STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XLVIII Synthesis of Dithioesters from P,S-Containing Reagents and Carboxylic Acids and Their Derivatives

Article abstract of DOI:10.1016/S0040-4020(01)96883-8

2,4-Bismethylthio-1,3,2,4-dithiadiphosphetane 2,4-disulfide, IIa, is prepared from O,O-dimethyldithiophosphoric acid, Ia, and P4S10 at 160 deg C. 2,4-Bis(4-phenoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, IIc, and 2,4-bis(4-phenyl-thiolphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, IId, are prepared at 160 deg C from P4S10 and diphenylether and diphenylsulfides, respectively.Carboxylic acids RCOOH (R=CH3, C2H5, n-C3H7, n-C4H9, C6H5CH2, C6H5) react with compound Ia at 130 deg C to give the corresponding methyl dithioesters.Carboxylic acids RCOOH (R=C6H5-CH2, C6H5) react with compound Ib at 200 deg C for 15 min to give the corresponding ethyl dithioesters, while low boiling acids (R=CH3, C2H5, n-C3H7) yielded mixtures of the corresponding ethyl dithioester and ethyl carboxylate.Carboxylic acid chlorides RCOCl (R=ClCH2, C2H5, t-C4H9, C6H5CH2, C6H5, p-NO2C6H4) react with compound IIa at 80 deg C to give the corresponding methyl dithioesters in good yields.S-Substituted thioesters react with IIc at 85 deg C to give the corresponding dithioesters in good yields.Dihydro-2(3H)-furanone, VI, and 5-methyl-2(3H)-furanone, VII, react with IIa at 80 deg C to give dihydro-2(3H)-thiophenethione, VIII and 2,2'-dithiobis(5-methyl thiophene), IX, respectively.Also XI reacts with IIa, IIc, and IId to give VIII in nearly quantitative yields.

Full text of DOI:10.1016/S0040-4020(01)96883-8

Vol. 40, No. 14, pp.
the U.S.A.
to
1984
Ltd.
a)
STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XLVIII
Synthesis of Dithioesters from P,S-Containing Reagents and
Carboxylic Acids and Their Derivatives
U.PEDERSEN, B.YDE, and S.-O.LAWESSON
Department of Organic Chemistry, Chemical Institute
University of Aarhus, DK-8000 Aarhus C
DENMARK
in UK 12 December 1983)
Abstract
prepared from O,O-dimethyldithiophosphoric
at
acid,
and
dithiadiphsophetane
and
are prepared at 160°C from
and diphenylether and
respectively. Carboxylic acids RCOOH (R
react with compound
nylsulfides,
at
give the corresponding methyl dithioesters.
boxylic acids RCOOH (R =
react with compound
Ib at
thioesters,
for 15 min to give the corresponding ethyl
while low boiling acids (R
CH,,
yielded mixtures of the corresponding ethyl dithioester and
ethyl carboxylate. Carboxylic acid chlorides (R
react with compound
at
to give the corresponding methyl dithioesters in
good yields. S-Substituted thioesters react with
at
to give the corresponding dithioesters in good yields.
with
and
at
to give
VIII
thiophene
respectively. Also
XI reacts with
and
to give VIII in nearly quan-
titative yields.
Dithioesters are of great importance because of their wide application in organic
synthesis and industry (e.g. as vulcanization
the synthesis of Dyes,"
starting material for
. . ...). Some methods for
their preparation are mentioned in a recent review.6 Another more recent method
is the reaction of tertiary amides
with 0,0-diethyldithiophosphoric acid, Ib,
Ib
R-C-N<
R-C-N<
Scheme 1
XLVII B. Yde,
and
Tetrahe-
dron
(1984)
l
On leave from the National Research
Dokki, Cairo, Egypt
2663

2664
N. M.
et al.
or thiation of S-substituted thioesters
with
(LR)
LR
110
R-C-S-R'
Scheme 2
dithioesters of N-protected amino acids
For the preparation of thiopeptides
which are prepared by mild methods to avoid racemization.
can be used,
In attempts to find effective and mild methods for the preparation of
thioesters we have studied the P,S-containing reagents
and
S
RO
SH
R
R
CH,
R
R =
b:
b:
(LR)
c:
d:
Fig.1
This paper reports on the reactions of I and II with carboxylic acids and their
derivatives.
RESULTS AND DISCUSSIONS.
A, Starting materials
The commercially available O,O-dimethyldithiophosphoric acid,
Ib, are easily prepared from
and
and methanol
diethyl dithiophosphoric acid,
respectively." In a recent paper
the reaction of
with meth-
or ethanol,
anol at 160
fide
produced
in low yield
RO
RO
ROH
R
R
CH,
R
CH,
Ib:
Scheme
3
The low yield is certainly due to the reaction of methanol with
to give side
products. However, when
and
are heated at 160
for a short time
and
is
isolated in
by reacting
yield.
at 180
is commercially available and
prepared
with diphenylether and diphenylsulfide, respectively.
Reactions of I
Carboxylic acids react with excess of
methyl dithioester in reasonable yields.
at
130
Also some carboxylic acid (RCOOH, R
to give the corresponding ethyl
CH,, give mixtures of the cor-
to give the corresponding
react with Ib at 200
esters while low-boiling acids (R
responding ethyl dithioesters and ethyl carboxylates (Table 1, entries l - 11) .

