The Preparation of Mannich Bases Related to Gramine

Abstract

Recent interest in the chemistry of Mannich bases derivable from indole (1,2) and its derivatives (3, 4) prompts us to report on work done in this field some years ago. At that time it was deemed desirable to add the indole nucleus to the list of basically substituted heterocyclic systems under investigation as

Mannich reactions of activated 4,6-dimethoxyindoles

“…General. 1 H and 13 C NMR spectra were recorded on a Bruker AC300F ( 1 H: 300MHz, 13 C: 75.5 MHz) or a Bruker AM500 spectrometer. The chemical shifts (δ) and coupling constants (J) are expressed in ppm and hertz respectively.…”

“…UV/Vis (λmax, nm, ε, cm -1 M -1 ): 212 (40,000), 248 (31,000), 319 (14,900). 1 H NMR (300 MHz, CDCl3): δH 3.67, 4.19, 4.87 (each 2H, 3s, CH2), 3.78, 3.88 (each 3H, 2s, OMe), 6.33 (1H, s, H8), 7.13-7.33 (13H, m, aryl), 7.34 (2H, d, J 7.0 Hz, aryl). 13 C NMR (75 MHz, CDCl3): δC 47.0, 55.8, 63.5 (CH2), 56.9, 57.1 (OMe), 90.…”

“…UV/Vis (λmax, nm, ε, cm -1 M -1 ): 213 (34,300), 319 (15,300). 1 H NMR (300 MHz, CDCl3): δH 1.16 (9H, s, t-Bu), 3.74, 3.93 (each 3H, 2s, OMe), 4.21, 4.91 (each 2H, 2s, CH2), 6.30 (1H, s, H8), 7.17-7.33 (10H, m, aryl). 13 C NMR (75 MHz, CDCl3): δC 27.5 (Me), 41.6 (CMe), 54.5, 59.5 (CH2), 55.8, 57.0 (OMe), 90.2 (C8), 125.…”

“…Indole 1 undergoes the classic Mannich reaction with formaldehyde and dimethylamine to give 3-(dimethylaminomethyl)indole 2, which is also a natural product known as gramine. 1,2 The application of similar reaction conditions with the activated 4,6-dimethoxyindole 3 gave the related 4,6-dimethoxygramine 4. 3 5,7-Dimethoxyindole 5 has also been reported to give the corresponding 5,7-dimethoxygramine 6 in 36% yield.…”

Simple preparation of new N-aryl-N-(3-indolmethyl) acetamides and their spectroscopic analysis

“…As a result of their biological and synthetic importance, a variety of methods have been reported for the preparation of 3-substituted indoles, using indol or 3-indolcarboxyaldehyde as starting materials. Generally, the Mannich reaction 6,7 and the catalyzed Friedel-Crafts alkylation reactions of indoles [8][9][10][11] are considered as a powerful carboncarbon bond process to afford the 3-indolylmethanamine derivatives 1. However, another synthetic route to these compounds by using 3-indolcarboxyaldehyde via its imino derivatives formation is valid.…”