthesis of 2-{2-pyrrolylmethyl)- and 2-(2-indolylmethyl)tetrahydropyridines by condensation of 2-cyanopyridines with appropriate pyrrole or indole derivatives followed by ketone reduction, quaternization and sodium borohydride reduction are described. The acid-induced cyclization of 2-(2-pyrrolylmethyl)tetrahydropyridines affords 4,5,6,7,8,9-hexahydro-4,8-methanopyrrolo[2,3-d]azocine systems (pyrrolo[3,2-f]-morphans), although the method fails with N-benzyl substituted pyrroles. The acid treatment of 2-(2-indolylmethyl)tetrahydropyridines and of 2-indolyl tetrahydro-2-pyridyl ketones is not a suitable procedure for the preparation of indolo[3,2-f]morphans, because of the protonation of indole nucleus or carbonyl group, respectively.     

Reactions of Indole and Its Derivatives with Cotarnine. Rearrangement of 5-(1-Indolyl)-4-methoxy-6-methyl- 5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolines

A synthetic route to compounds of the indolyltetrahydroisoquinoline series was developed on the basis of the reaction of cotarnine with indole derivatives. Aminoalkylation of indole and its derivatives with cotarnine occurs regioselectively at the nitrogen atom of the indole fragment to give the corresponding 5-(1-indolyl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolines. The products were found to undergo rearrangement into isomeric 5-(3-indolyl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolines which constitute a new class of indolyltetrahydroisoquinoline systems.     

Naphth[1,2-d]oxazole intermediates in the preparation of 3-hydroxy-4-(1-alkyl-3-methyl-5-hydroxy-4-pyrazolyl)-azo-1-naphthalenesulfonamide dyes

Acylation of 4-amino-3-hydroxy-1-naphthalenesulfonic acid ( 3 ) with benzoyl chloride in pyridine gave pyridinium 3-hydroxy-4-(N-benzoylamino)-1-naphthalenesulfonate ( 12 ) which was converted by thionyl chloride followed by diethylamine into N,N-diethyl-2-phenylnaphth[1,2-d]oxazole-5-sulfonamide ( 14 ). The naphthoxazole moiety was hydrolyzed with potassium hydroxide and the resulting N,N-diethyl-4-amino-3-hydroxy-1-naphthalenesulfonamide ( 11 ) coupled with 1-alkyl-3-methyl-5-pyrazolones. The 2-phenylnaphth[1,2-d]oxazole intermediates and various by-products were investigated.     

Synthesis of some substituted pyridylsydnones

Synthesis of the I-oxide ( 2 ) of the photochromic N-(3-pyridyl) sydnone ( 1 ), of N-(5-bromo-3-pyridyl) sydnone ( 3 ), and the I-oxide ( 4 ) of 3 were undertaken in order to study the effect on photochromism exerted by substituents on the pyridine ring. Compounds 2 and 3 were prepared via the corresponding aminopyridines and N-pyridylglycines by the general procedure used earlier to prepare 1 . The required amines, 3-aminopyridine I-oxide and 3-amino-5-bromopyridine, were obtained by Hofmann rearrangement of the corresponding amides. An excellent preparation of 5-bromonicotinamide was developed involving bromination in thionyl chloride followed by reaction of the bromoacid chloride with ammonia in chloroform. Proof of structure for 2 and 3 was accomplished by acid hydrolysis to the corresponding hydrazines, which were isolated, respectively, as acetophenone 3-pyridylhydrazone I-oxide and as 5-bromo-3-pyridylhydrazine hydrochloride. These products were identical with samples prepared by reduction of the respective diazotized amines. Sydnone 4 eluded preparation by this general procedure. 3-Amino-5-bromopyridine I-oxide was prepared conveniently from 5-bromonicotinamide but attempts to prepare the corresponding glycine by catalytic hydrogenation of a mixture of the amine and butyl glyoxylate afforded, in acid solution, N-(3-pyridyl)glycine and, in neutral or alkaline solution, the I-oxide of N-(3-pyridyl)glycine. Both products resulted from the reductive cleavage of the bromine atom. Neither 2 nor 3 was photochromic.     

