Hydrolysis and aminolysis of alkyl xanthate esters and cellulose analogues

Article abstract of DOI:10.1139/v99-107

The hydrolysis and aminolysis of a series of S-substituted O-alkylxanthate esters was studied in 20% v/v aqueous methanol at 35°C. The pH-rate profiles of the hydrolyses showed water and hydroxide-ion-catalyzed reactions. The reaction of 2,4-dinitrophenyl cellulose xanthate (CelXDNP) and p-nitrobenzyl cellulose xanthate (CelXNB) with polyalanine and lysozyme produced a covalent bond between the polypeptide and the cellulose matrix, as shown by solid-state ¹³C NMR. However, the nature of the bonding could not be identified. The reaction of nucleophiles (H₂O, OH^-, RNH₂) and xanthic esters was consistent with an addition-elimination mechanism through a tetrahedral intermediate. Bronsted plots against the pK_a of the nucleophile (β_nu) or the nucleofuge of the substrate (β_lg) were used to characterize the rate-determining step. The pK_a values of the nucleophiles ranged between -1.74 and 15.74, and for the nucleofuges, they were in the range of 10.50-0.92. For nucleophiles with pK_a values up to about 10, β_lg was 0.10-0.15, and β_nu changed from 0.48 to 0.35 for the strongest electron-withdrawing nucleofuge. It was concluded that the water-catalyzed hydrolyses, and also aminolyses with moderately basic amines, occur with rate-determining formation of the tetrahedral intermediate. For strong bases such as hydroxide ion, the disappearance of the intermediate becomes the slowest step. The reaction of cellulose xanthic esters with external nucleophiles as hydroxide ion and amines shows simple first-order kinetics and is slower than alkyl or sugar xanthates, probably due to the diffusion effect through the tight cybotactic region of cellulose.

Full text of DOI:10.1139/v99-107

1050
Hydrolysis and aminolysis of alkyl xanthate
esters and cellulose analogues
Eduardo Humeres, Valdir Soldi, Marilene Klug, Mauricéa Nunes,
Célia M.S. Oliveira, and Patrick J. Barrie
Abstract: The hydrolysis and aminolysis of a series of S-substituted O-alkylxanthate esters was studied in 20% v/v
aqueous methanol at 35°C. The pH–rate profiles of the hydrolyses showed water and hydroxide-ion-catalyzed reactions.
The reaction of 2,4-dinitrophenyl cellulose xanthate (CelXDNP) and p-nitrobenzyl cellulose xanthate (CelXNB) with
polyalanine and lysozyme produced a covalent bond between the polypeptide and the cellulose matrix, as shown by
solid-state 13C NMR. However, the nature of the bonding could not be identified. The reaction of nucleophiles (H2O,
OH–, RNH2) and xanthic esters was consistent with an addition–elimination mechanism through a tetrahedral
intermediate. Brφnsted plots against the pKa of the nucleophile (βnu) or the nucleofuge of the substrate (βlg) were used
to characterize the rate-determining step. The pKa values of the nucleophiles ranged between –1.74 and 15.74, and for
the nucleofuges, they were in the range of 10.50–0.92. For nucleophiles with pKa values up to about 10, βlg was
0.10–0.15, and βnu changed from 0.48 to 0.35 for the strongest electron-withdrawing nucleofuge. It was concluded that
the water-catalyzed hydrolyses, and also aminolyses with moderately basic amines, occur with rate-determining
formation of the tetrahedral intermediate. For strong bases such as hydroxide ion, the disappearance of the intermediate
becomes the slowest step. The reaction of cellulose xanthic esters with external nucleophiles as hydroxide ion and
amines shows simple first-order kinetics and is slower than alkyl or sugar xanthates, probably due to the diffusion
effect through the tight cybotactic region of cellulose.
Key words: hydrolysis, aminolysis, alkyl xanthic esters, cellulose xanthic esters, sugar xanthic esters.
