Synthesis of derivatives of indole and quinoline by the intramolecular catalytic cyclization of allylanilines

An effective method for the isolation of 3-methyl-2-ethylindole and 2,4-dimethyl-quinoline by the intramolecular cyclization of N-(1-methyl-2-butenyl)- and 2-(1-methyl-2-butenyl)anilines under the action of the catalyst PdCl₂ (DMSO)_n was developed. The influence of the nature of the solvent, the temperature, and the concentration of the catalyst on the yield and the ratio of the reaction products was investigated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 325–327, March, 1986.     

Syntheses of substituted 2-(1-methyl-5-nitro-2-benzimidazolyl)quinolines

Reaction of N-methyl-2-amino-4-nitroaniline ( 1 ) with lactic acid afforded 2-(1-hydroxyethyl)-1-methyl-5-nitrobenzimidazole ( 2 ). Oxidation of compound 2 with chromic acid in acetic acid gave 2-acetyl-1-methyl-5-nitrobenzimidazole ( 3 ). Reaction of compound 3 with substituted 2-aminobenzaldehyde ( 4 ) under basic conditions yielded substituted 2-(1-methyl-5-nitro-2-benzimidazolyl)quinolines ( 5 ). Condensation and cyclization of o-aminoacetophenone (or substituted o-aminobenzophenones) with compound 3 under acetic condition afforded compound 7 . Condensation and cyclization of compound 1 with indole-3-carboxaldehyde ( 11 ) in ethanol in the presence of excess nitrobenzene gave 3-(1-methyl-5-nitro-2-benzimidazolyl)indole ( 12 ).     

4-Acetyl-1-(R-benzylidene)-3-(5-nitro-2-furfuryl)thiosemicarbazides — Carriers of synthones for obtaining thiazole and triazole rings

The corresponding thiosemicarbazonium salts, which form 4-acetyl- and 2,4-di-acetyl-1-benzylidene-3-(5-nitro-2-furfuryl)thiosemicarbazides with acetic anhydride, were obtained by the reaction of 5-nitrofurfuryl bromide with 1-benzyl-idenethiosemicarbazides. Under the influence of bases the monoacetylated derivatives undergo cyclization to the corresponding 2-benzylidenehydrazino-5-(5-nitro-2-furyl)thiazoles. Intramolecular cyclization of the monoacetylated products to 3-methyl-5-[(5-nitro-2-furfuryl)thio]-1,2,4-triazole, which is accompanied by the elimination of the corresponding benzaldehyde, occurs in the presence of hydrochloric acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 699–704, May, 1988.     

Fusion of 2-(furan-2-yl)thiazole to 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-benzimidazole

Methylation of 5(6)-nitro-1H-benzimidazole with methyl iodide in the presence of potassium hydroxide and N-methylpyrrolidin-2-one gave a mixture of isomeric 1-methyl-5-nitro- and 1-methyl-6-nitro-1H-benzimidazoles which were reduced with tin in concentrated aqueous HCl on heating. The resulting amines reacted with furan-2-carbonyl chloride in N-methylpyrrolidin-2-one to give furan-2-carboxamides which were treated with excess P₂S₅ in pyridine. Oxidation of isomeric furan-2-carbothioamides with K₃[Fe(CN)₆] in alkaline medium afforded a mixture of intramolecular cyclization products, 2-(furan-2-yl)-6-methyl-6H-imidazo[4,5-g][1,3]benzothiazole and 2-(furan-2-yl)-8-methyl-8H-imidazo[4,5-g][1,3]benzothiazole which were separated by column chromatography and identified.     

Short Syntheses of (±)-Grandisol and (±) Lineatin via,a common Intermediate

A 6-step synthesis of (±)-grandisol ( 1 ) is presented, which involves dichloroketene addition to 3-methyl-3-butenyl acetate ( 4 ), reductive dechlorination of the adduct 6 to the ketone 7 and saponification to 8 , aldolization of 7 or 8 with acetone and cyclization to the bicyclic ketone 9 , Wolff-kishner, reduction to 14 , and finally ring opening to 1. Since 9 is a known intermediate of the synthesis of (±)-lineatin ( 2 ), the latter can now be obtained in 6 steps.     

