Mechanisms of acid decomposition of dithiocarbamates. 1. Alkyl dithiocarbamates

Article abstract of DOI:10.1021/jo971869b

The acid decomposition of some substituted methyldithiocarbamates was studied in water at 25°C in the range of rio -5 and pH 5. The pH-rate profiles showed a bell-shaped curve from which were calculated the acid dissociation constants of the free and conjugate acid species and the specific acid catalysis rate constants k(H). The Bronsted plot of k(H) vs pK(N), the dissociation constant of the conjugate acid of the parent amine, suggests that the acid cleavage occurs through two mechanisms that depend on the pK(N). The plot presents a convex upward curve with a maximum at pK(N) 9.2, which is consistent with the cleavage of the dithiocarbamate anion through a zwitterion intermediate and two transition states. For pK(N) < 9.2, the N-protonation is slower than the C-N bond breakdown. Inverse SIE showed that the zwitterion is formed through a late transition state. At pK(N) > 9.2, the C-N bond breakdown is the slowest step, and according to the inverse SIE, the transition state changes rapidly with the increase of pK(N) to a late transition state. The plot shows a minimum at pK(N) ?10, indicating that a new mechanism emerges at higher values, and it is postulated that it represents a path of intramolecular S to N proton-transfer concerted with the C-N bond breakdown. The thiocarbonyl group acts as a powerful electron- withdrawing group, decreasing the basicity of the nitrogen of the parent amine by 14.1 pK units.

Full text of DOI:10.1021/jo971869b

1598
J . Org. Chem. 1998, 63, 1598-1603
Mech a n ism s of Acid Decom p osition of Dith ioca r ba m a tes. 1. Alk yl
Dith ioca r ba m a tes
Eduardo Humeres,* Nito A. Debacher, M. Marta de S. Sierra, J ose´ Dimas Franco, and
Aldo Schutz
Department of Chemistry, Universidade Federal de Santa Catarina, 88040-900 Florianopolis SC, Brazil
Received October 9, 1997
The acid decomposition of some substituted methyldithiocarbamates was studied in water at 25
°C in the range of Ho -5 and pH 5. The pH-rate profiles showed a bell-shaped curve from which
were calculated the acid dissociation constants of the free and conjugate acid species and the specific
acid catalysis rate constants kH. The Brønsted plot of kH vs pKN, the dissociation constant of the
conjugate acid of the parent amine, suggests that the acid cleavage occurs through two mechanisms
that depend on the pKN. The plot presents a convex upward curve with a maximum at pKN 9.2,
which is consistent with the cleavage of the dithiocarbamate anion through a zwitterion intermediate
and two transition states. For pKN < 9.2, the N-protonation is slower than the C-N bond
breakdown. Inverse SIE showed that the zwitterion is formed through a late transition state. At
pKN > 9.2, the C-N bond breakdown is the slowest step, and according to the inverse SIE, the
transition state changes rapidly with the increase of pKN to a late transition state. The plot shows
a minimum at pKN ∼10, indicating that a new mechanism emerges at higher values, and it is
postulated that it represents a path of intramolecular S to N proton-transfer concerted with the
C-N bond breakdown. The thiocarbonyl group acts as a powerful electron-withdrawing group,
decreasing the basicity of the nitrogen of the parent amine by 14.1 pK units.
In tr od u ction
acid catalysis has been observed,2,4 whereas in other
examples it was not detected.8,9 Previous works on
carbamates10-12 and monothiocarbamates8 have studied
the effect of amine basicity on the reaction rate, general
acid catalysis of the expulsion of weakly basic amines,
and the rate of protonation of the leaving nitrogen, which
is kinetically significant in some of these reactions.
N-Alkyldithiocarbamic acids are relatively stable, and
the kinetics of their decomposition can be measured in a
wide pH range. At the same time, the UV spectra of the
species formed at different acidity of the medium can be
observed, allowing in some cases the acid dissociation
constants to be determined directly.