Résumé : Opérant à 35°C, dans un mélange à 20% v/v de méthanol aqueux, on a étudié l’hydrolyse et l’aminolyse
d’une série d’esters O-alkylxanthiques S-substitués. Les profils pH–vitesse de réaction d’hydrolyse montrent que l’eau
et l’ion hydroxyde catalysent les réactions. Les réactions du cellulose xanthate de 2,4-dinitrophényle (CeIXDNP) et du
cellulose xanthate de p-nitrophényle (CelXNB) avec la polyalanine et la lysosyme conduisent à la formation d’une
liaison covalente entre le polypeptide et la matrice de cellulose, comme on a pu le montrer par RMN du 13C à l’état
solide. Toutefois, il n’a pas été possible de déterminer la nature de la liaison. La réaction des nucléophiles (H2O, OH–,
RNH2) avec les esters xanthiques est en accord avec un mécanisme d’addition–élimination impliquant un intermédiaire
tétraédrique. On a utiliser les courbes de Brønsted en fonction du pKa du nucléophile (βnu) ou du nucléofuge du
substrat (βlg) pour caractériser l’étape cinétiquement limitante. Les valeurs de pKa des nucléophiles s’étalent de –1,74 et
15,74 alors que celles des nucléofuges vont de 10,50 à 0,92. Pour les nucléophiles de valeurs de pKa allant
jusqu’environ 10, les valeurs de βlg va de 0,10 à 0,15 alors que pour βnu elles vont de 0,48 à 0,35 pour le nucléofuge
portant le groupe électroattracteur le plus fort. On en conclut que l’hydrolyse catalysée par l’eau et l’aminolyse à l’aide
d’amines de basicité modérée se produisent avec formation cinétiquement limitante de l’intermédiaire tétraédrique. Pour
des bases fortes, telles que l’ion hydroxyde, la disparition de l’intermédiaire devient l’étape la plus lente. La cinétique
de la réaction des esters xanthiques de la cellulose avec des nucléophiles externes, tels que l’ion hydroxyde et les
amines, est du premier ordre simple et ces réactions sont plus lentes que celles des xanthates d’alkyles ou de sucres; ce
résultat est probablement dû à l’effet de diffusion à travers la région cybotactique compacte de la cellulose.
Mots clés : hydrolyse, aminolyse, esters xanthiques d’alkyles, esters xanthiques de la cellulose, esters xanthiques
de sucres.
[Traduit par la Rédaction] Humeres et al. 1056
Received December 2, 1998.
This paper is dedicated to Jerry Kresge in recognition of his many achievements in chemistry.
E. Humeres,1 V. Soldi, M. Klug, M. Nunes, and C.M.S. Oliveira. Departamento de Química, Universidade Federal de Santa
Catarina, Florianópolis, SC, 88040-900, Brazil.
P.J. Barrie. Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, U.K.
1Author to whom correspondence may be addressed. Telephone: 55 48 331 9219. Fax: 55 48 331 9711.
e-mail: humeres@mbox1.ufsc.br
Can. J. Chem. 77: 1050–1056 (1999)
© 1999 NRC Canada

Humeres et al.
1051
anhydrous sodium sulfate, and distilled under vacuum: bp
160°C/8 mmHg (lit. (14) 143°C/3 mmHg); λmax (ethanol)
280 nm.
Introduction
Xanthic esters have been used in the synthesis of trithio-
carbonates (1), in Friedel–Crafts reaction (2), Chugaev’s re-
action (3), and in the synthesis of thiols (4, 5), and also as
derivatives for the isolation of carbohydrates (6). The hydro-
lysis of xanthic esters occurs as shown in eq. [1], and they
react with amines displacing the thiol and forming a thion-
carbamate ester (5). Thioncarbamates have shown high spec-
ificity as collectors in the flotation of sulfide minerals (7).
