Journal of Molecular Structure 595 (2001) 1±6

www.elsevier.com/locate/molstruc

A 13C NMR study of the structure of four cinnamic acids and their
methyl esters
A.M.S. Silva a, I. Alkorta b, J. Elguero b,*, V.L.M. Silva a
a
Departamento de QuõÂmica, Universidade de Aveiro, Campus UniversitaÂrio de Santiago,
P-3810-193 Aveiro, Portugal
b
Instituto de QuõÂmica MeÂdica (CSIC), Calle Juan de la Cierva, 3, E-28006 Madrid, Spain
Received 27 November 2000; accepted 18 December 2000

Abstract
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
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.
The two `anomalies' disappear in DMSO solution. These observations can be rationalized using simple GIAO/B3LYP/6-31G p
calculations. q 2001 Elsevier Science B.V. All rights reserved.
Keywords: Cinnamic acids; Cinnamic esters; Solid state NMR; 13C NMR; GIAO calculations

1. Introduction and 4a are disordered, while compounds 2a and

3a exist in the IZZ conformation, at least predo-
We selected for a structural study using 13C minantly. When the para-substituent can adopt
NMR spectroscopy (in solution and in the solid two conformations, namely methoxy and hydroxy,
state, CPMAS) four cinnamic acids whose X-ray it is planar and on the same side as the acrylic
structures were known [1]: 1a p-methoxy chain with regard to the phenyl ring. We have
(MXCINN) [2], 2a p-hydroxy (COUMAC01) [3], also synthesized and studied the corresponding
3a p-methyl (JADVUF) [4] and 4a p-chloro methyl esters, 1b±4b, for comparative purposes:
(PCTCIN) [5]. All these compounds crystallize no X-ray structure of the esters has been reported
as dimers I, often with dynamic proton disorder, [1]. The eight compounds have been and still are
as usually carboxylic acids do [6]. Compounds 1a 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
* Corresponding author. Tel.: 134-91-411-0874; fax: 134-91-
BSB, used for imaging Azheimer's plaque [7],
564-4853. and the trans-cinnamides used for control of
E-mail address: iqmbe17@iqm.csic.es (J. Elguero). solid state photodimerizations [8].
0022-2860/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved.
PII: S 0022-286 0(01)00486-0
2 A.M.S. Silva et al. / Journal of Molecular Structure 595 (2001) 1±6

Table 1
13
C chemical shifts of cinnamic acids (in ppm). In bold, splitted signals and splitting in ppm

Compound Cond. CO2H CH(CO) CH(Ar) Cipso Cortho Cortho 0 Cmeta Cmeta 0 Cpara p-R

1a Solid 173.4 117.9 144.6 125.5 128.6 132.9 111.9 117.9 162.1 55.5 (MeO)
splitting, Dd 4.3 6.0
1a DMSO 167.9 116.5 143.8 126.9 130.0 130.0 114.4 114.4 161.0 55.3 (MeO)
2a Solid 172.1 117.0 146.8 127.3 127.3 136.2 114.4 117.0 157.1 ±
splitting, Dd 8.9 2.6
2a DMSO 168.0 115.4 144.3 125.3 130.2 130.2 115.8 115.8 159.7 ±
3a Solid 173.2 117.2 146.1 130.8 126.6 132.3 129.7 130.8 142.3 21.6 (Me)
splitting, Dd 5.7 1.1
3a DMSO 167.8 118.1 144.0 131.6 128.3 128.3 129.6 129.6 140.2 21.1 (Me)
4a Solid 174.7 117.2 146.1 131.2 128.4 133.6 128.4 128.4 133.6 ±
splitting, Dd 5.2 0.0
4a DMSO 167.5 120.1 142.6 133.2 130.0 130.0 129.0 129.0 134.8 ±

(3:1 mixture of acetic/concentrated hydrochloric acid

heated at 708C) reactions.
The one-dimensional 13C NMR spectra were
obtained in DMSO-d6 solutions at room temperature
on a Bruker AMX 300 spectrometer working at
75 MHz. All the chemical shifts are expressed in
parts per million reported to external TMS. 13C
assignments were made using HETCOR and HMBC
experiments (delay for long-range J C/H couplings
were optimized for 7 Hz). 13C 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
has been carried out at the B3LYP/6-31G p 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
2. Experimental mentioned computational level.