Several dithiocarbamates, in particular, ethylene bis-
(dithiocarbamate) metallic salts (Zn, Mn, Cu, Fe), are
well-known fungicides. However, their mechanisms of
action upon fungi are speculative1 because their mech-
anisms of decomposition, depending on the basicity of the
amine, have not been studied in detail2 (eq 1). The
reaction of acid cleavage has been postulated to occur
through a concerted intramolecular S to N hydron
transfer and C-N bond breakdown3,4 and (or) through a
zwitterionic intermediate.5-8 Also, in some cases, general
In this work, we studied the pH-rate profiles of the
acid decomposition of substituted methyldithiocarbam-
ates in order to characterize the dependence of the rate
constants on the basicity of the parent amine and the
mechanisms involved. The acid cleavage of aryl and
cycloalkyldithiocarbamates is different,8 and they will be
studied in subsequent papers.
* To whom correspondence should be addressed. Tel.: 55 48 231
9219. Fax: 55 48 231 9711. E-mail: humeres@mbox1.ufsc.br or
humeres@qmc.ufsc.br.
(1) (a) Thorn, G. D.; Ludwig, R. A. The Dithiocarbamates and
Related Compounds; Elsevier: Amsterdam, 1962. (b) Cremlyn, R. J .
In Herbicides and Fungicides; McFarlane, M. R., Ed.; The Chemical
Society Spec. Publ.: London, 1976. (c) Cremlyn, R. J . Pesticides.
Preparation and Mode of Action; Wiley: Chichester, 1978. (d) Corbett,
J . R.; Wright, K.; Baillie, A. C. The Biochemical Mode of Action of
Pesticides; Academic: London, 1984.
(2) (a) Miller, D. M.; Latimer, R. A. Can. J . Chem. 1962, 40, 246.
(b) Reid, D. H., Sr. rep. Organic Compounds of Sulphur, Selenium and
Tellurium; Chem. Soc.: London, 1970; Vol. 1; 1973; Vol. 2; 1975; Vol.
3.
Exp er im en ta l Section
All reagents were of analytical grade. Amines were distilled
before use or crystallized as ammonium salts. Carbon disul-
fide was purified over metallic mercury and phosphorus
pentaoxide followed by distillation.13 The absorptivity of
carbon disulfide in ethanol at 314 nm was found to be 44.4
cm-1‚M-1
.
(3) J oris, S. J .; Aspila, K. I.; Chakrabarti, C. L. Anal. Chem. 1970,
42, 647.
(4) De Filippo, D.; Deplano, P.; Devillanova, F.; Trugu, E. F.; Verani,
G. J . Org. Chem. 1973, 38, 560.
(5) Takami, F.; Tokuyama, K.; Wakahara, S.; Maeda, W. Chem.
Pharm. Bull. 1973, 21, 329.
(6) Takami, F.; Tokuyama, K.; Wakahara, W.; Maeda, T. Chem.
Pharm. Bull. 1973, 21, 1311.
(7) , Takami, F.; Tokuyama, K.; Wakahara, W.; Maeda, T. Chem.
Pharm. Bull. 1973, 21, 594.
(8) Ewing, S. P.; Lockshon, D.; J encks, W. P. J . Am. Chem. Soc.
1980, 102, 3072.
(9) Hallaway, M. Biochim. Biophys. Acta. 1959, 36, 538.
(10) Caplow, M.; Yager, M. J . Am. Chem. Soc. 1967, 89, 4513.
(11) Caplow, M. J . Am. Chem. Soc. 1968, 90, 6795.
(12) J ohnson, S. L.; Morrison D. L. J . Am. Chem. Soc. 1972, 94, 1323.
(13) Brauer, G., Ed. Handbook of Preparative Inorganic Chemistry;
Academic: New York, 1963; Vol. 1, p 652.