S-p-Nitrobenzyl O-ethylxanthate (EXNB)
EXK (2.2 g) dissolved in 10% aqueous EtOH, was al-
lowed to react at room temperature with a solution of 2.1 g
of p-nitrobenzyl bromide (acetone–ethanol). The reaction
was followed by the appearance of the maximum at 280 nm.
KBr was eliminated by filtration, and the solvent was evapo-
rated in a rotatory evaporator. The product was recrystallized
in ethanol: mp 61.6°C.
H2O
+
R2SH
+
COS
R1OH
[1]
R1O C(S) SR2
R3NH2
S-Phenyl O-ethylxanthate (EXP)
+
R1O C(S) NHR3 R2SH
A solution of sodium ethoxide prepared from 2.3 g of
sodium in 50 mL of dried ethanol was slowly added to a so-
lution of 12 g of thiophosgene dissolved in 100 mL of chlo-
roform at 0°C, and it was allowed to react for 3 h to obtain a
solution of ethyl chlorothionoformate that was washed with
water and dried over anhydrous magnesium sulfate. The sol-
vent was stripped off in a rotatory evaporator, and the prod-
uct was used without further purification (15a, b). The
reaction of 1 g of sodium thiophenolate in 5 mL of dried
ethanol with 1 g of ethyl chlorothionoformate produced EXP
after 15 min of reaction at room temperature. Crystals of
NaCl were filtered off, and the solution was treated with an
aqueous solution of phosphate buffer at pH 8, the product
then being extracted with diethyl ether and dried over anhy-
drous magnesium sulfate. Evaporation of diethyl ether left a
yellow oil that was identified as EXP:TLC, alumina, hex-
ane:ethyl acetate (1:1), one spot; λmax 285 nm; after reaction
with NaOH, λmax 265 nm (thiophenol); after reaction with
ethylamine, λmax 245 nm (thioncarbamate) (15c).
The study of the reactivity of xanthate ester moieties co-
valently bound to cellulose showed that the reaction of water
was much faster compared to small analogue molecules (8).
The water-catalyzed hydrolysis of p-nitrobenzyl (CelXNB)
and 2,4-ditrophenyl cellulose xanthate (CelXDNP) occurs
through two parallel processes (9, 10). The faster hydrolysis
was ascribed to the reaction of the C-2 + C-3 isomers,
whereas the slower hydrolysis corresponds to the C-6 iso-
mer. The fast hydrolysis is due to an entropic effect of a
well-oriented water molecule catalyzed by a second mole-
cule that acts as a general base, as shown by proton inven-
tory. Nucleophiles such as hydroxide ions and amines do not
discriminate between the isomers, and the kinetics are first
order (9).
In this paper, we seek to extend a previous study of the
hydrolysis and aminolysis of a series of S-substituted O-
ethylxanthate esters (11), to include sugar analogues and
2,4-dinitrophenyl cellulose xanthate, CelXDNP, a cellulose
ester with a better leaving group, in order to get an insight
into the mechanism of nucleophilic attack on cellulose
xanthate esters and small molecule analogues.
S-p-Nitrophenyl O-ethylxanthate (EXNP)
Ethyl chlorothionoformate (3.5 g), obtained as described
above, was added to 1.45 g of p-nitrothiophenol in 1.0 mL
of pyridine, and then the temperature was raised to 60°C for
1 h. The precipitate was dissolved in 30 mL of chloroform
and washed with water, subsequently being dried and then
concentrated in a rotatory evaporator. Crystals were obtained
after 8 h in the refrigerator: mp 51°C (lit. (16) 50°C).
Experimental
All reagents were of analytical grade and were used with-
out further purification except the amines that were previ-
ously distilled in a high efficiency distilling column and kept
under nitrogen atmosphere at low temperature.
The solid-state 13C CP/MAS TOSS NMR measurements
were performed using a Bruker MSL-300 spectrometer. All
S-2,4-Dinitrophenyl O-ethylxanthate (EXDNP)
1
EXK (9.2 g) dissolved in 30 mL of water was mechani-
cally shaken with a solution of 10.1 g of 1-fluoro-2,4-di-
nitrobenzene in 300 mL of methylene chloride, for 64 h at
room temperature. The methylene chloride phase was washed
with water and dried over anhydrous magnesium sulfate.
