The Synthesis Of Some Substituted 3 Indoles

Author : Roy Vernon Jardine
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (142 download)

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Download or read book The Synthesis of Some 3-indolyl Thioethers written by Roy Vernon Jardine and published by . This book was released on 1964 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Several possible synthetic sequences leading to the formation of 3-alkylthioindoles have been investigated. The Williamson ether synthesis involving reactions between either 3-haloindoles and salts of mercaptans in dimethylformamide, or indolyl mercaptide and aralkyl halides in tetrahydrofuran were generally unsuccessful. This was attributed, in the case of the haloindoles, to the unstable nature of the haloindole involved. Separate experiments showed for example, that under the general conditions employed, 3-bromoindole was almost quantitatively converted into indole. However, there was evidence that some 3 alkylthioindole had been formed but this could not be isolated from the mixture. In the second case, preferential reaction on the nitrogen atom, rather than on the sulphur atom of 3-indolyl mercaptides by benzyl iodide thwarted attempts to secure the expected thioindole. Although thioethers have been prepared by the reaction of Grignard reagents with sulfenyl halides, the reaction between indolyl magnesium bromide and ethyl sulfenyl chloride, proved to be very complex, affording a mixture containing not only the expected indolyl thioether, but also significant amounts of diindolyl sulphide and 3-ethylindole. Isolation of the 3-ethyl thioindole by distillation methods proved to be impractical due to much decomposition. Although G.L.C. appeared to effectively separate the products of the reaction this method also was impractical. Several experiments which aimed at the elucidation of the route by which these transformations occurred failed to provide satisfaction. Two routes to alkyl 3-indolyl thioethers were found to be useful. The first of these employed the well known Fischer indole synthesis to the cyclization of the phenylhydrazone of ethylthioacetaldehyde using boron trifluoride as catalyst. Difficulties encountered in the preparation of the required acetals from which the phenylhydrazones could be made, limited somewhat, the general applicability of this method. The second, and apparently more general method involved the synthesis and subsequent reduction of 1,2-dithiolo indole- 3(4H)-thione, followed by treatment with a suitably activated organic halide. The resulting indole dithiocarboxy esters could be hydrolysed readily to substituted 3-alkylthio-2-indole: arboxylic acids, which were easily decarboxylated to afford the required 3-alkylthioindoles, Finally, a spectrophotometric*method to determine the position of substitution of the pyrrole ring of the indole nucleus has been developed. It was shown that position of the signal for the C 2 proton in indole or 3-substituted indoles was strongly dependent upon the solvent employed for the spectral determination. On the other hand, the signal position for the proton was much less affected by the nature of the solvent used. The utility of this solvent effect on the chemical shift to distinquish between 2 and 2 substitution of the indole nucleus has been pointed out. Nuclear Magnetic Resonance bpectrometry.