Samarium diiodide reduction of cinnamic acids

Article abstract of DOI:10.1002/jccs.200400136

The method for measuring SmI₂ reduction rates is expanded to a wider range of organic compounds by using not only GC or GC/MS, but also HPLC as the detecting tool. The reduced substrates are not only confined to water insoluble compounds or low boiling compounds only. Water soluble cinnamic acid derivatives of high boiling points are chosen for this application. The absolute rate constants of SmI₂ reduction of cinnamic acid in the presence of hexamethyl phosphoramide or t-butanol is considered as a suitable proton source in this reaction. The rates are dependent on substrates and additives as: Rate · [t-BuOH][Cinnamic acid] and Rate · [HMPA][Cinnamic acid] The reduction rates of α-methylcinnamic acid, 2-methylcinnamic acid, 4-methylcinnamic acid, 2-methoxycinnamic acid, 3-methoxycinnamic acid, 4-methoxycinnamic acid, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, 4-hydroxycinnamic acid, 2-chlorocinnamic acid, 3-chlorocinnamic acid, 4-chlorocinnamic acid were carefully measured to study the substituent effect.

Full text of DOI:10.1002/jccs.200400136

Journal of the Chinese Chemical Society, 2004, 51, 917-921
917
Samarium Diiodide Reduction of Cinnamic Acids
Tzuen-Yeuan Lin* (
), Ming-Ren Fuh (
Department of Chemistry, Soochow University, Taipei, Taiwan, R.O.C.
) and Chi-Yu Tsau (
)
The method for measuring SmI2 reduction rates is expanded to a wider range of organic compounds by us-
ing not only GC or GC/MS, but also HPLC as the detecting tool. The reduced substrates are not only confined
to water insoluble compounds or low boiling compounds only. Water soluble cinnamic acid derivatives of
high boiling points are chosen for this application.
The absolute rate constants of SmI2 reduction of cinnamic acid in the presence of hexamethylphosphor-
amide or t-butanol is considered as a suitable proton source in this reaction. The rates are dependent on sub-
strates and additives as:
Rate 4 [t-BuOH][Cinnamic acid]
and Rate 4 [HMPA][Cinnamic acid]
The reduction rates of a-methylcinnamic acid, 2-methylcinnamic acid, 4-methylcinnamic acid, 2-meth-
oxycinnamic acid, 3-methoxycinnamic acid, 4-methoxycinnamic acid, 2-hydroxycinnamic acid, 3-hydroxy-
cinnamic acid, 4-hydroxycinnamic acid, 2-chlorocinnamic acid, 3-chlorocinnamic acid, 4-chlorocinnamic
acid were carefully measured to study the substituent effect.
Keywords: Samarium diiodide; Cinnamic acids.
INTRODUCTION
Samarium diiodide has been used as a powerful reduc-
we plan to expand the application of this method to a wider
range of organic compounds by using not only GC or GC/
MS, but also HPLC as the detecting tools. Then the reduced
substrates will not only be confined to water insoluble com-
pounds or low boiling compounds only. The first target cho-
sen for this application is a series of cinnamic acid deriva-
tives that are generally water soluble and with high boiling
points. In this paper, we report the absolute rate constants of
SmI2 reduction of cinnamic acids in the presence of hexa-
methylphosphoramide or t-butanol which is considered as a
suitable proton source in this reaction. Substituent effect is
carefully observed to show clearly the electronic effect on
this SmI2 reduction.
ing agent over the last decade.1 Some kinetic studies by using
product analysis or stopped-flow technique have been done
to try to clarify the ambiguity in mechanism.2 To achieve the
kinetic measurement of air- and moisture-sensitive SmI2 re-
duction, especially for relatively slower reactions, we have
developed the first reliable method3 to trace the concentra-
tions of reduced substrates, rather than those of SmI2. By so
doing, we are able to obtain the reaction rates. In our previous
work, we have successfully measured the rate constants for
electron transfer of SmI2 to the carbonyl compounds and the
sulfoxides.4 Rates of alkyl halides and 2-heptanone reduced
by SmI2 (Barbier reaction) under different conditions were
also obtained.5 Proton has been chosen to catalyze this kind
of reduction for ketone and epoxide, although it is obviously
less effective than the well known HMPA(hexamethyl pho-
phoramide).6 We furthermore probed the conjugate system
and successfully measured reduction rates of substituted
cinnamates and studied the substituent effect.7 GC/MS was
also used to measure the rates of haloadamantanes8 and to
more conveniently identify the reaction products during the
reaction course. All of these results are useful for understand-
ing the SmI2 reduction mechanism. Therefore, in this work
RESULTS AND DISCUSSION
For the reaction of
SmI2
CH CH
CO H
2
(1)
CH
2
CHCO2H
2
LC (Liquid chromatography) was used to determine the con-
centrations of cinnamic acid and its derivatives. LC assay is
particularly useful for the measurements of cinnamic acid
and its derivatives since these water soluble compounds are
* Corresponding author. Tel: 02-2881-9471 ext. 6810; fax: 02-2881-1053; e-mail: tylin@mail.scu.edu.tw

