The Journal of Organic Chemistry
NOTE
product as a colorless oil: δH (300 MHz, CDCl3) 6.86 (d, J = 701.20 Hz,
1 H), 4.26 (dt, J = 7.96, 5.92 Hz, 4 H), 3.67 (t, J = 6.19 Hz, 4 H), 2.15
(quintet, J = 6.03 Hz, 4 H); δC (75.5 MHz, CDCl3) 62.3 (d, J = 5.60 Hz),
40.5, 33.0 (d, J = 6.69 Hz); δP (121.5 MHz, CDCl3) 8.08; HRMS (ESI)
calcd for C6H14Cl2O3P 235.0052 ([M þ H]þ), found 235.0051.
Bis(4-chlorobutyl) Phosphonate (2j). According to GP2, 20.2 mL
of 4-chlorobutanol (ABCR-Chemicals, technical grade, 85%) in CH2Cl2
(100 mL) was reacted with PCl3 (5 mL) in CH2Cl2 (30 mL) to give crude
phosphonate that was distilled (140 °C, 0.02 mbar) to yield 12.7 g (84%) of
pure product as a colorless oil: δH (300 MHz, CDCl3) 6.82(d,J= 696.88 Hz,
1 H), 4.12 (dt, J = 8.11, 5.74 Hz, 4 H), 3.58 (t, J = 5.93 Hz, 4 H), 1.88 (t,
J = 3.00 Hz, 8 H); δC (75.5 MHz, CDCl3) 64.9 (d, J = 5.84 Hz), 44.3, 28.6,
27.8 (d, J = 6.39 Hz); δP (121.5 MHz, CDCl3) 7.81; HRMS (ESI) calcd for
C8H18Cl2O3P 263.0365 ([M þ H]þ), found 263.0356.
16 mL of Et2O were reacted with 2.1 mL of NEt3 to yield 2.85 g (83%)
of product as a viscous slightly yellow oil that crystallized over time: δH
(300 MHz, CDCl3) 3.76 (d, J = 6.15 Hz, 4 H), 0.98 (s, 18 H); δC (75.5
MHz, CDCl3) 77.5 (d, J = 6.77 Hz), 32.1 (d, J = 8.57 Hz), 26.1; δP
(121.5 MHz, CDCl3) 60.1; HRMS (ESI) calcd for C10H24O3PS
255.1178 ([M þ H]þ) found 255.1177.
O,O-Dicyclohexyl S-Hydrogen Phosphorothioate (3g). Ac-
cording to GP3, 5.0 g of dicyclohexyl phosphonate and 0.68 g of sulfur in
15 mL of Et2O were reacted with 3.0 mL of NEt3 to yield 3.81 g (67%)
of product as a yellow, highly viscous oil: δH (300 MHz, CDCl3) 5.76
(bs, 1 H), 4.49 (qt, J = 9.04, 4.39 Hz, 1 H), 1.98ꢀ1.89 (m, 4 H),
1.78ꢀ1.68 (m, 4 H), 1.65ꢀ1.45 (m, 6 H), 1.45ꢀ1.19 (m, 6 H); δC
(75.5 MHz, CDCl3) 78.2 (d, J = 6.15 Hz), 33.2 (d, J = 4.41 Hz), 33.1
(d, J= 4.91 Hz), 25.2, 23.6; δP (121.5 MHz, CDCl3) 57.2; HRMS (MALDI)
calcd for C12H24O3PS: 279.1178 ([M þ H]þ), found 279.1165
Bis(2-methoxyethyl) Phosphonate (2k). According to GP1,
33.9 mL of 2-methoxyethanol was reacted to give the crude phosphonate that
was distilled (85 °C, 0.02 mbar) to yield 15.7 g (81%) of pure product as a
colorless oil: δH (300 MHz, CDCl3) 6.91 (d, J= 715.61 Hz, 1 H), 4.31ꢀ4.12
(m, 4 H), 3.59 (t, J = 4.61 Hz, 4 H), 3.38 (s, 6 H); δC (75.5 MHz, CDCl3)
71.4 (d, J = 5.40 Hz), 64.6 (d, J = 6.14 Hz), 58.9; δP (121.5 MHz, CDCl3)
9.20; HRMS (ESI) calcd for C6H16O5P 199.0730 ([M þ H]þ), found
199.0725.
O,O-Bis(2-chloroethyl) S-Hydrogen Phosphorothioate (3h).
According to GP3, 10.0 g of bis(2-chloroethyl) phosphonate and 1.70 g of
sulfur in 35 mL of Et2O were reacted with 7.4 mL of NEt3 to yield 7.11 g
(62%) of product as a yellow viscous oil: δH (300 MHz, CDCl3) 6.85
(bs, 1 H), 4.26 (dt, J = 9.51, 5.76 Hz, 4 H), 3.75 (t, J = 5.80 Hz, 4 H); δC
(75.5 MHz, CDCl3) 67.7 (d, J = 5.00 Hz), 42.2 (d, J = 8.65 Hz); δP
(121.5 MHz, CDCl3) 59.0; HRMS (ESI) calcd for C4H10Cl2O3PS
238.9460 ([M þ H]þ), found 238.9455.
