Efficient use of trimethylsulfonium methylsulfate as a reagent for the epoxidation of carbonyl-containing compounds

Article abstract of DOI:10.1039/a907053b

A process for the efficient conversion of trimethylsulfonium methylsulfate into dimethylsulfonium methanide, thence epoxides, has been devised. Thus dimethyl sulfate and dimethyl sulfide are caused to react in the presence of either a mineral acid or an o

Full text of DOI:10.1039/a907053b

View Article Online / Journal Homepage / Table of Contents for this issue
Efficient use of trimethylsulfonium methylsulfate as a reagent for
the epoxidation of carbonyl-containing compounds
a
a
b
a
Julie Forrester, Ray V. H. Jones, Peter N. Preston and Elizabeth S. C. Simpson †
a
Zeneca Agrochemicals Ltd, Process Technology Department, Grangemouth Works,
Earls Road, Grangemouth, UK FK3 8XG
Department of Chemistry, Heriot-Watt University, Riccarton, Edinburgh, UK EH14 4AS
b
Received (in Cambridge, UK) 31st August 1999, Accepted 20th September 1999
A process for the efficient conversion of trimethylsulfonium methylsulfate into dimethylsulfonium methanide, thence
epoxides, has been devised. Thus dimethyl sulfate and dimethyl sulfide are caused to react in the presence of either a
mineral acid or an organic acid. The anion of trimethylsulfonium methyl sulfate is converted by the acid into methyl
hydrogen sulfate, which in turn reacts with excess dimethyl sulfide to form trimethylsulfonium hydrogen sulfate. The
outcome is that both methyl groups of dimethyl sulfate are converted into the desired trimethylsulfonium salt, thence
dimethylsulfonium methanide; the process is mediated by low boiling dimethyl sulfide which can be recycled, and the
by-product (K SO ) is more easily disposed of than potassium methyl sulfate.
2
4
Introduction
the questions: could the methyl sulfate anion in trimethyl-
sulfonium methyl sulfate be converted in situ into methyl hydro-
gen sulfate, and would this react with a further equivalent of
dimethyl sulfide in situ? If this could be achieved, a method of
utilizing both methyl groups from dimethyl sulfate would be
available. This would result in the formation of two equiv-
alents of trimethylsulfonium cation thence two equivalents of
dimethylsulfonium methanide on treatment with base; overall,
two equivalents of epoxide would ensue from one equivalent of
dimethyl sulfate. An illustration of how sulfuric acid could be
used for achieving efficient conversion to epoxide is shown in
Scheme 3 from which it should be noted that the epoxidation
1,2
Trimethylsulfonium methyl sulfate (1) is an inexpensive, effi-
cient precursor of dimethylsulfonium methanide (2), a valuable
reactive intermediate for the transformation of aldehydes and
3
ketones into epoxides (see Scheme 1). Generation of the ylide
Scheme 1
2
from the salt 1 can be effected under homogeneous or phase
2
transfer conditions; an important feature of the latter method
is that it is not necessary to add a phase transfer catalyst.
The use of dimethyl sulfate as a methylating agent for
dimethyl sulfide has important advantages compared with alkyl
halides: thus the products do not contain corrosive chloride
ions, and the process does not involve the use of gaseous start-
ing materials (e.g. MeCl, MeBr). Dimethyl sulfate is also less
expensive than the corresponding methyl halides but it has one
serious drawback — generally only one of the two methyl groups
available is utilised in epoxide formation. This is effectively a
yield loss of 50% and the effluent loading is higher, contain-
ing one equivalent of an alkali methyl sulfate salt per mole of
dimethyl sulfate used. The aim of the present study was to
devise an efficient process for using both methyl groups of
dimethyl sulfate for epoxidation through ylides derived from
sulfonium species.
Scheme 3
by-product would be dimethyl sulfide (bp 38 ЊC) which can be
contained and recycled using standard industrial process
technology.
4
5
We have reported earlier that methyl hydrogen sulfate (3)
methylates dimethyl sulfide at ambient temperature to produce
trimethylsulfonium hydrogen sulfate (4) (Scheme 2). This led to
Results and discussion
It was demonstrated at the outset that no reaction occurred
between trimethylsulfonium methyl sulfate and an excess of
dimethyl sulfide (1.5 mol equiv.) after 7 h at 35 ЊC; thus no
Scheme 2
1
change was apparent in the integrated H NMR singlet reson-
ϩ
Ϫ
4
ances at δ = 3.0 (Me S ) and 3.55 ppm (MeSO ), respectively. In
3
contrast, when concentrated sulfuric acid (0.5 mol equiv.) was
added to the above mixture, an exothermic reaction occurred,
†
Present address: Process Technology Department, Avecia Ltd,
Grangemouth Works, Earls Road, Grangemouth, UK FK3 8XG.
J. Chem. Soc., Perkin Trans. 1, 1999, 3333–3335
This journal is © The Royal Society of Chemistry 1999
3333

