A Study of Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides: Kinetics of Oxidation of Leucine and Isoleucine in Aqueous Acid Medium

Article abstract of DOI:10.1515/znb-2004-0110

To study the variation of oxidative strengths of N-chloro- arenesulphonamides with substitution in the benzene ring, six mono- and five di-substituted N-chloro-arenesulphonamides are employed as oxidants for studying the kinetics of oxidation of two neutral amino acids, L-leucine and L-isoleucine in aqueous acid medium. The N-chloro-arenesulphonamides studied are of the constitution: ArSO₂NaNCl·H₂O (where Ar = C₆H₅, 4-CH₃C₆H₄, 4-C₂H₅C₆H₄, 4-FC₆H ₄, 4-ClC₆H₄, 4-BrC₆H₄, 2,3-(CH₃)₂C₆H₃, 2,4-(CH ₃)₂C₆H₃, 2-CH₃-4-Cl ₂C₆H₃, 2,4-Cl₂C₆H ₃, and 3,4-Cl₂C₆H₃). The reactions show second order kinetics in [oxidant], fractional order in [amino acid] and inverse dependence on [H⁺]. Addition of the reduced product of the oxidants or variation in ionic strength of the medium has no significant effect on the rates of oxidations. A two-pathway mechanism is considered to explain the experimental results. Effective oxidizing species of the oxidants is Cl ⁺ in different forms. Therefore the oxidising strengths of N-chloro-arenesulphonamides depend on the ease with which Cl⁺ is released from them. The study reveals that the introduction of substituent in the benzene ring of the oxidant affects both the kinetic and thermodynamic data for the oxidations The electron releasing groups such as CH₃ generally inhibit the rates, while electron-withdrawing groups such as Cl enhance this ability, as the electron withdrawing groups ease the release of Cl⁺ from the reagents and hence increase the oxidising strengths. The on E_a and log A and validity of the Hammett and isokinetic relationships for the oxidations are also analysed.

Full text of DOI:10.1515/znb-2004-0110

A Study of Substituent Effect on the Oxidative Strengths of
N-Chloroarenesulphonamides: Kinetics of Oxidation of Leucine
and Isoleucine in Aqueous Acid Medium
Mahesha Shetty and B. Thimme Gowda
Department of Post-Graduate Studies and Research in Chemistry, Mangalore University,
Mangalagangothri-574 199, Mangalore, India
Reprint requests to Prof. B. T. Gowda. Fax: 91 824 2287 367. E-mail: gowdabt@yahoo.com
Z. Naturforsch. 59b, 63 – 72 (2004); received July 16, 2003
To study the variation of oxidative strengths of N-chloro-arenesulphonamides with substitution
in the benzene ring, six mono- and five di-substituted N-chloro-arenesulphonamides are employed
as oxidants for studying the kinetics of oxidation of two neutral amino acids, L-leucine and L-
isoleucine in aqueous acid medium. The N-chloro-arenesulphonamides studied are of the consti-
tution: ArSO NaNCl·H O (where Ar = C H , 4-CH C H , 4-C H C H , 4-FC H , 4-ClC H ,
2
2
6
5
3
6
4
2
5
6
4
6
4
6
4
4
-BrC H , 2,3-(CH ) C H , 2,4-(CH ) C H , 2-CH -4-ClC H , 2,4-Cl C H , and 3,4-Cl C H ).
6 6 6 6 6 6
4 3 2 3 3 2 3 3 3 2 3 2 3
The reactions show second order kinetics in [oxidant], fractional order in [amino acid] and inverse
dependence on [H ]. Addition of the reduced product of the oxidants or variation in ionic strength of
+
the medium has no significant effect on the rates of oxidations. A two-pathway mechanism is consid-
+
ered to explain the experimental results. Effective oxidizing species of the oxidants is Cl in different
forms. Therefore the oxidising strengths of N-chloro-arenesulphonamides depend on the ease with
+
which Cl is released from them. The study reveals that the introduction of substituent in the benzene
ring of the oxidant affects both the kinetic and thermodynamic data for the oxidations The electron
releasing groups such as CH generally inhibit the rates, while electron-withdrawing groups such as
3
+
Cl enhance this ability, as the electron withdrawing groups ease the release of Cl from the reagents
and hence increase the oxidising strengths. The on Ea and logA and validity of the Hammett and
isokinetic relationships for the oxidations are also analysed.
Key words: Kinetics, Oxidation, Leucine, Isoleucine, N-Chloroarenesulphonamides
Introduction
ported the preparation and spectroscopic character-
ization of several sodium salts of mono- and di-
substituted N-chloro-arenesulphonamides [12 – 14]. In
this paper, we report the results of kinetic studies
on the oxidations of two neutral amino acids, L-
leucine and L-isoleucine by six mono- and five di-
substituted N-chloro-arenesulphonamides of the con-
stitution ArSO NaNCl·H O.
