The Journal of Organic Chemistry
Page 10 of 15
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A mixture of tribenzyl phosphite (1.0 equiv.) and benzyl bromide (0.1 equiv.) were continuously
pumped through the microreactor with a flow rate of 10 µl/min. Reaction progress was monitored by 1H
and 31P NMR as a function of residence times. After 25 min. of residence time the quantitative amount
of the desired product 3c was observed. After collecting the desired fraction, the remaining excess of
alkyl halide was removed under reduced pressure on a vacuum evaporator in 2 minutes to give a
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colorless oil (0.32 g/h; 90% yield). H NMR (200 MHz, CDCl3) δ (ppm) = 7.39-7.25 (m, 15H), 4.89 (d,
4H, J = 8.3 Hz), 3.16 (d, 2H, J = 21.73 Hz); 31P NMR (81 MHz, CDCl3) δ (ppm) = 27.60; 13C NMR (50
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MHz, CDCl3) δ (ppm) = 32.76 (d, JPC = 137.6 Hz, P(O)CH2, CH2), 66.34 (d, JPC = 6.7 Hz,
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2xP(O)OCH2, CH2), 125.73 (d, JPC = 3.5 Hz, p-PhCH2P(O), CH), 126.68 (s, 4x o-PhCH2OP(O), CH),
127.10 (s, 2x p-PhCH2OP(O), CH), 127.29 (s, 4x m-PhCH2OP(O), CH), 127.33 (d, JPC = 3.9 Hz, m-
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PhCH2P(O), CH), 128.65 (d, JPC = 6.6 Hz, o-PhCH2P(O), CH), 129.97 (d, JPC = 9.1 Hz, ipso-
PhCH2P(O), >C<), 135.10 (d, JPC = 5.8 Hz, 2x ipso-PhCH2O, >C<). H and 31P NMR data were
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consistent with those previously reported.18
Diethyl methylphosphonate (3d)
A mixture of triethylphosphite (1.0 equiv.) and methyl iodide (1.0 equiv.) was continuously pumped
through the microreactor with a flow rate of 30 µl/min. Reaction progress was monitored by 1H and 31
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NMR as a function of residence times. After 8.33 min. of residence time the quantitative amount of the
desired product 3d was observed. After collecting the desired fraction, the remaining excess of alkyl
halide was removed under reduced pressure on a vacuum evaporator in 1 minute to give a colorless
oily product (1.9 g/h; ≥ 99% yield).1H NMR (200 MHz, CDCl3) δ (ppm) = 4.16 – 3.95 (m, 4H), 1.44 (d,
3H, J = 17.4 Hz), 1.29 (t, 6H, J = 7.1 Hz); 31P NMR (81 MHz, CDCl3) δ (ppm) = 30.61; 13C NMR (50
MHz, CDCl3) δ (ppm) = 9.35 (d, 1JPC = 144.2 Hz, P(O)CH3), 14.64 (d, 3JPC = 6.1 Hz, 2xP(O)OCH2CH3),
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59.61 (d, JPC = 6.1 Hz, 2xP(O)CH2). H and 31P NMR data were consistent with those previously
reported.16
Diisopropyl methylphosphonate (3e)
A mixture of triisopropyl phosphite (1.0 equiv.) and methyl iodide (1.0 equiv.) was continuously
pumped through the microreactor with a flow rate of 30 µl/min. The reaction progress was monitored
by 1H and 31P NMR as a function of residence times. After 8.33 min. of residence time the quantitative
amount of the desired product 3e was observed. After collecting the reaction mixture, the remaining
excess of alkyl halide was removed under reduced pressure on a vacuum evaporator in 1 minute to
give a product as colorless oily liquid (1.6 g/h; ≥ 99% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) = 4.78
– 4.55 (m, 2H), 1.42 (d, 3H, J = 17.7 Hz), 1.29 (d, 12H, J = 6.56 Hz); 31P NMR (81 MHz, CDCl3) δ
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(ppm) = 28.57; 13C NMR (50 MHz, CDCl3) δ (ppm) = 11.40 (d, JPC = 145.3 Hz, P(O)CH3), 22.64 (d,
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22.64 (d, JPC = 3.4 Hz, 2xP(O)OCH(CH3)2), 68.54 (d, JPC = 6.2 Hz, 2xP(O)OCH). H and 31P NMR
data were consistent with those previously reported.19,20
Diisopropyl ethylphosphonate (3f)
A mixture of triisopropyl phosphite (1.0 equiv.) and ethyl iodide (1.5 equiv.) was continuously pumped
through the microreactor with a flow rate of 30 µl/min. The reaction progress was monitored by 1H and
31P NMR as a function of residence times. After 8.33 min. of residence time the quantitative amount of
the desired product 3f was observed. After collecting the reaction mixture, the remaining excess of
alkyl halide was removed under reduced pressure on a vacuum evaporator to give a colorless oily
product (1.7 g/h; ≥ 99% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) = 4.75 – 4.55 (m, 2H), 1.80 – 1.54
(m, 2H), 1.28 (d, 2H, J = 6.1 Hz), 1.21 – 0.99 (m, 3H); 31P NMR (81 MHz, CDCl3) δ (ppm) = 31.75; 13
NMR (125 MHz, CDCl3) δ (ppm) = 6.71 (d, JPC = 6.9 Hz, P(O)CH2CH3), 19.99 (d, JPC = 143.8 Hz,
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P(O)CH2), 24.03 (d, JPC = 4.1 Hz, 2xP(O)OCH(CH3)2), 69.80 (d, JPC = 6.6 Hz, 2xP(O)OCH). H and
31P NMR data were consistent with those previously reported21,22 and those predicted NMR data
calculated using Advance Chemistry Development, Inc. (ACD/Labs) Software V11.01.
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