N-Chlorosuccinimide-promoted synthesis of thiophosphates from thiols and phosphonates under mild conditions

Article abstract of DOI:10.1039/c3gc41839a

A very simple N-chlorosuccinimide-promoted synthesis of thiophosphates through the coupling of thiols and phosphonates is reported. Notably, the reactions were carried out in the absence of a base. Functional groups including fluoro, bromo and trifluoromethyl are all tolerated by the reaction conditions employed. Both aryl and alkyl thiols are coupled smoothly with a broad spectrum of phosphonates to afford the corresponding thiophosphates in good to excellent yields.

Full text of DOI:10.1039/c3gc41839a

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N-Chlorosuccinimide-promoted synthesis of
thiophosphates from thiols and phosphonates
Cite this: Green Chem., 2014, 16, 357
under mild conditions†
Yi-Chen Liu and Chin-Fa Lee*
A very simple N-chlorosuccinimide-promoted synthesis of thiophosphates through the coupling of thiols
and phosphonates is reported. Notably, the reactions were carried out in the absence of a base. Func-
tional groups including fluoro, bromo and trifluoromethyl are all tolerated by the reaction conditions
employed. Both aryl and alkyl thiols are coupled smoothly with a broad spectrum of phosphonates to
afford the corresponding thiophosphates in good to excellent yields.
Received 4th September 2013,
Accepted 26th October 2013
DOI: 10.1039/c3gc41839a
www.rsc.org/greenchem
Introduction
Thiophosphates are important skeletons in biology1 and
organic synthesis,2 as a result, the synthesis of thiophosphates
has gained much attention. Timperley and coworkers reported
the formation of thiophosphates through the coupling of the
corresponding phosphorochloridates or phosphorobromidates
with thiols in the presence of a base; however, the preparation
of phosphorochloridates and phosphorobromidates is
required [Scheme 1(a)]. A typical procedure for preparing phos-
phorochloridates and phosphorobromidates relied on reacting
H-phosphonates with chlorine and bromine in an organic
solvent, respectively. Chlorine and bromine are both toxic and
difficult to control.3 Kaboudin described a one-pot procedure
by the treatment of diethyl phosphonate with ammonium
acetate/sulfur/Al2O3 followed by addition of alkyl halides to
give thiophosphates; unfortunately, the substrate is limited to
diethyl phosphonate, and only alkyl substituents are intro-
duced to the sulfur atom in this system [Scheme 1(b)], more-
over, microwave-heating is required in this approach.4 Jensen
et al. reported that thiophosphates can be synthesized through
the coupling of sodium diethyl phosphonate with organic di-
sulfides [Scheme 1(c)],5 but again there are several limitations
to using this approach. First, a strong base (i.e., NaH) is
necessary to generate the sodium diethyl phosphonate.
Notably, a strong base will generally reduce the functional
group compatibility. Second, one equiv. of disulfide is required
to produce the thiophosphate as the target molecule; however,
Scheme 1 Preparation of thiophosphates.
one equiv. of sodium thiolate6,7 will be generated as a waste.
Recently, a copper-catalyzed coupling of dialkyl phosphonates
with organic disulfides was reported by Zhao and coworkers
[Scheme 1(d)];8 again several synthetic limitations have been
observed by using this approach. First, the reaction is limited
to dialkyl phosphonates. Second, no alkyl disulfides are
involved in this system. Third, an additional base is required.
In addition, thiophosphates have shown potential applications
in chemical biology; and transition metals are generally
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan 402,
Republic of China. E-mail: cfalee@dragon.nchu.edu.tw; Fax: +886 4 2286-2547;
Tel: +886 4 2284-0411 ext. 810
†Electronic supplementary information (ESI) available: Spectral data for new
products. See DOI: 10.1039/c3gc41839a
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avoided for use in the final step for the preparation of biologi-
We examined the scope of the substrates based on the opti-
cal molecules in order to exclude the presence of transition mized reaction conditions above as demonstrated in Table 2.
metal-contaminant. Aryl thiols bearing electron-donating and electron-withdrawing
From the substrate generality and conditions employed, a groups reacted with a variety of phosphonates to give the
general direct coupling of thiols with H-phosphonates in tran- corresponding thiophosphates in good to excellent yields.
sition metal-free and mild conditions is highly desirable for Notably, this system shows good functional group compatibility.
preparing thiophosphates. Building on our previous work,9 we Functional groups including fluoro (Table 2, entries 2 and 19),
now report a general method to prepare thiophosphates bromo (Table 2, entries 3 and 7), trifluoromethyl (Table 2,
through N-chlorosuccinimide-promoted10–12 P–S bond for- entries 9, 10, 16 and 17) are all tolerated by the reaction con-
mation between phosphonates and thiols. Importantly, this ditions. Sterically demanding substituted aryl thiols did not
approach is simple and the reactions are carried out in one decrease the reactivity of the reactions, and afforded the pro-
pot without an additive base [Scheme 1(e)].
ducts with satisfying yields (Table 2, entries 7, 8, 14 and 18).
Based on the promising results for aryl thiols in Table 2, we
then turned our attention to the coupling reaction of alkyl
thiols with phosphonates. The results are summarized in
Table 3. Alkyl thiols such as cyclohexanethiol (4a), 2-methyl-
butane-1-thiol (4b), hexanethiol (4c) and benzylthiol (4d) were
coupled smoothly with phosphonates to give the corres-
ponding thiophosphates in good to excellent yields.
Results and discussion
Thiophenol 1a and diphenyl phosphonate 2a were used as
model substrates to determine the optimized reaction con-
ditions. The results are summarized in Table 1. A trace
amount of desired product was detected using 1.1 equiv. of
N-iodosuccinimide (Table 1, entry 1), because the intermediate
sulfenyliodide is too reactive to react with diphenyl phospho-
nate; this results in the formation of diphenyl disulfide as a
side product. Interestingly, a 23% yield of the target, 3a was
afforded when N-bromosuccinimide was used instead of
N-iodosuccinimide (Table 1, entry 2). To our delight, a 78%
yield of 3a was achieved when the reaction was carried out by
using 1.1 equiv. of N-chlorosuccinimide (NCS, Table 1, entry 3).
No improvement was observed when Et3N was added as a base
(Table 1, entry 4).9 The control experiment showed that no
product was formed in the absence of N-chlorosuccinimide
(Table 1, entry 5). We then studied the influence of solvent
(Table 1, entries 6–11) and found that MeCN was superior to
THF, ether, dioxane, DMF and DMSO.
