微环境影响下的乙酰基香豆素与吲哚的固相光反应

本文研究了乙酰基香豆素及其衍生物与吲哚的混晶在微环境影响下的固相光反应，并用固体紫外光谱、固体荧光光谱和X-射线粉末衍射技术考察了混晶的特征。实验结果表明，3-乙酰基香豆素及其7-乙酰氧基、7-苯甲酰氧基、5,6-苯并和6-溴衍生物与吲哚的固相光反应分别得到1:2缩合产物1～5，而6-硝基衍生物与吲哚的固相光反应却得到开环脱羰加成产物6。通过IR、MS、^1H NMR和元素分析结果确定了这六个新产物的结构。固体光谱的测试结果表明，取代乙酰基香豆素与吲哚间混晶的形成，分子间存在相互作用，使分子所处的微环境条件发生了变化。     

The Reaction of Indole with Propiolic Acid

The reaction of indole with propiolic acid ia 1 : 1 mole ratio gave an adduct (I) of 2 : 1 addition with decarboxylation. The reaction of indole with propiolic acid methyl ester gave a 2 : 1 adduct (II). Hydrolysis of adduct II yield the corresponding carboxylic acid (IV). Decarboxylation of IV also gave I. The mechanism of title reaction were fully studied.     

Synthesis of novel 3‐ and 5‐substituted indole‐2‐carboxamides

The preparation of several novel 3,5‐substituted‐indole‐2‐carboxamides is described. A 5‐nitro‐indole‐2‐carboxylate was elaborated to the 3‐benzhydryl ester, N‐substituted ester, and carboxylic acid intermedi ates, followed by conversion to the amide and then reduction of the 5‐nitro group to the amine. Indole‐2‐carboxamides with 3‐benzyl and 3‐phenyl substituents were prepared in four steps from either a 3‐bromo indole ester using the Suzuki reaction or from a 3‐keto substituted indole ester. N‐Alkylation of ethyl indole‐2‐carboxylate, followed by amidation and catalytic addition of 9‐hydroxyxanthene gave a 3‐xanthyl‐indole‐2‐carboxamide analog and a spiropyrrolo indole as a side product.     

Studies of the formation of all-carbon quaternary centres, en route to lyngbyatoxin A. A comparison of phenyl and 7-substituted indole systems

Copper mediated allylic substitutions and conjugate additions to geranyl, cinnamyl and allylic indole compounds have been investigated with the aim of finding a method for the creation of the all-carbon quaternary centre present in the natural product lyngbyatoxin A. Reaction conditions have been found giving a 68% SN2' selectivity in the copper mediated addition of PhMgBr to geranyl chloride, as well as 99% and 95% SN2' selectivity in the copper catalysed addition of EtMgBr to cinnamyl chloride and acetate, respectively. When the optimised reaction conditions were applied to the corresponding allylic compounds containing a 7-substituted indole moiety, the regioselectivity was reversed giving only the SN2 product. The allylic indole-containing substrates were also found to be unproductive in Pd- or Mo-catalysed SN2'-type substitution reactions. In related studies, copper catalysed conjugate addition of EtMgBr to the tricyclic lactam 6-methyl-pyrrolo[3,2,1-ij]quinolin-4-one gave a maximum of 20% of the 1,4-addition product.     

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).     

Palladium-catalyzed benzylic-like nucleophilic substitution of benzofuran-, benzothiophene- and indole-based substrates by dimethyl malonate anion

The palladium-catalyzed benzylic-like nucleophilic substitution of acetates derived from benzofuran, benzothiophene and indole was investigated. The asymmetric substitution on racemic 1-(2-benzofuryl)ethyl acetate gave disappointing results, but the substitution product was obtained in 98% ee from (S)-1-(2-benzofuryl)ethyl acetate with overall retention of configuration.     

The Reaction of Indole Magnesium Bromide with Ketones I. The Reaction of Indole Magnesium Bromide with Cyclohexanone

Indole magnesium bromide, produced by reacting indole with n-butyl magnesium bromide in ether, was reacted with cyclohexanone at ice or room temperature to yield 1-(indol-I-yl)-cyclohexanol (I), which is unstable and may be decomposed easily into indole and cyclohexanone in acidic condition. Indole magnesium bromide reacted with cyclohexanone in refluxing benzene or in anisole at 80°C, to form two products, 1-(indol-3-yl)-cyclohexanol (II) and 1-(indol-3-yl)-cyclohexene (III). (II) could be converted to (III) by heating (II) in phosphoric acid. Reaction of III with maleic anhydride gave a Diels-Alder adduct (IV). Reaction of indole magnesium bromide with cyclohexanone in anisole at 130°C yielded (III) and a trimolecular condensation product of cyclohexanone (V).     

