Synthesis of P(O)-S organophosphorus compounds by dehydrogenative coupling reaction of P(O)H compounds with aryl thiols in the presence of base and air

Article abstract of DOI:10.1016/j.tet.2017.04.035

The synthesis method of P(O)-S organophosphorus compounds by dehydrogenative coupling reaction of P(O)H compounds and aryl thiols was developed. The reaction was carried in the presence of a base and air, and exhibited good characters such as metal-free,

Full text of DOI:10.1016/j.tet.2017.04.035

Accepted Manuscript
Synthesis of P(O)-S organophosphorus compounds by dehydrogenative coupling
reaction of P(O)H compounds with aryl thiols in the presence of base and air
Wei He, Xiao Hou, Xinjin Li, Liang Song, Qing Yu, Zhongwei Wang
PII:
S0040-4020(17)30406-4
10.1016/j.tet.2017.04.035
TET 28636
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 19 February 2017
Revised Date: 12 April 2017
Accepted Date: 13 April 2017
Please cite this article as: He W, Hou X, Li X, Song L, Yu Q, Wang Z, Synthesis of P(O)-S
organophosphorus compounds by dehydrogenative coupling reaction of P(O)H compounds with aryl
thiols in the presence of base and air, Tetrahedron (2017), doi: 10.1016/j.tet.2017.04.035.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Synthesis of P(O)-S organophosphorus compounds by
dehydrogenative coupling reaction of P(O)H
Leave this area blank for abstract info.
compounds with aryl thiols in the presence of base and air
Wei Hea , Xiao Houa , Xinjin Lib , Liang Songa, Qing Yua,  and Zhongwei Wanga, 
a Shandong University of Science and Technology, College of Materials Science and Engineering, Qingdao 266590, China
b Shandong University of Technology, College of Chemical Engineering, Zibo 255091, China
O
R1 P H
R2
O
Na2CO3
22 examples
up to 90 % yield
H S R3
R1 P S R3
R2
+
DMF, rt, air
R1= phenyl, aryl, alkoxyl; R2= phenyl, aryl, alkoxyl; R3= aryl
Mild reaction conditions
Broad substract scope
Metal-free
Operational simplicity
Under air atmosphere

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Synthesis of P(O)-S organophosphorus compounds by dehydrogenative coupling
reaction of P(O)H compounds with aryl thiols in the presence of base and air
Wei Hea , Xiao Houa , Xinjin Lib , Liang Songa, Qing Yua,  and Zhongwei Wanga, 
a Shandong University of Science and Technology, College of Materials Science and Engineering, Qingdao 266590, China
b Shandong University of Technology, College of Chemical Engineering, Zibo 255091, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The synthesis method of P(O)-S organophosphorus compounds by dehydrogenative coupling
reaction of P(O)H compounds and aryl thiols was developed. The reaction was carried in the
presence of a base and air, and exhibited good characters such as metal-free, mild reaction
temperature, excellent substrate tolerance and with moderate to good yields. A plausible
mechanism was proposed.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Thiophosphate
Thiophosphonate
Diphenylphosphine oxide
Aryl thiols
Dehydrogenative coupling
NCS, MeCN
rt, 30 min
KI, TBPB
1. Introduction
O
DMSO, rt, 4-8 h
O
P
R2
O
P
R2
R1O P
H
3
3
R1
H
+
+ R SH
R1
S R3
CuI (5 mol%), Et3N
DMF, rt, 5 h
R SH
LiOBu-t
CHCl3, rt, 0.5 h
Sulfur-containing organophosphorus compounds, such as
thiophosphates and thiophosphonates, have attracted much
attention in recent decades due to their widespread application in
pharmaceuticals and agrochemicals.1,2 Accordingly, study on the
synthesis of these compounds is extensive. The reported methods
for the synthesis of thiophosphates and thiophosphonates include
Michaelis-Arbuzov reaction between P(OR)3 and RSO2Cl,3
nucleophilic substitution of R2P(O)Cl with RSH,4 coupling-
reductive reactions between R2P(O)H and RSO2Cl,5 direct
coupling reaction between R2P(O)H and RSH,6 and others.7
OR2
(R3 = aryl)
(R1, R2= aryl, alkyl)
(R1, R2= aryl, alkyl)
CuBr2 (5 mol%)
0.5 eq DCDMH
CH2Cl2, rt, 10 min
0.5 eq DDQ, DMF, rt
Na2CO3
DMF
rt, 3h
This work
O
P
R2
R1
H
+ R3SH
(R1= phenyl, aryl, alkoxyl
R2= phenyl, aryl, alkoxyl)
Recently, the direct coupling reaction of H-phosphine
oxides/H-phosphinate esters and thiols has got much attention
because of the atom economic character. Lee et al. and Kaboudin
et al. reported the reaction of H-phosphinate esters with thiol
prompted by NCS,8 CuI/Et3N9 and 1,3-Dichloro-5,5-
dimethylhydantoin (DCDMH),10 respectively. Pan et al. reported
the reaction of H-phosphine oxides with thiols using tert-butyl
peroxybenzoate (TBPB) and KI as additives.11 While, Yang et al.