Conclusions
In conclusion, we report a convenient protocol for the syn-
thesis of thiophosphates through the N-chlorosuccinimide-
promoted coupling of thiols with phosphates. Both aryl and
alkyl thiols are coupled smoothly with a variety of phosphates
to provide the corresponding thiophosphates in good to excel-
lent yields in the absence of a base. Importantly, it is not
necessary to functionalize the starting materials, and this one-
pot procedure can be completed within 30 min. Functional
groups including fluoro, bromo and trifluoromethyl are all tol-
erated by the reaction conditions employed. Applications of
N-chlorosuccinimide-promoted coupling reaction for carbon–
carbon and carbon–heteroatom bond formations are underway
in our laboratory.
Table 1 Optimize the reaction conditionsa
Experimental
General information
All chemicals were purchased from commercial suppliers and
used without further purification. TLC analyses were per-
formed on Merck DC-Alufolien with Kieselgel 60F-254, and
were visualized with UV light. Purifications were performed by
flash chromatography on silica gel 60 (Merck, 230–400 mesh
ASTM). NMR spectra were recorded on a Varian Unity Inova-
600 or a Varian Mercury-400 instrument using CDCl3 as the
solvent. Chemical shifts are reported in parts per million
(ppm) and referenced to the residual solvent resonance. Coup-
ling constants (J) are reported in hertz (Hz). Standard abbrevi-
ations indicating multiplicity were used as follows: s = singlet,
d = doublet, t = triplet, dd = double doublet, q = quartet, m =
multiplet. IR spectra were measured using a Bruker Equinox
55 or Bruker Tensor 27 spectrophotometer. High resolution
mass spectra (HRMS) were recorded on an electron ionization
Entry
X
Solvent
Yieldb (%)
1
2
I
Toluene
Toluene
Toluene
Toluene
Toluene
THF
Ether
Dioxane
DMF
Trace
23
78
76
—
81
75
79
76
Br
Cl
Cl
—
Cl
Cl
Cl
Cl
Cl
Cl
3
4c
5
6
7
8
9
10
11
DMSO
MeCN
Trace
85
a Reaction conditions: thiophenol (1.0 mmol), N-halosuccinimide
(1.1 mmol), under a nitrogen atmosphere in solvent (1.5 mL) at rt for
20 min for the first step; diphenyl phosphonate (1.0 mmol) was added,
and reacted at rt for 10 min for the second step. b Isolated yield. c Et3N
(1.0 mmol) was added in the second step.
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Table 2 NCS-promoted synthesis of thiophosphates from aryl thiols
and phosphonatesa
Table 2 (Contd.)
Entry
14
1
2
3
Yield (%)
71
Entry
1
1
2
3
Yield (%)
81
1g
2c
2a
2
3
4
5
2a
2a
2a
53
50
50
85
15
16
1b
1i
2c
2c
62
76
17
18
1h
1f
2c
2c
93
70
1a
1b
6
7
2b
2b
94
96
19
1c
2c
66
a Reaction conditions unless otherwise stated: aryl thiol (1.0 mmol),
NCS (1.1 mmol), under a nitrogen atmosphere in MeCN (1.5 mL) at rt
for 20 min for the first step; phosphonate (1.0 mmol) was added, and
reacted at rt for 10 min for the second step.
8
2b
82
time-of-flight (EI-TOF) mass spectrometer at the National
Chung Hsing University.
9
2b
2b
58
84
General procedure for Table 1
A Schlenk tube equipped with a magnetic stir bar was charged
with N-chlorosuccinimide (0.15 g, 1.1 mmol), thiophenol 1a
(1.0 mmol) and solvent (1.5 mL). After the mixture was stirred
for 20 min, diphenylphosphonate 2a (1.0 mmol) was added by
a syringe under a nitrogen-filled balloon. After being stirred
for another 10 min at room temperature, the resulting solution
was directly filtered through a pad of silica gel and then
washed with ethyl acetate (20 mL) and concentrated to give the
crude material which was then purified by column chromato-
graphy (SiO2, hexane) to afford 3a.
10
11
12
1c
1e
2b
2b
60
83
Representative example of Table 1
13
1a
72
O,O,S-Triphenylphosphorothioate (entry 11, 3a). Following
the general procedure for Table 1, using thiophenol (0.103 mL,
1.0 mmol, 1.0 equiv.), N-chlorosuccinimide (0.15 g, 1.1 mmol,
1.1 equiv.), MeCN (1.5 mL) and diphenylphosphonate
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Table 3 NCS-mediated coupling of alkyl thiols with phosphonatesa
2871, 1949, 1868, 1775, 1718, 1593, 1489, 1457, 1442, 1367,
1270, 1157, 1071, 1025, 1007, 920, 827, 746 cm−1; HRMS-EI
calcd for C18H15O3PS: 342.0480, found: 342.0484.
General procedure for Table 2
A Schlenk tube equipped with a magnetic stir bar was charged
with N-chlorosuccinimide (0.15 g, 1.1 mmol), aryl thiol 1
(1.0 mmol) and MeCN (1.5 mL). After the mixture was stirred
for 20 min, phosphonate 2 (1.0 mmol) was added by a syringe
under a nitrogen-filled balloon. After being stirred for another
10 min at room temperature and diluted with ethyl acetate
(20 mL), the resulting solution was directly filtered through a
pad of silica gel and then washed with ethyl acetate (20 mL)
and concentrated to give the crude material which was then
purified by column chromatography (SiO2, hexane) to yield 3.
S-(4-Methoxyphenyl) O,O-diphenylphosphorothioate (3b).
Following the general procedure for Table 2, using 4-meth-
oxythiophenol (0.123 mL, 1.0 mmol) and diphenylphospho-
nate (0.192 mL, 1.0 mmol), and then purification by column
chromatography (SiO2, hexane) provides 3b as a colorless oil
(301 mg, 81% yield). 1H NMR (400 MHz, CDCl3) δ 3.77 (s, 3 H),
6.83–6.85 (m, 2 H), 7.17–7.22 (m, 6 H), 7.31–7.39 (m, 6 H);
13C NMR (100 MHz, CDCl3) δ 55.2, 114.7 (d, J = 8.2 Hz), 115.0
(d, J = 2.7 Hz), 120.3 (d, J = 5.4 Hz), 125.4, 129.6, 136.8 (d, J =
5.5 Hz), 150.2 (d, J = 8.2 Hz), 160.8 (d, J = 2.7 Hz); 31P NMR
(162 MHz, CDCl3) δ 16.17; IR (CHCl3): ν 3069, 3013, 2919,
2839, 1592, 1491, 1459, 1408, 1271, 1251, 1206, 1184, 1161,
1107, 1071, 1026, 1007, 938, 829, 769, 689 cm−1; HRMS-EI
calcd for C19H17O4PS: 372.0585, found: 372.0595.
