A 13C NMR study of the structure of four cinnamic acids and their methyl esters

Article abstract of DOI:10.1016/S0022-2860(01)00486-0

The 13C NMR spectra, both in DMSO solution and in the solid state of four cinnamic acids (p-methoxy, p-hydroxy, p-methyl, p-chloro) and their corresponding methyl esters have been recorded. The two main results in the solid state are: (i) the only significant difference between acids and esters chemical shifts concerns the C=O group which, on average, appears at 173 ppm in the acids and 168 ppm in the esters; (ii) the signals of the ortho and meta carbons both in the acids and the esters are splitted. The two "anomalies" dissapear in DMSO solution. These observations can be rationalized using simple GIAO/B3LYP/6-31G* calculations.

Full text of DOI:10.1016/S0022-2860(01)00486-0

Journal of Molecular Structure 595 ꢀ2001) 1±6
www.elsevier.com/locate/molstruc
1
3
A C NMR study of the structure of four cinnamic acids and their
methyl esters
a
A.M.S. Silva , I. Alkorta , J. Elguero , V.L.M. Silva
b
b,
a
*
a
Departamento de Qu Âõ mica, Universidade de Aveiro, Campus Universit a rio de Santiago,
P-3810-193 Aveiro, Portugal
Instituto de Qu Âõ mica M e dica #CSIC), Calle Juan de la Cierva, 3, E-28006 Madrid, Spain
b
Received 27 November 2000; accepted 18 December 2000
Abstract
1
3
The C NMR spectra, both in DMSO solution and in the solid state of four cinnamic acids ꢀp-methoxy, p-hydroxy, p-methyl,
p-chloro) and their corresponding methyl esters have been recorded. The two main results in the solid state are: ꢀi) the only
signi®cant difference between acids and esters chemical shifts concerns the CyO group which, on average, appears at 173 ppm
in the acids and 168 ppm in the esters; ꢀii) the signals of the ortho and meta carbons both in the acids and the esters are splitted.
p
The two `anomalies' disappear in DMSO solution. These observations can be rationalized using simple GIAO/B3LYP/6-31G
calculations. q 2001 Elsevier Science B.V. All rights reserved.
1
3
Keywords: Cinnamic acids; Cinnamic esters; Solid state NMR; C NMR; GIAO calculations
1
. Introduction
and 4a are disordered, while compounds 2a and
a exist in the IZZ conformation, at least predo-
3
1
3
We selected for a structural study using
C
minantly. When the para-substituent can adopt
two conformations, namely methoxy and hydroxy,
it is planar and on the same side as the acrylic
chain with regard to the phenyl ring. We have
also synthesized and studied the corresponding
methyl esters, 1b±4b, for comparative purposes:
no X-ray structure of the esters has been reported
[1]. The eight compounds have been and still are
the subject of great interest mainly for their prop-
erties ꢀnote that compound 2b is known as methyl
p-coumarate). Related to these compounds are
BSB, used for imaging Azheimer's plaque [7],
and the trans-cinnamides used for control of
solid state photodimerizations [8].
NMR spectroscopy ꢀin solution and in the solid
state, CPMAS) four cinnamic acids whose X-ray
structures were known [1]: 1a p-methoxy
ꢀ
3
ꢀ
MXCINN) [2], 2a p-hydroxy ꢀCOUMAC01) [3],
a p-methyl ꢀJADVUF) [4] and 4a p-chloro
PCTCIN) [5]. All these compounds crystallize
as dimers I, often with dynamic proton disorder,
as usually carboxylic acids do [6]. Compounds 1a
*
Corresponding author. Tel.: 134-91-411-0874; fax: 134-91-
64-4853.
E-mailaddress: iqmbe17@iqm.csic.es ꢀJ. Elguero).
5
0022-2860/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-2860ꢀ01)00486-0

