Synthesis of 2-(perfluoroalkyl)- and 2-(perfluoroaryl)benzimidazoles by oxidative intramolecular cyclization of perfluoroalkyl and aryl imidamides

Full text of DOI:10.1021/jo952224j

3902
J . Org. Chem. 1996, 61, 3902-3905
Sch em e 1
Syn th esis of 2-(P er flu or oa lk yl)- a n d
2-(P er flu or oa r yl)ben zim id a zoles by
Oxid a tive In tr a m olecu la r Cycliza tion of
P er flu or oa lk yl a n d Ar yl Im id a m id es
Masafumi Kobayashi and Kenji Uneyama*
Department of Applied Chemistry, Faculty of Engineering,
Okayama University, Okayama 700, J apan
Received December 18, 1995
Because of the synthetic importance of fluoro-function-
alized heterocycles,1 a variety of approaches to the
syntheses of fluorinated heterocycles have been studied.
Fluorinated benzimidazoles show insecticidal and her-
bicidal activities.2 The general procedure for the syn-
thesis of the fluorinated benzimidazoles involves the
direct trifluoromethylation3 or perfluoroalkylation4 of
benzimidazoles and condensation of o-phenylenediamine
or o-nitroaniline with trifluoroacetic acid or perfluoro-
alkanoic acid.5 Since trifluoroethanimidamide deriva-
tives 26 and perfluoroalkyl and aryl imidamides 3-5 are
easily available, these fluoro-functionalized imidamides
would be converted to the corresponding fluorinated
benzimidazoles by intramolecular carbon-nitrogen bond
formation. Photoinduced7 and oxidative intramolecular
cyclizations by sodium hypochlorite8 and lead(IV) acetate9
have been demonstrated.
We have previously reported the preparation of 2-(tri-
fluoromethyl)benzimidazoles by electrochemical oxidative
cyclization of 210 and Lewis acid-promoted cyclization of
the electrochemically prepared p-benzoquinone imine
derivatives 11.11 In this note, we describe a detailed
study on the electrochemical and the oxidant-promoted
reactions of perfluoroalkyl and aryl imidamides and
related imidamides.
Perfluoroalkyl and aryl imidamides 3, 4, and 5 (R2 )
C3F7, C7F15, and C6F5, respectively) were easily prepared
from N-aryl perfluoroalkyl and aryl imidoyl chlorides 112
in reasonable yields as shown in Scheme 1. The imid-
amide 7 was prepared by the reaction of ethyl ortho-
acetate 6 with p-anisidine.13 The preparation of 9 was
achieved by the reaction of p-anisidine with the benz-
imidoyl chloride which was prepared by the reaction of
benzamide 8 with PCl5.14
The electrooxidation of 2 in dry acetonitrile gave the
desired benzimidazole 10 quantitatively (Table 1, entry
1). On the other hand, electrooxidation in MeOH pro-
vided quinone imine acetal 12 selectively (entry 2). This
result suggests that intermolecular nucleophilic attack
of methanol on an electron-deficient cationic aromatic
ring is faster than intramolecular attack by an imine
nitrogen. Oxidation of 2 by CAN in acetonitrile provided
the desired benzimidazole 10 in 86% yield (entry 3). In
contrast, oxidation by DDQ gave a very poor yield (22%)
of 10 along with recovered 2 (50%) (entry 4). However,
oxidation of 2 by tert-butyl hypochlorite or NCS resulted
in predominant formation of the chlorinated compound
1315 (entries 5 and 6). This result also demonstrates that
intermolecular nucleophilic reaction of chloride ion with
the electron-deficient aromatic ring of 14 is faster than
intramolecular carbon-nitrogen bond formation. Inter-
estingly, reaction with lead(IV) acetate gave a mixture
of benzimidazole 10 (20%), the p-benzoquinone imine
derivative 11 (33%), and its methyl acetal 12 (13%)
(Scheme 2). Compound 11 could arise via 15a by
hydrolysis of the intermediate 15c. Replacement of
acetoxy group of 15c with methanol or water would
produce 12 which may be more stable than 15c (Scheme
3) and is thus isolable. When the same reaction was
conducted in the presence of an equimolar amount of
methanol, the methanol adduct 12 was formed prefer-
entially (entry 8). Similarly, 11 became a major product
(1) Filler, R.; Kobayashi, Y. Biomedicinal Aspects of Fluorine
Chemistry; Kodansha Ltd.: Tokyo, 1982. Hudlicky, M. Chemistry of
Organic Fluorine Compounds; Ellis Horwood: New York, 1976.