α-Oxides in reaction with N-H acids of the heterocyclic series

Anumber of 1-methyl-4-(2-hydroxyalkyl)-3-nitro-1,2,4-triazol-5-ones and their derivatives were obtained by reaction of 1-methyl-3-nitro1,2,4-triazol-5-one with -epoxides. The fact of intramolecular nucleophilic substitution of the nitro group in hydroxy derivatives of 3-nitro-1,2,4-triazol-5-one with cyclization to 2-methyl-3-oxo-5,6-dihydrooxazolo[3,2-b]-1,2,4-triazoline was established.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1407–1410, October, 1977.     

Eine Synthese methylierter Epoxyhydroazulenone durch intramolekulare [4 + 3]-Cycloaddition einer aus 1,1-Dichloro-6-(3-methylfur-2-yl)hexan-2-on erzeugten Oxyallyl-Zwischenstufe

A synthesis of Methylated Epoxyhydroazulenones by Intramolecular [4 + 3] Cycloaddition of an Oxyallyl Intermediate, Generated from 1,1-Dichloro-6-(3-methyl-2-furyl)hexan-2-one (Z)-3-Methylpent-2-en-4-yn-1-ol ( 7 ) was transformed to 2-(4-chlorobutyl)-3-methylfuran ( 4b ) and 2-(but-3-enyl)-3-methylfuran ( 10a ) by C-alkylation and 5-exo-dig cyclization. The Grignard derivative formed from 4b gave 1,1-dichloro-6-(3-methylfur-2-yl)hexan-2-onc ( 1b ) on reaction with dichloroacetyl chloride. This dichloromethyl ketone undergoes a base-induced cyclization to form diastereoisomeric 7-chloro-1,2,3,6,7,8a-hexahydro-4-methyl-8H-3a,6-epoxyazulen-8-ones ( 3bα and 3bβ ) by way of an intramolecular [4+3] cycloaddition of an oxyallyl intermediate 2b. By dechlorination and hydrogenation of 3bβ , the tricyclic hydroepoxyazulenones 18 and 19 have been synthesized.     

Rapid synthesis of new 2-methyl-7-nitro-5-substituted-2,3-dihydroimidazo[5,1-b]oxazole as potential antibacterial drugs through one-pot cyclization and Suzuki–Miyaura coupling

Original 2-methyl-7-nitro-5-substituted-2,3-dihydroimidazo[5,1-b]oxazoles were prepared by reacting 1-(2,5-dibromo-4-nitro-1H-imidazol-1-yl)propan-2-ol and various arylboronic acids through “one-pot” cyclization and Suzuki–Miyaura reactions under microwave irradiation.     

Syntheses of di- and tetrahydropyrroles

By the Michael's condensation of 3-methyl-1-nitro-1-butene with esters of α-acetoglutaric and acetosuccinic acids and of 2-methyl-1-nitropropene with acetylacetone we have synthesized the corresponding γ-nitrocarbonyl compounds, which have been converted by reductive cyclization into 3-ethoxycarbonyl-4-isopropyl-3-methoxycarbonylethyl-2-methyl-Δ¹-pyrroline, 3-ethoxycarbonyl-3-ethoxycarbonylmethyl-4-isopropyl-2-methyl-Δ¹-pyrroline, and 3-acetyl-2, 4, 4-trimethyl-Δ¹-pyrroline, respectively.     

Reactions of 1,2-Dimethyl-5-nitroimidazole,novel methods of conversion of the 2-Methyl group to a nitrile

1, 2-Dimethyl-5-nitroimidazole( 1 )and N,N-dimethylformamide dicyclohexylacetal gave the 2-(β-dimethylaminovinyl) analog 2 and with iodine and pyridine gave the 2-(1-pyridinium)methyl compound 3 . Benzoyl chloride-triethylamine and 1 led to benzoylation of the 2-methyl group to give ketone 9 as the enol benzoate. Nitrous acid or nitrosylsulfuric acid with 9 or its enol ester afforded the oximinoketone 10 which was cleaved with thionyl chloride to give 2-cyano-1-methyl-5-nitroimidazole ( 11 ) in high overall yield. 1-Ethyl-2-methylbenzimidazole ( 22 ) was converted to 2-cyano-1-ethylbenzimidazole ( 25 ) similarly. Reaction of 1 with ethyl oxalyl chloride and triethylamine afforded ethyl 1-methyl-5-nitro-2-imidazolepyruvate ( 19 ) as the enol oxalate. Nitrous acid and 19 gave the oximino pyruvate 20 which effervesced on mild heating to give 2-cyano-1-methyl-5-nitroimidazole ( 11 ). The preparation of 1-methyl-5-nitro-2-imidazoleacetonitrile ( 39 ) is reported.     

