Polyfunctional imidazoles: V. Synthesis of 1-aryl-4-chloro-5-di(TRI) fluoromethyl-1H-imidazoles

Article abstract of DOI:10.1134/S1070428012030104

1-Aryl-4-chloro-1H-imidazole-5-carbaldehydes and 1-aryl-4-chloro-1H- imidazole-5-carboxylic acids reacted with sulfur(IV) fluoride to give, respectively, 1-aryl-4-chloro-5-difluoromethyl- and 1-aryl-4- chloro-5-trifluoromethyl-1H-imidazoles. Pleiades Publ

Full text of DOI:10.1134/S1070428012030104

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 3, pp. 394–398. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © V.A. Chornous, A.N. Grozav, A.V. Bezdudnyi, M.V. Vovk, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 3,
pp. 399–402.
Polyfunctional Imidazoles: V.* Synthesis of 1-Aryl-4-chloro-
5-di(tri)fluoromethyl-1H-imidazoles
V. A. Chornousa, A. N. Grozava, A. V. Bezdudnyib, and M. V. Vovkb
a Bukovinian State Medical University, Teatral’naya pl. 2, Chernovtsy, 58000 Ukraine
e-mail: chornous@inbox.ru
b Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 5, Kiev, 02660 Ukraine
Received July 18, 2011
Abstract—1-Aryl-4-chloro-1H-imidazole-5-carbaldehydes and 1-aryl-4-chloro-1H-imidazole-5-carboxylic
acids reacted with sulfur(IV) fluoride to give, respectively, 1-aryl-4-chloro-5-difluoromethyl- and 1-aryl-4-
chloro-5-trifluoromethyl-1H-imidazoles.
DOI: 10.1134/S1070428012030104
Imidazole derivatives containing a partly or com-
pletely fluorinated methyl group in the 5-position
exhibit a broad spectrum of pharmacological activity.
5-Difluoromethylimidazoles can be used for the treat-
ment of atherosclerosis, chronic renal insufficiency [2],
inflammatory diseases, faulty immunoregulation [3],
and parasitic diseases [4]. 5-Trifluoromethyl-substitut-
ed imidazoles in turn were patented as therapeutic
agents for the treatment of vascular [5] and central
nervous systems [6] and inflammatory [7, 8] and auto-
immune diseases [9].
ensuring fluorination of oxygen-containing groups
under more severe conditions. In fact, by heating
5-formylimidazoles Іa–If with sulfur(IV) fluoride for
18 h at 65–95°C under pressure we obtained 1-aryl-4-
chloro-5-difluoromethyl-1H-imidazoles ІІa–IIf in 53–
64% yield (Scheme 1).
Scheme 1.
Cl
Cl
N
N
SF4
CHO
CHF2
N
N
Analysis of structures of bioactive 5-di(tri)fluoro-
methylimidazoles shows that they generally contain
additional substituents in positions 1 and 2 of the ring.
Their 1,4-substituted analogs have been studied to
a lesser extent, which stimulated our interest in the
synthesis of new 5-di(tri)fluoromethylimidazoles
having a chlorine atom in the 4-position. It is known
that the presence of chlorine atoms could favor some
biological properties [10–12].
Ar
Ar
Ia–If
IIa–IIf
Ar = 4-ClC6H4 (a), 2-MeC6H4 (b), 3-MeC6H4 (c), 4-MeC6H4 (d),
4-MeOC6H4 (e), 1-C10H7 (f).
The formation of difluoromethyl group is con-
firmed by the presence in the H NMR spectra of ІІa–
1
IIf of characteristic triplets at δ 6.58–6.72 ppm with
a coupling constant of 52.0 Hz, and in the 13C NMR
spectra, of triplets at δC 107–118 ppm with a coupling
constant of 233–235 Hz. The 19F NMR spectra of
compounds ІІa and IIc–IIe contained doublets at
δF –111 ppm from fluorine nuclei in the CHF2 group
(2JHF = 50–53 Hz). However, imidazoles ІІb and IIf
having sterically hindered 2-methylphenyl or 1-naph-
thyl substituent in position 1 displayed in the 19F NMR
spectra an AB part of ABX spin system. Presumably,
magnetic nonequivalence of fluorine atoms in the
Known 5-difluoromethylimidazoles were synthe-
sized as a rule by fluorination of the corresponding
5-formylimidazoles with (dialkylamino)sulfur tri-
fluorides in methylene chloride at room temperature
[2–4]. We found that 1-aryl-4-chloro-1H-imidazole-5-
carbaldehydes Іa–If [13] failed to react with (dialkyl-
amino)sulfur trifluorides under analogous conditions.
