Reaction of thiourea dioxides with amines

Article abstract of DOI:10.1007/s11176-005-0015-6

The reaction mechanism of thiourea dioxides with ammonia and primary aliphatic amines involves direct nucleophile (ammonia or amine) reactions with thiourea dioxides, followed by dissociation of the resulting adduct to form the sulfoxylate ion. 2004 MAIK "Nauka/Interperiodica".

Full text of DOI:10.1007/s11176-005-0015-6

Russian Journal of General Chemistry, Vol. 74, No. 9, 2004, pp. 1383 1385. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 9, 2004,
pp. 1491 1494.
Original Russian Text Copyright
2004 by Makarov, Kudrik, Terskaya, Davydov.
Reaction of Thiourea Dioxides with Amines
S. V. Makarov, E. V. Kudrik, I. N. Terskaya, and K. A. Davydov
Ivanovo State University of Chemistry and Technology, Ivanovo, Russia
Received October 23, 2002
Abstract The reaction mechanism of thiourea dioxides with ammonia and primary aliphatic amines
involves direct nucleophile (ammonia or amine) reactions with thiourea dioxides, followed by dissociation of
the resulting adduct to form the sulfoxylate ion.
Sulfur-containing compounds with S S or C S
bonds, such as sodium dithionite Na2S2O4, sodium
hydroxymethanesulfinate HOCH2SO2Na, and thiourea
dioxide (NH2)2CSO2 (I) are widely used in chemistry
and chemical technology as reducers [1, 2]. One of
the most important application fields of thiourea and
their oxidation products, trioxides, is guanidine syn-
thesis [3 5] vigorously developed over the past years
[6, 7]. This is explained by an important biological
role of nitric oxide whose precursor in the living body
is L-arginine, as well as by the search for new phar-
maceuticals [5]. It should be noted that the kinetics of
thiourea oxide reactions with amines have not been
explored, and all research into thiourea oxides have
been focused on guanidine synthesis.
nite formation (Fig. 1). Dithionite is not formed in
the absence of oxygen. The reaction rate of compound
I and its analogs with amines increases with amine
concentration (Fig. 2) and depends on amine nature
(Fig. 1) (the pHs of 0.65 M solutions of primary
amines, methylamine, and isobutylamine are almost
the same).
Let us now consider the kinetics of an anaerobic
reaction of compounds I and V ([(NH2)2CSO2]0 1.2
3
2
10 , [CH3NH2]0 5 10 , and [O2]0 2.4 10 4 M). The
induction period was 35 s (Fig. 3). According to [8],
during this time the oxygen concentration decreases
to zero. The stoichiometric ratio for thiourea reaction
with oxygen is 1:2 [8]. Consequently, if the reaction
occurred similarly to that between compound I and
OH , the concentration of (NH2)2CSO2 would de-
In the present work we report on the results of a
kinetic study of the reactions of thio- (I), N-methyl-
thio- (II), and N-phenylthioureas (III) with ammonia
(IV) and primary aliphatic amines [methylamine (V)
and isobutylamine (VI)] in aqueous solutions.
4
crease by 1.2 10 M (the concentration of oxygen
4
in water at 25 C is 2.4 10 M [8]). However, the
concentration of (NH2)2CSO2 within 35 s has de-
4
creased by 6 10 M. Consequently, sulfoxylate
formation in the reaction between compounds I and V
involves a fairly stable intermediate. Probably, the
latter is an adduct of the nucleophile (methylamine)
It was previously shown [8] that decomposition of
thiourea in air-saturated strongly alkaline solutions
involves dithionite formation preceded by an induc-
tion period. In anaerobic conditions no dithionite was
formed. These data led the referees to a conclusion
that the S2O24 ion and its equilibrium SO2 radical
anion are formed by reactions of the decomposition
product of thiourea dioxide dianion, sulfoxylate SO22 ,
with oxygen and its reduced forms, superoxide O2 and
hydrogen peroxide HO2. These reactions occur during
the induction period. Since dithionite is accumulated
after the induction period, i.e. in the absence of
oxygen, SO22 and SO2 react with superoxide and its
reduction product peroxide, which was proved
experimentally.
A
3
0.8
4
0.6
0.4
2
1
0.2
0
100 200 300 400 500 600 , s
Fig. 1. Variation of the optical density (A) at (1, 2) 270
and (3, 4) 315 nm in the course of thiourea dioxide reac-
tions with (1, 3) methylamine and (2, 4) isobutylamine
We found that, like what is observed in alkaline
solutions, the aerobic decomposition of thiourea di-
oxides in primary amine solutions involves no dithio-
3
(298 K, [(NH ) CSO ] 1.2 10 , [amine] 0.65 M).
2 2
2 0
0
1070-3632/04/7409-1383 2004 MAIK Nauka/Interperiodica

