Tautomerization of 2-acetylcyclohexanone in assemblies of cationic surfactants

Article abstract of DOI:10.1039/b415219k

The kinetic study of the keto-enol interconversion of 2-acetylcyclohexanone (ACHE) has been performed in organic solvents such as dimethylsulfoxide, 1-propanol, 2-propanol, methanol, dioxane, tetrahydrofuran and acetonitrile, as well as in aqueous micella

Full text of DOI:10.1039/b415219k

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P A P E R
Tautomerization of 2-acetylcyclohexanone in assemblies of
cationic surfactants
Emilia Iglesias
´
Departamento de Quımica Fısica e E. Q. I., Facultad de Ciencias, Universidad de La Corun˜a,
15071 La Corun˜a, Spain. E-mail: qfemilia@udc.es
´
Received (in Montpellier, France) 30th September 2004, Accepted 23rd November 2004
First published as an Advance Article on the web 27th January 2005
The kinetic study of the keto-enol interconversion of 2-acetylcyclohexanone (ACHE) has been performed in
organic solvents such as dimethylsulfoxide, 1-propanol, 2-propanol, methanol, dioxane, tetrahydrofuran and
acetonitrile, as well as in aqueous micellar solutions of the cationic surfactants tetradecyltrimethylammonium
chloride and tetradecyltrimethylammonium bromide at 25 1C. Either the solvent-assisted or H+-catalyzed
reaction rates of tautomerization are reduced in both organic solvents and in micellar medium. In 70% v/v
solvent–water or at fixed concentration of any cationic surfactant, the observed rate constant moderately
increases with [H+]. The nitrosation of the enol has also been studied in micellar solutions of both cationic
and anionic surfactants. Under experimental conditions of first-order dependence on [H+], [nitrite], and
[Xꢀ] (X = Cl or Br), the presence of cationic micelles reduces strongly the rate of nitrosation, whereas in
the presence of anionic micelles, the first-order rate constant, ko, goes through a maximum on increasing the
surfactant concentration.
KE = 0.72. The absorption band centred at 291 nm (eEH
=
15 300 Mꢀ1 cmꢀ1) due to the enol, shifts in alkaline medium to
Introduction
Aqueous micellar solutions are highly anisotropic solvents
whose properties change gradually between those of pure water
to those of hydrocarbon-like liquids on going from the bulk
water phase to the interior of the micelle (the micellar core).1–5
Because of this, the presence of micelles affects reaction rates
and equilibria. The keto-enol equilibrium of 1,3-dicarbonyl
compounds is largely influenced in aqueous micellar media due
to its extremely sensitive dependence on the solvent nature.6–9
The origin of this phenomenon resides in the difference of
molecular interactions between the solvent and the keto or enol
tautomers. Hydrogen-bonding interactions with solvent mole-
cules stabilize the keto tautomer, which predominates in
hydrogen-bond donor solvents, whereas aprotic and/or apolar
solvents increase the enol content due to enol stabilization by
intramolecular hydrogen bonding.
Under equilibrium conditions, more than 40% of the total 2-
acetylcyclohexanone (ACHE) concentration exists in water in
the enol form. This percentage increases strongly in organic
solvents such as dioxane. On the other hand, since the tauto-
merization in the ACHE system occurs slowly, it is possible to
study the approach to equilibrium by using conventional
methods.
higher wavelength (lmax = 309 nm, eE = 32 000 Mꢀ1 cmꢀ1
)
due to the enolate formation. The overall pKa was determined
as 9.85. The subsequent acidification of an alkaline solution of
ACHE yields the enol tautomer in stoichiometric proportions,
which then tautomerizes slowly to the keto form until the
equilibrium proportions are reached again. The kinetic features
of enol ketonization in water have been investigated. The
observed rate constant, ko, remains practically unchanged on
varying the ionic strength of the aqueous medium. Never-
theless, ko increases smoothly with [H+], resulting in ko
=
k
M
w + kH[H+] with kw = 1.4 ꢁ 10ꢀ3 sꢀ1 and kH = 5.8 ꢁ 10ꢀ3
ꢀ1 sꢀ1 at 25 1C in water; these values are strongly reduced in
D2O. In contrast, the rates of enol-ketonization are highly
accelerated in aqueous buffered solutions of acetic acid–acetate
and its chloride derivatives. The measured rate constants
increase with both the pH of the reaction medium and the
total buffer concentration.
Moreover, we showed that the enol of ACHE reacts with
nitrosating agents XNO (X = H2O, Cl, Br or SCN) to give the
C-nitroso compound (Scheme 1). The reaction performed in
water showed a first-order dependence with respect to both
[nitrite] and [ACHE]; nevertheless, contrary to other common
nitrosation reactions, the observed rate constant increases with
both [H+] and [Xꢀ] (X = Cl, Br or SCN) by following
nonlinear relationships.