Therefore, we used sulfur(IV) fluoride [14] as reagent
* For communication IV, see [1].
394

POLYFUNCTIONAL IMIDAZOLES: V.
395
CHF2 group results from restricted rotation of that
group due to effect of the aryl substituent on N1.
sure reactor was charged with 1 mmol of aldehyde Іa–
If, 0.2 ml of water, and 4.30 g (4 mmol) of sulfur(IV)
fluoride, and the mixture was heated for 16–18 h at
65–70°C (Іa) or 90–95°C (Іb–If). The reactor was
cooled, volatile products were degassed, and the mix-
ture was poured onto 50 g of ice, neutralized to pH 7
with sodium hydrogen carbonate, and extracted with
methylene chloride. The extract was dried over anhy-
drous sodium sulfate and evaporated, and the residue
was purified by chromatography on silica gel using
ethyl acetate–hexane (3:1) as eluent.
5-Trifluoromethylimidazoles are synthesized most
frequently by cyclocondensation of trifluoromethyl-
containing building blocks, trifluoroacetylhydrazones
[15–17] and trifluoroacetimidoyl chlorides [18, 19].
Less common methods involve photochemical tri-
fluoromethylation of imidazoles [20]. Fluorination of
carboxy group with molybdenum hexafluoride [21] or
sulfur tetrafluoride [22] was used previously only for
the transformation of imidazole-4,5-dicarboxylic acids
into 4,5-bis(trifluoromethyl)imidazoles. We extended
the synthetic potential of this method to obtain
4-chloro-5-trifluoromethylimidazoles. For this purpose
aldehydes Іa–Ic and Ie–Ig were oxidized with potas-
sium permanganate to 4-chloro-1H-imidazole-5-car-
boxylic acids ІІІa–IIIf in 68–82% yield. The reaction
of acids ІІІa–IIIf with sulfur tetrafluoride at 100–
130°C under pressure afforded 61–69% of the corre-
sponding 1-aryl-4-chloro-5-trifluoromethyl-1H-imid-
azoles IVa–IVf (Scheme 2).
4-Chloro-1-(4-chlorophenyl)-5-difluoromethyl-
1H-imidazole (ІІa). Yield 64%, mp 68–70°C. 1H NMR
spectrum, δ, ppm: 6.72 t (1H, CHF2, J = 52.0 Hz),
7.35 d (2H, Harom, J = 8.4 Hz), 7.47 d (2H, Harom, J =
8.4 Hz), 7.51 s (1H, 2-H). 13C NMR spectrum, δC,
1
ppm: 118.15 t (CHF2, JCF = 235.1 Hz), 120.15 t (C5,
2JCF = 25.1 Hz); 127.29, 129.82, 133.87, 135.91
3
(Carom); 133.42 t (C4, JCF = 7.5 Hz), 138.23 (C2).
19F NMR spectrum: δF –111.04 ppm (CHF2, J =
53.4 Hz). Found, %: C 45.87; H 2.42; N 10.85.
C10H6Cl2F2N2. Calculated, %: C 45.66; H 2.30;
N 10.65.
Scheme 2.
Cl
Cl
4-Chloro-5-difluoromethyl-1-(2-methylphenyl)-
1H-imidazole (ІІb). Yield 60%, mp 62–64°C. 1H NMR
spectrum, δ, ppm: 2.08 s (3H, CH3), 6.60 t (1H, CHF2,
N
N
KMnO4
SF4
Ia–Ic, Ie–Ig
COOH
CF3
N
N
13
J = 52.0 Hz), 7.25–7.42 m (5H, Harom, 2-H). C NMR
Ar
Ar
spectrum, δC, ppm: 16.95 (CH3), 108.06 t (CHF2,
IIIa–IIIf
IVa–IVf
2
1JCF = 233.94 Hz), 120.30 t (C5, JCF = 25.2 Hz);
І, Ar = Ph (g); ІІІ, IV, Ar = Ph (a), 4-ClC6H4 (b), 2-MeC6H4 (c),
3-MeC6H4 (d), 4-MeOC6H4 (e), 1-C10H7 (f).
126.55, 127.92, 130.14, 130.91, 134.13, 135.76 (Carom);
3
132.18 t (C4, JCF = 7.5 Hz), 138.58 (C2). 19F NMR
spectrum, δF, ppm: –114.60 (AB part of ABX spin
system, JFF = 330.7, JFH = 52.8 Hz), –110.08 (AB part
of ABX spin system, JFF = 329.4, JFH = 52.9 Hz).