The chemistry of N-halo-arenesulphonamides is
of interest due to their distinct physical, chemi-
cal and biological properties. They act as halo-
nium cations, hypohalite species and N-anions which
behave both as bases and nucleophiles. The di-
verse properties are due to their oxidising action
in aqueous, partial aqueous and non-aqueous me-
dia [1 – 11]. Although two members of this class
of reagents, commonly known as chloramine-T and
chloramine-B have been extensively studied, there
are no efforts in altering the electron environment
around the nitrogen atom of the sulphonamide group
2
2
Results and Discussion
Stoichiometry and product analysis
The stoichiometry of amino acid (AA) – substi-
by making appropriate substitution in the benzene tuted N-chloro-arenesulphonamide (NCSBS) oxida-
+
ring, to get Cl released either at ease or with tions was determined by equilibrating varying ratios of
difficulty, to produce N-chloro-arenesulphonamide [NCSBS] to [AA] in aqueous HClO at room temper-
4
of required oxidising capacity. Hence in an ef- ature. The major products of oxidations were the cor-
fort to introduce N-chloro-arenesulphonamides of responding aldehydes. The observed 1:1 stoichiometry
different oxidizing strengths, we have recently re- may be represented by the following equation.
0
932–0776 / 04 / 0100–0063 $ 06.00 ꢀc 2004 Verlag der Zeitschrift f u¨ r Naturforschung, T u¨ bingen · http://znaturforsch.com
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4
M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
3
2
2
3
−1 −1
1
(
0 [NCSBS]0 10 [Leu/Ile]0 10 [HClO4]
10 kobs(dm mol s )
Table 1. Pseudo-second or-
der rate constants (kobs) for
the oxidation of L-leucine
−
3
−3
−3
mol dm
)
(mol dm
)
(mol dm
)
4-X-C6H4SO2NaNCl·H2O where X =
H
CH3 C2H5
F
Cl
Br
Leu
Ile
(Leu) and L-isoleucine (Ile)
1
1
1
1
1
.0
.0
.0
.0
.0
2.0
2.0
2.0
2.0
2.0
1.0
2.0
3.0
5.0
10.0
14.8
6.7
4.5
2.6
1.4
9.2
5.3
3.3
1.5
1.0
21.0
9.9
5.7
2.6
1.6
12.0
8.5
6.0
3.3
2.3
17.0
12.0
8.5
5.0
3.0
41.2
29.5
13.0
7.5
by sodium salts of mono-
and di-substituted N-chloro-
arenesulphonamides (NCSBS)
in aqueous perchloric acid at
4.4
303 K (I = 0.30 mol dm 3).
−
1
1
1
1
1
.0
.0
.0
.0
.0
2.0
2.0
2.0
2.0
2.0
1.0
2.0
3.0
5.0
10.0
10.8
8.3
6.8
4.0
2.5
10.8
7.2
4.4
3.7
2.3
17.7
12.5
7.0
3.6
2.5
17.8
12.0
9.6
4.7
2.7
30.3
20.0
13.9
7.5
40.1
30.0
22.4
11.6
6.9
4.9
i-X-j-YC6H3SO2 NaNCl·H2O, i-X-j-Y =
2
,3-(CH3)2 2,4-(CH3)2 2-CH3,4-Cl 2,4-Cl2 3,4-Cl2
Leu
1
1
1
1
1
.0
.0
.0
.0
.0
2.0
2.0
2.0
2.0
2.0
1.0
2.0
3.0
5.0
10.0
9.5
5.8
4.2
2.9
2.0
9.3
6.2
4.4
2.4
1.5
25.6
18.7
11.7
6.3
35.9
25.9
17.5
12.0
8.3
30.6
19.6
13.9
7.6
3.8
3.8
Ile
1
1
1
1
1
.0
.0
.0
.0
.0
2.0
2.0
2.0
2.0
2.0
1.0
2.0
3.0
5.0
10.0
8.5
5.3
4.4
2.7
1.7
8.3
5.7
4.8
3.3
1.9
10.1
7.4
6.1
3.4
2.4
16.2
12.6
10.7
5.1
22.6
14.3
8.4
3.9
2.1
2.5
−
+
−
−
ArSO NCl +RCH(NH )COO +H O
butanol (2:2:1 ν/ν) as the solvent system and iodine
2
3
2
as spray reagent. The R values of the reduced arene-
→
ArSO NH +RCHO+Cl +NH +CO
2
f
2
2
3
sulphonamides were virtually identical with the values
of the corresponding pure arenesulphonamides.
Ar = C H (1), 4-CH -C H (2), 4-C H -C H (3),
6
5
3
6
4
2
5
6
4
4
-F-C H4 (4), 4-Cl-C H (5), 4-Br-C H (6), 2,3-
6 6 4 6 4
(
CH ) -C H (7), 2,4-(CH ) -C H (8), 2-CH -4-Cl-
3 2 6 3 3 2 6 3 3
Kinetic measurements
C H (9), 2,4-Cl -C H (10), and 3,4-Cl -C H (11).
6
3
2
6
3
2
6
3
R = (CH ) CHCH (Leu) and CH CH CH(CH ) (Ile).
