On the Synthesis and Reactions of Indole-2-carboxylic Acid Hydrazide

Summary.  Indole-2-carboxylic acid hydrazide was prepared and allowed to react with aromatic aldehydes in acidic medium to give the corresponding hydrazone derivatives in good yields. The hydrazones were cyclized to indolo[2,3-d]pyridazine derivatives by refluxing with acetyl chloride. The indole carbohydrazide was converted to 2-triazolylindoles which acted as starting materials for several indole derivatives. A number of new indole derivatives were also prepared and structurally confirmed. Received October 17, 2000. Accepted (revised) December 12, 2000     

The Glc Separation of Indole Amines and Indole Alcohols as Heptafluorobutyryl Derivatives

Abstract

Indole amines and indole alcohols were converted to heptafluoro-butyryl (HFB) derivatives by an acyl transfer reaction with heptafluoro-butyrylimidazole. The indole NH group as well as all amino and hydroxyl groups were acylated. The HFB derivatives have excellent gas chroma-tographic properties and can be used with either hydrogen flame or electron capture detection systems. Mass spectra of the HFB derivatives of biologic N, N-dialkyl indole amines are very characteristic; these compounds can be identified easily by GLC-MS methods.     

1,2,3,9a-Tetrahydro-9H-imidazo[1,2-a]indoles

When derivatives of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one or 1-carbamoylmethyl-2-methylene-2,3-dihydroindole are reacted with lithium aluminum hydride, derivatives of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indole are formed. Under the same conditions 1-(N-phenylcarbamoylmethyl)-2-methylene-2,3-dihydroindole is not cyclized to an imidazo[1,2-a]indole. WHen treated with proton acids imidazo[1,2-a]indoles are converted to 3H-indolium salts. Opening of the imidazolidine ring is also found when imidazo[1,2-a]indole is acylated with benzoyl chloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 227–230, February, 1987.     

Studies on the biological activity of gem-difluorinated 3,3-spirocyclic indole derivatives

The biological activities of a series of 3,3-spirocyclic indole derivatives containing CF₂, phosphine oxide,indole, and cyano functional groups were evaluated, and these derivatives were found to exhibit antiTMV, fungicidal, and insecticidal activities.     

Indole derivatives. 135. 5-[2-(4-Methoxyphenyl)ethenyl]indolines and indoles

5-[2-(4-Methoxyphenyl)ethenyl]indolines were obtained from 5-formyl-1-methyl- or 5-forrayl-1-benzylindolines by the Witting reaction with 4-methoxybenzylidenetriphenylphosphorane. Their dehydrogenation led to the formation of the corresponding compounds of the indole series. The corresponding hydroxy compounds were obtained by demethylation of the methoxyindole with boron tribromide and were converted into the acetoxy derivatives of indoline and indole.For communication 134, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 911–914, July, 1989.     

Transfer of functionalized carbon fragments via substituted 5, 10-methylentetetrahydrofolate models. : Approach to dihydroindole and indole alkaloids.

4-(2-N(1)-tosyl-N(3)-methyl-4-,4-dimethylimidazolidyl)-3-ketobutanoate reacts with tryptamine, in the presence of acetic acid, to give primary “carbon transfer” products, which can be conveniently converted to synthetically useful indole and dihydroindole derivatives.     

2-(三甲氧基苯基)色胺盐酸盐的合成

2,3,4-及3,4,5-三甲氧基苯乙酮苯腙在多聚磷酸存在下进行Fischer反应,可生成相应的吲哚(1_a,1_b),但2,4,6-三甲氧基苯乙酮苯腙必须用无水氯化锌催化环化才能得到相应的吲哚(1_c)。1_a、1_b、1_c经Vilsmier反应生成相应的吲哚-3-醛(2_a,2_b,2_c);经与硝基甲烷缩合得到相应的2-(三甲氧基苯基)-3-(2-硝基乙烯基)吲哚(3_a,3_b,3_c);3_a及3_b用LiAlH₄还原即可制备成相应的色胺盐酸盐(4_a和4_b),3_b还被制成苦味酸盐(4_b)。     

Synthesis of pyrrolo[3,2-b]indole derivatives

The reaction of N-acetylindoxyl hydrazone with ketones in alcohol gave N-acetylindoxyl alkylindenehydrazones, which were converted to pyrrolo[3,2-b]indole derivatives by treatment with glacial acetic acid. Pyrrolo[3,2-b]indole derivatives were also obtained in the reaction of N-acetylindoxyl hydrazone with ketones in glacial acetic acid. The structures of the synthesized products were confirmed by data from the IR, UV, PMR, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 201–205, February, 1982.     

