The retroaldol reaction of cinnamaldehyde

J. PETERGUTHRIE,' JOHNCOSSAR,BRIANA. DAWSON,

KEVINJ. COOPER, A N D KATHLEEN
F. TAYLOR
Department of Chemistv. University of' Western Onmrio, London, Ont.. Catlarla N6A 5B7
Received November 15. 1983

J . PETERGUTHRIE, KEVIN J . COOPER,JOHN COSSAR, BRIAN A. DAWSON, and KATHLEEN F. TAYLOR. Can. J. Chem. 62,
1441 (1984).
Rate and equilibrium constants have been measured for the hydration and retroaldol reactions of cinnamaldehyde. The
equilibrium constant for the 1,4-addition of water to cinnamaldehyde is 4.42 x lo-'. The rate constants for hydroxide catalyze(?
reaction, extrapolated to zero hydroxide concentration (to correct for the addition of hydroxide to the aldol carbonyl), are: k,,
= 2.20 x l O - ' ~ - ' s - ' ; kOI = 0.456 M-I S-'; and k': = 9.08 x 1 0 - ' ~ ' s - ' .The rate of the formation reaction was measured
by adding small amounts of acetaldehyde to alkaline solutions of benzaldehyde: ky, = 0.63 M-' s-' and K,,,,,,ll = 1480 M-'.
The course of the synthetically useful reaction of acetaldehyde with benzaldehyde is discussed in the light of these results.

J. PETERGUTHRIE, KEVINJ. COOPER, JOHN COSSAR, BRIAN A. DAWSON et KATHLEEN F. TAYLOR. Can. J. Chem. 62,1441
Can. J. Chem. Downloaded from cdnsciencepub.com by 110.136.217.121 on 12/03/23

(1984).
On a mesurt les constantes de vitesse et d'tquilibre des reactions d'hydratation et rttroaldolique du cinnamaldkhyde. La
constante d'kquilibre de I'addition-1,4 de I'eau sur le cinnamaldkhyde est de 4,42 x lo-'. Les constantes de vitcsse pour la
rtaction catalyste par I'hydroxyde, extrapoltes i une concentration d'hydroxyde tgale a zkro (pour corriger ['addition de
I'hydroxyde sur le carbonyle de l'aldol), sont de ky, = 2,02 X M-I s-I; k;, = 0,456 M-' s-I; et k:, = 9,08 x lo-'
M-I s-I. On a mesurk la vitesse de la rCaction de formation en ajoutant de petites quantitts d'acCtaldChyde a des solutions
alcalines de benzaldkhyde: k:, = 0,63 M-I s-I and Kglobal = 1480 M - I . A la lumikre de ces rksultats, on discute du ddroulement
de la rtaction de l'acktaldthyde avec le benzaldkhyde qui prtsente de l'intkret comme rtaction de synthkse.
[Traduit par le journal]

Introduction
We have reported a study (1) of the equilibrium constants for
aldol condensation reactions. Since we consider it important to
have a reliable set of rate and equilibrium constants for a set of
simple aldol reactions and need such data for an examination of
rate-equilibrium correlations for the aldol reaction, we have
undertaken the investigation of the kinetics of various aldol
reactions, studying them in the reverse sense to avoid the diffi-
culties of side reactions which plague the kinetics of aldol
reactions in the forward sense. The case of cinnamaldehyde is
of interest because it is cited as a textbook example of thermo-
dynamic control in the aldol reaction (2), yet has not been
studied kinetically. Meyers and Durandatta (3) have reported a
method for preparing the aldol corresponding to cinnam-
aldehyde, i.e. 3-hydroxy-3-phenylpropanal. This compound
proved essential to the investigation, because the equilibrium
constant for dehydration to cinnamaldehyde is quite large and
cannot be measured directly by studying the hydration of
cinnamaldehyde, yet must be known to sort out the kinetics.

