COUPLING KINETICS OF 4-SULFOBENZENEDIAZONIUM ION WITH 2,4-THIAZOLIDINEDIONE, ITS 3-METHYL DERIVETIVE AND 3-METHYL-5-ISOXAZOLONE

Article abstract of DOI:10.1135/cccc19942022

3- and 4-substituted derivatives of 2,4-thiazolidinedione were prepared as potential biologically active fungicides.The kinetics of coupling of 4-sulfobenzenediazonium salt with 2,4-thiazolidinedione and 3-methyl-2,4-thiazolidine dione have been studied and the results have been compared with kinetic data od coupling reaction of 3-methyl-5-isoxazolone.

Full text of DOI:10.1135/cccc19942022

2
022
Kavalek, Machacek, Sterba:
COUPLING KINETICS OF 4-SULFOBENZENEDIAZONIUM ION
WITH 2,4-THIAZOLIDINEDIONE, ITS 3-METHYL DERIVATIVE
AND 3-METHYL-5-ISOXAZOLONE
Jaromir KAVALEK, Vladimir MACHACEK and Vojeslav STERBA
Department of Organic Chemistry,
University of Pardubice, 532 10 Pardubice, The Czech Republic
Received May 9, 1994
Accepted May 23, 1994
3
- and 4-substituted 5-phenylazo derivatives of 2,4-thiazolidinedione were prepared as potential
biologically active fungicides. The kinetics of coupling of 4-sulfobenzenediazonium salt with
,4-thiazolidinedione and 3-methyl-2,4-thiazolidinedione have been studied and the results have been
2
compared with kinetic data of coupling reaction of 3-methyl-5-isoxazolone.
A detailed account of reactions of substituted thioureas with chloroacetic acid giving
1
,2
2
-imino-4-thiazolidinedione derivatives has been given in the reviews . As many of
the reaction products exhibit biological activity, most of the references cited there deal
with the synthesis of compounds with potential biological activity.
Arylazo compounds or their hydrazo tautomers are mostly prepared by reaction of
arenediazonium salts with aromatic hydroxy and amino compounds or by reaction with
compounds containing methylene group activated by one or two neighbouring, strongly
3
–6
electron-attracting groups
.
Substituted 2,4-thiazolidinediones have the methylene group activated by the neigh-
bouring carbonyl group and sulfur atom. It is easily deprotonated to give the carbanion
1
which can react with electrophilic agents inclusive of benzenediazonium ions. The
base-catalyzed reaction of 3-methyl-5-isoxazolone (which also has an activated
methylene group) with some substituted benzenediazonium ions gives azo compounds
7
with high fungicidal activity (e.g. commercial derivative “Drazoxolon”, I).
The present paper deals with the synthesis of a series of substituted phenylazo deri-
vatives of 2,4-thiazolidinedione IIa – IIf which were submitted to biological screening
tests. At the same time, kinetics of coupling of 4-sulfobenzenediazonium salt with
2
,4-thiazolidinedione (III) and 3-methyl-2,4-thiazolidinedione (IV) was studied. The re-
sults were compared with analogous data on the coupling reaction with 3-methyl-5-
isoxazolone (V).
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Coupling Kinetics of 4-Sulfobenzenediazonium Ion
2023
EXPERIMENTAL
Reagents
2
,4-Thiazolidinedione (III) was prepared from chloroacetic acid and thiourea by boiling on water
8
bath for 12 h according to the known procedure . 3-Methyl-2,4-thiazolidinedione (IV) was prepared
by methylation of the dione III according to the known procedure . 3-Methyl-5-isoxazolone (V) was
9
prepared from hydroxylamine hydrochloride and ethyl 3-oxobutanoate according to reported proce-
1
0
dure . 5-(Substituted phenylazo)-2,4-thiazolidinediones (IIa – IIf) were prepared by coupling of the
respective diazonium salts with the dione III in acetate buffer solution. For their melting points and
elemental analyses see Table I.
TABLE I
Physico-chemical properties of 5-(substituted phenylazo)-2,4-thiazolidinediones IIa – IIf
Calculated/Found
Compound
M.p., °C
Yield, %
%
C
% H
IIa
IIb
IIc
IId
IIe
IIf
194.5 – 196
232 – 233
247 – 249
265 – 268
113 – 115
220 – 223
60
30
85
85
70
75
42.28
2.50
42.28
2.40
42.28
2.00
36.02
6.23
40.60
0.90
50.18
9.92
2.36
2.46
4
2.36
2.20
4
2.36
2.52
4
2.01
2.09
3
2.27
2.39
4
3.44
3.30
4
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