mentioned the reaction of H-phosphine oxides with thiols
prompted by catalytic CuBr2 and 1.5 equiv. 2,3-Dichloro-5,6-
dicyano-4-benzoquinone (DDQ).12 In these reactions, metal
catalyst or other reaction promoters were needed. Han et al. has
reported the modification of the Atherton–Todd reaction of
secondary phosphine oxide with thiols in chloroform by the aid
of LiOBu-t.13 But, the organophosphorus reactant is limited to
secondary phosphine oxide and the promoters are limited to use
of chloroform and LiOBu-t.
Scheme 1. Synthesis of thiophosphates and thiophosphonates.
As we focused our attention on the environmental friendly
synthesis of sulfur-containing organophosphorus compounds, we
are interested to find that the direct dehydrogenative coupling
reaction of H-phosphine oxide, H-phosphonate and H-phosphite
with aryl thiol can readily proceed with the presence of base in
varied solvents. Herein we report the investigation of this
method.
2. Results and discussion
In the initial work, diphenylphosphine oxide (1a) and 4-
methyl benzenethiol (2a) were used as model reactants to
optimize the reaction conditions. It was found 1a and 2a can
react under various conditions (Table 1). Firstly, the reaction was
carried out in the presence of KOH in EtOH at room temperature.
To our delight, the desired product (3a) was obtained in a yield
———
 Corresponding author. E-mail: laura9751@163.com
 Corresponding author. E-mail: wangzhongwei@fusilinchem.com

ACCEPTED MANUSCRIPT
2
Tetrahedron
of 40% within 8 h (Table 1, entry 1). Encouraged by this result,
obtained for the meta-substituted and ortho-substituted substrates
(Scheme 2, 3j-3o).
we next surveyed a range of base under the same conditions
(Table 1, entries 2-5). These results showed that Na2CO3 has a
good effect, which afforded 3a in 70% yield. When the dosage of
1a was increased to 2.0 equiv, the product yield of 3a was
reduced to 48% unexpectedly (Table 1, entry 6). The effect of
solvents was also investigated (Table 1, entries 7-13). It was
found the proceeding of this reaction was greatly influenced by
solvent. Only a trace amount of desired product can be detected
when using CH3OH as solvent (Table 1, entry 7). And other
solvents, such as H2O, CH2Cl2, CH3CN and DMSO resulted in
lower yields (Table 1, entries 8, 11, 12 and 13). However, when
the reaction was carried in n-BuOH or DMF, the product 3a were
given in 84% or 87% yields, respectively (Table 1, entries 9 and
10). Since the reaction can be finished in relatively shorter time
in DMF, DMF was selected as the optimal solvent.
A series of P(O)H compounds were further examined to
expand the synthesis utility of this method. Diarylphosphine oxides
with methyl or Cl groups at para-position of the benzene ring
performed with moderate yields (Scheme 2, 3p and 3q). Under the
similar
reaction
conditions,
9,10-Dihydro-9-oxa-10-
phosphaphenanthrene 10-oxide (DOPO) could also couple with 4-
(tert-butyl)benzenethiol to furnish the corresponding product in
45% yield (Scheme 2, 3r). In addition to secondary phosphine
oxide, the coupling reaction between H-phosphinates or H-
phosphonate with aryl thiols also proceeded well to provide the
target compounds in moderate yields (Scheme 2, 3s-3v).
O
O
Na2CO3
R1
R3
S
R3
R1
P
H
S
P
H
+
Table 1. Optimization of reaction conditionsa
DMF, air, rt, 3h
R2
R2
1
3
2
£¨R1, R2 = phenyl, aryl, alkoxyl, R3 = aryl£©
O
P
O
O
P
S
P
S
S
NH2
2
2
2
3a, 87%
3c, 73%
3b, 90%
Entry
1
Base
KOH
Solvent
CH3CH2OH
CH3CH2OH
CH3CH2OH
CH3CH2OH
CH3CH2OH
CH3CH2OH
CH3OH
Yieldb(%)
40
O
O
P
O
P
P
S
NH
Br
S
NO2
S
Ac
2
2
2
3f, 72%
3e, 27%
3d, 88%
2
K2CO3
44
O
P
O
P
O
S
S
S
S
Cl
P
S
F
3
NaHCO3
Na2CO3
CH3CH2ONa
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
61
2
2
2
3i, 57%
3h, 63%
3g, 75%
4
70
O
P
O
P
O
P
5
6c
34
S
S
2
2
2
MeO
48
3k, 81%
3l, 83%
3j, 81%
OMe
O
P
O
P
O
P
7
Trace
45
S
S
2
2
2
8
H2O
3o, 70%
3n, 62%
3m, 77%
9d
10e
11
12
13
n-BuOH
DMF
84
O
P
S
O
O
P
O
87
S
Cl
P S
2
2
CH2Cl2
14
3p, 58%
3r, 45%
3q, 57%
CH3CN
43
O
O
O
O
P
S
P
S
P
S
DMSO
34
O
O
O
aUnless otherwise noted, the reactions were performed by adding 1a (1.2
mmol), 2a (1 mmol) and base (1.2 mmol) in solvent (5 ml) at room temperature
for 8 h. bIsolated yields. c1a (2 mmol), 2a (1 mmol). dReactions were performed
for 24 h. eReactions were performed for 3 h.
