Indoles ring fission

Formation of a 1,2-disubstituted hydrazine by acid hydrolysis of an appropriately substituted pyrazolidine has been noted (67HC(22)l), but the most interesting ring fission of pyrazolidines involves the N(l)—N(2) bond of 1-phenylpyrazolidines (421). If, instead of phenylhydrazone, compound (421) is used in the Fischer indole synthesis, N- aminopropylin-doles are formed (73T4045). Scheme 39 shows the reaction with cyclohexanone. 

The mode of biosynthesis of none of these alkaloids is known but, in the case of the iboga group, some guesses have been made (39, 63, 64), all of which start from the amino acids, tryptophan and dihydroxy-phenylalanine, and involve a fission of the latter s aromatic ring. A more sophisticated approach (65), starting from precursors of the aromatic amino acids, namely shikimic and prephenic acids, is apparently not in agreement with recent work on other indole alkaloids (66). The genesis of most indole alkaloids appears to stem from tryptophan and three... 

In hdn of indole and quinoline and hdo of benzofuran N- and O-heterocyclics of the type occurring in petroleum residua, shale oils, and coal) over a sulphided Co-Mo/AI2O3 catalyst (617 K, 48 atm) ring hydrogenation preceded C-N or C-0 fission and was rate-determining. Selectivity to alkylcyclohexanes over alkylbenzenes was > 90%. 

Chlorophenol is also reactive and irradiation in water leads to its conversion into resorcinoP" or in methanol to yield 3-methoxyphenol in 94% yield. Photoamidation with N-methylacetamide of 3-chlorophenol is also efficient and resnlts in the formation of the phenol 241 in a yield of 77%. Intramolecnlar amidation arises on irradiation of 242 in basic methanol. This resnlts in the formation of the indole derivative 243 as well as the methoxylated prodnct 244. More complex halophenols such as 245 are also photochemically reactive, but this yields a complex mixture of products including a benzofuran. The formation of this must be similar to the cychzations described earlier and involves the attack of a radical, produced by the C—I bond fission, on the other ring . 3-Nitrophenol is converted on irradiation in aqueous solution into a variety of products such as nitrocatechols, nitroresorcinol and resorcinol itself... 

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 fission of the 2,3-bond in indole alkaloids, by means of formic acid and formamide, provides a route for the release of the d/e ring unit, and therefore a method for the interconversion of appropriate alkaloids. Thus, 2,3-seco-2,3-dihydroreserpine (127), prepared in this way from reserpine (126), reacts with trichloroethyl chloroformate to give mainly the urethane (128), reduction of which gives the d/e unit (129). Alkylation of (129) with tryptophyl bromide then gives 2,3-seco-2,3-dihydrodeserpidine (130), which one oxidation with mercuric acetate affords a low yield of deserpidine (131), together with a small amount of 3-wo-deserpidine (Scheme 19). "... 

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