S0022-3263(97)01869-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/05/1998

Acid Decomposition of Dithiocarbamates
J . Org. Chem., Vol. 63, No. 5, 1998 1599
Ta ble 1. Dissocia tion a n d Ra te Con sta n ts Rela ted to th e Acid Clea va ge of S-Su bstitu ted Meth yld ith ioca r ba m a tes in
Wa ter a t 25 °Ca
RCH2NHC(S)SH
no.
order
kH,
R
σI
pK+
pKa
pKN
104ko, s-1
M-1‚s-1
1
2
3
4
5
6
7
8
9
CF3
0.42b
0.36b
-1.81c
-5.60c
-4.5e
1.55c
2.00c
2.69f
2.85c
2.82c
2.95c
2.89e
3.02f
3.05e
5.70d
7.52d
172 ( 10
0.61 ( 0.05
0.21 ( 0.01
CH2NH+
C6H5
20.9 ( 0.2
3
0.10b
9.35g
CH2OMe
CH2OH
0.07b
-4.50c
-4.65c
-4.20c
-3.9e
9.20d
18.2 ( 0.6
15.2 ( 0.2
3.2 ( 0.1
1.29 ( 0.07
1.00 ( 0.09
0.29 ( 0.02
0.05b
9.50d
NH3+(CH2)5
0.00f
9.94h
H
C3H7
CH3
0.00b
10.67g
10.59d
10.70g
-0.03b
-0.05b
-4.08i
-4.10e
0.35j
0.54 ( 0.02
4.78 ( 0.04
a
b
d
This work unless indicated; pKN:pKa of the parent amine. Reference 15a. c From the pH-rate profile. Kortum, G., Vogel, W.,
Andrussow, K., Eds. Dissociation Constants of Organic Acids in Aqueous Solution; IUPAC-Butterworths: London, 196. e Reference 5.
f Extrapolated from eq 3. Perrin, D. D. Dissociation Constants of Organic Bases in Aqueous Solution; Butterworths: London, 1965.
g
Extrapolated from the series H3N+(CH2)nN+H3, for n ) 6. Extrapolated from eq 4. Reference 8.
h
i
j
The dithiocarbamates were obtained at room temperature
from the aqueous solution of the corresponding amine, adding
equimolar amounts of carbon disulfide.2a,8,14 In order to have
the amine as the free base, a small excess of sodium hydroxide
was added. The N-(2-aminoethyl) and N-(6-amino-n-hexy-
l)dithiocarbamate sodium salts were prepared from a solution
of the amine buffered at pH 9.5 with sodium carbonate. All
dithiocarbamate salts were crystallyzed in ethanol, except the
N-(2-hydroxyethyl)dithiocarbamate, which was a syrup.
Acid Dissocia tion Con sta n ts. The pK+ and pKa (eq 2) of
the substituted methyldithiocarbamates were in general cal-
culated from the pH-rate profiles of the acid decomposition
(see below). The experimental values of pK+ ) -4.1 and pKa
) 3.05,5,14c of ethyl dithiocarbamate coincided with the kineti-
cally-calculated values.
F igu r e 1. pH-rate profile of the acid decomposition of N-(2-
Kin etics. The decomposition of the dithiocarbamate in
water was followed spectroscopically in the region of 270-280
nm at 25 °C on a Cary 219 spectrophotometer. The initial
concentration was ca. 10-4 M. The acidity ranged between Ho
-4.92 and pH 5. Between pH 2 and 5 the solutions were
buffered at least at two buffer concentrations, and no general
acid catalysis was observed.
Kinetics were all first order. A generalized minimum least-
squares program was used to fit the experimental points to
the theoretical curve of the pH-rate profiles.
aminoethyl)dithiocarbamate in water at 25 °C.
The values obtained from the pH-rate profiles of these
same compounds were used to calculate eq 4 for the pK+
of the conjugate dithiocarbamic acids. Values from the
literature for compounds 3, 7, and 9 were also used for
the calculation.5
pK+ ) -3.91σ1 - 4.20 (n ) 7, r ) 0.952) (4)
Resu lts
Kin et ics of t h e Decom p osit ion of Su b st it u t ed
N-Meth yld ith ioca r ba m a tes. The pH-rate profiles of
the acid decomposition of compounds 1, 4, 5, 6, and 9 in
Table 1 present the same bell-shaped curve as the (2-
aminoethyl)dithiocarbamate (2) shown in Figure 1. The
shape might be due to a change in the rate-limiting step
caused by the acidity of the medium, or it might also be
due to the dissociation of the reactive species. Since the
values of pK+ and the pKa for methyl and ethyldithio-
carbamates (calculated from the pH-rate profile) coincide
with the experimental values, the reaction occurs accord-
ing to Scheme 1, through any of the species SH2+, SH, or
S-. The observed first-order rate constant can be ex-
Acid Dissocia tion Con sta n ts of Su bstitu ted Me-
th yld ith ioca r ba m a tes. Considering the dissociations
of the substituted methyldithiocarbamates (eq 2), the
LFER between pKa and σI15,16 was determined from the
experimental value of compound 9,5 whereas for com-
pounds 2, 4, 5, and 6 the pKa values were calculated from
the pH-rate profiles as shown in eq 3 (Table 1).
