1340 J . Org. Chem., Vol. 61, No. 4, 1996
Me´debielle et al.
8-(Non a flu or obu tyl)h yp oxa n th in e (15a H), 8-(Non a flu -
or obu tyl)xa n th in e (16a H), a n d 5-(Iod o-n on a flu or obu ta -
n e)u r a cil (19bH) were described in reference 8c.
(CI/NH3): m/ e ) 213 (M + H+), 230 (M + NH4+). Anal. Calcd
C 56.60, H 3.30, N 13.20. Found. C 57.01, H 3.45, N 13.58.
2-[2′-(tr iflu or om eth yl)p h en yl]im id a zole (7eH): white col-
umns, mp ) 160 °C (MeOH); TLC (EtOAc): Rf ) 0.60; 19F
6-(Non aflu or obu tyl)pter idin e-2,4(1H,3H)-dion e (18aH):
beige powder, mp > 260 °C; TLC (CH2Cl2-EtOH, 85:15): Rf
) 0.50; 19F NMR (acetone-d6/CFCl3): δF -81.1 (CF3), -112.6
1
NMR (DMSO-d6/CFCl3): δF -62.5 (CF3); H NMR (CDCl3
+
DMSO-d6): δH 7.72 (H-4 or H-5, 1H, singulet), 7.86 (H-2, 1H,
singlet), 8.1-8.42 (H-aromatic, 4H, multiplet); mass (CI/
NH3): m/ e ) 213 (M + H+), 230 (M + NH4+). Anal. Calcd C
56.60, H 3.30, N 13.20. Found. C 56.95, H 3.65, N 13.48.
1
(CF2R), -121.3 (CF2â), -124.7 (CF2γ); H NMR (Acetone-d6):
δH 9.18 (H-7, 1H, singlet), 10.92 (H-1, 1H, broad singlet), 11.37
(H-3, 1H, broad singlet); mass (CI/NH3): m/ e ) 383 (M + H+),
400 (M + NH4+). Anal. Calcd C 31.41, H 0.78, N 14.60.
Found. C 31.65, H 0.95, N 14.85.
Electr olysis of 1-Iod o-2-(tr iflu or om eth yl)ben zen e in
th e P r esen ce of th e 2-(4′-m eth oxyp h en yl)im id a zole An -
ion (10-). After evaporation of the EtOAc extracts, 1.7 g of
an orange oil was obtained as crude material which was
purified by silica gel chromatography (EtOAc) to give 687 mg
(2.16 mmol, 55%) of 2-(4′-m eth oxyp h en yl)-4(5)-[2-(tr iflu o-
r om eth yl)p h en yl]im id a zole (10cH): white plates, mp )
248 °C (benzene); TLC (EtOAc): Rf ) 0.50; 19F NMR
(DMSO-d6/CFCl3): δF -62.8 (CF3); 1H NMR (DMSO-d6): δH
3.80 (OCH3, 3H, singlet), 7.61 (H-5, 1H, broad singlet), 6.97
and 7.90 (AA′BB′, 4H, J ) 8Hz, aryl H’s of the methoxyphenyl
ring), 7.82-8.1 (H-aromatic, 4H, multiplet); mass (CI/NH3):
m/ e ) 319 (M + H+), 336 (M + NH4+). Anal. Calcd C 64.15,
H 4.08, N 8.80. Found. C 64.25, H 4.58, N 8.93.
8-(Non a flu or obu tyl)-1,3-d im eth ylxa n th in e (17a H): or-
ange powder, mp > 260 °C; TLC (CH2Cl2-EtOH, 75:25): Rf
) 0.50; 19F NMR (DMSO-d6/CFCl3): δF -81.2 (CF3), -110.0
(CF2R), -120.2 (CF2â), -122.4 (CF2γ); 1H NMR (DMSO-d6):
δH 3.17 (CH3, 3H, singlet), 3.45 (CH3, 3H, singlet); mass (CI/
NH3): m/ e ) 399 (M + H+), 416 (M + NH4+). Anal. Calcd C
21.91, H 0.68, N 16.39. Found. C 22.31, H 0.72, N 16.78.