Entry
1
4
2
5
Yield [%]
88
2a
2
3
4
5
2a
2a
2a
2b
87
75
74
74
C6H15SH4c
4a
6
7
4b
4d
2b
2b
92
71
S-(4-Fluorophenyl) O,O-diphenylphosphorothioate (3c). Fol-
lowing the general procedure for Table 2, using 4-fluorothio-
phenol (0.107 mL, 1.0 mmol) and diphenylphosphonate
(0.192 mL, 1.0 mmol), and then purification by column
chromatography (SiO2, hexane) provides 3c as a colorless oil
(190 mg, 53% yield). 1H NMR (400 MHz, CDCl3) δ 7.00–7.05
(m, 2 H), 7.19–7.26 (m, 6 H), 7.33–7.37 (m, 4 H), 7.43–7.47 (m,
2 H); 13C NMR (150 MHz, CDCl3) δ 115.3, 116.7 (dd, J = 2.4,
21.8 Hz), 120.4 (d, J = 4.8 Hz), 125.7, 129.8, 137.4 (q, J = 4.7
Hz), 150.2 (d, J = 8.6 Hz), 163.7 (dd, J = 3.8, 250.1 Hz); 31P NMR
(162 MHz, CDCl3) δ 15.19; 19F NMR (376 MHz, CDCl3) δ −111.8
(s); IR (CHCl3): ν 3069, 1590, 1488, 1457, 1399, 1272, 1182,
8
9
4a
4b
2c
2c
68
89
10
4d
2c
67
1158, 1093, 1071, 1025, 1008, 939, 833, 766, 688 cm−1
HRMS-EI calcd for C18H14FO3PS: 360.0385, found: 360.0376.
;
a Reaction conditions unless otherwise stated: alkyl thiol (1.0 mmol),
S-(4-Bromophenyl) O,O-diphenylphosphorothioate (3d). Fol-
NCS (1.1 mmol), under a nitrogen atmosphere in MeCN (1.5 mL) at rt lowing the general procedure for Table 2, using 4-bromothio-
for 20 min for the first step; phosphonate (1.0 mmol) was added, and
reacted at rt for 10 min for the second step.
phenol (0.189 mL, 1.0 mmol) and diphenylphosphonate
(0.192 mL, 1.0 mmol), and then purification by column
chromatography (SiO2, hexane) provides 3d as a colorless oil
(212 mg, 50% yield). 1H NMR (400 MHz, CDCl3) δ 7.18–7.23
(m, 6 H), 7.31–7.35 (m, 6 H), 7.42–7.44 (m, 2 H); 13C NMR
(0.192 mL, 1.0 mmol) and then purification by column chrom-
atography (SiO2, hexane) provides 3a as a colorless oil (290 mg,
85% yield). 1H NMR (400 MHz, CDCl3) δ 7.16–7.30 (m, 6 H),
7.31–7.37 (m, 7 H), 7.48–7.51 (m, 2 H); 13C NMR (100 MHz,
CDCl3) δ 115.3, 120.3, (d, J = 2.7 Hz), 125.5, 129.2, 129.4, 129.5,
129.7, 135.1 (d, J = 5.4 Hz), 150.2 (d, J = 9.1 Hz); 31P NMR
(162 MHz, CDCl3) δ 15.52; IR (CHCl3): ν 3064, 2959, 2929,
(100 MHz, CDCl3) δ 115.3, 120.3 (d, J = 4.6 Hz), 125.7, 129.2,
129.8, 132.5 (d, J = 2.8 Hz), 136.6 (d, J = 5.4 Hz), 150.1; 31P
NMR (162 MHz, CDCl3) δ 14.49; IR (CHCl3): ν 3068, 2919,
2851, 1942, 1899, 1778, 1590, 1488, 1387, 1273, 1181, 1085,
1070, 1025, 1009, 939, 817, 765, 689, 619, 590, 545, 512 cm−1
HRMS-EI calcd for C18H14BrO3PS: 419.9585, found: 419.9592.
;
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O,O-Diphenyl S-p-tolylphosphorothioate (3e). Following the
O,O-Dibutyl S-naphthalen-1-yl phosphorothioate (3i). Fol-
general procedure for Table 2, using 4-methylbenzenethiol lowing the general procedure for Table 2, using 1-naphthale-
(0.124 mL, 1.0 mmol) and diphenylphosphonate (0.192 mL, nethiol (0.140 mL, 1.0 mmol) and dibutylphosphonate
1.0 mmol), and then purification by column chromatography (0.203 mL, 1.0 mmol), and then purification by column
(SiO2, hexane) provides 3e as a yellow oil (160 mg, 50% yield). chromatography (SiO2, hexane) provides 3i as a yellow oil
1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3 H), 7.11–7.21 (m, 8 H), (290 mg, 82% yield). 1H NMR (400 MHz, CDCl3) δ 0.79–0.83
7.30–7.38 (m, 6 H); 13C NMR (100 MHz, CDCl3) δ 21.1, 115.4, (m, 6 H), 1.18–1.27 (m, 4 H), 1.45–1.52 (m, 4 H), 3.97–4.10 (m,
120.4 (d, J = 5.5 Hz), 125.5, 129.2, 129.7, 130.2 (d, J = 2.8 Hz), 4 H), 7.42 (t, J = 7.8 Hz, 1 H), 7.50 (t, J = 7.2 Hz, 1 H), 7.56 (t, J =
135.2 (d, J = 5.5 Hz), 140.0, 150.3 (d, J = 9.1 Hz); 31P NMR 7.6 Hz, 1 H), 7.82–7.91 (m, 3 H), 8.52 (d, J = 8.4 Hz, 1H);
(162 MHz, CDCl3) δ 15.93; IR (CHCl3): ν 3097, 3072, 3043, 13C NMR (100 MHz, CDCl3) δ 13.3, 18.3, 32.0 (d, J = 6.4 Hz),
2962, 2922, 2869, 1942, 1906, 1865, 1639, 1594, 1488, 1456, 67.7 (d, J = 7.3 Hz), 123.5 (d, J = 8.2 Hz), 125.4 (d, J = 3.6 Hz),
1400, 1378, 1263, 1158, 1071, 1025, 919, 809, 757, 689 cm−1
HRMS-EI calcd for C19H17O3PS: 356.0636, found: 356.0630.
