Reaction of 4-Benzylidene-2-methyl-5-oxazolone with Amines, Part 2: Influence of substituents in para-position in the phenyl ring and a substituent on Amine Nitrogen Atom on the reaction kinetics

Article abstract of DOI:10.1002/kin.10039

An influence of a structure of the amine (benzylamine, N-methyl-benzylamine, N-isopropyl-benzylamine, N-methyl-butylamine, N-ethyl-butylamine, sec-butylamine, and tert-butylamine) on a rate constant of the ring-opening reaction of 4-benzylidence-2-methyl-

Full text of DOI:10.1002/kin.10039

Reaction of 4-Benzylidene-
2-methyl-5-oxazolone with
Amines, Part 2: Influence
of Substituents in Para-
Position in the Phenyl Ring
and a Substituent
on Amine Nitrogen Atom
on the Reaction Kinetics
B. BETLAKOWSKA,1 B. BANECKI,2 C. CZAPLEWSKI,1 L. LANKIEWICZ,1 W. WICZK1
1
´
´
Faculty of Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk, Poland
2
´
´
Intercollegiate Faculty of Biotechnology, University of Gdansk & Medical Academy of Gdansk,
´
Kladki 24, 80-822 Gdansk, Poland
Received 9 March 2001; accepted 24 August 2001
ABSTRACT: An influence of a structure of the amine (benzylamine, N-methyl-benzylamine,
N-isopropyl-benzylamine, N-methyl-butylamine, N-ethyl-butylamine, sec-butylamine, and tert-
butylamine) on a rate constant of the ring-opening reaction of 4-benzylidene-2-methyl-5-
oxazolone (Ox) was studied. The good correlation between logarithm of the rate constants and
Charton’s steric substituent constant as well as good correlation with a form of the simple
branching equation indicate that there is a steric effect because of substitution at C1 carbon
atom of nucleophile which decreases the reaction rate. Additionally, an influence of a structure
of the benzylidene moiety of Ox on a rate of the oxazolone ring-opening reaction was studied.
Correspondence to: W. Wiczk; e-mail: ww@chemik.chem.univ.
gda.pl.
Contract grant sponsor: Polish State Committee for Scientific
Research.
Contract grant number: BW-8000-5-0230-4.
2002 Wiley Periodicals, Inc.
c

REACTION OF 4-BENZYLIDENE-2-METHYL-5-OXAZOLONE WITH AMINES
149
The substituents ( OH, OCH3, N(CH3)2, Cl, NO2) in para-position of the phenyl ring of
Ox substantially modified the rate of the reaction with benzylamine in acetonitrile. The rate of
the Ox ring-opening reaction decreased with increase of the electron-donating properties of the
substituent. A good correlation between the rate constants of the reaction of 4-(40-substituted-
benzylidene)-2-methyl-5-oxazolones with benzylamine and the electron density at the reaction
center (carbon C5 of the oxazolone ring), calculated using ab initio method, and the Hammett
C
substituent constants, and CR equation were established.
Chem Kinet 34: 148–155, 2002; DOI 10.1002/kin.10039
2002 Wiley Periodicals, Inc. Int J
INTRODUCTION
Oxazolones, the activated form of carboxylates formed
from amino acids, are applied for the peptide bond
formation. They are widely used especially in syn-
thesis of dehydropeptides. 4-Benzylidene-substituted
oxazolones are very suitable intermediates for syn-
thesis of peptides containing dehydrophenylalanine
(dehydropeptides) [1,2]. Disappearing, after treatment
with an amine, a characteristic absorption band of
4-benzylidene-2-methyl-5-oxazolone (Ox) at 325 nm
was utilized to study the kinetics and mechanism of the
ring-opening reaction of oxazolone [3]. The spectroki-
netic method can be also used to study the influence of
structural modifications of amines on the rate of this re-
action. The influence of structural modification on the
reactivity of molecules is often interpreted qualitatively
in terms of steric effects. Many different scales of steric
subsituent constants were proposed. The Taft’s Es
Figure 1 Structure of 4-benzylidene-2-methyl-5-oxazolo-
ne and reaction scheme.
constants , which were defined as independent in the
studied reaction.
c
In this paper we used the Hancock’s Es [8]
and Charton’s ␯ [10–13] substituent constants, sim-
ple branching equation [18–20] for the qualitative
interpretation of the influence of the steric effects on
the ring-opening reaction of Ox with different amines.