Results and discussion

The retroaldol reaction of cinnamaldehyde can be followed
spectrophotometrically; when cinnamaldehyde, as a solution in
acetonitrile, is injected into aqueous sodium hydroxide solution
there is a smooth disappearance of the absorbance at 285 nm,
which follows a simple first-order rate law; see Fig. 1. Thus
one can see no sign of the two stages which are believed to be
essential for this reaction; eq. [ l ] 1 I I I I I I I I
40008 WBBB 120800 lWBBB 2!Zkl888
t (8)
FIG. 1 . Absorbance vs. time for the reaction of 7.82 X lo-' M
cinnamaldehyde in 0.1 N NaOH. Followed at 285 nm, using 10-cm
cells.

aldol, 3-phenyl-3-hydroxy-2-butanal, is injected into aqueous

The two phases of the reaction are quite apparent when the sodium hydroxide solution; the absorbance at 285 nm first rises
and then, about 1000 times more slowly, falls again; see Fig.
I Author to whom correspondence may be addressed. 2. The rate of the slow fall in absorbance is essentially identical
 1442 CAN. J . CHEM. VOL. 62, 1984
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FIG. 2. Absorbance vs. time for the reaction of 5.33 X M 3-hydroxy-3-phenylpropanal in 0.1 N NaOH. (a) Initial phase, appearance
of cinnamaldehyde. (b) Final phase, disappearance of cinnamaldehyde. Followed at 285 nm, using 10-cm cells.

to the rate of disappearance of the absorbance of cinnam-
aldehyde when the latter is used to initiate reaction. Analysis of
the two-phase kinetic data permits evaluation of the rate con-
stants. For the system of interest, where a low concentration of
aldol product undergoes retroaldol cleavage, the rate of the
second-order aldol formation process, described by k32, is neg-
ligible. A rigorous solution of the kinetics equations is possible
following the procedure described in Moore and Pearson (4),
but to an excellent approximation the two stages of the reaction
can be treated independently. For the fast reaction,
A = A, + a exp (-A2t)
and for the slow reaction,
A = A, + p exp (-A,t)
where: -a = C ~ ~ ~ ~ E P , /=
A ,C; ~ E starting
, from cinnam-
aldehyde; P = c ~ ~ ~ ~ Estarting
, / A from
~ the aldol; A, k,, +
7 steps evaluated in this work, extrapolated to zero hydroxide
k,,; A, = k12/(l + k21Lk23);EI = extinction coefficient for
cinnamaldehyde; and C, = initial concentration of cinnam-
aldehyde ( i = 1) or aldol ( i = 2). Then:
kZ1= l a l A I / ~ t ~ I
k2, = A2 - kZI
,412 = h,(1 + k~llk23)
Table 1 shows the results of applying this analysis to the
experimental data for cinnamaldehyde and the corresponding
aldol. The individual rate constants show the expected first-
order dependence upon the hydroxide concentration, but there
is clearly a decrease in k;, and kij2 as the hydroxide concen-
tration increases; see Fig. 3. This phenomenon has been ob-
served for crotonaldehyde, and is attributed to ionization of the
carbonyl hydrate, or equivalently to addition of hydroxide to
the aldehyde carbonyl, leading to a lower concentration of the
kinetically significant form of the aldol. Since both k& and k;,
respond to hydroxide concentration in the same way, it is best
to fit A2/[OH-] to the equation:
Similar equations apply to ki1and k;,, but propagation of errors
leads to greater scatter, and the effect is close to the limits of
detection fork;,. We calculated values for k;, and ki, from the
individual values of kl1 and k;,, and then averaged them. Table
2 shows the second-order rate constants for the individual
concentration.
The value of a which we obtained was 4.66 t 1.17; it is
easily shown that a = KJK, (1 + 1/Khydration). The hydration
constant may be estimated, using the linear free energy
We use the following notation for rate constants: k,, are the rate
constants obtained from the analysis described at a given value of
[OH-]; kk = ki,/[OH-] are the apparent second-order (third-orderfor
k,,) rate constants; and k: are the second- or third-order rate constants
corrected for hydrate ionization to zero hydroxide ion concentration.
All rate constants refer to species at covalent hydration equilibrium.
 GUTHRIE E T AL.