The kinetics of oxidations were carried out un-
3
2
2
3
2
3
In a typical experiment, a mixture of leucine der pseudo-second order conditions with [amino acid]
−
3
(
0.02 mol dm ), sodium salt of N-chloro-4-chloro- ꢀ [NCSBS] (by 5 – 50 times). The reactions were
−
3
arenesulphonamide (NC4CBS) (0.001 mol dm ) and initiated by the rapid addition of known amounts
perchloric acid (0.03 mol dm ) was made up to 50 ml of oxidant solution (0.0005– 0.004 mol dm ), pre-
with water. The mixture was allowed to stand for equilibrated at a desired temperature, to mixtures
−
3
−3
2
4 h to ensure completion of reaction. It was then containing the required amounts of amino acid
−
3
treated with an excess of saturated solution of 2,4- (0.005– 0.04 mol dm ), perchloric acid (0.01–
−
3
dinitro-phenylhydrazine and set aside for 10 h. The 0.10 mol dm ), sodium nitrate and water in the boil-
precipitated 2,4-dinitrophenyl-hydrazone (DNP) was ing tube, thermostated at the same temperature. The
filtered off, dried, recrystallised from ethanol and its progress of the reactions was monitored for at least two
melting point was determined. In all the cases, car- half-lives by the iodometric determination of unreacted
bon dioxide and ammonia were detected by baryta oxidant at regular intervals of time. The pseudo-second
water and Nessler’s reagent, respectively. The pres- order rate constants (kobs) were computed by graphical
ence of aldehydes were also confirmed by the spot methods and the values were reproducible within ± 3%
tests. The reduced products of the oxidants, the sub- error.
stituted arenesulphonamides (ArSO NH ) were iden-
The kinetic data on the oxidations of Leu and
2
2
tified by TLC [15] using petroleum ether-chloroform- Ile by eleven mono- and di-substituted N-chloro-
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M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
65
ArSO2NaNCl·H2O,
Kinetic orders observed in
Table 2. Kinetic data for
the oxidation of L-leucine
where Ar =
Leu
[Leu]
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.5
0.5
Ile
[Ile]
0.4
0.4
0.3
0.4
0.3
0.6
0.4
0.4
0.4
0.5
0.4
[
NCSBS]
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
[HClO4]
−1.1
−1.1
−1.1
−1.0
−1.0
−1.0
−0.7
−0.9
−0.9
−0.9
−1.0
[NCSBS]
2.0
[HClO4]
−0.8
−0.7
−1.0
−0.9
−1.1
−1.1
−0.7
−0.7
−0.7
−1.1
−1.1
(Leu) and L-isoleucine (Ile)
C6H5
by sodium salts of mono-
and di-substituted N-chloro-
arenesulphonamides (NCSBS)
in aqueous perchloric acid.
4
4
4
4
4
2
2
2
2
3
-CH3C6H4
-C2H5C6H4
-FC6H4
-ClC6H4
-BrC6H4
,3-(CH3)2C6H3
,4-(CH3)2C6H3
-CH3-4-ClC6H3
,4-Cl2C6H3
,4-Cl2C6H3
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
Fig. 1. Plots of kobs versus [Leu]; 103 [NCSBS] = 33.3 Fig. 2. Plots of kobs versus [Ile]; 103 [NCSBS] = 33.3
−
−3
HClO ] = 3.33 I = 1.0 mol dm ; Temp.: 303 K. NCSBS: [HClO4] = 3.33 I = 1.0 mol dm ; Temp.: 303 K. NCSBS :
4
3
[
4
-X-C H SO NaNCl, where X = H, CH , C H , F, Cl or Br 4-X-C6H4SO2NaNCl, where X = H, CH3, C2H5, F, Cl or Br
6 5
4 2 3 2
and i-X-j-Y-C H SO NaNCl, where i-X-j-Y = 2,3-(CH ) , and i-X-j-Y-C6H3 SO2NaNCl, where i-X-j-Y = 2,3-(CH3)2,
6
3
2
3 2
2
,4-(CH ) , 2-CH -4-Cl, 2,4-Cl , 3,4-Cl .
2,4-(CH3)2, 2-CH3-4-Cl, 2,4-Cl2, 3,4-Cl2.
3
2
3
2
2
arenesulphonamides (NCSBS) (1-11), under varying changes in [oxidant]0, establishing second order de-
NCSBS], [AA], [HClO ], solution composition, and pendence of the rate on [NCSBS]0.
[
4
temperature of the medium, are shown in Tables 1, 2
and Figures 1, 2.
Effect of varying [AA]0
+
At constant [NCSBS] and [H ], the rates increased
0
Effect of varying [oxidant]0
with increase in [AA] with fractional order depen-
At constant [AA] (5 – 50 fold excess over dences in [AA] for all the oxidations. The plots of kobs
0
+
[
oxidant] ) and [H ], the second order plots of 1/[oxi- versus [AA] were linear with finite intercepts on the
0
dant] versus time were linear up to 70% completion of ordinates (Figs. 1 and 2), indicating the operation of
the reactions. The pseudo-second order rate constants a two-pathway mechanism for the oxidation of amino
computed from the plots remained unaffected by the acids by all the reagents.
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M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
Effect of varying [H+]
Path 1
K1
SH+ −ꢁꢀ− S+H+
+
(fast)
The rates decreased with increase in [H ], at fixed
NCSBS] and [AA] , with varying inverse order de-
pendences in [H ] (Tables 1 and 2).
[
k2
0
0
ArSO2NH2Cl)+ +S −ꢁ −− ꢀ− Intermediate (Y)
(
(fast)
+
k−2
k3
Y+(ArSO2NH2Cl)+
−→
products
(slow)
Effect of varying ionic strength and other parameters
of the medium
Path 2
K
4
(ArSO2NH2Cl)+
−ꢀ
ꢁ
+
2
k5
−→
Variation in either the ionic strength of the medium
or addition of the reduced products of the oxidants,
substituted arenesulphonamides (SBSA), to the reac-
tion mixtures had no significant effect on the rates
of oxidations. The rates were measured at different
temperatures under varying [AA]. The constants of
both the pathways in the two-pathway mechanism
have been calculated at each temperature as described
later. Activation parameters corresponding to these
constants have also been computed from the Arrhenius
and Eyring plots.
