Synthesis of (E)-cinnamyl ester derivatives via a greener Steglich esterification

Article abstract of DOI:10.1016/j.bmc.2018.04.007

Cinnamic acid derivatives are known antifungal, antimicrobial, antioxidant, and anticancer compounds. We have developed a facile and mild methodology for the synthesis of (E)-cinnamate derivatives using a modified Steglich esterification of (E)-cinnamic acid. Using acetonitrile as the solvent, rather than the typical chlorinated solvent, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the coupling agent enables ester conversion in 45 min with mild heating (40–45 °C) and an average yield of 70% without need for further purification. These conditions were used to couple (E)-cinnamic acid with 1° and 2° aliphatic alcohols, benzylic and allylic alcohols, and phenols. This work demonstrates a facile and greener methodology for Steglich esterification reactions.

Full text of DOI:10.1016/j.bmc.2018.04.007

Accepted Manuscript
Synthesis of (E)-cinnamyl ester derivatives via a greener Steglich esterification
Andrew B. Lutjen, Mackenzie A. Quirk, Allycia M. Barbera, Erin M. Kolonko
PII:
S0968-0896(18)30052-X
https://doi.org/10.1016/j.bmc.2018.04.007
BMC 14290
DOI:
Reference:
Bioorganic & Medicinal Chemistry
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Received Date:
Revised Date:
Accepted Date:
11 January 2018
30 March 2018
3 April 2018
Please cite this article as: Lutjen, A.B., Quirk, M.A., Barbera, A.M., Kolonko, E.M., Synthesis of (E)-cinnamyl ester
derivatives via a greener Steglich esterification, Bioorganic & Medicinal Chemistry (2018), doi: https://doi.org/
10.1016/j.bmc.2018.04.007
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Synthesis of (E)-cinnamyl ester derivatives
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via a greener Steglich esterification
Andrew B. Lutjen, Mackenzie A. Quirk, Allycia M. Barbera, Erin M. Kolonko*
Department of Chemistry and Biochemistry, Siena College, Loudonville, NY 12211, United States

Bioorganic & Medicinal Chemistry
Synthesis of (E)-cinnamyl ester derivatives via a greener Steglich esterification
Andrew B. Lutjen, Mackenzie A. Quirk, Allycia M. Barbera, and Erin M. Kolonko
Department of Chemistry and Biochemistry, Siena College, 515 Loudon Road, Loudonville, NY 12211, United States
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Cinnamic acid derivatives are known antifungal, antimicrobial, antioxidant, and anticancer
compounds. We have developed a facile and mild methodology for the synthesis of (E)-
cinnamate derivatives using a modified Steglich esterification of (E)-cinnamic acid. Using
acetonitrile as the solvent, rather than the typical chlorinated solvent, and 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (EDC) as the coupling agent enables ester conversion in 45
minutes with mild heating (40-45 °C) and an average yield of 70% without need for further
purification. These conditions were used to couple (E)-cinnamic acid with 1° and 2° aliphatic
alcohols, benzylic and allylic alcohols, and phenols. This work demonstrates a facile and greener
methodology for Steglich esterification reactions.
Available online
Key words:
Steglich esterification
(E)-Cinnamic acid
Cinnamyl ester derivatives
Green solvent
2009 Elsevier Ltd. All rights reserved.
1. Introduction
dicyclohexylcarbodiimide (DCC), to form an O-acylisourea
intermediate. For ester synthesis, the addition of N-
(E)-Cinnamaldehyde and (E)-cinnamic acid (1), natural
products isolated from cinnamon, and their derivatives are known
to have antifungal, antimicrobial, antioxidant, and anticancer
properties.1–4 The facile synthesis of libraries of cinnamic acid
derivatives could enable further investigations of these
properties. In order to synthesize small libraries efficiently using
a routine methodology, a reaction that is general for a variety of
commercially available alcohol substrates and that does not
require additional purification steps is required. In addition, a
primary goal for this work was to use the esterification reaction
in an introductory undergraduate laboratory curriculum, and thus,
a methodology that 1) uses a non-halogenated solvent system, 2)
has a short reaction time (setup, reaction, and workup in < 4h),
and 3) works with non-anhydrous solvents under air was needed.
(E)-Cinnamyl ester derivatives have previously been synthesized
from (E)-cinnamic acid and alcohols by Fischer esterification5,6
or by the use of acyl chloride intermediates;2,3,7 however, these
methods would not fit the requirements for our methodology. In
contrast, carbodiimide coupling reactions, such as the Steglich
esterification, have been used to facilitate the esterification of
cinnamic acid and various alcohols8–14 and do not require high
temperatures or reactive acyl halide intermediates.
(dimethylamino)pyridine (DMAP) is required to minimize the
formation of the unproductive acyl migration byproduct, which is
competitive with the nucleophilic attack of the alcohol on the O-
acylisourea intermediate. The intramolecular acyl migration
byproduct formation is slow compared to nucleophilic attack of
amino groups. Under conditions using an excess of DMAP, an
acyl pyridinium intermediate is formed,18 which then reacts with
the alcohol to regenerate DMAP and to form the ester product.
Carbodiimide coupling reactions are often performed in
anhydrous chlorinated solvents or dimethylformamide (DMF)
under a nitrogen atmosphere. These solvent systems are
hazardous to the environment and human health and are rated
“undesirable” in green chemistry solvent selection guides.19
2. Results and discussion
2.1. Solvent modification
To develop a methodology that met our requirements of a less
hazardous solvent system with short reaction times and moderate
temperature, the Steglich esterification conditions were modified
by substituting the solvent with a less hazardous option. Initial
attempts with using recommended green solvents (e.g. ethyl
acetate and acetone) did not yield product. Acetonitrile is a rated
“usable” by the ACS Green Chemistry Institute and a preferable
alternative to DMF.19 This solvent has been used for Steglich
esterification reactions previously, although products were
1.1. Steglich esterification
The Steglich esterification (Figure 1) utilizes a carbodiimide
along with N-(dimethylamino)pyridine (DMAP) to activate an
acid and enable ester formation.9,15–17 In this reaction, the acid is
activated by the carbodiimide, traditionally N,N’-
f—irs—t —
 Corresponding author. E-mail: ekolonko@siena.edu (E. Kolonko)

Figure 1. General mechanism of the Steglich esterification reaction
kobs
purified via chromatography after workup.20–23 To simplify
purification of the ester product, DCC was substituted for the
water soluble carbodiimide reagent 1-ethyl-3-(3-
O
O
EDC
DMAP (3 eq)
O
H O
O H
+
ACN-d3
5 eq
dimethylaminopropyl)carbodiimide (EDC). This reagent enables
an efficient aqueous extraction workup, eliminates the need for a
chromatography purification step, and generates a urea byproduct
that does not pose a health or environmental hazard.24–26 In
addition, the alcohol substrates were used as the limiting reagent,
as excess cinnamic acid could be removed in the extraction step
and many of the alcohols used would require additional
purification post-extraction if used in excess.
