A high yielding, one-pot synthesis of O,S-dialkyl dithiocarbonates from alcohols using Mitsunobu's reagent

Article abstract of DOI:10.1016/j.tetlet.2006.10.149

A novel Mitsunobu-based protocol has been developed for the synthesis of O,S-dialkyl dithiocarbonates from a variety of primary, secondary and tertiary alcohols using carbon disulfide, in good to excellent yields. This protocol is mild and efficient compa

Full text of DOI:10.1016/j.tetlet.2006.10.149

Tetrahedron Letters 48 (2007) 149–151
A high yielding, one-pot synthesis of O,S-dialkyl
dithiocarbonates from alcohols using Mitsunobu’s reagent
Devdutt Chaturvedi* and Suprabhat Ray
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India
Received 25 December 2005; revised 18 October 2006; accepted 26 October 2006
Available online 20 November 2006
Abstract—A novel Mitsunobu-based protocol has been developed for the synthesis of O,S-dialkyl dithiocarbonates from a variety
of primary, secondary and tertiary alcohols using carbon disulfide, in good to excellent yields. This protocol is mild and efficient
compared to other reported methods.
Ó 2006 Elsevier Ltd. All rights reserved.
O,S-Dialkyl dithiocarbonates (xanthates) are a versatile
source of radicals,1 intermediates in the synthesis of
thiols,2 thiocarbonates,3 alkenes,4 alkanes,5 S-activated
carbanions6 and photosensitisers7 for the polymeriza-
tion of vinyl monomers. They have also been used in
the synthesis of natural products,8 Claisen rearrange-
ment,9 and are also important for biological activities.10
Traditionally, they are prepared from an alcohol in a
three-step process.11 The reaction involves the use of
strong bases such as sodium hydride, sodium amide or
potassium t-butoxide in polar aprotic solvents like
DMSO,12 DMF13 or diglyme.14 Phase-transfer catalysis
and crown ethers have also been used with strong bases
specifically for the preparation of dithiocarbonates from
unfunctionalized alcohols.15 However, most of these
methods suffer from limitations such as long reaction
times, use of expensive strongly basic reagents, and
tedious work-up. Consequently, there is continued
interest in developing new and convenient methods for
the synthesis of dithiocarbonates using mild reaction
conditions. Our group16 has been engaged over several
years on the development of new methodologies for
the synthesis of carbamates and dithiocarbamates using
cheap and safe reagents like CO2 and CS2. Recently we
reported17 the synthesis of carbamates- and dithio-
arbamates from the corresponding alcohols using
Mitsunobu’s reagent. Based on our recent work,17 we
report herein a chemoselective, highly efficient and mild
synthesis of O,S-dialkyl dithiocarbonates of primary,
secondary and tertiary alcohols using Mitsunobu’s
reagent.
Thus we carried out18 the synthesis of dithiocarbonates
by mild thiocarbonation of alcohols with carbon di-
sulfide and an alcohol in the presence of Mitsunobu’s
reagent.
We assume that the unstable dithiocarbonic acid 1
generated from the alcohol and CS2 reacts with the
Mitsunobu zwitterion 2 formed from Ph3P and diethyl
azodicarboxylate, to furnish the stabilized zwitterionic
species 3 which in turn undergoes S-alkylation giving
rise to the formation of the dithiocarbonate ester as
shown in Scheme 1.
Thus, various alcohols were reacted using Mitsunobu’s
reagent and carbon disulfide solution in dry dimethyl-
sulfoxide (DMSO) at room temperature for 4–8 h, to
afford O,S-dialkyl dithiocarbonates in good to excellent
yields (76–98%) as shown in Table 1. Isomeric O,S-di-
alkyl dithiocarbonates were prepared by altering the
order of addition of the respective alcohols (Table 1,
entries 2 and 18, 10 and 19) We examined several
solvents such as n-heptane, n-hexane, DMSO, DMF
and HMPA of which dry DMSO proved to be the most
suitable. The overall reaction is shown in Scheme 2.
Keywords: Mitsunobu’s reagent; Carbon disulfide; Alcohols; Dithio-
carbonates; Thiocarbamation.
In conclusion, we have developed a convenient and effi-
cient protocol for the one-pot, four-component coupling
of various alcohols with a variety of primary, secondary
*
Corresponding author. Tel.: +91 522 2612411/18x4334; e-mail:
ddchaturvedi002@yahoo.co.in
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.10.149

150
D. Chaturvedi, S. Ray / Tetrahedron Letters 48 (2007) 149–151
R6
C
R4
R6
C
S
C
R5
SH
R5
+CS
OH
2
O
1
2
R4
COOEt
Ph3P
N
COOEt
N
Ph P EtOOC N N COOEt
+
3
COOEt
Ph3P
N N COOEt
H
1 + 2
3
R6
S
C
R5
C
O
S
R4
R1
R3
R6
R1
S
R2
R5
C
R2
OH
C
R4
O
EtO2CNHNHCO2Et
O
PPh
S
3 +
+
+
3
R3
4
R4
R6
R1
R2
S C
S
O
R5
Ph3P=O
+
R3
O,S-dialkyl dithiocarbonate
Scheme 1. Proposed mechanism of formation of the dithiocarbonates.