In a previous work, the characterization of the keto-enol
equilibrium of ACHE in water in both acid and basic medium
was presented.10 In aqueous neutral or acid medium, a mixture
of both keto and enol tautomers exists at equilibrium; the
corresponding equilibrium constant has been measured to be
These experimental findings were interpreted on the basis of
a reaction mechanism, in which the slow reaction path is the
Scheme 1
T h i s j o u r n a l i s & T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 5
N e w J . C h e m . , 2 0 0 5 , 2 9 , 4 5 7 – 4 6 4
457

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O - C internal rearrangement of the NO+ group occurring in
the chelate–nitrosyl complex intermediate that is generated at
steady-state concentrations in the preceding reaction step
between the enol and the nitrosation agent, XNO.11 The same
reaction mechanism has been proposed in the interpretation of
previous results obtained in the nitrosation of different sub-
strates, like 2-acetylcyclopentanone9 or aliphatic nitro com-
pounds,12 but the presence of the intermediate was not
required in the mechanistic explanation of the results obtained
in the nitrosation of many simple enols13,14 or even in enols of
other 1,3-dicarbonyl compounds.15
Results and discussion
Tautomerization
General features. Addition of an aliquot of a concentrated
dioxane solution of ACHE to a neutral or acidic water sample
caused a loss of the intensity of the maximum absorption band
centred at 291 nm. In contrast, an increase of the absorbance at
291 nm was observed when an aliquot of a solution in water of
ACHE was diluted into a high volume of any organic solvent
or into an aqueous micellar medium. These findings indicate
that tautomerization of ACHE occurs at rates sufficient for
monitoring the effects of various solvents on the reaction rate.
Several organic solvents and aqueous micellar solutions of
surfactants forming micelles were investigated. The reaction
can occur via an acid-catalyzed (kH) pathway and an uncata-
lyzed (ku) pathway [eqn. (2)]:
The present report details the results obtained in the kinetic
study of both keto enolization and enol nitrosation of ACHE
performed in organic solvents and in aqueous micellar solu-
tions of cationic surfactants forming micelles.
Experimental
ko = ku + kH[H+]
(2)
2-Acetylcyclohexanone, a Merck product of the highest avail-
able purity, was used as supplied. Surfactants, dodecyltrimethy-
lammonium bromide (DTABr), tetradecyltrimethylammonium
bromide (TTABr), cetyltrimethylammonium bromide (CTABr)
and sodium dodecyl sulfate (SDS), of the highest purity were
used without further purification; tetradecyltrimethylammo-
nium chloride (TTACl) was prepared by using an ion exchange
resin. Organic solvents of spectrophotometric grade were from
Merck. All other reagents were also purchased from Merck and
used as received. Aqueous solutions were prepared with doubly
distilled water obtained from a permanganate solution. Freshly
prepared solutions were used in all experiments.
A double-beam UV-visible spectrophotometer, equipped
with a thermostatted cell holder, was used in monitoring
reaction rates by following the changes in absorbance at l =
291 nm due to the enol absorption. A matched pair of quartz
cells with a c = 1 cm light path was used. Kinetic measure-
ments were carried out under pseudo-first-order conditions,
with ACHE being the limiting reagent. In every case, the
experimental data (absorbance A and time t) fit to eqn. (1):
Organic solvents. Rates of tautomerization have been mea-
sured as a function of [H+] (HCl) in 70% v/v aqueous mixtures
(the water concentration was equal to 16.7 M in every case) of
the organic solvents dimethylsulfoxide (DMSO), 1-propanol
(1-PrOH), 2-propanol (2-PrOH), methanol (MeOH), tetrahy-
drofuran (THF), dioxane and acetonitrile (MeCN). A moderate
catalysis by H+ according to eqn. (2) was observed. The linear
least-squares fitting of ko versus [H+] affords the values of ku
and kH, which are listed in Table 1 along with some properties
of the solvent. Also in Table 1 is given ku, measured, when
possible, in 96.7% v/v organic solvent–water ([H2O] = 1.85 M).
In dioxane or MeCN no enolization reaction seemed to occur
under these conditions (the absorbance at 291 nm remained
unchanged during at least 3 h). For comparative purposes, data
obtained for enol ketonization in water are also included .
As the observed process is an approach to equilibrium, ko is the
sum of the rate constants of the forward (keo, enolization) and
backward (kko, ketonization) reactions. The separation of both
rate constants is possible through eqn. (3) if the keto-enol
equilibrium constant in the corresponding medium, K0E, is
known. The calculation of K0E can be done using the appropriate
combination of initial (A0) and infinite (AN) absorbance values
measured in the same kinetic experiment [eqn. (1)]. The expres-
sions of eqn. (4) were used to relate these parameters with the total
concentration of ACHE, where eEH represents the molar extinc-
tion coefficient of the enol and c, the optical path length (= 1 cm).
A = AN + (AN ꢀ A0)eꢀk t
(1)
o
where A0, AN and A mean absorbance readings at times 0,
infinity and t, respectively, and ko represents the pseudo-first-
order rate constant.
To measure rates of nitrosation, the decrease in absorbance
at 291 nm was monitored as a function of time. In contrast
with the tautomerization process, here the AN values are in
every case close to zero (AN o 0.05) due to complete con-
sumption of the enol, the limiting reagent, whilst the initial
absorbance readings are also constant but equal to approxi-
mately 0.90. The observed rate constant of tautomerization is
the sum of the rate constants corresponding to enol ketoniza-
tion, kko, and keto enolization: keo (ko = kok + keo).