kobs = 0.00651 ± 0.00006 M-1s-1
0.08
0.07
0.06
0.05
0.04
0.03
0.02
0.01
0
[ester](alkene)
[ester](CH2)
ester fit
2.2. Relative rate comparison
[acid](alkene)
acid fit
The relative rates of the modified Steglich esterification
reaction in different solvent systems, ACN-d3, CD2Cl2, CDCl3,
and DMF-d7, were determined by monitoring the reaction
1
between (E)-cinnamic acid and ethanol in situ via H NMR
0
1000
2000
3000
4000
5000
6000
7000
8000
spectroscopy (Figure 2). Previous studies have reported that the
initial nucleophilic attack of the deprotonated acid on the
carbodiimide reagent is the rate-limiting step of the reaction
(Figure 1).15,27 To minimize any possible complications, the
esterification reactions were performed with an excess of both
alcohol and DMAP.18 The reaction time-course was fitted to a
second-order kinetic model28 (Figure 2) of a bimolecular reaction
between acid and EDC to obtain relative rate constants in each
solvent (Table 1). At 25 C, the rate of the reaction in CD2Cl2 and
CDCl3 was approximately three times and two times faster than
that of the reaction in ACN-d3 (Table 1), respectively. However,
the reaction was two times faster in ACN-d3 than in DMF-d7.
These rate data indicate that as a solvent system for the Steglich
esterification reaction, acetonitrile is within the spectrum of rates
Time (s)
p
˜
n
18
15
12
9
t = 8004 s
4447 s
2535 s
1527 s
1210 s
889 s
//
//
//
//
//
//
//
7
5
Table 1. Observed relative second order rate constants for the
esterification reaction between (E)-cinnamic acid and ethanola
3
568 s
Solvent
Relative rate constant (M-1s-1)
0.00651  0.00006
0.0183  0.0004
1
247
s
//
acetonitrile-d3
dichloromethane-d2
chloroform-d
7.8
7.7
7.6
7.5
7.4
7.3
7.2
7.1
4.4
4.3
4.2
4.1
ppm
Figure 2. Modeled rate curves (middle) and 1H NMR spectrum data
0.0128  0.0002
(bottom) for the reaction between (E)-cinnamic acid (red) and ethanol to
form (E)-ethyl cinnamate (blue) in acetonitrile-d3 (top). Integrated peaks
are highlighted in the 1H NMR spectra and correspond to the ester alkene
(1H, ),the acid alkene (1H, ) , and the ester methylene (2H, ).
Relative integrations were converted to concentration (M). The rate of the
reaction was modeled using a section-order reaction.
dimethylformamide-d7
0.00332 0.00003
aThe relative rate constant data is based on a second-order kinetic model:15,27
acid + EDC  ester + urea (d[ester]/dt = k[acid][EDC]).

for commonly used solvents such as chloroform,
dichloromethane, and dimethylformamide.
column purification, based on NMR analysis.
Using this method, we synthesized a series of (E)-cinnamyl
ester derivatives (7-41, Table 2). Primary (2a-g) and secondary
(3a-c) aliphatic alcohols and benzyl (4a-n) and allylic (5)
alcohols form esters readily at 40-45 C. Phenols containing both
electron donating (6a-d) and electron withdrawing (6e-i)
substituents can also be reacted readily with (E)-cinnamic acid
under the same conditions. The reaction is tolerant to functional
groups such as amide (6a), aldehyde (6d), ketone (6g), and nitrile
(6h); however, strongly nucleophilic functionalities such as
amino and additional hydroxy groups compete with the desired
ester formation. More sterically hindered benzyl alcohols (4b-c)
and vanillin (6d) required additional heat (60 C) to enable
appreciable yields at reaction times of 45 min. Moderate yields
(e.g. 3b and 6i) under the standard conditions (40-45 C, 45 min)
can be improved with longer reaction times (room temperature,
24 h) or increased temperature (60 C). Ester products between
2.3. Synthesis of cinnamyl ester derivatives
Based on this kinetic data and using a rough approximation of
doubled rate for a 10 C temperature increase, the modified
Steglich esterification reaction was performed at 40-45 C. These
conditions were chosen to enable a rate similar to that of
dichloromethane at room temperature, while also remaining
below the boiling point of acetonitrile to avoid use of a reflux
condenser. A variety of alcohols were used to assess the tolerance
of the reaction to steric and electronic effects with respect to the
alcohol. After 45 minutes, analysis of the reaction between
cinnamic acid and benzyl alcohol by TLC demonstrated loss of
the alcohol. Solvent removal followed by an acid-base extraction
workup provided the ester product without the need for flash
Table 2. Cinnamyl ester derivatives synthesized via the modified Steglich esterification
a Standard conditions: (E)-cinnamic acid (1.2 eq), alcohol (1 eq), EDC (1.5 eq), DMAP (3 eq), acetonitrile, 40-45 C, 45 min.
b Reaction performed at 60 C for 45 min.
c Reaction performed at room temperature for 24 h.

(E)-cinnamic acid and tertiary alcohols could not be isolated
under these conditions, which is currently a limitation compared
to chlorinated solvent systems.29 Increasing temperature to reflux,
the addition of HOBt, or additional reaction time (24 h) did not
yield any isolated product between t-butyl alcohol and (E)-
cinnamic acid. Additional NMR kinetics and computational
studies are currently underway to investigate the mechanism and
constraints of this reaction in more detail.
method, and fitting acid and ester concentration to the second-
order reaction:
acid + EDC  ester + urea (d[ester]/dt = k[acid][EDC]).
1H NMR time course spectra and modeled rate curves can be
found in Figure 2 (acetonitrile-d3) and in the Supplementary
Information.