3u, 52%b
3t, 72%
3s, 63%
O
O
P
S
O
3v, 72%b
Under the optimized reaction conditions, we then
investigated the scope and limitations of the substrates of the
reaction. As listed in Scheme 2, the investigated varied aryl thiols
readily reacted with diphenylphosphine oxide to form
thiophosphinates in moderate to good yields. Aryl thiols bearing
electron-donating group at the para-position such as methyl,
amino, and tert-butyl groups coupled with diphenylphosphine
oxide to generate the expect products in good yields (Scheme 2,
3a-3c). Thiophenol is also a viable substrate with 88% yield of
target compound (Scheme 2, 3d). The aryl thiol with strong
electron-withdrawing group of -NO2 leaded to lower yields of the
desired product (Scheme 2, 3e), while the other electron-
withdrawing groups resulted in moderate yields of
thiophosphinates (Scheme 2, 3f-3i). The steric hindrance also
affected the reaction between diphenylphosphine oxide and aryl
thiols. To our delight, slightly lower but still good yields were
aUnless otherwise noted, the reactions were performed by adding P(O)H
compounds (1.2 mmol), thiols (1 mmol) and DMF (10 ml) at room
temperature for 3 h. Isolated yields. bReactions were performed for 6 h.
Scheme 2. Reactions of P(O)H compounds with thiolsa
In order to understand the mechanism, controlled
experiments were performed (Scheme 3). Phenyl disulfide
(confirmed by NMR) with 91% yield was readily formed from
2d in the present of both Na2CO3 and air (Scheme 3, eq 1). None
of phenyl disulfide was formed when the reaction was carried
without Na2CO3 in air or with Na2CO3 under N2 atmosphere
(Scheme 3, eq. 2, 3). Thus both Na2CO3 and the O2 in the air
played important roles in the formation of phenyl disulfide, and
this similar phenomenon was also well reported by other
literatures.15 Under the standard conditions, 1a and phenyl

ACCEPTED MANUSCRIPT
3
3. Conclutions
disulfide reacted fairly well, and 87% yield of corresponding 3d
was generated (Scheme 3, eq 3). However, only traced amount of
3d was found when the reaction of 1a and PhSSPh was carried in
air without Na2CO3. And when the reaction was carried with
Na2CO3 under N2 atmosphere, a yield of 48% was observed
(Scheme 3, eq. 4). Since 1a is an acid, it completed the react with
Na2CO3 only in half an hour (traced by TLC, Scheme 3 eq.5).
After addition of 2d to the reaction mixture of 1a and Na2CO3,
normal yield of 84% target compound was get. But if the first
step reaction of 1a with Na2CO3 and the continue second step
reaction with 2d were performed under N2, only 14% yield of 3d
was obtained (Scheme 3, eq 6).
In summary, the sulfur-containing organophosphorus
compounds synthesis method by coupling reaction of P(O)H
compounds with aryl thiols was developed. The reaction can be
carried out without the presence of metal catalysts at room
temperature and air atmosphere, and afforded the products in
moderate to good yields. The method exhibited a great
functionality tolerance for the substrates. A plausible mechanism
was proposed.18
4. Experimental section
4.1. General information
Na2CO3
Ph SH
Ph
S
S
Ph
(1)
Reagents and solvents were purchased from commercial
DMF, air, rt, 1.5h
91%
suppliers and used without additional purification. H NMR，31P
1
O
NMR and 13C NMR spectra were recorded on a BrukerARX-400.
O
without Na2CO3
DMF, air, rt, 3h
+
FT-IR spectra were obtained with
spectrophotometer. Mass spectra were obtained on an Agilent
LC-MS 1100 instrument. High resolution mass data were
a
Nicolet 380
Ph
Ph
P
H
Ph
Ph
S
S
Ph
Ph
Ph
P
S Ph
(2)
Ph
Ph
trace
O
P
recorded on a Thermo Fisher Scientific LTQ FT Ultra
O
Na2CO3
instrument. Elemental analysis was performed with
ElementerVario EL Ⅲ instrument. Melting points were recorded
on a SGW X-4 melting point apparatus and the thermometer is
uncorrected.
