8-Carbolinium salts, 1-alkyl

The alkylation of carboline derivatives has been repeatedly studied. The first quaternary A-alkyl carbolinium salts to be described were those prepared in connection with the elucidation of the structure of harmine (methiodide, methochloride, and methosulfate Other j8-carbolinium salts were subsequently prepared in connection with systematic studies of the site of alkylation and of the... 

Further alkylation of the anhydro-bases derived, by treatment with strong base, from quaternary 1-alkyl-a-, 2-alkyl-j8-, 2-alkyl-y-, and l-alkyl-8-carbolinium salts takes place at the indole nitrogen which in the anhydro-bases is a center of high electron density (see Section VI). 

The products of these double-alkylation sequences in the j8-carboline series, 2,9-dialkyl-j8-carbolinium salts, react with base to yield the corresponding quaternary hydroxides. Pyrolysis of the salts leads to dealkylation at the pyr-N with the production of the corresponding ind-A-alkyl-j8-carbohnes. ... 

Quaternization with alkyl halides of 3,4-dihydro-jS-carboline and its derivatives takes place at the pyr-N. Quaternary 3,4-dihydro-j8-carbolinium salts (309) derived from harmaline, 3,4-dihydro-j8-carboline, 6-methoxy-3,4-dihydro-j8-carboline, and 1 -methyl-3,4-dihydro-j8-carboline have been described. Further... 

The third structural possibility, the formulation of the compounds as pseudo-bases (445) was eliminated in the case of the anhydro-bases derived from p /r-iV -alkyl-l-methyl-3,4-dihydro-j8-carbolinium salts on the basis of their ultraviolet absorption spectra. A structure such as 445 demands indole-type absorption (A jax 280 mp) which was not encountered in the spectra of the anhydro-bases under discussion. This is in accord with general experience. Pseudo-bases are generally found only when dehydration to anhydro-bases is structurally impossible Indole-type absorption was indeed found in the case of the product obtained by treatment of 3,4-dihydro-)3-carboline methiodide (452 R = H) with alkali.In acid solution this compound gave the expected absorption (A jax 355 mp). In alkaline solution, however, an indole-type absorption (A jax 285 mp) was observed. On this basis formulation of the product as a derivative of 2-formylindole (454) ( max 315 mp) was rejected. Although the indole-type absorption is in accord with the pseudo-base structure 453 (R = H), the elemental analysis and molecular weight were not compatible with this formulation and the product was regarded as a dimeric anhydro-base (455). 

Tertiary pyr-i r-alkyl-l,2,3,4-tetrahydro-j8- and -y-carboline derivatives can be quatemized at the same site to give 2,2-dialkyl-l,2,3,4-tetrahydro-j8- and -y-carbolinium salts. Tertiary tetrahydro-j8-carboline derivatives have been reported to 3deld pyr-iV -oxides. ... 

The third structural possibility, the formulation of the compounds as pseudo-bases (445) was eliminated in the case of the anhydro-bases derived from yr-JV-alkyl-l-methyl-3,4-dihydro-jS-carbolinium salts on the basis of their ultraviolet absorption spectra. A structure such as 445 demands indole-type absorption 280 mfi) which was not... 

In 2011, Driver and coworkers synthesized dimebolin by utilizing a ruthenium-catalyzed nitrenoid insertion reaction that they developed (Scheme 16.10) [21]. Azide 49 was readily prepared from 48 by a two-step sequence, consisting of treatment with sodium nitrite and sodium azide, and alkylation of pyridine. Addition of catalytic RuClg hydrate to 49 formed putative ruthenium nitrenoid 50 [22], which then underwent regioselective C-H amination at the C4 position of the pyridinium ion to give y-carbolinium salt 51 in 91% yield. Deprotonation of the N-H group of 51, followed by alkylation with 52, appended the requisite pyridine... 

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