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024
Kavalek, Machacek, Sterba:
Kinetic Measurements
All kinetic experiments were carried out at 25 °C, using the VSU-2P apparatus (Zeiss, Jena). Coup-
ling of 4-sulfobenzenediazonium salt with the dione III and its methyl derivative IV was carried out
in a quartz cell located in thermostated cell compartment of the spectrophotometer; 1 ml of aqueous
solution of substrate (III or IV) and potassium chloride was mixed with 1 ml of acetate or phosphate
−3
buffer. After temperation, 0.1 ml 1 . 10 M diazotized sulfanilic acid solution was added, and absorb-
ance was measured at 365 nm. The ionic strength was adjusted at 0.5 by addition of potassium
chloride. Kinetic experiments of 4-sulfobenzenediazonium salt with isoxazolone V were carried out
in the same way as those of the compounds III and IV. The buffer used was chloroacetate, the ab-
11
sorbance changes were followed at 400 nm. Sulfanilic acid was diazotized by the procedure given in ref. .
RESULTS AND DISCUSSION
Coupling reactions of diazotized sulfanilic acid with the compounds III – V were stu-
died in aqueous buffer solutions at 25 °C. In all the cases, concentration of the sub-
strates was at least ten times higher than that of the diazonium salt, the reactions
proceeding thus as pseudomonomolecular. The time dependence of log (A − A ) was
∞
t
linear in the whole conversion range investigated (80 to 90% conversion). Influence of
pH and concentrations of the mentioned reactants on the rate constant was determined,
and the results are presented in Tables II and III. The experimental rate constants are
TABLE II
−1
Rate constants kexp(s ) of coupling of diazotized sulfanilic acid with isoxazolone V, dione III and its
methyl derivative IV at various substrate concentrations
3,a
kexp . 10
Entry
b
c
d
V
III
IV
1
2
3
4
5
6
7
8
2.5 (0.5)
0.33 (0.1)
0.67 (0.2)
1.01 (0.3)
1.98 (0.6)
2.42 (0.75)
5.15 (1.6)
6.00 (2.0)
8.5 (3.0)
2.0 (1.5)
4.5 (3.0)
7.2 (4.5)
10.0 (6.0)
12.2 (7.5)
–
5.4 (1.0)
7.8 (1.5)
–
–
–
–
–
–
–
a
3
−1
−1
Substrate concentrations (c . 10 mol l for V and IV, and c . 10 mol l for III) are given in paren-
b
−2 −1
c
−7 −1
d
−7 −1
thesis. pH 2.70; k K = 1 . 10 s . pH 5.17; k K = 2.2 . 10
s
.
pH 6.48; k K = 5.5 . 10 s .
2 a
2
a
2
a
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Coupling Kinetics of 4-Sulfobenzenediazonium Ion
2025
directly proportional to concentration of the substrates except for higher concentrations
of the compound III. In this case the kexp value increases more slowly due probably to
association of the compound III. The dependence log kexp vs pH is linear with the slope
equal to unity.
In the cases of the methyl derivative IV and isoxazolone V the deprotonation of CH2
group gives only one monoanion from each compound. The coupling reaction mechan-
ism of the substrate IV is given in Scheme 1, the mechanism for the isoxazolone V
being similar.
SCHEME 1
The final tautomer equilibrium is very rapid and is shifted almost completely in fa-
1
2
vour of the hydrazo compound which thus represents the main reaction product. The
rate-limiting step can be either deprotonation of CH group or the reaction of the
2
formed anion with diazonium ion. In the former case, the reaction rate would be di-
rectly proportional to buffer concentration and independent of diazonium salt concen-
tration; i.e. with excess substrate, the reaction would be of zero order. So far, this
mechanism was observed only in reactions of benzenediazonium ions with nitroe-
1
3
thane . In the latter case, i.e. if the reaction of the carbanion with diazonium cation
were rate-limiting, the kexp values would be directly proportional to concentration of
substrate and inversely propotional to the proton concentration (for pH lower than pKa
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

