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J. Hanusek et al. / Tetrahedron Letters 48 (2007) 417–419
reactions of phosphorus(III) species, but they include
NH2
R
H2N
N
R
kinetic values measured for the reaction of: aryldiethyl
phosphines with ethyl iodide7 q = ꢀ1.0; for the reaction
of triarylphosphines with elemental sulfur8 q = ꢀ2.5
and for the reaction of triarylphosphines and triaryl-
phosphites with9 diphenyl trisulfide q = ꢀ1.1. In
determining possible transition state structures these
values can be compared with equilibrium data measured
for the proton transfer to phosphines, measured in
nitromethane using Taft substituent constants10
q* = ꢀ2.6 which is very similar to the reaction constant
determined for the protonation of amines11 q = ꢀ2.77.
P+
S
S
S
S
S
P
N
+
R
R
R
R
S
1
H2N
R
S
+
S
P
R
C
S
N
R
2
R = Ph, CH3O
Scheme 1.
phosphonium intermediate formed into triphenylphos-
phine sulfide or trimethyl thiophosphate and thiocarba-
moyl isothiocyanate (2) (Scheme 1).
Given the product analysis, it is likely that the sulfurisa-
tion reaction proceeds by initial nucleophilic attack of
phosphorus(III) on the disulfide linkage to generate a
phosphonium ion intermediate as shown in Scheme 1.
Either formation or breakdown of the intermediate
could be the rate limiting step and both steps would
have transition states with positively charged phospho-
rus compared with the reactant state. The relatively
small reaction constant measured here of about ꢀ1.0
indicates the development of a partial positive charge
on phosphorus in the transition state. If the first step
is rate limiting, then the observed q-value suggests an
early transition state with a little build up of charge on
phosphorus. If the second step is rate limiting, then
the reaction constant is the sum of two values for the
two steps (Scheme 1), probably with opposite signs.
The reaction constant for the formation of intermediate
qI is expected to be about ꢀ2.8. It is therefore unlikely
that the second step is rate limiting and the observed
q-value is indicative of rate limiting formation of the
phosphonium ion with less than half of the unit positive
charge developed on phosphorus in the transition state
as a result of bond formation.
Thiocarbamoyl isothiocyanate (2) itself has not been
described in the literature, presumably because of its
high reactivity and instability. N,N-Dimethylthiocarba-
moyl isothiocyanate has been characterised and is stable
for a couple of days4 at ꢀ15 ꢁC; at an ambient temper-
ature N,N-dimethylthiocarbamoyl isothiocyanate read-
ily undergoes4,5 dimerisation ([4+2] cycloaddition) to
give 2-dimethylamino-5-dimethylthiocarbamoyl-1,3,5-
thiadiazin-4,6-dithione.
To demonstrate6 the presence of the reactive thio-
carbamoyl isothiocyanate during the course of the
sulfurisation reaction we added an external nucleophile,
4-nitroaniline, to the reaction mixture to act as a trap.
After reaction work-up, 1-(4-nitrophenyl)dithiobiuret
(3) was obtained in almost quantitative yield, which is
the expected product of nucleophilic addition of 4-nitro-
aniline to thiocarbamoyl isothiocyanate (Scheme 2).
The kinetics of the sulfurisation reaction were also
studied spectrophotometrically. The absorbance due
to 1 decreased exponentially with time from which
was obtained a pseudo first-order rate constant which
varied linearly with the concentration of the substi-
tuted triphenylphosphines to give the corresponding
second-order rate constant. These second-order rate
constants were high. For example, for triphenylphos-
phine k = 1.32 · 104 l molꢀ1 sꢀ1 and trimethyl phos-
This conclusion is supported by the activation para-
meters for the sulfurisation reaction which were
determined from kinetic data measured in acetonitrile
at four temperatures: DH5 = 13.3 kJ molꢀ1 and DS5
=
ꢀ121 J molꢀ1 Kꢀ1. The entropy of activation is very
negative and is consistent with a bimolecular association
step leading to the transition state. This is consistent
with the first step being rate limiting but may also con-
tain a contribution from the entropy change associated
with increased solvation of charge in the transition state.
phite k = 3.03 · 103 l molꢀ1 sꢀ1
.
A Hammett plot for the data, rꢀp against the second-
order rate constants for the seven substituted triphenyl-
phosphines is linear, and the slope generates a reaction
constant q = ꢀ0.86.
Acknowledgements
The authors acknowledge the financial support from the
Ministry of Education, Youth and Sports of the Czech
Republic (Project No. MSM 0002 162 7501) and
EPSRC. The authors also thank Avecia Biotechnology,
Grangemouth, UK, for xanthane hydride.
The interpretation of the Hammett q-value in terms of
charge distribution in the transition state requires a ref-
erence reaction, ideally a corresponding q-value for an
equilibrium reaction. There are a limited number of
Hammett correlations in the literature which relate to
NO2
S
4-nitroaniline
S
S
C
S
C
References and notes
H2N C
N C
N
N
H2N
H
1. (a) Eckstein, F.; Gish, G. Trends Biochem. Sci. 1989, 14,
97–100; Zon G.; (b) Stec, W. J. In Oligonucleotides and
Analogues: A Practical Approach; Eckstein, F., Ed.;
H
2
3
Scheme 2.