KE0
1 þ KE0
1
keo ¼ ko
and kko ¼ ko
ð3Þ
1 þ KE0
KE
A0 ¼ eEH
‘
½ACHEꢂ0 and
1 þ KE
ð4Þ
KE0
1 þ KE0
A
¼ eEH
‘
½ACHEꢂ0
1
Table 1 Solvent characteristics and the uncatalyzed, ku, and H+-catalyzed, kH, rate constants for the enolization of the keto tautomer of ACHE
in 70% v/v organic solvent–water mixture at 25 1C
ea
m/Db
ku/10ꢀ4 sꢀ1
kH/10ꢀ3 molꢀ1dm3 sꢀ1
K0E
ku/ sꢀ1d
c
Solvent
H2O
78.5
46.5
20.5
19.9
32.7
7.6
1.8
13.9e
5.8e
0.72
1.8
2.8
2.8
2.0
3.1
1.9
2.0
DMSO
1-PrOH
2-PrOH
MeOH
THF
4.05
1.65
1.65
1.71
1.74
0.45
3.54
5.71 ꢃ 0.04
6.10 ꢃ 0.01
6.19 ꢃ 0.04
3.92 ꢃ 0.03
2.76 ꢃ 0.04
1.03 ꢃ 0.05
0.087 ꢃ 0.036
1.94 ꢃ 0.06
1.33 ꢃ 0.02
1.24 ꢃ 0.05
2.05 ꢃ 0.04
1.27 ꢃ 0.05
2.74 ꢃ 0.06
2.64 ꢃ 0.05
0.84 ꢁ 10ꢀ4
2.74 ꢁ 10ꢀ4
—
2.73 ꢁ 10ꢀ4
—
Dioxane
MeCN
a
2.2
35.9
B0
B0
Relative dielectric constant. Dipole moment; D = 3.336 ꢁ 10ꢀ30 cm. Average value of at least ten determinations. In 96.7% solvent–water,
b
c
d
e
no added acid. Ref. 10.
458
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Fig. 1 (A) Variation of ko (ꢄ) and of 1/ko (m) obtained in the keto-enol tautomerization of ACHE in aqueous micellar solutions of TTACl at
[H+] = 0.030 M as a function of the surfactant concentration. The solid line fits eqn. (5); for parameters see text. (B) Plot of eqn. (5) in the linear
form; the straight line represents the linear regression (1300 ꢃ 30) + (20.4 ꢃ 0.3) ꢁ (1/[TTACl]m).
To obtain K0E, it is indispensable to know KE, the keto-enol
equilibrium constant in water. Several methods have been
followed to estimate KE. In the first one,10 we checked the Beer–
Lambert law validity in water under nonequilibrium condi-
tions; the resulting value was KE = 0.72. In a second method,11
the effect of aqueous b-cyclodextrin solutions on the position
of the keto-enol equilibrium in ACHE system was used to
obtain KE = 0.69. In a third method,6 we followed the
procedure developed in the case of benzoylacetone,7 which
analyzes the changes in the absorption spectrum of the sub-
strate as a function of surfactant concentration: a fixed amount
of ACHE was dissolved in aqueous micellar solutions of
variable surfactant concentration; after giving the solutions
enough time to reach equilibrium, the absorbance readings at
291 taken at different [surfactant] were quantitatively analyzed.
The derived value was KE = 0.75. Therefore, in this study we
used the mean value of KE = 0.72 to obtain K0E reported in
Table 1 by applying eqn. (4).
diluted into 3.0 ml of an aqueous solution containing the rest of
the reagents. In dioxane, ACHE exists in the enol (EH) form;
in fact, the initial absorbance (A0 = eEHc[ACHE]0) at 291 nm
takes a constant value of around A0 = 0.900, whatever the
[surfactant].
Upon increasing the surfactant concentration over the cmc
(critical micelle concentration), that is, the micellar pseudo-
phase, the observed rate constant (ko) decreases, but the
reciprocal plot of ko against [TTACl] is not a straight line;
nevertheless, the values of (kw ꢀ ko)ꢀ1, with kw being the rate
constant measured in the absence of surfactant, increase
proportional to 1/[TTACl]m, see Fig. 1. These facts indicate
that the reaction also goes in the micellar phase, even though
the rate is lower than that in water. The corresponding reaction
mechanism appears in Scheme 2, where Dn indicates micellized
surfactant. Taking into account that the overall reaction rate is
the sum of the rate in water and in the micellar phase, the
expression of ko derived from Scheme 2 is given in eqn. (5),
originally derived by Menger and Portnoy.16
The tautomerization rates assisted by the solvent (i.e., ku) are
lower than the half-value determined in water and no clear
trend with the solvent polarity or the dielectric constant is
observed. The bimolecular rate constant for the water-assisted
kw þ kmu Ks½TTAClꢂm
ko ¼
ð5Þ
1 þ Ks½TTAClꢂm
tautomerization can be determined as kH O = ku/[H2O] = 2.5 ꢁ
2
The nonlinear regression analysis of the experimental points by
means of eqn. (5) gives the solid curve drawn in Fig. 1(A) for
10ꢀ5 Mꢀ1 sꢀ1 10
.
If one assumes the same value for the rate in
70% v/v organic solvents–water, then the expected value of ku
in these water mixtures, where [H2O] = 16.7 M, is 4.2 ꢁ 10ꢀ4
kw = (1.51 ꢃ 0.01) ꢁ 10ꢀ3 sꢀ1; kum = (6.96 ꢃ 0.03) ꢁ 10ꢀ4 sꢀ1
;
Ks = 51.3 ꢃ 0.9 Mꢀ1 and the cmc = 3.5 ꢁ 10ꢀ3 M. The
extrapolated kw is in good agreement with that measured in water
at the same [H+]; likewise, kum compares quite well with the ku
values determined in aqueous mixtures of DMSO or alcohols
(Table 1). This rate constant measures the reactivity at the
positively charged micellar interface, where [H+] would be negli-
gible due to electrostatic repulsions and the concentration of water
is also reduced. Both characteristics explain the agreement be-
tween kmu and ku, the latter being measured in DMSO of alcohols.