;
125.8, 126.2, 126.8, 128.3, 130.0 (d, J = 3.6 Hz), 134.0 (d, J =
1.8 Hz), 134.5 (d, J = 3.6 Hz), 135.0 (d, J = 5.4 Hz); 31P NMR
O,O-Dibutyl S-phenyl phosphorothioate (3f).8 Following the (162 MHz, CDCl3) δ 23.32; IR (CHCl3): ν 3056, 2961, 2933,
general procedure for Table 2, using thiophenol (0.103 mL, 2873, 1267, 1590, 1564, 1432, 1381, 1256, 1146, 1120, 1060,
1.0 mmol) and dibutylphosphonate (0.203 mL, 1.0 mmol), and 985, 903, 799, 772, 730 cm−1; HRMS-EI calcd for C18H25O3PS:
then purification by column chromatography (SiO2, hexane) 352.1262, found: 352.1256.
provides 3f as a yellow oil (257 mg, 85% yield). 1H NMR
O,O-Dibutyl S-(4-(trifluoromethyl)phenyl)phosphorothioate
(400 MHz, CDCl3) δ 0.88 (t, J = 7.4 Hz, 6 H), 1.30–1.40 (m, 4 H), (3j). Following the general procedure for Table 2, using 4-tri-
1.59–1.66 (m, 4 H), 4.06–4.17 (m, 4 H), 7.33–7.36 (m, 3 H), fluoromethylthiophenol (0.137 mL, 1.0 mmol) and dibutylpho-
7.55–7.58 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 13.4, 18.5, sphonate (0.203 mL, 1.0 mmol), and then purification by
31.9 (d, J = 7.3 Hz), 67.6 (d, J = 6.3 Hz), 126.5, 128.8 (d, J = column chromatography (SiO2, hexane) provides 3j as a color-
2.8 Hz), 129.1 (d, J = 1.9 Hz), 134.3 (d, J = 4.5 Hz); 31P NMR less oil (226 mg, 58% yield). 1H NMR (400 MHz, CDCl3) δ
(162 MHz, CDCl3) δ 23.60; IR (CHCl3): ν 3063, 2961, 2934, 0.88–0.94 (m, 6 H), 1.26–1.40 (m, 4 H), 1.61–1.68 (m, 4 H),
2874, 1641, 1583, 1471, 1442, 1383, 1258, 1194, 1120, 1060, 4.07–4.21 (m, 4 H), 7.60 (d, J = 8.4 Hz, 1 H), 7.72 (d, J = 8.0 Hz,
1021, 819, 783, 747, 692 cm−1
.
1 H), 7.78–7.84 (m, 2 H); 13C NMR (150 MHz, CDCl3) δ 13.3,
O,O-Dibutyl S-(4-methoxyphenyl)phosphorothioate (3g). 18.4, 31.9 (d, J = 6.8 Hz), 67.9 (d, J = 6.6 Hz), 123.6 (q, J = 270.9
Following the general procedure for Table 2, using 4-meth- Hz), 125.9, 130.7 (q, J = 32.8 Hz), 131.9 (d, J = 6.6 Hz), 134.1
oxythiophenol (0.123 mL, 1.0 mmol) and dibutylphosphonate (d, J = 5.4 Hz); 31P NMR (162 MHz, CDCl3) δ 22.06; 19F NMR
(0.203 mL, 1.0 mmol), and then purification by column (376 MHz, CDCl3) δ −64.5 (s); IR (CHCl3): ν 2963, 2936, 2876,
chromatography (SiO2, hexane) provides 3g as a yellow oil 1640, 1608, 1465, 1401, 1326, 1264, 1168, 1130, 1106, 1091,
1
(310 mg, 94% yield). H NMR (400 MHz, CDCl3) δ 0.91 (t, J = 1063, 1015, 889, 836, 772, 702 cm−1; HRMS-EI calcd for
7.4 Hz, 6 H), 1.33–1.41 (m, 4 H), 1.60–1.66 (m, 4 H), 3.80 (s, C15H22F3O3PS: 370.0979, found: 370.0970.
3 H), 4.06–4.15 (m, 4 H), 6.86–6.88 (m, 2 H), 7.46–7.48 (m,
O,O-Dibutyl S-(3-(trifluoromethyl)phenyl)phosphorothioate
2 H); 13C NMR (100 MHz, CDCl3) δ 13.4, 18.5, 32.0 (d, J = (3k). Following the general procedure for Table 2, using 3-tri-
9.4 Hz), 55.2, 67.6 (d, J = 7.3 Hz), 114.8 (d, J = 1.8 Hz), 116.4 (d, fluoromethylthiophenol (0.140 mL, 1.0 mmol) and dibutylpho-
J = 8.2 Hz), 136.2 (d, J = 2.7 Hz), 160.3; 31P NMR (162 MHz, sphonate (0.203 mL, 1.0 mmol), and then purification by
CDCl3) δ 24.32; IR (CHCl3): ν 3070, 2960, 2937, 1634, 1593, column chromatography (SiO2, hexane) provides 3k as a yellow
1574, 1494, 1463, 1383, 1290, 1245, 1176, 1043, 1016, 1008, oil (316 mg, 84% yield). 1H NMR (400 MHz, CDCl3) δ 0.88–0.96
993, 906, 830, 798, 731 cm−1; HRMS-EI calcd for C15H25O4PS: (m, 6 H), 1.30–1.40 (m, 4 H), 1.60–1.67 (m, 4 H), 4.08–4.20 (m,
332.1211, found: 332.1204.
4 H), 7.49 (t, J = 7.8 Hz, 1 H), 7.61–7.63 (m, 1 H), 7.78–7.84 (m,
S-(2-Bromophenyl) O,O-dibutylphosphorothioate (3h). Fol- 2 H); 13C NMR (150 MHz, CDCl3) δ 13.1, 18.4, 31.8 (d, J =
lowing the general procedure for Table 2, using 2-bromothio- 6.8 Hz), 67.8 (d, J = 6.8 Hz), 123.3 (q, J = 271.1 Hz), 125.4, 128.2
phenol (0.124 mL, 1.0 mmol) and dibutylphosphonate (d, J = 6.8 Hz), 129.5, 130.8, 131.4 (q, J = 32.0 Hz), 137.5 (d, J = 4.8
(0.203 mL, 1.0 mmol), and then purification by column Hz); 31P NMR (162 MHz, CDCl3) δ 22.27; 19F NMR (376 MHz,
chromatography (SiO2, hexane) provides 3h as a yellow oil CDCl3) δ −64.5 (s); IR (CHCl3): ν 3076, 2963, 2876, 1465, 1423,
(366 mg, 96% yield). 1H NMR (400 MHz, CDCl3) δ 0.88–0.93 1384, 1324, 1263, 1169, 1130, 1069, 986, 899, 799, 697 cm−1
;
(m, 6 H), 1.32–1.41 (m, 4 H), 1.61–1.67 (m, 4 H), 4.11–4.20 (m, HRMS-EI calcd for C15H22F3O3PS: 370.0979, found: 370.0970.
