CF ), 132.27, 134.82 (C1), 148.27 (C᎐N); m/z 221 (Mϩ, 1%), 186
(100), 77 (62).
C, 55.69; H, 5.15; N, 14.43%); νmax (KBr)/cmϪ1 3273 (NH), 1638
(C᎐O), 1520 (NO , as stretch), 1345 (NO , s stretch); λ
max
᎐
3
᎐
2
2
N-[2,2,2-Trifluoro-1-(trifluoromethyl)ethyl]benzimidoyl
chloride (1b). Formed using the general procedure outlined
above but using a 12 h reflux. The product was an oil, formed in
98% yield (Found: C, 40.75; H, 2.12; N, 4.88; F, 40.28; Cl, 11.97.
C10H6F6ClN requires C, 41.47; H, 2.09; N, 4.48; F, 39.36; Cl,
(dioxane)/nm 265 (ε = 11300); δH (270 MHz, CDCl3; TMS) 1.28
(3H, t, J = 7.31 Hz, CH3), 3.52 (2H, dq, J = 7.31, 5.68 Hz, CH2),
6.44 (1H, br s, NH), 7.94 (2H, d, J = 8.98 Hz, H3 & H5),
8.27 (2H, d, J = 8.98 Hz, H2 & H6); δC (68 MHz, CDCl3–
CD3COCD3) 14.73 (CH3), 35.31 (CH2), 123.71, 128.81, 140.98
12.24%); νmax (KBr)/cmϪ1 1654 (C᎐N); λ
(dioxane)/nm 253
(C1), 149.68 (C4), 165.48 (C᎐O); m/z 194 (Mϩ, 38%), 150 (100),
᎐
᎐
max
(ε = 40404); δH (270 MHz, CDCl3; TMS) 5.12 (1H, septet,
J = 6.2 Hz, CH), 7.54 (3H, m, H3, H4 & H5), 8.12 (2H, d,
J = 8.6 Hz, H2 & H6); δC (68 MHz, CDCl3) 67.34 (septet,
JFC = 31.2Hz, CH), 125.99 (q, JFC = 284.8 Hz, CF3), 128.76,
130.00, 133.45, 134.23 (C1), 154.94 (C-C1).
104 (50), 76 (52).
N-Isopropyl-p-nitrobenzamide. Formed in 68% yield; mp
151–153 ЊC (Found: C, 57.54; H, 5.90; N, 13.49. C10H12N2O3
requires C, 57.69; H, 5.80; N, 13.46%); νmax (KBr)/cmϪ1 3302
(NH), 1637 (C᎐O), 1519 (NO , as stretch), 1348 (NO , s
᎐
2
2
N-(2,2,2-Trifluoroethyl)-p-nitrobenzimidoyl chloride (1c). Bp
169–171 ЊC, 1.5 mmHg (Found: C, 40.38; H, 2.41; N, 10.36; F,
21.01; Cl, 13.62. C9H6ClF3N2O2 requires C, 40.55; H, 2.27; N,
stretch); λmax (dioxane)/nm 266 (ε = 11000); δH (270 MHz,
CDC13; TMS) 1.28 (6H, d, J = 6.59 Hz, CH3), 4.28 (1H, septet,
J = 6.59 Hz, CH), 6.49 (1H, br s, NH), 7.94 (2H, d, J = 8.98 Hz,
H3 & H5), 8.24 (2H, d, J = 8.98 Hz, H2 & H6); δC (68 MHz,
CDCl3–CD3COCD3) 22.54 (CH3), 42.41 (CH), 123.61, 128.16,
10.51; F, 21.38; Cl, 13.30%); νmax (KBr)/cmϪ1 1663 (C᎐N), 1526
᎐
(NO2, as stretch), 1352 (NO2, s stretch); λmax (dioxane)/nm 266
(ε = 13600), 212 (ε = 8000); δH (270 MHz, CDCl3; TMS) 4.22
(2H, q, J = 9.1 Hz, CH2), 8.23 (2H, d, J = 9.1 Hz, H2 & H6),
8.30 (2H, d, J = 9.1 Hz, H3 & H5); δC (68 MHz, CDCl3; CDCl3)
55.38 (q, JFC = 33.3 Hz, CH2), 123.95 (1C, q, JFC = 278.3 Hz,
CF3), 124.01 (C3 & C5), 128.47 (C2 & C6), 130.70 (C1), 139.94
140.56 (C1), 149.26 (C4), 164.79 (C᎐O); m/z 208 (Mϩ, 15%), 193
᎐
(15), 150 (40).