On the other hand, the absorbance at infinite time (AN), that
is, once the keto-enol equilibrium is established, increases with
[TTACl] due to the presence of micelles. This enhances the enol
concentration, which is proportional to AN { = eEHc[ACHE]o-
KaEp/(1 + KEap)}, where KaEp is given by eqn. (6), and has been
determined experimentally at each [TTACl] as the quotient of
the experimental readings of AN and (A0 ꢀ AN). In contrast,
the difference A0 ꢀ AN, which is proportional to the concentration
s
ꢀ1, which is practically equal to the rate constant measured in
70% MeOH–water. In DMSO and 1-PrOH and 2-PrOH, the
measured ku is slightly higher, whereas in THF, dioxane, and
MeCN, ku values are considerably lower. In fact, the compar-
ison between the results obtained in DMSO and in MeCN, that
is, two solvents of quite similar dielectric constants and dipole
moments, shows that ku obtained in DMSO is more than 60
times that in MeCN. A key difference between both solvents is
that whereas DMSO is a good hydrogen-bond acceptor,
MeCN is neither a good hydrogen-bond acceptor nor donor.
The alcohols are good H-bond donors and acceptors, whilst
THF and dioxane are H-bond acceptors, even though their
solvation capabilities are notably lower. Therefore, it can be
concluded that the H-bond donor or acceptor ability of a
solvent is the most important property in controlling solvent-
assisted rates of tautomerization. Finally, the H+-catalyzed
tautomerization rates, that is, the kH values, no longer depend
on the solvent nature, but they are clearly lower than the value
measured in pure water. By decreasing the water content, one
also decreases the acidity of H3O+ and its solvation.
Aqueous micellar solutions. Rates of tautomerization of
ACHE in aqueous micellar solutions of TTACl have been
measured at fixed [H+] (0.030 M, HCl). To start the reaction,
10 ml of a stock ACHE (0.18 M) solution in dioxane were
Scheme 2
N e w J . C h e m . , 2 0 0 5 , 2 9 , 4 5 7 – 4 6 4
459

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Fig. 2 Influence of [TTACl] on both experimental AN and (A0 ꢀ AN);
Fig. 3 Variation of KEap, determined from AN/(A0 ꢀ AN), as a func-
tion of the micellized surfactant concentration. The solid line fits
eqn. (7); for parameters, see text.
solid lines fit eqns. (8) and (9), respectively; for parameters, see text.
of the keto form, diminishes upon increasing the TTACl
concentration, see Fig. 2.
The fit of eqn. (8) to the experimental points displayed in Fig. 2
draws the ascending curve with the following values of the
unknown parameters: A0KE/(1 + KE) = 0.385 ꢃ 0.008; Ks =
49 ꢃ 6 Mꢀ1 and (K0s + KEKs)/(1 + KE) = 23 ꢃ 3 Mꢀ1; in the
same manner, the descending curve was drawn as the fit of eqn.
(9) to the experimental data with A0/(1 + KE) = 0.519 ꢃ 0.008;
½EHꢂw þ ½EHꢂm
A
1
KEap
¼
¼
ð6Þ
½KHꢂw þ ½KHꢂm A0 ꢀ A
1
Under equilibrium conditions, the reaction scheme that considers
all possible distributions is displayed in Scheme 3. From this
scheme, the expression of eqn. (6) can be transformed into eqn. (7)
to give the variation of KaEp as a function of micellized [TTACl].
The corresponding plot can be seen in Fig. 3, clearly displaying a
curvature, meaning that the association of the keto form to the
micelle is not negligible, in contrast to other cases.7–9,15
K0s = 3.9 ꢃ 0.8 Mꢀ1 and (K0s + KEKs)/(1 + KE) = 22 ꢃ 2 Mꢀ1
.
From these results, one gets KE = 0.74 and A0 = 0.903, in perfect
agreement with the expected values. The good concordance in the
values obtained for the same parameter from the various treat-
ments that have been applied constitutes an indubitable proof of
the validity of the proposed reaction mechanism.
ꢀ
ꢁ
Kinetic experiments at fixed [surfactant] and variable [H+]
have also been performed. To start the reaction under these
experimental conditions, 100 ml of a stock equilibrated solution
of ACHE in water was diluted into 3 ml of a micellar solution.
The increase in absorbance at 291 nm due to the neat conver-
sion of the keto form into the enol form (mainly solubilized in
the micellar phase) was monitored with time. The variation of
the observed rate constant as a function of [H+] in 0.22 M of
the cationic surfactants TTACl and TTABr is shown in Fig. 4.
The least-squares adjustment of the experimental points yields
the kou and koH values reported in Table 2. A similarity between
these results and those determined in DMSO or in propyl
alcohols can be noted, which could indicate a priori that, in the
KE 1 þ Ks½TTAClꢂm
KEap
¼
ð7Þ
1 þ Ks0 ½TTAClꢂm
The curve in Fig. 3 was drawn by the fit of eqn. (7) to the
experimental points with KE = 0.71 ꢃ 0.03; Ks = 51 ꢃ 2 Mꢀ1
;
K0s = 4.0 ꢃ 0.3 Mꢀ1, and correlation coefficient (cc) = 0.999.
A good concordance between the Ks values determined here
and in the analysis of ko can be seen. Similarly, KE agrees
perfectly with the values determined in previous studies, vide
supra.6,10–11 Notice also the lower association to micelles of the
keto than the enol form; the value of K0s implies that less than
10% of the total ACHE concentration is in the micellar phase
in its ketonic form. In fact, for other 1,3-dicarbonyl com-
pounds the association of the keto form has not been detected.