pKa ) -2.56σ1 + 2.94 (n ) 5, r ) 0.992) (3)
(14) (a) Delepine, M. Comp. Rend. 1907, 144, 1125. (b) Klopping,
A. L.; van der Kerk, G. J . M. Rec. Trav. Chim. Pays-Bas 1951, 70,
917. (c) Frank, A. W. Phosphorus, Sulfur, Silicon 1990, 54, 109.
(15) (a) Charton, M. J . Org. Chem. 1964, 29, 1222. (b) Charton, M.
Prog. Phys. Org. Chem. 1981, 13, 119.
(16) (a) Exner, O. In Advances in Linear Free Energy Relationships;
Chapman N. B., Shorter, J ., Eds.; Plenum: New York, 1972; Chapter
1. (b) Hansch, C.; Leo, A.; Hoekman, D. Exploring QSAR; American
Chemical Society: Washington, DC, 1995; Vol. 2.
+
pressed by eq 5, where aH ) antilog (-pH or Ho), and ko
ko
kobs
)
(5)
Ka
aH
aH
K+
+
+ 1 +
+

1600 J . Org. Chem., Vol. 63, No. 5, 1998
Humeres et al.
Ta ble 2. Solven t Isotop e Effect for th e Acid
Decom p osition of Som e N-Alk yld ith ioca r ba m a tes in
Wa ter a t 25 °C
RCH2NHC(S)SH
H
R
koD/ko
kD/kH
+
CH2NH3
2.21 ( 0.10
2.40 ( 0.14
2.33 ( 0.03
3.05 ( 0.10
2.90 ( 0.13
3.14 ( 0.18
3.05 ( 0.04
4.00 ( 0.13
CH2OMe
(CH2)5NH3
CH3
+
reactivity of aliphatic cations, information is too scarce
to provide a confident explanation of the increase of pK+
and kH for the acid decomposition of 1.15b,18
Solven t Isotop e Effect. The SIE on ko was deter-
mined for alkyldithiocarbamates with pKN from 7.52 to
10.70 (Table 2). Since ko ) kH Ka, the inverse SIE was
calculated from eq 6. Sulfur acids present low isotopic
D
H
D
kD k0 Ka
)
‚
(6)
H
kH
k0
Ka
fractionation factors (φS-L ) 0.40-0.46),19 giving an
D 20
average value of 1.31 for the ratio KaH/Ka
,
which was
considered constant because of the small range of pKa
values of the compounds studied.
F igu r e 2. Brønsted plot of the specific acid catalysis rate
constants and the pKN of the leaving amine for the acid
decomposition of substituted methyldithiocarbamates in water
at 25 °C: b, piperidinedithiocarbamate;8 k2, rate constant of
the N-protonation; k3, rate constant of the C-N bond cleavage.