(2) J oshi, K.; J ain, R.; Dandia, A.; Sharma, K. J . Fluorine Chem.
1992, 56, 1.
(3) Kimoto, H.; Fujii, S.; Cohen, L. J . Org. Chem. 1982, 47, 2867.
(4) Me´debielle, M.; Pinson, J .; Save´ant, J .-M. J . Am. Chem. Soc.
1991, 113, 6872.
(5) Belcher, R.; Sykes, A.; Tatlow, J . J . Chem. Soc. 1954, 4159.
Sykes, A.; Tatlow, J . J . Chem. Soc. 1952, 4078. Bishop, B.; J ones, A.;
Tatlow, J . J . Chem. Soc. 1964, 3076.
(6) Uneyama, K.; Yamashita, F.; Sugimoto, K.; Morimoto, O. Tetra-
hedron Lett. 1990, 31, 2717.
(7) Branco, P. S.; Prabhakar, S.; Lobo, A. M.; Williams, D. J .
Tetrahedron 1992, 48, 6335.
(8) Grenda, V.; J ones, R.; Gal, G.; Sletzinger, M. J . Org. Chem. 1965,
30, 259. Haruki, E.; Inaike, T.; Imoto, E. Bull. Chem. Soc. J pn. 1965,
38, 1805.
(9) Chaudhury, S.; Debroy, A.; Mahajan, M. P. Can. J . Chem. 1982,
60, 1122.
(10) Uneyama, K.; Kobayashi, M. J . Org. Chem. 1994, 59, 3003.
(11) Uneyama, K.; Kobayashi, M. Tetrahedron Lett. 1991, 32, 5981.
Kobayashi, M.; Uneyama, K.; Hamada, N.; Kashino, S. J . Org. Chem.
1995, 60, 6402.
(12) Tamura, K.; Mizukami, H.; Maeda, K.; Watanabe, H.; Uneyama,
K. J . Org. Chem. 1993, 58, 32.
(14) Hontz, A. C.; Wagner, E. C. Organic Syntheses; Wiley: New
York, 1963; Collect Vol. IV, p 383.
(15) The hydrolysis of 13 followed by trifluoroacetylation and
methylation gave the corresponding N-(2-chloro-4-methoxyphenyl)-N-
methyl-2,2,2-trifluoroacetamide whose spectroscopic data (IR and 1H
NMR) are superimposable with those of an authentic sample.
(13) DeWolte, R. H. J . Org. Chem. 1962, 27, 490.
