Hydrolysis mechanisms for the acetylpyridinephenylhydrazone ligand in sulfuric acid

Article abstract of DOI:10.1021/jo000085m

The excess acidity method was applied to rate data obtained for 2-acetylpyridinephenylhydrazone hydrolysis in strong acid media using various aqueous/organic solvents, and it was observed that the reaction rate decreases with increasing permittivity of the medium. Two hydrolysis mechanisms are indicated. Below 0.6 M H₂SO₄, no hydrolysis was observed; between 0.6 and 6.0 M H₂SO₄, the substrate hydrolyzes by an A-S_E2 mechanism and switches to an A-2 mechanism at higher acidity. This change of mechanism was justified on the basis of the syn and anti rotational conformers of the diene -N(1)D=C-C=N(2)- group; the greater stability of the former can be explained by the formation of hydrogen bonds between the proton and the N₍₁₎ and N₍₂₎ nitrogen atoms, giving rise to a very stable five-membered ring. If the syn conformer is predominant, then no hydrolysis is observed; above 0.6 M, the attack of a second proton gives rise to a balance between the syn and anti forms, the latter being responsible for the hydrolysis of the hydrazone group.

Full text of DOI:10.1021/jo000085m

J . Org. Chem. 2000, 65, 3781-3787
3781
Hyd r olysis Mech a n ism s for th e Acetylp yr id in ep h en ylh yd r a zon e
Liga n d in Su lfu r ic Acid
Bego n˜ a Garc ´ı a,* Mar ´ı a S. Mu n˜ oz, Saturnino Ibeas, and J os e´ M. Leal
Universidad de Burgos, Departamento de Qu ı´ mica, Laboratorio de Qu ´ı mica F ı´ sica, 09001 Burgos, Spain
Received J anuary 21, 2000
The excess acidity method was applied to rate data obtained for 2-acetylpyridinephenylhydrazone
hydrolysis in strong acid media using various aqueous/organic solvents, and it was observed that
the reaction rate decreases with increasing permittivity of the medium. Two hydrolysis mechanisms
are indicated. Below 0.6 M H
2
SO
4 2 4
, no hydrolysis was observed; between 0.6 and 6.0 M H SO , the
substrate hydrolyzes by an A-S
E
2 mechanism and switches to an A-2 mechanism at higher acidity.
This change of mechanism was justified on the basis of the syn and anti rotational conformers of
the diene -N(1)dC-CdN(2)- group; the greater stability of the former can be explained by the
formation of hydrogen bonds between the proton and the N(1) and N(2) nitrogen atoms, giving rise
to a very stable five-membered ring. If the syn conformer is predominant, then no hydrolysis is
observed; above 0.6 M, the attack of a second proton gives rise to a balance between the syn and
anti forms, the latter being responsible for the hydrolysis of the hydrazone group.
In tr od u ction
E
Sch em e 1. AS -2 Mech a n ism
Cyclometalated complexes constitute an important tool
to activate the C-H bond, forming transition-metal
complexes the structures of which have often been
suggested as intermediate species in many metal-
1
catalyzed chemical reactions. In particular, cyclopalla-
dated complexes possess a highly reactive metal-carbon
σ bond, which becomes stabilized by further coordination
to metal of a donor heteroatom; these compounds mani-
fest quite a rich chemistry, of growing interest among
2
scientists after the contributions by Cope et al. and
3
Dunina et al. Processes such as conversion and storing
of solar energy can actually be interpreted on the basis
of the photochemical activity of these coordination com-
plexes, a number of which exhibit remarkable biochemi-
cal activity and liquid crystal properties4,5 and can be
used to introduce heavy metal and fluorescent markers
in proteins and polypeptides.6
In a previous paper, we reported on the deprotonation
in basic medium of five orthometalated complexes, struc-
turally based on 2-acetylpyridinephenylhydrazones co-
ordinated to Pd(II), to which different radicals can be
behavior observed depending on the medium acidity. At
low acidities, no hydrolysis was observed; however, at
7
attached; they contain some basic nitrogen atoms, and
therefore, they are susceptible to protonation. However,
in acidic medium, these complexes undergo chemical
reactions with not yet well-known mechanisms. In an
attempt to delineate such mechanisms, we studied the
hydrolysis of the ligand 2-acetylpyridinephenylhydra-
zone, the structure of which is shown in the Schemes 1
and 2; in this work, we report on the different kinetic
intermediate acidities (between 0.6 and 6.0 M H
the reaction proceeds by rate-determining proton attack
to the imine nitrogen (A-S 2 mechanism). At higher
acidities (between 6.5 and 11.8 M H SO ), the reaction
proceeds by nucleophilic attack of a water molecule on
the protonated substrate (A-2 mechanism). Given that
the ligand has three basic nitrogen atoms, the acidities
of the proton-transfer sites needed to establish the
reaction mechanisms were also determined.