1,6-Stannatropic strategy: effective generation and cyclization of 1,5-dipoles from o-stannylmethylated thioanilides or phenyl isothiocyanates

[reaction: see text] A new method for the generation of 1,5-dipoles from o-stannylmethylated thioanilides via 1,6-stannatropy under neutral conditions was developed. Cyclization of the 1,5-dipoles afforded indole derivatives effectively. The strategy has potential for application to the generation of alternative 1,5-dipoles from o-stannylmethylated aryl isothiocyanates leading to indole derivatives having a stannylthio group that was readily converted to other functional groups.     

An efficient synthesis of 4-(phenylsulfonyl)-4H-furo[3,4-b]indoles

The fused heterocycle 4-(phenylsulfonyl)-4H-furo[3,4-b]indole, which is an indole-2,3-quinodimethane synthetic analogue, is prepared in five steps from indole in 46% yield. A similar sequence is used to synthesize C-3 derivatives (3-methyl, 3-phenyl, and 3-heptyl). Thus, indole-3-carbaldehyde (1) is protected as the N-phenylsulfonyl derivative 2 and converted to the ethylene acetal 6. Lithiation at C-2 followed by treatment with an aldehyde affords the expected hydroxy acetals 7 and 8. Exposure to acid effects cyclization to the furoindoles 5 and 9. Furthermore, C-1 lithiation of furo[3,4-b]indole 9c followed by treatment with methyl iodide affords disubstituted furo[3,4-b]indole 10.     

The chemistry of homophthalic acid: a new synthetic strategy for construction of substituted isocoumarin and indole skeletons

Homophthalic acid was reacted with thionylchloride/DMF and chloroethylformate/NEt₃ in the presence and absence of NaN₃. In all cases completely different isocoumarin derivatives were obtained. These unusual isocoumarin derivatives were isolated and characterized and their formation mechanisms are discussed. The homophthalic acid monomethyl ester was converted into the corresponding isocyanate. Reaction of the isocyanate with different amines produced the urea derivatives. Base-supported condensation reactions of these products gave first an indolinone derivative, which underwent further intermolecular condensation to give substituted indole derivatives. However, when the condensation reaction was carried out in the presence of acetic anhydride, the intermolecular reactions were suppressed. This methodology opens up a new way of synthesizing of various five-membered ring substituted indole derivatives.     

Development of a novel synthetic method for ring construction using organometallic complexes and its application to the total syntheses of natural products

Organometallic complexes are useful tools in synthetic organic chemistry. We investigated a novel synthetic method for ring construction using organometallic complexes and synthesized natural products and biologically active substances using these methods. Metalacycles formed from an early transition metal and diene, enyne, and diyne are stable under the reaction conditions and they are easily converted into compounds with functional groups by the addition of various agents. We have developed a novel synthetic method of heterocycles from enyne and diene using Cp2ZrBu2. The total syntheses of (-)-dendrobine, (+/-)-mecembrane, and (+/-)-mecembrine were achieved using this procedure. To synthesize these natural products as a chiral form, a novel palladium-catalyzed asymmetric allylic amination was developed, and chiral 2-arylcyclohexenylamine derivatives were synthesized. From these compounds, the total syntheses of (-)-mesembrane, (-)-mesembrine, (+)-crinamine, (-)-haemanthidine, and (+)-pretazetine were achieved. By further development of this procedure, a chiral 2-siloxymethylcyclohexenylamine derivative could be synthesized and the novel synthesis of indole derivatives was developed from this compound. From this indole derivative, (-)-tsubifoline and (-)-strychnine were synthesized.     

A straightforward synthesis of indole and benzofuran derivatives

A new methodology for the synthesis of indole and benzofuran derivatives has been devised. The starting materials, ortho-substituted aryl diynes, have been easily converted into new unsaturated bis-indolyl and bis-benzofuran derivatives and into 2-ethynylindole and 2-ethynylbenzofuran. Both these products have been further elaborated into more complex unsaturated indole-benzofuran and bis-benzofuran derivatives.     