S0022-3263(95)02224-9 CCC: $12.00 © 1996 American Chemical Society

Notes
entry
J . Org. Chem., Vol. 61, No. 11, 1996 3903
Ta ble 1. Oxid a tion of Im id a m id e 2
yield (%)
Ta ble 2. Electr och em ica l P r ep a r a tion a of Ben zim id a zole
Der iva tives
the first oxidation wave
reagents
solvent
10
11
12 13
imidamide
R2
E1 (V) vs Ag/AgClb
yield (%)
1a
2b
3c
4d
5f
6g
7h
8i
electrooxidation MeCN
electrooxidation MeOH
100
2
3
4
5
7
9
CF3
1.08
1.14
1.23
0.94
0.76
0.76
10 (100)
16 (95)
17 (95)
18 (77)
19 (92)
20 (60)
81
C3F7
C7F15
C6F5
CH3
CAN
MeCN
86
DDQ
t-BuOCl
NCS
dioxane
DMF
DMF
22e
82
80
C6H5
Pb(OAc)4
Pb(OAc)4
Pb(OAc)4
CH2Cl2
CH2Cl2/MeOH
CH2Cl2/H2O
20 33
5
13 75
13
a
trace 91
Imidamides (0.5 mmol); MeCN (7 mL); NaClO4 (0.4 mmol);
anode, glassy carbon; cathode, platinum foil; 5 mA/cm2; 60 °C; 2.2
9j
11
F/mol; undivided cell. Imidamides (3.3 × 10-3 mol L-1); MeCN
b
a
2 (4 mmol); MeCN (35 mL); NaClO4 (1 mmol); anode, glassy
(15 mL); NaClO4 (0.1 mol L-1); Pt wire electrodes; Ag/AgCl
carbon; cathode, platinum foil; 5 mA/cm2; 60 °C; 2.2 F/mol;
electrode for the reference electrode; scan rate, 0.2 V s-1
.
b
undivided cell. 2 (0.25 mmol); MeOH (8 mL); NaClO4 (0.4 mmol);
anode, glassy carbon; cathode, platinum foil; 5 mA/cm2; 60 °C; 2.2
F/mol; undivided cell. c 2 (0.5 mmol); CAN (2.2 equiv); MeCN (5
dominantly promote nucleophilic attack on the aromatic
ring. The acetate formed in lead(IV) acetate oxidation
is intermediate, providing a mixture of 10, 11, and 12.
The electrochemical method for the preparation of 10 was
found to be more advantageous than any other chemical
oxidation so far examined. Not only the trifluoromethyl
imidamide 2 but also perfluoroalkyl 3 and 4 and per-
fluoroaryl 5 imidamides were readily converted to the
corresponding benzimidazoles in excellent yields (Table
2). Of particular interest is the fact that electrooxidation
of the non-fluorinated imidamides 7 and 9 in a MeCN-
NaClO4-(C)-(Pt) system also provided the desired benz-
imidazoles 19 and 20, in good yields.
d
mL); rt; 5 min. 2 (0.25 mmol), DDQ (1.5 equiv); 1,4-dioxane (4
mL); reflux; 12 h. e Recovery of 2 (50%). f 2 (0.5 mmol); t-BuOCl
g
(2.2 equiv); DMF (5 mL); rt; 2 h. 2 (0.5 mmol); NCS (2.2 equiv);
DMF (5 mL); rt; 2 h. 2 (0.25 mmol); Pb(OAc)4 (1.2 equiv); CH2Cl2
(5 mL); rt; 2 h. 2 (0.25 mmol); Pb(OAc)4 (1.2 equiv); CH2Cl2 (5
mL); MeOH (0.25 mmol); rt; 5 min. 2 (0.25 mmol); Pb(OAc)4 (1.2
h
i
j
equiv); CH2Cl2 (5 mL); H2O (2.0 mmol); rt; 2 h.
Sch em e 2
Cyclic voltammetry of trifluoromethylated imidamide
2 shows an irreversible wave which suggests deprotona-
tion occurs soon after one-electron oxidation. The first
oxidation wave E1 appeared at about 1.08 V (vs Ag/AgCl)
while non-fluorinated imidamide 7 had the corresponding
oxidation wave at about 0.76 V (vs Ag/AgCl). The value
of E1 increased proportionally to the perfluoroalkyl chain
length [1.08, 1.14, and 1.23 V (vs Ag/AgCl) for 2 (R2 )
CF3), 3 (R2 ) C3F7), and 4 (R2 ) C7F15), respectively]. The
comparison of oxidation potentials of compounds 5 (R2 )
C6F5) and 9 (R2 ) C6H5) clearly revealed the fluorinated
phenyl compound 5 was less oxidizable. The electro-
chemical cyclization of both fluorinated and non-fluori-
nated imidamides occurred smoothly independently on
the oxidizability of the substrates.