Ph
S
Ph
+
P
H
S S
DMF, air, rt, 3h
(3)
Ph
87%
Ph
O
O
Na2CO3
Ph
P
S Ph
+
Ph
P
H
Ph
S S Ph
4.2. Typical Procedure for the Preparation of 3a-3t.
DMF, N2, rt, 3h
(4)
(5)
Ph
Ph
P(O)H compounds 1 (1.2 mmol), thiols 2 (1.0 mmol), and
Na2CO3 (1.2 mmol) were placed in a Schlenk tube. Then DMF
(10 mL) was added. The reaction mixture was stirred at room
temperature for 3 h. After the reaction was completed (monitored
by TLC), H2O (20.0 mL) was added, and the mixture was
extracted by CH2Cl2 (3*10.0 mL). The combined organic layer
was dried over anhydrous Na2SO4, filtered, and concentrated by
rotary evaporation. The crude reaction mixture was purified by
flash column chromatography on silica gel to afford the
corresponding product.
48%
O
O
O
Na2CO3
Ph-SH
Ph
S
P
S Ph
Ph
P
Na
Ph
P
H
DMF, air, rt, 2h
DMF, air, rt, 1.5h
Ph
Ph
Ph
84%
Ph
O
P
O
Na2CO3
+
Ph
H
(6)
Ph
P
Ph SH
DMF, N2, rt, 3h
Ph
Ph
14%
Scheme 3. Mechanistic Experiments
4.2.1. S-(4-methylphenyl) diphenylphosphinothioate (3a):
Based on the previous reports14-17 and our experiment results,
a plausible reaction mechanism of the reaction between P(O)H
compounds and aryl thiols in the presence of base was proposed
(Scheme 4). Under the action of Na2CO3 and air, thiols 2 undergo
homocoupling reaction to form disulfides 4, in which Na2CO3
acted as a base and thus was critical and indispensable. At the
same time, P(O)H compounds 1 reacts with Na2CO3 to give
intermediate 1’. The intermediate 1’ then reacts with disulfides 4
to afford compound 3 and 2’. 2’ further converted to raw material
of 2 with the presence of Na2CO3 and air, until the reaction
completed.
o
1
White solid (282 mg, 87 %). M.p.: 106-107 C. H NMR (400
MHz, CDCl3): δ 7.85 (dd, J1 = 13.2 Hz, J2 = 7.2 Hz, 4 H), 7.51-
7.49 (m, 2H), 7.44-7.40 (m, 4H), 7.32 (d. J=6.8 Hz, 2H), 6.99 (d,
J=7.6 Hz, 2H), 2.23 (s, 3H). 31P NMR (162 MHz, CDCl3): δ
41.2(s, 1P). 13C NMR (100 MHz, CDCl3): δ 21.2, 122.3 (d, J =
5.1 Hz), 128.5 (d, J = 13.1 Hz), 130.0 (d, J = 1.4 Hz), 131.7 (d, J
= 10.2 Hz), 132.3 (d, J = 2.9 Hz), 132.7 (d, J = 105.8 Hz), 135.4
(d, J = 3.6 Hz), 139.2 (d, J = 2.9 Hz). MS (ESI, m/z): 324.9
(M+H)+.
4.2.2. S-(4-aminophenyl) diphenylphosphinothioate (3b):
o
1
O
White solid (290 mg, 90 %). M.p.: 163-165 C. H NMR (400
MHz, CDCl3): δ 7.86-7.82 (m, 4 H), 7.52-7.48 (m, 2H), 7.45-
7.41 (m, 4H), 7.17-7.15 (m, 2H), 6.48-6.46 (m, 2H), 3.74 (br,
2H). 31P NMR (162 MHz, CDCl3): δ 41.1(s, 1P). 13C NMR (100
MHz, CDCl3): δ112.3 (d, J = 4.6 Hz), 115.6, 128.5 (d, J = 10.1
Hz), 131.7 (d, J = 8.2 Hz), 132.1 (d, J = 2.8 Hz), 132.9 (d, J =
83.6 Hz), 137.0 (d, J = 2.7 Hz), 147.6 (d, J = 1.8 Hz).
R1
P
R2
H
R3
SH
2
1
Na2CO3,air
Na2CO3
O
P
R2
O
R1
R3
R3
R3
S S
4
4.2.3. S-(4-(tert-butyl)phenyl) diphenylphosphinothioate (3c):
R1
S
+
P
R2
Na
o
1
White solid (266 mg, 73 %). M.p.: 118-119 C. H NMR (400
MHz, CDCl3): δ 7.86-7.82 (m, 4 H), 7.53-7.49 (m, 2H), 7.46-
7.42 (m, 4H), 7.36-7.34 (m, 2H), 7.22-7.21 (m, 2H), 1.24 (s, 9H).