3.3. General procedure for the preparation of 7-41
2.4. Summary
(E)-Cinnamic acid (1) (0.167 g, 1.13 mmol), EDC (0.270 g,
1.4 mmol), DMAP (0.343 g, 2.8 mmol), and the alcohol (2a-6i)
(0.97 mmol) were combined with acetonitrile (15 mL). The
reaction mixture was stirred at 40-45 C in a water bath for 45
minutes. Reactions involving aromatic alcohols were monitored
for loss of alcohol by TLC (aluminum-backed silica gel plates,
1:4 ethyl acetate/hexanes). The solvent was removed under
reduced pressure. The residue was dissolved in diethyl ether (25
mL), and the solution was washed with 3 M HCl (2 x 20 mL),
saturated sodium bicarbonate (2 x 20 mL), and brine (20 mL).
The organic layer was dried with MgSO4 and filtered, and the
solvent was removed under reduced pressure to yield the
corresponding ester. The spectral data are summarized below for
Our group has developed modified Steglich esterification
conditions using acetonitrile and EDC as the carbodiimide in an
effort to eliminate the need for additional purification steps and
to make the solvent system less hazardous to the environment
and human health. Kinetic studies of acetonitrile compared to
traditional solvent systems for the Steglich esterification
demonstrated that the reaction rate was not substantially affected
by the greener solvent system. The conditions were used to make
a small library of (E)-cinnamyl ester derivatives by coupling (E)-
cinnamic acid with 1° and 2° aliphatic alcohols, benzyl and
allylic alcohols, and phenols. This work provides an alternative
methodology for the preparation of (E)-cinnamyl ester
derivatives that have potential utility in a variety of biological
applications. In addition, it demonstrates the utility of acetonitrile
as a less hazardous solvent system for carbodiimide coupling
reactions.
1
each compound. H and 13C NMR spectra can be found in the
Supplementary Information.
3.3.1. (E)-Ethyl cinnamate (7)
7 was synthesized according to the general procedure using
ethanol, 2a (0.97 mmol, 0.060 mL) to yield a light yellow liquid
1
(132 mg, 77%). H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 16.0
3. Experimental section
Hz, 1H), 7.63 – 7.48 (m, 2H), 7.47 – 7.34 (m, 3H), 6.46 (d, J =
16.0 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H);
13C NMR (126 MHz, CDCl3) δ 167.00, 144.58, 134.51, 130.21,
128.88, 128.05, 118.32, 60.50, 14.33; HRMS ESI calcd for
C11H12O2 (M+Na)+ 199.0730, found 199.0730.
3.1. General experimental procedures
All commercially available reagents and solvents were used as
received without further purification. The 1H and 13C NMR
spectra were measured on a Bruker AVANCE HD 500 MHz (126
MHz for 13C) NMR Spectrometer with trimethylsilane as the
internal standard. Chemical shifts () are reported in ppm, and
coupling constants (J) are reported in hertz (Hz). Signals are
reported as singlet (s), doublet (d), triplet (t), quartet (q),
multiplet (m), or combinations of the above. HRMS data were
acquired on a Bruker Maxis Impact HD Q-TOF Mass
Spectrometer with a standard electrospray ionization source and
are reported as m/z. Melting points (m.p.) were determined using
a Mel-Temp capillary melting point apparatus with a Vernier
temperature probe.
3.3.2. (E)-Methyl cinnamate (8)
8 was synthesized according to the general procedure using
methanol, 2b (0.97 mmol, 0.040 mL) to yield a light yellow solid
(86 mg, 55%). m.p. 31.2-32.2 C; 1H NMR (500 MHz, CDCl3) δ
7.73 (d, J = 16.0 Hz, 1H), 7.60 – 7.47 (m, 2H), 7.45 – 7.36 (m,
3H), 6.47 (d, J = 16.0 Hz, 1H), 3.84 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 167.42, 144.87, 134.41, 130.28, 128.89, 128.07,
117.82, 51.70; HRMS ESI calcd for C10H10O2 (M+Na)+
185.0573, found 185.0569.
3.3.3. (E)-Propyl cinnamate (9)
3.2. Relative rate determination
9 was synthesized according to the general procedure using
propanol, 2c (0.97 mmol, 0.073 mL) to yield a light yellow liquid
(127 mg, 69%). H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 16.0
Hz, 1H), 7.63 – 7.50 (m, 2H), 7.45 – 7.37 (m, 3H), 6.47 (d, J =
16.0 Hz, 1H), 4.20 (t, J = 6.7 Hz, 2H), 1.76 (qt, J = 7.4, 6.7 Hz,
2H), 1.02 (t, J = 7.4 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ
167.08, 144.55, 134.50, 130.19, 128.86, 128.04, 118.31, 66.15,
22.11, 10.45; HRMS ESI calcd for C12H14O2 (M+Na)+ 213.0886,
found 213.0889.
1
EDC (21.7 mg, 0.113 mmol, 2 eq) and DMAP (20.8 mg,
0.170 mmol, 3 eq) were dissolved in deuterated solvent (0.75
mL). Ethanol (16.55 L, 0.283 mmol, 5 eq) was added followed
by (E)-cinnamic acid (8.4 mg, 0.0567 mmol, 1 eq). The solution
was quickly mixed by pipette and added to a 5 mm NMR tube.
1H NMR spectra were acquired at 25 C at two, five, or ten
minute intervals for at least three half-lives of the reaction. To
account for sample mixing and loading time, a timer was used to
estimate t=0 at the addition of the cinnamic acid, and the NMR
spectrum timepoints were adjusted accordingly.
3.3.4. (E)-Hexyl cinnamate (10)
10 was synthesized according to the general procedure using
hexanol, 2d (0.93 mmol, 0.116 mL) and corresponding amounts
of cinnamic acid, EDC, and DMAP to yield a light yellow liquid
1
Relative integrations of the ester and acid alkene H signals
1
and the ester methylene H signal over time were determined
1
(205 mg, 95%). H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 16.0
using the Reaction Monitoring plugin in the Mnova NMR
processing software. The relative integrations were converted to
concentration (M) by comparison to the total alkene integration
(ester alkene + acid alkene = 1H = 0.0756 M) for each spectrum.
The rate of these reactions was simulated with COPASI28 using a
parameter estimation routine and the Levenberg-Marquardt
Hz, 1H), 7.62 – 7.49 (m, 2H), 7.46 – 7.35 (m, 3H), 6.47 (d, J =
16.0 Hz, 1H), 4.23 (t, J = 6.8 Hz, 2H), 1.79 – 1.68 (m, 2H), 1.48
– 1.39 (m, 2H), 1.39 – 1.32 (m, 4H), 0.98 – 0.88 (m, 3H); 13C
NMR (126 MHz, CDCl3) δ 167.09, 144.53, 134.51, 130.19,
128.86, 128.04, 118.33, 64.74, 31.48, 28.71, 25.66, 22.56, 14.01;

HRMS ESI calcd for C15H20O2 (M+Na)+ 255.1356, found
255.1359.