Moreover, taking into account that AN = eEHc([EH]w
[EH]m), the expression in eqn. (7), and that [ACHE]0
+
=
[EH]w + [EH]m + [KH]w + [KH]m, it is easy to arrive at
eqns. (8) and (9) to relate the variation of both AN and (A0 ꢀ AN
)
as a function of [Dn], the micellized surfactant concentration.
KE
1þKE
A0
ð1 þ Ks½DnꢂÞ
A
¼
ð8Þ
ð9Þ
1
K0 þKEKs
s
1 þ
½Dnꢂ
1þKE
ꢀ
ꢁ
1 þ Ks0 ½Dnꢂ
1
A0
1þKE
A0 ꢀ A
¼
1
K0 þKEKs
s
1 þ
½Dnꢂ
1þKE
Fig. 4 Influence of [H+] on the observed rate constant obtained for
the tautomerization of ACHE at a fixed surfactant concentration equal
to [TTACl] = 0.22 M or [TTABr] = 0.25 M.
Scheme 3
460
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Table 2 Rate constants obtained in the study of the keto-enolization reaction of ACHE in aqueous micellar solutions of the indicated surfactants
by investigating the variation of ko as a function of [H+] (HCl)
kou /10ꢀ4 sꢀ1
kHo /10ꢀ3 molꢀ1 dm3 sꢀ1
K0E
a
Surfactant
cmc/M
TTACl (0.22 M)
TTABr (0.25 M)
3.5 ꢁ 10ꢀ3
6.78 ꢃ 0.01
5.60 ꢃ 0.03
Average value of at least nine determinations obtained from the values of A0 and AN
1.51 ꢃ 0.02
1.75 ꢃ 0.03
4.5
4.8
3.0 ꢁ 10ꢀ3
a
.
Scheme 5
method for enol detection. In aqueous acid medium of sodium
nitrite (a stable salt), the nitrosating agents are generated in the
protonation of HNO2, as indicated in Scheme 5.20 The con-
Scheme 4
centration of NO+ is very small due to the low value of KNO
=
presence of micelles, the tautomerization reaction occurs in a
region of low hydration, such as the micellar interface. Never-
theless, the H+-catalyzed pathway cannot take place in this site
due to electrostatic repulsion of H+ ions by the positively
charged micellar interface. Therefore, we consider Scheme 4 to
interpret the experimental facts, which includes the fast dis-
tribution of both KH and EH between the water and micellar
pseudo-phases and the slow conversion of excess keto into
the enol.
3.5 ꢁ 10ꢀ7 Mꢀ1 (reaction 1 of Scheme 5); however, it is the
most reactive nitrosating agent for the acid medium. In the
presence of nonbasic anions, such as Clꢀ, Brꢀ, SCNꢀ, etc., new
nitrosating agents, generally called XNO with X = Cl, Br, etc.,
appear (reaction 2 of scheme 5). The concentration of XNO is
always higher than that of NO+, because KXNO is higher than
K
NO and equal to 1.14 ꢁ 10ꢀ3 for ClNO, 0.051 for BrNO, and
32 Mꢀ2 for SCNNO (all data at 25 1C).21–23 Therefore, it is
expected to observe catalysis by Xꢀ in nitrosation reactions,
even though the reactivity of XNO is lower than that of NO+
and decreases in the order ClNO o BrNO o SCNNO, but
the concentration effect overwhelms in many cases the low
reactivity.
The total concentration of the initial keto form is given by:
[KH]o = [KH]w + [KH]m = [ACHE]o/(1 + KE), with KE
=
0.72. On the other hand, rate = (ku + kH[H+])[KH]w + kum
[KH]m. From these considerations and Scheme 4, the observed
rate constant may be expressed by eqn. (10), which predicts a
linear dependence of ko vs. [H+], in agreement with the
experiments.
The nitrosation of the enol of ACHE in the presence of
micelles has been studied at [H+] = 0.015 and 0.030 M and at
[nitrite] = 1.7 ꢁ 10ꢀ3 M. The [ACHE] (B6 ꢁ 10ꢀ5 M) was
always much smaller than that of nitrite. To start the reaction,
an aliquot (B10 ml) of a stock dioxane solution of ACHE was
added to the sample (V = 3 ml) containing the rest of the
reagents. The nitrosation of ACHE in water goes through an
‘unusual’ reaction mechanism for nitrosation.11 However,
under the above experimental conditions, the reaction rate
shows a first-order dependence on [H+], [nitrite], and [Xꢀ],
that is, ko = (k1 + k2[Xꢀ])[H+][nitrite], where k1 and k2
correspond to nitrosation via NO+ and XNO, respectively.
The reason for working under these conditions is to facilitate
the interpretation of micellar effects.
ꢀ
ꢁ
ku þ kmu Ks0 ½Dnꢂ þ kH½Hþꢂ
ko ¼ kou þ koH½Hþꢂ ¼
ð10Þ
ꢀ
ꢁ
ð1 þ KEÞ 1 þ K0 ½Dnꢂ
s
The predicted values of kuo and koH by application of eqn. (10) in
the case of [Dn] = 0.22 M and the results previously deter-
mined for ku, kmu , K0s, KE and kH, affords kou = 6.2 ꢁ 10ꢀ4 sꢀ1
and kHo = 1.79 ꢁ 10ꢀ3 Mꢀ1 sꢀ1, in perfect agreement with the
experimental results shown in Table 2.