View Article Online
a
a
Table 1 Reaction of trimethylsulfonium methyl sulfate and dimethyl sulfide with mineral acids and Amberlyst resin
Ϫ
1
Acid–MeSO4 (mol.
H NMR integration
ϩ
Ϫ
4
Acid
equiv.–mol. equiv.)
Time/h
Temp./ЊC
ratio (CH ) S :CH SO
% Reaction
3
3
3
c
HCl (36%)
1
1.5
6
6
6
6
40
40
35–40
35–40
29:1
5.7:1
~80%
25%
100%
~20%
H PO (85%)
3
4
Ϫ
4
PhSO H
4
No peak for CH SO
3
3
b
Amberlyst
4:1
a
b
Trimethylsulfonium methyl sulfate (1.0 equiv.) and dimethyl sulfide (2.0 equiv.). For a polymer supported acid, the mole equivalent cannot be
c
calculated. Mixture used in subsequent epoxidation reaction.
1
and H NMR analysis indicated a 30% conversion to trimethyl-
spectrometer; chemical shifts are quoted in ppm downfield from
tetramethylsilane and 3-(trimethylsilyl)propanesulfonic acid,
sodium salt (DSS), and coupling constants are in Hertz.
Amberlyst 15 was purchased from Aldrich.
sulfonium hydrogen sulfate and methyl hydrogen sulfate after
8 h at room temperature. The reaction of Me S MeSO –
Me S–concentrated H SO was then repeated (40 ЊC, 6 h) with
ϩ
Ϫ
4
3 4
2
2
4
a molar ratio of 1:1.5:2, respectively. After 6 h at 40 ЊC
7
and standing at room temperature, the product consisted of
1
-(2,4-Dichlorophenyl)pentan-1-one (5) and 2-butyl-2-(2,4-
1
8
two layers with the lower layer at pH zero; H NMR analysis of
dichlorophenyl)oxirane (6)
this layer indicated an almost quantitative conversion to tri-
methylsulfonium hydrogen sulfate. The latter was then used
Compounds 5 and 6 were prepared by known methods. NMR
spectral data are as follows: Compound 5 δH (CDCl –TMS)
6
3
for epoxidation using our procedure described earlier: 1-(2,4-
0
3
.75–1.9 (m, 7H, (CH ) CH ), 2.87 (t, 2H, CH ), 7.15–7.5 (m,
2 2 3 2
dichlorophenyl)pentan-1-one (5) [1 mol equiv.], potassium
H, aromatic H).
Compound 6 δ (CDCl –TMS) 0.5–2.4 (m, 9H, (CH ) CH ),
H
3
2
3
3
2
.6–3.0 (m, 2H, CH O), 7.0–7.5 (m, 3H, aromatic H).
2
Reaction of trimethylsulfonium methyl sulfate, dimethyl sulfide
and sulfuric acid
Dimethyl sulfide (3.60 g, 0.058 mol) was added to a solution of
trimethylsulfonium methyl sulfate (5.97 g, 0.029 mol) in water
(0.5 ml). 98% Sulfuric acid (5.8 g, 0.058 mol) was added drop-
wise to the stirred mixture which was then heated to 40 ЊC and
stirred for 6 h. The product was held unagitated for 16 h after
which it consisted of two layers with a large lower aqueous layer
hydroxide (5 equiv.) and trimethylsulfonium cation (1.05 equiv.)
were allowed to react in tert-butyl alcohol at room temperature
to afford the epoxide 6 in 73% yield. The use of hydrochloric,
phosphoric, benzene sulfonic acid and a strong cation exchange
resin (Amberlyst 15) was then evaluated in respect of the
pre-epoxidation step as described above (see Table 1).
1
of pH = 0. A sample of this layer was removed for H NMR
Ϫ
The use of hydrochloric acid showed a significant rise in the
analysis. δ (DMSO d –DSS) 2.1 (s, 1H, (CH ) S), 3.0 (s, 13H,
H
6
3 2
ϩ
Ϫ
4
ϩ
Ϫ
(
CH ) S :CH SO , ratio but phosphoric acid showed only a
(CH ) S ), 3.5 (s, 0.1H, CH SO ).
3
3
3
3 3 3 4
slight increase under the same conditions. Benzenesulfonic acid,
using a four-fold molar excess, resulted in complete conversion,