918 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Lin et al.
Table 1. Dependence of pseudo-first-order rate constants on
initial concentration of t-cinnamic acid
difficult to be extracted to the organic layer for GC (gas chro-
matography) analysis. Biphenyl was utilized as an internal
standard to minimize the errors of sample preparation and en-
hance the precision and accuracy of LC analysis. For exam-
ple, the retention times of t-cinnamic acid and biphenyl were
approximately 3.88 and 11.91 min., respectively. The LC
quantitative measurement was established by the peak area
ratio of t-cinnamic acid/biphenyl. Good linearity (r2 = 0.99)
from 0.1 to 2.0 mM was determined. The detection limit of
this newly developed LC method was approximately 0.05
mM based upon three times signal-to-noise ratio. In addition,
the recovery of the sample preparation procedure was exam-
ined. Known amounts (0.5, 1.0, 2.0 mM) of t-cinnamic acid
were added to a tetrahyrofuran solution and then extracted by
the procedure described in the experimental section. Accept-
able recoveries ranging from 80.4 to 96.5% were measured.
Pseudo-first-order rate constants were obtained by
[t-Cinnamic acid]0, M
kps, sec-1
4.0 ´ 10-3
2.0 ´ 10-5
2.0 ´ 10-3
1.9 ´ 10-5
[t-BuOH] = 8.3 ´ 10-2 M; [SmI2] = 0.11 M; T = 30 °C; kps
represents pseudo-first-order rate constant
we solved this problem simply by taking the initial rates for
slow reactions since at the beginning of the reaction, the lin-
earity for the first-order relationship still can be obtained.
Fig. 2 shows the catalytic effect of t-BuOH on reduction of
t-cinnamic acid by SmI2. Good linearity was achieved to give
a relationship as follows:
k
ps = k1’[t-BuOH]
(2)
(3)
plotting log(Ct-C ) versus time for more than two half-lives.
4
Since Rate = kps[t-Cinnamic acid]
therefore,
Here Ct and C represent the concentration of cinnamic acid
4
at time t and infinity, respectively (Fig. 1). The first order rate
of decay of this substrate was also tested by using different
initial concentrations of the reactant (Table 1). The product
was characterized as hydrocinnamic acid with an authentic
sample by HPLC.
Rate = k1’[t-BuOH][t-Cinnamic acid]
(4)
The slope of the straight line obtained can be used to calculate
k1’ as 8.3 ´ 10-3 sec-1 M-1 which is dependent on [SmI2] and
temperature. Based on Flowers and coworkers’ study,2(e),2(f)
Both t-BuOH and hexamethylphosphoramide (HMPA)
catalyze this reduction. Yet as expected, HMPA is more effi-
cient than t-BuOH. However, in the presence of HMPA, the
pseudo-first-order linear plot can be obtained only for fast re-
actions (within 10 minutes) while the curvature appeared for
slow reactions. This can be accounted for by the slow reac-
tion between SmI2 and HMPA.9 Under our reaction condition,
Fig. 1. Pseudo-first-order rate plot of SmI2 reduction
of trans-cinnamic acid; [SmI2] = 1.1 ´ 10-1 M,
[t-BuOH] = 8.4 ´ 10-2 M, [cinnamic acid]o = 2.0
´ 10-3 M, T = 30 °C.
Fig. 2. Dependence of t-BuOH concentration on
pseudo-first-order rate constant [SmI2] = 1.1 ´
10-1 M, [cinnamic acid]o = 2.0 ´ 10-3 M, T = 30
°C.