The Hammett equation as well as the CR equation [29]
were applied for quantitative analysis of the influ-
ence of substituents in 4-(40-substituted-benzylidene)-
2-methyl-5-oxazolones (Fig. 1) on the reaction rate
with benzylamine. For the purpose of our studies,
we prepared Ox analogues with electron-donating or
electron-withdrawing substituents in the phenyl ring,
such as OH, OCH3, N(CH3)2, Cl, and NO2.
c
[4–7] and Hancock’s Es [8] constants were based
on the rate constants of the acidic hydrolysis of a
substituted ester and a reference ester, while Fellous’
and Luft’s Es constants were based on hydroboration
reaction of alkenes by bis(1,2-dimethylpropyl)borane
[9]. Charton [10–13] defined the steric parameter, ␯,
from the intrinsic size of the substituent defined by
its average van der Waals radius, while Beckhouse
[14,15] based his parameter on differences between
the heat of formation of the tert-butyl derivative of
R [R C(CH3)3] and that of the methyl derivative
[R CH3]. Statistical evidence was put forward, sug-
gesting that v was the better measure of steric effects
MATERIALS AND METHODS
c
than Es [16,17]. Because the steric effects cannot be
analyzed using a single steric parameter, the expanded
branching equation was introduced by Charton [18–
20].
Synthesis of 4-(40-Substituted-
benzylidene)-2-methyl-5-oxazolones
In organic chemistry many empirical models for a
descriptionofrelationsbetweenstructureandreactivity
have emerged. The most successful model describing
an influence of substituents on the reaction rate was
based on the classical Hammett equation [21–25] and
its further modifications [6,26–29]. The Hammett
model assumed a direct correlation between the influ-
ence of substituents on the reaction rate and substituent
The synthesis of 4-benzylidene-2-methyl-5-oxazolone
(Ox) and its purification was described in the previ-
ous paper [3], and therefore in this paper we include
only a brief description of the synthesis. The gen-
eral procedure of the oxazolone preparation is as fol-
lows: 0.183 mol of sodium acetate and 0.62 mol of
acetic anhydride were added to a round-bottom flask
(500 ml) containing 0.25 mol of acetylglycine and

150
BETLAKOWSKA ET AL.
0.37 mol of an appropriate benzaldehyde. The result-
ing mixture was refluxed under nitrogen for 1.5 h. Af-
ter that, the obtained solution was cooled and placed
into a refrigerator for crystallization. The formed crys-
tals were filtered off, washed with water, and dried.
The crude product was recrystallized from carbon
tetrachloride.
4-(p-Hydroxy)benzylidene-2-methyl-5-oxazolone
(HO Ox, yield 72%). H NMR (400 MHz, CDCl3):
1
(ppm) = 2.33 (s, 3H, CH3
C ), 7.12 (s, H, Ar
CH , ␥-lactone), 7.20 (d, 2H, JH = 8.8 Hz, aro-
matic), 8.12 (d, 2H, JH = 8.8 Hz, aromatic); FT-IR
(KBr):
(cm 1) = 3431.5, 3291.8, 918.9, 892.2
(O H), 3070.1 (w, H C , ␥-lactone), 1776.2 (s,
C
w,
O, ␥-lactone), 1655.7, 1601.9, 1492.6 (s, m,
in ring), 1450.8, 1425.9 (aromatic
C N
1H NMR and FT-IR Analysis of Para-
Substituted 4-Benzylidene-2-methyl-5-
oxazolones
ring), 1303.6, 1263.7, 1230.5 (w, s, s, C O C ,
␥-lactone).
All amines used in kinetic measurements were pur-
chased form Aldrich and were used without any addi-
tional purification.