Found, %: C 54.13; H 3.65; N 11.75. C11H9ClF2N2.
Calculated, %: C 54.45; H 3.74; N 11.54.
The structure of compounds IVa–IVf was consist-
ent with their spectral parameters. In particular, their
19F NMR spectra contained a singlet belonging to CF3
group at δF –55 to –56 ppm, while the CF3 carbon atom
and C5 resonated in the 13C NMR spectra as quartets at
δC 119–120 and 115–117 ppm, respectively.
4-Chloro-5-difluoromethyl-1-(3-methylphenyl)-
1H-imidazole (ІІc). Yield 53%, oily substance.
1H NMR spectrum, δ, ppm: 2.42 s (3H, CH3), 6.69 t
(1H, CHF2, J = 52.0 Hz), 7.20–7.41 m (4H, Harom),
EXPERIMENTAL
13
7.51 s (1H, 2-H). C NMR spectrum, δC, ppm: 22.14
The IR spectra were recorded in KBr on a UR-20
(CH3), 108.47 t (CHF2, 1JCF = 233.2 Hz), 119.73 t (C5,
2JCF = 25.2 Hz); 126.14, 127.84, 129.89, 130.70,
1
spectrometer. The H and 13C NMR spectra were
measured from solutions in CDCl3 on a Bruker Avance
DRX-500 spectrometer at 500.13 and 125.75 MHz,
respectively, using tetramethylsilane as internal refer-
3
134.26, 135.95 (Carom); 132.25 t (C4, JCF = 7.5 Hz),
138.20 (C2). 19F NMR spectrum: δF –111.50 ppm, d
(CHF2, JFH = 53.1 Hz). Found, %: C 54.18; H 3.56;
N 11.73. C11H9ClF2N2. Calculated, %: C 54.45;
H 3.74; N 11.54.
19
ence. The F NMR spectra were obtained on a Varian
Gemini instrument (188.14 MHz; solvent CDCl3,
internal reference CCl3F).
1-Aryl-4-chloro-5-difluoromethyl-1H-imidazoles
ІІa–IIf (general procedure). A 100-ml steel high-pres-
4-Chloro-5-difluoromethyl-1-(4-methylphenyl)-
1H-imidazole (ІІd). Yield 63%, mp 52–54°C. 1H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

CHORNOUS et al.
396
spectrum, δ, ppm: 2.40 s (3H, CH3), 6.68 t (1H, CHF2,
J = 52.0 Hz), 7.28 s (4H, Harom), 7.48 s (1H, 2-H).
13C NMR spectrum, δC, ppm: 21.10 (CH3), 108.25 t
(CHF2, 1JCF = 233.9 Hz), 120.21 t (C5, 2JCF = 25.2 Hz);
125.68, 130.06, 132.83, 140.75 (Carom); 133.69 t (C4,
3JCF = 7.0 Hz), 140.20 (C2). 19F NMR spectrum:
δF –111.47 ppm, d (CHF2, J = 56.8 Hz). Found, %:
C 54.28; H 3.86; N 11.43. C11H9ClF2N2. Calculated,
%: C 54.45; H 3.74; N 11.54.
spectrum, δ, ppm: 7.44–7.51 m (5H, Harom), 8.04 s (1H,
2-H). 13C NMR spectrum, δC, ppm: 119.25 (C5);
126.19, 128.84, 128.89, 136.63 (Carom); 135.79 (C4),
140.48 (C2), 159.23 (COOH). Found, %: C 53.67;
H 3.12; N 12.55. C10H7ClN2O2. Calculated, %:
C 53.95; H 3.17; N 12.58.
4-Chloro-1-(4-chlorophenyl)-1H-imidazole-5-
carboxylic acid (ІІІb). Yield 82%, mp 205–207°C. IR
spectrum, ν, cm–1: 2560–2830 (COOH), 1710 (C=O).
1H NMR spectrum, δ, ppm: 7.50 d (2H, Harom, J =
8.2 Hz), 7.58 d (2H, Harom, J = 8.2 Hz), 8.28 (1H, 2-H).
13C NMR spectrum, δC, ppm: 119.20 (C5); 128.15,
128.75, 133.43, 133.47 (Carom); 135.13 (C4), 140.49
(C2), 159.40 (COOH). Found, %: C 46.57; H 2.42;
N 10.75. C10H6Cl2N2O2. Calculated, %: C 46.72;
H 2.35; N 10.90.