ꢁ
Y
ArSO2NCl2 +ArSO2NH2(slow)
+
ArSO2NCl2 +H3O
−→ H2OCl +ArSO2NHCl (fast)
+
H2OCl +S −→ products
+
+
ArSO2NHCl +H
−→ (ArSO2NH2Cl)
Scheme 1.
where [Y] = k [ArSO NH Cl ] [S] / {k + k3
2
2
−2
+
+
ArSO NH Cl ] + k [S]} as [ArSO NH Cl ] =
2
2
0
2
2
+
[
ArSO NH Cl ] −[Y] and [S] ∼ [S].
2
2
0
Since k is small and [S] ꢀ [ArSO NH Cl ] ,
3
2
+
k [ArSO NH Cl ] is negligibly small compared to
3
2
2
0
other terms in the denominator, and eq. (1) becomes:
Sodium salts of N-chloro-benzenesulphonamide
+
and its substituted compounds (NCSBS) are fairly −d[ArSO2NH2Cl ]/dt =
strong electrolytes in aqueous solution. They furnish
[S]
1+K [S])
+
+
K k [ArSO NH Cl ] [ArSO NH Cl ]
2
3
2
2
0
different reactive species depending upon pH of the
medium. The possible oxidising species in acid solu-
where K = k /k
.
2
2
−2
−
tions of NCSBS are ArSO NCl , ArSO NHCl, HOCl
2
+
2
+
+
With [ArSO NH Cl ] [ArSO NH Cl ] ≈ [ArSO -
and ArSO NCl at low [H ], and ArSO NH Cl and
2
2
0
2
2
2
2
+
2
+
+
NH Cl ] , the rate law in eq. (2) becomes:
H OCl at high [H ].
2
2
Amino acids Leu and Ile exist in the acid/base equi-
librium in acidic solutions:
+
−
d[ArSO NH Cl ]/dt =
2
2
+
2
K k [ArSO NH Cl ] [S]/(1 + K [S])
(3)
2
3
2
2
2
+
RCH2CH(N H3)COO +H+
(S)
+
−
RCH2CH(N H3)COOH
ꢀ
+
(
SH )
Rearranging eq. (3), we obtain eq. (4):
2
The second order kinetics in [NCSBS], fractional or-
der in [AA] and higher inverse dependence of the rate
on [H ] and other observed effects for the oxidation
−
{d[NCSBS]/[NCSBS] }/dt = K k [S]/(1+K [S])
2
3
2
(4)
+
of Leu and Ile by all the N-chloro-arenesulphonamides
may be explained by a two-pathway mechanism shown
in Scheme 1. It is supported by the fact that the direct
plots between the rate constants and [AA] (Figs. 1 and
The left-hand side of eq. (4) may be written as:
2
−
{d[NCSBS]/[NCSBS] }/dt = d{1/[NCSBS]}/dt
=
kp1
2
) gave better correlations than the double reciprocal
plots. Further, in acidic aqueous solutions of N-chloro- Hence eq. (4) becomes eq. (5):
arenesulphonamides, the corresponding N,N-dichloro
kp1 = K k [S]/(1+K [S])
(5)
(6)
2
3
2
compounds are produced, which are insoluble in water
but soluble in organic solvents.
We also have:
S] = K [SH ]/[H ]
Applying the steady state approximation to the in-
termediate Y in path 1, the rate of the reaction going
through path 1 is given by
+
+
[
1
Therefore eq. (5) takes the form:
+
+
+
+
+
−
d[ArSO NH Cl ]/dt = k [ArSO NH Cl ][Y] (1)
kp1 = K K k [SH ]/{[H ]+K K [SH ]} (7)
2
2
3
2
2
1
2
3
1 2
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M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
67
3
−1 −1
s ) at Temp. (K)
ArSO2NaNCl·H2O,
10 k (dm mol
Table 3. The calculated con-
stants k and k for paths 1 and
ꢁ
where Ar =
Leu
Ile
2
98
303
2.8
1.8
2.6
3.6
6.5
7.0
2.4
2.8
308
3.3
313
4.0
298
3.0
303
4.8
308
6.0
4.3
6.7
7.9
13.2
14.5
4.1
3.7
5.9
313
11.0
6.3
11.6
11.6
16.9
16.9
5.7
5.3
8.0
14.5
10.3
2
of the mechanism at differ-
C6H5
1.1
1.0
1.3
2.5
5.7
5.4
2.0
1.8
6.5
9.3
5.3
ent temperatures for the oxida-
tion of L-leucine (Leu) and L-
isoleucine (Ile) by sodium salts
of mono- and di-substituted N-
chloro-arenesulphonamides in
aqueous perchloric acid.