The Witkop-Winterfeldt oxidation converts tetrahydropyridoindoles into pyrroloquinolones and cinnolines by an unprecedented scaffold rearrangement

The Fischer indole reaction between phenylhydrazines and tosyl-4-piperidone furnishes tetrahydropyrido[4,3-b]indoles. In a Witkop-Winterfeldt-oxidation using ozone such indole derivatives are converted into medium-sized dicarbonyl ring systems, which cyclize to pyrroloquinolones. A detailed study of the reaction intermediates and the characterization of a cinnoline betaine side product formed by an unprecedented ring closure mechanism are reported.     

Enzymatic formation of indole-containing unnatural cyclic polyprenoids by bacterial squalene:hopene cyclase

[reaction: see text] Two indole-containing substrate analogues, in which a C20 isoprene unit is connected to indole (3-(geranylgeranyl)indole and 3-(farnesyldimethylallyl)indole), were synthesized and tested for enzymatic cyclization by squalene:hopene cyclase from Alicyclobacillus acidocaldarius. Interestingly, 3-(geranylgeranyl)indole was not a substrate for the bacterial squalene cyclase, while 3-(farnesyldimethylallyl)indole was efficiently converted to a 2:1 mixture of unnatural novel products.     

Investigation of the products of the reaction of epichlorohydrin with aromatic amines

The action of hydrogen halides on 7a,8-dihydro-7H-azirino[1,2-]benz[g]indole gives 2-halomethyl-2,3-dihydro-1H-benz[g]indoles and 3-halo-1,2,3,4-tetrahydrobenzo[h]quinolines, which were converted to the corresponding N-nitroso derivatives and then to the isonitroso derivatives. 2-(Benzoxymethyl)-2,3-dihydro-1H-benz[g]indole hydrohalides were obtained by heating 1-benzoyl-2-halomethyl-2,3-dihydro-1H-benz[g]indoles. The reaction of 3-halo-1,2,3,4-tetrahydrobenzo[h]quinolines with thionyl chloride at room temperature gives 3-halo-6-chloro-1,2,3,4-tetrahydrobenzo[h]quinolines, while refluxing with thionyl chloride gives 6-chlorobenzo[h]quinoline.See [1] for communication XVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 342–346, March, 1973.     

Recyclable graphite oxide catalyzed Friedel-Crafts addition of indoles to α,β-unsaturated ketones

The Friedel-Crafts addition of indoles to α,β-unsaturated ketones, and nitro styrenes was studied with graphite oxide as catalyst. Various indole derivatives were synthesized in good to excellent yields. The preparation of graphite oxide catalyst from simple and readily available starting materials makes this method more affordable. The heterogeneous graphite oxide can be easily recovered and recycled up to five cycles without loss of activity.     

New pyrylium derivatives in the indole series

Nitrogen-unsubstituted 2,3-dihydroindole and its homologs, as well as 1,2,3,4-tetrahydro-- carbolines, react with 2,6-dimethyl-4-methoxypyrylium perchlorates to give N-pyrylated derivatives of indole, which are converted to the corresponding pyridine bases by the action of ammonium salts and form 1-aminopyridinium derivatives with hydrazine hydrate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1531–1533, November, 1972.     

Preparation,lithiation and transformation of N-(benzotriazol-1-ylmethyl) heterocycles

Indole, carbazole, pyrrole, imidazole, benzimidazole, 2-methyl- and 2-phenylbenzimidazole, and 1, 2, 4-triazole have each been converted into their N-(benzotriazol-1-ylmethyl) derivatives. The pyrrole, indole, and carbazole adducts undergo smooth lithiation at the inter-ring methylene group and subsequent reaction there with electrophiles. For the imidazole, benzimidazole, and triazole systems, lithiations at other molecular positions competed.     

Synthesis of dihydrolysergol analogues

As a part of a search for novel biological active ergoline derivatives, the indole ring present in the ergoline skeleton (indole[4,3‐f,g]quinoline) was converted into different heterocyclic ring systems such as quinazoline 2 , benzofurane 3 and benzoxazole 4 . Due to the paramount importance of chirality to attain biological activity, natural dihydrolysergic acid 1 was chosen as starting material and a synthetic pathway conservative in term of chirality was followed.