Conformations of E-2-phenyl-3(2′-furyl)propenoic acid and its methyl ester in various solvents - An NMR study

Article abstract of DOI:10.1016/j.molstruc.2004.11.052

The conformations of E-2-phenyl-3(2′-furyl)propenoic acid and its methyl ester were investigated by NMR spectroscopy. Applying various solvents (methanol, chloroform and dimethyl sulfoxide) the possible conformers in solutions were studied by two-dimensional NOESY measurements. Irrespective to the solvents and whether the investigated moiety was the ester or the acid dimer, no conformational preferences could be identified experimentally.

Full text of DOI:10.1016/j.molstruc.2004.11.052

Journal of Molecular Structure 744–747 (2005) 273–276
www.elsevier.com/locate/molstruc
Conformations of E-2-phenyl-3(20-furyl)propenoic acid and
its methyl ester in various solvents—an NMR study
*
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P. Forgo, K. Felfoldi, I. Palinko
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Department of Organic Chemistry, University of Szeged, Dom ter 8, Szeged H-6720 Hungary
Received 6 September 2004; revised 11 November 2004; accepted 11 November 2004
Available online 18 January 2005
Abstract
The conformations of E-2-phenyl-3(20-furyl)propenoic acid and its methyl ester were investigated by NMR spectroscopy. Applying
various solvents (methanol, chloroform and dimethyl sulfoxide) the possible conformers in solutions were studied by two-dimensional
NOESY measurements. Irrespective to the solvents and whether the investigated moiety was the ester or the acid dimer, no conformational
preferences could be identified experimentally.
q 2005 Elsevier B.V. All rights reserved.
Keywords: E-2-phenyl-3(20-furyl)propenoic acid and its methyl ester; 2D NOESY measurements; Conformers in various solvents (methanol, chloroform or
dimethyl sulfoxide).
1. Introduction
dimeric acids has not been performed yet. After studying
the potential energy surfaces of these simplified systems [4]
one can envisage various conformers. Expectedly, when
solvent is present certain conformers may predominate,
presumably depending on the properties of the solvent.
Thus, it may be of interest to study the effect of solvents on
the conformational properties of the molecules. A handy
method for such an investigation is NMR spectroscopy.
In this contribution results of 2D NOESY measurements
are described. The study aimed at learning about possible
conformational preferences of E-2-phenyl-3(20-furyl)pro-
penoic acid and its methyl ester in various solvents.
Cinnamic acid derivatives are important intermediates in
the shikimic acid metabolic pathway of higher plants. They
also have interesting structure-forming properties via strong
OH/O hydrogen bonds (in acids [1]) in solution and
C–H/O close contacts (in acids [1] and also in esters [2]) in
the solid state. Upon replacing the phenyl group with
heteroatom-containing aromatic ring, like a furyl group in
position 3, further possibilities for aggregate formation
opens via (aromatic)C–H/(furyl)O intermolecular hydro-
gen bonds [3].
Theoretically, intramolecular C–H/O bonds may also
appear making certain conformers predominant. These
interactions in various 2-furyl- and 2-pyridyl-substituted
3-phenyl propenoic acids have already been investigated
computationally [4]. In order to make ab initio calculations
feasible these systems were simplified: monomeric acids
were used instead of the dimers, even though the latter are
known to be typical forms of appearance even in the gas
phase. This type of simplification seems to be general [5], to
our knowledge conformational analysis by computations for
2. Experimental
2.1. Materials
The model compounds were E-2-phenyl-3(20-furyl)pro-
penoic acid (1) and its methyl ester (2) (Fig. 1).
They were prepared by a modified version of the Perkin
condensation [6] and esterification. For the synthesis of the
acid 2-furylaldehyde (Aldrich) and phenylacetic acid
(Aldrich) were applied, esterification was done in dimethyl
sulfoxide (DMSO)/KOH/CH3Cl solution of the acid [7].
* Corresponding author. Tel.: C36 62 544 288; fax: C36 62 544 200.
´ ´
E-mail address: palinko@chem.u-szeged.hu (I. Palinko).
0022-2860/$ - see front matter q 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2004.11.052

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P. Forgo et al. / Journal of Molecular Structure 744–747 (2005) 273–276
274
the title molecules. Two-dimensional NOESY exper-
iments were carried out at room temperature on a Bruker
DRX 500 instrument in dilute solution to avoid the
conformation influencing effects of intermolecular hydro-
gen bonds between the solute molecules. 0.6 ml of the
solution was transferred to a 5 mm diameter Wilmad
NMR tube and the standard phase sensitive NOESY
pulse sequence (TPPI) was used to obtain the two-
dimensional maps. As a result of the good 1H NMR
spectral dispersion, only a small fraction of the spectra
(w3.5 ppm, 1 K complex datapoints) at the higher
chemical shifts was detected with a carrier frequency
placed at 6.8 ppm. 64 transients were collected to each of
the 256 F1 increments and 2 s relaxation delay was set
between each individual transients, resulting in 14.5 h
long experimental time. Squared cosine function was
applied as window functions in both detected and
incremented dimensions prior to Fourier transformation
and a standard baseline correction function was used in
both dimensions in order to remove baseline distortions
from the two-dimensional map.
Fig. 1. The molecules studied.
Fig. 2. The s-trans and the s-cis conformers of the ester (2) following
Ref. [10]
2.2. NOESY measurements
For visualisation, HF/3-21G optimised conformers were
used, found typical after performing a preliminary confor-
mational search (HyperChem package [8], PM3 semi-
empirical code [9]).
Three different solvents (DMSO-d6, chloroform-d and
methanol-d4) were used to study dipolar interactions of
Fig. 3. The HF/3-21G optimised typical conformers for the ester: (a) s-cis
and (b) s-trans
Fig. 4. The HF/3-21G optimised typical conformers for the acid dimers: (a)
s-cis–s-cis and (b) s-trans–s-cis