Studies on organophosphorus
2665
R
CH,
b:
Scheme
As to the mechanism for the reaction
with carboxylic acid it is suggested
incidentally easily prepared by
(By heating or standing,
III is partly transformed into III').
that at first water is eliminated to give III,
acylation of
mixture of III and III'
However,
A
(R
CH,) does not give any dithioester on heating
is present almost quantitative yields of methyl
(130
when
or
dithiobenzoate are isolated. Also III (III') (R
and Ib produce ethyl
thiobenzoate in
yield.
From these results we do believe that the reaction of
I with carboxylic acids can go via III (III').
C. Reactions of II
1) Acid Chlorides.
Carboxylic acid chlorides react with
benzene to give the methyl dithiocarboxylate in reasonable yields (Table
tries 15-20).
in refluxing
During the reaction also S-methyl thiocarboxylates is isolated. As
contains various nucleophilic sites, different mechanisms can account for
the formation of dithioesters. 1) Acylation on sulfur would give the
methyl thioester, which gives the dithioester after thionation. 2) Acylation on
another sulfur would give an acylating reagent (compare III
ranges to give the dithioester in one step.
III') which rear-
2) Esters and S-substituted thioesters. Methyl benzoate reacts with
at
200
to give methyl dithiobenzoate in reasonable yields (entry 26) and it is
obvious that a transesterification has taken place. Ethyl benzoate gives, as ex-
pected, mixtures of products.
Attempts to transfer S-substituted thioesters to
the corresponding dithionoesters by reaction with
in refluxing THF did not
meet with success. However,
yields (entries 21-24).
in refluxing
the dithioesters are formed in good
S
0
85
Scheme
5
3) Lactones and thiolactones.
It is known
that VI reacts smoothly with
to give the
X. Now it has been found that
transforms VI into VIII that means that oxygen in the ring is exchanged with
During the reaction samples are taken from the reaction mixture but
sulfur.
neither X nor
acted with
XI were detected (GLC). VII was also re-
was the final product. The reaction of ethyl
at elevated gave the same
and IX
tanoate with

N. M.
2666
0
VIII
Scheme
6
Experimental data for the preparation of dithioesters from acids, III,
acid chlorides,
Table 1.
Entry
thioloesters and esters
Time (hr)
Reagent
Yield
1
Me
Me
OH
3
3
3
3
3
1 3 0
1 3 0
1 3 0
2
Et
OH
OH
OH
OH
OH
n-Pr
Me
Me
Me
Me
Et
Et
Et
Et
Et
Me
Et
Me
Me
Me
Me
Me
Me
Me
3
4
53"
455
5
6
1 3 0
Ph
3
1
Me
200
200
200
200
200
Ib
Ib
Ib
Ib
Ib
7
a
Et
OH
OH
OH
OH
0 . 8
n-Pr
1 . 5
0 . 5
0.2
9
1 0
11
Ph
Ph
Ph
Ph
505
12
14
16
815
130
200
0 . 5
0. 1
0.2
4
775
895
2 5
130
80
80
80
80
80
80
Cl
Cl
Cl
Cl
Cl
Cl
4
Et
4
17
18
Ph
4
4
715
827
20
21
5
8
8
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
8 5
8 5
22
IIC
IIC
72'
74'
8 5
23
24
Ph
Me
Me
8 5
65'
80
8
25
26
200
1 4 0
1 4 0
625
0 . 5
Et0
12
2 7
6
*ethyl carboxylate;