5-(Non a flu or obu tyl)cytosin e (20a H): white powder, mp
> 260 °C; TLC (alumina plates, CHCl3-MeOH-H2O, 60:35:
0.5): Rf ) 0.50; 19F NMR (DMSO-d6/CFCl3): δF -81.2 (CF3),
-116.6 (CF2R), -124.3 (CF2â), -128.7 (CF2γ); 1H NMR
(DMSO-d6): δH 8.45 (H-6, 1H, singlet); mass (CI/NH3): m/ e
) 330 (M + H+), 347 (M + NH4+). Anal. Calcd C 29.17, H
1.21, N 12.76. Found. C 29.22, H 1.45, N 12.89.
Electr olysis of 1-(4′-Iod o-tetr a flu or op h en yl)im id a zole
in th e P r esen ce of th e 2-Meth yl-5-n itr oim id a zole An ion
(9-). When 90% of the substrate had reacted (as checked by
cyclic voltammetry), the solution was cooled and neutralized
with 100 mL of 2 N HCl; the resulting precipitate was filtered,
carefully washed with water (4 × 50 mL), and triturated with
hot Et2O to yield 0.46 g (1.35mmol, 35%) of the chromato-
graphically pure compound (TLC): 4-[2′,3′,5′,6′-tetr a flu or o-
4′-(im id a zol-1′′-yl)p h e n yl]-1H -2-m e t h yl-5-n it r oim id a -
zole (9bH): white plates, mp ) 185 °C (benzene); TLC
(EtOAc): Rf ) 0.50; 19F NMR (DMSO-d6/CFCl3): δF - 120.2
(2F, AA′XX′d-d, J ) 23, 12, 3, 3, and 1 Hz, F-2′ and F-6′),
-160.4 (2F, AA′XX′, J ) 21, 10, 3, and 3 Hz, F-3′ and F-5′);
1H NMR (DMSO-d6): δH 2.55 (CH3, 3H, singlet), 7.22 (H-4,
1H, singlet), 7.45 (H-5, 1H, singlet), 7.96 (H-2, 1H, singlet);
mass (CI/NH3): m/ e ) 342 (M + H+), 359 (M + NH4+). Anal.
Calcd C 45.75, H 2.05, N 20.52. Found. C 45.86, H 2.35, N
20.82.
5-(Iod o-n on a flu or obu ta n e)cytosin e (20bH): creme pow-
der, mp > 260 °C; TLC (alumina plates, CHCl3-MeOH-H2O,
60:35:0.5): Rf ) 0.30; 19F NMR (DMSO-d6/CFCl3): δF -68.7
(CF2I), -109.3 (CF2R), -116.2 (CF2â), -120.4 (CF2γ); 1H NMR
(DMSO-d6): δH 8.65 (H-6, 1H, singlet); mass (CI/NH3): m/ e
) 328 (M - I + H+ + NH4+), 455 (M + NH4+). Anal. Calcd C
21.97, H 0.91, N 9.61. Found. C 22.02, H 1.06, N 9.85.
Compound 21a H: After 0.80 F/mol of starting material, the
electrolysis solution was directly analyzed by 19F NMR: 19F
NMR (DMSO-d6/CFCl3): δF -79.2 (CF3), -98.2 (CF2R), -117.5
(CF2â) which was assigned to the structure described in the
text.
A Typ ica l P r oced u r e for th e Electr olysis of 1-Iod o-2-
(tr iflu or om eth yl)ben zen e in th e P r esen ce of th e Ur a cil
An ion . Into 100 mL of DMSO containing 4.6 g (25 mmol) of
the tetramethylammonium salt of uracil and 1.20 mmol of
phthalonitrile were added 2.17 g (10 mmol) of NEt4BF4 and
then 1.0 g (3.94 mmol) of 1-iodo-2-(trifluoromethyl)benzene.