Condensed imidazo-1,2,4-azines. 4. Synthesis of 1,4-Dihydroimidazo[1,5-c]-1,2,4-triazine derivatives

The reaction of 2-methyl-4(5)-nitro- and 2-methyl-4(5)-nitro-5(4)-bromoimidazoles with -halo ketones was investigated, during which a number of 1-acylmethyl-substituted 2-methyl-4-nitro- and 2-methyl-4-nitro-5-bromoimidazoles were obtained. 1,4-Dihydro derivatives of imidazo[1,5-c]-1,2,4-triazine were synthesized by reaction of the latter with hydrazine and its monosubstituted derivatives. The structures of the 1-acylmethyl-substituted 2-methyl-4-nitro-5-bromoimidazoles and 1,4-dihydro derivatives of imidazo[1,5-c]-1,2,4-triazine were confirmed by their IR, PMR, and mass spectra.See [1–3] for Communications 1–3, respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 833–837, June, 1981.     

Synthesis of new thietanylpyrimidine and thietanylimidazole derivatives

New thietanyl-substituted derivatives of pyrimidine-2,4(1H,3H)-dione and imidazole were synthesized. The alkylation of 6-methylpyrimidine-2,4(1H,3H)-diones with 2-chloromethylthiirane in water involved the N¹ atom of the pyrimidine ring and afforded 6-methyl-1-(thietan-3-yl)-pyrimidine-2,4(1H,3H)-diones. Under analogous conditions 6-aminopyrimidine-2,4(1H,3H)-dione gave rise to 6-(thietan-3-ylamino)pyrimidine-2,4(1H,3H)-dione. Unsymmetrically substituted 2-methyl-4(5)-nitro- and 5(4)-bromo-2-methyl-4(5)-nitro-1H-imidazoles reacted with 2-chloromethylthiirane to produce mixtures of isomeric 2-methyl-4(5)-nitro-1-(thietan-3-yl)-1H-imidazoles and 5(4)-bromo-2-methyl-4(5)-nitro-1-(thietan-3-yl)-1H-imidazoles.     

Synthetic routes towards tetrazolium and triazolium dinitromethylides

Tetrazolium-5-dinitromethylide sodium salt has been prepared (91%) by cyclization of 1-amino-1-hydrazino-2,2-dinitroethene with nitrous acid in water. 5-Imino-1-(hydroxyiminonitromethyl) derivatives were obtained by nitration of 2-(5-amino-1,3-dimethyl-1H-1,2,4-triazol-4-ium-4-yl)- and 2-(5-amino-4-methyl-1H-tetrazolium-1-yl)acetate complex salts. Treatment of 4-methyl-1-(2-oxopropyl)-1-tetrazolium methylsulfate with nitric and sulfuric acid gave methyl (3-nitro-1,2,4-oxadiazol-5-yl)amine (27%) probably via dinitromethylide followed by cyclization and loss of nitrogen.__________Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 127–134, January, 2005.     

On the reaction of 3-nitro-1,2-phenylenediamine with ethyl acetoacetate. Condensed dihydrodiazepinones

Condensation of 3-nitro-1,2-phenylenediamine with ethyl acetoacetate in boiling xylene gave two isomeric 2,3-dihydro-4-methyl-9-nitro- and 2,5-dihydro-4-methyl-6-nitro-1H-1,5-benzodiazepin-2-ones, the 9-nitro derivative thermal rearrangement product N-isopropenyl-4-nitrobenzimidazolone and a non cyclic acetoacetamide derivative. At room temperature these reactants afforded 2,3-dihydro-2-ethoxycarbonyl-methyl-2-methyl-4-nitrobenzimidazole.     