Samarium Diiodide Reduction of Cinnamic Acids
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 919
SmI2 can be tentatively assumed as first order in this reaction.
Therefore,
Rate = k2’[HMPA][t-Cinnamic acid]
(9)
for the linear part of this graph, and the slope obtained can be
used to calculate k2’ which is dependent on [SmI2] and tem-
perature. Under our reaction condition, k2’ is approximated
to be 7.9 sec-1M-1. Again by assuming first order for SmI2,
Rate = k1[SmI2] [t-BuOH][t-Cinnamic acid]
(5)
which makes k1 to be 7.5 ´ 10-2 sec-1M-2 with 0.11 M of SmI2.
Compared to SmI2 reduction of cinnamates,7 t-BuOH is not
that effective in the acid case. This can be explained by the
higher polarity of the acid than that of the ester. The catalytic
effect of t-BuOH can be attributed by its protonation of the
carbonyl group of cinnamic acid to make it easier to be re-
duced,
Rate = k2[SmI2] [HMPA][t-Cinnamic acid]
(10)
k2 can be calculated to be 71.8 sec-1M-2 with 0.11 M of SmI2.
The mechanism is proposed as follows:
Scheme I
(6)
Fig. 3 shows the catalytic effect of HMPA on reduction
of t-cinnamic acid by SmI2. The induction period of this fig-
ure can be explained by the slow reaction between SmI2 and
HMPA, i.e., a small amount of HMPA is consumed by SmI2.
The following relationship can be derived as
k
ps = k2’[HMPA]
(7)
for the linear part of this graph.
Since Rate = kps[t-Cinnamic acid]
therefore,
(8)
A series of different substituted cinnamic acids were
examined to study the electronic effect and steric effect on
this reduction (Table 2).
It is clear that electron-withdrawing groups such as
chlorine and methoxy groups at the meta position are effec-
tively accelerating the reaction, and all of the electron-
donating groups obviously inhibit this reduction. This result
fully supports the mechanisms proposed above in which the
electron transfer is the rate determining step.
Finally, temperature effect was examined (Table 3) and
which shows a similar result with that of our previous
work,4-8 i.e., this reduction is favored at higher temperature.
CONCLUSION
Fig. 3. Dependence of HMPA concentration on
pseudo-first-order rate constant [SmI2] = 1.1 ´
10-1 M, [cinnamic acid]o = 2.0 ´ 10-3 M, T = 30
°C.
In summary, by HPLC analyzing method, we have ob-
tained the pseudo-first-order rate constants for the reduction