MHz, CDCl3) δ 166.43, 144.24, 134.59, 130.10, 128.84, 128.02,
118.92, 72.75, 31.76, 25.45, 23.83; HRMS ESI calcd for
C15H18O2 (M+Na)+ 253.1199, found 253.1199.
3.3.5. (E)-3-Methylbutyl cinnamate (11)
3.3.11. (E)-Diphenylmethyl cinnamate (17)
11 was synthesized according to the general procedure using
isoamyl alcohol, 2e (0.93 mmol, 0.100 mL) and corresponding
amounts of cinnamic acid, EDC, and DMAP to yield a colorless
liquid (189 mg, 93%). 1H NMR (500 MHz, CDCl3) δ 7.71 (d, J =
16.0 Hz, 1H), 7.63 – 7.48 (m, 2H), 7.47 – 7.32 (m, 3H), 6.46 (d, J
= 16.0 Hz, 1H), 4.27 (t, J = 6.9 Hz, 2H), 1.78 (nonet, J = 6.9 Hz,
1H), 1.63 (q, J = 6.9 Hz, 2H), 0.99 (d, J = 6.6 Hz, 6H); 13C NMR
(126 MHz, CDCl3) δ 167.07, 144.54, 134.50, 130.19, 128.86,
128.05, 118.33, 63.23, 37.46, 25.15, 22.51; HRMS ESI calcd for
C14H18O2 (M+Na)+ 241.1199, found 241.1200.
17 was synthesized according to the general procedure using
diphenylmethanol, 4a (0.97 mmol, 180 mg) to yield a white solid
1
(197 mg, 65%). m.p. 79.8-80.5 C; H NMR (500 MHz, CDCl3)
δ 7.79 (d, J = 16.0 Hz, 1H), 7.60 – 7.54 (m, 2H), 7.46 – 7.36 (m,
11H), 7.35 – 7.30 (m, 2H), 7.05 (s, 1H), 6.60 (d, J = 16.0 Hz,
1H); 13C NMR (126 MHz, CDCl3) δ 165.98, 145.44, 140.28,
134.37, 130.41, 128.91, 128.53, 128.17, 127.93, 127.20, 118.04,
77.00; HRMS ESI calcd for C22H18O2 (M+Na)+ 337.1199, found
337.1191.
3.3.6. (E)-2-Methylpropyl cinnamate (12)
3.3.12. (E)-9-Anthracenemethyl cinnamate (18)
12 was synthesized according to the general procedure using
isobutyl alcohol, 2f (0.97 mmol, 0.090 mL) to yield a yellow
liquid (127 mg, 64%). 1H NMR (500 MHz, CDCl3) δ 7.72 (d, J =
16.0 Hz, 1H), 7.66 – 7.49 (m, 2H), 7.47 – 7.33 (m, 3H), 6.48 (d, J
= 16.0 Hz, 1H), 4.02 (d, J = 6.7 Hz, 2H), 2.04 (nonet, J = 6.7 Hz,
1H), 1.02 (d, J = 6.7 Hz, 6H); 13C NMR (126 MHz, CDCl3) δ
167.07, 144.55, 134.50, 130.20, 128.86, 128.05, 118.31, 70.67,
27.86, 19.17; HRMS ESI calcd for C13H16O2 (M+Na)+ 227.1043,
found 227.1044.
18 was synthesized according to the general procedure at 60
C using 9-anthracenemethanol, 4b (0.97 mmol, 202 mg) to yield
1
a yellow solid (267 mg, 81%). m.p. 127.1-127.8 C; H NMR
(500 MHz, CDCl3) δ 8.57 (s, 1H), 8.43 (dd, J = 8.9, 1.0 Hz, 2H),
8.08 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 16.0 Hz, 1H), 7.62 (ddd, J =
9.0, 6.5, 1.4 Hz, 2H), 7.54 (ddd, J = 8.4, 6.5, 1.1 Hz, 2H), 7.52 –
7.44 (m, 2H), 7.43 – 7.33 (m, 3H), 6.47 (d, J = 16.0 Hz, 1H),
6.32 (s, 2H); 13C NMR (126 MHz, CDCl3) δ 167.19, 145.30,
134.34, 131.44, 131.16, 130.30, 129.22, 129.13, 128.83, 128.08,
126.70, 126.30, 125.14, 124.01, 117.81, 58.96; HRMS ESI calcd
for C24H18O2 (M+Na)+ 361.1199, found 361.1199.
3.3.7. (E)-Cyclohexylmethyl cinnamate (13)
13 was synthesized according to the general procedure using
cyclohexanol, 2g (0.97 mmol, 0.114 mL) to yield a light yellow
3.3.13. (E)-1-Naphthalenemethyl cinnamate (19)
1
oil (209 mg, 92%). H NMR (500 MHz, CDCl3) δ 7.71 (d, J =
19 was synthesized according to the general procedure at 60
C using 1-naphthalenemethanol, 4c (0.97 mmol, 153 mg) to
16.0 Hz, 1H), 7.58 – 7.52 (m, 2H), 7.48 – 7.34 (m, 3H), 6.47 (d, J
= 16.0 Hz, 1H), 4.05 (d, J = 6.6 Hz, 2H), 1.93 – 1.60 (m, 5H),
1.40 – 1.14 (m, 3H), 1.05 (qd, J = 12.1, 3.0 Hz, 2H); 13C NMR
(126 MHz, CDCl3) δ 167.13, 144.53, 134.53, 130.20, 128.87,
128.06, 118.35, 69.73, 37.26, 29.75, 26.41, 25.72; HRMS ESI
calcd for C16H20O2 (M+Na)+ 267.1356, found 267.1355.
1
yield a light yellow solid (183 mg, 65%). m.p. 62.7-64.0 C; H
NMR (500 MHz, CDCl3) δ 8.08 (br d, J = 8.7 Hz, 1H), 7.90 (dd,
J = 8.1, 1.6 Hz, 1H), 7.87 (d, J = 8.3 Hz, 1H), 7.73 (d, J = 16.0
Hz, 1H), 7.61 (br d, J = 6.8 Hz, 1H), 7.58 (ddd, J = 8.4, 6.9, 1.5
Hz, 1H), 7.53 (ddd, J = 8.0, 6.9, 1.3 Hz, 1H), 7.50 – 7.45 (m,
3H), 7.39 – 7.33 (m, 3H), 6.49 (d, J = 16.0 Hz, 1H), 5.71 (s, 2H);
13C NMR (126 MHz, CDCl3) δ 166.86, 145.28, 134.35, 133.77,
131.72, 131.55, 130.34, 129.34, 128.87, 128.73, 128.11, 127.56,
126.62, 125.97, 125.32, 123.64, 117.86, 64.71; HRMS ESI calcd
for C20H16O2 (M+Na)+ 311.1043, found 311.1040.