Sch em e 3
Exp er im en ta l Section
P r ep a r a tion s of Im id a m id e Der iva tives. Meth od A (2,10
3, 4, a n d 5). A mixture of N-arylimidoyl chloride (5 mmol) and
p-anisidine (12 mmol) containing Et3N (10 mmol) in acetonitrile
(10 mL) was stirred at the reflux (80 °C) for 2 h. The reaction
mixture was extracted with AcOEt (100 mL × 3) and 1% HCl
(100 mL) and then washed with brine (50 mL). The organic
layer was dried over anhydrous MgSO4 followed by the filtration
through activated carbon and then condensed. The residue was
recrystallized from benzene-hexane.
on reacting 2 with lead(IV) acetate in a wet dichloro-
methane (75%, entry 9).
Cationic intermediate 14 could undergo competitive
electrophilic reaction inter- and intramolecularly. Nu-
cleophiles such as nitrate, used in CAN oxidation, and
perchlorate in electrooxidation are too weak to attack to
the aromatic nucleus, so that intramolecular cyclization
leading to 10 becomes preferred, while stronger nucleo-
philes such as water, methanol, and chloride ion pre-
N ,N ′-Bis(4-m e t h oxyp h e n yl)-2,2,3,3,4,4,4-h e p t a flu or o-
bu ta n im id a m id e (3): Colorless crystals (95%), mp 63-64 °C;
IR (CHCl3) 3444, 3044, 2844, 1670, 1166 cm-1 1H NMR (200
;
MHz, CDCl3) δ 3.65 (s, 6 H), 6.51 (d, 4 H, J ) 9.1 Hz), 6.60 (d,
4 H, J ) 9.1 Hz); 19F NMR (188 MHz, CDCl3) δ 36.1 (m, 2 F),

3904 J . Org. Chem., Vol. 61, No. 11, 1996
Notes
45.4-46.2 (br, 2 F), 81.8 (t, 3 F, J ) 8.5 Hz); GCMS (m/ z) 424
(M+, 3), 302 (8), 255 (M+ - C3F7, 14), 122 (65), 77 (100). Anal.
Calcd for C18H15F7N2O2 (424.32): C, 50.95; H, 3.56; N, 6.60.
Found: C, 51.22; H, 3.28; N, 6.59.
N,N′-Bis(4-m et h oxyp h en yl)-2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-
pen tadecaflu or ooctan im idam ide (4): Colorless crystals (88%);
solution of lead(IV) acetate (1.2 mmol) in CH2Cl2 (2 mL). After
2 h the solvent was evaporated under reduced pressure, and the
residue was extracted with AcOEt (5 mL × 5) and washed with
aqueous Na2CO3 (2 mL) and with brine (2 mL). The organic
layer was dried over anhydrous MgSO4 and concentrated. The
residue was chromatographed on silica gel (5% AcOEt-hexane),
affording 10,10 11,10 and 12 in 20%, 33%, and 13% yields,
respectively.
mp 42-43 °C; IR 3444, 3000, 2840, 1668, 1150 (CHCl3) cm-1
;
1H NMR (200 MHz, CDCl3) δ 3.68 (s, 6 H), 6.53 (d, 4 H, J ) 9.1
Hz), 6.62 (d, 4 H, J ) 9.1 Hz); 19F NMR (188 MHz, CDCl3) δ
35.7 (m, 2 F), 38.9-40.8 (br, 8 F), 43.3-43.8 (br, 2 F), 81.1 (t, 3
F, J ) 9.7 Hz); GCMS (m/ z) 502 (M+ - NHC6H4OCH3, 25) 255
(M+ - C7F15, 100), 122 (95). Anal. Calcd for C22H15F15N2O2
(624.34): C, 42.32; H, 2.42; N, 4.49. Found: C, 42.72; H, 2.03;
N, 4.24.