Discu ssion
Br øn sted P lot. The maximum in the nonlinear
Brønsted-type plot of Figure 2 is a classical piece of
evidence for a change in the structure of the transition
state of the rate-determining step. The convex upward
curve observed in the range of pKN of 7-10 indicates that
the mechanism of cleavage consists of two consecutive
transition states that change their effective charge on the
nitrogen atom with opposite dependence.16a,21,22 Up to
pKN ) 9.2, the specific acid catalysis rate constant
increases in accordance with growth of the positive
Sch em e 1
charge on the nitrogen, while at higher values of pKN
a
decrease of that charge favors the cleavage. This type
of dependence is consistent with a cleavage of the
dithiocarbamate anion through a zwitterion. In this
range of pKN, a concerted mechanism with asynchronous
proton transfer and C-N bond breakdown has to be ruled
out because of the absence of general acid catalysis and
the observed inverse solvent isotope effect. The possibil-
ity of this path will be discussed below. At a pKN value
of about 10.2, a minimum of kH indicates a change of
mechanism and the rate increases rapidly with the
basicity of the parent amine. These two paths of the
decomposition reaction are shown in Scheme 2. Along
one route, the anion S- is protonated on the nitrogen in
a specific acid catalysis step and the zwitterion SH(
formed decomposes into products. Along the other path,
the free dithiocarbamic acid decomposes through a
concerted mechanism. Applying steady-state approxima-
in general is equal to the average value of kobs at the
plateau of the profile due to the rather large difference
between K+ and Ka (eq 2). Also, ko is kinetically equiva-
lent to kOH KW/K+, k1, or kHKa depending on which
reactive species is actually involved. However, the
kinetic alternative of decomposition of the conjugate acid
with specific base catalysis has to be disregarded, since
ko is of the order of 10-3-10-4 s-1, and consequently kOH
should be 1014-1017 M-1 s-1, much larger than the
diffusion-controlled rate constant. In Table 1 are shown
ko and kH for the series of substituted methyldithiocar-
bamates, and the Brønsted plot of the specific acid
catalysis rate constants kH vs the pKN of the parent amine
is shown in Figure 2.
(17) Stock, L. M.; Wasielewski, M. R. Prog. Phys. Org. Chem. 1981,
13, 253.
(18) Staley, R. H.; Taagepera, M.; Henderson, W. G.; Koppel, I.;
Beauchamp, J . L.; Taft, R. W. J . Am. Chem. Soc. 1977, 99, 326.
(19) Schowen, K. B. J . In Transition States of Biochemical Processes;
Gandour, R. D., Schowen, R. L., Eds.; Plenum: New York, 1978;
Chapter 6.
(20) Melander, L.; Saunders, W. H., J r. Reaction Rates of Isotopic
Molecules; Wiley: New York, 1980; Chapter 7.
(21) Williams, A. Acc. Chem. Res. 1989, 22, 387.
(22) Leffler, J . E.; Grunwald, E. Rates and Equilibria in Organic
Reactions; Wiley: New York, 1963; Chapter 7.
(Trifluoroethyl)dithiocarbamate (1) presents a pK+
value that is 4 units higher than expected from eq 4 and
also reacts faster than the corresponding DTC with
similar pKN. Several contributions (polar effect, π induc-
tive effect, carbon-fluorine hyperconjugation, 1,3-pp
interactions) may affect the behavior of this substituent.17
Concerning the role of the trifluoromethyl group in the

Acid Decomposition of Dithiocarbamates
J . Org. Chem., Vol. 63, No. 5, 1998 1601
Sch em e 2
is substituted by sulfur, the substituent constant in-
creases to +1.39.8 Considering that the substitution of
the second oxygen produces the same effect, the sub-
stituent constant of the adjacent dithiocarboxylate group
should be σCSS ) +1.80, and therefore, pK( is expected
to be some 15 pK units lower than pKN. This value
indicates that the protonation of water by the zwitterion
is thermodinamically favorable and k-2 should be of the
order of 1010 s-1 23,24
allowing an estimation of k2 and
,
consequently k3. The ratio k3/k2 is much smaller than
K(, and k3 ≈ kHK(. On the other hand, at the maximum
of the Brønsted plot (compound 4), k2 should be equal to
k3 ) 1.14 × 105 s-1, and therefore, pK( ) -4.94, that is
14.1 pK units lower than pKN, similar to the value
obtained above (eq 11). The experimental values of kH
and the calculated values for k2 and k3 are shown in
Figure 2.
tion on SH(, the rate law of disappearance of the total
+
substrate ST ) S- + SH + SH2 is given by eq 7, where
pK( ) pKN - 14.1
(11)
So, ST and ST,∞ are the total concentration of the substrate
at zero time, time t, and infinite time, respectively (see
the Supporting Information).