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, K2CO3,
acetone at re¯ux) of the corresponding cinnamic The 13C chemical shifts of the eight compounds are
acids 1a, 3a and 4a. Ester 2b was prepared from 4- gathered in Tables 1 (acids) and 2 (esters). The two
hydroxycinnamic acid 2a by a sequence of transfor- CH carbons of esters 1b, 3b and 4b have already been
mations: benzylation (benzyl chloride, K2CO3, DMF reported by Brazilian authors [15]. Leaving aside, for
at re¯ux), saponi®cation (aqueous NaOH and the moment, the splitting observed in the solid state
methanol heated at 708C), methylation (methyl for ortho and meta carbons of almost all compounds
sulfate, K2CO3, acetone at re¯ux) and debenzylation (only the meta carbons of 4a and 4b coincide), the
 A.M.S. Silva et al. / Journal of Molecular Structure 595 (2001) 1±6 3

Table 2
13
C chemical shifts of methyl cinnamates (in ppm). In bold, splitted signals

Compound Cond. CO2Me CH(CO) CH(Ar) Cipso Cortho Cortho 0 Cmeta Cmeta 0 Cpara p-R and CO2Me

1b Solid 167.4 116.8 143.0 126.7 127.3 134.6 109.7 117.7 161.0 54.8 (MeO)
splitting, Dd 7.3 8.0
1b DMSO 167.1 115.1 144.4 126.7 130.2 130.2 114.4 114.4 161.2 55.3 (MeO)
51.4 (CO2Me)
2b Solid 169.8 115.5 145.7 127.3 124.8 134.2 113.8 115.5 159.1 ±
splitting, Dd 9.4 1.7
53.8 (CO2Me)
2b DMSO 167.2 114.0 144.9 125.1 130.5 130.5 115.9 115.9 160.0 51.4 (CO2Me)
3b Solid 167.5 116.7 146.8 131.7 125.7 131.7 126.5 131.7 140.8 21.1 (Me)
splitting, Dd 6.0 5.2
50.8 (CO2Me)
3b DMSO 166.9 116.7 144.7 131.3 128.5 128.5 129.6 129.6 140.6 21.1 (Me)
51.5 (CO2Me)
4b Solid 167.7 118.0 144.5 132.8 127.4 136.9 127.4 127.4 136.9 ±
splitting, Dd 9.5 0.0
53.9 (CO2Me)
4b DMSO 166.6 118.7 143.2 133.0 130.2 130.2 129.0 129.0 135.1 ±
51.6 (CO2Me)

Table 3
13
C absolute shieldings s and estimated 13C chemical shifts d (both in ppm) of cinnamic acids. The predicted values are in italics

Compound CO2H CH(CO) CH(Ar) Cipso Cortho(CyC) Cortho 0 (CH) Cmeta(CyC) Cmeta 0 (CH) Cpara p-R

1aE s 33.31 84.07 48.68 69.12 68.78 60.87 85.65 a 78.03 36.72 137.20 (MeO)
d 164.6 111.1 148.4 126.8 127.2 135.5 109.4 117.4 161.0 55.1
Dd 8.3 8.0
d average 131.4 113.4
2aE s 33.39 84.03 48.99 69.14 68.97 59.95 81.90 a 80.69 39.58 ±
d 164.5 111.1 148.0 126.8 127.0 136.5 113.4 114.6 158.0
Dd 9.5 1.2
d average 131.8 114.0