3.3.8. (E)-Isopropyl cinnamate (14)
14 was synthesized according to the general procedure using
isopropanol, 3a (0.97 mmol, 0.074 mL) to yield a yellow liquid
1
(115 mg, 62%). H NMR (500 MHz, CDCl3) δ 7.69 (d, J = 16.0
Hz, 1H), 7.59 – 7.49 (m, 2H), 7.45 – 7.34 (m, 3H), 6.44 (d, J =
16.0 Hz, 1H), 5.17 (heptet, J = 6.3 Hz, 1H), 1.34 (d, J = 6.3 Hz,
6H); 13C NMR (126 MHz, CDCl3) δ 166.52, 144.29, 134.56,
130.12, 128.85, 128.39, 128.01, 118.83, 67.80, 21.95; HRMS
ESI calcd for C12H14O2 (M+Na)+ 213.0886, found 213.0886.
3.3.14. (E)-Benzyl cinnamate (20)
20 was synthesized according to the general procedure using
benzyl alcohol, 4d (0.93 mmol, 0.097 mL) and corresponding
amounts of cinnamic acid, EDC, and DMAP to yield a light
yellow liquid (175 mg, 76%). 1H NMR (500 MHz, CDCl3) δ 7.77
(d, J = 16.0 Hz, 1H), 7.58 – 7.53 (m, 2H), 7.47 – 7.40 (m, 7H),
7.40 – 7.35 (m, 1H), 6.53 (d, J = 16.0 Hz, 1H), 5.29 (s, 2H); 13C
NMR (126 MHz, CDCl3) δ 166.78, 145.18, 136.09, 134.39,
130.35, 128.90, 128.61, 128.29, 128.26, 128.21, 128.12, 117.91,
66.37; HRMS ESI calcd for C16H14O2 (M+Na)+ 261.0886, found
261.0885.
3.3.9. (E)-1-Methylpropyl cinnamate (15)
15 was synthesized according to the general procedure using
2-butanol, 3b (0.97 mmol, 0.090 mL) to yield a light yellow
liquid (102 mg, 51%). 1H NMR (500 MHz, CDCl3) δ 7.70 (d, J =
16.0 Hz, 1H), 7.61 – 7.49 (m, 2H), 7.47 – 7.36 (m, 3H), 6.46 (d, J
= 16.0 Hz, 1H), 5.01 (h, J = 6.3 Hz, 1H), 1.77 – 1.68 (m, 1H),
1.68 – 1.58 (m, 1H), 1.31 (d, J = 6.3 Hz, 3H), 0.97 (t, J = 7.5 Hz,
3H); 13C NMR (126 MHz, CDCl3) δ 166.68, 144.27, 134.57,
130.11, 128.85, 128.02, 118.82, 72.34, 28.94, 19.56, 9.73;
HRMS ESI calcd for C13H16O2 (M+Na)+ 227.1043, found
227.1043.
3.3.15. (E)-2-Bromobenzyl cinnamate (21)
21 was synthesized according to the general procedure using
2-bromobenzyl alcohol, 4e (0.93 mmol, 174 mg) and
corresponding amounts of cinnamic acid, EDC, and DMAP to
yield a colorless oil (125 mg, 42%). 1H NMR (500 MHz, CDCl3)
δ 7.79 (d, J = 16.1 Hz, 1H), 7.63 (dd, J = 8.0, 1.2 Hz, 1H), 7.59 –
7.54 (m, 2H), 7.50 (dd, J = 7.6, 1.7 Hz, 1H), 7.44 – 7.40 (m, 3H),
7.37 (td, J = 7.5, 1.2 Hz, 1H), 7.23 (td, J = 7.7, 1.7 Hz, 1H), 6.55
(d, J = 16.0 Hz, 1H), 5.37 (s, 2H); 13C NMR (126 MHz, CDCl3) δ
166.55, 145.51, 135.46, 134.34, 132.91, 130.44, 129.91, 129.72,
128.92, 128.18, 127.54, 123.50, 117.63, 65.88; HRMS ESI calcd
for C16H13BrO2 (M+Na)+ 338.9991, found 338.9990.
3.3.10. (E)-Cyclohexyl cinnamate (16)
16 was synthesized according to the general procedure using
cyclohexanol, 3c (0.93 mmol, 0.100 mL) and corresponding
amounts of cinnamic acid, EDC, and DMAP to yield a colorless
1
oil (129 mg, 58%). H NMR (500 MHz, CDCl3) δ 7.69 (d, J =
16.0 Hz, 1H), 7.59 – 7.51 (m, 2H), 7.46 – 7.34 (m, 3H), 6.46 (d, J
= 16.0 Hz, 1H), 4.92 (tt, J = 9.2, 3.9 Hz, 1H), 2.01 – 1.90 (m,
2H), 1.84 – 1.72 (m, 1H), 1.66 – 1.57 (m, 1H), 1.57 – 1.48 (m,
2H), 1.50 – 1.37 (m, 2H), 1.37 – 1.25 (m, 1H); 13C NMR (126

3.3.16. (E)-3-Bromobenzyl cinnamate (22)
128.87, 128.08, 127.93, 124.39, 120.47, 118.19, 110.52, 61.82,
55.48; HRMS ESI calcd for C17H16O3 (M+Na)+ 291.0992, found
291.0989.
22 was synthesized according to the general procedure using
3-bromobenzyl alcohol, 4f (0.97 mmol, 0.116 mL) to yield a light
yellow oil (227 mg, 74%). 1H NMR (500 MHz, CDCl3) δ 7.77 (d,
J = 16.0 Hz, 1H), 7.60 (t, J = 1.9 Hz, 1H), 7.58 – 7.53 (m, 2H),
7.50 (ddd, J = 8.0, 2.0, 1.1 Hz, 1H), 7.45 – 7.39 (m, 3H), 7.37
(ddd, J = 7.8, 1.8, 1.0 Hz, 1H), 7.28 (t, J = 7.8 Hz, 1H), 6.52 (d, J
= 16.0 Hz, 1H), 5.24 (s, 2H); 13C NMR (126 MHz, CDCl3) δ
166.58, 145.56, 138.38, 134.27, 131.32, 131.12, 130.47, 130.16,
128.93, 128.17, 126.69, 122.64, 117.84, 117.55, 65.33; HRMS
ESI calcd for C16H13BrO2 (M+Na)+ 338.9991, found 338.9987.