4
4
4
4
4
2
2
2
2
3
-CH3C6H4
-C2H5C6H4
-FC6H4
-ClC6H4
-BrC6H4
,3-(CH3)2C6H3
,4-(CH3)2C6H3
-CH3-4-ClC6H3
,4-Cl2C6H3
,4-Cl2C6H3
2.1
3.3
2.4
3.1
3.6
7.7
6.2
2.2
2.3
2.7
5.3
4.5
3.1
3.9
5.7
10.8
13.6
3.0
2.7
3.7
3.8
4.7
4.2
5.2
7.7
8.5
10.1
3.1
13.3
4.4
6.3
9.3
8.8
14.6
10.7
11.3
17.0
13.0
16.9
18.0
8.9
5.3
11.3
6.2
15.4
0 k (dm mol
4
ꢁ
3
−1 −1
)
1
s
C6H5
1.1
1.5
2.2
2.0
1.9
5.0
1.2
1.9
4.5
4.5
3.1
2.2
1.7
3.4
2.8
3.5
7.2
2.2
2.4
5.4
5.6
5.0
2.5
2.3
4.5
3.3
5.4
10.2
3.7
2.7
6.8
7.4
5.6
2.9
3.5
5.0
3.8
8.8
14.2
4.3
4.6
7.9
10.8
7.9
2.5
1.6
3.1
2.0
3.6
4.3
5.9
9.4
2.0
2.3
2.8
4.3
4.0
5.2
3.1
5.0
5.0
9.4
13.2
2.5
2.9
4.2
6.1
4.7
7.0
3.5
6.5
4
4
4
4
4
2
2
2
2
3
-CH3C6H4
-C2H5 C6H4
-F C6H4
-ClC6H4
-BrC6H4
,3-(CH3)2C6H3
,4-(CH3)2C6H3
-CH3-4-ClC6H3
,4-Cl2C6H3
,4-Cl2C6H3
2.2
3.2
4.6
5.4
1.6
1.5
2.2
3.1
3.2
6.5
11.6
15.1
3.4
3.8
5.8
7.2
6.5
Fig. 3a. Plot of log kobs versus σp (NCSBS) for Fig. 3b. Plot of log k
versus σp (NCSBS) for
obs
leucine oxidation. 103 [NCSBS] = 33.3 [HClO ] = isoleucine oxidation. 10 [NCSBS] = 33.3 [HClO ] =
3
4
4
3
.33 I = 1.0 mol dm 3; Temp.: 303 K. NCSBS: 4-X- 3.33 I = 1.0 mol dm ; Temp.: 303 K. NCSBS: 4-X-
−
−3
C H SO NaNCl, where X = H, CH , C H , F, Cl, or Br. C H SO NaNCl, where X = H, CH , C H , F, Cl, or Br.
6
4
2
3
2
5
6
4
2
3
2
5
If K is small, then the rate law in eq. (5) will take the or
2
form:
+
2
kp2 = K k /[H ]
(9)
4
5
+
+
kp1 = K k [S] = K K k [SH ]/[H ]
(8)
2 3
1 2 3
The combined rate law for both pathways is therefore
given by eq. (10) or (11):
The rate law for the reaction in path 2 has been deduced
in a similar way:
2
+ 2
+
+
+ 2
−
{d[NCSBS]/[NCSBS] }/dt = K k /[H ]
kobs = {K K k [SH ]/[H ]} +{K k /[H ] } (10)
4
5
1
2
3
4 5
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M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
ArSO2NaNCl·H2O,
Values calculated from k
Optimised values
Table 4. Activation
parameters for path
#
#
∆G#
∆S#
where Ar =
Ea
logA
∆H
∆S
Ea
logA
kJ mol 1)
−
(kJ mol ) (J K mol ) (kJ mol ) (kJ mol
−1ꢁ
−1
−1
−1ꢁ
−1
)
(J K mol
−1
−1
)
(
1
of the mechanism
Leu
for the oxidation of
L-leucine (Leu) and
L-isoleucine (Ile) by
sodium salts of mono-
and di-substituted N-
chloro-arenesulphon-
amides in aqueous
perchloric acid.
C6H5
79.8
59.6
77.9
45.5
38.7
42.6
46.0
86.2
49.4
47.9
63.8
13.2
9.5
12.8
7.4
6.5
7.2
7.3
14.3
8.6
8.4
11.0
77.1
59.2
77.8
44.4
35.3
42.0
41.5
82.6
47.9
46.8
62.7
−1.3
−46.4
+7.0
−107.0
−132.0
−98.9
−120.0
+16.9
−87.9
−87.5
−37.3
77.5
78.6
77.7
76.8
75.3
75.1
77.9
77.5
74.6
73.3
74.0
79.8
13.2
13.0
13.2
13.3
13.6
13.6
13.1
13.2
13.7
13.9
13.8
−1.3
−4.9
−2.0
+0.8
+5.8
+6.4
−2.6
−1.3
+8.3
+12.5
+9.8
4
4
4
4
4
2
2
2
2
3
-CH3C6H4
-C2H5C6H4
-FC6H4
-ClC6H4
-BrC6H4
,3-(CH3)2C6H3
,4-(CH3)2C6H3
-CH3-4-ClC6H3
,4-Cl2C6H3
,4-Cl2C6H3
80.9
79.9
79.1
77.6
77.0
80.1
79.8
76.9
75.6
76.5
Ile
C6H5
66.8
51.7
66.0
62.3
44.9
59.6
50.1
44.3
56.4
57.4
50.0
11.2
8.4
11.0
10.5
7.8
10.4
8.1
7.1
60.7
49.7
65.4
61.0
43.5
59.4
45.7
39.4
55.0
53.0
41.0
−50.9
−90.6
−27.0
−48.4
−100.8
−38.3
−104.3
−125.7
−71.4
−70.2
−114.9
77.5
77.2
76.6
75.7
74.0
73.5
77.3
77.5
76.6
74.3
75.8
66.8
67.1
67.3
66.4
64.8
64.2
68.0
68.2
67.5
65.3
66.5
11.2
11.0
11.1
11.3
11.5
11.6
11.0
11.0
11.1
11.5
11.2
−50.9
−54.5
−52.6
−49.4
−44.0
−42.1
−54.7
−55.7
−53.0
−45.7
−49.9
4
4
4
4
4
2
2
2
2
3
-CH3C6H4
-C2H5C6H4
-FC6H4
-ClC6H4
-BrC6H4
,3-(CH3)2C6H3
,4-(CH3)2C6H3
-CH3-4-ClC6H3
,4-Cl2C6H3
,4-Cl2C6H3
9.3
9.9
8.3
Fig. 4a. Plot of log k versus σp (NCSBS) for leucine oxi-
ꢁ
Fig. 4b. Plot of log k versus σp (NCSBS) for leucine oxi-
dation. NCSBS : 4-X-C H SO NaNCl, where X = H, CH ,
dation. NCSBS: 4-X-C H SO NaNCl, where X = H, CH ,
6
4
2
3
6
4
2
3
C H , F, Cl, or Br.