3aE s 33.35 82.12 48.20 64.41 70.70 62.32 66.35 66.98 54.85 167.57 (Me)
d 164.5 113.1 148.9 131.8 125.2 134.0 129.7 129.1 141.9 23.1
Dd 8.8 0.6
d average 129.6 129.4
3aZ s 34.74 80.20 50.44 64.27 70.80 62.83 66.60 67.02 54.97 167.61 (Me)
d 164.2 114.9 147.4 131.9 125.1 133.5 129.5 129.0 141.7 23.0
Dd 8.4 0.5
d average 129.3 129.2
4aE s 33.67 80.43 49.60 63.66 70.05 61.84 66.76 66.74 50.22 ±
d 164.2 114.9 147.4 132.6 125.8 134.5 129.3 129.3 146.7
Dd 8.7 0.0
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 have calculated only the E isomers. At this level of the
very similar. If we average the calculated absolute theory, s TMS ˆ 189:69 ppm while, experimentally,
shieldings of ortho and meta carbons, the only differ- Jameson has measured s TMS ˆ 188:1 ^ 0:9 ppm
ences affect the CyO carbon of the carboxylic groups [16,17]. A linear regression of experimental values
(not that of the ester groups). If these four signals are in DMSO solution against absolute shieldings (for
excluded, Eq. (1) is obtained. ortho and meta carbons, average values), leads to
Eq. (2).
d13 Csolid ˆ 1:0025 ^ 0:0016†d13 Csolution ; n ˆ 54;
d13 Csolution ˆ 199:7 ^ 1:2† 2 1:054 ^ 0:015†s 13 C;
2
R ˆ 0:9999
1† n ˆ 39; R2 ˆ 0:992
2†
This equations predicts for the carboxylic groups in
the solid state values close to 168.2 ppm, that is, In Table 3 we have also reported the ®tted and
5.2 ppm higher ®eld than the average experimental predicted (underlined) values using Eq. (2).
values (173.4 ppm). Concerning the ®tted values, they reproduce reason-
Therefore, both acids and esters behave normally in ably well the values in solution (compare Tables 1 and
the solid state and only two aspects of the CPMAS 3). There are some differences that can be assigned to
spectra deserve further study: (i) the `anomalous' the moderate level of the calculations, for instance,
CyO chemical shift of acids; (ii) the splitting of Cpara of 4a appears at about 135 ppm (Table 1) whilst
carbons ortho and meta both in acids and esters as the calculations correspond to 147 ppm, obviously the
well as their assignment; note that the average value ipso chlorine effect is not well reproduced. Three
of the splitted signals coincides with the value in solu- carbon atoms deviate systematically: CyO
tion. (,3 ppm), CH(CO) (,5 ppm) and CH(Ar)
With this aim we carried out a series of GIAO/ (, 2 5 ppm).
B3LYP/6-31G p calculations on compounds 1a, 2a, To discuss the chemical shifts of the ±CHyCH±
3a and 4a. This level is suf®cient for our purposes. CO2H moiety, we need to take into account the dimer-
For compounds 1a, 2a and 4a we used the E confor- ization of carboxylic acids in the solid state as well as
mations while for compound 3a we calculated the two their strong hydrogen bonds with DMSO in solution
conformations, 3aE and 3aZ. In the case of 1aE and [18]. First we have compared the absolute shieldings
2aE the calculated conformation of the methoxy and of formic acid 5 and its dimer 5/5 and transformed
hydroxy groups are as represented (Me and H on the them into d values by means of Eq. (2). On dimeriza-
same side as the CHyCH±CO2H moiety) because tion, the carbon of formic acid moves from 154.3 to
they are like this in the crystal (MXCINN [2] and 163.7 ppm Dd ˆ 9:4 ppm†: This explains why the
COUMAC01 [3]). The absolute shieldings are calculated values (monomers, Table 3) are about
reported in Table 3. 163±164 ppm and the solid state data (dimers, Table
The differences between the calculated absolute 1) are close to 173 ppm in the solid state. In solution,
shieldings of 3aZ and 3aE are too small to be relevant an intermediate situation is found (168 ppm) which
for our purpose; therefore for the other compounds we should correspond to hydrogen bonds with DMSO.
 A.M.S. Silva et al. / Journal of Molecular Structure 595 (2001) 1±6 5

Then, we have studied the effect of the dimerization and small in the case of the OH Dd ˆ 1:2 ppm†:
on acrylic acid 6 to ®nd out if the effect of its dimer- All these conclusions agree fairly well with the
ization, 6/6, extends over the ole®n moiety. According experimental observations.
to the calculations (s values transformed into d
through Eq. (2)), the CyO moves from 161.8 to
169.3 ppm Dd ˆ 7:5 ppm†; the CH(CO) from 125.2 4. Conclusions
to 127.9 Dd ˆ 2:7 ppm† and the terminal CH2
remains unchanged (134.0 and 133.8 ppm). Although, Simple GIAO calculations allow to rationalize the
qualitatively, these effects correspond to those splittings observed for ortho and meta carbons of
observed when Tables 1 and 3 are compared, we cinnamic acids in the solid state. In solution, the
decided to study a more related model: a dimer of free rotation about the single bonds linking the phenyl
cinnamic and formic acids, 3aE/5. The effects ring to CHyCH±CO2R and X substituents suppresses
(again transformed into d values through Eq. (2)) the splitting averaging the signals. Moreover, the
are 17.7 ppm for the CvO and 12.0 ppm for the calculations allow an assignment of the splitted
CH(CO); all other signals are affected by less than signals, thus offering an alternative to a problem of
1 ppm. great experimental dif®culty since it requires very