O,O-Diethyl S-Hydrogen Phosphorothioate (3a). According
to GP3, 10.0 mL of diethyl phosphonate and 2.74 g of sulfur in 50 mL
of Et2O were reacted with 11.9 mL of NEt3 to yield 10.48 g (80%) of
product as a yellow oil: δH (250 MHz, CDCl3) 7.99 (bs, 1 H), 4.09
(dq, J = 9.36, 7.09 Hz, 4 H), 1.27 (t, J = 7.08 Hz, 6 H); δC (62.9 MHz,
CDCl3) 64.3 (d, J = 5.57 Hz), 15.8 (d, J = 7.70 Hz, CH3); δP (101.3 MHz,
CDCl3) 58.0; HRMS (ESI) calcd for C4H12O3PS 171.0239 ([M þ H]þ),
found 171.0234 (33.1%).
O,O-Bis(3-chloropropyl) S-Hydrogen Phosphorothioate
(3i). According to GP3, 10.0 g of bis(3-chloropropyl) phosphonate
and 1.50 g of sulfur in 30 mL of Et2O were reacted with 6.50 mL of NEt3
to yield 6.33 g (56%) of product as a yellow viscous oil: δH (300 MHz,
CDCl3) 6.42 (bs, 1 H), 4.28 (dt, J = 8.46, 5.90 Hz, 4 H), 3.69 (t,
J = 6.27 Hz, 4 H), 2.17 (quintet, J = 5.97 Hz, 4 H); δC (75.5 MHz,
CDCl3) 64.9 (d, J = 5.36 Hz), 40.7, 32.8 (d, J = 8.06 Hz); δP (121.5 MHz,
CDCl3) 60.1; HRMS (ESI) calcd for C6H14Cl2O3PS 266.9773
([M þ H]þ), found 266.9779.
O,O-Dipropyl S-Hydrogen Phosphorothioate (3b). Accord-
ing to GP3, 10.0 g of dipropyl phosphonate and 2.12 g of sulfur in 45 mL
of Et2O were reacted with 9.2 mL of NEt3 to yield 10.62 g (89%) of
product as a yellow oil: δH (300 MHz, CDCl3) 6.85 (bs, 1 H), 4.07
(dt, J = 8.47, 6.71 Hz, 4 H), 1.74 (sextet, J = 7.06 Hz, 4 H), 0.98 (t,
J = 7.41 Hz, 6 H); δC (75.5 MHz, CDCl3) 69.9 (d, J = 5.91 Hz), 23.4 (d,
J = 7.84 Hz), 10.0; δP (121.5 MHz, CDCl3) 59.1; HRMS (ESI) calcd for
C6H16O3PS 199.0552 ([M þ H]þ), found 199.0557.
O,O-Bis(4-chlorobutyl) S-Hydrogen Phosphorothioate
(3j). According to GP3, 4.03 g of bis(4-chlorobutyl) phosphonate and
0.54 g of sulfur in 15 mL of Et2O were reacted with 2.32 mL of NEt3 to
yield 3.73 g (83%) of product as a yellow oil: δH (300 MHz, CDCl3)
6.28 (bs, 1 H), 4.15 (dt, J = 8.39, 5.80 Hz, 4 H), 3.60 (t, J = 6.06 Hz, 4 H),
1.90 (m, 8 H); δC (75.5 MHz, CDCl3) 67.5 (d, J = 5.68 Hz), 44.4, 28.7,
27.4 (d, J = 7.92 Hz); δP (121.5 MHz, CDCl3) 59.5; HRMS (ESI) calcd
for C8H18Cl2O3PS 295.0086 ([M þ H]þ), found 295.0091.
O,O-Diisopropyl S-Hydrogen Phosphorothioate (3c). Ac-
cording to GP3, 10.0 mL of diisopropyl phosphonate and 2.12 g of sulfur
in 45 mL of Et2O were reacted with 9.2 mL of NEt3 to yield 9.59 g (81%)
of product as a yellow oil: δH (300 MHz, CDCl3) 7.10 (bs, 1 H),
4.86ꢀ4.69 (m, 2 H), 1.36 (d, J = 2.96 Hz, 6 H), 1.34 (d, J = 2.95 Hz, 6 H);
δC (75.5 MHz, CDCl3) 73.5 (d, J = 5.71 Hz), 23.5 (d, J = 5.51 Hz), 23.5
(d, J = 5.64 Hz); δP (121.5 MHz, CDCl3) 56.3; HRMS (ESI) calcd for
C6H16O3PS: 199.0552 ([M þ H]þ), found 199.0545.