2 4
SO ),
E
2
4
(
1) Crabtree, R. H. Chem. Rev. 1985, 85, 245.
2) Cope, C. A.; Friederich, E. C. J . J . Am. Chem. Soc. 1968, 90,
(
9
1
1
09.
(3) Dunina, V. V.; Zalevskaya, O. A.; Potapop, V. M. Usp. Khim.
Exp er im en ta l Section
988, 57, 434.
(4) Newkome, G. R.; Puckett, W. Q. E.; Kiefer G. E. Inorg. Chem.
The ligand 2-acetylpyridinephenylhydrazone was synthe-
985, 24, 811.
8
sized as described elsewhere; the other reagents were com-
(
5) Halpern, J . Inorg. Chim. Acta 1985, 41, 100.
mercially available. The spectral curves were recorded on a
(6) Sokolov, V. I.; Nechaeva, K. S.; Reutov, O. A. Zh. Org. Khim.
1
983, 19, 1103.
7) Diez-Izarra, J . L.; Garc ´ı a, B.; Ibeas, S.; Leal, J . M.; Garc ´ı a-
Herbosa, G.; Mu n˜ oz, A. React. Funct. Polym. 1998, 36, 227.
(
(8) Espinet, P.; Garc ´ı a, G.; Herrero, F. J .; J eannin, Y.; Philoche-
Levisalles, M. Inorg. Chem. 1989, 28, 4207.
1
0.1021/jo000085m CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/18/2000

3
782 J . Org. Chem., Vol. 65, No. 12, 2000
Garc ´ı a et al.
Sch em e 2. A-2 Mech a n ism
F igu r e 1. UV-vis absorption spectral curves of a 10-
4
M
O.
HP8452A spectrophotometer with a diode array detection
system and equipped with a temperature cell-holder adapter
electrically regulated and controlled by computer. The pH
readings were taken with a pHM92 Lab Radiometer pH-meter
2
-acetyl-pyridinephenylhydrazone solution in 10% DMSO/H
2
T ) 25 °C.
Ta ble 1. p KSH+ Va lu es a s a F u n ction of Solven t
P er m ittivity, E, a n d Wa velen gth s of Ma xim u m
((0.01 units). Since the substrate is only sparingly soluble in
pure water, to determine the solvent effect on the kinetics the
experiments were carried out using different aqueous/organic
solvents, containing dimethyl sulfoxide (DMSO) and ethanol
Absor p tion , λm a x
solvent
pKSH+
ꢀ
λmax (nm)
10% DMSO/H O
30% EtOH/H2O
50% EtOH/H2O
2
4.9
4.7
4.4
78.049
404
408
412
(EtOH), in the following percentages: 10% v/v DMSO/H
2
O,
5
0
3
0% v/v EtOH/H O, and 50% v/v EtOH/H O. Sulfuric acid was
2
2
64.4
53.450
used to attain the required acidity in the medium. Sulfuric
acid solutions were prepared by careful addition of the ap-
2 4
propriate amounts of commercial H SO to a 100 mL bottle
containing a known amount of doubly distilled deionized water,
the resulting acidity being determined by titration. Solutions
tion was observed. In all experiments the working temperature
was 25 °C. All kinetic runs were performed in duplicate.
of the substrate in 30% v/v EtOH/H
freshly prepared directly in the quartz cell by syringing 0.30
mL of pure ethanol to 1.4 mL of the adequate H SO solution;
after reaching thermal equilibrium, 0.30 mL of the proper
2
O mixtures were always
Resu lts a n d Discu ssion
2
4
Figure 1 shows the set of spectral curves of a 10-
4
M
-4
substrate solution, recorded upon variation of medium
acidity in 10% DMSO/H O mixture; sets similar to this
sample of the substrate dissolved in pure ethanol (6.67 × 10
M) was added to the cell. A similar procedure was used with
the other solvents.
2
were recorded with the other mixed solvents. The pro-
+
The pH readings were measured directly with a glass
electrode, which was calibrated in an aqueous medium.