According to the calculations, the splitting of large monocrystals (several millimeters) and an
ortho and meta carbons can be analyzed, in a NMR instrument provided with a goniometer.
®rst approximation, as coming independently
from the acrylic substituent (Cortho) and from the
p-substituent (Cmeta). The ortho carbon which is on Acknowledgements
the same side as the ±CHyCH±CO2R residue
appears at 125±127 ppm and that on the other We would like to express our thanks to the FCT of
side at 134±136 ppm Dd ˆ 8±9 ppm† indepen- Portugal and University of Aveiro for funding the
dently of the p-substituent (because meta effects Research Unit No. 62/94 and also to FCT for a grant
are usually small). The meta carbon chemical (A.M.S.S., FMRH/BSAB/153/2000). Financial
shifts depend on the p-substituent (because ortho support from the DGICYT of Spain through the
effects are large). In that case, two situations are SAF 97-0044-C02 project also is gratefully acknowl-
possible: (i) the X substituent has an axial edged. Sincere thanks are expressed to Prof. JoaÄo
symmetry (CH3 3, Cl 4) and both meta carbons Rocha and Ms. Ana Paula Zhu, University of Aveiro,
are very similar (Dd null or very small); (ii) the for the CPMAS NMR spectra.
substituent has two planar conformations with
regard to the phenyl ring (OCH3 1, OH 2). References
According to the calculations, the difference is
large in the case of the methoxy Dd ˆ 8:0 ppm† [1] F.H. Allen, J.E. Davies, J.J. Galloy, O. Johnson, O. Kennard,
6 A.M.S. Silva et al. / Journal of Molecular Structure 595 (2001) 1±6

C.F. Macrae, E.M. Mitchell, G.F. Mitchell, J.M. Smith, D.G. Adamo, S. Clifford, J. Ochterski, G.A. Petersson, P.Y. Ayala,
Watson, J. Chem. Inf. Comput. Sci. 31 (1991) 187. Q. Cui, K. Morokuma, D.K. Malick, A.D. Rabuck, K. Ragha-
[2] R.F. Bryan, D.P. Freyberg, J. Chem. Soc., Perkin Trans. 2 vachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz, B.B.
(1975) 1835. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.
[3] R.F. Bryan, P.G. Forcier, Mol. Cryst. Liq. Cryst. 60 (1980) Gomperts, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham,
157. C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe,
[4] S. Kashino, H. Oka, M. Haisa, Acta Crystallogr. Sect. C 45 P.M.W. Gill, B.G. Johnson, W. Chen, M.W. Wong, J.L.
(1989) 154. Andres, M. Head-Gordon, E.S. Replogle, J.A. Pople, Gaus-
[5] J.P. Glusker, D.E. Zacharias, H.L. Carrell, J. Chem. Soc., sian 98, Gaussian, Inc., Pittsburgh, PA, 1998.
Perkin Trans. 2 (1975) 68. [10] A.D. Becke, J. Chem. Phys. 98 (1993) 5648.
[6] G.R. Desiraju, Crystal Engineering. The Design of Organic [11] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
Solids, Elsevier, Amsterdam, 1989 (p. 121). [12] P.A. Hariharan, J.A. Pople, Theor. Chim. Acta 28 (1973) 213.
[7] D.M. Skovronsky, B. Zhang, M.-P. Kung, H.F. Kung, J.Q. [13] R. Ditch®eld, Mol. Phys. 27 (1974) 789.
Trojanowski, V.M.-Y. Lee, Proc. Natl Acad. Sci. USA 97 [14] F.J. London, Phys. Radium 8 (1937) 397.
(2000) 7609. [15] F.F. Camio, I.P. de Arruda Campos, J. Gruber, J. Chem. Res. S
[8] Y. Ito, H. Hosomi, S. Ohba, Tetrahedron 56 (2000) 6833. (1998) 270.
[9] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. [16] A.K. Jameson, C.J. Jameson, Chem. Phys. Lett. 134 (1987)
Robb, J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgomery, 461.
R.E. Stratmann, J.C. Burant, S. Dapprich, J.M. Millam, A.D. [17] I. Alkorta, J. Elguero, Struct. Chem. 9 (1998) 187.
Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. [18] T. Bernhard, H. Zimmermann, U. Haeberlen, J. Chem. Phys.
Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. 92 (1990) 2178.