Carbolines anhydro-bases

Support for this suggestion comes from many quarters. Reduction of the jS-carboline anhydro-bases with sodium and alcohol or with tin and hydrochloric acid gives the 1,2,3,4-tetrahydro derivatives, as does catalytic reduction over platinum oxide in an alkaline medium. On the other hand, catalytic reduction with platinum oxide in acetic acid results in the formation of the 5,6,7,8-tetrahydro-j3-carbolinium derivatives (see Section III,A,2,a). It should be noted, however, that reduction of pyrido[l,2-6]indazole, in which the dipolar structure 211 is the main contributor to the resonance hybrid, could not be effected with hydrogen in the presence of Adams catalyst. 

That alkylation of the anhydro-bases takes place at the indole nitrogen atom in the jS-carboline series was established conclusively by the identity of the product (429), prepared by treatment of pyr-N-ethyl-jS-carboline anhydro-base (428) with ethyl iodide, with 2,9-diethyl-jS-carbolinium iodide (429) obtained from the reaction of imi-A-ethyl-jS-carboline (430) with ethyl iodide (see Section IV, A, 2). 

That the ind-N atom in the anhydro-bases is the basic center is also obvious from a consideration of the ultraviolet absorption spectra of the anhydro-bases. In aqueous 0.1 A hydrochloric acid as well as in neutral alcoholic solutions each carboline anhydro-base gives rise to an ultraviolet absorption spectrum identical with that of the parent carbolinium salt. In alkaline solutions (pH above 11.5 in the case of the... 

Formation of a quinonoid carboline-type anhydro-base requires loss of resonance stabilization of the indole moiety. In the carboline anhydro-bases this is counterbalanced by the preservation of a 677 system in the hetero ring. No such balancing factor is present in the case of 3,4-dihydro-j3-carboline derivatives. Formation of the exocyclic anhydro-base in the latter case preserves benzenoid resonance. It is noteworthy that in the two cases where formation of a carboUne-type anhydro-base was reported in dihydro derivatives additional aromatic conjugation is present. 

This dimeric formulation also accounts for the thermal disproportionation of the compound into a mixture of 2-methyl-l,2,3,4-tetrahydro-jS-carbohne and 2-methyl-jS-carboline anhydro-base. Normal pseudobase formation (453 R = CHs ) takes place in the case of 9-methyl-3,4-dihydro-j3-carbohne methiodide (452 R = CHg). Neither the dimeric anhydro-base nor the -methyl pseudo-base undergo a base-catalyzed disproportionation reaction to give the 1,2,3,4-tetrahydro-and the l-oxo-l,2,3,4-tetrahydro-jS-carboline in a manner analogous... 

The determination of pA values of the carboline anhydro-bases has led to further speculation concerning the relative contributions of structures a and b to the ground states of the molecules. The -pKa... 

Armit and Robinson suggested that it was necessary to represent the structure of a carboline anhydro-base as a compromise between a quinonoid and a dipolar structure. In more current terminology, this means that they (cf. 421-424) should be considered as resonance hybrids of structures a and b in which the tendency to attain the fuUy aromatic sextet of 7r-electrons is balanced by that to effect neutralization of the charges. 

The carboline anhydro-bases are appreciably more basic than the parent oarbolines. Thus a pA value of 10.6 was reported for pyr-N-methyl-j8-carboline anhydro-base, for pyr-A-propyl-jS-carboline anhydro-base, and for pyr-A -methyl-l-methyl-jS-carboline anhydro-base a pKa value of 10.6 for sempervirine and values between 10.5 and 10.7 for serpentine, alstonine, and related alkaloids. A study of the relative basicities of simple a-, j8-, and y-oarboline anhydro-bases led to values of 7.75,11.11,11.20, and 10.54 for the... 

The dihydro-j8-carboliniuin salt 450 has been reported to form a pseudobase (451) on treatment with alkali. It is of interest that the pK value for this compoundi - as found to be 11.7, i.e., of the same order of magnitude as those of the jS-carboline anhydro-bases. 

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