However, the measurable pH(R) readings differed by a δ
quantity from the value measured using the buffer corre-
cedure used to calculate pKSH values based on UV-vis
1
2,13
spectroscopic measurements was previously described;
the values are listed in Table 1 along with the solvent
permittivity, ꢀ, and the wavelength of maximum absorp-
tion. In view of the basic character of the N atoms of the
ligand, and given the dissociation constant of pyridinium
ion, pKSH ) 5.2, it is reasonable to ascribe these
constants to N(1)-protonation of the pyridine moiety; on
the other hand, given that the structure of 2-acetyl-
9
sponding to the system in pure water. Thus, due to the
aqueous/organic mixtures used as solvents, it was necessary
to correct the pH values using the equation pH* ) pH(R) - δ;
the δ parameter was essentially constant for a given aqueous/
organic mixture at constant temperature; its amount was
+
1
4
negligible for 10% DMSO-H
for 30% and 50% EtOH/H O, respectively. Outside the pH
2 4
range, the proton concentration C for each H SO concentra-
2
O and tends to 0.085 and 0.16
8
2
pyridinephenylhydrazone was shown to be planar, the
+
H
proton entering in the “pyridine” N(1) atom becomes
hydrogen-bonded to the “imine” N(2) nitrogen atom,
forming a stable five-membered ring that establishes the
syn structure (II) (Schemes 1 and 2) of the diene group.
No hydrolysis was observed with this conformer. The
1
0
tion was taken from literature sources. The Lambert-Beer
law was assessed at all wavelengths used.
The kinetic study was carried out by monitoring the
decrease with time of the substrate absorbance reading,
measured at the maximum wavelength. In all cases, the
reaction was followed at least up to 90%, which corresponds
to a reaction time larger than 3.32 ln 2/kobs, kobs being the
+
pKSH values decreased as the solvent permittivity
+
decreased; these variations in pKSH were ascribed to
1
1
observed rate constant. Within the acidity range investigated,
no dependence of the rate constant on the substrate concentra-
medium effects, these being defined as the ratio between
(
12) Garc ´ı a, B.; Leal, J . M. Collect. Czech. Chem. Commun. 1987,
52, 1087.
(13) Garc ´ı a, B.; Palacios, J . C. Ber. Bunsen-Ges. Phys. Chem. 1988,
92, 696.
(14) Pine, S. H.; Hendrickson, J . B.; Cram, D. J .; Hammond, G. S.
In Qu ı´ mica Org a´ nica, 2nd ed.; McGraw-Hill: Mexico D.F., 1993.
(9) Perrin, D. D.; Dempsey, B. Buffers for pH and Metal Ion Control;
Chapman and Hall: New York, 1979; pp 77-93.
(
10) Cox, R. A.; Yates, K. J . Am. Chem. Soc. 1978, 100, 3861.
11) Espenson J . H. Chemical Kinetics and Reactions Mechanims;
(
2
nd ed.; McGraw-Hill: New York, 1995.

Hydrolysis Mechanisms for Acetylpyridinephenylhydrazone
J . Org. Chem., Vol. 65, No. 12, 2000 3783
To determine the reaction mechanism at medium and
high acidity levels, available methods of dealing with
1
8
kinetic data such as those of Zucker-Hammett, Bun-
nett,19 LFER, and Cox-Yates
20
21,22
can be used. The three
first treatments have the advantage of introducing the
acid concentration in terms of the Hammett acidity
2
3
function, H
o
;
o
however, as H was originally defined
using aniline as the reference base, which is structurally
very distinct from the substrate used here, the excess
acidity method proposed by Cox-Yates was preferred,
yielding consistent results. The excess acidity, which
represents the extra acidity of the medium due to its
nonideal behavior, manifests the very useful property of
being 0 in the standard state of activity coefficients unity
and has become a powerful tool to study the effect of
medium acidity upon the rate and equilibrium of a
reaction, thus enabling us distinguish between three
2
4
hydrolysis mechanisms:
(
i) A-1 Mech a n ism . If the starting material is SH+,
the substrate predominantly protonated under the reac-
tion conditions, then the following mechanism applies:
K
2+
SH2
+
+
2+
F igu r e 2. Absorption UV-vis spectral curves corresponding
to hydrolysis of 2-acetylpyridinephenylhydrazone in 10.37 M
SH + H y
z SH2 fast
(2)
2 4
H SO ; time interval, 400 s.
k1
9
2
2
+
2+
SH
8 A slow
(3)
(4)
the proton’s activity coefficients in the solvent used and
in water.15 As already reported, a bathochromic shift
was also observed as the solvent polarity decreases.