2
A.M.S. Silva et al. / Journal of Molecular Structure 595 #2001) 1±6
Table 1
1
C chemical shifts of cinnamic acids ꢀin ppm). In bold, splitted signals and splitting in ppm
3
Compound
Cond.
CO
2
H
CHꢀCO)
117.9
CHꢀAr)
144.6
C
ipso
C
ortho
C
ortho
0
C
meta
C
meta
0
C
para
p-R
1a
Solid
splitting, Dd
DMSO
173.4
125.5
128.6
4.3
130.0
132.9
111.9
6.0
114.4
117.9
162.1
55.5 ꢀMeO)
1
a
a
167.9
172.1
116.5
117.0
143.8
146.8
126.9
127.3
130.0
114.4
161.0
157.1
55.3 ꢀMeO)
±
2
Solid
127.3
8.9
130.2
136.2
114.4
2.6
115.8
117.0
splitting, Dd
DMSO
2
a
a
168.0
173.2
115.4
117.2
144.3
146.1
125.3
130.8
130.2
115.8
159.7
142.3
±
3
Solid
126.6
5.7
128.3
132.3
129.7
1.1
129.6
130.8
21.6 ꢀMe)
splitting, Dd
DMSO
3
a
a
167.8
174.7
118.1
117.2
144.0
146.1
131.6
131.2
128.3
129.6
140.2
133.6
21.1 ꢀMe)
±
4
Solid
128.4
5.2
130.0
133.6
128.4
0.0
129.0
128.4
splitting, Dd
DMSO
4a
167.5
120.1
142.6
133.2
130.0
129.0
134.8
±
ꢀ3:1 mixture of acetic/concentrated hydrochloric acid
heated at 708C) reactions.
1
3
The one-dimensional C NMR spectra were
obtained in DMSO-d solutions at room temperature
6
on a Bruker AMX 300 spectrometer working at
75 MHz. All the chemical shifts are expressed in
parts per million reported to external TMS.
1
3
C
assignments were made using HETCOR and HMBC
experiments ꢀdelay for long-range J C/H couplings
1
3
were optimized for 7 Hz). C NMR CPMAS spectra
were recorded at 100 MHz on a Bruker MSL 400
spectrometer using 5 s of recycle delay, a 908 pulse
of 4.2 ms, SW ˆ 300 ppm and AQ ˆ 41 ms:
All the calculations have been performed with the
Gaussian 98 package [9]. Full geometry optimization
p
has been carried out at the B3LYP/6-31G level [10±
12] maintaining a symmetry plane for all the systems
considered. The absolute NMR shieldings have been
calculated with the GIAO method [13,14] at the
mentioned computational level.
2
. Experimental
The cinnamic acids 1a±4a are commercially avail-
able ꢀAldrich). The esters 1b, 3b and 4d were
3. Results and discussion
prepared by methylation ꢀmethyl sulfate, K CO ,
3
2
1
3
acetone at re¯ux) of the corresponding cinnamic
acids 1a, 3a and 4a. Ester 2b was prepared from 4-
hydroxycinnamic acid 2a by a sequence of transfor-
mations: benzylation ꢀbenzyl chloride, K CO , DMF
The C chemical shifts of the eight compounds are
gathered in Tables 1 ꢀacids) and 2 ꢀesters). The two
CH carbons of esters 1b, 3b and 4b have already been
reported by Brazilian authors [15]. Leaving aside, for
the moment, the splitting observed in the solid state
for ortho and meta carbons of almost all compounds
ꢀonly the meta carbons of 4a and 4b coincide), the
2
3
at re¯ux), saponi®cation ꢀaqueous NaOH and
methanol heated at 708C), methylation ꢀmethyl
sulfate, K CO , acetone at re¯ux) and debenzylation
2
3