2
5
C H , F, Cl, or Br.
2
5
or
plots, respectively. These constants were used to recal-
+
+
ꢁ
+ 2
culate the rate constants from the rate law in eq. (11), as
kobs = {k[SH ]/[H ]} +{k /[H ] },
(11)
+
[H ] was varied. The recalculated values agreed rea-
ꢁ
where k = K K k and k = K k .
sonably well with the experimental constants (Table
1
2 3
4 5
The plots of kobs versus [AA] were linear with finite not shown) testing the validity of the rate law and pro-
intercepts on the ordinate (Figs. 1 and 2), in confor- viding support to the suggested mechanism. Further,
mity with the rate law in eq. (11). The constants k and the values of k and k’ were calculated at different tem-
k’ were calculated from the slopes and intercepts of the peratures by varying [substrate] at each temperature
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M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
69
ꢁ
ArSO2NaNCl·H2O,
Values calculated from k
Optimised values
Table 5. Activation
parameters for path
#
#
∆G#
∆S#
where Ar =
Ea
logA
∆H
∆S
Ea
logA
kJ mol 1)
−
(kJ mol ) (J K mol ) (kJ mol ) (kJ mol
−1ꢁ
−1
−1
−1ꢁ
−1
)
(J K mol
−1
−1
)
(
2
of the mechanism
Leu
for the oxidation of
L-leucine (Leu) and
L-isoleucine (Ile) by
sodium salts of mono-
and di-substituted N-
chloro-arenesulphon-
amides in aqueous
perchloric acid.
C6H5
66.0
53.1
52.2
45.5
75.1
55.8
70.4
48.9
37.1
46.8
49.4
7.7
5.4
5.5
4.3
9.5
6.5
8.5
4.8
2.8
4.8
5.2
65.9
53.0
52.1
45.2
75.0
55.3
70.3
42.2
36.3
43.9
46.0
−97.6
−142.4
−139.3
−163.9
−63.6
95.4
96.1
94.3
94.9
94.2
92.5
95.5
95.3
93.3
93.1
93.4
66.0
7.7
7.6
7.9
7.8
7.9
8.2
7.7
7.8
8.1
8.1
8.1
−97.6
−99.9
−94.0
−95.7
−93.8
−87.8
−97.8
−97.0
−90.3
−90.0
−90.9
4
4
4
4
4
2
2
2
2
3
-CH3C6H4
-C2H5C6H4
-FC6H4
-ClC6H4
-BrC6H4
,3-(CH3)2C6H3
,4-(CH3)2C6H3
-CH3-4-ClC6H3
,4-Cl2C6H3
,4-Cl2C6H3
66.7
64.9
65.4
64.9
63.1
65.9
65.6
63.6
63.5
63.8
−122.7
−83.3
−175.2
−188.0
−162.5
−156.6
Ile
C6H5
66.1
47.0
55.7
42.7
44.8
47.3
42.0
46.6
53.3
44.6
40.2
7.9
4.4
6.2
4.8
4.5
5.7
3.6
4.4
5.6
4.3
3.5
63.8
47.0
53.9
47.0
40.2
50.7
41.0
42.1
45.8
38.9
39.3
−101.8
−160.8
−133.0
−154.3
−174.2
−135.7
−180.7
−175.7
−161.9
−181.1
−180.5
94.7
95.7
94.2
93.7
93.0
91.8
95.8
95.3
94.8
93.8
94.0
66.1
67.2
65.8
65.3
64.5
63.4
67.2
66.9
66.4
65.3
65.5
7.9
7.7
8.0
8.0
8.2
8.4
7.7
7.8
7.8
8.0
8.0
−101.8
−105.5
−100.5
−99.0
4
4
4
4
4
2
2
2
2
3
-CH3C6H4
-C2H5C6H4
-FC6H4
-ClC6H4
-BrC6H4
,3-(CH3)2C6H3
,4-(CH3)2C6H3
-CH3-4-ClC6H3
,4-Cl2C6H3
,4-Cl2C6H3
−96.5
−92.4
−105.5
−104.1
−102.6
−99.0
−99.5
ꢁ
Fig. 5a. Plot of log k versus σp (NCSBS) for isoleucine ox- Fig. 5b. Plot of log k versus σp (NCSBS) for isoleucine ox-
idation. NCSBS: 4-X-C H SO NaNCl, where X = H, CH , idation. NCSBS: 4-X-C6H4SO2NaNCl, where X = H, CH3,
6
4
2
3
C H , F, Cl, or Br.