Nitrosation
1,3-Diketones are readily nitrosated in water to yield 2-nitro-
soketones, which are usually stable as oxime tautomers when
an H atom is attached to the C-2.17–19 The reaction involves
enolization of the ketone, followed by electrophilic nitrosation
of the enol. Therefore, the nitrosation reaction is a good
Cationic surfactants. In the presence of TTACl, HCl was
used to control acidity, while HBr was used in the case of
TTABr, DTABr and CTABr micelles. On the other hand,
Fig. 5 Plot of ko against (A) [TTACl], obtained in the nitrosation of ACHE in aqueous micellar solutions of TTACl at [H+] = 0.030 M (HCl), and
(B) [TTABr], obtained in the nitrosation of ACHE in aqueous micellar solutions of TTABr at [H+] equal to (ꢄ) 0.030 and (m) 0.015 M, controlled
with HBr, and at [nitrite] = 1.7 ꢁ 10ꢀ3 M at 25 1C.
N e w J . C h e m . , 2 0 0 5 , 2 9 , 4 5 7 – 4 6 4
461

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Table 3 Experimental conditions and parameters of eqn. (11) for the nitrosation of ACHE in aqueous micellar solutions of the cationic surfactants
at [nitrite] = 1.7 ꢁ 10ꢀ3 M at 25 1C (for the definition of the various terms, see text).
Surfactant
cmc/M
[acid]/M
Factor
d/10ꢀ3 sꢀ1
dcal/10ꢀ3 sꢀ1a
f/10ꢀ2 sꢀ1
fcal/10ꢀ2 sꢀ1a
Ks/Mꢀ1
TTACl
DTABr
TTABr
3 ꢁ 10ꢀ3
1 ꢁ 10ꢀ2
3 ꢁ 10ꢀ3
3 ꢁ 10ꢀ3
3 ꢁ 10ꢀ4
HCl (0.030)
HBr (0.030)
HBr (0.015)
HBr (0.030)
HBr (0.013)
16
4.5
8
7.0 ꢃ 02
9.9 ꢃ 0.2
5.2 ꢃ 0.1
9.7 ꢃ 0.2
4.3 ꢃ 0.3
6.8
0.9 ꢃ 0.6
4.56 ꢃ 0.15
2.7 ꢃ 0.4
4.9 ꢃ 0.2
2.3 ꢃ 0.6
1.0
4.2
2.1
4.2
1.8
56 ꢃ 4
37 ꢃ 1
58 ꢃ 3
53 ꢃ 1
65 ꢃ 6
12.3
4.4
5
o2b
11.6
3.6
CTABr
a
Rate constants used to calculate dcal and fcal [eqn. (11)] were taken from ref. 11: k1 = 110 Mꢀ2
s
ꢀ1; k2 = kClNOKClNO = 787 Mꢀ3
s =
At the highest [CTABr] used, 0.02 M;
ꢀ1; k2
kBrNOKBrNO = 4130 Mꢀ3
s
ꢀ1; KNO = 3 ꢁ 10ꢀ7
M
ꢀ1; KClNO = 1.14 ꢁ 10ꢀ3
M
ꢀ2; KBrNO = 0.051 Mꢀ2
.
b
Fig. 6 Reciprocal plot of ko against (A) [TTACl] and (B) [TTABr] obtained in the nitrosation of ACHE in aqueous micellar solutions of TTACl
at [H+] = 0.030 M (HCl) and of TTABr at [H+] equal to (ꢄ) 0.030 M and (m) 0.015 M, controlled with HBr, and at [nitrite] = 1.7 ꢁ 10ꢀ3 M.
under the above experimental conditions, the maximum con-
ꢀ
Clꢀ or Brꢀ, whose concentrations in water increase with
[TTACl] and [TTABr], respectively (near 20% of the counter-
ions are ionized), that is [Xꢀ]0 = [Xꢀ]ad + cmc + a[TTAX]m,
where [Xꢀ]ad is the added amount with the acid (HCl or HBr);
cmc is the critical micelle concentration, and a is the degree of
micelle ionization.24,25 Therefore, considering a priori reaction
only in the water phase, then rate = kw[EH]w[XNO]w. The
symbol XNO refers to the nitrosation agents present under the
experimental conditions, that is, NO+ and ClNO or BrNO,
respectively, in the presence of Clꢀ or Brꢀ. All these considera-
tions lend us to eqn. (11), in which k1 = kNOKNO = 110 Mꢀ2
centration of NO2 is lower than 0.13 ꢁ 10ꢀ3 M, hence, one
cannot expected a significant displacement of the surfactant
.
ꢀ
counterions Clꢀ or Brꢀ due to ionic exchange with NO2
Whatever the cationic surfactant, ko decreases as the [surfac-
tant] increases (Fig. 5 shows two representative cases). How-
ever, the overall inhibition factor varies with the nature of the
counterion (higher with Clꢀ than with Brꢀ) and with the
hydrocarbon chain length (Table 3). In addition, a comparison
between Fig. 2 and Fig. 6 shows, firstly, that nitrosation is
faster than tautomerization and, secondly, that the overall
inhibition observed in nitrosation is higher than in tautomer-
ization.
Still, the results displayed in Fig. 6 indicate that, whereas the
reciprocal plot of ko against [TTACl] makes a good straight
line, in the case of TTABr the variation of 1/ko is not a linear
function of [TTABr]. Similar behaviour is observed with
DTABr. The former finding is often attributed to the absence
of reaction in the micellar phase, whereas the latter is typical of
reaction occurring in both water and micellar phases.
s
ꢀ1 has been determined for the nitrosation by NO+ in water in
the absence of micelles; in the same manner, k2 = kXNOKXNO
,
equal to 787 or 4130 Mꢀ3 sꢀ1 when Xꢀ = Clꢀ or Brꢀ,
respectively, refers to nitrosation via ClNO or BrNO; Ks is
the binding constant of the enol to micelles and [TTAX]m is the
micellized surfactant concentration.