Table 1. Conversion of alcohols into dithiocarbonates of general formula Ia
Entry
R1
R2
R3
R4
R5
R6
Time (h)
Yields (%)
1
Phenyl
H
H
H
H
H
H
H
H
n-Butyl
n-Butyl
H
H
H
H
Methyl
H
H
H
H
H
H
H
H
H
n-Butyl
H
H
H
H
H
H
H
Phenyl
n-Hexyl
n-Propyl
n-Octyl
Cyclohexyl
n-Butyl
Phenyl
4-Methoxyphenyl
n-Octyl
n-Dodecyl
Phenyl
Benzyl
3-Methoxybenzyl
n-Dodecyl
Cyclohexyl
n-Butyl
n-Octyl
2-Phenethyl
n-Butyl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
n-Butyl
H
5
4
5
5
6
5
6
5
6
7
6
5
5
4
6
8
5
4
7
92
97
86
93
85
82
85
83
84
76
80
83
89
98
90
76
93
96
77
2b
3
2-Phenethyl
2-Phenethyl
n-Propyl
i-Amyl
n-Butyl
2-Naphthyloxyethyl
2-Naphthyloxyethyl
n-Butyl
n-Butyl
n-Hexyl
n-Heptyl
n-Octyl
n-Heptyl
n-Pentyl
2-Naphthyloxyethyl
3-(2-Naphthyloxy)prop-1-yl
n-Hexyl
n-Propyl
H
H
H
H
H
H
H
H
H
H
H
H
n-Butyl
H
H
n-Butyl
4
5
6
7
8
9
10b
11
12
13
14
15
16
17
18b
19b
H
H
H
H
H
H
H
n-Butyl
n-Dodecyl
a All the products were characterized by IR, NMR and mass spectral data.
b Entries 2 and 18 and entries 10 and 19 are isomeric products.
tion of C–S bonds, essential in numerous organic
syntheses.
R1
R3
R4
R6
R1
R3
S
R4
R6
a
R2
OH
+
R2
S
O
R5
HO
R5
Acknowledgements
I
Scheme 2. Reagents and conditions: (a) dry DMSO, DEAD/Ph3P,
CS2, rt, 4–8 h.
The authors thank Dr. Nitya Anand for his fruitful sug-
gestions and the SIAF division of CDRI for providing
spectroscopic and analytical data.
and tertiary alcohols via a Mitsunobu zwitterion. This
reaction generates the corresponding O,S-dialkyl dithio-
carbonates in high yields. Furthermore, this method
exhibits substrate versatility, mild reaction conditions
and experimental convenience. This synthetic protocol
is believed to offer a more general method for the forma-
References and notes
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151
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128.7, 140.10, 142.20 (aromatic region), 172.2 (C@S) ppm;
Mass: m/e (%) = 274 (91), 197 (39), 105 (42), 91 (100);
Analysis: C15H14OS2, Calcd C, 65.66; H, 5.14; S, 23.37.
Found: C, 65.89; H, 5.02; S, 23.55.
O,S-n-Heptyl-3-phenylpropyl dithiocarbonate (entry 2): Oil,
2. Isola, M.; Ciuffarin, E.; Sangromora, L. Synthesis 1976,
326–327.
3. (a) Degani, I.; Fochi, R.; Regondi, V. Synthesis 1981, 149–
151; (b) Baker, R.; Mahony, M.; Swain, C. J. J. Chem.
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5. Barton, D. H. R.; Combie, S. W. J. Chem. Soc., Perkin
Trans. 1 1975, 1574–1586.
IR (neat): 1088, 1194, 1226 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d = 0.93–0.96 (t, 3H, J = 6.9 Hz, CH3 of n-hexyl),
1.29–1.48 (m, 8H of CH2 of n-hexyl), 2.26–2.30 (m, 2H,
PhCH2CH2CH2), 2.56–2.59 (t, 2H, J = 6.3 Hz, PhCH2),
2.90–2.93 (t, 2H, J = 6.5 Hz, PhCH2CH2CH2–S), 3.64–
3.69 (t, 2H, J = 7.1 Hz, OCH2), 7.08–7.25 (m, 5H, Ar–H);
13C NMR (100 MHz, CDCl3): d = 14.5, 23.2, 26.8, 30.5,
32.5 (C–S), 33.9, 34.5, 68.3 (O–CH2), 125.8, 128.3, 128.8,
139.2, 172 (C@S) ppm; Mass: m/e (%) = 296 (84), 197 (38),
99 (54), 85 (63), 71 (45), 43 (100); Analysis: C16H24OS2,
Calcd C, 64.81; H, 8.16; S, 21.63. Found: C, 65.12; H,
7.93; S, 21.25.