C2H5, F, Cl, or Br.
2
5
(
Table 3). The activation parameters for both the path- ing relations were found to be valid. The oxidant with
ways corresponding to these constants have also been the p-ethyl group in the ring (3) showed deviations
ꢁ
computed from the plots of logk or logk versus 1/T from the linearity. Hence the correlations are shown
ꢁ
and log(k/T) or log(k /T) versus 1/T (Table 4 and 5). with and without reagent 3.
Applicability of the Hammett equation has also been
tested for the oxidation of both Leu and Ile by all the
Leucine:
logkobs = −0.253+1.05σp (r = 0.82)
mono-substituted oxidants. The plots of logk versus
i
logkobs = −0.327+1.53σp (r = 0.96) (except ethyl)
σp were reasonably linear (Figs. 3 – 5) and the follow-
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0
M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
Fig. 6a. Plot of ∆H= versus ∆S= (leucine: Path 1). i-X-
ꢂ
ꢂ
ꢂ
ꢂ
Fig. 7a. Plot of ∆H versus ∆S (isoleucine: Path 1). i-X-
C H SO NaNCl, where i-X = 4-H, 4-CH , 4-C H , 4-F, 4-
C H SO NaNCl, where i-X = 4-H, 4-CH , 4-C H , 4-F, 4-
Cl or 4-Br and i-X-j-Y-C H SO NaNCl, where i-X-j-Y =
6
4
2
3
2
5
6
4
2
3
2
5
6
3
2
Cl or 4-Br and i-X-j-Y-C H SO NaNCl, where i-X-j-Y =
,3-(CH ) , 2,4-(CH ) , 2-CH -4-Cl, 2,4-Cl , 3,4-Cl .
3 2 3 2 3 2 2
2
,3-(CH ) , 2,4-(CH ) , 2-CH -4-Cl, 2,4-Cl , 3,4-Cl .
6
3
3
2
3 2
3
2
2
2
Fig. 6b. Plot of ∆H= versus ∆S= (leucine: Path 2). i-X-
ꢂ
ꢂ
C H SO NaNCl, where i-X = 4-H, 4-CH , 4-C H , 4-F, 4-
ꢂ
ꢂ
6
4
2
3
2
5
Fig. 7b. Plot of ∆H versus ∆S (isoleucine: Path 2). i-X-
Cl or 4-Br and i-X-j-Y-C H SO NaNCl, where i-X-j-Y =
6
3
2
C H SO NaNCl, where i-X = 4-H, 4-CH , 4-C H , 4-F, 4-
6
4
2
3
2
5
2
,3-(CH ) , 2,4-(CH ) , 2-CH -4-Cl, 2,4-Cl , 3,4-Cl .
3 2 3 2 3 2 2
Cl or 4-Br and i-X-j-Y-C H SO NaNCl, where i-X-j-Y =
6
3 2
2
,3-(CH ) , 2,4-(CH ) , 2-CH -4-Cl, 2,4-Cl , 3,4-Cl .
3 2 3 2 3 2 2
logk = −0.502+1.36σp (r = 0.94)
logk = −0.550+1.70σp (r = 0.97) (except ethyl)
The enthalpies and the free energies of activations
ꢁ
for the oxidations of Leu and Ile by all the N-chloro-
arenesulphonamides have been correlated. The plots
of ∆H (kJ mol ) versus ∆S (J K mol ) cor-
responding to both k and k were reasonably linear
logk = −3.641+1.48σp (r = 0.89) (except ethyl)
Isoleucine:
ꢂ
−1
ꢂ
−1
−1
ꢁ
logkobs = −0.094+1.37σp (r = 0.89)
logkobs = −0.159+1.79σp (r = 0.96) (except ethyl)
logk = −0.281+1.47σp (r = 0.96);
logk = −0.322+1.75σp (r = 0.99) (except ethyl)
(Figs. 6 and 7) with iso-kinetic temperatures of 311
and 310 K (Leu), and 266 and 294 K (Ile), respectively,
which are within the temperature ranges employed or
closer to the range used in the present investigations
(293– 313 K).
ꢁ
logk = −3.503+1.61σp (r = 0.97) (except ethyl)
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M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
71
Table 6. Melting points of mono- and di-substituted arenesulphonamides and sodium salts of their N-chloro compounds
1
– 11.
◦
◦
Substituted
M.p.( C)
Sodium salts of N-chloro-
M.p.( C)
arenesulphonamides
C6H5SO2NH2
obs (lit.)
152-152
138-139
99-101 (99-100)
125 (124-125)
143 (142-143)
162 (162)
138-140
140-142
arenesulphonamides
C6H5SO2NaNCl·H2O (1)
obs (lit.)
172-173
167-170
194
4
4
4
4
4
2
2
2
2
3
-CH3C6H4 SO2NH2
-C2H5C6H4SO2NH2
-FC6H4SO2NH2
-ClC6H4SO2NH2
-BrC6H4SO2NH2
,3-(CH3)2C6H3SO2NH2
,4-(CH3)2C6H3SO2NH2
-CH3,4-ClC6H3SO2NH2
,4-Cl2C6H3SO2NH2
,4-Cl2C6H3SO2NH2
4- CH3C6H4SO2NaNCl·H2O (2)
4- C2H5C6H4SO2NaNCl·H2O (3)
4-FC6H4SO2NaNCl·H2O (4)
4-ClC6H4SO2NaNCl·H2O (5)
4-BrC6H4SO2NaNCl·H2O (6)
2,3-(CH3)2C6H3SO2NaNCl·H2O (7)
2,4-(CH3)2C6H3SO2NaNCl·H2O (8)
2-CH3,4-ClC6H3SO2NaNCl·H2O (9)
2,4-Cl2C6H3SO2NaNCl·H2O (10)
3,4-Cl2C6H3SO2NaNCl·H2O (11)
198
191(190)
179(178)
167
154
172
158-160
178-180 (179-180)
141-143 (134-135)
210
192
Leucine:
vated complexes is evident from the negative entropies
of activations.