4-Chloro-5-difluoromethyl-1-(4-methoxyphen-
yl)-1H-imidazole (ІІe). Yield 61%, oily substance.
1H NMR spectrum, δ, ppm: 3.85 s (3H, CH3O), 6.68 t
(1H, CHF2, J = 52.0 Hz), 6.96 d (2H, Harom, J =
8.8 Hz), 7.32 d (2H, Harom, J = 8.8 Hz), 7.49 s (1H,
2-H). 13C NMR spectrum, δC, ppm: 55.4 (CH3O),
1
2
108.62 t (CHF2, JCF = 234.3 Hz), 120.35 t (C5, JCF
=
25.3 Hz); 114.74, 126.49, 128.24, 159.87 (Carom);
4-Chloro-1-(2-methylphenyl)-1H-imidazole-5-
carboxylic acid (ІІІc). Yield 68%, mp 240–242°C. IR
spectrum, ν, cm–1: 2520–2870 (COOH), 1710 (C=O).
1H NMR spectrum, δ, ppm: 2.00 s (3H, CH3), 7.31–
3
133.88 t (C4, JCF = 7.2 Hz), 140.21 (C2). 19F NMR
spectrum: δF –111.32 ppm, d (CHF2, J = 50.7 Hz).
Found, %: C 51.35; H 3.33; N 10.63. C11H9ClF2N2O.
Calculated, %: C 51.08; H 3.51; N 10.83.
13
7.43 m (4H, Harom), 8.17 s (1H, 2-H). C NMR spec-
trum, δC, ppm: 16.81 (CH3), 119.39 (C5); 126.47,
127.34, 129.25, 130.34, 134.57, 136.19 (Carom); 135.38
(C4), 140.40 (C2), 159.07 (COOH). Found, %:
C 55.67; H 3.72; N 11.65. C11H9ClN2O2. Calculated,
%: C 55.83; H 3.83; N 11.84.
4-Chloro-5-difluoromethyl-1-(1-naphthyl)-1H-
1
imidazole (ІІf). Yield 59%, mp 58–60°C. H NMR
spectrum, δ, ppm: 6.58 t (1H, CHF2, J = 52.0 Hz),
7.25 d (1H, Harom, J = 8.0 Hz), 7.44–7.63 m (5H,
13
H
arom), 7.93–8.02 m (2H, Harom, 2-H). C NMR spec-
1
trum, δC, ppm: 107.90 t (CHF2, JCF = 236.4 Hz),
121.49 t (C5, JCF = 25.1 Hz); 121.71, 124.89, 125.76,
2
4-Chloro-1-(3-methylphenyl)-1H-imidazole-5-
carboxylic acid (ІІІd). Yield 70%, mp 183–184°C. IR
spectrum, ν, cm–1: 2520–2850 (COOH), 1710 (C=O).
1H NMR spectrum, δ, ppm: 2.34 s (3H, CH3), 7.21–
127.18, 128.06, 128.27, 130.23, 130.74, 131.27, 134.04
3
(Carom); 132.25 t (C4, JCF = 7.0 Hz), 139.42 (C2).
19F NMR spectrum, δF, ppm: –113.24 (AB part of ABX
spin system, JFF = 311.2, JFH = 53.41 Hz), –112.98 (AB
part of ABX spin system, JFF = 310.8, JFH = 52.7 Hz).
Found, %: C 60.57; H 3.41; N 10.13. C14H9ClF2N2.
Calculated, %: C 60.34; H 3.26; N 10.05.
13
7.40 m (4H, Harom), 8.08 s (1H, 2-H). C NMR spec-
trum, δC, ppm: 19.44 (CH3), 119.19 (C5); 126.52,
128.17, 128.76, 129.15, 133.43, 135.47 (Carom); 135.91
(C4), 140.51 (C2), 159.13 (COOH). Found, %:
C 56.00; H 3.71; N 11.75. C11H9ClN2O2. Calculated,
%: C 55.83; H 3.83; N 11.84.
1-Aryl-4-chloro-1H-imidazole-5-carboxylic acids
ІІІa–IIIf (general procedure). Aldehyde Іa–Ic or Ie–
Ig, 0.01 mol, was dispersed in 40 ml of 80% aqueous
dioxane, 5.22 g (0.02 mol) of potassium permanganate
was added in portions over a period of 30 min under
stirring and cooling with water, and the mixture was
stirred for 2 h. Excess KMnO4 was decomposed by
treatment with solid Na2SO3 until violet color disap-
peared. The mixture was diluted with 50 ml of water,
the precipitate was filtered off, the filtrate was
acidified with concentrated hydrochloric acid, and the
precipitate was filtered off, dried, and recrystallized
from acetic acid.