N 1-(4,4-Dim e t h oxy-2,5-cycloh e xa d ie n -1-ylid e n e )-N 2-
(4-m et h oxyp h en yl)-2,2,2-t r iflu or oet h a n im id a m id e (12):
Orange oil (13 %), bp 250-251 °C (2.5 Torr); IR (neat) 2952,
1
2840, 1648, 1150 cm-1; H NMR (200 MHz, CDCl3) δ 3.18 (s, 6
H), 3.77 (s, 3 H), 6.15-6.60 (br, 4 H), 6.77 (d, 2 H, J ) 9.0 Hz),
6.97 (d, 2 H, J ) 9.0 Hz); 19F NMR (188 MHz, CDCl3) δ 90.3 (s,
3 F); GCMS (m/ z) 354 (M+, 80) 339 (M+ - CH3, 60) 323 (M+
-
N , N ′ -B i s ( 4 -m e t h o x y p h e n y l ) p e n t a f l u o r o b e n z -
im id a m id e (5): Colorless crystals (88%); mp 65-66 °C; IR
(CHCl3) 3460, 3400, 3068, 2844, 1640, 1198 cm-1; 1H NMR (200
MHz, CDCl3) δ 3.73 (s, 6 H), 6.60-7.05 (br, 8 H); 19F NMR (188
MHz, CDCl3) δ 0.5-2.0 (m, 2 F), 9.5-11.0 (br, 1 F), 23.5-25.1
(br, 2 F); GCMS (m/ z) 422 (M+, 20), 300 (M+ - NHC6H4OCH3,
100). Anal. Calcd for C21H15F5N2O2 (422.35): C, 59.72; H, 3.58;
N, 6.63. Found: C, 59.78; H, 3.38; N, 6.78.
Meth od B (7). A mixture of ethyl orthoacetate (6) (10 mmol)
and p-anisidine (50 mmol) containing TsOH (1 mmol) was stirred
at 140 °C for 3 h. When most of the ethanol was distilled out,
the reaction mixture was poured into ice water (20 mL) and
extracted with AcOEt (20 mL × 3). The extracts were then
washed with brine (20 mL) and were dried over anhydrous
MgSO4. The condensed residue was chromatographed on silica
gel (50% AcOEt-hexane).
N,N′-Bis(4-m eth oxyp h en yl)eth a n im id a m id e (7): Color-
less crystals (72%); mp 102-103 °C; IR (CHCl3) 3472, 3400, 3056,
2844, 1644 cm-1; 1H NMR (200 MHz, CDCl3) δ 1.86-2.08 (br, 3
H), 3.79 (s, 6 H), 6.1-6.2 (br, 1 H), 6.8-7.2 (br, 8 H); GCMS
(m/ z) 270 (M+, 14), 148 (M+ - NHC6H4OCH3, 100). Anal. Calcd
for C16H18N2O2 (270.33); C, 71.09; H, 6.71; N, 10.36. Found: C,
70.82; H, 6.94; N, 10.32.
Meth od C (9). A mixture of N-(4-methoxyphenyl)benzamide
(8) (10 mmol) and PCl5 (12 mol) was stirred at 140 °C for 5 h.
When the generation of HCl stopped, pyridine (12 mmol) and
p-anisidine (15 mmol) were slowly added and the mixture was
stirred at 80 °C for 1 h. Distillation gave 9.
OCH3, 75) 202 (M+ - NHC6H4OCH3, 100). Anal. Calcd for
17H17F3N2O3 (354.33): C, 57.63; H, 4.83; N, 7.91. Found: C,
C
57.62; H, 5.04; N, 8.26.
Cyclic Volta m m etr y of Im id a m id es. Imidamide (0.05
mmol) and NaClO4 (1.5 mmol) was dissolved in MeCN (15 mL)
and N2 was bubbled for 30 min. After the bubbling, the cyclic
voltammogram was measured at a scan rate of 0.2 V s-1; Pt wire
electrodes and Ag/AgCl electrode as a reference electrode were
employed.