31P NMR (162 MHz, CDCl3): δ 41.5(s, 1P). 13C NMR (100 MHz,
CDCl3): δ31.1, 34.6, 122.3 (d, J = 4.6 Hz), 126.3 (d, J = 1.9 Hz),
128.5 (d, J = 11.0 Hz), 131.7 (d, J = 8.3 Hz), 132.2 (d, J = 1.8
3
air
R3
1'
SNa
2'
Scheme 4. Proposed reaction mechanism

ACCEPTED MANUSCRIPT
4
Tetrahedron
Hz), 132.8 (d, J = 85.5 Hz), 135.2 (d, J = 2.8 Hz), 152.3 (d, J =
(162 MHz, CDCl3): δ 41.2 (s, 1P). 13C NMR (100 MHz, CDCl3):
1.8 Hz).
δ 21.2, 125.7 (d, J = 3.7 Hz), 128.5 (d, J = 10.1 Hz), 128.9, 129.8
(d, J = 1.9 Hz), 131.7 (d, J = 7.4 Hz), 132.3 (d, J = 2.8 Hz), 132.4
(d, J = 3.6 Hz), 132.7 (d, J = 84.6 Hz), 136.1 (d, J = 2.8 Hz),
139.0 (d, J = 1.8 Hz).
4.2.4. S-phenyl diphenylphosphinothioate (3d): White solid
o
(271 mg, 88 %). M.p.: 84-86 C. IR (KBr):1203, 1108, 746, 560
1
cm-1. H NMR (400 MHz, CDCl3): δ 7.85 (dd, J1 = 13.2 Hz, J2 =
8.0 Hz, 4H), 7.53-7.49 (m, 2H), 7.46-7.42 (m, 6H), 7.26-7.18 (m.
3H). 31P NMR (162 MHz, CDCl3): δ 41.3 (s, 1P). 13C NMR (100
MHz, CDCl3): δ 126.3 (d, J = 5.1 Hz), 128.5 (d, J = 13.1 Hz),
128.9 (d, J = 1.4 Hz), 129.1 (d, J = 1.4 Hz), 131.6 (d, J = 10.2
Hz), 132.3 (d, J = 2.9 Hz), 132.6 (d, J = 106.5 Hz), 135.4 (d, J =
3.6 Hz). MS (ESI, m/z): 311.0 (M+H)+. Anal. calcd. For
C18H15OPS(%): C,69.66; H, 4.87. Found: C, 69.95; H, 5.01.
4.2.11. S-(3-methylphenyl) diphenylphosphinothioate (3k):
o
1
White solid (263 mg, 81 %). M.p.: 103-105 C. H NMR (400
MHz, CDCl3): δ 7.87-7.83 (m, 4H), 7.52-7.49 (m, 2H), 7.46-7.42
(m, 4H), 7.24-7.22 (m, 2H). 7.09-7.04 (m, 2H), 2.21 (s, 3H). 31P
NMR (162 MHz, CDCl3): δ 42.0 (s, 1P). 13C NMR (100 MHz,
CDCl3): δ 21.2, 125.7 (d, J = 4.6 Hz), 128.5 (d, J = 11.1 Hz),
128.9, 129.8 (d, J = 1.9 Hz), 131.7 (d, J = 8.2 Hz), 132.3 (d, J =
1.8 Hz), 132.4 (d, J = 2.7 Hz), 132.7 (d, J = 85.5 Hz), 136.1 (d, J
= 3.7 Hz), 139.0.
4.2.5. S-(4-nitrophenyl) diphenylphosphinothioate (3e):
o
1
Yellow solid (96 mg, 27 %). M.p.: 105-107 C. H NMR (400
MHz, CDCl3): δ 8.04 (d, J = 8.8 Hz, 2H), 7.86 (dd, J1 = 12.8 Hz,
J2 = 6.8 Hz, 4H), 7.68 (d, J = 8.4 Hz, 2H), 7.58-7.54 (m, 2H),
7.50-7.46 (m, 4H). 31P NMR (162 MHz, CDCl3): δ 41.9 (s, 1P).
13C NMR (100 MHz, CDCl3): δ 123.9, 128.9 (d, J = 13.2 Hz),
131.6 (d, J = 10.9 Hz), 131.8 (d, J = 107.2 Hz), 132.9 (d, J = 2.9
Hz), 135.1 (d, J = 4.4 Hz), 136.1 (d, J = 4.4 Hz), 147.9 (d, J = 2.2
Hz).