with no methyl sulfate anion remaining. The use of Amberlyst
Epoxidation of 1-(2,4-dichlorophenyl)pentan-1-one (5) using the
reaction mixture from above
1
5 resulted in a slight increase in the ratio to 4:1, but the resin
To the above reaction mixture containing trimethylsulfonium
cation (assumed 0.058 mol) was added tert-butyl alcohol (4.10
g, 0.055 mol) and 1-(2,4-dichlorophenyl)pentan-1-one (13.38 g,
absorbed the liquid and the reaction mixture became very
viscous. Further work would be required to optimise the
quantity of Amberlyst 15 required.
0
.055 mol). This mixture was stirred and potassium hydroxide
The reaction mixture produced from the use of hydrochloric
acid was also used for epoxidation as described above. Two
equivalents of 1-(2,4-dichlorophenyl)pentan-1-one (5) were
used per equivalent of trimethylsulfonium methyl sulfate and
the product epoxide 6 was isolated in 54% yield. This yield
could be improved by allowing the reaction of trimethyl-
sulfonium methyl sulfate and dimethyl sulfide to go to com-
pletion, either by allowing a longer reaction time, by increasing
the temperature or by adding a larger excess of hydrochloric
acid. It may be noted that the mixture produced from this
reaction will contain the trimethylsulfonium cation with two
(
15.4 g, 0.275 mol) was added in portions. The colour of
the mixture changed quickly to yellow and an exotherm was
observed; cooling with an ice bath was applied. Half of the
potassium hydroxide was added and the mixture was stirred for
1
h, then the remainder was added over 20 min. The mixture
was very viscous but became less so during the 3 h stirring
period. The mixture was held unagitated over 2 days. Samples
were removed periodically for gas chromatographic analysis
(
Shimadzu GC-9A instrument with a Shimadzu C-R3A
Chromatopac Integrator). The column was of fused silica
(2 m × 3 mm) with 5% OVI7 stationary phase; the oven tem-
perature was 180 ЊC. Samples (~0.5 ml) were added to a mixture
of dichloromethane (~1 ml) and water (~1 ml) and shaken. The
lower dichloromethane layer (1 µl) was injected, showing reten-
tion times for 1-(2,4-dichlorophenyl)pentan-1-one (5) and the
epoxide 6 = 8.4 and 7.7 min, respectively.
Ϫ
Ϫ
4
different counter ions (Cl and HSO ).
Conclusions
A new, efficient epoxidation method has been devised based on
dimethyl sulfate (1 equiv.) and dimethyl sulfide (2 equiv.) to
produce trimethylsulfonium cation (2 equiv.), utilizing both
methyl groups present in dimethyl sulfate. Sulfuric acid is used
to generate methyl hydrogen sulfate as an intermediate, but
other acids, e.g. hydrochloric acid, can also fulfil the same role.
The progress of reaction was monitored by GC % areas for
ketone 5 and epoxide 6 at the following times: end of KOH
addition (1 h, 20 min; ratio of 5:6 = 86:13), 3 h (5:6 = 25:68)
and 48 h (5:6 = 9:89); the yield of 6 after 48 h was 73%. 3
To the bulk reaction mixture was added water (50 cm ) and
the solvents were then evaporated by distillation, up to a
Experimental
3
column head temperature of 55 ЊC. Water (ca. 250 cm ) was
1
H NMR spectra were recorded on a Bruker WP-SY (80 MHz)
added and the lower organic layer was separated and washed
3
334
J. Chem. Soc., Perkin Trans. 1, 1999, 3333–3335