1384
MAKAROV et al.
1.0
A
1
105, mol l 1 s
2
1.8
1.4
1
4
3
2
0.5
0
1
1.0
0.6
0.2
0
100
200
300
400
500
, s
0.4 0.8 1.2
1.6
20
[Amine]0, M
Fig. 3. Variation of the optical density (A) at 315 nm
in the course of thiourea dioxide reaction with methyl-
3
Fig. 2. Initial rate of thiourea dioxide reactions with
(1) methylamine and (2) isobutylamine vs. initial amine
amine at 298
K
{[(NH ) CSO ] 1.2 10
M;
2 2
2 0
[CH NH ] , M: (1) 0.05, (2) 0.18, (3) 0.81, and
3
2 0
3
concentration at 298 K ([(NH ) CSO ] 1.2 10 M).
(4) 6.45}.
2 2
2 0
by the thiourea dioxide carbon. Similar results were
obtained in the reactions of thiourea dioxides with
ammonia and isobutylamine.
tration decrease rate constant for (NH2)2CSO2 in
0.65 M MeNH2 is 0.21 s . Therefore, we can omit
the decomposition stage from the overall reaction
scheme of amines and thiourea dioxides.
1
A mechanism suggesting such adduct formation in
the reaction of (NH2)2CSO2 with morpholine was pre-
viously proposed by Maryanoff et al. [3]. The referees
failed to isolate this adduct solid but detected it by
TLC. Thus, on the basis of our and published data we
can propose the following reaction sequence of
thiourea dioxides with primary amines.
The reaction with ammonia is much slower and,
therefore, decomposition of thiourea dioxides cannot
be neglected here. In this connection thiourea dioxide
decomposition rate constants in alkaline solutions at
pH values corresponding to ammonia solutions were
determined experimentally and taken into account in
the calculation of rate constants for type (1) reactions.
k1
The highest rate constants are characteristic of
thiourea dioxides reactions with methylamine and the
lowest, for the reactions with ammonia. Thus, the rate
NHNR CSO22 + RNH2
R NC(NH2)(NHR)SO2
RN C(NH2)(NHR)SO2, (1)
k2
HR NC(=NH)NHR + SO22 , (2)
1
constant k1 (l mol 1 s ) of the reactions of compounds
I III with methylamine at 25 C are 0.14, 0.05, and
R = H, Me, i-Bu; R = H, Me, Ph.
0.09, with isobutylamine, 0.07, 0.03, and 0.05, and
3
4
4
In addition, reactions of SO22 and SO2 with O2,
O2, and HO2, as well as SO2 dimerization into
S2O24 occur in aerobic conditions [8].
with ammonia 10 , 3 10 , and 6 10 , respec-
tively. Probably, the key role here belongs to nucleo-
philicity of the amine. As known [9], there is a cor-
relation between basicity and nucleophilicity for
nucleophiles of the same type. Ammonia is a weaker
base than aliphatic amines [9]. This is an explanation
for its lower reactivity toward thiourea dioxides. The
lower reactivity of isobutylamine compared with
methylamine is probably explained by the fact that
the increased steric bulk of the nucleophile destabilizes
the transition state and, consequently, adversely
affects the reactivity of the nucleophile. The lower
reactivity of compounds II and III toward ammonia
and amines IV VI, as compared to compound I, is,
too, explained by steric reasons.
The constant of reaction (1) can be determined
from the [NH2NHR CSO2] dependence at various
initial concentrations of methylamine ([CH3NH2]0 >>
[NH2NHR CSO2]0).
v = k[NH2NHR CSO2],
k = k1[RNH2]0.
(3)
In was found that in alkaline media thiourea di-
oxides decompose much slower than react with
methylamine and isobutylamine. Thus, the first-order
rate constant for (NH2)2CSO2 decomposition in 0.5 M
Interestingly, Miller et al. [4] explained by steric
reasons the rate-constant order of thiourea trioxides,
4
1
NaOH at 298 K is 6.25 10
s
[8], and the concen-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004

REACTION OF THIOUREA DIOXIDES WITH AMINES
1385
(NH2)2CSO3 > C6H5NHNH2CSO3 > (C6H5NH)2CSO3,
in reactions with glycine. The results of glycine reac-
tions with N-phenylthiourea trioxide derivatives with
various substituents in the benzene ring gave evidence
showing that electronic effects only slightly affect
reaction rate: Any ortho-substituent decelerated the
reaction.
The concentrations of compounds I III and dithio-
nite were measured spectrophotometrically following
the optical density at 270, 260, 270, and 315 nm,
respectively (the
of dithionite at 315 nm is
1
8043 l mol 1 cm [11]; the values for alkaline solu-
tions of thioureas are higher that those for neutral
media because of deprotonation [8] are pH-dependent;
this difference was accounted for in the calculations).
Experiments in aerobic conditions were performed at
a constant initial concentration of oxygen (2.4
Comparison of the results of the reactions of thio-
urea dioxides with oxygen and amines led us to the
following conclusions. The first process involves
initial C S bond fission in thiourea dioxides to form
the sulfoxylate ion. With ammonia and primary ali-
phatic amines, a different mechanism is operative.
Even though this process, too, gives sulfoxylate, but
it is formed by direct reaction of the nucleophile
(amine) with thiourea dioxide and subsequent decom-
position of the resulting adduct.
4
10 M [8] in air-saturated aqueous solutions at 25 C)
in a hermetic cell.
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1
IR spectrum (KBr), , cm : 960, 995, 1085 (965, 990,
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22.70. C2H8N2O3S. Calculated, %: C 17.14; H 5.71;
N 20.00; S 22.86. PhNHNH2CSO2: mp 95 C (95
1
96.5 C [4]). IR spectrum (KBr), , cm : 1010, 1090
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004