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W. Qiu, D.J. Burton / Journal of Fluorine Chemistry 155 (2013) 45–51
4.1.1. Representative general procedure for the preparation of diethyl
-difluoro benzylic phosphonate (7): diethyl -difluoro-4-
nitrobenzylphosphonate (7a)
(m), 681 (m) cmꢀ1. HRMS: calc’d for C11H14F2O4P [M+, –NO]
179.0598, obsv’d 279.0602.
a
,
a
a,a
A 100-mL flask fitted with a stir bar and a condenser topped
with a nitrogen inlet was charged with 2.67 g (10.0 mmol) of
diethyl bromodifluoromethylphosphonate, 1.25 g (11 mmol) of Cd
and 10 mL of dry DMF. The mixture was stirred at room
temperature for 2 h. 19F NMR analysis revealed the formation of
(EtO)2P(O)CF2CdX (two doublets at ꢀ122.8 and ꢀ123.6 ppm with
J = 83 Hz, the ration of the two doublets was 1:1) in 91% NMR yield
based on starting phosphonate (EtO)2P(O)CF2Br. The unreacted Cd
was removed by filtration through a medium frit funnel under a
nitrogen atmosphere and the filtrate was treated with 0.69 g
(7.0 mmol) of CuCl and 1.5 g (6.0 mmol) of 4-nitroiodobenzene at
room temperature for 3 h. 100 mL of ether was added to the
reaction mixture and the precipitated solids were removed by
filtration and washed with 50 mL of ether. The combined ether
solutions were washed with NH4Cl(aq) and H2O, dried over
Na2SO4, and evaporated to give a residue, which was further
purified by silica gel column chromatography. Eluent (CH2Cl2/
EtOAc 9:1) gave 1.55 g (84%) of 7a, mp 47–48 8C. 19F NMR: ꢀ110.1
(d, J = 111 Hz). 1H NMR: 1.35 (t, J = 7 Hz, 6 H), 4.26 (m, 4 H), 7.83 (d,
J = 8 Hz, 2 H), 8.33 (d, J = 8 H, 2 H). 13C NMR: 16.4 (d, J = 6 Hz), 65.2
(d, J = 7 Hz), 117.3 (td, J = 264, 216 Hz), 123.6 (s), 127.8 (s), 139.0
(td, J = 22, 14 Hz), 149.5 (s). 31P NMR 5.3 (t, J = 110 Hz). GC–MS (m/
z) (relative intensity) 309 (M+, 0.31), 279 (M+ –NO, 3.18), 263 (M+ –
NO2, 0.42), 172 (CF2C6H4NO2+, 8.92), 137 {(EtO)2P(O)+, 28.49}, 109
{(HO)(EtO)P(O)+, 100}. FTIR: (CCl4) 2986 (m), 2933 (w), 2914 (w),
1614 (w), 1533 (s), 1351 (s), 1275 (s), 1068 (s), 1047 (s), 1026 (vs),
856 (m) cmꢀ1. HRMS: calc’d for C11H14F2NO5P [M+] 309.0578,
obsv’d: 309.0578.
4.1.5. Diethyl a,a-difluoro-2-chlorobenzylphosphonate (7e)
88%; bp 111 8C (0.03 mm). 19F NMR: ꢀ105.4 (d, J = 114 Hz). 1
H
NMR: 134 (t, J = 7 Hz, 6 H), 4.25 (m, 4 H), 7.34–7.46 (m, 3 H), 7.63
(d, J = 7 Hz, 1 H). 13C NMR: 16.4 (d, J = 5 Hz), 64.9 (d, J = 7 Hz), 118.1
(td, J = 265, 219 Hz), 126.7 (s), 129.5 (td, J = 8.2 Hz), 130.2 (td,
J = 21, 14 Hz), 131.8 (s), 131.9 (s), 132.8 (m). 31P NMR: 5.7 (t,
J = 114 Hz). GC–MS (m/z) (relative intensity): 263 (M+, –Cl, 20.63),
235 (M+ –Cl– 28, 8.25), 207 (M+ –Cl– 56, 15.53), 161, 163
(CF2C6H4Cl+, 82.52, 25.97), 109 {(HO)(EtO)P(O)+, 100}. FTIR: (CCl4):
2985 (m), 2933 (w), 2913 (w), 1596 (w), 1277 (s), 1128 (s), 1069 (s),
1040 (s), 1025 (s), 981 (m), 939 (m) cmꢀ1
.