O,O-Bis(2-methoxyethyl) S-Hydrogen Phosphorothioate
(3k). According to GP3, 10.0 g of bis(2-methoxyethyl) phosphonate
and 1.78 g of sulfur in 40 mL of Et2O were reacted with 7.72 mL of NEt3
to yield 2.50 g (22%) of product as a yellow viscous oil: δH (300 MHz,
CDCl3) 7.09 (bs, 1 H), 4.36ꢀ4.17 (m, 4 H), 3.70 (t, J = 4.53 Hz, 4 H),
3.46 (s, 6 H); δC (75.5 MHz, CDCl3) 71.6 (d, J = 6.63 Hz), 66.3 (d,
J = 5.51 Hz), 59.0; δP (121.5 MHz, CDCl3) 66.7; HRMS (ESI) calcd for
C6H15NaO5PS 253.0270 ([M þ Na]þ), found 253.0261 (34.1).
O,O-Diethyl S-Trifluoromethyl Phosphorothioate (4a). To
a solution of reagent 1 (257.2 mg, 0.78 mmol) in CH2Cl2 (4.0 mL) was
added a solution of 3a (165.8 mg, 0.97 mmol) in CH2Cl2 (3.6 mL)
which subsequently was stirred for 16 h. The solution was concentrated
under HV and then distilled (45 °C, 0.02 mbar) to yield O,O-diethyl
S-trifluoromethyl phosphorothioate (4a) (41.5 mg, 22%) as a colorless
oil: δH (300 MHz, CDCl3) 4.40ꢀ4.20 (m, 5 H), 1.41 (td, J = 7.08,
0.94 Hz, 6 H); δC (75.5 MHz, CDCl3) 127.8 (qd, J = 310.43, 5.39 Hz),
65.2 (d, J = 5.70 Hz), 15.75 (d, J = 7.48 Hz); δP (121.5 MHz, CDCl3)
13.3 (q, J = 7.56 Hz); δF (188.3 MHz, CDCl3) ꢀ34.33 (d, J = 7.60 Hz).
O,O-Diisopropyl S-Trifluoromethyl Phosphorothioate
(4c). To a solution of reagent 1 (252.6 mg, 0.77 mmol) in CH2Cl2
(4.0 mL) was added a solution of 3c (188.6 mg, 0.95 mmol) in CH2Cl2
(3.6 mL) which subsequently was stirred for 48 h. The solution was
concentrated under HV and then distilled (45 °C, 0.02 mbar) to yield O,
O-diisopropyl S-trifluoromethyl phosphorothioate (4c) (39.8 mg, 20%)
O,O-Dibutyl S-Hydrogen Phosphorothioate (3d). According
to GP3, 10.0 mL of dibutyl phosphonate and 1.81 g of sulfur in 50 mL of
Et2O were reacted with 7.8 mL of NEt3 to yield 9.93 g (86%) of product as a
yellow oil: δH (300 MHz, CDCl3) 7.41 (bs, 1 H), 4.10 (q, J = 7.46 Hz, 4 H),
1.69 (quintet, J = 7.18 Hz, 4 H), 1.42 (sextet, J = 7.44 Hz, 4 H), 0.94
(t, J = 7.36, 6 H); δC (75.5 MHz, CDCl3) 68.1 (d, J = 5.93 Hz), 32.0
(d, J = 7.75 Hz), 18.7, 13.6; δP (121.5 MHz, CDCl3) 58.4; HRMS (ESI)
calcd for C8H19NaO3PS 249.0685 ([M þ Na]þ), found 249.0683.
O,O-Diisobutyl S-Hydrogen Phosphorothioate (3e). Ac-
cording to GP3, 10.0 g of diisobutyl phosphonate and 1.82 g of sulfur
in 40 mL of Et2O were reacted with 8.0 mL of NEt3 to yield 10.15 g
(87%) of product as a yellow oil: δH (300 MHz, CDCl3) 6.72 (bs, 1 H),
3.87 (dd, J = 7.67, 6.68 Hz, 4 H), 2.00 (nonaplet, J = 6.69 Hz, 2 H), 0.97
(d, J = 6.72 Hz, 12 H); δC (75.5 MHz, CDCl3) 74.2 (d, J = 6.30 Hz), 28.9
(d, J = 7.98 Hz), 18.7; δP (121.5 MHz, CDCl3) 59.2; HRMS (ESI) calcd
for C8H20O3PS 227.0865 ([M þ H]þ), found 227.0857.
O,O-Dineopentyl S-Hydrogen Phosphorothioate (3f). Ac-
cording to GP3, 3.0 g of dineopentyl phosphonate and 0.48 g of sulfur in
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dx.doi.org/10.1021/jo200522w |J. Org. Chem. 2011, 76, 4189–4193