Stereoselective preparation of methylenecyclobutane-fused angular tetracyclic spiroindolines via photosensitized intramolecular [2+2] cycloaddition with allene

Irradiation of 3-(hexa-4,5-dienyl)indole derivatives in the presence of 3′,4′-dimethoxyacetophenone by a high-pressure mercury lamp through Pyrex glass gave the corresponding [2+2] cycloaddition products stereoselectively in high yields. The major product was a methylenecyclobutane-fused angular tetracyclic spiroindoline derivative produced by the [2+2] cycloaddition through a parallel orientation. The minor product was a hexahydromethanocarbazole derivative through a crossed orientation. Electron-withdrawing substituents, such as acyl or alkoxycarbonyl, on the indole nitrogen were suitable for this reaction.     

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.     

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 ).     

A strategy to avoid anomalous O‐alkylation of 4‐hydroxyindole by diethyl bromomalonate

Alkylation of 4‐hydroxyindole with diethyl bromomalonate under standard conditions (potassium carbonate‐acetone) gave the expected indolyloxymalonate ester 3 together with the anomalous indolyloxy‐2‐bro‐momalonate 4 . Depending on conditions, the ratio of the two products varied between 4:1 and 1:2. Protection of the indole nitrogen by a carbobenzyloxy group eliminated formation of the anomalous product.     

Platinum-catalyzed multistep reactions of indoles with alkynyl alcohols

PtCl2 effectively catalyzes the multistep reaction of N-methyl indole (1 a) with pent-3-yn-1-ol (2 a) in THF at room temperature for 2 h to give indole derivative 3 a, which contains a five-membered cyclic ether group at C3 in 93% yield. Under similar reaction conditions, various substituted N-methyl indoles 1 b-h and indole (1 i) reacted efficiently with 2 a to afford the corresponding indole derivatives 3 b-h and 3 i in 48-91 and 72% yields. The results showed that N-methyl indoles with electron-donating substituents were more reactive affording higher product yields than those with electron-withdrawing groups. Likewise, various substituted but-3-yn-1-ols 2 b-e and other longer chain alkynyl alcohols 2 f-i also underwent a cyclization-addition reaction with N-methyl indole (1 a) to provide the corresponding cyclization-addition products 3 j-m and 3 a, 3 j, and 3 n-o in good to excellent yields. The present platinum-catalyzed cyclization-addition reaction can be further extended into N-methyl pyrrole. Mechanistically, the catalytic reaction proceeds by an intramolecular hydroalkoxylation of alkynyl alcohol to afford cyclic enol ether followed by the addition of the C--H bond of indole to the unsaturated moiety of cyclic enol ether providing the final product. Experimental evidence to support this proposed mechanism is provided.     

Electrophilic substitution reaction of indole,part XXIV: Synthesis,characterization, and crystal structure of a novel heterocyclic compound

The reaction of indole with cyclohexanone in the presence of the Lewis acid, boron trifluoride diethyl etherate, resulted in the synthesis of a novel and interesting product ( 1 ) in addition to the bis(indolyl)methane system ( 2 ). The structure of this novel compound has been determined by NMR (¹H and ¹³C) and X‐ray crystal structure analysis. Compound 1 is a (1:2) addition reaction product of indole with cyclohexanone. The spiro six‐membered ring is in the classic chair conformation. An epoxide bridge at C‐4a/C‐10b and the two hydroxyl groups at C‐5a, C‐10a are all on the same side of the central five membered ring. J. Heterocyclic Chem., (2011).     

