Base-sensitive indoles

Indoles 371 are selectively acylated at the 3-position to give high yields of compounds 372 on treatment with a wide variety of acyl chlorides in dichloromethane in the presence of chloro(diethyl)aluminium or chloro(dimethyl)-aluminium. The reaction proceeds under mild conditions (at 0 °C or rt, mainly for 1.5 h) and is applicable to indoles bearing various functional groups (both acid and base sensitive indoles) without NH protection (Equation 84) <20000L1485>. 

The direct and selective 3-acylation of both acid- and base-sensitive indoles 6 can be efficiently achieved using acyl chlorides and alkyl aluminum chlorides without NH protection (Scheme 2.3). When acyl chlorides are used for the acylation of indoles, liberation of hydrogen chloride is unavoidable, and the reaction results in the production of tar materials mainly due to polymerization of indole. Alkylaluminum compounds are utilized to scavenge the acid in the acylation with acyl chlorides. The reaction proceeds cleanly to give 3-acylindoles 7 without any by-product formation. The use of triethylaluminum leads to lower yields, probably because a nucleophilic attack of the alkyl group to acyl chloride occurs competitively. As expected, the use of aluminum... 

Indoles, pyrroles and carbazoles themselves are suitable substrates for palladium-catalyzed amination. An initial study of this reaction using DPPF-ligated palladium as catalyst showed that these reactions occurred readily with electron-poor aryl halides. With unactivated aryl bromides, the reaction with pyrrole or indole resulted in good yield, but reaction times were long and the temperature was 120 °C. Thus, an improved catalyst system was necessary for reactions to occur in a more general fashion and with temperature- or base-sensitive substrates. 

In general the described method is advantageous based on the use of inexpensive readily available starting materials, mild conditions, as all steps can be run below zero and for its avoidance of either acidic or strong basic conditions enabling the elaboration of sensitive indole derivatives to elevated temperatures, acids or strong bases. 

Table 4 illustrates the use of the CAR technique to develop CL kinetic-based determinations for various analytes in different fields. As can be seen, the dynamic range, limit of detection, precision, and throughput (—80-100 samples/ h) are all quite good. All determinations are based on the use of the TCPO/ hydrogen peroxide system by exception, that for p-carboline alkaloids uses TCPO and DNPO. A comparison of the analytical figures of merit for these alkaloids reveals that DNPO results in better sensitivity and lower detection limits. However, it also leads to poorer precision as a result of its extremely fast reactions with the analytes. Finally, psychotropic indole derivatives with a chemical structure derived from tryptamines have also been determined, at very low concentrations, by CAR-CLS albeit following derivatization with dansyl chloride. 

Vaarman A, Kask A, Maeorg U. 2002. Novel and sensitive high-performance liquid chromatographic methods based on electrochemical coulometric assay detection for simultaneous determination of catecholamines, kynure-nine and indole derivatives of tryptophan. J Chrom B 769 145-153. 

Some indolylthiohydantoin derivatives that have aldose reductase inhibitory activity [75] were investigated electroanalytically by voltammetric determination. Based on this study, a simple, rapid, sensitive and validated voltammetric method was developed for the determination of the compounds that are readily oxidized at carbon-based electrodes. Oxidation of the indolic compounds occurs on the nitrogen atom in the indole ring of the molecule [162]. 

Recently, in seeking a colorimetric method more sensitive than the Elson-Morgan test (20y), Dische and Borenfreund88 have developed a technique needing only 5y of the amino sugar. The method is based on the deamination of the hexosamine to give the corresponding 2,5-anhydro-hexose with Walden inversion at C2. The anhydro derivatives yield stable characteristic colors when treated with indole in dilute hydrochloric acid, well suited to quantitative colorimetric estimation. 

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