4.2.12. S-(2-methoxyphenyl) diphenylphosphinothioate (3l):
Colorless oil (283 mg, 83 %). H NMR (400 MHz, CDCl3): δ
1
7.89-7.85 (m, 4H), 7.70 (d, J=6.0 Hz, 1H), 7.47-7.44 (m, 2H),
7.40-7.37 (m, 4H), 7.20 (t, J=6.4 Hz, 1H), 6.84 (t, J=6.0 Hz, 1H),
6.68 (t, J=6.4 Hz, 1H), 3.60 (s, 3H). 31P NMR (162 MHz,
CDCl3): δ 41.4 (s, 1P). 13C NMR (100 MHz, CDCl3): δ 55.5,
111.1, 114.1 (d, J = 3.7 Hz), 121.2 (d, J = 1.8 Hz), 128.3 (d, J =
10.1 Hz), 130.7, 131.6 (d, J = 8.3 Hz), 132.2 (d, J = 2.8 Hz),
133.1 (d, J = 84.5 Hz), 137.6(d, J = 3.7 Hz), 159.4 (d, J = 2.8
Hz).
4.2.6. S-(4-acetamidophenyl) diphenylphosphinothioate (3f):
o
1
White solid (263 mg, 72 %). M.p.: 146-147 C. H NMR (400
MHz, CDCl3): δ 9.66 (br, 1H), 7.86-7.81 (m, 4H), 7.56-7.54 (m,
2H), 7.50-7.43 (m, 6H), 7.22 (d, J = 8.4 Hz, 2H), 2.1 (s, 3H). 31P
NMR (162 MHz, CDCl3): δ 42.6 (s, 1P). 13C NMR (100 MHz,
CDCl3): δ 24.5, 118.1 (d, J = 5.8 Hz), 120.3, 128.8 (d, J = 13.1
Hz), 131.5 (d, J = 10.2 Hz), 132.2 (d, J = 106.4 Hz), 132.6 (d, J =
2.1 Hz), 136.4 (d, J = 2.9 Hz), 140.4, 169.4.
4.2.13. S-(3-methoxyphenyl) diphenylphosphinothioate (3m):
White solid (243 mg, 77 %). M.p.: 89-90 oC. 1H NMR (400 MHz,
CDCl3): δ 7.88-7.84 (m, 4H), 7.53 -7.50 (m, 2H), 7.46-7.43 (m,
4H), 7.10 (t, J=6.0 Hz, 1H), 7.05-7.03(m, 1H), 6.98-6.97 (m,
1H), 6.80-6.78 (m, 1H). 3.66 (s, 3H) 31P NMR (162 MHz,
CDCl3): δ 41.3 (s, 1P). 13C NMR (100 MHz, CDCl3): δ 55.3,
115.6, 119.7 (d, J = 2.7 Hz), 127.1 (d, J = 3.6 Hz), 127.6 (d, J =
3.7 Hz), 128.6 (d, J = 11.0 Hz), 129.8 (d, J = 1.9 Hz), 131.7(d, J
= 8.2Hz), 132.3(d, J = 1. 9Hz), 132.6 (d, J = 85.5Hz), 159.6.
4.2.7. S-(4-fluorophenyl) diphenylphosphinothioate (3g):
White solid (245 mg, 75 %). M.p.: 94-96 oC. 1H NMR (400 MHz,
CDCl3): δ 7.85 (dd, J1 = 13.2 Hz, J2 = 7.6 Hz, 4H), 7.52-7.48 (m,
2H), 7.45-7.43 (m, 6H), 6.89 (t, J = 8.0 Hz, 2H). 31P NMR (162
MHz, CDCl3): δ 41.4(d, J = 3.9 Hz, 1P). 19F NMR (376 MHz,
CDCl3): δ -111.6 (d, J = 5.6 Hz, 1F). 13C NMR (100 MHz,
CDCl3): δ 116.3 (dd, J1 = 21.9 Hz, J2 = 1.4 Hz), 121.2 (t, J = 4.3
Hz), 128.6 (d, J = 13.2 Hz), 131.6 (d, J = 10.2 Hz), 132.3 (d, J =
106.4 Hz), 132.5 (d, J = 3.0 Hz), 137.4 (dd, J1 = 8.8 Hz, J2 = 3.7
Hz), 163.4 (dd, J1 = 248.7 Hz, J2 = 2.2 Hz).
4.2.14. S-(2-ethylphenyl) diphenylphosphinothioate (3n):
o
White solid (201 mg, 62 %). M.p.: 66-68 C. IR (KBr):1435,
1198, 1106, 750, 694, 562, 552cm-1. 1H NMR (400 MHz,
CDCl3): δ 7.84-7.80 (m, 4 H), 7.51-7.48 (m, 3H), 7.44-7.41 (m,
4H), 7.22-7.19 (m, 1H), 7.15-7.14 (m, 1H), 7.02-7.00 (m, 1H),
2.75 (q, J=6.0Hz, 2H), 1.12 (t, J=6.0Hz, 3H). 31P NMR (162
MHz, CDCl3): δ 40.7(s, 1P). 13C NMR (100 MHz, CDCl3): δ
14.9, 27.4, 125.0(d, J = 3.7 Hz), 126.4 (d, J = 1.9 Hz), 128.5 (d, J
= 10.1 Hz), 129.1, 129.5, 131.5 (d, J = 8.3Hz), 132.3 (d, J =
1.8Hz), 132.8 (d, J = 85.4 Hz), 136.8 (d, J = 2.8 Hz), 148.4 (d, J
=3.7 Hz). MS (ESI, m/z): 339.1 (M+H)+. HRMS (ESI): calcd.