However, in more highly acidic media a decrease in
the substrate peak due to hydrolysis was observed; the
observed rate constants, kobs, were calculated by nonlin-
ear least-squares regression,17 using eq 1,
16
A2+ + H O f P fast
2
involving a fast preequilibrium protonation of SH+,
followed by rate-determining unimolecular reaction of
either to some intermediate species A , which
subsequently reacts quickly, or directly to products. The
relevant rate equation is
2
+
2+
SH
2
-kobst
A ) A - (A - A )e
(1)
∞
o
∞
CSH
+
k1
log kobs - log
- log CH
+
) log
+
where A and A stand for the initial and final absorbance
readings and A those at different reaction times, respec-
tively. The initial values introduced to calculate these
o ∞
CSH22+ + CSH
+
KSH22+
q
m m*X (5)
parameters are A
absorbance measured) - 0.25A
o
, the first reading, and A
∞
) 1.25* (last
q
o
, kobs) 2/(total reaction
where the slope parameter m measures the position of
the transition state and correlates the activity coefficients
of the substrate with those of the transition state, eq 6;
the m* parameter, defined in eq 7, relates the activity
coefficients of the substrate and those of the standard
base used as a reference in the definition of X:
time). This procedure has the advantage that the ab-
sorbance readings need not to be taken at constant time
intervals, nor is it necessary to monitor the reaction to
completion.17 The computer program used for the fitting
of data is based on the Macquart-Lavengur method;
after introducing the initial estimated values, the process
is iterated until convergence is achieved for the minimum
fSH
+
fH
+
fSH fH
+ +
q
q
log
) m log
) m m*X
(6)
(7)
2
value of the ø parameter.
fq
fSH
2
2+
As an example, Figure 2 shows the spectral curves
recorded at different time intervals. Table 2 summarizes
the kobs values determined at different acidity levels for
each of the different aqueous/organic solvents used.
fSH
+
fH
+
f f
+
B H
log
) log
) m*X
fSH22+
fBH
+
2 4
Figure 3 shows the change of kobs with H SO concentra-
q
To find out the m value and therefore to be able to
establish the reaction mechanism, the proper value for
m* corresponding to protonation equilibrium in high
tion using three different mixed solvents; the profiles of
the three plots are similar and exhibit two stretches with
different slopes; in the first stretch (0.6-6.0 M), kobs
increased with an increase in acidity only very slowly
compared to the sharp increase observed above 6.0 M
2
+
acidity, pKSH2 , must also be determined. The plot of the
left-hand side of eq 5 vs X should give a straight line,
H
2
SO
4
, this feature reflecting that another mechanism
(
(
(
18) Zucker, L.; Hammett, L. P. J . Am. Chem. Soc. 1939, 61, 2791.
19) Bunnett, J . F. J . Am. Chem. Soc. 1961, 83, 4956.
20) Bunnett, J . F.; Olsen F. P. Chem. Commun. 1965, 601; Can. J .
is taking over at higher acidity.
(
15) Bates, R. G. Determination of pH. Theory and Practice; J ohn
Wiley & Sons: New York, 1973.
16) Zhou, J . W.; Li, Y. T.; Tang, Y. W.; Song, X. Q. J . Solution Chem.
995, 24, 625.
17) Moore, P. J . Chem. Soc., Faraday Trans. 1 1972, 68, 1890.
Chem. 1966, 44, 1899.
(21) Cox, R. A. Acc. Chem. Res. 1987, 20, 27.
(22) Cox, R. A. Adv. Phys. Org. Chem. 2000, in press.
(23) Hammett, L. P.; Deyrup, A. J . J . Am. Chem. Soc. 1932, 54, 2721.
(24) Cox, R. A.; Yates, K. Can. J . Chem. 1981, 59, 1560.
(
1
(

3
784 J . Org. Chem., Vol. 65, No. 12, 2000
Garc ´ı a et al.