4 H), 7.17–7.21 (m, 1 H), 7.28–7.32 (m, 1 H), 7.32–7.63 (m, O,O-Dibutyl S-(4-fluorophenyl)phosphorothioate (3l). Fol-
1 H), 7.79–7.81 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 13.3, lowing the general procedure for Table 2, using 4-fluorothio-
18.4, 31.9 (d, J = 7.3 Hz), 67.9 (d, J = 6.4 Hz), 127.8 (d, J = 1.8 phenol (0.107 mL, 1.0 mmol) and dibutylphosphonate
Hz), 128.1 (d, J = 7.3 Hz), 128.5 (d, J = 5.5 Hz), 129.9, 133.3, (0.203 mL, 1.0 mmol), and then purification by column
136.1 (d, J = 4.5 Hz); 31P NMR (162 MHz, CDCl3) δ 22.03; IR chromatography (SiO2, hexane) provides 3l as a colorless oil
1
(CHCl3): ν 3062, 2962, 2934, 2874, 1633, 1562, 1452, 1428, (190 mg, 60% yield). H NMR (400 MHz, CDCl3) δ 0.91 (t, J =
1383, 1260, 1149, 1109, 1060, 1018, 900, 836, 753 cm−1
HRMS-EI calcd for C17H21BrO3PS: 380.0211, found: 380.0207.
;
7.4 Hz, 6 H), 1.31–1.41 (m, 4 H), 1.60–1.67 (m, 4 H), 4.04–4.18
(m, 4 H), 7.03–7.07 (m, 2 H), 7.53–7.57 (m, 2 H); 13C NMR
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(150 MHz, CDCl3) δ 13.3, 18.4, 31.9 (d, J = 7.4 Hz), 67.7 (d, J = (154 mg, 62% yield). 1H NMR (400 MHz, CDCl3) δ 3.79–3.84
6.6 Hz), 116.3 (dd, J = 2.6, 22.5 Hz), 121.6 (q, J = 9.2 Hz), 136.5 (m, 9 H), 6.87–6.90 (m, 2 H), 7.45–7.48 (m, 2 H); 13C NMR
(q, J = 4.5 Hz), 163.1 (dd, J = 3.0, 248.1 Hz); 31P NMR (100 MHz, CDCl3) δ 54.0 (d, J = 6.3 Hz), 55.2, 115.0 (d, J =
(162 MHz, CDCl3) δ 23.37; 19F NMR (376 MHz, CDCl3) δ −113.3 1.8 Hz), 115.8 (d, J = 6.4 Hz), 136.2 (d, J = 4.5 Hz), 160.5; 31P
(s); IR (CHCl3): ν 2962, 2935, 2875, 1640, 1590, 1491, 1465, NMR (162 MHz, CDCl3) δ 27.46; IR (CHCl3): ν 3070, 3007,
1383, 1258, 1232, 1158, 1060, 1017, 988, 891, 834, 783, 2955, 2849, 1639, 1592, 1494, 1462, 1408, 1291, 1250, 1177,
727 cm−1; HRMS-EI calcd for C14H22FO3PS: 320.1011, found: 1024, 832, 791, 768 cm−1; HRMS-EI calcd for C9H13O4PS:
320.1020.
248.0272, found: 248.0269.
O,O-Dibutyl S-p-tolylphosphorothioate (3m). Following the
O,O-Dimethyl S-(3-(trifluoromethyl)phenyl)phosphorothio-
general procedure for Table 2, using 4-methylbenzenethiol ate (3q). Following the general procedure for Table 2, using
(0.124 mL, 1.0 mmol) and dibutylphosphonate (0.203 mL, 3-trifluoromethylthiophenol (0.140 mL, 1.0 mmol) and
1.0 mmol), and then purification by column chromatography dimethylphosphonate (0.094 mL, 1.0 mmol), and then purifi-
(SiO2, hexane) provides 3m as a colorless oil (262 mg, 83% cation by column chromatography (SiO2, hexane) provides 3q
yield). 1H NMR (400 MHz, CDCl3) δ 0.88–0.92 (m, 6 H), as a colorless oil (216 mg, 76% yield). 1H NMR (400 MHz,
1.31–1.40 (m, 4 H), 1.59–1.66 (m, 4 H), 2.33 (s, 3 H), 4.05–4.17 CDCl3) δ 3.82–3.87 (m, 6 H), 7.50 (t, J = 7.8 Hz, 1 H), 7.63–7.65
(m, 4 H), 7.12–7.15 (m, 2 H), 7.42–7.45 (m, 2 H); 13C NMR (m, 1 H), 7.77–7.82 (m, 2 H); 13C NMR (150 MHz, CDCl3) δ 54.3
(100 MHz, CDCl3) δ 13.3, 18.4, 20.9, 31.9 (d, J = 7.3 Hz), 67.5 (d, J = 6.0 Hz), 123.3 (q, J = 271.1 Hz), 125.8, 127.5 (d, J =
(d, J = 6.4 Hz), 122.6 (d, J = 6.3 Hz), 129.9, 134.4 (d, J = 5.4 Hz), 2.7 Hz), 129.8 (d, J = 1.8 Hz), 131.0 (t, J = 4.3 Hz), 131.6 (q, J =
139.0; 31P NMR (162 MHz, CDCl3) δ 24.00; IR (CHCl3): ν 3025, 32.8 Hz), 137.7 (d, J = 4.8 Hz); 31P NMR (162 MHz, CDCl3)
2961, 2934, 2874, 1493, 1464, 1382, 1257, 1119, 1060, 1018, δ 25.47; 19F NMR (376 MHz, CDCl3) δ −64.4 (s); IR (CHCl3):
893, 810, 728 cm−1; HRMS-EI calcd for C15H25O3PS: 316.1262, ν 2958, 2855, 1640, 1449, 1423, 1325, 1263, 1169, 1127, 1022,
found: 316.1260.
O,O-Dimethyl S-phenyl phosphorothioate (3n). Following 286.0040, found: 286.0033.