4-Chloro-1-(4-methoxyphenyl)-1H-imidazole-5-
carboxylic acid (ІІІe). Yield 74%, mp 248–250°C. IR
spectrum, ν, cm–1: 2520–2825 (COOH), 1710 (C=O).
1H NMR spectrum, δ, ppm: 3.81 s (3H, CH3O), 7.03 d
(2H, Harom, J = 8.0 Hz), 7.36 d (2H, Harom, J = 8.0 Hz),
13
7.96 s (1H, 2-H). C NMR spectrum, δC, ppm: 55.47
(CH3O), 113.88 (Carom), 119.32 (C5), 127.52 and
129.51 (Carom), 135.55 (C4), 140.57 (C2), 159.23
(COOH), 159.36 (Carom). Found, %: C 52.37; H 3.43;
N 11.23. C11H9ClN2O3. Calculated, %: C 52.29;
H 3.59; N 11.09.
4-Chloro-1-phenyl-1H-imidazole-5-carboxylic
acid (ІІІa). Yield 80%, mp 208–210°C. IR spectrum,
4-Chloro-1-(1-naphthyl)-1H-imidazole-5-carbox-
ylic acid (ІІІf). Yield 73%, mp 227–230°C. IR spec-
trum, ν, cm–1: 2510–2890 (COOH), 1715 (C=O).
1
ν, cm–1: 2510–2810 (COOH), 1715 (C=O). H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

POLYFUNCTIONAL IMIDAZOLES: V.
397
1H NMR spectrum, δ, ppm: 7.22 d (1H, Harom, J =
8.4 Hz), 7.55–8.09 m (6H, Harom), 8.13 s (1H, 2-H).
13C NMR spectrum, δC, ppm: 120.57 (C5); 121.48,
125.05, 125.29, 126.72, 127.77, 128.20, 129.57,
129.94, 133.28, 133.39 (Carom); 135.65 (C4), 141.26
(C2), 158.94 (COOH). Found, %: C 61.42; H 3.25;
N 10.45. C14H9ClN2O2. Calculated, %: C 61.66;
H 3.33; N 10.27.
4-Chloro-1-(3-methylphenyl)-5-trifluoromethyl-
1H-imidazole (IVd). Yield 65%, mp 39–41°C.
1H NMR spectrum, δ, ppm: 2.38 s (3H, CH3), 7.31–
13
7.52 m (4H, Harom), 8.19 s (1H, 2-H). C NMR spec-
2
trum, δC, ppm: 20.63 (CH3), 115.43 q (C5, JCF
=
1
37.7 Hz), 120.03 q (CF3, JCF = 267.8 Hz); 123.63,
126.95, 129.28, 130.79. 131.37, 139.40 (Carom); 134.66
19
(C4), 140.77 (C2). F NMR spectrum: δF –55.04 ppm
(CF3). Found, %: C 50.51; H 2.96; N 10.49.
C11H8ClF3N2. Calculated, %: C 50.69; H 3.09; N 10.75.
1-Aryl-4-chloro-5-trifluoromethyl-1H-imidazoles
IVa–IVf (general procedure). A 100-ml steel high
pressure reactor was charged with 1 mmol of acid
ІІІa–IIIf, 0.2 ml of water, and 10.8 g (10 mmol) of
sulfur tetrafluoride, and the mixture was heated for
16 h at 100–110°C (ІІІa, IIIb) or 120–130°C (ІІІc–
IIIf). The reactor was cooled, volatile products were
degassed, and the mixture was poured onto 50 g of ice,
neutralized to pH 7 with sodium hydrogen carbonate,
and extracted with methylene chloride. The extract was
dried over anhydrous sodium sulfate and evaporated,
and the residue was purified by chromatography on
silica gel using ethyl acetate–hexane (4:1) as eluent.
4-Chloro-1-(4-methoxyphenyl)-5-trifluorometh-
yl-1H-imidazole (IVe). Yield 64%, mp 50–52°C.