Electr osyn th esis of Ben zim id a zoles. Imidamide (4 mmol)
was dissolved in MeCN (40 mL) containing NaClO4 (1 mmol)
and electrooxidized at 60 °C in an undivided beaker type cell
(20 cm tall and 3 cm in diameter) with the use of a glassy carbon
(Toyo carbon FE-4, 4.0 × 1.5 × 0.3 cm) anode and a platinum
foil (2.0 × 1.5 cm) cathode under a constant current of 5 mA/
cm2 for 2.1 F/mol. After the electrolysis, the solvent was
evaporated under reduced pressure, and the residue was ex-
tracted with AcOEt (20 mL × 3) and washed with water (20
mL) and with brine (20 mL). The organic layer was dried over
anhydrous Na2SO4, concentrated, and chromatographed on silica
gel (10 % AcOEt-hexane).
1-(4-Meth oxyp h en yl)-2-(1,1,2,2,3,3,3-h ep ta flu or op r op yl)-
6-m eth oxyben zim id a zole (16): Colorless crystals (95%); mp
1
107-108 °C; IR (CHCl3) 3060, 2844, 1168 cm-1; H NMR (200
MHz, CDCl3) δ 3.76 (s, 3 H), 3.92 (s, 3 H), 6.43 (d, 1 H, J ) 2.5
Hz), 7.03 (dd, 1 H, J ) 2.5 Hz, J ) 9.0 Hz), 7.06 (d, 2 H, J ) 9.0
Hz), 7.30 (d, 2 H, J ) 9.0 Hz), 7.81 (d, 1 H, J ) 9.0 Hz); 19F
NMR (188 MHz, CDCl3) δ 37.1 (s, 2 F), 55.5 (q, 2 F, J ) 9.9 Hz),
81.8 (t, 3 F, J ) 9.9 Hz); GCMS (m/ z) 422 (M+, 100), 303 (80).
Anal. Calcd for C18H13F7N2O2 (422.30): C, 51.20; H, 3.10; N,
6.63. Found: C, 51.35; H, 3.02; N, 6.34.
N,N′-Bis(4-m eth oxyp h en yl)ben zim id a m id e (9): Colorless
crystals (61%); mp 115-116 °C; IR (CHCl3) 3460, 3396, 2962,
2844, 1626 cm-1 1H NMR (200 MHz, CDCl3) δ 3.74 (s, 6 H),
;
6.6-7.9 (br, 13 H); GCMS (m/ z) 332 (M+, 14), 210 (M+
-
NHC6H4OCH3, 100). Anal. Calcd for C21H20N2O2 (332.10): C,
75.88; H, 6.06; N, 8.43. Found: C, 76.01; H, 6.04; N, 8.38.
CAN Oxid a tion of 2. A mixture of 2 (0.5 mmol) and CAN
(1.2 mmol) was dissolved in MeCN (5 mL) and stirred at rt. After
5 min the solvent was evaporated under reduced pressure, and
the residue was extracted with AcOEt (5 mL × 5) and washed
with water (2 mL) and with brine (2 mL). The organic layer
was dried over anhydrous MgSO4, concentrated, and chromato-
graphed on silica gel (10% AcOEt-hexane). Recrystallization
of the major portion from benzene-hexane, afforded benzimid-
azole 1010 in 86% yield.
1-(4-Meth oxyp h en yl)-2-(1,1,2,2,3,3,4,4,5,5,6,6,7,7,7-p en ta -
d eca flu or oh ep tyl)-6-m eth oxyben zim id a zole (17): Colorless
crystals (95%); mp 76-77 °C; IR (CHCl3) 2992, 2844, 1152 cm-1
;
1H NMR (200 MHz, CDCl3) δ 3.75 (s, 3 H), 3.92 (s, 3 H), 6.42 (d,
1 H, J ) 2.3 Hz), 7.02 (dd, 1 H, J ) 2.3 Hz, J ) 8.8 Hz), 7.06 (d,
2 H, J ) 8.9 Hz), 7.30 (d, 2 H, J ) 8.9 Hz), 7.81 (d, 1 H, J ) 8.8
Hz); 19F NMR (188 MHz, CDCl3) δ 35.7 (s, 2 F), 39.2 (s, 2 F),
39.9 (s, 2 F), 40.6 (s, 2 F), 41.6 (s, 2 F), 56.2 (q, 2 F, J ) 9.7 Hz),
81.0 (t, 3 F, J ) 9.7 Hz); GCMS (m/ z) 303 (M+ - C6F13, 100).