Research on photochemical and thermochemical reactions between indole and quinones in the absence of solvent

The solid state photochemical reaction of indole with 1,4-naphthoquinone yielded 5H-dinaphtho[2,3-a:-2′,3′-c]carbazole-6,11,12,17-tetrone ( 1 ) in addition to 2-(3-indolyl)-1,4-naphthoquinone ( 2 ) which was also the only product in the solution photoreaction. Solventless thermochemical reactions of indole with phenanthrenequinone in the presence or absence of zinc chloride gave 10-(1H-indol-3-yl)-9-phenanfhrenol ( 3 ) and 9,10-dihydro-9-(1H-indol-3-yl)-10-(3H-indol-3-ylidene)-9-phenanthrenol ( 4 ) or 10,10-di-1H-indol-3-yl-9(10H)-phenanthrenone ( 5 ), respectively. All of these products were only obtained in trace amount in corresponding solution reactions, and are different from the adduct 10-hydroxy-10-(1H-indol-3-yl)-9(10H)-phenanthrenone ( 6 ) obtained in the solution photoreaction. A possible mechanism for formation of 4 and 5 is described in terms of electron pair donor/acceptor complexation.     

A new method for the synthesis of [1,4]diazepino[6,5-b]indole derivatives

Reactions of 3-[(N-aryl-N-chloroacetyl)amino]-2-formylindoles with substituted anilines gave 1,4-diaryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indol-4-ium chlorides and those with 4-aminopyridine yielded 4-amino-1-(1-aryl-2-oxo-2,5-dihydro-1H-pyrido[3,2-b]indol-3-yl)pyridinium chlorides. Reduction of 1,2,3,6-tetrahydrodiazepinoindol-4-ium chlorides afforded the corresponding hexahydro derivatives. An alternative synthesis of 1-(4-nitrophenyl)-3-oxo-4-phenyl-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole from 3-[N-(4-nitrophenyl)amino]-2-[(phenylimino)methyl]indole was developed. The method involves the following sequence of transformations: reduction, chloroacetylation, and intramolecular alkylation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2193–2199, December, 2006.     

Pyridylethyl: A versatile protecting group. Part II. The protection of heterocyclic N-H groups

Pyrrole, indole, carbazole and imidazole have been protected as N-[2-(4-pyridyl)ethyl] derivatives. Deprotection occurred under mild conditions after quaternisation. 3-Bromoindole was prepared by bromin-ation of the protected parent indole.     

Reactions of indoles with ortho esters,N,N-dimethylformamide and N,N-dimethylacetamide dialkyl acetals

Indole and N-methylindole react with oxa stabilized carbocations generated in situ from orthoformates to yield tris(3-indolyl)methane. The unsymmetrical isomers, e.g. 2-(N-methyl-3-indolyl)di(N-methyl-3-indolyl)-methane ( 4 ), were not formed as established by an independent synthesis. N,N-Dimethylacetamide dimethyl-acetal reacted with 2-alkyl substituted indoles to produce 1,1-bis(3-indolyl)ethanes ( 3 ).     

A study of the Claisen—Eschenmoser reaction for hydroxymethylbenzofurans and-indoles

N,N-Dimethylacetamide dimethyl acetal reacted with 5(7)-substituted 2-(hydroxy-methyl)benzofurans to give N,N-dimethyl-2-(2-methylbenzofuran-3-yl)acetamides. Analogous reactions with 3-(hydroxymethyl)indole and 1-hydroxy-6-methyl-1,2,3,4-tetrahydro-carbazole afforded N,N-dimethyl-3-(3-indolyl)propionamide and N, N-dimethyl-2-(6-methyl-1,2,3,4-tetrahydrocarbazol-1-yl)acetamide, respectively. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 314–318, February, 2007.     

Methylpyridylbenzimidazoles. Part I. Mono,bis-quaternary salts and related polymethyne dyes

The reaction of 2-(4-methyl-2-pyridyl)benzimidazole with long chain alkyl halides led to N-alkylation at the imidazole ring. The bases obtained were selectively quaternized at the azine and azole nitrogen atoms. The pyridinium salts gave the corresponding polymethyne dyes. Spectral (nmr and uv) and surface properties are briefly discussed.