1H NMR spectrum, δ, ppm: 3.38 s (3H, CH3O), 7.12 d
(2H, Harom, J = 8.8 Hz), 7.47 d (2H, Harom, J = 8.8 Hz),
13
8.14 s (1H, 2-H). C NMR spectrum, δC, ppm: 55.30
2
(CH3O), 115.72 q (C5, JCF = 37.1 Hz), 119.91 q (CF3,
1JCF = 257.9 Hz); 114.45, 127.24, 128.05, 160.06
19
(Carom); 130.97 (C4), 141.03 (C2). F NMR spectrum:
δF –55.71 ppm (CF3). Found, %: C 47.91; H 2.76;
N 10.38. C11H8ClF3N2O. Calculated, %: C 47.76;
H 2.91; N 10.13.
4-Chloro-1-phenyl-5-trifluoromethyl-1H-imid-
1
4-Chloro-1-(1-naphthyl)-5-trifluoromethyl-1H-
azole (IVa). Yield 69%, mp 47–49°C. H NMR spec-
1
imidazole (IVf). Yield 65%, mp 72–74°C. H NMR
trum, δ, ppm: 7.27–7.37 m (2H, Harom), 7.51–7.55 m
13
spectrum, δ, ppm: 7.25 d (1H, Harom, J = 7.5 Hz), 7.63–
7.74 m (3H, Harom), 7.81 m (1H, Harom, J = 7.5 Hz),
8.12 d (1H, Harom, J = 8.0 Hz), 8.22 d (1H, Harom, J =
(3H, Harom), 8.20 s (1H, 2-H). C NMR spectrum, δC,
2
ppm: 117.35 q (C5, JCF = 38.7 Hz), 119.98 q (CF3,
1JCF = 267.8 Hz); 126.25, 129.43, 130.07, 135.01
13
19
(Carom); 132.80 (C4), 138.61 (C2). F NMR spectrum:
8.0 Hz), 8.32 (1H, 2-H). C NMR spectrum, δC, ppm:
2
1
116.94 q (C5, JCF = 38.9 Hz), 119.99 q (CF3, JCF
=
δF –56.07 ppm (CF3). Found, %: C 48.55; H 2.37;
N 11.13. C10H6ClF3N2. Calculated, %: C 48.70;
H 2.45; N 11.36.
267.8 Hz); 121.23, 125.36, 126.32, 127.25, 128.36,
129.78, 130.97, 133.46 (Carom); 130.73 (C4), 141.83
(C2). 19F NMR spectrum: δF –55.86 ppm (CF3). Found,
%: C 56.47; H 2.58; N 9.25. C14H8ClF3N2. Calculated,
%: C 56.68; H 2.72; N 9.44.
4-Chloro-1-(4-chlorophenyl)-5-trifluoromethyl-
1H-imidazole (IVb). Yield 67%, mp 46–48°C.
1H NMR spectrum, δ, ppm: 7.63 d (2H, Harom, J =
8.1 Hz), 7.68 d (3H, Harom, J = 8.1 Hz), 8.22 s (1H,
2-H). 13C NMR spectrum, δC, ppm: 115.69 q (C5,
REFERENCES
1
2JCF = 37.7 Hz), 119.98 q (CF3, JCF = 269.1 Hz);
1. Chornous, V.A., Grozav, A.N., Bratenko, M.K., and
128.61, 129.46, 133.46, 134.93 (Carom); 131.43 (C4),
140.89 (C2). 19F NMR spectrum: δF –56.22 ppm (CF3).
Found, %: C 42.44; H 1.57; N 9.58. C10H5Cl2F3N2.
Calculated, %: C 42.73; H 1.79; N 9.97.
Vovk, M.V., Russ. J. Org. Chem., 2011, vol. 47, p. 1527.
2. Adams, C., Hu, Q.-Y, Ksander, G.M., and Papillon, J.,
WO Patent Appl. no. 2008076336, 2008; Chem. Abstr.,
2008, vol. 149, no. 104710y.
4-Chloro-1-(2-methylphenyl)-5-trifluoromethyl-
1H-imidazole (IVc). Yield 61%, mp 38–40°C.
1H NMR spectrum, δ, ppm: 2.04 s (3H, CH3), 7.35–
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7.50 m (4H, Harom), 8.14 s (1H, 2-H). C NMR spec-
2
trum, δC, ppm: 16.37 (CH3), 115.69 q (C5, JCF
=
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37.7 Hz), 119.94 q (CF3, JCF = 267.8 Hz); 126.85,
126.92, 128.07, 130.66. 130.95, 135.39 (Carom); 133.68
19
(C4), 141.00 (C2). F NMR spectrum: δF –56.38 ppm
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C11H8ClF3N2. Calculated, %: C 50.69; H 3.09; N 10.75.
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