3.3.22. (E)-3-Methoxybenzyl cinnamate (28)
28 was synthesized according to the general procedure using
3-methoxybenzyl alcohol, 4l (0.93 mmol, 174 mg) and
corresponding amounts of cinnamic acid, EDC, and DMAP to
1
yield a light yellow oil (225 mg, 90%). H NMR (500 MHz,
CDCl3) δ 7.77 (d, J = 16.0 Hz, 1H), 7.60 – 7.50 (m, 2H), 7.49 –
7.36 (m, 3H), 7.33 (t, J = 7.8 Hz, 2H), 7.03 (ddd, J = 7.4, 1.5, 0.8
Hz, 1H), 7.02 – 6.97 (m, 1H), 6.91 (ddd, J = 8.3, 2.6, 1.0 Hz,
1H), 6.53 (d, J = 16.0 Hz, 1H), 5.26 (s, 2H), 3.86 (s, 3H); 13C
NMR (126 MHz, CDCl3) δ 166.75, 159.80, 145.22, 137.60,
134.38, 130.36, 129.66, 128.90, 128.12, 120.44, 117.87, 113.78,
113.71, 66.23, 55.27; HRMS ESI calcd for C17H16O3 (M+Na)+
291.0992, found 291.0993.
3.3.17. (E)-4-Bromobenzyl cinnamate (23)
23 was synthesized according to the general procedure using
4-bromobenzyl alcohol, 4g (0.93 mmol, 174 mg) and
corresponding amounts of cinnamic acid, EDC, and DMAP to
1
yield a light yellow solid (277 mg, 94%). m.p. 76.6-77.9 C; H
NMR (500 MHz, CDCl3) δ 7.76 (d, J = 16.0 Hz, 1H), 7.60 – 7.48
(m, 4H), 7.47 – 7.37 (m, 3H), 7.37 – 7.30 (m, 2H), 6.50 (d, J =
16.0 Hz, 1H), 5.23 (s, 2H); 13C NMR (126 MHz, CDCl3) δ
166.63, 145.46, 135.12, 134.28, 131.75, 130.46, 129.94, 128.93,
128.14, 122.30, 117.61, 65.53; HRMS ESI calcd for C16H13BrO2
(M+Na)+ 338.9991, found 338.9987.
3.3.23. (E)-4-Methoxybenzyl cinnamate (29)
29 was synthesized according to the general procedure using
4-methoxybenzyl alcohol, 4m (0.97 mmol, 134 mg) to yield a
1
white solid (260 mg, >99%). m.p. 59.4-60.9 C; H NMR (500
MHz, CDCl3) δ 7.73 (d, J = 16.0 Hz, 1H), 7.56 – 7.51 (m, 2H),
7.42 – 7.35 (m, 5H), 6.97 – 6.91 (m, 2H), 6.49 (d, J = 16.0 Hz,
1H), 5.21 (s, 2H), 3.84 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
166.86, 159.68, 145.00, 134.42, 130.28, 130.15, 128.88, 128.19,
128.08, 118.06, 114.00, 66.20, 55.30; HRMS ESI calcd for
C17H16O3 (M+Na)+ 291.0992, found 291.0989.
3.3.18. (E)-2-Chlorobenzyl cinnamate (24)
24 was synthesized according to the general procedure using
2-chlorobenzyl alcohol, 4h (0.97 mmol, 140 mg) to yield a light
yellow oil (189 mg, 71%). 1H NMR (500 MHz, CDCl3) δ 7.78 (d,
J = 16.0 Hz, 1H), 7.61 – 7.53 (m, 2H), 7.52 – 7.48 (m, 1H), 7.46
– 7.43 (m, 1H), 7.43 – 7.40 (m, 3H), 7.37 – 7.29 (m, 2H), 6.54 (d,
J = 16.0 Hz, 1H), 5.40 (s, 2H); 13C NMR (126 MHz, CDCl3) δ
166.58, 145.46, 134.33, 133.80, 133.75, 130.42, 129.87, 129.61,
129.50, 128.91, 128.15, 126.91, 117.63, 63.68; HRMS ESI calcd
for C16H13ClO2 (M+Na)+ 295.0496, found 295.0493.
3.3.24. (E)-3,4-Dimethoxybenzyl cinnamate (30)
30 was synthesized according to the general procedure using
3,4-dimethoxybenzyl alcohol, 4n (0.97 mmol, 0.140 mL) to yield
1
a white solid (142 mg, 51%). m.p. 62.6-63.5 C; H NMR (500
MHz, CDCl3) δ 7.75 (d, J = 16.0 Hz, 1H), 7.56 – 7.51 (m, 2H),
7.44 – 7.36 (m, 3H), 7.02 (dd, J = 8.1, 2.0 Hz, 1H), 6.98 (d, J =
2.0 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H), 6.50 (d, J = 16.0 Hz, 1H),
5.21 (s, 2H), 3.93 (s, 3H), 3.91 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 166.87, 149.20, 149.08, 145.12, 134.40, 130.34,
128.90, 128.58, 128.10, 121.37, 118.00, 111.92, 111.11, 66.50,
55.95, 55.93; HRMS ESI calcd for C18H18O4 (M+Na)+ 321.1097,
found 321.1092.
3.3.19. (E)-3-Chlorobenzyl cinnamate (25)
25 was synthesized according to the general procedure using
3-chlorobenzyl alcohol, 4i (0.97 mmol, 0.110 mL) to yield a
1
colorless oil (135 mg, 51%). H NMR (500 MHz, CDCl3) δ 7.77
(d, J = 16.0 Hz, 1H), 7.59 – 7.53 (m, 2H), 7.46 – 7.39 (m, 4H),
7.36 – 7.29 (m, 3H), 6.52 (d, J = 16.0 Hz, 1H), 5.25 (s, 2H); 13C
NMR (126 MHz, CDCl3) δ 166.61, 145.56, 138.12, 134.51,
134.29, 130.48, 129.89, 128.94, 128.39, 128.21, 128.17, 126.19,
117.56, 65.41; HRMS ESI calcd for C16H13ClO2 (M+Na)+
295.0496, found 295.0495.
