1342
Dolensky, Kirk:
1
2
141.60, 3 C (Tr); 129.40, 6 CH (Tr); 128.44, 3 CH, JCH = 161.6 d, JCH = 7.5 t (Tr); 128.30,
4
1
2
4
6 CH (Tr); 127.40 t, JCF = 1.7, JCH = 191.0 d, JCH = 9.3 d (C4Im i or C5Im i); 122.68 t, JCF
2.6, JCH = 192.1 d, JCH = 17.5 d (C4Im i or C5Im i); 106.40 t, JCF = 236.0, JCH = 188.2 d
(CHF2); 75.63 (Tr). 19F NMR (CDCl3): –113.5 d, JFH = 51.9 (CHF2). For C23H18F2N2 (360.4)
=
1
2
1
1
2
calculated: 76.65% C, 5.03% H, 7.77% N; foun d: 76.55% C, 5.15% H, 7.76% N.
[2-(Difluoromethyl)imidazol-1-yl]fluoro(1-trityl-1H-imidazol-2-yl)methane (17). M.p. 150–
165 °C with decom p. (from dieth yl eth er). Th e com poun d is also un stable in CDCl3 solution
if stored at room tem perature for exten ded periods (days). 1H NMR (CDCl3): 7.71 br s, 1 H
3
(HIm i); 7.35– 7.24 m , 9 H (Tr); 7.24 d, 1 H, JHH = 1.2 (HIm i); 7.11–7.05 m , 6 H (Tr); 6.95 br s,
3
2
2
1 H (HIm i); 6.88 d, 1 H, JHH = 1.2 (HIm i); 6.59 d, 1 H, JHF = 47.7 (CHF); 6.29 t, 1 H, JHF
=
53.0 (CHF2). 13C NMR (CDCl3): 141.31 d, JCF = 28.5 (C2Im i-CHF-Im i); 141.27, 3 C (Tr);
2
2
1
2
139.64 t, JCF = 27.7 (C2Im i-CHF2); 129.27, 6 CH, JCH = 159.6 d, JCH = 6.4 t (Tr); 128.52, 3 CH,
1JCH = 161.8 d, JCH = 7.4 t (Tr); 128.34, 6 CH, JCH = 162 d, Σ<1JCH = 14 m (Tr); 128.25 d,
2
1
1
2
4
1
2
4JCF = 1.0, JCH ≈ 205 d, JCH = 10.0 d (CHIm i); 127.51 d, JCF = 1.7, JCH = 192.1 d, JCH = 9.4 d
4
1
2
(CHIm i); 129.99 d, JCF = 2.7, JCH = 192.8 d, JCH1 = 17.1 d (CHIm i); 122.38 dt, JCF = 2.8, 1.0,
1JCH ≈ 196 d, JCH ≈ 17 d (CHIm i); 109.18 dd, JCF = 237.3, 238.1, JCH = 191.7 d (CHF2);
2
1
1
4
1
84.45 ddd, JCF = 203.9, JCF = 3.7, 2.4, JCH = 168.8 d (CHF); 75.89 (Tr). 19F NMR (CDCl3):
2
2
5
2
–112.9 ddd, 1 F, JFF = 313.6, JFH = 53.0, JFF = 7.6 (CHF2); –116.6 dd, 1 F, JFF = 313.6,
2JFH = 53.0 (CHF2); –122.6 dd, JFH = 47.9, JFF = 7.6 (CHF). HRMS (FAB+) for C27H22F3N4
(MH) calculated: 459.1797; foun d: 459.1799; daugh ter fragm en ts of MH, m/z (assign m en t):
243 (Tr), 309 (Tr-Im i), 341 (Tr-Im i-CHF), 118 (H-Im i-CHF2). For C27H21F3N4 (458.5) calcu-
lated: 70.73% C, 4.62% H, 12.22% N; foun d: 70.73% C, 4.76% H, 12.16% N.
2
5
2-(Difluoromethyl)imidazole (3). M.p. 119–120 °C (from CHCl3; decom p. above 165 °C).
2
1H NMR (CDCl3): 10.1–9.4 br s, 1 H (NH); 7.17 br s, 2 H (HIm i); 6.75 t, 1 H, JHF = 54.2
2
1
(CHF2). 13C NMR: 140.27 t, JCF = 28.3 (C2Im i); 108.72 t, JCF = 235.9 (CHF2); ≈123 very br s
(C4Im i an d C5Im i). 19F NMR (CDCl3): –113.8 d, JFH = 54.2 (CHF2). For C4H4F2N2 (118.1) cal-
2
culated: 40.69% C, 3.41% H, 23.72% N; foun d: 40.71% C, 3.40% H, 23.70% N.
2-(Difluoromethyl)imidazole hydrochloride (3·HCl). M.p. 162–168 °C (from iPrOH/Et2O; with
decom p.). pKa1 = 3.4 at 25 °C. 1H NMR (DMSO-d6): 10.2–8.2 br s, 2 H (NH·HCl); 7.72 s, 2 H
2
2
(HIm i); 7.38 t, 1 H, JHF = 52.6 (CHF22). 13C NMR (DMSO-d6): 137.72 t, JCF = 30.5, ΣJCF,CH
=
1
1
90 (C2Im i); 121.69 s, JCH = 199.8 d, JCH = 12.5 d (C4Im i an d C5Im i); 107.12 t, JCF = 237.7,
1JCH = 199.4 d (CHF2). 19F NMR (DMSO-d6): –115.4 d, JFH = 52.6 (CHF2). For C4H5ClF2N2
2
(154.6) calculated: 31.09% C, 3.26% H, 18.13% N; foun d: 31.33% C, 3.27% H, 17.91% N.
4-(Difluorom eth yl)-1H-im idazole (4)
a) A stirred solution of 1.00 g (3.0 m m ol) of aldeh yde 12 in 40 m l of dich lorom eth an e
was cooled to –65 °C an d 1.2 m l of Deoxo-Fluor (6.5 m m ol) was added dropwise. Th e reac-
tion m ixture was allowed to warm slowly to room tem perature an d was stirred for th ree
days. Th e m ixture was th en poured in to 100 m l of CH2Cl2 an d extracted th ree tim es with
100 m l of water. Th e organ ic ph ase was dried over an h ydrous MgSO4 an d evaporated to dry-
n ess. Th e resultin g solid (831 m g) was separated by colum n ch rom atograph y (40 g,
CH2Cl2/Et2O, 100 : 0 to 8 : 2) to give 271 m g (35%) of TrOH (as a result of partial
detritylation ), 55 m g (6%) of startin g aldeh yde 12 an d 454 m g (43%) of 4-(difluoro-
m eth yl)im idazole 15.
b) Com poun d 15 (1.07 g, 2.97 m m ol) was dissolved in 25 m l of acetic acid an d 8 m l of
h ydroch loric acid (1:5) was added at room tem perature. Th e m ixture was stirred overn igh t
Collect. Czech. Chem. Commun. (Vol. 67) (2002)