The solvent was stripped off in a rotatory evaporator, and
the residue was crystallized in methanol: mp 43.0°C; λmax
267 nm; ms, mol. wt. 288 g mol–1. Anal. (calculated values
for C9H8N2O5S2 in parentheses): C 37.5 (37.5), H 2.7 (2.8),
N 9.7 (9.7), S 21.5 (22.0).
xanthate esters were identified by H NMR and IR spectra.
S-Ethyl O-ethylxanthate (EXE)
Potassium O-ethylxanthate (EXK) was obtained using the
classical procedure (12), adding carbon disulfide to a cooled
solution of potassium hydroxide in ethanol. The product was
recrystallized twice in ethanol; λmax (ethanol) 301 nm.
S-ethyl O-ethylxanthate was obtained after refluxing for 4 h,
using an equimolar amount of EXK and ethyl bromide in
ethanol. The product was washed with water, dried over an-
hydrous sodium sulfate, and distilled under vacuum: bp
76°C/10 mmHg (1 mmHg = 133.3 Pa) (lit. (13) 78°C/18 mmHg);
λmax 283 nm.
Methyl -D-glucopyranoside 6-(S-benzyl xanthate)
(MGXB)
CS2 (2.5 mL) was added to a solution of 22.9 g of α-
methyl-D-glucopyranoside in 23.6 mL of water, with mag-
netic stirring at room temperature, and then, slowly, 6 mL of
20 M NaOH was also added. After being allowed to react
S-Benzyl O-ethylxanthate (EXB)
EXK and benzyl bromide (1:1 mol) were refluxed for 6 h
in ethanol. The product was washed with water, dried over
© 1999 NRC Canada

1052
Can. J. Chem. Vol. 77, 1999
Fig. 1. pH–rate profile of the hydrolysis of S-phenyl O-
ethylxanthate at 35°C in 20% v/v aqueous methanol, µ = 0.1
(KCl).
for 5 h, the solution was neutralized with acetic acid cooled
to 10°C. Benzyl bromide, 11.0 g, in 20 mL of methylene
chloride, was then put in slowly, and the stirring was kept
up for 2 h. The product was extracted with chloroform, and
the solution was dried over anhydrous sodium sulfate. The
solvent was evaporated under vacuum. The product was pu-
rified by column chromatography using alumina and eluted
°
25
with hexane–CCl4–ethanol: Rf 0.66; λmax 284 nm;
+80.3° (lit. +79.8°) (6).
=
[α]D
S
R
CH2
S
C O CH2
HO
O
HO
OH
_
OCH3
)
6
R = H ( MGXB), NO2 ( MGX
The preparation of methyl α-D-glucopyranoside 6-(S-p-
nitrobenzyl xanthate) (MGX-6) has been already reported
(10).
2,4-Dinitrophenyl cellulose xanthate (CelXDNP) and p-
nitrobenzyl cellulose xanthate (CelXNB) were obtained
from commercial cotton tissue as described previously (9,
10), and were characterized from the degree of substitution
DS (number of xanthate ester groups per 100 glucoanhy-
dropyranose units) and the solid-state 13C NMR spectra.
Results
pH–rate profiles
The pH–rate profiles of the series of S-substituted O-ethyl
xanthates were obtained in 20% v/v aqueous methanol at
35°C. They are all similar to the example shown in Fig. 1,
where kobs is the rate constant extrapolated to zero buffer
concentration, and can be expressed by eq. [2]. There is
Reaction of CelXDNP and CelXNB with polypeptides
The reaction of cellulose esters with polyalanine (mol. wt.
