Reaction of 4,6-Dimethoxy-3-methylindole With Aromatic Aldehydes: a Simple Synthesis of Calix[3]indoles

Abstract

2,7:2,7:2,7-Linked calix [3] indoles (3a-d) have been prepared by the reaction of 4,6-dimethoxy-3-methylindole (1) and benzaldehydes with phosphoryl chloride or by a direct reaction of di (4,6-dimethoxy-3-methylindol-2-yl) phenylmethanes (2a-d) with phosphoryl chloride. An X-ray crystal structure determination of the macrocycle (3d) is reported. 4,6-Dimethoxy-3-methylindolemethanols (9) and (10) were prepared and reacted with phosphoryl chloride to study the mechanism of formation of the macrocycle.

Synthesis of new indole benzylic alcohols as potential precursors of calixindoles

“…However, the 1 H NMR spectrum of the crude product showed no evidence of a macrocyclic compound, and the broadened signals indicated a polymeric material. It has been shown previously that the 2-substituted hydroxyethanamides gave higher yields of calix [3]indoles than the 7-substituted isomers. 5 Treatment of the 2-glyoxylic acid chloride 10 with a one-third equivalent of tris (2-aminoethyl)amine in dichloromethane at room temperature for 1 hour gave the tris indol-2'-yl glyoxylamide 12 in 45% yield (Scheme 2).…”

“…Furthermore, acid treatment of the tris-indole methanol 7 also failed to give the desired calix [3]indole. This failure presumably is caused by the nonideal length of the tether.…”

“…[1][2][3][4] These compounds can be achieved in two ways. One is the reaction of the indole with an aryl aldehyde in the presence of phosphoryl chloride.…”

“…In general the flattened partial cone conformer was found to be preferred over the cone conformer, but the cone conformer could be stabilised to some extent by the use of amido substituents on the linking methine carbon atoms. 5 Thus, the 7-and 2-indolyl hydroxyethanamides 1 and 2 respectively were converted into a mixture of the flattened partial cone calix [3]indole 3 and the cone calix [3]indole 4 (Scheme 1). In the cone conformer 4, the carbonyl oxygen atom of the amide substituent is hydrogen bonded to the adjacent indole NH atom and thus provides some conformational stability.…”

“…Calix [3]indoles have been synthesised from activated 3-substituted-4,6-dimethoxyindoles with the three indole rings linked by carbon bridges through the C2 and C7 positions. [1][2][3][4] These compounds can be achieved in two ways.…”