898, 833, 799, 766, 697 cm−1; HRMS-EI calcd for C9H10F3O3PS:
the general procedure for Table 2, using thiophenol (0.103 mL,
O,O-Dimethyl S-(4-(trifluoromethyl)phenyl)phosphorothio-
1.0 mmol) and dimethylphosphonate (0.094 mL, 1.0 mmol), ate (3r). Following the general procedure for Table 2, using
and then purification by column chromatography (SiO2, 4-trifluoromethylthiophenol (0.137 mL, 1.0 mmol) and
hexane) provides 3n as a yellow oil (157 mg, 72% yield). 1H dimethylphosphonate (0.094 mL, 1.0 mmol), and then purifi-
NMR (400 MHz, CDCl3) δ 3.80–3.84 (m, 6 H), 7.34–7.38 (m, cation by column chromatography (SiO2, hexane) provides 3r
3 H), 7.55–7.58 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 54.1 (d, as a colorless oil (265 mg, 93% yield). 1H NMR (400 MHz,
J = 5.4 Hz), 125.8 (d, J = 7.3 Hz), 129.0 (d, J = 2.8 Hz), 129.3 (d, CDCl3) δ 3.84–3.89 (m, 6 H), 7.20–7.25 (m, 1 H), 7.30–7.34
J = 2.7 Hz), 134.4 (d, J = 5.5 Hz); 31P NMR (162 MHz, CDCl3) (m, 1 H), 7.64–7.66 (m, 1 H), 7.74–7.77 (m, 1 H); 13C NMR
δ 26.81; IR (CHCl3): ν 3060, 3004, 2954, 2919, 2851, 1962, 1887, (150 MHz, CDCl3) δ 54.3 (d, J = 6.0 Hz), 128.0 (d, J = 2.4 Hz),
1810, 1721, 1638, 1580, 1474, 1443, 1257, 1182, 1020, 918, 831, 128.0 (dd, J = 7.8, 106.2 Hz), 130.3 (d, J = 3.0 Hz), 133.4 (d, J =
796, 768, 694 cm−1; HRMS-EI calcd for C8H11O3PS: 218.0167, 2.4 Hz), 136.4 (d, J = 4.4 Hz); 31P NMR (162 MHz, CDCl3)
found: 218.0160.
δ 25.14; 19F NMR (376 MHz, CDCl3) δ −64.4 (s); IR (CHCl3):
O,O-Dimethyl S-naphthalen-1-yl phosphorothioate (3o). Fol- ν 3062, 3003, 2954, 2851, 1636, 1562, 1450, 1427, 1257, 1182,
lowing the general procedure for Table 2, using 1-naphthalene- 1109, 1030, 833, 757, 720, 646 cm−1; HRMS-EI calcd for
thiol (0.140 mL, 1.0 mmol) and dimethylphosphonate C9H10F3O3PS: 286.0040, found: 286.0044.
(0.094 mL, 1.0 mmol), and then purification by column
S-(2-Bromophenyl) O,O-dimethyl phosphorothioate (3s).
chromatography (SiO2, hexane) provides 3o as a yellow oil Following the general procedure for Table 2, using 2-bromo-
(191 mg, 71% yield). 1H NMR (400 MHz, CDCl3) δ 3.71–3.76 thiophenol (0.124 mL, 1.0 mmol) and dimethylphosphonate
(m, 6 H), 7.42 (t, J = 7.8 Hz, 1 H), 7.50 (t, J = 7.4 Hz, 1 H), 7.59 (0.094 mL, 1.0 mmol), and then purification by column
(t, J = 7.4 Hz, 1 H), 7.81–7.88 (m, 3 H), 8.50 (d, J = 8.4 Hz, 1 H); chromatography (SiO2, hexane) provides 3s as a yellow oil
13C NMR (100 MHz, CDCl3) δ 54.3 (d, J = 6.4 Hz), 122.8 (d, J = (208 mg, 70% yield). 1H NMR (400 MHz, CDCl3) δ 3.83–3.87
8.2 Hz), 125.5 (d, J = 5.5 Hz), 126.4, 127.1, 128.5, 130.3 (d, J = (m, 6 H), 7.60–7.62 (m, 2 H), 7.70–7.72 (m, 2 H); 13C NMR
3.7 Hz), 134.1 (d, J = 1.9 Hz), 134.5 (d, J = 3.7 Hz), 135.1 (d, J = (100 MHz, CDCl3) δ 54.2 (d, J = 5.5 Hz), 122.2, 124.9, 126.0,
5.4 Hz); 31P NMR (162 MHz, CDCl3) δ 26.31; IR (CHCl3): 130.7, 131.1, 134.2 (d, J = 5.4 Hz); 31P NMR (162 MHz, CDCl3)
ν 3056, 3006, 2954, 2851, 1722, 1637, 1590, 1564, 1503, 1456, δ 25.30; IR (CHCl3): ν 3097, 3046, 3005, 2958, 2855, 1688, 1576,
1380, 1336, 1256, 1183, 1020, 914, 831, 801, 771, 601, 1496, 1459, 1401, 1328, 1264, 1173, 1091, 1011, 837, 759,
569 cm−1; HRMS-EI calcd for C12H13O3PS: 268.0323, found: 767 cm−1; HRMS-EI calcd for C8H10BrO3PS: 295.9272, found:
268.0320.
295.9265.
S-(4-Methoxyphenyl) O,O-dimethyl phosphorothioate (3p).
S-(4-Fluorophenyl) O,O-dimethyl phosphorothioate (3t). Fol-
Following the general procedure for Table 2, using 4-meth- lowing the general procedure for Table 2, using 4-fluorothio-
oxythiophenol (0.123 mL, 1.0 mmol) and dimethylphospho- phenol (0.107 mL, 1.0 mmol) and dimethylphosphonate
nate (0.094 mL, 1.0 mmol), and then purification by column (0.094 mL, 1.0 mmol), and then purification by column
chromatography (SiO2, hexane) provides 3p as a yellow oil chromatography (SiO2, hexane) provides 3t as a colorless oil
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(156 mg, 66% yield). 1H NMR (400 MHz, CDCl3) δ 3.80–3.85 1H NMR (400 MHz, CDCl3) δ 0.83–0.87 (m, 3 H), 1.17–1.33 (m,
(m, 6 H), 7.04–7.09 (m, 2 H), 7.53–7.57 (m, 2 H); 13C NMR 6 H), 1.55–1.62 (m, 2H), 2.89–2.96 (m, 2 H), 7.18–7.25 (m, 2 H),
(150 MHz, CDCl3) δ 54.1 (d, J = 6.6 Hz), 116.5 (d, J = 21.5 Hz), 7.28–7.38 (m, 8 H); 13C NMR (100 MHz, CDCl3) δ 13.8, 22.2,
120.9 (q, J = 3.5 Hz), 136.6 (q, J = 12.8 Hz), 163.2 (dd, J = 3.2, 27.8, 30.4 (d, J = 5.4 Hz), 30.9, 31.6 (d, J = 3.7 Hz), 120.5 (d, J =
248.9 Hz); 31P NMR (162 MHz, CDCl3) δ 26.51; 19F NMR 4.6 Hz), 125.4, 129.6, 150.0 (d, J = 8.2 Hz); 31P NMR (162 MHz,
(376 MHz, CDCl3) δ −112.8 (s); IR (CHCl3): ν 2957, 2853, 1642, CDCl3) δ 22.23; IR (CHCl3): ν 3069, 3044, 2957, 2930, 2857,
1590, 1491, 1460, 1399, 1258, 1232, 1183, 1160, 1022, 835, 792, 1591, 1489, 1457, 1378, 1272, 1185, 1161, 1071, 1025, 930, 770,
767 cm−1; HRMS-EI calcd for C8H10FO3PS: 236.0072, found: 689 cm−1; HRMS-EI calcd for C18H23O3PS: 350.1106, found:
236.0081.
