Thesis-Final 03 June 2011 pdf - Jacobs University

Results and discussion Chapter 3
The experimental data proved that the type of organic base also plays an important
role especially, in the synthesis of mono acyl chlorogenic acids (esters) as well as
producing di-substituted chlorogenic acids or esters.
It was concluded that for the di-substituted chlorogenic acids or esters; triethylamine
being a stronger base (pKa ~ 10) and perhaps it can deprotonate one of the axial
hydroxyl groups, whose acidity is higher than that of normal alcohols due to very
strong intramoleculer hydrogen bond. Therefore, the substitution may occur at axial
H-4 proton as well as equatorial H-3 proton or H-1 proton. Therefore, triethylamine
was preferred for the synthesis of the di-acyl and poly-acyl substituted chlorogenic
acids or esters. Whereas, pyridine is a weak organic base (pKa ~ 7) and it can not
deprotonate the C-4 hydroxyl group. Hence, the reactivity of pyridine among the three
hydroxyl groups is determined by the relative nucleophilicity and steric factors.
Therefore, based on outcome of the experimental data pyridine is the most appropriate
solvent for the mono substituted chlorogenic acids or esters.
Interestingly, 1 H-NMR spectrum of the Troc protected mono subtituted chlorogenic
acid derivatives for example; (1S, 3R, 4R, 5R)-1-(β, β, β-trichloroethoxycarbonyl)-4-
dimethoxycinnamoyl quinide (75), showed that the substitution was occurred at H-4
axial proton instead of H-3 equatorial proton which is generally most preferred.
Presumably, dielectric behaviour of the Troc protecting group and steric hindarence
caused by a large protecting group allowed 3,4-dimethoxychloride to attach to the
least preferred axial H-4 proton.
The same results were observed in the synthesis of (1S, 3R, 4R, 5R)-1-(β, β, β-
trichloroethoxycarbonyl)-4-cinnamoyl quinide, (74), (1S,3R,4R,5R)-1-(β, β, β-
trichloroethoxycarbonyl)-4-acetylferuloyl quinide, (76) (1S,3R,4R,5R)-1-(β, β, β-
trichloroethoxycarbonyl)-4-acetyl p-coumaroyl quinide, (77), (1S,3R,4R,5R)-1-(β, β,
β-trichloroethoxycarbonyl)-4-diacetylcaffeoyl quinide, (78).
113