4-(p-Dimethylamino)benzylidene-2-methyl-5-oxazol-
1
one ((CH3)2N Ox, yield 78%). H NMR (400 MHz,
CDCl3): (ppm) = 2.43 (s, 3H, CH3
C ), 3.10 (s, 6H,
(CH3)2 N), 6.72 (d, 2H, JH = 9.0 Hz, aromatic), 7.16
(s, 1H, Ar CH , ␥-lactone), 8.00 (d, 2H, JH = 9.0
Hz, aromatic); FT-IR (KBr): (cm 1) = 3070.1 (w,
H C , ␥-lactone), 2907.7, 2823.6 (w, w, (CH3)2N ),
1776.2 (s, C O, ␥-lactone), 1655.7, 1601.9, 1492.6
Kinetic Measurements
A course of the ring-opening reaction of Ox with an
aminewasstudiedbyrecordinganabsorbancedecrease
of the substrate at an absorbance maximum of the long-
wavelength band and at a maximum of the increased
absorbance of a product using a Specord UV/VIS Carl
Zeiss Jena spectrophotometer equipped with 12-bytes
analogue-to-digital converter and the computer pro-
gram Mult ver. 3.12 (Ambex, Warsaw, Poland). For one
experimental curve 4096 data points were collected. In
the kinetic measurements, concentration of the oxa-
zolone (c = 5.25 10 5 M) was the same in all exper-
iments. The ring-opening reaction was performed in
acetonitrile (MeCN) at 293 K. The concentrations of
benzylamine (BzA), N-methylbenzylamine (MBzA),
and N-methylbutylamine (MBuA) were varied in a
range from 0.025 to 0.36 M, whereas the kinetic mea-
surements with application of sec-butylamine (s-BuA),
tert-butylamine (t-BuA), N-isopropylbenzylamine (i-
PrBzA), and N-ethylbutylamine (EtBuA) were per-
formed for the amine concentration equal to 0.059 M.
In the case of kinetic studies of the reaction of an ap-
propriate para-substituted in the benzylidene moiety
oxazolone with BzA, the molar ratio of BzA to an ap-
propriate oxazolone was about 500.
(s, m, w,
C
N
in ring), 1450.8, 1425.9 (aromatic
ring), 1303.6, 1263.7, 1230.5 (w, s, s, C O C in
␥-lactone), 1192.5 (s, C N ).
4-(p-Methoxy)benzylidene-2-methyl-5-oxazolone
(CH3O Ox, yield 68%). 1H NMR (400 MHz, CDCl3):
(ppm) = 2.40 (s, 3H, CH3
C ), 3.98 (s, 3H,
CH3O ), 6.97 (d, 2H, JH = 9.0 Hz, aromatic), 7.12
(s, H, Ar CH ,␥-lactone), 8.07 ppm (d, 2H,
JH = 9.0 Hz, aromatic); FT-IR (KBr): (cm 1) =
3070.1 (w, H C , ␥-lactone), 3009.0, 2832.9 (w,
w, CH3O Ar), 1776.2 (s, C O, ␥-lactone), 1655.7,
1601.9, 1492.6 (s, m, w,
C
N
in ring), 1450.8,
1425.9 (aromatic ring), 1303.6, 1263.7, 1230.5 (w, s,
s, C O C , ␥-lactone).
4-(p-Nitro)benzylidene-2-methyl-5-oxazolone
1
(NO2 Ox, yield 70%). H NMR (400 MHz, CDCl3):
(ppm) = 2.46 (s, 3H, CH3
C ), 7.14 (s, H, Ar
CH , ␥-lactone), 8.27 (d, 4H, JH = 1.3 Hz, aro-
matic); FT-IR (KBr): (cm 1) = 3070.1 (w, H C
,
␥-lactone), 1776.2 (s, C O, ␥-lactone), 1655.7,
1601.9, 1492.6 (s, m, w,
C
N
in ring), 1519.8,
The reaction was monitored until more than 98%
of the substrate disappeared. The rate constant calcu-
lations with assumed pseudo-first-order kinetic model
as well as the correlation calculations were performed
using the Origin ver. 6.1 program (Microcal Software,
Inc., Northampton, MA).
1343.9, 764.7, 748.9 (s, m, m, m, NO2 Ar), 1450.8,
1425.9 (aromatic ring), 1303.6, 1263.7, 1230.5 (w, s,
s, C O C , ␥-lactone).
4-(p-Chloro)benzylidene-2-methyl-5-oxazolone
1
(Cl Ox, yield 75%). H NMR (400 MHz, CDCl3):
(ppm) = 2.44 (s, 3H, CH3
C ), 7.11 (s, H, Ar CH ,
␥-lactone), 7.43 (d, 2H, JH = 8.6 Hz, aromatic), 8.05
(d, 2H, JH = 8.6 Hz, aromatic); FT-IR (KBr):
(cm 1) = 3070.1 (w, H C , ␥-lactone), 1776.2
(s, C O, ␥-lactone), 1655.7, 1601.9, 1492.6 (s, m,
Theoretical Calculations
The PM3 method (MOPAC 6 packet) was used for the
oxazolones’ geometry optimization [30]. The atomic
charges were calculated from Mulliken populations
computed from the ab initio 6-31G* wave function,
using the GAMES program [31].
w,
C
N
in ring), 1450.8, 1425.9 (aromatic
ring), 1303.6, 1263.7, 1230.5 (w, s, s, C O C ,
␥-lactone), 529.7 (s, Cl ).