3.3.25. (E)-2,3-Dimethoxybenzyl cinnamate (31)
31 was synthesized according to the general procedure using
ethanol, 4o (0.97 mmol, 162 mg) to yield a white solid (235 mg,
85%). m.p. 68.3-69.1 C; 1H NMR (500 MHz, CDCl3) δ 7.75 (d,
J = 16.0 Hz, 1H), 7.58 – 7.50 (m, 2H), 7.46 – 7.35 (m, 3H), 7.10
(t, J = 7.9 Hz, 1H), 7.04 (dd, J = 7.8, 1.6 Hz, 1H), 6.95 (dd, J =
8.1, 1.7 Hz, 1H), 6.51 (d, J = 16.0 Hz, 1H), 5.34 (s, 2H), 3.92 (s,
3H), 3.91 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 166.80, 152.76,
147.65, 145.00, 134.43, 130.28, 129.99, 128.88, 128.08, 124.07,
121.73, 118.05, 112.75, 61.73, 61.10, 55.84; HRMS ESI calcd
for C18H18O4 (M+Na)+ 321.1097, found 321.1090.
3.3.20. (E)-4-Chlorobenzyl cinnamate (26)
26 was synthesized according to the general procedure using
4-chlorobenzyl alcohol, 4j (0.93 mmol, 133 mg) and
corresponding amounts of cinnamic acid, EDC, and DMAP to
1
yield a white solid (220 mg, 87%). m.p. 59.8-60.8 C; H NMR
(500 MHz, CDCl3) δ 7.75 (d, J = 16.0 Hz, 1H), 7.58 – 7.51 (m,
2H), 7.44 – 7.40 (m, 3H), 7.38 (s, 4H), 6.50 (d, J = 16.0 Hz, 1H),
5.24 (s, 2H); 13C NMR (126 MHz, CDCl3) δ 166.67, 145.46,
134.61, 134.30, 134.17, 130.46, 129.66, 128.93, 128.80, 128.15,
117.64, 65.51; HRMS ESI calcd for C16H13ClO2 (M+Na)+
295.0496, found 295.0495.
3.3.26. (E)-Cinnamyl cinnamate (32)
32 was synthesized according to the general procedure using
cinnamyl alcohol, 5 (0.97 mmol, 130 mg) to yield colorless oil
1
(130 mg, 51%). H NMR (500 MHz, CDCl3) δ 7.79 (d, J = 16.0
3.3.21. (E)-2-Methoxybenzyl cinnamate (27)
Hz, 1H), 7.60 – 7.55 (m, 2H), 7.48 – 7.44 (m, 2H), 7.44 – 7.40
(m, 3H), 7.40 – 7.35 (m, 2H), 7.33 – 7.29 (m, 1H), 6.76 (dt, J =
15.8, 1.4 Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.41 (dt, J = 15.9,
6.4 Hz, 1H), 4.92 (dd, J = 6.4, 1.4 Hz, 2H); 13C NMR (126 MHz,
CDCl3) δ 166.74, 145.13, 136.31, 134.44, 134.28, 130.38,
128.94, 128.66, 128.16, 128.12, 126.69, 123.36, 117.98, 65.17;
HRMS ESI calcd for C18H16O2 (M+Na)+ 287.1043, found
287.1046.
27 was synthesized according to the general procedure using
2-methoxybenzyl alcohol, 4k (0.97 mmol, 0.130 mL) to yield a
1
light yellow viscous oil (231 mg, 89%). H NMR (500 MHz,
CDCl3) δ 7.76 (d, J = 16.0 Hz, 1H), 7.59 – 7.52 (m, 2H), 7.46 –
7.38 (m, 4H), 7.35 (ddd, J = 8.2, 7.5, 1.8 Hz, 1H), 7.00 (td, J =
7.5, 1.1 Hz, 1H), 6.94 (dd, J = 8.3, 1.0 Hz, 1H), 6.53 (d, J = 16.1
Hz, 1H), 5.34 (s, 2H), 3.89 (s, 3H); 13C NMR (126 MHz, CDCl3)
δ 166.93, 157.59, 144.87, 134.50, 130.23, 129.76, 129.58,

3.3.27. (E)-4-Acetimidophenyl cinnamate (33)
3.3.33. (E)-4-Acetophenyl cinnamate (39)
33 was synthesized according to the general procedure using
4-acetimidophenol, 6a (0.97 mmol, 147 mg) to yield a white
solid (188 mg, 69%). m.p. 198.9-200.5 C; H NMR (500 MHz,
39 was synthesized according to the general procedure using
4-hydroxyacetophenone, 6g (0.97 mmol, 134 mg) to yield a
white crystalline solid (157 mg, 61%). m.p. 126.9-128.9 C; H
1
1
CDCl3) δ 7.89 (d, J = 16.0 Hz, 1H), 7.66 – 7.59 (m, 2H), 7.57 –
7.52 (m, 2H), 7.48 – 7.42 (m, 3H), 7.39 (br s, 1H), 7.16 – 7.11
(m, 2H), 6.65 (d, J = 16.0 Hz, 1H), 2.19 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 168.24, 165.59, 146.95, 146.72, 135.58, 134.14,
130.75, 129.01, 128.32, 122.02, 120.87, 117.17, 24.51; HRMS
ESI calcd for C17H15NO3 (M+Na)+ 304.0944, found 304.0943.
NMR (500 MHz, CDCl3) δ 8.08 – 8.02 (m, 2H), 7.92 (d, J = 16.0
Hz, 1H), 7.66 – 7.56 (m, 2H), 7.51 – 7.42 (m, 3H), 7.35 – 7.30
(m, 2H), 6.66 (d, J = 16.0 Hz, 1H), 2.64 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 196.88, 164.80, 154.59, 147.35, 134.71, 134.01,
130.96, 129.98, 129.07, 128.40, 121.83, 116.76, 26.60; HRMS
ESI calcd for C17H14O3 (M+Na)+ 289.0835, found 289.0831.
3.3.28. (E)-2,6-Dimethoxyphenyl cinnamate (34)
3.3.34. (E)-4-Cyanophenyl cinnamate (40)
34 was synthesized according to the general procedure using
2,6-dimethoxyphenol, 6b (0.97 mmol, 150 mg) to yield a white
solid (202 mg, 73%). m.p. 152.2-152.8 C; H NMR (500 MHz,
CDCl3) δ 7.92 (d, J = 16.0 Hz, 1H), 7.68 – 7.52 (m, 2H), 7.51 –
7.33 (m, 3H), 7.19 (t, J = 8.5 Hz, 1H), 6.76 (d, J = 16.0 Hz, 1H),
6.67 (d, J = 8.5 Hz, 2H), 3.86 (s, 6H); 13C NMR (126 MHz,
CDCl3) δ 164.69, 152.51, 146.48, 134.40, 130.49, 128.91,
128.81, 128.31, 126.26, 116.99, 104.97, 56.21; HRMS ESI calcd
for C17H16O4 (M+Na)+ 307.0941, found 307.0938.