1000–5000) and lysozyme was studied in dried acetone and
in water saturated at pH 10, with the polypeptide at room
temperature under nitrogen atmosphere. The product was
exhaustively washed with water, ethanol, and diethyl ether,
and finally dried under vacuum. The modified celluloses
were analyzed by solid-state 13C NMR.
[2]
kobs = kH2O + kOH[OH–]
a pH-independent region with rate constant kH2O of the
water-catalyzed reaction, followed at high pH by a hydrox-
ide-catalyzed reaction with second-order rate constant kOH
.
Table 1 shows the rate constants obtained, including those of
some cellulose and sugar xanthate esters. The continuous
line in Fig. 1 was drawn using the rate constant values of
Table 1.
For the water-catalyzed hydrolysis of CelXNB and CelXDNP,
there are two parallel reactions with rate constants k′H2O for
the fast hydrolysis and k′ ′H2O for the slower one. We have
included these values in order to compare them with those of
the series of S-substituted O-ethylxanthates and methylglu-
cose xanthates analogues.
Kinetics
The hydrolyses and aminolyses were carried out in 20%
v/v aqueous methanol, at 35°C. The kinetics were followed
spectrophotometrically by the disappearance of the xanthate
at appropriate wavelengths during at least three half-lives
and were always pseudo-first order. The pH and pKa values
were corrected to the appropiate temperature (17).
In the range of pH 3–11, the hydrolyses were carried out
in the presence of buffers at 10–30 mM concentrations, and
the value of kobs was extrapolated to zero buffer concentra-
tion.
For the aminolyses, the amine itself acted as buffer. For
each ester and amine, the reaction was measured at three
pH values in the range of pKa ±1 of the amine. For each
amine, the second-order rate constant kN for the aminolysis
by the free amine was obtained from a plot of k2, the sec-
ond-order rate constant at each pH, against the molar frac-
tion of the free amine. The ester concentration was ca. 10–4
M, and the amine concentration was 0.03–0.1 M. The ionic
strength was maintained at 0.1 (KCl).
Aminolyses
The aminolyses were carried out in 20% aqueous metha-
nol and at low ionic strength (0.1 M KCl), because the low
solubility of xanthate esters produces plots of kobs vs. NT, to-
tal amine concentration, that deviate from linearity due to
changes in the activity coefficients of the species involved
(18).
The aminolyses were carried out with ethylenediamine
(EDA, pK1), ethanolamine (EA), and n-butylamine (BA).
© 1999 NRC Canada

Humeres et al.
1053
Table 1. Rate constants for the hydrolysis of some xanthate
Table 2. Second-order rate constants for the aminolysis of some
esters in 20% v/v aqueous methanol at 35°C.a
xanthic esters by free amines at 35°C.a
Ester
pKa(RSH)
kH2O (s–1)
kOH (M–1 s–1)
Ester
EDA
7.27
EA
BA
10.27
3.26 × 10–6
1.57 × 10–6
1.35 × 10–6
5.20 × 10–6
2.54 × 10–6
3.70 × 10–5
1.33 × 10–6
4.57 × 10–7
2.97 × 10–3e
2.27 × 10–3b,c
3.83 × 10–2
13.7 × 10–2
10.5 × 10–2c
92.9 × 10–2c
13.8c
2.84
5.39
2.65 × 10–2c
pKa(RNH+3 )
9.21
102 kN (M–1 s–1)
2.90
8.15
8.40
2.50
13.5
20.6
38.7
EXE
EXB
EXNB
EXP
EXNP
EXDNP
MGXB
MGX-6d
CelXNB
10.50
9.43
8.60
6.43
4.50
0.92
9.43
8.60
8.60
EXE
EXB
0.27
0.59
1.03
0.46
2.38
4.02
10.8
9.45
6.25
14.7
EXNB
CelXNBb
EXP
EXNP
EXDNP
CelXDNP
12.0
3.45
29.6
32.3
138.7
36.3
k′H2O
k′ ′H2O 4.29 × 10–5e
k′H2O
1.37 × 10–2
k′ ′H2O 6.52 × 10–5
CelXDNP
0.92
37.5 × 10–2c
23.8
aIn 20% v/v aqueous methanol; µ = 0.1 (KCl).
bReference 9.
aµ = 0.1 (KCl).
b20% aqueous dioxane.
c
µ = 1.0 (KCl).
dReference 10.
e10% aqueous ethanol.