REACTION OF 4-BENZYLIDENE-2-METHYL-5-OXAZOLONE WITH AMINES
151
RESULTS AND DISCUSSION
Influence of a Substituent on Amine
Nitrogen Atom
The reaction spectra of oxazolone (Ox) with BzA
(c = 0.014 M) in acetonitrile recorded at the wave-
lengths range 230–370 nm are presented in Fig. 2. A
disappearance of a long-wave band with maximum at
= 325 nm (a band related to the substrate) and a
building-up of an absorption band at the wavelength
shorter than 300 nm (connected with an absorption of
a product) with isosbestic point at = 295 nm are ob-
served (Fig. 2).
Figure 3 The dependence of the reaction rate constants as
a function of the concentration of butylamine, benzylamine,
N-methylbutylamine, and N-methylbenzylamine.
Additionally, the course of the reactions with all amines
studied were also monitored by HPLC method. The re-
action’s chromatogram was always a sum of the sub-
strates and one product only.
is nonlinear. As it was discussed in the previous paper
[3], the nonlinear dependence of the rate constant on an
amine concentration could be described assuming that
the Ox ring-opening reaction with an amine proceeded
as parallel reactions according to the equation
Reaction rates v (the oxazolone absorbance decays
versus time) were analyzed assuming a pseudo-first-
order kinetics, because of the 500 times higher con-
centration of the amine than that of the oxazolone. The
obtained relationships between the pseudo-first-order
rate constant and amine concentration kobs = f (Camine
)
d[Ox]/dt = k0 + k1[Ox][amine] + k2[Ox][amine]2
for n-BuA, BzA, MeBuA, and MeBzA are illustrated
in Fig. 3.
(1)
The dependence of kobs vs Camine (n-BuA, BzA,
MeBuA, and MeBzA) as can be observed in Fig. 3
in which the k0 rate constant is connected with the
ring-opening reaction caused by other nucleophile than
amine present in a solution [32,33]. The calculated,
based on Eq. (1), rate constants and statistical param-
eters describing the quality of the fit are presented in
Table I. As can be seen from the data presented in
Table I, the first two terms in Eq. (1) are not mean-
ingful from the statistical point of view and can be
disregarded, thus simplifying Eq. (1) to the form
d[Ox]/dt = k2[Ox][amine]2
(2)
The fit of experimental data to that equation gives al-
most the same k2 and statistical parameters of the fit as
obtained using Eq. (1). However, the fit of the experi-
mental data to the equation
d[Ox]/dt = k[amine]n
(3)
gives a very good correlation coefficient, but because
of the high correlation between the fitting parameters
(k and n) calculated from this equation, the rate con-
stant and the exponent differ substantially from those
obtained from Eq. (2) (see Table II). All these fits indi-
cate that the ring-opening reaction of Ox with an amine
in acetonitrile solution is the second-order reaction ac-
cording to an amine. The lack of possibility to record
Figure 2 Reaction spectra of 4-benzylidene-2-methyl-
5-oxazolone with benzylamine (cBzA = 0.059 M) in
acetonitrile.

152
BETLAKOWSKA ET AL.
Table I Calculated [according to Eq. (1)] Rate Constants of the Ring-Opening Reaction of
4-Benzylidene-2-methyl-5-oxazolone with Amines and Statistical Parameters Describing the Quality of the Fit
Amine
k0
k1
k2
100r2
F
Sest
10
Ndp
n-BuAa
N-MeBuA
BzA
4
5
1
10 4 ( 5 10
10 5 ( 3 10
10 4 ( 6 10
)
)
)
0.011 ( 0.045)
5.7 10 2 ( 1.3 10
1.3 10 3 ( 1.6 10
1.2 10 3 ( 1.9 10
8.46 ( 0.45)
1.34 ( 0.07)
0.87 ( 0.06)
99.79 1630
99.84 3532
99.76 1640 1.5 10
10
1
8
10
14
11
11
4
4
4
3
4
3
4
2
3
3
)
)
)
10
5
N-MeBzA
3.5 10 6 ( 8.8 10
)
0.119 ( 0.007) 99.75 1401
2
aData from preceding paper in this series [3].