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P. Forgo et al. / Journal of Molecular Structure 744–747 (2005) 273–276
275
Table 1
1H-NMR chemical shifts (in ppm) of 1 and 2 in three different solvents (CDCl3, methanol-d4 (MeOD) and DMSO-d6)
#
1
2
CDCl3
MeOD
DMSO-d6
CDCl3
MeOD
DMSO-d6
ZCH
COOH
COOMe
Ar
30
40
7.81
7.70
–
7.58
7.73
–
7.67
–
7.62
–
11.69
–
12.59
–
–
3.76
7.22–7.45
5.77
6.24
7.35
3.73
7.15–7.43
5.81
6.29
7.45
3.69
7.20–7.50
5.97
6.44
7.67
7.22–7.46
5.86
7.17–7.41
5.80
6.27
7.42
7.20–7.45
5.93
6.25
6.43
50
7.36
7.66
3. Results and discussion
respectively. It is to be noted that a preliminary confor-
mational search (see Section 2) could not identify s-trans–s-
trans arrangement for the acid dimer.
3.1. Preliminary considerations
The 2D NOESY measurements were performed in three
different solvents, each representing distinct solvent types
(DMSO-dipolar, aprotic; methanol-polar, protic; chloro-
form-(nearly) apolar) were performed. It was expected that
the analysis of these measurements would indicate preferred
arrangements from the possible conformers. These possible
conformer classes are the s-trans and s-cis arrangements for
the ester and the s-trans–s-trans, s-trans–s-cis, and s-cis–s-
cis arrangements for the acid dimers, following the notation
of Ref. [10] (i.e. concentrating of the relative positions of
the olefinic double bound and the conjugated double bond in
the furyl ring) (Fig. 2).
3.2. NMR measurements
Three different solvents (DMSO-d6, methanol-d4 and
chloroform-d) were selected in order to study the solution
structure of the two model compounds (1 and 2). Table 1
1
shows the H-NMR chemical shift assignment for the two
compounds.
Small but significant changes in chemical shifts were
observed as the solvent was changed (Fig. 5).
The H-50 proton of the furan ring was the most sensitive
to the solvent: approximately 0.3 ppm chemical shift
increase was observed in DMSO relative to that was
found in chloroform. H-30 and H-40 protons of the furan ring
Examples of the ab initio optimised conformers are
depicted in Figs. 3 and 4 for the ester and the acid dimer,
Fig. 5. 1H-NMR spectra of (a) (1) and (b) (2) in CDCl3 (bottom), methanol-d4 (middle) and DMSO (top)

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P. Forgo et al. / Journal of Molecular Structure 744–747 (2005) 273–276
276
Fig. 6. 2D NOESY spectrum of (a) 1 (in CDCl3) and (b) 2 (in CDCl3).
carried an approximate 0.2 ppm chemical shift increase.
The chemical shift of the olefinic proton was increased
by 0.2 ppm as we went to hydrophilic solvents from
chloroform. Less important and significant was the
solvent dependent chemical shift change in the methoxy
protons.
4. Conclusions
Through studying the 2D NOESY spectra of both
molecules in various solvents (CDCl3, methanol-d4 or
DMSO) it has been learnt that both substituents of the
propenoic acid retain high rotational freedom, thus, there is
no predominating conformer irrespective to the solvent and
the two molecules studied.
The solution conformation was monitored by the
application of two-dimensional NOESY experiments. The
1
good dispersity of the H-NMR spectrum allowed us to
investigate the NOESY interactions of the model com-
pounds in these solvents (Fig. 6).
Acknowledgements
Since H-30 and H-40 were separated well from the
aromatic protons resonating at higher chemical shifts, it
was straightforward to analyse the interactions of these
hydrogens. The close space proximity results in a strong
NOE signal in the spectrum for both compounds
regardless of the solvent. The simultaneous appearance
of the NOESY cross-peaks of H-30 to H-200, H-600 and
aCH indicate that both furyl and phenyl groups have fast
rotational freedom in all solutions. Consequently, pre-
ferred rotamer populations of the furyl ring based on
NOESY interactions between H-30-ZCH and H-30-H-
200,H-600 cannot be unambiguously determined. The H-40
proton has only correlations to protons in the furyl ring
(H-30 and H-50). The labile carboxylic OH protons
disappear from the methanol-d4 spectra due to replace-
ment with deuterium, furthermore, the spectra recorded
in DMSO-d4 and CDCl3 solutions show broad signals as
a result of the fast exchange with the solvent residual
water, resulting in no NOESY correlations to these
protons.
This work was supported by the National Science Fund
of Hungary through grant OTKA T034184. The financial
help is highly appreciated.
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