SOLID-STATE PHOTOCHEMISTRY OF INDOLES WITH NAPTHALENE AND PHENANTHRENE

Abstract— Solid-state irradiation of mixed crystals prepared by meltinga 1:3 molar mixture of indole and phenanthrene followed by resolidifying the melt gave an adduct 2a in 13.5% yield. An adduct 2b was obtained by irradiation of the mixed crystals of 3-methylindole and phenanthrene. Irradiation of the same mixtures of indoles and phenanthrene in solution gave no photoproduct. Irradiation of the mixed crystals of indole and naphthalene gave a similar photoadduct 3a, which was also formed in solution. The 1:1 mixed crystals of indole and phenanthrene and of indole and naphthalene were characterized by various spectroscopic methods. Among them powder X-ray diffraction spectral analysis and differential scanning calorimetry revealed that the former mixed crystal is a simple mixture of microcrystals of indole and phenanthrene, while the latter forms a molecular compound.     

Fischer indolization and its related compounds—VII : Development of abnormal fischer indolization of ortho-methoxyphenylhydrazone to provide a synthetic method for useful indole derivatives possessing an active methine group at C6 and novel 3,6′-biindole derivatives

Fischer indolization of ethyl pyruvate 2-methoxyphenylhydrazone (1) with p-toluene-sulfonic acid in benzene in the presence of an enolizable dicarbonyl or an indolic compound gave either an indole product having an active methine group at C₆ or a novel type of 3,6′-biindole compound. Structures of the products were established by NMR spectra and chemical evidence.     

Reactivity and regioselectivity in the synthesis of spiroindoles via indole o-quinodimethanes. An experimental and computational study

The 1,3-dipolar cycloaddition reactions of stable nitrile oxides with indole o-quinodimethanes have been examined. In all cases the ‘exo-anti’ addition products, dispiroisoxazolines, were isolated in moderate to good yields (25-47%). In addition, from the reaction of one of the indole quinodimethanes with mesitonitrile oxide the ‘exo-syn’ addition product was isolated in 7% yield along with the remarkable indole quinodimethane dimerization and cycloaddition product, which was isolated in 13% yield. An analogous dimerization and cycloaddition product was isolated in 18% yield from the reaction of the N-acetyl-indole quinodimethane with mesitonitrile oxide. In the case of the reaction of the N-benzoylindole quinodimethane with the 2,6-dichlorobenzonitrile oxide an oxime was also isolated in 13% yield. The proposed reaction mechanism is supported by semiempirical (AM1) MO calculations via FMO interactions. The observed selectivity was explained by an investigation of the transition states carried out also for analogous dispiroisoxazolines.     

A synthesis of potential new antiarrhythmic agents

N‐Ethylation of substituted ethyl 1H‐indole‐2‐carboxylates with iodoethane and potassium carbonate gave substituted ethyl 1‐ethyl‐1H‐indole‐2‐carboxylates. The later compounds on treatment with a range of aryl amines with varying structural complexity, gave the desired ethyl 1H‐indole‐2‐carboxamide analogues.     

In situ vinylindole synthesis. Diels-alder reactions with maleimides to give tetrahydrocarbazoles

Tetrahydrocarbazoles have been prepared in one-flask syntheses from indoles, ketones or aldehydes, and maleimides, with acid catalysis. The reactions involve a condensation of the indole with the ketone or aldehyde, followed by an in situ trapping of the vinylindole in a Diels-Alder addition with a maleimide. Isomerization of the double bond into the indole nucleus gave the tetrahydrocarbazoles which were isolated ( 6, 9 , and 10 ). Variation of the indole, carbonyl compound, and maleimide has been explored. The predominant stereochemistry of the tetrahydro ring in the products is all-cis, although a second stereoisomer has been isolated. Two regioisomers were generated from all unsymmetrical 2-alkanones, except 2-butanone, which gave the single isomer 9a . Aromatization of tetrahydrocarbazoles 6 to carbazoles 7 was accomplished with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.     

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.     

Synthesis of indolo[2,1-a]isoquinolines by CF3COOH-induced cyclization

Indolo[2,1-a]isoquinoline alkaloids and related compounds have been known to have interesting biological activities, such as antileukemic and antitumor activities. We found that 1-(3,4-dimethoxyphenethyl)indole gave 2,3-dimethoxyindolo[2,1-a]isoquinoline and 1-(3,4-dimethoxyphenylacetyl)indole gave 2,3-dimethoxy-6-oxoindolo[2,1-a]isoquinoline, respectively, by an intramolecular cyclization carried out in boiling trifluoroacetic acid.