one compares methyl carbonate with ethyl dithiocarbonate (2a).
While a change of the alkoxy group has little influence on the
nucleophilicity (cf 2a/2b) the dithiocarbamate anions 3a–e are
approximately one order of magnitude more nucleophilic than the
dithiocarbonate ions 2a and 2b due to the smaller electronegativity
and larger +M effect of nitrogen compared to oxygen.
The lower line of Scheme 5 shows that cyclic dithiocarbamates
3b,c are approximately two times more nucleophilic than 3a and
the series 3c/3d/3e shows the expected slight reduction in the
nucleophilicity due to the different electronegativity of the atom
in position 4 of the heterocycle ring.
Conclusions
The reactivities of thiocarboxylate 1, dithiocarbonate 2 and
dithiocarbamate ions 3 toward benzhydrylium ions were found
to follow correlation (1), which enables us to include these ions in
our comprehensive nucleophilicity scale.4 Though they are much
weaker Brønsted bases than the corresponding oxygen analogues,
they are considerably more nucleophilic (Fig. 3).
As previous investigations on the nucleophilicities of alkyl
thiolates (dianions of cysteine and mercaptoacetic acid) were
performed in aqueous solution,8 we now attempted to measure
the rate constants of the reactions of potassium hexane-1-thiolate
4 with benzhydrylium ions in acetonitrile. For unknown reasons,
the decay of the benzhydrylium ions was not monoexponential,
despite the use of a large excess of 4-K/18-crown-6. As a
consequence, only approximate rate constants could be derived
for the reactions with 4. Table 2 shows that thiocarboxylate anion
1 and thiocarbamate anions 2 are approximately 7 and 30 times
less reactive than 4 and that the nucleophilicity of 4 is comparable
to that of the dithiocarbamates 3.
Nucleophilicity parameters
When values of log k for the reactions of 1–3 with the
benzhydrylium ions (Table 2) were plotted against the previously
published electrophilicity parameters E, linear correlations were
observed for log k < 8.5, indicating the applicability of eqn (1)
(Fig. 2). The slopes of these correlation lines yield the nucleophile-
specific sensitivity parameters sN and the intercepts on the
abscissa give the nucleophilicity parameters N, which are listed in
Table 2.
Fig. 3 A comparison of the nucleophilicities of 1–3 with other types of
nucleophiles in acetonitrile (N values from ref. 5).
The poor correlation between the nucleophilic reactivities and
pKa values, particularly when nucleophiles with different central
atoms are compared, has so far inhibited quantitative predictions
of the rates of additions and substitutions involving sulphur
nucleophiles. Since, on the other hand, numerous examples have
shown that the benzhydrylium-derived N and sN parameters are
applicable to Michael additions and also to SN2 reactions, it has
now become possible to estimate the rates of numerous reactions
involving the synthetically important S-nucleophiles 1–3 using eqn
(1) and the reactivity parameters given in Table 2.
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft (SFB 749) for fi-
nancial support. Valuable suggestions by Prof. Shinjiro Kobayashi,
Dr. Armin R. Ofial, Dr. Mahiuddin Baidya and Johannes Ammer
are gratefully acknowledged.
Notes and references
1 (a) S. Sato and N. Furukawa, In Science of Synthesis, 2005, 18, 821-
968; (b) F. Duus in Comprehensive Organic Chemistry, Vol. 3 D. N.
Jones, Ed, Pergamon Press, Oxford, 1979, pp 373-487; (c) T.-C. Zheng,
M. Burkart and D. E. Richardson, Tetrahedron Lett., 1999, 40, 603–
606; (d) C. T. Supuran, F. Briganti, S. Tilli, W. R. Chegwidden and A.
Scozzafava, Bioorg. Med. Chem., 2001, 9, 703–714; (e) J. Chiefari, R. T.
A. Mayadunne, C. L. Moad, G. Moad, E. Rizzardo, A. Postma, M. A.
¨
Skidmore and S. H. Thang, Macromolecules, 2003, 36, 2273–2283; (f) O.
Gu¨zel and A. Salman, Bioorg. Med. Chem., 2006, 14, 7804–7815; (g) C.
Lai and B. J. Backes, Tetrahedron Lett., 2007, 48, 3033–3037; (h) D.
J. C. Prasad and G. Sekar, Org. Lett., 2011, 13, 1008–1011; (i) V. K.
Akkilagunta and R. R. Kakulapati, J. Org. Chem., 2011, 76, 6819–6824.
Fig. 2 Plots of log k for the reactions of 1–3 with benzhydrylium ions
(Table 2) versus their electrophilicity parameters E (Table 1) in acetonitrile
at 20 ◦C.
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