Indoles oxindole reaction with

Baeyer confirmed his results by the total synthesis of oxindole, isatin and indole. Nitration ofphenylacetic acid, isolation of the o-nitro isomer, and reduction of the latter followed by ring closure gave oxindole. Reaction with nitrous acid ( .e. potassium nitrate and sulfuric acid) gave isatin oxime, from which by reduction, dehydrogenation with iron(lll) chloride and final hydrolysis, isatin itself was obtained. 

The stable tautomer of indole-2-thiol is the thione, thiooxindole, and this compound and simple derivatives are conveniently prepared from the corresponding oxindoles by reaction with phosphorus pentasulfide (69CPB550). Like the pyrrole analogs, these compounds are quite oxygen sensitive. Spande has reviewed other aspects of the synthesis of sulfur-substituted indoles, including methods for the synthesis of compounds with carbocyclic sulfur substituents (79HC(25-3)199). 

Monoterpene Bases.—Yohimbine-Corynantheine (and Related Oxindoles)-Pier aline Group. It is well known that 3,4-dehydroyohimbane (35a) is reduced by zinc-acetic acid to a mixture of yohimbane (35c) and i/ -yohimbane (35d) however, when 10-methoxy-3,4-dehydroyohimbane (35b) was similarly treated, a 2,3,4,7-tetrahydro-derivative (17 % yield) was formed as well as the corresponding 10-methoxy-yohimbanes. It was shown that this did not arise by further reduction of either of the methoxy-yohimbanes and no explanation is yet available for this interesting difference. Reserpine, a 6-methoxyindole, underwent C(3)-N(4) bond fission on reaction with zinc-acetic acid, as did indoles with no ring A methoxy-group. Cleavage of the C(3)-N(4) bond with the formation of N(4)-cyano-C(3)-alkoxy- or hydroxy-seco-derivatives was observed when yohimbine, i/ -yohimbine, and methyl reserpate were subjected to von Braun degradation conditions in alcohol or aqueous solution. 

The conversion of 3-substituted indoles into their corresponding oxindoles can be brought about by reaction with dimethylsulfoxide in acid the scheme below shows a reasonable mechanism for the process - once again a small concentration of P-protonated indole is the key. In a comparable sequence using Swem conditions, MeaS" adds hrst to the indole P-position. Dimethyldioxirane converts N-methoxycarbonyl-indoles (or -oxindoles) into 3-hydroxy-oxindoles. ... 

The efficient conversion of 3-substituted indoles into their corresponding oxindoles can be brought about by reaction with dimethylsulfoxide in acid the scheme below shows a reasonable mechanism for the process. ... 

There are also excellent total syntheses of spirotryprostatins which do not apply intermolecular functionalisation of the indole 3-position with a C5 prenyl-type precursor and are, therefore, not discussed in detail. Carreira and co-workers started from 3-diazo-2-oxindole, which was used in a Rh(I)-catalysed cyclopropanation of 1,3-pentadiene. The resulting cyclopropane was subjected to Mgl2-catalysed ring expansion and added to an imine affording the spiro[5.5] partial structure [130, 131]. Overman and Rosen built up the indole system by intramolecular Heck reaction of a functionalised iodoaniline [132,133]. In a model study building up the indole system, Cacchi and co-workers synthesised 3-prenylindoles via Pd-catalysed cyclisation of orf/io-alkynyltrifluoroacetanilides with prenyl esters [134]. 

A variety of methods have been developed for the selective installation of chirality at oxindole C3 that involve transfer of functionality from indole C2. The Vedejs group has prepared a small collection of chiral DMAP (4-(lV,A-dimethylamino) pyridine) derivatives bearing conformationally restricted side chains that have been employed as nucleophilic catalysts to direct the transfer of indolyl C2 acetate or carboxylate groups to oxindole C3 with excellent enantiofacial selectivity [15]. As illustrated in Scheme 1, indolyl acetate 1 was converted to the chiral oxindole 3 (94%, 91% ee) using DMAP catalyst 2, while the opposite sense of enantioselec-tivity was observed when indolyl carboxylate 4 was treated with DMAP catalyst 5 to afford 6 as the major oxindole adduct (99%, 94% ee). In addition to probing modifications of the DMAP side chains, it was demonstrated that the overall rate of the reaction catalyzed by DMAP 2 was decreased when the indolyl acetate 1 contained a branched isopropyl substituent at C3 however, good enantioselectivity was observed with the branching substituent (82%, 94% ee). It was also... 

The iron-catalysed reaction of heteroarenes, including indoles, pyrroles, thiophene, and furan, with 3-methyl-2-quinonyl boronic acids allows the formation of alkylated products, such as (68), rather than the more usual alkenylated products. The unusual alkylation, at the 5-position, of oxindoles to give products such as (69) has been reported using the acid-catalysed reaction with benzylic alcohols in nitromethane. Silylation of indole, at the 3-position, to give (70) has been achieved using a cationic ruthenium(II) sulfide complex as a catalyst. A sulfur-stabilized silicon electrophile is formed resulting in a Wheland intermediate which is deprotonated by sulfur atom. ... 

Indole has been separated from carbazole and diphenylamine on silica gel, copper sulphate-impregnated silica gel, on alumina and on cellulose with aqueous and non-aqueous systems (212). The color reactions with six different spray reagents following two-dimensional separations on silica gel H have been studied (213) for a wide range of indoles and skatole on cellulose detected by its fluorescence with 2,4-dinitrophenylpyridinium chloride (213a). Indole and oxindole alkaloids have been separated in 10 neutral and 10 alkaline solvents (214). 

The conversion of indoles to oxindoles can be achieved in several ways. Reaction of indoles with a halogenaling agent such as NCS, NBS or pyridin-ium bromide perbromide in hydroxylic solvents leads to oxindoles[l]. The reaction proceeds by nucleophilic addition to a 3-haloindolenium intermediate. 

The oxidation of 3-substituted indole to oxindoles can also be done with a mixture of DMSO and cone, hydrochloric acid[6-9]. This reaction probably involves a mechanism similar to the halogenation with a protonated DMSO molecule serving as the electrophile[10]. 

Ha.logena.tlon, 3-Chloroindole can be obtained by chlorination with either hypochlorite ion or with sulfuryl chloride. In the former case the reaction proceeds through a 1-chloroindole intermediate (13). 3-Chloroindole [16863-96-0] is quite unstable to acidic aqueous solution, in which it is hydroly2ed to oxindole. 3-Bromoindole [1484-27-1] has been obtained from indole using pytidinium tribromide as the source of electrophilic bromine. Indole reacts with iodine to give 3-iodoindole [26340-47-6]. Both the 3-bromo and 3-iodo compounds are susceptible to hydrolysis in acid but are relatively stable in base. 

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