6. (a) Degani, I.; Fochi, R.; Regondi, V. Synthesis 1979, 178–
180; (b) Tanaka, K.; Yamagichi, N.; Tanikaga, R.; Kaji,
A. Bull. Soc. Chem. Jpn. 1976, 52, 3619–3627.
7. Okatawa, M.; Nakai, T.; Otsuji, Y.; Imoto, E. J. Org.
Chem. 1965, 30, 2025–2030.
O,S-1-Propylbutyl-3-phenylpropyl dithiocarbonate (entry
3): Oil, IR (neat): 1090, 1199, 1220 cmÀ1 1H NMR
;
8. Curran, D. P. Synthesis 1988, 417–439, and 489–513.
9. (a) Ferrier, R. J.; Vethavisar, N. J. Chem. Soc., Chem.
Commun. 1970, 1385–1386; (b) Baldwin, J. E.; Holfe, G.
A. J. Am. Chem. Soc. 1971, 93, 6307–6308; (c) Nakai, T.;
Ari-Izumi, A. Tetrahedron Lett. 1976, 27, 2335–2338.
10. Alexander, B. H.; Gertler, S. I.; Oda, T. A.; Bown, R. T.;
Ihndris, R. W.; Beroza, M. J. Org. Chem. 1960, 25, 626–
632.
11. Dunn, A. D.; Rudorf, W. Carbon Disulfide in Organic
Chemistry; Ellis Haward: Chichester, 1989, p 316.
12. Meurling, P.; Sjoberg, K.; Sjoberg, B. Acta Chem. Scand.
1972, 26, 279–284.
(400 MHz, CDCl3): d = 0.94–0.97 (t, 6H, J = 6.5 Hz,
CH3), 1.32–1.36 (m, 4H, CH2CH3), 1.43–1.46 (m, 4H,
O–CH–CH2), 2.27–2.30 (m, 4H, PhCH2CH2CH2), 2.54–
2.57 (t, 2H, J = 6.4 Hz, PhCH2), 2.85–2.87 (t, 2H,
J = 6.6 Hz, PhCH2CH2– CH2–S), 3.20–3.24 (m, 1H, O–
CH), 7.08–7.25 (m, 5H, Ar–H); 13C NMR (100 MHz,
CDCl3) d = 14.3, 17.2, 32.7 (S–CH2), 34.2, 35.6, 72.3 (O–
CH), 126.4, 128.2, 128.8, 138.8, 172.5 (C@S) ppm; Mass,
m/e (%) = 310 (85), 197 (41), 99 (53), 105 (44), 91 (100%);
Analysis: C17H26OS2, Calcd C, 65.75; H, 8.44; S, 20.65.
Found: C, 65.33; H, 8.59; S, 20.99.
O,S-n-Nonyl-1-butylpentyl dithiocarbonate (entry 9): Oil,
13. Mori, T.; Taguchi, T. Synthesis 1975, 469–471.
14. Degani, I.; Forki, R.; Sunti, M. Synthesis 1977, 873–875.
15. Chenvert, R.; Paquin, R.; Rodrigue, A. Synth. Commun.
1981, 11, 817–821.
IR (neat): 1092, 1193,1226 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d = 0.91–0.93 (t, 9H, J = 6.6 Hz, CH3), 1.29–1.33
(m, 20H, CH2 of chain), 1.50–1.52 (t, 2H, J = 7.2 Hz
OCH2CH2 of nonyl group), 1.92–1.94 (m, 4H, SCHCH2),
2.52–2.54 (m, 1H, SCH), 3.54–3.56 (t, 2H, J = 7.1 Hz,
OCH2); 13C NMR (100 MHz, CDCl3), d = 14.0, 23.1,
26.3, 28.9, 29.8, 30.0, 30.3, 36.2, 40.6 (CH–S), 67.7
(CH2O), 172.4 (C@S) ppm; Mass, m/e (%) = 346 (89),
219 (44), 127 (75), 109 (52), 57 (82), 43 (91); Analysis:
C19H38OS2, Calcd C, 65.83; H, 11.05; S, 18.50. Found: C,
65.53; H, 11.20; S, 18.66.
16. (a) Chaturvedi, D.; Kumar, A.; Ray, S. Synth. Commun.
2002, 32, 2651–2656; (b) Chaturvedi, D.; Ray, S. Lett.
Org. Chem. 2005, 2, 742–744; (c) Chaturvedi, D.; Ray, S.