ꢀ
ꢁ
k1 þ k2½Xꢀꢂ þ k2a½TTAXꢂ
þ
ad
m
ko ¼
½H ꢂ½nitriteꢂ
1 þ Ks½TTAXꢂm
Nevertheless, the following reasons are in opposition to any
reaction in the micellar phase. Starting from Scheme 6, the
distribution of the enol between the water and micellar pseudo-
phases must be considered, with Ks being the equilibrium
constant. Then the total ACHE concentration is [ACHE]0 =
[EH]w + [EH]m ([KH] is negligible as the nitrosation is much
faster than tautomerization). The nitrosation is catalyzed by
d þ f½TTAXꢂm
1 þ Ks½TTAXꢂm
¼
ð11Þ
The plot of ko against [TTAX]m has been fit to this equation by
using nonlinear regression analysis. Full lines in Fig. 5(A) and
5(B) were constructed by application of eqn. (11) and the
values of d {¼ (k1 + k2[Xꢀ]ad)[H+][nitrite]}, f (= k2a [H+]
[nitrite]) and Ks listed in Table 3. These values are compared
with the calculated ones, dcal and fcal, relative to our experi-
mental conditions and using k1 and k2 determined in water and
reported in the table. The good agreement between f and fcal
rules out any possibility of reaction in the micellar phase, or, at
the least, indicates a very low contribution of this reaction
pathway. To understand this, one should keep in mind the very
low [XNO] in water and, consequently, in the micellar inter-
face, as well as the slower rate of nitrosation in the micellar
interface than in water. Moreover, the agreement of the Ks
values obtained here and in the previous section on the study of
tautomerization is in favour of the mechanistic treatment. In
Scheme 6
462
N e w J . C h e m . , 2 0 0 5 , 2 9 , 4 5 7 – 4 6 4

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Fig. 7 Plots of ko against [SDS] for the nitrosation of (A) 2-acetylcyclohexanone at [nitrite] = 1.7 mM in the presence of HClO4 and of (B)
2-acetylcyclopentanone at [nitrite] = 1.7 mM and 0.015 M of the indicated strong acid.
conclusion, the inhibition effect of cationic micelles in the
nitrosation of the enol by XNO is a consequence of the
reactants’ separation; the increase of the enol bound to micelles
parallels the increase of XNO in water. The different degree of
inhibition observed between TTACl and TTABr is because in
the latter the inhibition, due to separation of the reagents, is in
part overwhelmed by the increase in the concentration of
BrNO (KBrNO 4 KClNO) parallel with TTABr.
sample is in the enol form ([ACHE]0 = [EH]), whereas in the
case of ACPE, less that 30% of [ACPE]0 is in the enol form
{[EH] = [ACPE]0KE/(1 + KE) with KE = 0.40};9 in fact, the
initial absorbance readings, A0, are independent of [SDS] in the
case of ACHE, but increase with the [SDS] in the case of ACPE
[Fig. 8(A)].
The quantitative analysis of the ko–[SDS] profiles can be
accomplished by means of the simple pseudo-phase ion-
exchange model developed by Romsted.26 This treatment
considers the distribution of the EH between aqueous and
micellar pseudo-phases; the selective ion-exchange between the
reactive H+ ions and the inert Na+ ions of the surfactant, eqn.
(12) with KI = 0.6–1,27 and the independent reactivities in the
micellar (km) and aqueous (kw) phases.
Anionic surfactants. The influence of SDS on the nitrosation
rates of ACHE was analyzed under the same experimental
conditions as for cationic surfactants, except that the acid used
was HClO4. The results are compared with those obtained in
the nitrosation of 2-acetylcyclopentanone (ACPE),9 in which
the keto-enol tautomerization is fast but the kinetic features of
the nitrosation reaction in water are the same as for ACHE.11
Fig. 7 displays typical results of the variation of ko as a
function of [SDS]. The maxima in the ko–[SDS] profiles are for
nonsolvolytic reactions carried out in the presence of surfac-
tants with inert counterions. The rate equation for enol nitro-
sation under the experimental conditions of the present study is
rate = k[H+][nitrite][EH]. Binding of the enol (EH) and H+ to
SDS micelles begins at the cmc, hence the concentration of
both reagents in the small volume of the micelle explains the
sharp increase in ko; however, the continuous dilution of the
reaction within the micellar interface with the increase in [SDS]
causes a decrease in ko.
KI
Nawþ þ Hmþ ÐNaþm þ Hwþ
ð12Þ
By defining mH = [H+]m/[SDS]m, the molar ratio of H+
bound to micelles from the micellized surfactant can be
determined at each [SDS] at constant [H+]t (= [H+]w
+
[H+]m) by solving the quadratic equation in mH given in
eqn. (13); then, the variation of ko as a function of [SDS]m
can be described by eqn. (14).