For C20H19OPS (M+H)+: 339.09, found: 339.0958.
4.2.8. S-(4-chlorophenyl) diphenylphosphinothioate (3h):
o
1
White solid (210 mg, 63 %). M.p.: 104-105 C. H NMR (400
MHz, CDCl3): δ 7.87-7.81 (m, 4H), 7.55-7.51 (m, 2H), 7.48-7.43
(m, 4H), 7.39-7.37 (m, 2H), 7.17 (d, J = 8.4 Hz, 2H). 31P NMR
(162 MHz, CDCl3): δ 41.4 (s, 1P). 13C NMR (100 MHz, CDCl3):
δ 124.8 (d, J = 5.1 Hz), 128.7 (d, J = 13.1 Hz), 129.3 (d, J = 1.4
Hz), 131.6 (d, J = 10.2 Hz), 132.3 (d, J = 106.5 Hz), 132.5 (d, J =
2.9 Hz), 135.5 (d, J = 2.2 Hz), 136.5 (d, J = 3.6 Hz).
4.2.15. S-(2,6-dimethylphenyl) diphenylphosphinothioate
(3o): White solid (237 mg, 70 %). M.p.: 98-99 oC. IR
4.2.9. S-(4-bromophenyl) diphenylphosphinothioate (3i):
1
(KBr):1461, 1436, 1202, 1108, 785, 750, 692, 555, 524cm-1. H
o
1
White solid (220 mg, 57 %). M.p.: 102-103 C. H NMR (400
MHz, CDCl3): δ 7.87-7.82 (m, 4H), 7.51-7.48 (m, 2H), 7.45-7.40
(m, 4H), 7.33-7.29 (m, 4H). 31P NMR (162 MHz, CDCl3): δ 41.3
(s, 1P). 13C NMR (100 MHz, CDCl3): δ 123.8 (d, J = 2.9 Hz),
125.5 (d, J = 5.1 Hz), 128.7 (d, J = 13.1 Hz), 131.6 (d, J = 10.2
Hz), 132.2 (d, J = 106.4 Hz), 132.3 (d, J = 2.2 Hz), 132.6 (d, J =
2.9 Hz), 136.8 (d, J = 3.7 Hz).
NMR (400 MHz, CDCl3): δ 7.77-7.73 (m, 4 H), 7.54-7.52 (m,
2H), 7.44-7.40 (m, 4H), 7.12-7.09 (m, 1H), 7.02-7.00 (m, 2H),
2.29 (s, 6H). 31P NMR (162 MHz, CDCl3): δ 39.7(s, 1P). 13C
NMR (100 MHz, CDCl3): δ 22.6, 124.5(d, J = 4.6 Hz), 128.40 (d,
J = 1.8 Hz), 128.42 (d, J = 11.0 Hz), 129.3 (d, J = 1.9 Hz), 131.4
(d, J = 8.2Hz), 132.3 (d, J = 1.9 Hz), 133.2 (d, J = 84.6 Hz),
145.2 (d, J =2.6 Hz). MS (ESI, m/z): 339.1 (M+H)+. HRMS
(ESI): calcd. For C20H19OPS (M+H)+: 339.09, found: 339.0959.
4.2.10. S-(2-methylphenyl) diphenylphosphinothioate (3j):
White solid (263 mg, 81 %). M.p.: 69-71 oC. 1H NMR (400 MHz,
CDCl3): δ 7.87-7.83 (m, 4H), 7.51-7.48 (m, 2H), 7.45-7.41 (m,
4H), 7.24-7.22 (m, 2H). 7.08-7.03 (m, 2H), 2.21(s, 3H). 31P NMR
4.2.16. S-p-tolyl di-p-tolylphosphinothioate (3p): White solid
1
(203 mg, 58 %). M.p.: 79-82 oC. H NMR (400 MHz, CDCl3): δ

ACCEPTED MANUSCRIPT
5
7.74-7.70 (m, 4 H), 7.34-7.32 (m, 2H), 7.23-7.21 (m, 4H), 7.00-
6.98 (m, 2H), 2.35 (s, 6H), 2.23 (s, 3H). 31P NMR (162 MHz,
CDCl3): δ 41.5(s, 1P). 13C NMR (100 MHz, CDCl3): δ 21.1, 21.6,
122.9(d, J = 3.7 Hz), 129.2 (d, J = 11.0 Hz), 129.8 (d, J =
86.4Hz), 129.9, 131.7 (d, J = 8.3Hz), 135.2 (d, J = 2.8 Hz), 138.9
(d, J = 1.9 Hz), 142.7 (d, J =2.8 Hz).