#
#
Path 1: ∆H = 75.8+311∆S (r = 0.99)
#
#
Path 2: ∆H = 95.4+310∆S (r = 0.996)
Isoleucine:
Path 1: ∆H = 72.6+266∆S (r = 0.98)
Conclusion
Effective oxidising species of the oxidants em-
#
#
+
ployed in the present oxidations is Cl in different
#
#
forms, released from the oxidant. The introduction of
different substituents into the benzene ring of the ox-
Path 2: ∆H = 92.8+294∆S (r = 0.99)
Further, the effect of substitution in the N-chloro-
arenesulphonamides, on the energy of activation, (Ea)
has been analysed by optimising Ea values with ref-
erence to logA value of the parent oxidant, N-chloro-
benzenesulphonamide, through the equation,
+
idant affects the ability of it to release Cl and hence
its capacity to oxidise the substrate. The study revealed
that the introduction of electron releasing groups such
as CH , C H etc. into the benzene ring inhibit the ease
3
2
5
+
with which Cl is released from the oxidant, while
electron withdrawing groups such as Cl, Br etc. en-
hance this ability and and hence increased the oxidis-
ing strengths of the N-chloro-arenesulphonamides.
Ea = 2.303 RT(logA−logk ),
i
where k is the constant for the oxidant with a sub-
i
stituent. As may be seen (Tables 4 and 5), the ener-
gies of activation for the oxidation of either Leu or Ile
by the oxidants with electron releasing groups in the
benzene ring are slightly higher than that of the par-
Experimental Section
Materials and methods
The substituted arenesulphonamides, were prepared by
ent oxidant, while the Ea values are lower with the the chloro-sulphonation of the respective substituted ben-
zenes to the corresponding sulphonylchlorides and subse-
oxidants with electron withdrawing groups in the ben-
quent conversion of the latter to the respective amides by the
procedures reported earlier [12]. The sulphonamides were re-
crystallised to constant melting point (Table 6) from dilute
ethanol. The sodium salts of N-chloro-arenesulphonamides
zene ring. Enthalpies of activations have similar trends.
Similarly logA values were optimised with reference
to Ea value of the parent oxidant for both Leu and Ile
through the equation logA = logk +Ea/2.303 RT (Ta-
i
were then prepared by bubbling pure chlorine gas through
bles 4 and 5). The logA values have the reverse trend
clear aqueous solutions of substituted arenesulphonamides in
as anticipated. They are little higher for oxidants with
the electron withdrawing groups in the benzene ring,
while the effect of electron releasing groups on logA is
negligible. The free energies of activation for both the
pathways remain almost the same in both the optimi-
◦
M NaOH at 70 C for about 1 h [13]. The precipitated N-
4
chloro compounds were filtered, washed, dried and recrys-
tallised from water. Purity of all the reagents was checked
by determining their melting points (Table 6) and by estimat-
ing the amounts of active chlorine present in them. Both the
sations indicating the operation of similar mechanisms sulphonamides and their N-chloro compounds were charac-
in all the cases. The formation of more ordered acti- terized by their infrared and NMR spectra.
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7
2
M. Shetty – B. T. Gowda · Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides
Aqueous stock solutions of sodium salts of substituted further assayed by the standard method [16]. Aqueous stock
−3
−3
N-chloro-arenesulphonamides (0.01 mol dm ) were pre- solutions of these compounds (0.10 mol dm ) were used.
pared in double distilled water, standardized by the iodomet- All other reagents employed were of the accepted grades
ric method and preserved in dark coloured bottles to prevent of purity. Ionic strength of the medium was maintained
−3
their photochemical deteriorations.
at 0.30 mol dm using concentrated aqueous solution of
Pure samples of amino acids (AA), L-leucine (Leu) and sodium nitrate (E. Merck).
L-isoleucine (Ile) (CDH, India) were employed. They were
[
[
[
[
[
[
1] M. M. Campbell, G. Johnson, Chem. Rev. 78, 65
[9] B. T. Gowda, P. J. M. Rao, Bull. Chem. Soc. Jpn. 62,
(1978).
3303 (1989).
2] B. T. Gowda, D. S. Mahadevappa, Talanta 30, 359 [10] B. T. Gowda, P. Ramachandra , J. Chem. Soc. Perkin
(1983); Microchem. J. 28, 374 (1983).
Trans. 2, 1067 (1989); Proc. Indian Acad. Sci. (Chem.
Sci.) 102, 7, 471 (1990).
[11] B. T. Gowda, B. S. Moodithaya, Oxid. Commun. 24,
134 (2001).
[12] B. T. Gowda, K. Jyothi, J. D. D’Souza, Z. Naturforsch.
57a, 967 (2002).
[13] B. T. Gowda, J. D. D’Souza, B. H. A. Kumar, Z. Natur-
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