40 was synthesized according to the general procedure using
4-cyanophenol, 6h (0.97 mmol, 116 mg) to yield a white solid
(173 mg, 72%). m.p. 99.8-101.1 C; 1H NMR (500 MHz, CDCl3)
δ 7.93 (d, J = 15.9 Hz, 1H), 7.82 – 7.70 (m, 2H), 7.68 – 7.57 (m,
2H), 7.53 – 7.43 (m, 3H), 7.40 – 7.32 (m, 2H), 6.64 (d, J = 16.0
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 164.45, 154.16, 147.86,
133.85, 133.69, 131.14, 129.11, 128.45, 122.80, 118.31, 116.32,
109.68; HRMS ESI calcd for C16H11NO2 (M+Na)+ 272.0682,
found 272.0674.
1
3.3.29. (E)-3,5-Dimethylphenyl cinnamate (35)
3.3.35. (E)-2-Nitrophenyl cinnamate (41)
35 was synthesized according to the general procedure using
3,5-dimethylphenol, 6c (0.97 mmol, 0.118 mL) to yield a yellow
oil (141 mg, 58%). H NMR (500 MHz, CDCl3) δ 7.89 (d, J =
41 was synthesized according to the general procedure using
2-nitrophenol, 6i (0.97 mmol, 135 mg) to yield a light yellow
solid (114 mg, 44%). m.p. 77.3-78.0 C; H NMR (500 MHz,
1
1
16.0 Hz, 1H), 7.71 – 7.55 (m, 2H), 7.51 – 7.40 (m, 3H), 6.92 (s,
1H), 6.82 (s, 1H), 6.65 (d, J = 16.0 Hz, 1H), 2.37 (s, 6H); 13C
NMR (126 MHz, CDCl3) δ 165.60, 150.72, 146.33, 139.28,
134.27, 130.62, 128.99, 128.28, 127.56, 119.21, 117.52, 21.27.;
HRMS ESI calcd for C17H16O2 (M+Na)+ 275.1043, found
275.1043.
CDCl3) δ 8.13 (dd, J = 8.2, 1.6 Hz, 1H), 7.95 (d, J = 16.0 Hz,
1H), 7.70 (ddd, J = 8.1, 7.5, 1.6 Hz, 1H), 7.67 – 7.59 (m, 2H),
7.49 – 7.41 (m, 4H), 7.36 (dd, J = 8.2, 1.3 Hz, 1H), 6.70 (d, J =
16.0 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 164.35, 148.20,
144.17, 142.11, 134.60, 133.90, 131.07, 129.04, 128.54, 126.52,
125.75, 125.30, 115.96; HRMS ESI calcd for C15H11NO4
(M+Na)+ 289.0853, found 289.0831.
3.3.30. (E)-4-Methanoyl-2-methoxyphenyl
cinnamate (36)
Acknowledgments
36 was synthesized according to the general procedure at 60
C using vanillin, 6d (0.97 mmol, 145 mg) to yield a white solid
The authors thank the Siena College Center for Undergraduate
Research and Creative Activity for financial support and Dr.
Thomas Hughes, Dr. Stephen Deyrup, and Dr. Kristopher
Kolonko for helpful conversations. This research did not receive
any specific grant from funding agencies in the public,
commercial, or not-for-profit sectors.
1
(107 mg, 39%). m.p. 90.3-91.6 C; H NMR (500 MHz, CDCl3)
δ 10.00 (s, 1H), 7.93 (d, J = 16.0 Hz, 1H), 7.68 – 7.59 (m, 2H),
7.56 (d, J = 1.8 Hz, 1H), 7.54 (dd, J = 8.0, 1.8 Hz, 1H), 7.49 –
7.41 (m, 3H), 7.34 (d, J = 7.9 Hz, 1H), 6.69 (d, J = 16.0 Hz, 1H),
3.95 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 191.05, 164.30,
152.18, 147.38, 145.10, 135.23, 134.07, 130.90, 129.04, 128.41,
124.80, 123.57, 116.39, 110.89, 56.16; HRMS ESI calcd for
C17H14O4 (M+Na)+ 305.0784, found 305.0785.
References and notes
3.3.31. (E)-2-Chlorophenyl cinnamate (37)
37 was synthesized according to the general procedure using
2-chlorophenol, 6e (0.97 mmol, 0.100 mL) to yield a light yellow
solid (178 mg, 71%). m.p. 82.3-83.1 C; H NMR (500 MHz,
CDCl3) δ 7.96 (d, J = 16.0 Hz, 1H), 7.67 – 7.60 (m, 2H), 7.50
(dd, J = 7.9, 1.4 Hz, 1H), 7.49 – 7.42 (m, 3H), 7.34 (ddd, J = 8.1,
7.3, 1.6 Hz, 1H), 7.28 – 7.21 (m, 2H), 6.70 (d, J = 16.0 Hz, 1H);
13C NMR (126 MHz, CDCl3) δ 164.40, 147.35, 147.13, 134.08,
130.86, 130.36, 129.01, 128.41, 127.74, 127.06, 126.98, 123.84,
116.45; HRMS ESI calcd for C15H11ClO2 (M+Na)+ 281.0340,
found 281.0336.
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3.3.32. (E)-2,6-Dichlorophenyl cinnamate (38)
38 was synthesized according to the general procedure using
3,5-dimethylphenol, 6f (0.97 mmol, 158 mg) to yield a light
1
yellow solid (172 mg, 60%). m.p. 147.3.1-148.3 C; H NMR
(500 MHz, CDCl3) δ 8.00 (d, J = 16.0 Hz, 1H), 7.68 – 7.62 (m,
2H), 7.47 (dd, J = 5.0, 1.9 Hz, 3H), 7.42 (d, J = 8.1 Hz, 2H), 7.19
(dd, J = 8.4, 7.9 Hz, 1H), 6.73 (d, J = 16.0 Hz, 1H); 13C NMR
(126 MHz, CDCl3) δ 163.21, 148.05, 144.20, 133.97, 131.02,
129.18, 129.04, 128.65, 128.51, 127.10, 115.65; HRMS ESI
calcd for C15H10Cl2O2 (M+Na)+ 314.9950, found 314.9945.

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Supplementary Material
Supplementary data associated with this article can be found
1
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