(100 MHz, CDCl3): δ 16.0 (d, J = 7.3 Hz), 64.1 (d, J = 5.8 Hz),
126.6 (d, J = 7.3 Hz), 129.0 (d, J = 2.9 Hz), 129.4 (d, J = 2.2 Hz),
134.6 (d, J = 5.1 Hz).
4.3.2 O,O-diethyl S-p-tolylphosphorothioate (3v): Light
1
yellow oil (187 mg, 72 %). H NMR (400 MHz,CDCl3): δ7.44
(dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 4.26-
4.11 (m, 4H), 2.34 (s, 3H), 1.33-1.29 (td, J1 = 6.8 Hz, J2 = 0.8 Hz,
6H). 31P NMR (162 MHz, CDCl3): δ23.8 (s, 1P). 13C NMR (100
MHz, CDCl3): δ 16.0 (d, J = 7.3 Hz), 21.2, 64.0 (d, J = 6.6 Hz),
122.8 (d, J = 7.3 Hz), 130.2 (d, J = 2.2 Hz), 134.6 (d, J = 5.1 Hz),
139.3 (d, J = 2.9 Hz).
4.2.17. S-p-tolyl bis(4-chlorophenyl)phosphinothioate (3q):
o
1
White solid (231 mg, 57 %). M.p.: 107-109 C. H NMR (400
MHz, CDCl3): δ 7.78-7.74 (m, 4 H), 7.43-7.40 (m, 4H), 7.32-
7.30 (m, 2H), 7.04-7.02 (m, 2H), 2.26 (s, 3H). 31P NMR (162
MHz, CDCl3): δ 38.9(s, 1P). 13C NMR (100 MHz, CDCl3): δ
21.2, 121.6 (d, J = 3.7 Hz), 129.0 (d, J = 11.1 Hz), 130.2, 131.0
(d, J = 86.4Hz), 133.0 (d, J = 9.2 Hz), 135.3(d, J = 2.8 Hz), 139.1
(d, J =2.7 Hz), 139.6 (d, J =1.8 Hz).
Acknowledgments
4.2.18 .6((4(tertbutyl)phenyl)thio)6Hdibenzo[c,e][1,2]oxaphos
phinine 6-oxide(3r): Colorless oil (168 mg, 45 %). H NMR
This work was founded by Research Foundation of Qingdao
Fusilin Chemical Science &Technology Co., Ltd. (FSL-RF
2016), National Natural Science Foundation of China (Grant No.
21676285 and 21306214) and Qingdao Indigenous Innovation
Program (No. 15-9-1-76-jch).
1
(400 MHz, CDCl3): δ 7.96-7.92 (m, 1 H), 7.79-7.76 (m, 1H),
7.66-7.64 (m, 2H), 7.50-7.46 (m, 1H), 7.32-7.29 (m, 1H), 7.15-
7.01 (m, 6H), 1.19 (s, 9H). 31P NMR (162 MHz, CDCl3): δ 34.6(s,
1P). 13C NMR (100 MHz, CDCl3): δ 31.1, 34.6, 120.0 (d, J = 5.5
Hz), 120.3 (d, J = 4.6 Hz), 121.7 (d, J= 9.2 Hz), 123.0 (d, J = 9.2
Hz), 124.5, 124.7, 124.8 (d, J = 106.6 Hz), 126.1(d, J = 1.8 Hz),
128.5 (d, J =11.9 Hz), 130.4, 130.8 (d, J =7.3 Hz), 133.7 (d, J
=1.9 Hz), 135.9 (d, J =2.8 Hz), 136.5 (d, J =5.5 Hz), 150.8 (d, J
=8.3 Hz), 152.7 (d, J =2.7 Hz).
References and notes
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4.2.19. O-ethyl S-phenyl phenylphosphonothioate (3s): Yellow
oil (175 mg, 63 %). 1H NMR (400 MHz, CDCl3): δ 7.66 (m, 2H),
7.50 (t, J = 7.2 Hz, 1H), 7.40-7.35 (m, 2H), 7.32-7.27 (m, 3H),
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(d, J = 5.1 Hz), 128.2 (d, J = 14.6 Hz), 129.0 (d, J = 2.9 Hz),
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4.3 Procedure for the Preparation of 3u-3v.
P(O)H compounds 1 (1.2 mmol), thiols 2 (1.0 mmol), and
Na2CO3 (1.2 mmol) were placed in a Schlenk tube. Then DMF
(10 mL) was added. The reaction mixture was stirred at room
temperature for 6 h. After the reaction was completed (monitored
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1
yellow oil (127 mg, 52 %). H NMR (400 MHz, CDCl3): δ 7.59-
7.56 (m, 2H), 7.37-7.35 (m, 3H), 4.27-4.11 (m, 4H), 1.33-1.29
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ACCEPTED MANUSCRIPT
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Tetrahedron
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.
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