4.1.6. Diethyl -difluoro-4-methoxybenzylphosphonate (7f)
a,a
59%; bp 121 8C (0.3 mm). 19F NMR: ꢀ107.5 (d, J = 120 Hz). 1H
NMR: 1.31 (t, J = 7 Hz, 6 H), 3.82 (s, 3 H), 4.19 (m, 4 H), 6.96 (d,
J = 8 Hz, 2 H), 7.55 (d, J = 8 Hz, 2 H). 13C NMR: 16.4 (d, J = 5 Hz), 55.4
(s), 64.7 (d, J = 7 Hz), 113.9 (s), 118.3 (td, J = 263, 221 Hz), 124.7 (td,
J = 23, 14 Hz), 127.9 (td, J = 7, 2 Hz), 161.5 (s). 31P NMR: 6.90 (t,
J = 119 Hz). GC–MS (e/z) (relative intensity): 294 (M+, 3.66), 157
(CF2C6H4OMe+, 100), 109 {(HO)(EtO)P(O)+, 6.08}. FTIR (CCl4): 2984
(m), 2962 (w), 2935 (w), 1616 (m), 1516 (m), 1271 (s), 1254 (s),
1050 (s), 1025 (s), 979 (m) 948 (m), 833 (vs) cmꢀ1. HRMS: calc’d for
C
12H17F2O4P [M+] 294,0832, obsv’d 294.0834.
4.1.7. Diethyl -difluoro-4-ethoxycarbonylbenzylphosponate (7g)
a,a
84%; oil. 19F NMR: ꢀ109.8 (d, J = 114 Hz). 1H NMR: 1.32 (t,
J = 7 Hz, 6 H), 1.41 (t, J = 7 Hz, 3 H), 4.20 (m, 4 H, 7.71 (d, J = 8 Hz, 2
H), 8.14 (d, J = 8 Hz, 2 H). 13C NMR: 14.3 (s), 16.4 (d, J = 5 Hz), 61.4
(s), 64.8 (d, J = 7 Hz), 117.8 (td, J = 263, 217 Hz), 126.4 (td, J = 7,
2 Hz), 129.6 (s), 132.8 (s), 136.9 (td, J = 23, 14 Hz), 165.7 (s). 31P
NMR: 5.80 (t, J = 113 Hz). GC–MS (m/z) (relative intensity): 336
(M+, 1.40), 291 (M+ –OEt, 3.35), 199 (CF2C6H4CO2Et+, 26.60), 154
(CF2C6H4CO+, 100), 109 {(HO)(EtO)P(O)+, 59.20}. FTIR (CCl4): 2985
(m), 2933 (w), 1726 (s), 1275 (s), 1063 (s), 1049 (s), 1024 (vs), 981
(m), 943 (m) cmꢀ1. HRMS: calc’d for C14H19F2O5P [M+} 336.0938,
obsv’d 336.0932.
4.1.2. Diethyl
a,a-difluoro benzylphosphonate (7b)
80%; bp 85 8C (0.03 mm); 19F NMR: ꢀ108.9 (d, J = 116 Hz). 1H
NMR: 1.30 (t, J = 7 Hz, 6 H). 4.19 (m, 4 H), 7.47 (m, 3 H), 7.62 (m, 2
H). 13C NMR: 16.3 (d, J = 6 Hz), 64.8 (d, J = 7 Hz), 118.1 (td, J = 263,
218 Hz), 126.3 (td, J = 7, 2 Hz), 128.5 (s), 130.8 (s), 132.7 (td, J = 22,
14 Hz). 31P NMR 6.34 (t, J = 116 Hz). GC–MS (m/z) (relative
intensity) 264 (M+, 2.19), 127 (PhCF2+, 100), 137 {(Et))2P(O)+,
5.55}, 109 {HO)(EtO)P(O+), 37.64}, 77 (Ph+, 30.33). FTIR: (CCl4)
2984 (m), 2933 (w), 2913 (w), 1273 (s), 1129 (s), 1050 (s) 1025 (vs),
771 (m), 698 (m) cmꢀ1. HRMS: calc’d for C11H15F2O3P [M+]
264.0727, obsv’d 264.0715.
