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100 MHz) δ 134.9, 133.9, 132.3, 131.9, 129.9, 128.7, 102.5, 83.4.
HRMS was determined using the derivatized MS procedure: HRMS
m/z C12H14Cl5O4P [M + H+] calculated 428.9151, found 428.9143.
2,2,2-Trichloro-1-(2-nitrophenyl)ethan-1-ol (11).32 The com-
pound was obtained using general method A and was isolated as a
2,2,2-Trichloro-1-(3,5-dibromo-4-((4-methoxybenzyl)oxy)-
phenyl)ethan-1-ol (19). The compound was obtained using general
method A and was isolated as a colorless solid (4.41 g, 85%): 1H NMR
(CDCl3, 400 MHz) δ 7.79 (s, 2H), 7.54 (d, 2H, J = 7.7 Hz), 6.95 (d,
2H, J = 7.7 Hz), 5.12 (s, 1H), 4.99 (s, 2H), 3.83 (s, 3H), 3.44 (br. s,
1H); 13C NMR (CDCl3, 100 MHz) δ 160.1, 153.7, 133.6, 133.4,
130.5, 128.2, 118.1, 114.1, 102.5, 82.8, 74.79, 55.48 HRMS m/z
calculated for C16H13Br2Cl3O3 [M + Na+] 538.8189, found 538.8166.
2,2,2-Trichloro-1-(perfluorophenyl)ethanol (20).36 The compound
was obtained using general method A and was isolated as a colorless
1
pale brown solid (2.57 g, 98%): H NMR (CDCl3, 400 MHz) δ 8.09
(dd, 1H, J = 8.0, 1.1 Hz), 7.89 (dd, 1H, J = 8.1, 1.2 Hz), 7.69 (dt, 1H, J
= 8.0, 1.1 Hz), 7.56 (dt, 1H, J = 8.1, 1.2 Hz), 6.45 (d, 1H, J = 4.3 Hz),
3.63 (d, 1H, J = 4.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 150.1, 132.6,
130.6, 130.3, 129.2, 124.5, 102.1, 77.1. HRMS was determined using
the derivatized MS procedure: HRMS m/z calculated for
C12H15Cl3NO6P [M + H+] 405.9781, found 405.9777.
1
solid (2.29 g 72%): H NMR (CDCl3, 400 MHz) δ 5.59 (d, 1H, J =
10.0 Hz), 3.72 (d, 1H, J = 10.0 Hz); 13C NMR (CDCl3, 100 MHz,
only nonaromatic carbons reported) δ 101.3, 79.36; 19F NMR
(CDCl3, 377 MHz) δ −136.0, 150.6 (m), 160.6.
This compound was also produced in continuous flow, affording 11
(25.2 g, 93%) as a pale brown solid.
2,2,2-Trichloro-1-(3-nitrophenyl)ethan-1-ol (12).33 The com-
pound was obtained using general method A and was isolated as a
colorless solid (2.52 g, 93%): 1H NMR (CDCl3, 400 MHz) δ 8.52 (s,
1H), 8.26 (dd, 1H, J = 8.0, 1.3 Hz), 7.97 (d, 1H, J = 8,0), 7.58 (t, 1H, J
= 8.0 Hz), 5.34 (d, 1H, J = 3.7 Hz), 3.59 (d, 1H, J = 3.7); 13C NMR
(CDCl3, 100 MHz) δ 147.9, 136.8, 135.5, 128.9, 124.6, 124.5, 102.3,
83.5.
Methyl 4-Nitro-3-(2,2,2-trichloro-1-hydroxyethyl)benzoate (21).
The reaction scale was 1 mmol in 1 mL of DMSO, otherwise following
general method A. The compound was isolated as a pale yellow solid
1
(269 mg, 82%): H NMR (CDCl3, 400 MHz) δ 8.74 (d, 1H, J = 1.5
Hz), 8.21 (dd, 1H, J = 8.0, 1.5 Hz), 7.94 (d, 1H, J = 8.0 Hz), 6.39 (s,
1H), 3.98 (s, 3H), 3.77 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ
165.2, 152.5, 133.8, 132.3, 131.5, 129.8, 124.7, 101.87, 77.08, 53.23;
HRMS m/z calculated for C10H8Cl3NO5 [M + Na+] 349.9360, found
349.9359.
