Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2010) 2, 29.

Tryptamines result from the reaction of arylhydrazines with 4-chlorobutanal, usually used as an acetal derivative,[‌155‌–‌157‌] in a sequence which neatly utilizes the second nitrogen of the arylhydrazine to produce the amino group on the side-chain; this is known as the Grandberg synthesis,[‌158‌,‌159‌] the likely sequence for which is shown in ‌Scheme 34‌. Following formation of the arylhydrazone ‌86‌, intramolecular alkylation of the imine nitrogen generates an iminium salt ‌87‌ that loses a proton to produce the intermediate ‌88‌ which undergoes the rearrangement step (to give ‌89‌). The usual Fischer sequence via ‌90‌ gives ‌91‌, ring opening of which provides the indole oxidation level, but retains the second nitrogen as the side-chain amino group in the product tryptamine (‌92‌).

‌Meeeee 88‌ Meeeeeeee eee Meeeeee ee Meeeeeeee Meeeeeeeee Meeeeeeee[‌888‌]

Me eeeeeeeeee eeeeeeeee eeeee ee eee eeeeee eeeeeeeeeeeeee eeeeeeee eeeeeeeee ee Meeeeee ‌88.88.8.8.8.8.8.8.8‌. Meee, eeeeeeee ee Me-eeeeeeeeeee eeeeeeeeeeeeee eeee 8-eeeeeeeeee-8-eee ee 8-eeeeeeeee-8-eee eeee eeeeeeee eeeeeeeee eeeeeeee eeeeeeeeeee ee eeeeeeeeeeeeeee, eeeeeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeeee eee Meeeeeeeeeeeeee eee Meeeeeeeeeeeee ee Meeeeeeeeee Meeeeeee Meeeeee[‌888‌]

‌Meeeeeeeeee 88‌

M eeeeeee eeeee eee eeeeeee eeee eee Meeeeeeee eeeeeeee ee eee eeeeeeeeeee ee 8-eeeeeeeeeeeeeeeeee (‌88‌) ee eee eeeeeeeeeeeee, eee eeee, ee eeeeeeee eeee e eeeeee eeeeee eee eeeeeeeeeeee, eee eeeeee eeeeeeee ee eeeeeeee ee e 8-eeeeeeeeeee eeeee ee eee eeeeeee eeeeeeee, e.e. eeeeeeee ee eeeeeeeeeeeee (‌88‌) ee eeee eeeeeeeeeeeeeeeee[e]eeeeee-8-eeeeeeeeeee ‌88‌ (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeeee eeee 8-Meeeeeeeeeeeeeeeee eee Meeeeee Meeeeeeeeee Meeee Meeeeeeeeeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

Meeee 8-(8-Meeeeeeeee)-8M-eeeeee-8-eeeeeeeeeee (‌88‌); Meeeeee Meeeeeeee:[‌888‌]

[8-(Meeeeeeeeeeeee)eeeeee]eeeeeeeee eeeeeeeeeeeee (88 e, 88.8 eeee) eee 8-eeeeeeeeeeeee eeeeeeee eeeeee (8.8 e, 88 eeee) ee MeMM/M8M (8:8; 888 eM) eeee eeeeee ee eeeeee eee 8 e. Meeee eeeeeeeeeee ee eeeeeeee, eee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, MM8Me8/MeMM/MM8 88:8:8) ee eeee eee eeeeeee; eeeee: 8.88 e (88%); ee (eeeeeee eeee) 888°M.

References