2
026
Kavalek, Machacek, Sterba:
of the substrate). This dependence was observed in coupling reactions of all three sub-
strated V, III and IV. The reaction rate is given by Eq. (1):
+
′
+
+
−
r = kexp[ArN ] = k [ArN ] [SH] = k [ArN ] [S ] .
(1)
2
2
2
2
2
−
+
+
For pH << pK of the substrate SH, [S ] = K [SH]/[H ], so that k = k K [SH]/[H ].
a
a
exp
2
a
Dissociation of the dione III is represented in Scheme 2, and experimental dissoci-
ation constant is defined by Eq. (2):
+
Ka,exp = ([III ] + [III ]) [H ]/[III] .
(2)
C
N
SCHEME 2
As hydrogen atom at the NH group is much more acidic than that at CH group,
2
concentration of the anion III is higher than that of III by many orders of magnitude.
N
C
CH
+
But for pH << pKa,exp it is [III ] = K [III]/[H ], as it is the case with the N-methyl
derivative IV. The Ka value should be comparable with the K value of the methyl
C
a
CH
a
derivative IV.
Coupling with the compound III can take place both at carbon atom of the anion IIIC
and at nitrogen atom of the anion III ; the latter alternative results in formation of
N
triazene VII. In contrast to the products of C-coupling, triazenes are unstable in acidic
media, being split into the respective starting components.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Coupling Kinetics of 4-Sulfobenzenediazonium Ion
2027
The coupling kinetics was pseudomonomolecular in all the cases. Spectrum of the
product formed was similar to that of the coupling product from the N-methyl deriva-
tive IV. It did not change after acidification of the reaction product, which indicated
that no triazene was practically formed.
As the coupling mechanism is the same for both compounds III and IV, and substitu-
tion of NH hydrogen atom by methyl group does not influence fundamentally the reac-
tivity of the formed carbanion, the coupling rates (defined by e.g. k K ) should be
2
a
similar, which is in accord with the values found (Table II).
The isoxazolone V reacts faster than the diones IV and III by about 4.5 orders of
1
0
magnitude. The isoxazolone is a much stronger C-acid (pK 5.56; ref. ) than the diones
a
III and IV (rough estimate – by about 10 orders of magnitude). On the other hand, the
carbanion of isoxazolone is far more stable and, hence, less reactive toward diazonium
ions. The both factors act in opposite directions, but the former (i.e. magnitude of dis-
sociation constant) predominates.
Kinetic study of these azo coupling reactions had a practical purpose, viz. estimation
of optimum reaction conditions for preparation of these azo compounds which are
7
potential biologically active agents (fungicides) .
TABLE III
−1
Rate constants kexp(s ) of coupling of diazotized sulfanilic acid with isoxazolone V, dione III and its
methyl derivative IV at various pH
3,a
kexp . 10
Entry
b
c
d
V
III
IV
1
1
3
4
5
6
7
2.0 (2.34)
0.21 (4.74)
0.32 (5.05)
0.67 (5.35)
2.35 (5.85)
4.50 (6.35)
6.95 (6.80)
8.75 (7.05)
0.38 (5.39)
2.5 (2.40)
0.62 (5.50)
2.7 (2.51)
1.33 (6.50)
5.2 (2.71
8.20 (6.80)
–
–
–
–
–
–
a
b
−3
−1
c
−2
−1
d
−3
−1
pH given in parentheses. [V] = 1 . 10 mol l . [III] = 1 . 10 mol l . [IV] = 3 . 10 mol l .
This work was supported by the Grant Agency for Science of the Czech Republic, No. 203/93/2065.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

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Kavalek, Machacek, Sterba:
REFERENCES
. Brown F. C.: Chem. Rev. 61, 463 (1961).
1
2
3
4
5
6
7
8
9
. Kavalek J., Said El Bahaie, Sterba V.: Collect. Czech. Chem. Commun. 45, 263 (1980).
. Houben–Weyl: Methoden der organischen Chemie, Vol. X/3. Thieme, Stuttgart 1965.
. Patai S. (Ed.): The Chemistry of Diazonium and Diazo Groups. Wiley, London 1978.
. Saunders K. H., Allen R. L. M.: Aromatic Diazo Compounds, 3rd ed. Arnold, London 1985.
. Zollinger H.: Diazo and Azo Chemistry. Interscience, New York 1961.
. Imperial Chemical Industries Ltd.: Belg. 617, 389; Chem. Abstr. 59, 6413 (1963).
. Hamed A. E.: Thesis. University of Cairo, Cairo 1975.
. Lo C. P., Shrophire E. Y.: J. Org. Chem. 22, 999 (1957).
1
1
0. Katritzky A. R., Oeksne S., Boulton A. J.: Tetrahedron 18, 777 (1962).
1. Putter R. in: Methoden der organischen Chemie (E. Müller, Ed.), Vol. X/3, p. 20. Thieme,
Stuttgart 1965.
1
1
2. Zollinger H.: Azo and Diazo Chemistry; Aliphatic and Aromatic Compounds. Interscience, New
York 1961.
3. Machacek V., Panchartek J., Sterba V., Vecera M.: Collect. Czech. Chem. Commun. 33, 3154
(
1968).
Translated by the author (V. S.).
Collect. Czech. Chem. Commun. (Vol. 59) (1994)