J. Sulfur Chem. 2005, 26, 365–371; (d) Chaturvedi, D.;
Ray, S. Monatsh. Chem. 2006, 137, 201–206; (e) Chatur-
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Chaturvedi, D.; Ray, S. Monatsh. Chem. 2006, 137, 459–
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137, 465–469; (h) Chaturvedi, D.; Ray, S. J. Sulfur Chem.
2006, 27, 265–270; (i) Chaturvedi, D.; Ray, S. Monatsh.
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N.; Mishra, V.; Monatsh. Chem. 137, in press; (k)
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17, in press.
O,S-n-Dodecy1-1,1,-dibutylpentyl dithiocarbonate (entry
10): mp = 64 °C, IR (KBr): 1075, 1183, 1225 cmÀ1 1H
;
NMR (400 MHz, CDCl3): d = 0.88–0.91 (t, 12H, J=
6.9 Hz, CH3), 1.29–1.33 (m, 30H, J = 6.8 Hz, CH2 of
chain), 1.48–1.51 (t, 2H, J= 6.7 Hz, OCH2CH2 of dodecyl
group), 1.88–1.90 (m, 6H, S–C–CH2), 3.51–3.53 (t, 2H,
J = 7.2 Hz, OCH2); 13C NMR (100 MHz, CDCl3)
d = 14.0, 23.1, 26.3, 28.9, 29.8, 30.0, 30.3, 36.2, 40.3 (C-
S), 67.8 (CH2O), 172.6 (C@S) ppm; Mass, m/e (%) = 444
(91), 275 (49), 183 (52), 169 (65), 127 (76), 109 (54), 57
(77), 43 (100) Analysis: C26H52OS2 Calcd C, 70.20; H,
11.78; S, 14.40. Found: C, 70.53; H, 11.44; S, 14.31.
17. (a) Chaturvedi, D.; Kumar, A.; Ray, S. Tetrahedron Lett.
2003, 44, 7637–7639; (b) Chaturvedi, D.; Ray, S. Tetra-
hedron Lett. 2006, 47, 1307–1309.
18. Typical experimental procedure: O,S-Dibenzyl dithio-
carbonate (entry 1): Benzyl alcohol (1 ml, 9 mmol) and
CS2 (4 ml, in excess) were dissolved in dry DMSO (35 ml).
To the reaction mixture triphenylphosphine (2.2 g,
9 mmol) was added and then diethyl azodicarboxylate
(1.33 ml, 9 mmol) was added slowly in 2–3 small portions.
Next, benzyl alcohol (1 ml, 9 mmol) was added. The
reaction was stirred until completion (5 h) as checked by
TLC. The reaction mixture was then poured into distilled
water (50 ml) and extracted with ethyl acetate thrice. The
organic layer was separated and dried over anhydrous
sodium sulfate and then concentrated to obtain O,S-
dibenzyl dithiocarbonate as an oil (2.33 g, 92%). IR (neat):
O,S-n-Octy1-3(2-naphthyloxy-propyl)
(entry 16): mp = 110 °C, IR (KBr): 1078, 1187,
1229 cmÀ1 1H NMR (400 MHz, CDCl3): d = 0.92–0.94
dithiocarbonate
;
(t, 3H, J = 6.4 Hz, CH3), 1.29–1.33 (m, 10H, J = 6.7 Hz,
CH2), 1.48–1.50 (m, 2H, J = 7.0 Hz, OCH2CH2), 2.37–
2.39 (m, 2H, J = 6.5 Hz, O–CH2CH2CH2–S), 2.88–2.90 (t,
2H, J = 6.5 Hz, SCH2), 3.53–3.55 (t, 2H, J = 7.2 Hz,
OCH2), 7.04–7.78 (m, 7H, Ar–H); 13C NMR (100 MHz,
CDCl3) d = 14.1, 23.2, 26.3, 28.5, 29.9, 30.5, 32.6, 67.8 (O–
CH2 of n-octyl), 71.2 (naphthyl–O–CH2), 105.8, 118.8,
123.7, 126.4, 127.7, 129.3, 129.5, 134.6, 157.7 (aromatic),
172.5 (C@S) ppm; Mass, m/e (%) = 390 (95), 277 (44), 185
(62), 127(69), 113 (65), 57(73), 43 (100); Analysis:
C22H30O2S2, Calcd C, 67.65; H, 7.74; S, 16.42. Found:
C, 67.29; H, 7.92; S, 16.61.
1085, 1190, 1225 cmÀ1 1H NMR (400 MHz, CDCl3):
;
d = 4.28 (s, 2H, PhCH2S), 5.52 (s, 2H, PhCH2O), 7.20–
7.40 (m, 10H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3):
d = 38.2 (PhCH2S), 74.5 (PhCH2O), 127.4, 127.9, 128.5,