350.1101.
S-Benzyl O,O-diphenylphosphorothioate (5d). Following the
general procedure for Table 3, using α-toluenethiol (0.120 mL,
General procedure for Table 3
A Schlenk tube equipped with a magnetic stir bar was charged 1.0 mmol) and diphenylphosphonate (0.192 mL, 1.0 mmol),
with N-chlorosuccinimide (1.1 mmol), alkyl thiol 4 (1.0 mmol) and then purification by column chromatography (SiO2,
and MeCN (1.5 mL). After the mixture was stirred for 20 min, hexane) provides 5d as a yellow oil (263 mg, 74% yield). 1H
phosphonate 2 (1.0 mmol) was added by a syringe under a NMR (400 MHz, CDCl3) δ 4.11–4.15 (m, 2 H), 7.18–7.28 (m, 11 H),
nitrogen-filled balloon. After being stirred for another 10 min 7.30–7.35 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 35.7 (d, J =
at room temperature and diluted with ethyl acetate (20 mL) the 3.6 Hz), 120.6 (d, J = 4.6 Hz), 125.6, 127.8, 128.7, 128.9, 129.7,
resulting solution was directly filtered through a pad of silica 136.4 (d, J = 6.4 Hz), 150.1 (d, J = 8.2 Hz); 31P NMR (162 MHz,
gel and then washed with ethyl acetate (20 mL) and concen- CDCl3) δ 20.69; IR (CHCl3): ν 3065, 3032, 2942, 2851, 1950,
trated to give the crude material which was then purified by 1867, 1637, 1592, 1488, 1455, 1272, 1241, 1160, 1071, 1025,
column chromatography (SiO2, hexane) to yield 5.
S-Cyclohexyl O,O-diphenylphosphorothioate (5a). Following 356.0636, found: 356.0644.
1007, 922, 703, 691 cm−1; HRMS-EI calcd for C19H17O3PS:
the general procedure for Table 3, using cyclohexanethiol
O,O-Dibutyl S-cyclohexylphosphorothioate (5e). Following
(0.126 mL, 1.0 mmol) and diphenylphosphonate (0.192 mL, the general procedure for Table 3, using cyclohexanethiol
1.0 mmol), and then purification by column chromatography (0.126 mL, 1.0 mmol) and dibutylphosphonate (0.203 mL,
(SiO2, hexane) provides 5a as a colorless oil (306 mg, 88% 1.0 mmol), and then purification by column chromatography
yield). 1H NMR (400 MHz, CDCl3) δ 1.19–1.37 (m, 3 H), (SiO2, hexane) provides 5e as a colorless oil (226 mg, 74%
1.41–1.53 (m, 3 H), 1.64–1.69 (m, 2 H), 1.96–2.00 (m, 2 H), yield). 1H NMR (400 MHz, CDCl3) δ 0.86–0.96 (m, 6 H),
3.44–3.47 (m, 2 H), 7.17–7.21 (m, 2 H), 7.25–7.36 (m, 8 H); 13C 1.24–1.60 (m, 10 H), 1.65–1.77 (m, 6 H), 2.05–2.09 (m, 2 H),
NMR (100 MHz, CDCl3) δ 24.9, 25.6, 34.9 (d, J = 4.4 Hz), 46.9 3.26–3.29 (m, 1 H), 4.01–4.012 (m, 4 H); 13C NMR (100 MHz,
(d, J = 3.6 Hz), 120.5 (d, J = 4.5 Hz), 125.3, 129.5, 150.0 (d, J = CDCl3) δ 13.4, 18.6, 25.1, 25.7, 32.0 (d, J = 7.3 Hz), 35.1 (d, J =
8.2 Hz); 31P NMR (162 MHz, CDCl3) δ 21.64; IR (CHCl3): 5.5 Hz), 45.3 (d, J = 3.6 Hz), 66.9 (d, J = 6.4 Hz); 31P NMR
ν 3069, 3043, 2934, 2855, 2793, 1592, 1496, 1480, 1451, 1340, (162 MHz, CDCl3) δ 28.01; IR (CHCl3): ν 2960, 2933, 2873,
1275, 1241, 1193, 1180, 1166, 1157, 1100, 1025, 1006, 996, 950, 2856, 1252, 1148, 1121, 1061, 1020, 979, 888, 784, 727 cm−1
940, 903, 814, 772, 689 cm−1; HRMS-EI calcd for C18H21O3PS: HRMS-EI calcd for C14H29O3PS: 308.1575, found: 308.1570.
;
348.0949, found: 348.0956.
O,O-Dibutyl S-(2-methylbutyl)phosphorothioate (5f). Follow-
S-(2-Methylbutyl) O,O-diphenylphosphorothioate (5b). Fol- ing the general procedure for Table 3, using 2-methyl-1-buta-
lowing the general procedure for Table 3, using 2-methyl- nethiol (0.136 mL, 1.0 mmol) and dibutylphosphonate
1-butanethiol (0.136 mL, 1.0 mmol) and diphenylphosphonate (0.203 mL, 1.0 mmol), and then purification by column
(0.192 mL, 1.0 mmol), and then purification by column chromatography (SiO2, hexane) provides 5f as a colorless oil
chromatography (SiO2, hexane) provides 5b as a colorless oil (271 mg, 92% yield). 1H NMR (400 MHz, CDCl3) δ 0.89–1.00
1
(291 mg, 87% yield). H NMR (400 MHz, CDCl3) δ 0.81 (t, J = (m, 12 H), 1.21–1.28 (m, 1 H), 1.38–1.52 (m, 5 H), 1.65–1.72
7.4 Hz, 3 H), 0.88–0.90 (m, 3 H), 1.11–1.18 (m, 1 H), 1.35–1.41 (m, 5 H), 2.66–2.74 (m, 1 H), 2.82–2.88 (m, 1 H), 4.02–4.16 (m,
(m, 1 H), 1.55–1.60 (m, 1 H), 2.76–2.84 (m, 1 H), 2.91–2.99 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 10.8, 13.2, 18.2, 18.4, 28.0,
1 H), 7.17–7.21 (m, 2 H), 7.28–7.36 (m, 8 H); 13C NMR 31.8 (d, J = 7.3 Hz), 35.3 (d, J = 6.4 Hz), 37.1 (d, J = 4.5 Hz), 66.7
(100 MHz, CDCl3) δ 10.9, 18.2, 28.0, 35.4 (d, J = 5.4 Hz), 38.1 (d, J = 6.3 Hz); 31P NMR (162 MHz, CDCl3) δ 29.45; IR (CHCl3):
(d, J = 3.6 Hz), 120.4 (d, J = 4.6 Hz), 125.4, 129.6, 150.0 (d, J = ν 2962, 2934, 2875, 1258, 1064, 1020, 980, 784, 729 cm−1