The difference of free energy of activation between
transition states T2 and T3 is only 3.4 kcal‚mol-1 for
compound 4. This small difference means that both
transition states control the overall reaction rate. The
zwitterion intermediate is a high energy and almost a
high barrier intermediate. An important consequence of
these considerations is that solvent isotope effect experi-
ments will characterize the structure of a virtual transi-
tion state with the characteristics of both T2 and T3.
The pK( of the zwitterion is smaller than the solvated
proton, so therefore, the proton transfer for N-protonation
is thermodynamically unfavorable and general acid
catalysis is not expected to be observed, and this was
confirmed in our experiments.
According to the calculated values of k2 and k3 (Figure
2), the rate of N-protonation is faster than the C-N bond
cleavage, up to pKN ) 9.2. At higher values of pKN the
last step becomes the slowest. The rate of the C-N bond
cleavage decreases steadily to a minimum where pKN is
about 10.5 due to the higher stability of the zwitterion.
The curvature of the line of log k3 vs pKN suggests a
rather fast increase of the C-N bond cleavage at the
transition state in a short range of pKN values. This
interpretation is supported by the results of the solvent
isotope effect.
The minimum of log kH followed by a fast increase of
the basicity of the amine (Figure 2) characterizes a
change of mechanism.16a,22 It seems that no intermo-
lecular mechanism reasonably accounts for the fast
increase of the rate constant of decomposition of the
dithiocarbamates with increasing pKN. Both k3 and K(
decrease as the basicity of N increases. Path 1 in Scheme
2 represents a mechanism of direct intramolecular hy-
dron transfer concerted with the C-N bond breakdown,
in a pH-independent process, through the acid form of
the dithiocarbamate, which can be acid-base catalyzed
by a water molecule. This mechanism, without the
predissociation of the dithiocarbamic acid, must be an
energetically preferred alternative to the intermolecular
protonation of N, when its basicity and also the strength
of the C-N bond increases. Basicity of the nitrogen
increases faster than the acidity of the thiol sulfur, and
k2k3Ka
k1 +
dST
dt
k3 + k-2
-
)
(ST - ST,∞) -
Ka
aH
aH
K+
+
[
]
+ 1 +
+
k-2k-3
+ k-1 (2So - ST,∞ - ST)(ST,∞ - ST) (7)
(
)
k3 + k-2
When the reaction is carried out under acidic condi-
+
tions where aH . KN, the acid dissociation constant of
the parent amine, the reverse reaction constants k-3 and
k-1, are zero, and the experimental rate constant can be
expressed by eq 8, which is equivalent to eq 5, where the
numerator is ko. The rate constant of the concerted path
k2k3Ka
k1 +
k3 + k-2
kobs
)
(8)
Ka
aH
aH
K+
+
+ 1 +
+
is k1 and the term k2k3/(k3 + k-2) ) kH represents the
specific acid catalysis rate constant of the mechanism of
decomposition through the zwitterion. This expression
can also be written as eq 9, where K( ) k-2/k2 is the acid
dissociation constant of the N-protonated zwitterion.
k3
kH
)
(9)
(k3/k2) + K(
The pKN of substituted methylammonium ions is given
by eq 10,15a and substituents adjacent to the nitrogen
pKN ) -8.57σ1 + 10.29 (n ) 9, r ) 0.997)
(10)
atom, such as the dithiocarboxylate group CSS-, would
cause a constant decrease in pKN equal to -8.57σCSS
,
where σCSS is the substituent constant of the dithiocar-
boxylate. Since this group is conjugated to the nitrogen,
it is expected to have a high positive value because it
works as an electron sink. For N-protonated alkylcar-
bamates, -8.57σC was estimated8 to be -8.4, or σC
)
(23) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1.
(24) Williams, A. J . Am. Chem. Soc. 1976, 98, 5645.
