Synthesis of Chalcones with Mannich Side Chain

Abstract

Nineteen new compounds (chalcone with Mannich side chain) were synthesized in

this work, together with their intermediates.

Aminomethylation of vanillin was achieved by reaction of formaldehyde with

various amines (pyrrolidine, piperidine, moropholine, N-methylpiperazine, and N-

ethylpiperazine) in dioxane to obtain 4-hydroxy-3-methoxy-5-pyrrolidinomethyl-

benzaldehyde (1), 4-hydroxy-3-methoxy-5-piperidinomethylbenzaldehyde (2) 4-

hydroxy-3-methoxy-5-morpholinomethylbenzaldehyde (3), 4-hydroxy-3-methoxy-5-

N-methylpiperaznomethylbenzaldehyde (4), 5-N-Ethylpiperazinomethyl-4-hydroxy-

3-methoxybe-zaldehyde (5) respectively. These intermediates were reacted with 4-

methoxyacetophenone to obtain chalcones with Mannich side chain : 4-Hydroxy-3,4'-

dimethoxy-5-pyrrolidinomethylchalcone (6), 4-hydroxy-3,4'-dimethoxy-5-

piperlidinomethylchalcone

(7),

4-Hydroxy-3,4'-dimethoxy-5-morpholinomethyl

chalcone(8),4-hydroxy-3,4'-dimethoxy-5-N-methylpiperazino-methylchalcone

(9)

,

5-

N-ethylpipera-zinomethyl-4-hydroxy-3,4'-dimethoxychalcone

(10)

The chalcones : 4-hydroxy-4'-methoxychalcone and 4-hydroxy-4'-

methoxychalcone were prepared by reacting 3-hydroxy or 4-hydroxybenzaldehyde

with 4-methoxyacetophenone . The aminomethylation of chalones was done by

reaction with formaldehyde and suitable amines (dimethylamine, pyrrolidine,

piperidine, moropholine, N-methylpiperazine, and N-ethylpiperazine) in acetonitrile

to obtain 3-hydroxy-4'-methoxy-4-dimethylaminochacone (12), 3-hydroxy-4'-

iii

methoxy-4-pyrrolidinomethylchalcone (13), 3-hydroxy-4'-methoxy-4-piperlidino-

methylchalcone (14), 3-Hydroxy-4'-methoxy-4-morpholinomethylchalcone (15), 3-

hydroxy-4'-methoxy-4-(

N-methyl-piperazino

methyl)chalcone(16),3-hydroxy-4'-

methoxy-2,4-bis-(N-methylpiperaz-inomethyl)chalcone (17) and 4-(N-

ethylpiperazinomethyl)-3-hydroxy-4'-methoxychalcone(18),4-hydroxy-4'-methoxy-

3,5-bis-dimethylaminomethylchalcone (20), 4-hydroxy-4'-methoxy-3,5-bis-

pyrrolidinomethylchalcone (21), 4-hydroxy-4'-methoxy-3,5-bis-piperdinomethyl

chalcone (22), 4-hydroxy-4'-methoxy-morpholinomethylchalcone(23), 4-hydroxy-4'-

methoxy-3,5-bis-morpholinomethylchalcone(24), 4-hydroxy-4'-methoxy-3,5-bis-N-

methylpiperazinomethylchalcone (25), 3-(N-ethylpiperazinomethyl)-4-hydroxy-4'-

methoxychalcone (26)

3,5-bis-(N-ethylpiperazinomethyl)-4-hydroxy-4'-methoxy

chalcone

(27)

The final products were purified by thin layer and column chromatography. They

were identified along with their intermediates by spectroscopic methods: UV, IR,

NMR spectroscopy (

1

H,

13

C, ABT, COSY, NOESY, HSQC, HMBC) and Mass

spectrometry