N-[2,2,2-Trifluoro-1-(trifluoromethyl)ethyl]benzamide.
A
solution of benzamide (2.4g, 0.02 mol) and a catalytic amount
of dried toluene-p-sulfonic acid (0.2g, 1 mmol) in dry dichloro-
methane (100 ml) was sealed in a pressure reactor. The vessel
was flushed with dry nitrogen for one hour then the hexafluoro-
acetone gas was added to a pressure of approximately 10 psi.
The sealed reaction was stirred for 24 hours at room tem-
perature by which time the pressure had dropped. The vessel
was flushed through with nitrogen into water bubblers for
30 minutes before filtration, and the resulting yellow solution
was washed with water, dried (MgSO4) and the organic solvent
was removed.
Pyridine (3.32 g, 3.4 ml, 1.0 mmol) and trifluoroacetic
anhydride (4.40 g, 2.8 ml, 0.02 mol) were added simultaneously
dropwise, over 30 min, to an ice-cold well stirred solution of the
resulting solid (0.02 mol) in dry diethyl ether (30 ml). After
another hour at 0 ЊC the mixture was filtered to remove a white
precipitated solid.
(C᎐N), 149.55 (C4); m/z 266 (Mϩ, 3%), 231 (100), 185 (70), 102
᎐
(35), 76 (45).
N-[2,2,2-Trifluoro-1-(trifluoromethyl)ethyl]-p-nitrobenzimid-
oyl chloride (1f). The product was an oil; yield 97% (Found: C,
36.48; H, 1.59; N, 7.91; F, 34.6; C1, 11.06. C10H5F6C1N2O2
requires C, 35.9; H, 1.49; N, 8.37; F, 34.08; Cl, 10.60%); νmax
(KBr)/cmϪ1 1657 (C᎐N), 1529 (NO , as stretch), 1348 (NO ,
᎐
2
2
s stretch); λmax (dioxane)/nm 269 (ε = 18500); δH (270 MHz,
CDC13; TMS) 5.15 (1H, septet, J = 6.23 Hz, CH), 8.29 (2H, d,
J = 8.4 Hz, H3 & H5), 8.35 (2H, d, J = 8.45 Hz, H2 & H6); δC
(68 MHz, CDCl3) 66.51 (septet, JFC = 31.2 Hz, CH), 121.32 (q,
JFC = 282.6 Hz, CF3), 128.44, 130.92, 139.21, (C1), 150.67 (C4),
153.26 (C᎐N).
᎐
Amides. Most of the amides were synthesised by treating
the acid chloride with one equivalent of amine in dry ether, in
the presence of one molar equivalent of dry triethylamine.
Aqueous work up, using dichloromethane to solubilise the
amide in some cases, yielded solids which were recrystallised
from either ethanol or industrial methylated spirit (IMS). The
bis(trifluoromethyl) substituted amides were prepared from the
corresponding benzamide and hexafluoroacetone, as described
at the end of this section.
Solid sodium borohydride (0.378 g, 0.01 mol) was added
slowly to this solution, and the reaction mixture was stirred
at room temperature for 48 h. After addition of ice, hydro-
chloric acid was added to bring the pH to approximately 4.