4.1.8. Diethyl
a,a-difluoro-4-bromobenzylphosphonate (7h)
70%; bp 96 8C (0.02 mm). 19F NMR: ꢀ109.2 (d, J = 115 Hz). 1H
NMR: 1.31 (t, J = 7 Hz, 6 H), 4.21 (m, 4 H), 7.49 (d, J = 8 Hz, 2 H), 7.60
(d, J = 8 Hz, 2 H). 13C NMR: 16.4 (d, J = 6 Hz), 65.0 (d, J = 7 Hz), 118.1
(td, J = 263, 217 Hz), 126.7 (s), 129.5 (td, J = 8, 2 Hz), 131.8 (s) 132.7
(s). 31P NMR: 6.05 (t, J = 114 H). GC–MS (m/z) (relative intensity):
342, 344 (M+, 3.55, 3.39), 263 (M+, –Br, 16.74), 205, 207 (CF2C6H4Br+,
70.34, 66.95), 137 (24.15), 109 {(HO)(EtO)P(O)+, 100}. FTIR (CCl4):
2985 (m), 2933 (w), 1597 (m), 1398 (m), 1273 (s), 1059 (s), 1049 (s),
4.1.3. Diethyl
a,a-difluoro-2-nitrobenzylphosphonate (7c)
83%; oil; 19F NMR: ꢀ103.4 (d J = 99 Hz). 1H NMR: 136 (t, J = 7 Hz,
6 H), 4.29 (m, 4 H), 7.63 (m, 3 H), 7.84 (m, 1H). 13C NMR: 16.3 (d,
J = 6 Hz), 65.5 (d, J = 7 Hz), 117.2 (td, J = 266, 217 Hz), 124.0 (s),
125.4 (td, J = 22, 14 Hz), 129.9 (t, J = 8 Hz), 131.4 (s), 132.1 (s), 148.8
(s). 31P NMR: 4.63 (t, J = 98 Hz). GC–MS: (m/z) (relative intensity)
310 (M+ + 1, 0.12), 263 (M+ –NO2, 2.30), 172 (CF2C6H4NO2+, 6.84),
137 {(EtO)2P(O)+, 2.47}, 109 {(HO)(EtO)P(O)+, 42.57}. FTIR: (CCl4)
2986 (m), 2933 (w), 2913 (w), 1545 (s), 1370 (s), 1275 (s), 1042 (s),
1024 (vs), 981 (m), 938 (m), 783 (vs), 773 (s), 766 (s) cmꢀ1
.
4.1.9. Diethyl -difluoro-2-phenylbenzylphosphonate (7i)
a,a
65%; oil. 19F NMR: ꢀ109.2 (d, J = 115 Hz). 1H NMR: 1.25 (t,
J = 7 Hz, 6 H), 4.12 (m, 4 H), 7.21 (m, 1 H), 7.31–7.44 (m, 7 H), 7.76 (m.
1 H). 13C NMR: 16.3 (d, J = 5 Hz), 64.6 (d, J = 7 H), 119.4 (td, J = 265,
218 Hz), 127.0 (s), 127.1 (s), 127.2 (s), 128.3 (t, J = 8 Hz), 129.4 (s),
130.0 (td, J = 21. 14 H), 130.2 (s), 132.6 (s), 141.3 (s), 141.7 (d,
J = 3 Hz). 31P NMR 6.34 (t, J = 116 Hz). GC–MS (m/z) (relative
intensity): 340 (M+, 26.38), 203 (CF2C6H4Ph+, 78.90), 109 {(HO)(E-
tO)P(O)+, 17.66}. FTIR (CCl4): 2985 (m), 2933 (w), 2913 (w), 1482
1027 (vs), 941 (m), 982 (m) cmꢀ1
.
4.1.4. Diethyl -difluoro-3-nitrobenzylphosphonate (7d)
a,a
80%; oil; 19F NMR: ꢀ109.6 (d, J = 112 Hz). 1H NMR 1.36 (t,
J = 7 Hz, 6 H), 4.27 (m, 4 H), 7.69 (t, J = 8 Hz, 1 H), 7.99 (d, J = 8 Hz, 1
H), 8.37 (d, J = 8 Hz, 1 H), 8.47 (s, 1 H). 13C NMR: 16.4 (d, J = 6 Hz),
65.2 (d, J = 7 Hz), 117.1 (td, J = 264, 218 Hz), 121.6 (td, J = 7 Hz),
125.7 (s), 130.0 (s), 132.4 (td, J = 7, 2 Hz), 134.9 (td, J = 22, 14 Hz),
148.3 (s). 31P NMR: 5.36 (t, J = 111 Hz). GC–MS (m/z) (relative
intensity) 309 (M+, 0.18), 279 (M+ –NO, 0.93), 263 (M+ –NO2, 0.25),
172 (CF2C6H4NO2+. 27.10), 137 {(EtO)2P(O)+, 18.49}, 109 {(HO)(E-
tO)P(O)+., 100}. FTIR: (CCl4) 2986 (m), 2933 (w), 2914 (w), 1624
(w), 1539 (s), 1275 (s), 1065 (s), 1047 (s), 1024 (vs), 981 (m), 951
(m), 1273 (s), 1073 (s), 1048 (s), 1036 (s), 1024 (s), 980 (m) cmꢀ1
.
4.1.10. Diethyl
a,a-difluoro-3,5-
bis(trifluoromethyl)benzylphosphonate (7j)
83%; bp 71 8C (0.03 mm). 19F NMR: ꢀ63.5 (s, 6F), ꢀ110.2 (d,
J = 110 Hz, 2F). 1H NMR: 1.36 (t, J = 7 Hz, 6H), 4.28 (m, 4H), 8.03