8.2 Hz); 31P NMR (162 MHz, CDCl3) δ 22.58; IR (CHCl3): HRMS-EI calcd for C13H29O3PS: 296.1575, found: 296.1576.
;
ν 3070, 3044, 2963, 2930, 2876, 1591, 1489, 1458, 1430, 1380,
S-Benzyl O,O-dibutylphosphorothioate (5g). Following the
general procedure for Table 3, α-toluenethiol (0.120 mL,
1.0 mmol) and dibutylphosphonate (0.203 mL, 1.0 mmol), and
1333, 1272, 1185, 1161, 1071, 1025, 1007, 929, 770, 689 cm−1
HRMS-EI calcd for C17H21O3PS: 336.0949, found: 336.0952.
;
S-Hexyl O,O-diphenylphosphorothioate (5c). Following the then purification by column chromatography (SiO2, hexane)
general procedure for Table 3, using 1-hexanethiol (0.145 mL, provides 5g as a yellow oil (224 mg, 71% yield). 1H NMR
1.0 mmol) and diphenylphosphonate (0.192 mL, 1.0 mmol), (400 MHz, CDCl3) δ 0.91 (t, J = 7.4 Hz, 6 H), 1.32–1.41 (m, 4 H),
and then purification by column chromatography (SiO2, 1.57–1.64 (m, 4 H), 3.92–4.08 (m, 6 H), 7.23–7.37 (m, 5 H);
hexane) provides 5c as a colorless oil (261 mg, 75% yield). 13C NMR (100 MHz, CDCl3) δ 13.4, 18.5, 31.9 (d, J = 7.3 Hz),
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34.7 (d, J = 3.6 Hz), 67.0 (d, J = 5.4 Hz), 127.4, 128.4, 128.7, Center of Nanoscience and Nanotechnology (NCHU) are grate-
137.4 (d, J = 5.4 Hz); 31P NMR (162 MHz, CDCl3) δ 27.49; IR fully acknowledged for financial support. We also thank Prof.
(CHCl3) : ν 3089, 3064, 3031, 2961, 2935, 2874, 1639, 1496, Fung-E Hong (NCHU) for sharing his GC-MS instruments. C.F.
1457, 1432, 1383, 1260, 1149, 1120, 1061, 980, 894, 780, 730, L. is a Golden-Jade Fellow of Kenda Foundation, Taiwan.
701 cm−1; HRMS-EI calcd for C15H25O3PS: 316.1262, found:
316.12627.
S-Cyclohexyl O,O-dimethyl phosphorothioate (5h). Follow- References
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4676–4679; (e) J. A. Tunge and S. R. Mellegaard, Org. Lett.,
2004, 6, 1205–1207.
224.0633.
O,O-Dimethyl S-(2-methylbutyl)phosphorothioate (5i). Fol-
lowing the general procedure for Table 3, using 2-methyl-
1-butanethiol (0.136 mL, 1.0 mmol) and dimethylphosphonate
(0.094 mL, 1.0 mmol), and then purification by column
chromatography (SiO2, hexane) provides 5i as a yellow oil
1
(189 mg, 89% yield). H NMR (400 MHz, CDCl3) δ 0.92 (t, J =
6.8 Hz, 3 H), 1.00 (d, J = 6.4 Hz, 3 H), 1.21–1.28 (m, 1 H),
1.46–1.53 (m, 1 H), 1.66–1.71 (m, 1 H), 2.67–2.75 (m, 1 H),
2.82–2.89 (m, 1 H), 3.78–3.83 (m, 6 H); 13C NMR (100 MHz,
CDCl3) δ 10.9, 18.3, 28.0, 35.4 (d, J = 5.5 Hz), 37.2 (d, J = 3.6
Hz), 53.4 (d, J = 5.5 Hz); 31P NMR (162 MHz, CDCl3) δ 32.80; IR
(CHCl3): ν 2961, 2931, 2877, 2853, 1638, 1461, 1380, 1334,
1258, 1182, 1022, 925, 829, 794, 774, cm−1; HRMS-EI calcd for
C7H17O3PS: 212.0636, found: 212.0629.
S-Benzyl O,O-dimethyl phosphorothioate (5j). Following the
general procedure for Table 3, using α-toluenethiol (0.120 mL,
1.0 mmol) and dimethylphosphonate (0.094 mL, 1.0 mmol),
and then purification by column chromatography (SiO2,
hexane) provides 5j as a yellow oil (156 mg, 67% yield). 1H
NMR (400 MHz, CDCl3) δ 3.66–3.70 (m, 6 H), 4.02 (d, J = 14.4
Hz, 2 H), 7.27–7.37 (m, 5 H); 13C NMR (100 MHz, CDCl3) δ 34.7
(d, J = 3.7 Hz), 53.5 (d, J = 5.5 Hz), 127.5, 128.5, 128.7, 137.2 (d,
J = 5.4 Hz); 31P NMR (162 MHz, CDCl3) δ 30.94; IR (CHCl3):
ν 3063, 3030, 2953, 2851, 1638, 1496, 1455, 1261, 1183, 1015,
920, 829, 771, 702 cm−1; HRMS-EI calcd for C9H13O3PS:
232.0323, found: 232.0318.
12 (a) K. M. Schlosser, A. P. Krasutsky, H. W. Hamilton,
J. S. Reed and K. Sexton, Org. Lett., 2004, 6, 819–821;
(b) F. Kroll, R. Morphy, D. Rees and D. Gani, Tetrahedron
Lett., 1997, 38, 8573–8576; (c) J. S. Yadav, B. V. S. Reddy,
R. Jain and G. Baishya, Tetrahedron Lett., 2008, 49, 3015–
3018.
Acknowledgements
The National Science Council, Taiwan (NSC 101-2113-M-005-
008-MY3), the National Chung Hsing University and the
364 | Green Chem., 2014, 16, 357–364
This journal is © The Royal Society of Chemistry 2014