Ta ble 2. Va lu es of th e kObs Ra te Con sta n ts in H2SO4 a t 25 °C
30% EtOH/H2O
1
0% DMSO/H2O
50% EtOH/H2O
kobs × 10 (s-1)
5
[H2SO4] (M)
kobs × 10 (s-1)
5
[H2SO4] (M)
kobs × 10 (s-1)
5
[H2SO4] (M)
0
1
1
2
3
3
4
5
5
6
7
7
8
9
9
9
.65
.30
.95
.59
.24
.89
.54
.19
.84
.48
.13
.78
.43
.08
.40
.72
0.342 ( 0.001
0.691 ( 0.004
1.014 ( 0.001
1.399 ( 0.001
2.022 ( 0.002
2.724 ( 0.003
3.338 ( 0.002
4.304 ( 0.003
5.816 ( 0.002
8.261 ( 0.005
11.27 ( 0.01
15.55 ( 0.01
22.01 ( 0.02
29.03 ( 0.02
35.36 ( 0.02
44.00 ( 0.07
53.2 ( 0.2
3.03
4.03
4.54
5.04
5.55
6.05
6.56
7.31
7.56
7.82
8.07
8.32
8.57
8.83
9.33
9.58
9.83
10.09
10.34
0.771 ( 0.001
1.218 ( 0.001
1.582 ( 0.005
2.157 ( 0.002
2.897 ( 0.002
3.935 ( 0.007
5.706 ( 0.009
8.60 ( 0.02
3.24
3.96
4.32
4.68
5.04
5.22
5.40
5.58
5.76
5.94
6.12
6.30
6.48
6.66
6.84
7.02
7.20
7.38
7.56
7.92
8.29
8.65
0.481 ( 0.001
0.662 ( 0.002
0.789 ( 0.003
0.953( 0.002
1.089 ( 0.002
1.344 ( 0.003
1.599 ( 0.001
1.929 ( 0.003
1.994 ( 0.002
2.443 ( 0.003
2.977( 0.003
3.435 ( 0.007
3.571 ( 0.006
4.518 ( 0.004
5.203 ( 0.006
6.109 ( 0.009
6.595 ( 0.009
7.51 ( 0.01
11.34 ( 0.02
12.46 ( 0.02
15.47 ( 0.05
17.89 ( 0.01
20.49 ( 0.01
24.20 ( 0.01
30.47 ( 0.03
34.54 ( 0.06
37.65 ( 0.08
40.6 ( 0.1
1
1
1
1
1
1
0.05
0.37
0.70
1.02
1.35
1.67
57.8 ( 0.2
69.2 ( 0.4
44.2 ( 0.3
8.54 ( 0.01
72.5 ( 0.3
10.12 ( 0.03
10.64 ( 0.04
12.01 ( 0.03
13.93 ( 0.07
82.1 ( 0.6
82.4 ( 0.8
9
.01
determining transition state
K
2+
SH2
+
+
2+
SH + H y
z SH2 fast
(2)
(8)
k2
2
+
SH + nNu
98 P slow
2
where Nu stands for the nucleophile (normally water)
and n is the number of molecules. The relevant rate
equation derived for this mechanism is as follows
CSH
+
log kobs - log
- log CH
+
+
- n log aNu )
CSH22+ + CSH
k2
q
log
+ m m*X (9)
KSH22+
q
where m must be close to unity. To be able to plot the
2
left-hand side of eq 9 vs X, the k value should be
F igu r e 3. log kobs vs [H
phenylhydrazone at 25 °C using three different mixed solvents.
2 4
SO ] profile for 2-acetylpyridine-
previously determined if the equilibrium constant is
already known. This equation was applied successfully
to hydrolyses of benzoic acid derivatives and azo-
the ordinate of which provides log(k
1
/KSH22+); in addition,
the m value is greater than 1 and normally falls between
and 3. This treatment was applied to determine the
32-35
pyridines.
q
(
E
iii) A-S 2 Mech a n ism . Cox proposed a bimolecular
2
pathway for the reaction scheme, involving rate-deter-
mining proton transfer to the monoprotonated sub-
strate20
mechanism of a variety of hydrolyses, including a number
of esters, substituted benzaldehydes, and other sub-
strates,2
5-29
as well as the chromic acid oxidation of
propanal30 and glycolic acid.
3l
k2
9
+
+
2+
(
ii) A-2 Mech a n ism . This is like the A-1 mechanism
SH + H
8 SH slow
(10)
(11)
2
except that the diprotonated substrate, instead of react-
ing alone, reacts with an additional species in the rate-
SH 22 + + H O f P fast
2
(
25) Cox, R. A.; Goldman, M. F.; Yates, K. Can. J . Chem. 1979, 57,
2
960.
leading to the rate equation
log kobs - log CH+ ) log k + m m*X
(26) Cox, R. A.; Yates, K. J . Org. Chem. 1986, 51, 3619.