TABLE
1. Kinetic results for cinnamaldehyde"

(a) Reactions starting with cinnamaldehyde

[NaOH] P lo5 x A, lo4 x klz
0.1" 0.400 2 0.001 3.45 2 0.02 1.87 ? 0.15
0.06b 0.389 5 0.001 2.32 5 0.02 1.26 ? 0.10
0.03b 0.382 ? 0.001 1.05 ? 0.005 0.568 ? 0.045
0.1' *
1.55 0.004 4.15 ? 0.03 2.25 5 0.18
0.03' 1.38 2 0.003 *
1.10 0.01 0.595 ? 0.047
0.01' *
1.26 0.005 0.395 5 0.005 0.214 ? 0.017
0. I d 2.931 + 0.0003 3.63 + 0.001 1.96 & 0.16
0. Id 2.943 + 0.0092 3.61 5 0.04 1.97 t 0.16
O.le./ 0.963*0.0001 3.52*0.001 1.6950.44

(b) Reactions starting with 3-hydroxy-3-phenylpropanal

[NaOH] a lo2 X h2 lo2 X k z , 10' x kZ3
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0.098' 0.978 2 0.0042 3.688 5 0.011 2.90 2 0.20 0.771 * 0.207

0.046' 1.00 ? 0.0008 2.33 * 0.002 1.92 5 0.13 0.417 * 0.134
0.0096P 0.215 r 0.001 0.480 + 0.003 0.422 ? 0.029 0.0578 0.029*
0.0096h 2.08 5 0.0029 0.496 -' 0.002 0.423 '- 0.029 0.0731 0.029 *
0.0046' 1.02 t 0.0038 0.269 5 0.004 0.224 + O.OL6 0.0451 5 0.016

(c) Reactions starting with acetaldehyde plus benzaldehyde

[NaOH] lo4[PhCHO] lo5 [CH3CHO] a lo5kob,

"In aqueous solution at 25°C. p = 0.1 M (KCI); all pseudo first-order rate constants are in s-I.
" 1.70 X lo-' M cinnamaldehyde, I-cm cells.
' 7.82 X M cinnamaldehyde, I-cm cells.
'I 1.34 x M cinnamaldehyde, 10-cm cells.
"5.33 X M 3-hydroxy-3-phenylpropanal, 10-cm cells.
'Second phase of a reaction starting with 3-hydroxy-3-phenylpropanal.
' 1.07 X M 3-hydroxy-3-phenylpropanal, 10-cm cells.
" 1.07 X M 3-hydroxy-3-phenylpropanal, 10-cm cells.
' Followed at 310 nm.