+0.95, for the carboxylate group. When one oxygen atom

1602 J . Org. Chem., Vol. 63, No. 5, 1998
Humeres et al.
once the concerted mechanism is preferred, the rate
increases rapidly with pKN.
change of solvent isotope effect observed for compounds
2, 4, and 6 must be mainly a consequence of the change
H
of the ratio of K(H/K(D, which is equal to (k2D/k2H)(k-2
/
It has been observed that the delocalization of the
nitrogen electron pair into the dithiocarbamate group
shortens the C-N bond length, because of the higher
double-bond character, and modifies the infrared spectra
of dithiocarbamates.25-27 The barrier of internal rotation
about the C-N bond is considerably higher in N,N-
dialkylthioamides than in N,N-dialkylamides, due to the
higher double-bond character of the C-N bond.28-31 The
rotation increases in dilute acid and is solvent depend-
ent.32,33
k-2D). Since k-2 is diffusion controlled, with a low barrier
to hydron transfer, it does not depend much on K(. The
rate-limiting step is the encounter of the zwitterion with
a water molecule that should be independent of the
isotope, and the SIE should be unity, except for the
viscosity effect between H2O and D2O.39 Therefore, the
D
ratio K(H/K( reflects essentially the primary solvent
isotope effect on the O to N hydron transfer reaction.
Approximate values of primary solvent isotope effects for
hydron transfer may be obtained through the method
described by Schowen.40 The transition state for the O
to N hydron transfer is
To reach the structure of transition state I, the C-N
bond has to be twisted, thus inhibiting the resonance of
1-ø
O-----L--ø---N
where ø indicates the bond order of the bond being
formed. For the initial state (ø ) 0) there is no isotope
effect. The equilibrium inverse isotope effect (eq 13)
is equal to 3.11.40,41 The maximum primary isotope
K(
K(
(φ2O-L) (φ2
)
+-L
D
the thiocarbonyl group with the nitrogen and increasing
its basicity. The reaction may be catalyzed by a water
molecule. The basicity of the nitrogen also increases with
the breaking of the C-N double bond until the process
of hydron transfer S to N becomes thermodynamically
favorable. The internal rotation barrier of N,N-dialky-
lthioamides is very similar to that observed for the
cleavage of dithiocarbamates of strong basic amines,
suggesting that the twisting of the C-N bond is an
important component of the total kinetic barrier.
N
H
k2D/k2
)
)
(13)
(φ3
H
(φN-L
)
)
O
+-L
effect k2H/k2 ) 11.4 is reached at ømax ) 0.53. The plot
D
of k2H/k2 vs ø gives an inverse SIE only when ø > 0.97,
D
indicating that the transition state T2 is late or tight in
the reaction coordinate of formation of the zwitterion.
Since the contribution of the term k3D/k3 is small and
H
k-2H/k-2 is constant, the main contribution to the SIE
D
Solven t Isotop e Effect. The observed SIE of Table
2 is consistent with the proposed mechanisms. Consider-
ing that k3/k2 , K(, the inverse solvent isotope effect is
given by eq 12 according to the mechanism through the
comes from the primary effect. The inverse SIE increases
from compound 2 to compound 4, suggesting that for
compound 2 there is a partial transfer of the hydron at
the virtual transition state. If the maximum inverse SIE
D
zwitterion (Scheme 2). The ratio K(H/K( is difficult to
H
is obtained at equilibrium (ø ) 1) where k2D/k2 ) 3.11,
the experimental value of 3.14 agrees well for compound
4 and at the same time indicates that the secondary effect
due to the C-N bond fission is near unity.
D
H
D
H
D
H
D
kD k3 K(
k3
k3
k2
k-2
k-2
)
‚
)
(12)
H
D
H
(
) ( ) (
)
kH
k3
K(
k2
sec
pri
pri
H
The inverse secondary SIE k3D/k3 in terms of the
fractionation factors40,42,43 is equal to 1 for ø ) 0 and 0.90
for ø ) 1. Therefore, if the maximum primary inverse
SIE is reached at compound 4, the decrease from com-
pound 4 to 6 can be ascribed to an increase of the C-N
bond cleavage to a later transition state T3. These
conclusions are entirely consistent with the Brønsted plot
in the range of pKN 7.5-9.9. In this range of pKN, the
SIE reflects a virtual transition state that changes from
a partial hydron transfer to N to a partial C-N bond
cleavage.
assess because estimation of ∆pK for strong acids in
regions beyond the pKa of water is rather problematic.34-38
Since k3D/k3 is a secondary SIE, consequently small, the
H
observed effect shows that K(H/K( > 1, that is, the
D
N-protonation is stabilized in D2O. The magnitude of the
(25) Cox, B. G.; de Maria, P. J . Chem. Soc., Perkin Trans. 2 1977,
1385.