A.M.S. Silva et al. / Journal of Molecular Structure 595 #2001) 1±6
3
Table 2
1
C chemical shifts of methyl cinnamates ꢀin ppm). In bold, splitted signals
3
Compound Cond. CO Me CHꢀCO) CHꢀAr)
2
C
ipso
C
ortho
C
ortho
0
C
meta
C
meta
0
C
para
2
p-R and CO Me
1
b
b
Solid
splitting, Dd
DMSO
167.4
167.1
116.8
115.1
143.0
144.4
126.7 127.3 134.6 109.7 117.7 161.0 54.8 ꢀMeO)
7.3 8.0
126.7 130.2 130.2 114.4 114.4 161.2 55.3 ꢀMeO)
1
5
1.4 ꢀCO
2
Me)
2b
Solid
169.8
115.5
145.7
127.3 124.8 134.2 113.8 115.5 159.1
9.4 1.7
±
splitting, Dd
5
3.8 ꢀCO
2
2
Me)
Me)
2
3
b
b
DMSO
167.2
167.5
114.0
116.7
144.9
146.8
125.1 130.5 130.5 115.9 115.9 160.0 51.4 ꢀCO
Solid
131.7 125.7 131.7 126.5 131.7 140.8 21.1 ꢀMe)
6.0 5.2
splitting, Dd
5
0.8 ꢀCO
131.3 128.5 128.5 129.6 129.6 140.6 21.1 ꢀMe)
2
Me)
Me)
3
4
b
b
DMSO
166.9
167.7
116.7
118.0
144.7
144.5
5
1.5 ꢀCO
2
Solid
132.8 127.4 136.9 127.4 127.4 136.9
9.5 0.0
±
splitting, Dd
5
3.9 ꢀCO
2
2
Me)
Me)
4b
DMSO
166.6
118.7
143.2
133.0 130.2 130.2 129.0 129.0 135.1
±
5
1.6 ꢀCO
Table 3
1
3
13
C absolute shieldings s and estimated C chemical shifts d ꢀboth in ppm) of cinnamic acids. The predicted values are in italics
Compound CO
2
H
CHꢀCO) CHꢀAr)
C
ipso
C
orthoꢀCyC)
C
ortho
0
ꢀCH)
CmetaꢀCyC)
C
meta
0
ꢀCH)
C
para
p-R
a
1
2
3
3
4
aE
aE
aE
aZ
s
33.31
164.6
84.07
111.1
48.68
148.4
69.12
126.8
68.78
127.2
8.3
60.87
85.65
109.4
8.0
78.03
36.72 137.20 ꢀMeO)
d
Dd
135.5
117.4
161.0
55.1
±
d
average
131.4
113.4
a
s
d
33.39
164.5
84.03
111.1
48.99
148.0
69.14
126.8
68.97
127.0
9.5
59.95
81.90
113.4
1.2
80.69
39.58
158.0
136.5
114.6
Dd
d
average
131.8
114.0
s
33.35
164.5
82.12
113.1
48.20
148.9
64.41
131.8
70.70
125.2
8.8
62.32
134.0
66.35
129.7
0.6
66.98
129.1
54.85 167.57 ꢀMe)
141.9 23.1
d
Dd
d
average
129.6
129.4
s
34.74
164.2
80.20
114.9
50.44
147.4
64.27
131.9
70.80
125.1
8.4
62.83
66.60
129.5
0.5
67.02
54.97 167.61 ꢀMe)
d
Dd
133.5
129.0
141.7
23.0
d
average
129.3
129.2
aE
s
33.67
164.2
80.43
114.9
49.60
147.4
63.66
132.6
70.05
125.8
8.7
61.84
66.76
129.3
0.0
66.74
50.22
146.7
±
d
Dd
134.5
129.3
d
average
130.2
129.3
a
Same side as the Me ꢀor H) of the OMe ꢀor OH) group.

4
A.M.S. Silva et al. / Journal of Molecular Structure 595 #2001) 1±6
chemical shifts in solution and in the solid state are
very similar. If we average the calculated absolute
shieldings of ortho and meta carbons, the only differ-
ences affect the CyO carbon of the carboxylic groups
ꢀnot that of the ester groups). If these four signals are
excluded, Eq. ꢀ1) is obtained.
have calculated only the E isomers. At this level of the
theory, sTMS ˆ 189:69 ppm while, experimentally,
Jameson has measured s
ˆ 188:1 ^ 0:9 ppm
TMS
[16,17]. A linear regression of experimental values
in DMSO solution against absolute shieldings ꢀfor
ortho and meta carbons, average values), leads to
Eq. ꢀ2).
1
3
d C
13
ˆ ꢀ1:0025 ^ 0:0016†d Csolution;
n ˆ 54;
1†
solid
13
d C
13
ˆ ꢀ199:7 ^ 1:2† 2 ꢀ1:054 ^ 0:015†s C;
solution
2
R ˆ 0:9999
2
n ˆ 39;
R ˆ 0:992
ꢀ
ꢀ2†
This equations predicts for the carboxylic groups in
the solid state values close to 168.2 ppm, that is,
5.2 ppm higher ®eld than the average experimental
values ꢀ173.4 ppm).
Therefore, both acids and esters behave normally in
the solid state and only two aspects of the CPMAS
spectra deserve further study: ꢀi) the `anomalous'
CyO chemical shift of acids; ꢀii) the splitting of
carbons ortho and meta both in acids and esters as
well as their assignment; note that the average value
of the splitted signals coincides with the value in solu-
tion.
In Table 3 we have also reported the ®tted and
predicted ꢀunderlined) values using Eq. ꢀ2).
Concerning the ®tted values, they reproduce reason-
ably well the values in solution ꢀcompare Tables 1 and
3). There are some differences that can be assigned to
the moderate level of the calculations, for instance,
Cpara of 4a appears at about 135 ppm ꢀTable 1) whilst
the calculations correspond to 147 ppm, obviously the
ipso chlorine effect is not well reproduced. Three
carbon atoms deviate systematically: CyO
ꢀ,3 ppm), CHꢀCO) ꢀ,5 ppm) and CHꢀAr)
ꢀ, 2 5 ppm).
With this aim we carried out a series of GIAO/
p
B3LYP/6-31G calculations on compounds 1a, 2a,
To discuss the chemical shifts of the ±CHyCH±
3
a and 4a. This level is suf®cient for our purposes.
CO H moiety, we need to take into account the dimer-
2
For compounds 1a, 2a and 4a we used the E confor-
mations while for compound 3a we calculated the two
conformations, 3aE and 3aZ. In the case of 1aE and
2aE the calculated conformation of the methoxy and
hydroxy groups are as represented ꢀMe and H on the
ization of carboxylic acids in the solid state as well as
their strong hydrogen bonds with DMSO in solution
[18]. First we have compared the absolute shieldings
of formic acid 5 and its dimer 5/5 and transformed
them into d values by means of Eq. ꢀ2). On dimeriza-
tion, the carbon of formic acid moves from 154.3 to
163.7 ppm ꢀDd ˆ 9:4 ppm†: This explains why the
calculated values ꢀmonomers, Table 3) are about
163±164 ppm and the solid state data ꢀdimers, Table
1) are close to 173 ppm in the solid state. In solution,
an intermediate situation is found ꢀ168 ppm) which
should correspond to hydrogen bonds with DMSO.
same side as the CHyCH±CO H moiety) because
2
they are like this in the crystal ꢀMXCINN [2] and
COUMAC01 [3]). The absolute shieldings are
reported in Table 3.
The differences between the calculated absolute
shieldings of 3aZ and 3aE are too small to be relevant
for our purpose; therefore for the other compounds we