4-Nitro-3-(2,2,2-trichloro-1-hydroxyethyl)phenyl 4-Methylbenze-
nesulfonate (22). The reaction scale was 1 mmol in 1 mL of DMSO,
otherwise following general method A. The compound was isolated as
a thick brown oil (408 mg, 93%): 1H NMR (CDCl3, 400 MHz) δ 7.91
(d, 1H, J = 9.0 Hz), 7.73 (d, 2H, J = 8.3 Hz), 7.64 (d, 1H, J = 2.6 Hz),
7.34 (d, 2H, J = 8.3 Hz), 7.33 (d, 1H, J = 9.0 Hz), 6.38 (s, 1H), 3.57
(br. s, 1H); 13C NMR (CDCl3, 100 MHz) δ 151.9, 147.9, 146.4, 131.9
(d, J = 5.6), 130.3, 129.2, 128.7, 128.4, 126.4, 125.4, 124.8, 124.3,
101.5, 76.7, 21.9; HRMS m/z calculated for C15H12Cl3NO6S [M +
Na+] 461.9343, found 461.9337.
This compound was also produced in continuous flow, affording 12
(24.8 g, 92%) as a pale yellow solid.
2,2,2-Trichloro-1-(4-nitrophenyl)ethan-1-ol (13).2b The com-
pound was obtained using general method A and was isolated as a
1
yellow solid (2.43 g, 90%): H NMR (CDCl3, 400 MHz) δ 8.25 (d,
2H, J = 8.8 Hz), 7.84 (d, 2H, J = 8.8 Hz), 5.34 (d, 1H, J = 3.3 Hz),
3,58 (d, 1H, J = 3.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 148.6, 141.6,
130.5, 122.9, 102.2, 83.6.
4-(2,2,2-Trichloro-1-hydroxyethyl)benzonitrile (14). The com-
pound was obtained using general method A and was isolated as a
colorless solid (2.29 g, 92%): 1H NMR (CDCl3, 400 MHz) δ 7.77 (d,
2H, J = 8.4 Hz), 7.69 (d, 2H, J = 8.4 Hz), 5.27 (s, 1H), 3.64 (s, 1H);
13C NMR (CDCl3, 100 MHz) δ 139.9, 131.6, 130.2, 118.5, 113.3,
102.3, 83.7. HRMS was determined using the derivatized MS
procedure: HRMS m/z calculated for C13H15Cl3NO4P [M + H+]
385.9883, found 385.9878.
4-(2,2,2-Trichloro-1-hydroxyethyl)benzoic Acid (23). The reaction
was carried out according to general method B. The compound was
1
isolated as a colorless solid (2.13, 79%): H NMR (acetone-d6, 400
MHz) δ 8.06 (d, 2H, J = 8.0 Hz), 7.84 (d, 2H, J = 8.0 Hz), 6.45 (s,
1H), 5.45 (s, 1H); 13C NMR (acetone-d6, 100 MHz) δ 167.3, 142.7,
131.8, 130.5, 129.5, 104.0, 84.2; HRMS m/z calculated for C9H7Cl3O3
[M − H+] 266.9388, found 266.9394.
2,2,2-Trichloro-1-(3-chlorophenyl)ethan-1-ol (15).34 The com-
pound was obtained using general method A and was isolated as a
pale brown oil (2.23 g, 86%): 1H NMR (CDCl3, 400 MHz) δ 7.63 (s,
1H), 7.51 (d, 1H, J = 8.0 Hz), 7.40 (d, 1H, J = 8.0 Hz), 7.32 (t, 1H, J =
8.0 Hz), 5.19 (d, 1H, J = 3.8 Hz), 3.32 (d, 1H, J = 3.8 Hz); 13C NMR
(CDCl3, 100 MHz) δ 136.7, 133.9, 129.8, 129.5, 129.1, 127.7, 102.7,
83.9. HRMS was determined using the derivatized MS procedure:
HRMS m/z calculated for C12H15Cl4O4P [M + H+] 394.9549, found
394.9537.
1,1′-(1,4-Phenylene)bis(2,2,2-trichloroethan-1-ol) (24). An ddi-
tional 5 mL of DMSO was added to the reaction mixture, and the
reaction mixture was stirred overnight at room temperature, otherwise
following general method A, followed by chromatography with 1/1
pentane/dichloromethane as eluent. The compound was isolated as a
1
colorless solid (1.66 g, 44%): H NMR (CDCl3, 400 MHz) δ 7.65 (s,
2,2,2-Trichloro-1-(4-chlorophenyl)ethan-1-ol (16).8 The com-
pound was obtained using general method A and was isolated as a
colorless solid (2.05 g, 80%): 1H NMR (CDCl3, 400 MHz) δ 7.57 (d,
2H, J = 8.5 Hz), 7,38 (d, 2H, J = 8.5 Hz), 5.21 (d, 1H, J = 3.4 Hz),
3.28 (d, J = 3.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 135.7, 133.3,
130.7, 128.2, 102.9, 84.0.