an intermediate product spectrum did not allow, in ac-
cordance to Polster and Mauser [34,35] and Vajda and
Rabitz [36,37], to predict exact mechanism of the re-
action studied.
data for Hancock’s Esc substituent constant were fitted
according to equation
c
log(kX/kMe) = a + bEs
(4)
For all amines studied, the rate constant of Ox dis-
appearing at one amine concentration (0.059 M) was
also measured. The calculated pseudo-first-order rate
constants are presented in Table III. Introduction of a
second substituent on nitrogen atom or use of an amine
with branched alkyl chain caused a decrease in the re-
action rate. The decrease of the rate constants of this
reaction depends mostly on the size of a substituent,
whereas the influence of an amine basicity is signifi-
cantly lower. The basicities of benzylamines, in terms
of pKb, are about 4.4, whereas pKb for butylamines
are in a range 3.40–3.55. However, in spite of almost
one order lower basicity of BzA than n-BuA, the ob-
served rate constants of the Ox ring-opening reaction
for both amines are comparable. Moreover, within the
same type of amines (benzylamines, butylamines) the
differences between the rate constants are more diversi-
fied than their pKb’s. Therefore, in the case of the stud-
ied reaction, the reactivity of the amines should be in-
terpreted in terms of the steric effects. Several different
scales can be used for quantitative and qualitative inter-
pretation of the steric effects [4,8,9,11,14,18–20,38]. In
our paper for the qualitative interpretation of the influ-
ence of the steric effects on the ring-opening reaction
of Ox with different amines, the Hancock’s Esc [8] and
Charton’s ␯ [10–13] substituent constants and simple
branching equation [18–20] were used. The obtained
where a and b are fitted parameters, kX and kMe refer
to a substituent X and a reference subsituent (methyl
group), respectively. For the Charton’s ␯ substituent
constant we applied the equation
log kX = c + dv
(5)
As in Eq. (4) c and d are fitted parameters, and kX is the
rate constant that refers to a substituent X. The best cor-
relation was found for Charton’s ␯ substituent constant
(Fig. 4) especially in the series of primary amines (log
kX = 3.09( 0.69) 8.11( 0.88) v; 100r2, 97.71; F,
85.14; Sest, 0.209; Ndp, 4).
For series of N-substituted amines the correla-
tion was moderate (log kX = 2.18( 1.27) 3.89
( 2.38) v; 100r2, 73.69; F, 2.80; Sest, 1.309; Ndp, 3
for benzylamine series and log kX = 2.29( 0.60)
1.45( 1.36) v; 100r2, 52.96; F, 1.13; Sest, 0.602; Ndp,
3 for butylamine series). In the case of Hancock’s
c
Es substituentconstant, thecorrelationwasalsomode-
rate. The correlations are as follows: log(kX/kMe) =
c
0.74( 0.60) 0.66( 0.22) Es ; 100r2, 89.51; F,
8.54; Sest, 0.472; Ndp, 3 for benzylamine series,
c
and log(kX/kMe) = 0.33( 1.47) + 1.43( 1.21) Es ;
Table III The Pseudo-First-Order Rate Constants of
the Ring-Opening Reaction of 4-Benzylidene-2-methyl-
5-oxazolone with Amines (c = 0.059 M) in Acetonitrile
at 298 K
Table II Calculated [according to Eq. (3)] Rate Cons-
tants of the Ring-Opening Reaction of 4-Benzylidene-2-
methyl-5-oxazolone with Amines and Statistical
Parameters Describing the Quality of the Fit
1
Amine
k (s
)
3
4
6
3
3
4
4
5
BzA
3.11 10
6.24 10
4.19 10
4.80 10
2.52 10
4.66 10
3.75 10
1.59 10
N-MeBzA
N-iPrBzA
BuA
N-MeBuA
s-BuA
Amine
k
n
100r2
n-BuAa
N-MeBuA
BzA
15.8 ( 2.7)
1.07 ( 0.10)
0.85 ( 0.08)
0.114 ( 0.008)
2.37 ( 0.08)
1.75 ( 0.05)
1.98 ( 0.08)
1.94 ( 0.06)
99.9
99.79
99.76
99.72
N-MeBzA
N-EtBuA
t-BuA
aData from preceding paper in this series [3].