Table 3. Reaction of cellulose xanthate esters with polyalanine and lysozyme.
Ester
Polypeptide
C=O/mol
Area(C=O)
Area(C-1)
DSd
CelXDNPa
CelXDNPa
CelXDNPa
CelXNBe
CelXNBe
CelXNBe
CelXNBe
CelXNBh
PolyAlab
70.4–14.1c
129
2.46
16.95
22.8
24.8
26.2
34.7
21.3
1.2
26.29
23.64
43.4
12.1
19.5
21.8
20.5
12.3
0.1–0.7c
0.6
Lysozymeb
Lysozymef
PolyAlaf
129
0.4
70.4–14.1c
70.4–14.1c
129
2.9–14.6c
1.9–9.5c
1.2
PolyAlaf,g
Lysozymef
Lysozymef,g
Lysozymei
129
129
0.8
0.1
aDS = 7.9 (aminolysis); DS = 14.8 (NMR).
bIn dried acetone, 48 h reaction.
cFor molecular weight in the range of 5000 and 1000, respectively.
dNumber of moles of polypeptide per 100 glucopyranoside units.
eDS = 15.2 (aminolysis); DS = 27.6–35.2 (NMR), DS = 29.1 (S).
fIn aqueous saturated solution, 48 h reaction.
gAfter washing again exhaustively with water.
hDS = 6.76 (aminolysis); DS = 4.24 (NMR).
iIn aqueous solution, 148 h reaction. A DS = 1.07 with lysozyme would duplicate the weight of the CelXR.
The plots of kobs vs. NT were all linear and can be repre-
produced the bonding. The DS of the cellulose after reaction
was calculated from the area of the signal of the carbonyl
groups at about 177 ppm and the area of the signal due to
C-1 of cellulose in the region of 90–110 ppm according to
eq. [4]. In general, the DS was higher for CElXNB, probably
sented by eq. [3],
[3] kobs = ko + kN[N]
where ko is the rate constant including all the terms of hy-
drolysis, and kN and [N] are the second-order rate constant
and the concentration of the free amine, respectively. Table 2
shows the values of kN for the series of S-substituted O-
ethylxanthates and some cellulose xanthate esters analogues.
The reaction of CelXNB and CelXDNP with polyalanine
and lysozyme (Table 3) was followed by solid-state 13C NMR,
and the spectra did not change after extensive washing with
water, ethanol, and diethyl ether, showing that the poly-
peptide was covalently bound to the cellulose matrix. The
spectrum of each polypeptide was clearly superimposed on
that of the cellulose. However, the signal of the expected
thioncarbamate group at 190 ppm was not observed, and we
are unable to come to any conclusion as to which reaction
Area(CϭO)/number CϭO per mol
[4]
DS =
Area(C-1)
because the competitive hydrolysis is too fast for CelXDNP.
It is important to note that a DS of about 1.0 would dupli-
cate the weight of the cellulose ester in the reaction with
lysozyme.
It is possible that the intensity of the signal of the carbon
from the thiocarbonil group is too low to be detected. For
the polyalanine, the ratio of the signal due to C=O per mol
to one C=S should be in the range of 14–70, and for the
lysozyme, this ratio is 129:1. It is also possible that the weak
© 1999 NRC Canada

1054
Can. J. Chem. Vol. 77, 1999
Fig. 2. Brφnsted-type plot of the spontaneous hydrolysis of S-
substituted ethylxanthates (᭺) versus the pKa of the leaving
thiol, at 35°C in 20% v/v aqueous methanol, µ = 0.1 (KCl); ٗ,
sugar xanthates in 10% aqueous ethanol; ᭿, cellulose esters.