relation3 of Greenzaid et al. (5) as 3.52 +- 1.4 (error based on
the errors reported by Greenzaid et al. for their parameters).
This calculation required a u * value for Ph-CH(0H)-CH,,
which we estimate as u* (PhCH2CH2)+ u* (HOCH2CH2)-
u* (CH3CH2),using values of u* from Perrin et al. (3), and
estimating u* (HOCH2CH2)as 0.4u* (HOCH,) (3). K , for the
hydrate can be calculated (7) as 13.16. These values lead to a
predicted value of a = 5.4, in excellent agreement with the
value which was obtained.
In order to determine the overall equilibrium constant for
cinnamaldehyde formation we measured kinetics of the reac-
tion of benzaldehyde and acetaldehyde in aqueous alkali. It is
necessary to use excess benzaldehyde and low, limiting quan-
tities of acetaldehyde in order to keep the acetaldehyde concen-
tration low enough to preclude formation of crotonaldehyde.
This condition can be satisfied because of the very favorable
overall equilibrium constant for the condensation of acet-
aldehyde with benzaldehyde. Kinetics were carried out with
0.1 N NaOH and varying concentrations of benzaldehyde. In
each case the acetaldehyde was ca. 1/10 the benzaldehyde
concentration, low enough to ensure pseudo first-order kinet-
ics, high enough to give a useful absorbance change super-
imposed on the background absorption of benzaldehyde. Al-
=
,For RR'C=O + ~~0 R R I C ( O H )log = 1 .70zm* +
~ , K~~~~~~~~~
2.03A - 2.81, where A = number of aldehydic protons and K,,,,,,,,
is dimensionless, i.e. activity of water = 1 (5).
though the background absorbance was small enough for the
two lower concentrations of benzaldehyde to permit the reac-
tion to be followed at 285 nm, for the highest concentration of
benzaldehyde, 3.03 X lo-' M, it was necessary to follow the
reaction at 3 10 nm. A solution of benzaldehyde in 0.1 N NaOH
showed no absorbance change over times comparable to those
for the kinetics runs.
The observed rate of reaction is the rate of approach to
equilibrium and includes both forward and reverse reaction, as
is shown in eq. [2]
L2] kobs = kmv + kfwd LPhCH0]
Figure 4 shows that the points measured starting with cinnam-
aldehyde fall at the intercept of a line fitting the runs for
approach to equilibrium, as they must by our interpretation.
The best line through the points is kobr= (3.58 + 0.03) X
+ (0.0452 0~oo402),phCHOl, corresponding to an overall
apparent equilibrium constant of 1263 + 1 13 M-'.
The rate constant in the forward direction can be expressed
in terms of the rate constants of eq. [l] as kfwd= k3,k2,/(k2,+
k23). Using values of k% and ki, from Table 2 we obtain k;, =
0.56 * 0.05 M-? s-'.
As we discussed above for the reverse reactions, we must
consider the effect of hydroxide addition to the starting materi-
als for the condensation, in order to extract the true third-order
rate constants for the hydroxide catalyzed reaction at zero hy-
 1444 CAN. J. CHEM. VOL. 62, 1984

TABLE2. Rate constants at zero hy-

droxide concentration for the retro-
aldol reaction of cinnarnaldehyde"
2. 5 Rate constant Value
\ 2
Y
m 1 o3 x k':> 2.02 2 0.13
m 21 b 0.456 2 0.018
-1 2. 0 10' x k:),h 9.08 2 2.26
kS2 ' 0.63 2 0.06
"In aqueous solution at 25°C. p. =
1.5 0.1 M (KCI); average values for rate con-
stants.
bSecond-order rate constant for hy-
0.50 droxide catalyzed reaction. M - ' s-I.
'Third-order rate constant for hydrox-
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ide catalyzed reaction, M-' s - ' .

0. 40
d
'N
Y
0. 30

0.20

0. 12
15
0. 10

8.08
0
'N
Y 0.06

0. 04
10
0. 02 A
8. 00 0.02 0.04 a 06 0.08 0. in *
I
0)
[OH-I V

FIG. 3. Dependence of apparent second-order rate constants upon

[OH-]. Lines for kil and k;3 calculated using equations of the form of o
11
[3] with a = 4.66. The line for kl, represents the weighted average
value. Y
LD
m 5
droxide concentration. It may be shown that the correction 4

takes the form:

where b and c are analogous to a, defined above for the ketol,

but refer to acetaldehyde and benzaldehyde respectively. From
the literature values for the pKa of acetaldehyde hydrate (1 3.48,
ref. 8) and for the hydration constant for acetaldehyde (1.06, 0
ref. 9) we can calculate that b is 1.48; from the ec~uilibrium 0 I 2 3
constant for addition of hydroxide to benzaldehyde (b. 18, ref. I m3 C P ~ C H O I
lo) and the that is (lo), we can FIG, 4 , Dependence of rate for approach to
that is For NaoH these lead for reactions starting with acetaldehyde plus benzaldehyde upon
a net k;wd = kFwd/l.17. Thus k:z = 0.65 *0.06.
0
[ben~aldehyde]~. The points at [ben~aldehyde]~ = 0.0 represent reac-
A similar correction must be made to Kovcra,~,leading to Kovera~, tions starting with cinnarnaldehyde. The line is fitted by weighted least
= 1480 -+ 133 M-'. squares.
We have previously reported equilibrium constants for the
aldol condensation leading to cinnamaldehyde, and for the aldol addition step, our value, based on thermodynamic calcu-
dehydration step (1). For the dehydration, our value, based on lations using disproportionation reactions, was 39 (AGO =
thermodynamic calculations using disproportionation reac- -2.18 + 1.00). From the kinetics measured in this work the
tions, was 424 (AGO = -3.59 + 1.63); from the kinetics equilibrium constant is 6.5 + 0.8 (AGO = - 1.11 + 0.07), in
measured in this work the equilibrium constant is 226 + 17 not so satisfactory agreement. The discrepancy is just equal to
(AGO = -3.21 -+ 0.04), in satisfactory agreement. For the the combined uncertainties. Thus our use of disproportionation
 GUTHRIE ET AL. 1445