REACTION OF 4-BENZYLIDENE-2-METHYL-5-OXAZOLONE WITH AMINES
153
Figure 5 Absorption spectra of substituted 4-benzylidene-
2-methyl-5-oxazolones in acetonitrile.
Figure 4 The correlations between log kX and Charton’s
steric substituent constants ␯ for primary amines.
Ox. The absorption spectrum of the nitro-substituted
Ox is also long-wave-shifted but in this case the
strong auxochromophoric effect of the strong electron-
withdrawing group is manifested. Such changes of the
position of the absorption band indicate the interac-
tion between the phenyl ring, possessing the electron-
donating character, and the oxazolone moiety of the
compound, exhibiting electron-withdrawing charac-
ter, in spite of nonplanar conformation of Ox struc-
ture. Semiempirical calculations using PM3 method
revealed that the dihedral angle between phenyl and ox-
azolone rings is about 40 (from 37.7 for p-methoxy-
Ox to 47.7 for unsubstituted Ox).
100r2, 58.28; F, 1.40; Sest, 1.51; Ndp, 3 for butylamine
series.
The rate constants for all amines studied in the re-
action with Ox can be correlated with a form of the
simple branching equation [18–20]
log kNX1X2 = BNnN + BC1nC1 + B0
(6)
where nN is the number of C N bonds on the N
atom of the amine, and nC is the total number of
C C bonds on C1 atom of X1 and X2. Correla-
tion with Eq. (6) gave the regression equation log
A kind of a substituent in the phenyl ring has dis-
tinct influence on the reaction rate of Ox with BzA. The
calculated pseudo-first-order rate constants of the reac-
tion of oxazolone (c = 5 10 5 M) with benzylamine
(c = 0.029 M) are presented in Table IV.
kNX1X2
=
0.413( 0.250)nN 1.171( 0.151)nC1
0.778( 0.476), 100R2, 92.36; A100R2, 89.68; F,
31.42; Sest, 0.354; Ndp, 8; rnN,nC, 0. As BN was not sig-
nificant, the term in nN was dropped from Eq. (6). Cor-
The fastest decrease of the Ox absorbance was ob-
served for the nitro-subsituted compound, whereas the
slowest decrease was observed for the dimethylamino
one. Thus, the electron-donating substituents which in-
crease the electron density at the reaction center (car-
bon C5 in the oxazolone ring) distinctly slow down the
relation then gave the regression equation log kNX1X2
=
1.171( 0.171)nC1 1.397( 0.332), 100R2, 88.62;
A100R2, 86,73; F, 46.73; Sest, 0.402; Ndp, 8. Thus,
there is a steric effect because of substitution at C1
which decreases the reaction rate, in agreement with
the correlation with the v parameters, and it is additive.
Table IV The Pseudo-First-Order Rate Constants
of the Ring-Opening Reaction of Substituted at the
Phenyl Ring 4-Benzylidene-2-methyl-5-oxazolones
Influence of the para-Substituents
in the Phenyl Ring
5
(c = 5 10 M) with Benzylamine (c = 0.029 M) in
Acetonitrile at 298 K
Absorption spectra of substituents in the para-position
of 4-benzylidene-2-methyl-5-oxazolones, normalized
to unity at maximum of long-wave absorption band in
acetonitrile, are presented in Fig. 5.
The position of maximum of long-wave absorp-
tion band depends on the type of substituent in the
phenyl ring of the oxazolone. The electron-donating
substituents cause batochromic shift of the maximum
of absorption band as compared with unsubstituted
1
Substituent
k (s
)
6
5
4
4
3
2
N(CH3)2
OCH3
OH
H
Cl
6.26 10
6.20 10
4.98 10
3.66 10
1.06 10
2.37 10
NO2

154
BETLAKOWSKA ET AL.
ring-opening reaction with the nucleophile. An influ-
ence of substituents on a reaction rate is usually corre-
lated with the substituent constants using the Hammett
equation [21–25] or its modifications [6,26–28]. In
our studies we used the classical Hammett equation
log(k/k0) = , where k and k0 are rate constants ob-
tained for substituted and unsubstituted Ox, respec-
tively, is a reaction constant, and is a substituent
constant. The Hammett plot of the oxazolone ring-
opening reaction with benzylamine are presented in
Fig. 6.