27) Ali, M.; Satchell, D. P. N. J . Chem. Soc., Perkin Trans. 2 1991,
(
q
5
(12)
2
1
992, 1855.
(29) Motie, R. E.; Satchell, D. P. N.; Wassef, W. N. J . Chem. Soc.,
(32) Cox, R. A.; Smith, C. R.; Yates, K. Can. J . Chem. 1979, 57, 2952.
(33) Cox, R. A.; Yates, K. Can. J . Chem. 1982, 60, 3061.
Perkin Trans. 2 1993, 1807.
(
(
30) Alvarez, M. P.; Montequi, M. I. An. Quim. 1992, 88, 149.
31) Montequi, M. I.; Alvarez, M. P. An. Quim. 1989, 85, 331.
(34) Cox, R. A.; Onyido, I.; Buncel, E. J . Am. Chem. Soc. 1992, 114,
1358.

Hydrolysis Mechanisms for Acetylpyridinephenylhydrazone
J . Org. Chem., Vol. 65, No. 12, 2000 3785
q
As mentioned above, the m value is characteristic of
E
the type of mechanism; in the case of an A-S 2 scheme,
q
m should be less than 1. Equation 12 was applied to
hydration of alkylesters and some phenylacetylene de-
rivatives and hydrolyses of azocompounds and other
substrates.3
6-4l
The protonation acidity constant pKSH22+ needed for the
proposal of this mechanism was calculated at high acidity
by collecting and comparing the first spectral curves
recorded in each kinetic run of a series of experiments
similar to that of Figure 2, each performed at a different
2 4
acidity. Up to about 6.5 M H SO no significant spectral
changes were observed; the changes in the first spectral
curves, brought about by stepwise increase of medium
acidity, enable the establishment of the protonation
acidity range between 6.5 and 14.3 M H
2 4
SO using 10%
v/v DMSO/H O. Figure 4a displays the spectral curves
2
corresponding to dissociation of the doubly protonated
form of the substrate; the appearance of a distorted
isosbestic point reveals the presence of at least two
species in equilibrium. By increasing the organic com-
ponent in the solvent, the results became less accurate
because reliable literature data of proton concentrations
corresponding to H
are lacking.
2 4
SO concentration in mixed solvents
The observed shifts in wavelengths can actually be
attributed either to hydrolysis or to medium effects, or
both. For a proper treatment of the medium effects we
used the vector analysis method, already applied in
amides44 and pyrimidines protonation, and the excess
45
2
4
acidity method as well. Figure 4b shows the reconsti-
tuted absorbance curves after application of vector analy-
sis. The results were compared with those obtained using
the excess acidity method, as stated by eq 7. The
thermodynamic equation derived for equilibrium [2] is
as follows
log I - log CH
+
) m*X + pKSH22+
(13)
where I is the ionization ratio calculated from the
+
absorbances of the spectral curves, C
H
is the proton
concentration, and m*, the slope parameter characteristic
4
6,47
of the base, is 1.0 for primary aromatic amines,
0.6
for amides,4
4,46
0.8 for carbocations,
47,48
etc. The three
F igu r e 4. (a) Experimental absorbances corresponding to
protonation KSH22+ of 2-acetylpyridinephenylhydrazone in 10%
v/v DMSO/H O. (b) Reconstituted absorbances after applica-
2
methods described above lead to very close results using
the X values available for aqueous sulfuric acid; the
average value is pKSH22+ ) -5.8 ( 0.1 and m* ) 0.94 (
tion of vector analysis.
(
35) Ghosh, K.K.; Rajput, S. K.; Krihnani, K. K. J . Phys. Org. Chem.
992, 5, 39.
36) Cox, R. A.; McAllister, M.; Roberts, K. A.; Stang, P. J .; Tidwell,
T. T. J . Org. Chem. 1989, 54, 4899.
37) Cox, R. A.; Grant, E.; Whitaker, T.; Tidwell, T. T. Can. J . Chem.
990, 68, 1876.
0.03. This constant corresponds to protonation of the N(2)
site, the protonated form being responsible for further
hydrolysis of the substrate (Scheme 2).
Once the thermodynamic parameters are known, it is
feasible to carry out the kinetic calculations needed to
determine the hydrolysis mechanisms.