Studies on organophosphorus compounds-XLVIII
Experimental data for the preparation of
Table 2.
lactones at 80
from lactones
Yield
Solvent
benzene
Time (min)
Reagent
VI
XI
XI
XI
benzene
DME
DME
EXPERIMENTAL
spectra were recorded at 60
on a Varian
spectrometer in
TMS. IR spectra were recorded on a Beckman IR-18 spectrometer.
Mass spectra were recorded on a Micromass 7070F spectrometer operating at 70
using direct inlet.
Synthesis of
and 150 ml
three necked flask with mechanical stirring and
a) from methanol and
benzene are mixedinal
111 g (0.25 mole)
then 24 g (0.75 mole) methanol was
condenser. The mixture was heated to 80-90
dropped gradually with stirring (the reaction is exothermic), and then the reac-
tion mixture was kept at 160
for 20
and then cooled to
and fil-
The filtrate was then cooled to room temperature and the precipitated
tered,
compound is filtered and washed with anhydrous
Yield 55.5
284 (low intensity)* m/e 142
precise MS (Found:
ow mp mentioned in the
160
112
M+ 141.913;
for
:
(the 1
literature is due to an impure sample containing elemental
b) from compound
and
1.58 g (0.01 mole) of
2.21 g (0.005 mole)
and 10 ml anhydrous
are mixed in a 100 ml round flask
The reaction mixture was kept at 160
with stirring for 30
without condenser.
min. The reaction was worked up as in a). Yield 0.72 g
Synthesis of
111 g (0.25 mole)
100 ml 0-dichlorobenzene and g (2 mole) diphe-
ether are mixed in a 1
two necked flask with mechanical stirring and
for 25 min and then
and filtered. 200 ml anhydrous ether is addedtuthe filtrate
then cooled to room temperature. The precipitated compound is then filtered.
flux condenser. The mixture was heated under reflux at 180
cooled to
Yield 401 g
mp 189
187-189
MS: M+ 528.59 low intensity
264 base peaks. The precise mass
263.983 (Calc. 263.9832).
Synthesis of
111 g (0.25 mole)
100 ml 0-dichlorobenzene and 186 g (1 mole) diphe-
Yield 182 g
280 base peak. The precise mass
nylsulfide are mixed and completed as in the syntheses of
M+ 560.72 low intensity
MS:
mp 193
279.960 (Calc. 279.9604).
General procedure for the preparation of dithioesters from carbpxylic acids and
or Ib
A mixture of 0.005 mole of carboxylic acid and 5 ml of
or
are heated
(Table
l-11). The reaction mixture,
which is allowed to obtain room
temperature,
is extracted with 100 ml ether and washed with
Then it is
placed on a silica gel column and the dithioester is eluated by
Three carboxylic acids (RCOOH:
lowing:
are reacted with Ib as fol-
0.6 mole of carboxylic acid and 15 ml of Ib are heated (Table 1) and the
esters are isolated by
Procedure for the preparation of dithioesters from III, III'
0.005 mole of III are heated with 0.01 mole of compound
Ib or
Ib or
(Table
12-14).
The reaction mixture,
which is allowed to obtain room
and the dithioester is eluated
temperature,
with
is placed on a silica gel
General procedure for the preparation of dithioesters from acid chlorides and
0.005 mole of acid chloride and 1.42 g (0.005
mole) of
The solvent is stripped off and the
The dithioester is with ether/
are
in
anhydrous benzene (Table
residue is placed on a silica gel column,

N. M.
P.E.
General procedure for the preparation of dithioesters from thioloesters and
or
0.005 mole of thioloester and 0.005 mole of
DME are heated at 80 (Table 1, entries
or
in 10 ml anhydrous
The solvent is stripped off and
the residue is placed on a silica gel column. The dithioester is eluted with
Procedure for the preparation of methyl dithiobenzoate from methyl benzoate and
0.68 g (0.005 mole) methyl benzoate and 1.42
at 200 in 10 ml anhydrous
(0.005 mole)
(Table
are heated
26-28). The
reaction mixture, which is allowed to obtain room temperature, is placed on a
silica gel column.
Methyl dithiobenzoate is eluted with
Preparation of dithioesters from and ethyl benzoate or phenyl
0.005 mole of the ester and 1.42 g (0.005 mole) are refluxed in 10 ml
anhydrous xylene (Table 1). The reaction mixture, which is allowed to obtain
room temperature, is placed on a silica gel column and the dithioester is eluted
Transesterification is obtained for phenyl
Preparation of
VI. and
VIII. from
0.43 g (0.005 mole) of VI and 1.42 g (0.01 mole) of
in 10 ml anhydrous
benzene are heated for 50 min. The solvent is stripped off and the residue is
placed on a silica gel column. VIII is eluted with
Preparation of
none, XI, and
VIII, from
0.51 g (0.005 mole) of XI and
g (0.01 mole) of
in 10 ml anhydrous
benzene are heated for 30 min. The solvent is stripped off and the residue is
placed on
silica gel column.
VIII is eluted with
Preparation of
none, XI. and
VIII. from
or
0.51 g (0.005 mole) of XI and 0.01 mole of
or
in 10 ml anhydrous
DME are heated at 80
for 25 min.
The solvent is stripped off and the residue
VIII is eluted with
is placed on a silica gel column.
Preparation of
VII, and
-methyl-thiophene
-methyl-Z
IX; from 5
0.49 g (0.005 mole) of VII and 1.42 g (0.01 mole) of
benzene are heated at 80 for 60 min. The reaction mixture, which is allowed to
obtain room temperature, is placed on a silica gel column and IX is eluted with
and 0.2 g is obtained. 2.25
7.05-7.15 MS: 258 226 (M+-S), 129
85
in
ml anhydrous
6.85
97
base peak,
The
The known compounds are identified by IR,
NMR and MS
following data for the unknown compound methyldithiochloroacetate is found:
M+ 140 and precise mass M+ 139.9521
NMR
2.6
4.55
MS:
Acknowledgement
Thanks are expressed to
for a post-doctoral fellowship
US (N.M.Y.).
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