Methyl 3-hydroxyindole-2-carboxylate

The products of the base-catalyzed Stobbe condensation of 3-formylindole and of 2-formylpyrroles undergo acid-catalyzed cyclization to yield l-hydroxycarbazole-3-carboxylic esters and 4-hydroxyindole-6-carboxylic esters, respectively (73JPR295, 74JPR386, 76JPR816). The analogous condensation of dimethyl homophthalate with 2-formyi-l-methylpyrrole and with 3-formylindole produces (443 Hetero= l-methyl-2-pyrrolyl, 3-indolyl), (444) and (445) under acidic conditions (76JHC83). 

The reactions of the methyl furo[2,3-6]pyrrole-5-carboxylate (153) or its 6-methyl derivative (154) with DMAD proceed via [4 -I- 2] cycloaddition at the a,a -positions of the furan ring, giving cycloadducts which by subsequent 1,5-sigmatropic rearrangement give trimethyl 5-hydroxyindole-2,6,7-tricarboxylate (155) or its 1-methyl derivative (156) <94UP 70i-0i>. 

As part of an examination of an oxidative coupling of methyl 6-hydroxyindole-2-carboxylate with primary amines which enabled the development of a facile preparation of 2-substituted methyl pyrrolo[2,3-e]benzoxazole-5-carboxylates, the reaction of this indole with 1,2-diaminoethane and excess Mn02 gave compound (83) in an apparent intramolecular interception of a transient intermediate o-quinone monoimine (Equation (46)) <88JOC5163>. 

In the Nenitzescu synthesis of 5-hydroxyindoles, an A-aryl substituted amino-propenoic ester may be used, albeit with a low yield of product [2343]. Better yields may be obtained by reacting the quinone at ambient temperature with an enaminonitrile [3246]. The methylthio group may be removed by heating with Raney nickel. Magnesium methyl carbonate is sometimes used to carboxylate a methyl ketone but when it is warmed with the methyl ketone (35.3), it causes cyclization of the keto side-chain [2747]. A dioxopyrimidine aldehyde (35.4) is cyclized in moderate yield by heating with carbonate in DMF [2668]. 

A hemiquinone intermediate rather than an o-quinone resulted from the oxidation of methyl 6-hydroxyindole-2-carboxylate in dimethoxyethane with activated manganese dioxide. By reaction with benzylamine in dimethoxyethane solution the intermediate formed methyl 2-phenylpyrrolo[2,3,e]-benzo-xazole-5-carboxylate in 61% yield (ref.61). 

Deprotonation of C-hydrogen in indoles requires the absence of the much more acidic A-hydrogen i.e. the presence of an A-substituent like methyl, or if required, a removable group phenylsulfonyl, lithium carboxylate, and t-butoxycarbonyl have been used widely, dialkylaminomethyl, trimethylsilylethoxymethyl, and methoxymethoxy have also been recommended clearly in the last case the A-substituent cannot be introduced into an indole - it requires a preformed 1-hydroxyindole - but it is possible to reduce it off to leave an A-hydrogen-indole. t-... 

The VNS reaction of 4-nitroanisole with ethyl chloroacetate followed by the Knoevenagel condensation of the product with acetaldehyde affords a-(2-nitrophenyl)crotonate, which in the presence of f-BuOK in ferf-butanol undergoes cyclization into V-hydroxyindole-3-carboxylate (Scheme 76). Further alkylation of the latter compound with methyl iodide results in Af-methoxyindole. It is worth mentioning that in this reaction a partial loss of the alkene chain does happen to occur [194]. A similar phenomenon has been observed earlier in our laboratory [195]. 

Nevertheless, there are several other oxidation (dehydrogenation) routes to indoles from indolines. In a series of papers, Somei and colleagues used sodium tungstate to synthesize A-hydroxyindole derivatives from the corresponding indolines (Scheme 11, equations 1 and 2) [64, 103-107]. The simple l-hydroxy-6-nitroindole [106] and 4-, 6-, and 7-ethoxy-l-methoxyindoles were synthesized in similar fashion [107]. Pedras and coworkers employed the Somei method to prepare the natural phytoalexin methyl l-methoxyindole-3-carboxylate [108], and McNab and... 

In addition to the reagents for detection which are quoted in Table 88, many others have been mentioned in the literature [89, 90, 104] for urine metabolites [78] for serotonine metabolites [14] for hydroxyindoles and -tryptophans [35] with comprehensive data for hydroxyskatoles [19] for the methyl esters of indole-carboxylic acids [i2, 23, 63] for glucobrassicin. 2,4-Dinitrophenylhydrazine (Rgt. No. 82) is suitable for the often feebly reactive indole-aldehydes. 

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