The potential was set at the first reduction wave of the
catalyst. When 90% of the substrate had reacted (as checked
by cyclic voltammetry), the solution was cooled and neutralized
with 100 mL of 2 N HCl; the resulting precipitate was filtered,
carefully washed with water (4 × 50 mL), and triturated with
hot Et2O to yield 0.35 g (1.37mmol, 38%) of the chromato-
graphically pure compound (TLC) of 5-[2′-(tr iflu or om eth yl)-
p h en yl]-1H-p yr im id in e-2,4-d ion e (19cH): yellowish pow-
Electr olysis of 1-(4′-Iod o-tetr a flu or op h en yl)im id a zole
in th e P r esen ce of th e Ur a cil An ion (19-). As described
before, the resulting precipitate was filtered, carefully washed
with water (4 × 50 mL), and triturated with hot Et2O to yield
0.63 g (1.93 mmol, 50%) of the chromatographically pure
compound (TLC): 5-[2′,3′,5′,6′-tetr a flu or o-4′-(im id a zol-1′′-
yl)-p h en yl]-1H-2,4-p yr im id in e-2,4-d ion e (19d H): white
powder, mp > 260 °C; TLC (EtOAc-MeOH, 75:25): Rf ) 0.50;
19F NMR (DMSO-d6/CFCl3): δF -121.4 (2F, AA′XX′-d-d, J )
26, 10, 3, 3, 1, and 1 Hz, F-2′ and F-6′), -161.7 (2F, AA′XX′, J
) 25, 10, 3, and 3 Hz, F-3′ and F-5′); 1H NMR (DMSO-d6): δH
7.26 (H-4, 1H, singlet), 7.65 (H-5, 1H, singlet), 7.96 (H-6 of
the uracil, 1H, singlet), 8.01 (H-2, 1H, singlet); mass (CI/
NH3): m/ e ) 327 (M + H+), 344 (M + NH4+). Anal. Calcd C
47.85, H 1.84, N 17.18. Found. C 48.03, H 2.05, N 17.52.
der, mp > 260 °C; TLC (CHCl3-MeOH, 75-25): Rf ) 0.50; 19
F
NMR (DMSO-d6/CFCl3): δF -62.2 (CF3); 1H NMR (DMSO-
d6): δH 7.4-7.8 (H-aromatic, 4H, multiplet), 8.02 (H-6, 1H,
singlet), 11.4 (NH-1, 1H, singlet); mass (CI/NH3): m/ e ) 257
(M + H+), 274 (M + NH4+). Anal. Calcd C 51.56, H 2.73, N
10.93. Found. C 51.62, H 2.86, N 11.06.
Electr olysis of 1-Iod o-2-(tr iflu or om eth yl)ben zen e in
th e P r esen ce of th e Im id a zole An ion (7-). The potential
was set at the first reduction wave of the catalyst. When 90%
of the substrate had reacted (as checked by cyclic voltamme-
try), the solution was cooled and neutralized with 100 mL of
2 N HCl. The aqueous solution was extracted three times with
Et2O, and the organic solutions were combined, washed three
times with water, and dried over MgSO4. The solvent was
evaporated to yield 2.1 g of an orange oil which was purified
by silica gel chromatography (CH2Cl2/MeOH, 9:1 as eluent)
to give 290 mg (35%) of a mixture of the two isomers, 2-[2′-
(tr iflu or om eth yl)p h en yl]im id a zole (7eH) and the 4(5)-[2′-
(tr iflu or om eth yl)p h en yl]im id a zole (7fH). These two iso-
mers could be separated by preparative TLC (EtOAc as eluent)
to give as the more polar isomer the 4(5)-[2′-(tr iflu or om eth -
yl)p h en yl]im id a zole (7fH): white plates, mp ) 128 °C
(EtOH); TLC (EtOAc): Rf ) 0.45; 19F NMR (DMSO-d6/
CFCl3): δF -61.5 (CF3); 1H NMR (DMSO-d6): δH 7.35 (H-4 or
H-5, 1H, singlet), 7.7-8.02 (H-aromatic, 4H, multiplet); mass
Ack n ow led gm en t. We thank Dr. Y. Besace, Marie-
Noelle Rager (ENSCP), for their help with 19F NMR and
Nicole Morin (ENS, Paris) for recording the mass
spectra. P. Guiriec is acknowledged for his help with
1
the H NMR spectra. We wish to express our thanks
to Drs. H. Kimoto and S. Fujii (National Industrial
Research Institute of Nagoya, Nagoya, J apan) for many
helpful discussions regarding the chemistry of perfluo-
roalkylated imidazoles and for the gift of samples of
2-(tridecafluorohexyl)-4(5)-nitroimidazole and 4-(tride-
cafluorohexyl)-5-nitroimidazole. Rhoˆne-Poulenc-Rorer
is gratefully thanked for carrying out the biological
tests.
J O9515541