Synthesis of new bicyclic compounds containing fused sulfolane and pyrazolidine rings

3-Aryl-6а-methyl-6-nitro-1-carbamoylhexahydrothieno[2,3-d]pyrazole-4,4-dioxides, novel original bicyclic species consisting of fused pyrazolidine and sulfolane rings, and 1,4-adducts were obtained by reacting 2-benzylidene-3-methyl-4-nitro-3-thiolene-1,1-dioxide and its derivatives with semicarbazide.     

Type I and type II photochemical reaction of ω-isobutyryl-ω-methyl-2,3-benzocycloalk-2-en-1-ones

ω-Isobutyryl-ω-methyl-2,3-benzocycloalk-2-en-l-ones. (6a-c) undergo both type I and type II photoreactions. The type I/type II product ratio depends on the ring size; the six-membered ketone 6a is subject to type II reaction and the eight-membered ketone 6c is subject to type I reaction predominantly. The cyclization/elimination ratio of the type II reaction of 6 also depends on the ring size; the ratio decreases with increasing ring size.     

Parallel solid-phase synthesis of 2-arylamino-6H-pyrano[2,3-f]benzimidazole-6-ones

The parallel solid-phase synthesis of a hydrophilic psoralen analogue, 2-arylamino-6H-pyrano[2,3-f]benzimidazole-6-ones (2-arylaminoimidazocoumarins), has been developed. The resin-bound 7-fluoro-4-methyl-6-nitro-2-oxo-2H-1-benzopyran-3-carboxylic acid underwent aromatic substitution with primary amines, followed by reduction of the nitro group with tin(II) chloride. The cyclization of the o-dianilino intermediates was accomplished with aryl isothiocyanates in the presence of 1,3-diisopropylcarbodiimide (DIC). The final products were released from the resin with trifluoroacetic acid (TFA) and obtained in high purity and good isolated yield. The 2-arylaminoimidazocoumarins exhibit interesting spectral properties.     

Convenient,DBU-promoted anti-Markovnikov hydration of 2-methyl-1-(3-arylprop-2-yn-1-yl)-1H-imidazoles in wet NMP

During attempts to involve 5-methyl-2-phenyl-1-(3-phenyl-prop-2-yn-1-yl)-1H-imidazole in a base-promoted, allene-mediated cyclization of the alkyne moiety onto the nearby aromatic ring, substantial amount of the ketone resulting from hydration of the alkyne with adventitious water was discovered. The formation of the ketone of the anti-Markovnikov alkyne hydration was developed into a preparative method. This method, alternative to the common acid-and metal-catalyzed approaches, may be of particular utility when alkyne hydration needs to be performed in the presence of acid-labile groups.     

Reactions of 3-nitro-1,2,4-triazoles with alkylating agents. 6*. Alkylation of a neutral heterocycle by alcohols in acid media*

Reaction of 3-nitro-1,2,4-triazole and 5-methyl-3-nitro-1,2,4-triazole with secondary and tertiary alcohols in conc. H₂SO₄ takes place at the N(2) atom. Alkylation by 2-propanol occurs regioselectively to form the 1-isopropyl-3-nitro-and 1-isopropyl-3-methyl-5-nitro-1,2,4-triazoles. As a consequence of isomerization the alkylation using cyclohexyl or tert-butyl alcohols gives respectively a mixture of regioisomers substituted at atom N(1) (1-cyclohexyl-3-nitro-and 1-cyclohexyl-5-methyl-3-nitro-1,2,4-triazoles) and at atom N(2) (5-nitro-1-cyclohexyl-and 1-cyclohexyl-3-methyl-5-nitro-1,2,4-triazoles) and, in the second case, to 1-tert-butyl-3-nitro-1,2,4-triazole. * For Communication 5 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1680–1687, November, 2008.     

Total synthesis of (+)-brefeldin A

(+)-Brefeldin A was synthesized through an efficient route, which features (1) construction of the five-membered ring from a Crimmins aldol via tandem Li-I exchange and carbanion-mediated cyclization with concurrent removal of the chiral auxiliary, (2) introduction of the lower side chain (C10 to C16) via a Rh-catalyzed Michael addition of a vinyl boronic acid, (3) stereoselective reduction of the C7 ketone with SmI2, and (4) a 2-methyl-6-nitrobenzoic anhydride-mediated (Shiina) lactonization.