1
(
(
1
(
38) Cox, R. A. J . Phys. Org. Chem. 1991, 4, 233, 4.
(39) Ali, M.; Satchell, D. P. N. J . Chem. Soc., Perkin Trans 2 1992,
2
19.
40) J oseph, V. B.; Satchell, D. P. N.; Satchell, R. S.; Wassef, W. N.
J . Chem. Soc., Perkin Trans. 2 1992, 339.
41) Ali, M.; Satchell, D. P. N.; Le, V. T. J . Chem. Soc., Perkin Trans.
1993, 917.
(a ) A-S
were analyzed with eqs 5, 9, and 12, corresponding to
mechanisms A-l, A-2, and A-S 2, respectively; within the
first interval of low rate constants, ranging from 0.65 to
ca. 5.84 M H SO , the reaction follows an A-S 2 mecha-
E
2 Mech a n ism . The kinetic data of Figure 2
(
(
E
2
(
42) Buncel, E.; Onyido, I. Can. J . Chem. 1986, 64, 2115.
2
4
E
(43) Onyido, I.; Opara, L. U. J . Chem. Soc., Perkin Trans. 2 1989,
1
817.
44) Garc ´ı a, B.; Casado, R. M.; Castillo, J .; Ibeas, S.; Domingo, P.
L.; Leal, J . M. J . Phys. Org. Chem. 1993, 6, 101.
45) Garc ´ı a B.; Arcos J .; Domingo P. L.; Leal, J . M. Anal. Lett. 1991,
4, 391.
nism (Figure 5) (linear correlation coefficient, r ) 0.998),
(
according to which the rate-determining step should be
+
q
the attack of a proton to SH ; the value m ) 0.20 also
(
points to an A-S
E
2 mechanism.20 However, values of X
2
(
(
(
46) Cox, R. A.; Yates, K. Can. J . Chem. 1984, 62, 2155.
47) Cox, R. A.; Yates, K. Can. J . Chem. 1981, 59, 2116.
48) Garc ´ı a-Herbosa, G.; Mu n˜ oz, A.; Miguel, D.; Garc ´ı a-Granda, S.
10,24
are available in aqueous H
2
SO
4
only,
this fact ex-
plaining why the best results correspond to the solvent
with the highest water content. In this case, the rate
Organometallics 1994, 13, 1775.

3
786 J . Org. Chem., Vol. 65, No. 12, 2000
Garc ´ı a et al.
+
F igu r e 5. kobs - log c
scheme. T ) 25 °C.
H
2 4 E
vs X acidity plot in H SO for an A-S 2
constant k
2
) 3.35 10- M-1 s-1 was obtained for the rate-
6
determining step. The protonation of a base normally is
diffusion-controlled and, therefore, fast, with rate con-
stants accessible by nonconventional techniques designed
for fast reactions; however, among the wide variety of
F igu r e 6. log kobs - log (CSH+/(CSH+ + CSH22+)) - log CH+ - log
reactions that follow the A-S
E
2 mechanism, there is in
a
H2O 2 4
vs X excess acidity plot for an A-2 scheme in H SO . T )
value.2
1,36-43
principle no upper limit in the k
2
25 °C.
This mechanism can be interpreted by Scheme 1. The
attack of a second proton occurs on the “imine” N(2)
s- obtained using the acidity function X.22 The proposed
1
mechanism is given in Scheme 2.
nitrogen atom, the reaction site where hydrolysis occurs.
The X-ray diagrams performed with the ligand8,48 and
The rate constants increased with increasing solvent
permittivity, this increase being greater at higher acidity.
At constant acid concentration the change in reaction rate
is in the following order: 10% DMSO/H
30% EtOH/H O (ꢀ ) 64.45) > 50% EtOH/H
The rate constants of most reactions change with changes
in solvent permittivity, including elementary reactions;
in the lower acidity range, A-S 2 mechanism, the differ-
ence in the degree of solvation between the reagents and
the transition state explains the solvent influence, since
the transition state has a greater ionic character than
the reagents.
The influence of solvent permittivity on the rate
constant is much stronger in the high acidity range (A-2
mechanism). According to the transition-state theory, this
feature might be attributed to the larger charge separa-
tion and, therefore, to the greater stability of the transi-
tion state compared to reagents. The noticeable solvation
requirements of the hydrate make its stability to increase
considerably as the solvent dielectric constant increases,
this effect contributing to a decrease in activation energy.