The log(k/k0) correlates well with the classical
Hammett substituent constants log(k/k0) = 1.573
( 0.293) , 100r2, 87.79; F, 28.77; Sest, 0.469;
Ndp, 6. The correlation can be better after discarding the
data obtained for the hydroxyl substituent, log(k/k0) =
1.712( 0.154) , 100r2, 97.62; F, 123.2; Sest, 0.239;
Ndp, 5. The deviation observed for the hydroxyl group
can be explained as a result of existing specific interac-
tions between the substituent and the solvent (hydrogen
bonding) which cause decrease of electron density at
the reaction center and thereby increase of the reaction
rate. Furthermore, a very good correlation between log
(k/k0) and an atomic charge ( ) at the reaction center
(carbon C5 in the oxazolone ring) was obtained accord-
ing to the equation
Figure 7 Plot of log(k/k0) vs atomic charge at C5 carbon
atom of the oxazolone ring.
The outstanding correlations between log(k/k0)
and Hammett’s substituent constant , and between
log(k/k0) and the atomic charge at the reaction cen-
ter (C5) are a result of the good correlation be-
tween the substituent constant
and the atomic
charge at carbon C5, (C5) = 0.80703( 0.00011) +
0.00241( 0.00017) , 100r2, 98.04; F, 200.5; Sest,
0.0003, Ndp, 6.
We also performed studies in which we took into
account field (F) and mesomeric (M) effect of the
substituents separately [25,39], contrary to the previ-
ously used classical Hammett approach combining all
substituent-promoted effects into one substituent con-
stant . For that approach we applied multiple regres-
sion method to the equation
log(k/k0) = a + b (C5)
(7)
The calculated correlation is log(k/k0) = 538
( 57) + 667( 88) (C5); 100r2, 93.48; F, 57.34; Sest,
0.239; Ndp, 6, when all data points are included and log
(k/k0) = 563( 26) + 698( 32) (C5); 100r2, 99.38;
F, 478.0; Sest, 0.122; Ndp, 5, after exclusion of the data
point for OH (Fig. 7).
log(k/k0) = a + bF + cM
(8)
where F and M are field effect constant and me-
someric effect (Dewar–Grisdale) constant, respectively
[25,39]. The values of F and M constants were taken
from Ref. [39]. Satisfactory correlation between log
(k/k0) and substituent constants F and M was
established: log (k/k0) = 0.668( 0.439) + 2.023
( 0.613)F + 0.036( 0.195)M, 100r2, 83.48; F,
7.58; Sest, 0.631; Ndp, 6; rF,M, 0. As the value of
constant c was not significant, the term M was
dropped from Eq. (8). Correlation then gave the
regression equation log(k/k0) = 0.726( 0.273) +
2.080( 0.466)F, 100r2, 83.28; F, 19.93; Sest, 0.549;
Ndp, 6, which indicated that the substituent constant F
(field effect) had dominant significance.
The rate constants for the reaction of 4-(40-substi-
tuted-benzylidene)-2-methyl-5-oxazolones with ben-
zylamine can be correlated with the CR equation in
the form [29]
Figure 6 Plot of the Hammett equation log(k/k0) =
of the reaction of substituted 4-benzylidene-2-methyl-5-
oxazolones with benzylamine in acetonitrile.
log kX = C CX + R eX + h
(9)

REACTION OF 4-BENZYLIDENE-2-METHYL-5-OXAZOLONE WITH AMINES
155
where
is the electronic demand sensitivity elec-
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trical effect parameter and
fined by the relationship
is a parameter de-
CX
= l lX + d
(where
dX
CX
is the localized electrical effect parameter and
is the intrinsic delocalized electrical effect pa-
l
d
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r
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CONCLUSIONS
The steric hindrance due to the substitution at C1 car-
bon atom of amine seems to be a main factor responsi-
ble for the modification of the reaction rate constants of
the ring-opening reaction of 4-benzylidene-2-methyl-
5-oxazolone with different amines, even though it does
not completely explain all observed differences. The
original Hammett’s substituent constants take into ac-
count all effects connected with an influence of the sub-
stituents in the phenyl ring of 4-benzylidene-2-methyl-
5-oxazolones on the charge distribution at the reaction
center; but although the Hammett approach is good
enough for accurate description of the substituents in-
fluence on the reaction rate, the CR equation gave more
information about the electrical effects introduced by
substituents.
Authors thank the referees for a valuable suggestion.
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