A.M.S. Silva et al. / Journal of Molecular Structure 595 #2001) 1±6
5
Then, we have studied the effect of the dimerization
on acrylic acid 6 to ®nd out if the effect of its dimer-
ization, 6/6, extends over the ole®n moiety. According
to the calculations ꢀs values transformed into d
through Eq. ꢀ2)), the CyO moves from 161.8 to
and small in the case of the OH ꢀDd ˆ 1:2 ppm†:
All these conclusions agree fairly well with the
experimental observations.
1
69.3 ppm ꢀDd ˆ 7:5 ppm†; the CHꢀCO) from 125.2
4. Conclusions
to 127.9 ꢀDd ˆ 2:7 ppm† and the terminal CH
2
remains unchanged ꢀ134.0 and 133.8 ppm). Although,
qualitatively, these effects correspond to those
observed when Tables 1 and 3 are compared, we
decided to study a more related model: a dimer of
cinnamic and formic acids, 3aE/5. The effects
Simple GIAO calculations allow to rationalize the
splittings observed for ortho and meta carbons of
cinnamic acids in the solid state. In solution, the
free rotation about the single bonds linking the phenyl
ring to CHyCH±CO R and X substituents suppresses
2
ꢀ
are 17.7 ppm for the CvO and 12.0 ppm for the
again transformed into d values through Eq. ꢀ2))
the splitting averaging the signals. Moreover, the
calculations allow an assignment of the splitted
signals, thus offering an alternative to a problem of
great experimental dif®culty since it requires very
CHꢀCO); all other signals are affected by less than
1
ppm.
According to the calculations, the splitting of
large monocrystals ꢀseveral millimeters) and an
NMR instrument provided with a goniometer.
ortho and meta carbons can be analyzed, in a
rst approximation, as coming independently
from the acrylic substituent ꢀCortho) and from the
®
Acknowledgements
p-substituent ꢀCmeta). The ortho carbon which is on
the same side as the ±CHyCH±CO R residue
2
We would like to express our thanks to the FCT of
Portugal and University of Aveiro for funding the
Research Unit No. 62/94 and also to FCT for a grant
appears at 125±127 ppm and that on the other
side at 134±136 ppm ꢀDd ˆ 8±9 ppm† indepen-
dently of the p-substituent ꢀbecause meta effects
are usually small). The meta carbon chemical
shifts depend on the p-substituent ꢀbecause ortho
effects are large). In that case, two situations are
possible: ꢀi) the X substituent has an axial
ꢀA.M.S.S.,
FMRH/BSAB/153/2000).
Financial
support from the DGICYT of Spain through the
SAF 97-0044-C02 project also is gratefully acknowl-
edged. Sincere thanks are expressed to Prof. Jo aÄ o
Rocha and Ms. Ana Paula Zhu, University of Aveiro,
for the CPMAS NMR spectra.
symmetry ꢀCH 3, Cl 4) and both meta carbons
3
are very similar ꢀDd null or very small); ꢀii) the
substituent has two planar conformations with
regard to the phenyl ring ꢀOCH3 1, OH 2).
According to the calculations, the difference is
large in the case of the methoxy ꢀDd ˆ 8:0 ppm†
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