2- ion catalyzed hydrolysis was attempted we did not obtain a material

- with the nmr spectrum reported (3), but rather an oil, which gave a
- - solid on addition of n-pentane to an ether solution. The solid was
I recrystallized from CHCI?; mp 115- 117°C (dec.). The 2,4-dinitro-
phenylhydrazone of this solid was prepared and recrystallized from
ethanol/ethyl acetate; mp 250-251°C (lit. (12) mp for cinnam-
aldehyde 2,4-DNP 252°C). A solution of 2-(2-hydroxy-2-phenyl-
ethyl)-1.3-thiazolidine. (0.5 g) in acetonitrile (ca. 15 mL) was added
:--
I
1 over 5 min t0.a solution of HgClz in 80% acetonitrile-water ( I 0 mL)
I
at 0°C. After stirring 10 min, water (I5 mL) was added, and the white
1 precipitate filtered off. The filtrate was extracted using 1 : 1
I ether-pentane (4 X 25 mL), the extracts were dried (Na2S04),and the
. . ..
.. ..
. solvent evaporated to leave a pale yellow oil (0.25 g). The nmr spectra
. . .' , . . .. . !f
... .. (CDCI,) of this oil were consistent with 3-hydroxy-3-phenylpropanal;
i C3 ' H , 6 : 9 . 6 ( t , I H ) , 7 . 2 ( s , 5 H ) , 5 . 1 (t, IH),3.4(s, 1H),2.7 ( d o f t ,
4 -- - 2H); "c, 8: 202.0 (CHO), 142.8, 128.6, 127.8, 125.6 (Ph), 68.9,
rn
a 52.1 (CH(0H). CH?).
Can. J. Chem. Downloaded from cdnsciencepub.com by 110.136.217.121 on 12/03/23