920 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Lin et al.
Table 2. Substituent effect on SmI2 reduction of cinnamic acids
lin, Ireland). The chemicals were used as received without
further purification. THF was freshly distilled and immedi-
ately transferred to a glove box before use.
Cinnamic Acids
kps, sec-1
t-cinnamic acid
1.7 ´ 10-5
no reaction
no reaction
no reaction
no reaction
2.5 ´ 10-5
a-methylcinnamic acid
2-methylcinnamic acid
4-methylcinnamic acid
2-methoxycinnamic acid
3-methoxycinnamic acid
4-methoxycinnamic acid
2-hydroxycinnamic acid
3-hydroxycinnamic acid
4-hydroxycinnamic acid
2-chlorocinnamic acid
3-chlorocinnamic acid
4-chlorocinnamic acid
General Method
Both external and internal standards were necessary for
quantitative measurements of cinnamic acids. HP 1100 LC
quaternary pump with UV/VIS spectrometer and an auto-
sampler (Hewlett-Packard Co., Palo Alto, CA, USA) were
used for LC. The UV/VIS detector was set at 254 nm. A C18
column (3.2 ´ 15 mm, 5 mm, Merck LiChroCART RP-18,
Merck KgaA, Germany) with an on-line filter was used for
chromatography separation throughout the analysis. A gradi-
ent elution with two mobile phases was used: acetonitrile (A)
0.2% acetic acid (B). The gradient started with 40% A, went
up to 90% A between 5 and 8 min. and held for 7 min. The
column was then re-equilibrated for 10 min with 40% A. The
flow rate was 0.5 mL/min and the injection volume was 5 ml.
Most operations were carried out in the glove box. All the re-
actions proceeded in a temperature controlled compartment
in the glove box. In order to minimize the effect of free Sm
metal in the SmI2 solution, each set of experiments was con-
ducted by using the same batch of stock solution.11k The con-
centration of SmI2 was determined by I2 titration prior to reac-
tion. In a typical experiment, 0.025 mL of the 0.25 M cin-
namic acids in THF was injected into 3.0 mL of the SmI2 so-
lution and mixed thoroughly. Subsequently, at each time in-
terval, 0.30 mL of the reaction mixture was transferred into
0.30 mL of THF that contained biphnyl and I2. This proce-
dure was to ensure that the unreacted Sm(II) were quenched
by I2. The I2 quenching solution was freshly prepared with an
equal concentration of SmI2. After the mixture was removed
from the glove box, 1.4 mL of a 0.12 M HCl solution was
added to each quenched solution and was mixed by a Virtex
mixer. The mixed solution was then injected into HPLC for
analysis. A calibration curve was constructed by plotting the
ratio of the peak area of the substrate to the peak area of bi-
phenyl versus the concentration of substrates. Pseudo-first-
no reaction
no reaction
no reaction
no reaction
4.2 ´ 10-5
1.2 ´ 10-4
6.3 ´ 10-5
[SmI2] = 0.11 M; [cinnamic acids]0 = 2.0 ´ 10-3 M; [t-BuOH] =
8.3 ´ 10-3 M; T = 30 °C; kps represents pseudo-first-order rate
constant
Table 3. Temperature effect on reaction rate
T, °C
kps, sec-1
40
34
24
16
1.3 ´ 10-3
9.3 ´ 10-4
5.0 ´ 10-4
2.7 ´ 10-4
[SmI2] = 0.11 M; [t-cinnamic acid]0 = 2.0 ´ 10-3 M; [HMPA] =
6.9 ´ 10-2 M; kps represents pseudo-first-order rate constant
of cinnamic acids. Electron-withdrawing groups are effec-
tively accelerating this reaction via inductive effect. Radical
formation is proposed as the rate determining step.
EXPERIMENTAL
Chemicals
Samarium iodide, biphenyl, hexamethyl phosphor-
amide (HMPA), t-butyl alcohol, t-cinnamic acid, hydro-
cinnamic acid, a-methylcinnamic acid, 2-methylcinnamic
acid, 4-methylcinnamic acid, 2-methoxycinnamic acid, 3-
methoxycinnamic acid, 4-methoxycinnamic acid, 2-hydro-
xycinnamic acid, 3-hydroxycinnamic acid, 4-hydroxycin-
namic acid, 2-chlorocinnamic acid, 3-chlorocinnamic acid
and 4-chlorocinnamic acid were purchased from Aldrich
Chemical Company, Inc. (Milwaukee, WI, USA). Hydro-
chloric acid and iodine were purchased from Nacalai Tesque,
Inc. (Kyoto, Japan) and Wako Pure Chemical Industries, Ltd.
(Osaka, Japan). Tetrahydrofuran (THF), acetonitrile and
HPLC degree water were purchased from Labscan Ltd. (Dub-
order rate constants were obtained by plotting log(Ct-C ) ver-
4
sus time for more than two half-lives. Here Ct and C repre-
4
sent the concentration of cinnamic acids at time t and infinity,
respectively.
ACKNOWLEDGMENT
This work was financially supported by Soochow Uni-
versity.

Samarium Diiodide Reduction of Cinnamic Acids
Received October 29, 2003.
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 921
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