4H), 5.24 (d, 2H, J = 3.8 Hz), 3.36 (d, 2H, J = 3.1 Hz); 13C NMR
(CDCl3, 100 MHz) δ 136.2, 128.8, 102.9, 84.3, 84.2. HRMS was
determined using the derivatized MS procedure: HRMS m/z
calculated for C14H17Cl6O5P [M + H+] 506.9023, found 506.9020.
tert-Butyl 2-(2,2,2-Trichloro-1-hydroxyethyl)-1H-pyrrole-1-car-
boxylate (25). The compound was obtained using general method
1
1-(4-Bromophenyl)-2,2,2-Trichloroethan-1-ol (17).8 The com-
pound was obtained using general method A and was isolated as a
colorless solid (2.51 g, 82%): 1H NMR (CDCl3, 400 MHz) δ 7.52 (q, J
= 8.7 Hz, 4H), 5.18 (s, 1H), 3.32 (br. s, 1H); 13C NMR (CDCl3, 100
MHz) δ 133.8, 131.2, 131.0, 124.0, 102.8, 83.1.
A and was isolated as a dark red oil (1.93 g, 59%): H NMR (CDCl3,
400 MHz) δ 7.29 (m, 1H), 6.64 (m, 1H), 6.19 (t, 1H, J = 3.3 Hz), 5.98
(d, 1H, J = 7.7 Hz), 4.82 (d, 1H, J = 7.7 Hz), 1.61 (s, 9H); 13C NMR
(CDCl3, 100 MHz) δ 150.2, 128.8, 123.9, 117.0, 110.3, 102.7, 85.4,
78.5, 27.9; HRMS m/z calculated for C11H14Cl3NO3 [M + Na+]
335.9931, found 335,9926.
2,2,2-Trichloro-1-(2-chloro-6-fluorophenyl)ethanol (18).35 The
compound was obtained using general method A and was isolated
2,2,2-Trichloro-1-(thiophen-2-yl)ethan-1-ol (26).2b The com-
pound was obtained using general method A and was isolated as a
colorless solid (1.40 g, 60%): 1H NMR (CDCl3, 400 MHz) δ 7.41 (d,
1H, J = 5.0 Hz), 7.32 (d, 1H, J = 3.3 Hz), 7.05 (t, 1H, J = 5.0 Hz), 5.49
(d, 1H, J = 4.0 Hz), 3.29 (d, 1H, J = 4.0 Hz); 13C NMR (CDCl3, 100
M Hz) δ 137.4, 129.3, 127.2, 126.5, 102.6, 81.7.
1
as a colorless solid (2.43g, 87%): H NMR (CDCl3, 400 MHz) δ
7.36−7.28 (m, 2H), 7.09−7.04 (dd, 1H, J = 8.4, 2.8 Hz), 5.87 (d, 1H, J
= 9.6), 4.01 (t, 1H, J = 9.6 Hz); 13C NMR (CDCl3, 100 MHz) δ 163.1
(d, J = 995.3 Hz), 136.6 (d, J = 24.5 Hz), 131.2 (d, J = 43.4 Hz), 126.2,
121.1 (d, J = 45.6 Hz), 115.9 (d, J = 99.3 Hz), 101.8, 82.5; 19F NMR
(CDCl3, 377 MHz) δ 105.64. HRMS was determined using the
derivatized MS procedure: HRMS m/z calculated for C12H14Cl4FO4P
[M + H+] 412.9446, found 412.9442.
2,2,2-Trichloro-1-(pyridin-4-yl)ethanol (27).37 The compound was
obtained using general method A and was isolated as a yellow solid
(1.59 g, 70%): 1H NMR (DMSO-d6, 400 MHz) δ 8.61 (d, 2H, J = 6.0
Hz), 7.62 (d, 2H, J = 6.0 Hz), 7.55 (d, 1H, J = 5.9 Hz), 5.32 (d, 1H, J
= 5.9 Hz); 13C NMR (DMSO-d6, 100 MHz) δ 148.9, 145.8, 124.2,
This compound was also produced in continuous flow, affording 18
(22.8 g, 82%) as a colorless solid.
H
dx.doi.org/10.1021/jo402595r | J. Org. Chem. XXXX, XXX, XXX−XXX