- -
JmJ The sample was dissolved in a few milliliters of ether, and an equal
n, volume of petroleum ether was added. The bright yellow precipitate
-
. .
. . n m
was filtered off, and the clear, essentially colorless solution was
cooled with Dry Ice; fluffy white crystals formed and were filtered off,
but melted below 0°C on warming. This material was used for
kinetics.
.. .
. .. ...
.
:-
I Methods
. .
. .. : FIG. 5. Reaction coordinate diagram for the system starting with The procedure for kinetics was as previously described (13, 14).
acetaldehyde plus benzaldehyde. Free energies of activation were The reactions were f o k ~ w e dat 285 nm, except for the formation
calculated from the rate constants in Table 2 and ref. I I . experiment at highest benzaldehyde concentration. For this experi-
ment the adsorption due to benzaldehyde at 285 nm was too high to
reactions to estimate thermochemical quantities gives useful permit the reaction to be followed, sd it was followed at 310 nm.
approximate values. The final solutions from retroaldol kinetics experiments had absorb-
ances appropriate to the anticipated products. This will be illustrated
It is instructive to draw a reaction coordinate diagram for the for the 7th entry in Table 1. The initial and final absorbances (based
condensation of acetaldehyde with benzaldehyde, now that the on the least-squares parameters) were 3.20 and 0.267 respectively.
rate constants are available from this and earlier work (I I). The corresponding apparent extinction coefficients were 2.4 X lo4
Figure 5 shows such a diagram, and makes it clear that and 2.0 X lo3. The extinction coefficient for cinnamaldehyde at 285
3-hydroxybutanal and 2-butenal will indeed accumulate in the nm is 2.3 X lo4 (12); that for benzaldehyde at 285 nm is 1.5 x lo3,
early stages of a reaction, but will be replaced by the more (this work). From the overall equilibrium constant of 1480 M - ' we
slowly formed but more stable cinnamaldehyde at long times. can calculate that 2.65 X lo-' M cinnamaldehyde would be present
This picture is of course oversimplified, in that it ignores the at equilibrium, along with 1.3 1 x M benzaldehyde (and 1.3 1 X
possible further aldol reactions of 3-hydroxybutanal and lo-' M acetone, which would make a negligible contribution to the
2-butenal which would be expected to be competitive with the absorbance). The calculated apparent extinction coefficient is 1.96 X
lo3. The agreement is satisfactory, confirming that the reactions are
simple condensations. well behaved.
In terms of this simple picture, we can calculate that for
initial concentrations of [acetaldehyde] = [benzaldehyde] = I . J. P. GUTHRIE. Can. J. Chem. 56, 962 (1978).
0.01 M, the final concentration of cinnamaldehyde will be 2. C. D. GUTSCHE and D. J. PASTO.Fundamentals of organic chem-
0.00684 M, with 0.00085 M each of 3-hydroxybutanal and istry. Prentice-Hall, Englewood Cliffs, New Jersey. 1975.
crotonaldehyde, so that the yield is 68% and r = p. 925.
[cinnamaldehyde]/([acetaldol] + [crotonaldehyde]) = 4.03.
3. A. L. MEYERS,J. I,. DURANDATTA,
Chem. 40, 2025 (1975).
and R. MUNAVU. J. Org.
The predicted yield of cinnamaldehyde and the predicted value 4. J. W. MOOREand R. G. PEARSON. Kinetics and mechanism. 3rd
of r both increase at higher concentrations: 84%, r = 7 at 0.1 M ed. Wiley, New York. 1981. p. 296.
reactants; 90%, r = 9 at 1 M reactants. This is likely to prove 5. P. GREENZAID, Z. LUZ, and D. SAMUEL. J . Am. Chem. Soc. 89,
illusory because of the increasing rate of polymerization to be 749 ( 1967).
expected at higher concentrations of acetaldehyde; poly- 6. D. D. PERRIN, B. DEMPSEY, and E. P. SERIEANT.pK, Prediction
merization was neglected in these simple calculations, as were for organic acids and bases. Chapman and Hall, London. 1981.
the effects of solubility. 7. J. HINEand G. F. KOSER.J. Org. Chem. 36, 134%(1971).
8. R. P. BELLand P. T. MCTIGUE.J. Chem. Soc. 2983 (1960).
9. J. L. KURZ.J. Am. Chem. Soc. 89, 3524 (1967).
Experimental 10. P. GREENZAID. J. Org. Chem. 38, 3164 (1973).
Materials l I. J. P. GUTHRIE. Can. J. Chem. 52, 2037 (1974).
Cinnamaldehyde was redistilled in vacuum before use. 12. 1. HEILBRON. Dictionary of organic compounds. Edited by A. H.
3-Hydroxy-3-phenylpropnnai Cook, H. M. Bunbury, and D. H. Hey. Eyre and Spottiswoode,
This was prepared following the procedure reported by Meyers et London. 1965.
al. (3); their procedure, involving reaction of the lithium salt of 13. J. P. GUTHRIE. Can. J. Chem. 59, 45 (1981).
2-methyl-2-thiazoline with benzaldehyde, led to a product with 14. J. P. GUTHRIEand B. A. DAWSON.Can. J. Chem. 61, 171
the nmr spectrum expected (3) for 2-(2-hydroxy-2-phenylethy1)-2- (1983).
thiazoline, as did the aluminum amalgam reduction of this material to 15. 0. H. WHEELER and L. A. KAPLAN (Editors). Organic electronic
give 2-(2-hydroxy-2-phenylethy1)-1,3-thiazolidine. When mercuric spectral data. Vol. 3. Wiley, New York. 1966.