Fig. 3. Brφnsted-type plot of the hydroxide-catalyzed hydrolysis
of S-substituted ethylxanthates (᭺) versus the pKa of the leaving
thiol, at 35°C in 20% v/v aqueous methanol, µ = 0.1 (KCl); ٗ,
sugar xanthates; ᭿, cellulose esters; µ = 1.0 (KCl): EXE, EXP,
MGX-3, CelXNB, CelXDNP.
Hydrolyses
For the hydrolyses, Nu = H2O, OH–, the initial product is
a thioncarbonate that decomposes rapidly to R1OH and COS
as shown in eq. [1]. The tetrahedral intermediate might be
able to decompose through different pathways, but for EXE
it was found that EtSH appears at the same rate of disap-
pearance of the xanthic ester, and considering the difference
of the pKa values of ethanol and ethanethiol, the intermedi-
ate should decompose to product with C—SR2 bond fission
alone (22). This behavior should be similar when the pKa of
the nucleofuge thiol is lower.
The Brφnsted-type plot of Fig. 2 for the spontaneous hy-
drolysis of the S-substituted O-ethylxanthate series is linear
(the rate-determining step does not change), and βlg = 0.10,
suggesting that the virtual tetrahedral intermediate (23) pres-
ents a low perturbation of the C—S bond of an early transi-
tion state and that the rate-determining step must be the
nucleophilic attack of the water molecule to form the inter-
mediate. This conclusion supports the mechanism that has
been postulated for cellulose xanthate esters, where a second
water molecule acts as a general base catalyst for the
deprotonation of the intermediate (8–10). In Fig. 2, it can be
observed that small sugar xanthate molecules with hydro-
philic R1O moiety, such as MGXB and MGX-6, are some-
what less reactive than the ethyl analogue. However, the fast
spontaneous hydrolysis of the cellulose esters CelXDNP and
CelXNB, is 2 and 3 orders of magnitude faster than the O-
ethylxanthate, and it has been proposed that this is a conse-
quence of the supramolecular catalysis induced by the water
molecules of the cybotactic region of the polysaccharide on
the water molecule that acts as a nucleophile (9–10).
The Brφnsted plot of Fig. 3 for the hydroxide-ion-
catalyzed hydrolysis of the same O-ethylxanthate series is
also linear, but βlg = 0.34, indicating a later transition state
C=S signal was eliminated along with the side bands when
using the TOSS technique.
Discussion
It is reasonable to assume that the reaction of xanthate es-
ters with nucleophiles occurs, similar to the carboxylic es-
ters, according to eq. [5] (19, 20) by an addition reaction
that produces a tetrahedral intermediate followed by the
elimination of the thiolate moiety.
[5]
where
k1
[6]
knu =
1 + k–1/k2
Brφnsted plots of log knu against the pKa of the
nucleophile or the nucleofuge of the substrate, provide an in-
sight into the rate-determining step of the reaction (21). Lin-
ear plots indicate no change in the rate-determining step, and
βnu and β are related to the difference in charge between the
lg
initial and the corresponding transition state, that is, to the
bond order of the Nu—C or C—S bonds.
© 1999 NRC Canada

Humeres et al.
1055
Table 4. Brφnsted parameters for the reaction of S-substituted O-ethylxanthates in 20% v/v aqueous methanol at
35°C.a
e
Ester
pKlg
H2O
EDA
7.27
EA
pKnu
9.21
BA
OH–
βnu
–1.74
10.27
15.74
bc
EXE
EXB
10.50
9.43
8.60
8.60
6.43
4.50
0.92
0.92
0.48
0.46
0.37
0.33
0.36
0.32
0.35
0.20
EXNB
CelXNBg
EXP
EXNP
EXDNP
CelXDNP
d
c
c
c
c
c
f
βlg
0.10
0.15
0.12
0.15
0.34
aµ = 0.1 (KCl).
b20% aqueous dioxane.
cµ = 1.0 (KCl).
d Fast hydrolysis (k′), in 10% aqueous ethanol.
eCalculated considering only aminolyses.
f Without considering the cellulose esters.
g Reference 9.
because of a higher activation barrier for the intermediate
decomposition, and consequently, a change of rate-deter-
mining step: a fast intermediate formation is followed by a
slower decomposition. These arguments will be supported
by the discussion on the mechanism of aminolysis.