Several formulations have been developed to interpret
the effect of solvent permittivity on the reaction rates of
other Pd complexes with this ligand confirm a planar
structure and reveal proper bond distances and bond
2
O (ꢀ ) 78.5) >
2
angles quite favorable for coordination by hydrogen bond
to the two “pyridine” and “imine” N atoms.49 The very
2
O (ꢀ ) 53.44).
stable syn conformer (II) of the diene group is the only
structure existing at an acidity level below 0.6 M and is
responsible for the substrate hydrolysis. The attack of a
second proton on the N(2) atom of the hydrazone is
difficult in the case of syn conformers; thus, above 0. 6
5
0
E
2 4
M H SO , the rotation of the σ (C-H) bond is feasible,
giving rise to a balance between the syn (II) and anti (III)
rotational conformers, the former being more stable.
Since the number of anti conformers is very low and these
species are involved in the protonation, it is reasonable
to interpret the low k
on the concentration of anti conformers. Also the little
effect of acidity on k (Figure 3), points to the nonexist-
2
rate constant as a value dependent
2
ence of an acid-base balance within this acidity range,
as can be inferred from the value pKSH22+ ) -5.8.
(
b) A-2 Mech a n ism . Within the 6.4-11.6 M acidity
range the fitting of kinetic data to eq 9 is fairly good
Figure 6, linear correlation coefficient, r ) 0.999), the
(
m
51-53
ion-ion, ion-dipole, and dipole-dipole in solution.
q
) 0.86 value being reasonably close to unity, as
2
0
required by the A-2 mechanism. As in the above case,
the protonation occurs on the nitrogen hydrazone group
of the rotational anti conformer. However, above 6.4 M
this step is fast, as confirmed by the acid-base balance
established between the mono and diprotonated forms.
The rate-determining step is the nucleophilic attack of a
(
49) Scheiner, S. Hydrogen Bonding. A theoretical Perspective;
OUP: New York, 1997.
(
(
50) Funasaki, N.; Hada, S.; Neya, S. J . Phys. Chem. 1985, 89, 3046.
51) Connors, K. A. Chemical Kinetics. The study of Reaction Rates
in Solution; VCH: New York, 1990.
52) Pilling, M. J .; Seakins, P. W. Reaction Kinetics; OUP: New
York, 1995.
(
(
53) Zuman P.; Patel, R. C. Techniques in Organic Reactions
-
1
water molecule, with the rate constant k
2
) 0.309 M
Kinetics; Wiley: New York, 1984.

Hydrolysis Mechanisms for Acetylpyridinephenylhydrazone
J . Org. Chem., Vol. 65, No. 12, 2000 3787
dilution. In this work, the slope of the straight line should
be negative, consistently with the obvious fact that the
transition state is more polar than the positively charged
reagents. In the case of ion-dipole interactions (A-2
mechanism), the following formulation was developed for
the limit case of a zero approximation angle between the
ion and the dipole:51
2
N Ze
1
1
rq
ln k ) ln k -
-
(15)
∞
(
)
(
4πꢀ )2ꢀ RT r
o
r
ion
The slope of the plot log k vs 1/ꢀ depends on the relative
values of rion and r
Figure 7 plots the values log k vs 1/ꢀ
q
the radius of the transition state.
at different acid
r
concentrations. In this figure, the eqs 14 and 15 are
written out and a clear parallelism can be seen mainly
in the acidity range corresponding to the A-S 2 mecha-
E
nism; the negative slope is consistent with a transition
state positively charged and more polar than the reagent,
in accordance with the proposed mechanism; obviously,
the rion radius is smaller than r , consistent with the
q
proposed mechanism. The somewhat smaller parallelism
observed in the A-2 range can be explained by the lack
of acidity functions in the media under study, which
causes greater effects when the acid concentration is
increased.
r
F igu r e 7. Plot showing the variation of log kobs vs 1/ꢀ for the
hydrolysis reaction at different acidity levels.
For reactions between two ions (which is the case in an
A-S
E
2 mechanism), the dependence of log k vs 1/ꢀ
r
is as
follows11
Ack n ow led gm en t. The finantial support by the
spanish DGESIC, project PM97-0153, and J unta de
Castilla y Le o´ n, project BU08/97, are gratefully acknowl-
edged.
2
Nz z e
A
B
ln k ) ln k -
(14)
∞
(
4πꢀ )ꢀ RTr
o r q
where k
∞
is the constant in the reference state of infinite
J O000085M