(26) Wahlberg, A. Acta Chim. Scand. 1976, 30, 433.
(27) Chatt, J .; Duncanson, L. H.; Venanzi, L. M. Suom. Kemistil. B
1956, 29, 75.
(28) Loewenstein, A.; Melera, A.; Rigny, P.; Walter, W. J . Phys.
Chem. 1964, 68, 1597.
(29) Sandstrom, J . J . Phys. Chem. 1967, 71, 2318.
(30) Neuman, R. C., J r.; J onas, V. J . Phys. Chem. 1971, 75, 3532.
(31) Neuman, R. C., J r.; J onas, V. J . Org. Chem. 1974, 39, 292.
(32) Walter, W.; Schaumann, E. Chem. Ber. 1971, 104, 3361.
(33) Walter, W.; Franzen-Sleveking, M.; Schaumann, E. J . Chem.
Soc., Perkin Trans. 2 1975, 528.
(34) Rule, C. K.; LaMer, V. K. J . Am. Chem. Soc. 1938, 60, 1974.
(35) Ho¨gfeldt, E.; Bigeleisen, J . J . Am. Chem. Soc. 1960, 82, 15.
(36) Schubert, W. M.; Burkett, M. J . Phys. Chem. 1956, 78, 64.
(37) Pritchard, J . G.; Long, F. A. J . Am. Chem. Soc. 1958, 80, 4162.
(38) Laughton, P. M.; Robertson, R. E. In Solute-Solvent Interac-
tions; Coetzee, J . F., Ritchie, C. D., Eds.; Dekker: New York, 1969;
Chapter 7.
The new increase of SIE for compound 9 (ethylDTC)
represents a change of mechanism. Unfortunately, the
fractionation factor for the dithiocarbamic S-L bond is
(39) Perrin, C. L.; Dwyer, T. J .; Baine, P. J . Am. Chem. Soc. 1994,
116, 4044.
(40) Schowen, R. L. Progr. Phys Org. Chem. 1972, 9, 275.
(41) Gold, V. Adv. Phys. Org. Chem. 1969, 7, 259.
(42) Kresge, A. J . Pure Appl. Chem. 1964, 8, 243.
(43) Schowen, R. L. In Isotope Effects on Enzyme Catalyzed Reac-
tions; Cleland, W. W., O’Leary, M. H., Northrup, D. B., Eds.; University
Park: Baltimore, 1977; pp 64-69.

Acid Decomposition of Dithiocarbamates
J . Org. Chem., Vol. 63, No. 5, 1998 1603
not known so the estimation of the SIE at equilibrium is
impossible.
N intramolecular proton transfer of the dithiocarbamic
acid, concerted with the breaking of the C-N bond.
Ack n ow led gm en t. This manuscript was written in
part during the stay of E.H. at the Chemistry Depart-
ment of University College, London, as an Academic
Visitor. We thank Professor Brian Capon for his com-
ments. We dedicate this paper to Professor Waldemar
Adam, on his 60th birthday, for his outstanding contri-
bution to the physical organic chemistry of photon-
induced processes.
Con clu sion s
It is proposed that the acid cleavage of alkyldithiocar-
bamates occurs through two mechanisms, depending on
the pKN of the parent amine. At pKN < 10.5 they
decompose through a zwitterionic intermediate whose
N-protonation is slower than the C-N bond breakdown
when pKN < 9.2. At pKN > 9.2 the C-N bond breakdown
is the slowest step.
The thiocarbonyl group is a powerful electron sink that
decreases the basicity of the nitrogen of the parent amine
by 14.1 pK units.
Su p p or tin g In for m a tion Ava ila ble: Kinetics analysis to
obtain eq 7 (5 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
For parent amines with pKN higher than ca. 10, a new
mechanism emerges that is proposed to occur by an S to
J O971869B