The ethereal layer was separated, washed with brine, dried
(MgSO4) and the solvent removed. A flash column using
chloroform as eluant resulted in the isolation of a white solid
which was recrystallised from IMS. Yield, 3.95g (73%); mp
147–149 ЊC (lit.,41 149 ЊC) (Found: C, 44.23; H, 2.60; N, 5.13;
F, 42.01. Calcd for C10H7F6NO C, 44.28; H, 2.58; N, 5.17;
F, 42.07%); νmax (KBr)/cmϪ1 3280 (NH), 1663 (C᎐O); λ
N-(2,2,2-Trifluoroethyl)benzamide. Formed in 88% yield; mp
117–118 ЊC (lit.,40 115–116 ЊC) (Found: C, 53.29; H, 3.96; N,
6.84; F, 27.87. C9H8F3NO requires C, 53.21; H, 3.97; N, 6.89; F,
28.05%); νmax (KBr)/cmϪ1 3264 (NH), 1673 (C᎐O); λ
᎐
max
(dioxane)/nm 239 (ε = 3700); δH (270 MHz, CDCl3; TMS)
5.62 (1H, d septet, J = 6.97, 3.29 Hz, CH), 6.57 (1H, br d,
NH), 7.55 (3H, m, H3, H4 & H5), 7.83 (2H, d, J = 8.6 Hz,
H2 & H6); δC (68 MHz, CDCl3) 52.67 (qq, JFC = 33.3 Hz,
CH), 122.01 (q, JFC = 282.6 Hz, CF3), 127.67, 128.49, 132.53,
᎐
max
(dioxane)/nm 227 (ε = 9800); δH (270 MHz, CDC13; TMS) 4.03
(2H, dq, J = 4.4, 9.1 Hz, CH2), 7.37 (2H, dd, J = 7.7, 7.3 Hz, H3
& H5), 7.49 (1H, dd, J = 7.5, 7.3 Hz, H4), 7.81 (2H, d, J = 7.1
Hz, H2 & H6), 8.09 (1H, br t, NH); δC (68 MHz, CDCl3) 40.83
(q, JFC = 34.4 Hz, CH2), 117.98, 122.10, 124.15 (q, JFC 279.3 Hz,
CF ), 128.41, 131.95, 133.07 (C1), 168.55 (C᎐O); m/z 203 (Mϩ,
132.25 (C1), 168.55 (C᎐O); m/z 271 (Mϩ, 20%), 105 (100), 77
᎐
(60).
᎐
3
40%), 105 (100), 77 (43).
N-[2,2,2-Trifluoro-1-(trifluoromethyl)ethyl]-p-nitrobenz-
amide. The synthesis was carried out according to the above
procedure, using p-nitrobenzamide in place of benzamide, yield
3.90 g (62%); mp 167–168 ЊC (Found: C, 38.07; H, 1.87; N, 8.41;
F, 35.31. C10H6N2O3F6 requires C, 38.01; H, 1.91; N, 8.87; F,
36.07%); νmax (KBr)/cmϪ1 3264 (NH), 1673 (C᎐O), 1541 (NO ,
N-(2,2,2-Trifluoroethyl)-p-nitrobenzamide. Formed in 78%
yield; mp 128–130 ЊC (Found: C, 43.59; H, 3.12; N, 11.18; F,
22.62. C9H7F3N2O3 requires C, 43.56; H, 2.84; N, 11.29; F,
22.97%); νmax (KBr)/cmϪ1 3314 (NH), 1653 (C᎐O), 1525 (NO ,
as stretch), 1353 (NO2, s stretch); λmax (dioxane)/nm 262
(ε = 12200); δH (270 MHz, CDCl3; TMS) 4.11 (2H, dq, J = 4.2,
9.1 Hz, CH2), 8.04 (2H, d, J = 9.0 Hz, H2 & H6), 8.27 (2H, d,
J = 8.8 Hz, H3 & H5), 8.46 (1H, br t, NH); δC (68 MHz, CDCl3)
41.25 (q, JFC = 35.0 Hz, CH2), 124.28 (q, JFC = 278.3 Hz, CF3),
᎐
2
᎐
2
as stretch), 1340 (NO2, s stretch); λmax (dioxane)/nm 258
(ε = 11800); δH (270 MHz, CDCl3; TMS) 6.22 (1H, qq, J = 7.69
Hz, CH), 8.14 (2H, d, J = 8.98 Hz, H3 & H5), 8.35 (2H, d,
J = 8.98 Hz, H2 & H6), 10.16 (1H, br d, J = 7.69 Hz, NH);
δC (68 MHz, CDCl3) 55.96 (qq, JFC = 32.3 Hz, CH), 126.10 (q,
JFC = 278.3 Hz, CF3), 132.21 (C1), 132.49 (C3 & C5), 136.19
128.85 (C3 & C5), 139.07 (C1), 149.954 (C4), 166.86 (C᎐O); m/z
᎐
248 (Mϩ, 36%), 150 (100), 76 (20).
N-Ethyl-p-nitrobenzamide. Formed in 72% yield; mp 145–
146 ЊC (Found: C, 55.28; H, 5.28; N, 14.26. C9H10N2O3 requires
(C2 & C6), 136.57 (C4), 171.76 (C᎐O); m/z 316 (Mϩ, 12%), 150
᎐
(100), 104 (32), 76 (35).
J. Chem. Soc., Perkin Trans. 2, 2001, 1239–1246
1245