ꢂ
ꢃ
KI½Naþꢂ þ½Hþꢂ
b½Hþꢂt
m2H þ mH
ꢀ b
ꢀ
¼ 0
t
t
ðKI ꢀ 1Þ½SDSꢂm
ðKI ꢀ 1Þ ½SDSꢂm
ð13Þ
n
ꢄ
ꢅ
o
The qualitative analysis of the data shows that the maximum
catalytic effect is higher for ACPE (B5 fold) than for ACHE
(B2.5 fold) and that the [SDS] at which ko reaches its highest
value is, approximately, 0.07 M for ACPE but only 0.02 M for
ACHE. These two kinetic features reflect the importance of
reactant dilution. The enol of ACHE binds to SDS micelles (Ks =
78 Mꢀ1)6 stronger than the enol of ACPE (Ks = 23.7 Mꢀ1);9
moreover, the initial amount of ACHE added to the reaction
km
kw½Hþꢂtþ
KsNKs ꢀ kw mH½SDSꢂm
V2
ko¼
½nitriteꢂ ð14Þ
1 þ Ks½SDSꢂm
In these equations, b is the degree of micelle neutralization and
equals ([H+]m + [Na+]m)/[SDS]m (= mH + mNa); [Na+]t =
[SDS] + [nitrite]. In the case of ACPE, the numerator of eqn.
(14) appears multiplied by KE/(1 + KE) and the denominator
Fig. 8 (A) Variation of A0 as a function of [SDS] for ACHE (at l 291 nm) and for ACPE (at l 285 nm). (B) Plots of kcoor against the product
mH[SDS]m according to eqn. (13); kcoor = ko(1 + Ks[SDS]m) corresponding to ACHE. See Table 4 for plot parameters.
N e w J . C h e m . , 2 0 0 5 , 2 9 , 4 5 7 – 4 6 4
463

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Table 4 Experimental conditions and rate and equilibrium constants obtained for the nitrosation of ACHE and ACPE in aqueous SDS micellar
solutions at [nitrite] = 1.67 mM at 25 1C
Parameter
2-Acetylcylohexanone
2-Acetylcyclopentanone
[H+] = 0.015 M (HClO4 or HCl)
Intercept/10ꢀ3 sꢀ1
Slope/molꢀ1 dm3 sꢀ1
Intercept/10ꢀ3 sꢀ1
Slope/molꢀ1 dm3 sꢀ1
2.56 ꢃ 0.07
4.41 ꢃ 0.05
4.7 ꢃ 0.9
4.59 ꢃ 0.07
78
1.25 ꢃ 0.02
1.06 ꢃ 0.02
—
[H+] = 0.030 M (HClO4)
—
23.7
Ks/molꢀ1 dm3
KE
kw/molꢀ2 dm6 sꢀ1
km/molꢀ2 dm6 sꢀ1
KNs /molꢀ1 dm3
KI
0.72
0.40
170 (2209)
3.3
0.2028
0.7527
94–102 (13111
3.45–3.6
0.2028
)
0.7527
of eqn. (14) changes to 1 + [SDS]mKEKs/(1 + KE) in order to
account for the fraction of the substrate in the enol form, which
is the reactive species towards nitrosation. KNs represents the
equilibrium constant for the association of HONO to SDS
micelles, whose value was estimated as 0.20 molꢀ1 dm3 from
the variation of the free energy of transfer of HONO through
the water–micelle interface;28 V is the volume of the micellar
phase where the reaction takes place and equals 0.14 dm3
BQU2000-0239-C02-01 and BQU2003-04775-C02-01) is
gratefully acknowledged.
References
1
E. J. Fendler and J. H. Fendler, Catalysis in Micellar and Macro-
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231.
2
mol ,
ꢀ1 29 and Ks and KE have been previously determined from
direct measurements.6,9
Fig. 8(B) shows the linearization of eqn. (14) by plotting k
determined as ko(1
cor
o
3
4
,
+ Ks[SDS]m), against the product
C. A. Bunton, F. J. Nome, F. H. Quina and L. S. Romsted, Acc.
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mH[SDS]m. As expected, the plot is a straight line, from whose
slope one determines the reactivity in the micellar phase, km.
The results are listed in Table 4. The rate constant in the
micellar pseudo-phase is much smaller than the rate constant in
water due to the lower polarity of the micellar interface.
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is the consequence of the concentration of the reactants in the
small volume of the micelle.
5
6
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8
9
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Conclusions
The keto-enol tautomerization of 2-acetylcyclohexanone is
retarded in mixtures of organic solvents–water of 70% v/v.
The highest effect is observed in acetonitrile whereas the lowest
is in dimethylsulfoxide. Between them lie the cases of dioxane,
THF and alcohols. Aqueous micellar solutions of cationic
surfactants also retard the rates of tautomerization. The over-
all effect increases with the concentration of micelles and is due
to the distribution of the enol between the water and micellar
interface, where the reaction is slower than in the bulk water
phase; moreover, the H+-catalyzed pathway is not possible in
the micellar interface due to electrostatic repulsions. The
association of the keto tautomer is also detected, but the
binding constant is 20-fold lower than that of the enol. Rates
of nitrosation of the enol in aqueous acid medium are also
reduced by the presence of cationic micelles. Kinetic profiles
are satisfactorily explained by assuming that the reaction goes
only in the water phase; the increase in the concentration of the
nitrosating agent XNO parallels [TTAX] and the decrease of
[enol] in water is due to its partition between both pseudo-
phases. By contrast, the presence of anionic micelles of SDS
enhances the rate of nitrosation at low surfactant concentra-
tions due to the increase of the reactants’ concentration in the
micellar interface, because the reactivity in this region is much
lower than that in the bulk water phase.
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Acknowledgements
Financial support from the Direccio
´
(Ministerio de Ciencia y Tecnologı
n General de Investigacio
´
n
´
a) of Spain (Projects
464
N e w J . C h e m . , 2 0 0 5 , 2 9 , 4 5 7 – 4 6 4