View Article Online
3
with water (50 cm ) to afford the crude epoxide 6 (10.55 g); a
ised by the standard method (see above) using the product of
further batch (0.6 g) of expoxide 6 was isolated through extrac-
tion of the aqueous washings with dichloromethane (total
yield = 73% from GC analysis).
the hydrochloric acid reaction described above. The yield of
epoxide 6 was 54%.
References
Reaction of trimethylsulfonium methyl sulfate and dimethyl
sulfide in the presence of other acids (HCl, H PO , PhSO H,
Amberlyst 15)
1 T. Kutsuma, I. Nagayama, T. Okazaki, T. Sakamoto and S.
3
4
3
Akaboshi, Heterocycles, 1977, 8, 397.
P. Mosset and R. Greé, Synth. Commun., 1985, 15, 749.
2
Dimethyl sulfide was added to dimethyl sulfate and the acid was
then added slowly (see Table 1 for mol ratios); water (0.8 ml for
3 E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 1962, 84, 3782;
E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 1965, 87, 1353.
J. Forrester, R. V. H. Jones, P. N. Preston and E. S. C. Simpson,
J. Chem. Soc., Perkin Trans. 1, 1995, 2289.
I. Rusev and D. Chochkova, Khim. Ind. (Sofia), 1986 58, 445 (Chem.
Abstr., 107, 115953).
J. Forrester, R. V. H. Jones, P. N. Preston and E. S. C. Simpson,
J. Chem. Soc., Perkin Trans. 1, 1993, 1937.
4
5
6
a 88 mmol amount of Me S) was used as an additive for the
2
reaction with PhSO H. The mixtures were heated up to 40 ЊC
3
1
and progress monitored by H NMR analysis. The reaction
with Amberlyst 15 was carried out as follows: dimethyl sulfide
(
3.90 g, 0.064 mol) was added to a solution of trimethyl-
sulfonium methyl sulfate (6.12 g, 0.032 mol) in water (0.6 ml).
Amberlyst 15 (6.90 g) was added but the mixture was very
viscous. A second aliquot of dimethyl sulfide (5 ml) was added,
the mixture was stirred at 35–40 ЊC for 6 h and then held over-
night at room temperature. Water (5 ml) was added and samples
7 M. Ueda, Y. Seino and J. Sugiyama, Polym. J. (Tokyo), 1993, 25,
319.
G. R. Davies and A. G. Williams, Eur. Pat. Appl EP 93562 (1983);
Chem. Abstr., 100, 58802).
1
8
(
1
were removed for H NMR analysis. The ketone 5 was epoxid-
Paper 9/07053B
J. Chem. Soc., Perkin Trans. 1, 1999, 3333–3335
3335

View Article Online