In this particular case, sugar xanthates are faster than the
ethyl analogues, but a neighboring OH effect should be dis-
regarded because the cellulose xanthate esters hydrolyze ei-
ther at about the same rate (CelXNB) or much slower
(CelXDNP) (Fig. 3). Considering the critical micelle con-
centration of MGXB, it is possible that the rate acceleration
is due to micelle catalysis. With the present data, it is not
possible to understand the slow basic hydrolysis of
CelXDNP.
consistent with a mechanism where the rate-determining
step is the nucleophilic attack of the amine, and formation of
the tetrahedral intermediate that disappears in a fast step be-
cause sulfur can expel the leaving group better than oxygen
(19, 20). The situation is similar to that of the water-catalyzed
reaction, while for the hydrolysis catalyzed by hydroxide ion
the extent of the C—S bond breakage indicates that the in-
termediate is formed in a fast step, and the slower step is the
second one. A change in the rate-determining step accompa-
nies a significant change in the magnitude of βnu andβlg (19).
To compare a β-value with the calibrating equilibrium
(24), the effective charge on the amine N or thiol S of the
substrate has to be calculated. For primary alkyl amines, the
effective charge on the N should be very close to zero, and
the effective charge in the transition state should be essen-
tially equal to βnu. There is no information on the effective
charge on the thiol S of xanthate esters. However, this value
should be constant for the series of S-substituted esters, and
∆βlg values for the different nucleophiles do not change,
without consequences on the conclusions about the change
of the rate-determining step.
Aminolyses
When the nucleophile is an amine, the tetrahedral inter-
mediate is a zwitterion that must deprotonate at a diffusion-
controlled rate before forming the products (eq. [7]).
The second-order rate constants of the reaction of free
amines with xanthic esters are presented in Table 2. The re-
action allows the calculation of both βnu and βlg because the
Brφnsted plots are all linear. For the series of O-ethylxan-
thates, βnu decreases from 0.48 for EXE to 0.35 for EXDNP
(Table 4) because of the increasing electron-withdrawing ef-
fect of the nucleofuge that lowers the kinetic barrier and the
transition state that occurs earlier in the reaction coordinate.
On the other hand, the reaction of these amines with the
xanthate series, produced low βlg values. These results are
Aminolyses of cellulose xanthate esters are slower than
ethylxanthate analogues. Similar to the hydroxide ion-catalyzed
hydrolyses, the aminolyses were strictly first-order, but the
values of βnu were lower than those for the O-ethylxanthates
(Table 4). The slower attack by external nucleophiles can be
interpreted as a consequence of the restricted diffusion
through the tight cybotactic region. However, the lower βnu
values merit a more detailed study.
[7]
© 1999 NRC Canada

1056
Can. J. Chem. Vol. 77, 1999
9. E. Humeres, L.F. Sequinel, M. Nunes, C.M.S. Oliveira, and
P.J. Barrie. J. Phys. Org. Chem. 7, 287 (1994).
10. E. Humeres, L.F. Sequinel, M. Nunes, C.M.S. Oliveira, and
P.J. Barrie. Can. J. Chem. 76, 960 (1998).
11. E. Humeres, M. Klug, and V. Soldi. Atual. Fis.-Quim. Org.
136 (1984).
Acknowledgements
We thank the University College London for the solid-
state NMR spectra that were obtained through the ULIRS
Solid State NMR Service.
12. A.I. Vogel.
A textbook of practical organic chemistry.
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© 1999 NRC Canada