Anal. Calcd for C22H13F15N2O2 (622.32): C, 42.40; H, 2.11; N,
4.50. Found: C, 42.73; H, 2.10; N, 4.35.
Oxid a tion of 2 w ith t-Bu OCl or NCS. The imidamide 2
(0.5 mmol) was dissolved in DMF (3 mL) and stirred at 70 °C.
t-BuOCl (1.2 mmol) [or a DMF (2 mL) solution of NCS (1.2
mmol)] was added dropwise to the solution by syringe. After 2
h the solvent was evaporated under reduced pressure, and the
residue was extracted with AcOEt (5 mL × 5). The extracts were
washed with aqueous Na2S2O3 (2 mL), then with water (2 mL),
and finally with brine (2 mL). The organic layer was dried over
anhydrous MgSO4, concentrated, and chromatographed on silica
gel (5% AcOEt-hexane) to give 13 in 82% or 93% yield for
t-BuOCl or NCS, respectively.
1-(4-Meth oxyp h en yl)-2-(p en ta flu or op h en yl)-6-m eth oxy-
ben zim id a zole (18): Colorless crystals (77%); mp 132-133 °C;
1
IR (CHCl3) 2972, 2844, 1158 cm-1; H NMR (200 MHz, CDCl3)
δ 3.78 (s, 3 H), 3.84 (s, 3 H), 6.67 (d, 1 H, J ) 2.2 Hz), 6.96 (d,
2 H, J ) 8.8 Hz), 6.99 (dd, 1 H, J ) 2.2 Hz, J ) 8.8 Hz), 7.19 (d,
2 H, J ) 8.8 Hz), 7.76 (d, 1 H, J ) 8.8 Hz); 19F NMR (188 MHz,
CDCl3) δ 0.81-1.08 (m, 2 F), 11.5 (t, 1 F, J ) 21 Hz), 24.1-24.2
(m, 2 F); GCMS (m/ z) 420 (M+, 100), 405 (M+ - Me, 100), 300
(M+ - NHC6H4OMe, 30). Anal. Calcd for C21H13F5N2O2
(420.34): C, 60.01; H, 3.12; N, 6.66. Found: C, 60.21; H, 3.04;
N, 6.58.
N-(2-Ch lor o-4-m et h oxyp h en yl)-N′-(4-m et h oxyp h en yl)-
2,2,2-tr iflu or oeth a n im id a m id e (13): Colorless oil (93%); bp
1-(4-Me t h oxyp h e n yl)-2-m e t h yl-6-m e t h oxyb e n zim id -
270 °C (0.4 Torr); IR (neat) 3440, 3012, 2844, 1676, 1158 cm-1
;
a zole (19): Colorless crystals (92%); mp 75-79 °C; IR (CHCl3)
1H NMR (200 MHz, CDCl3) δ 3.74 (s, 3 H), 3.76 (s, 3 H), 6.55-
7.30 (br, 7 H); 19F NMR (188 MHz, CDCl3) δ 90.0-98.0 (br, 3
F); GCMS (m/ z) 360 (M+, 15), 358 (M+, 40), 323 (M+ - Cl, 100).
Anal. Calcd for C16H14ClF3N2O2 (358.75): C, 53.57; H, 3.93; N,
7.81. Found: C, 53.23; H, 3.72; N, 7.91.
1
3048, 2964, 2844 cm-1; H NMR (200 MHz, CDCl3) δ 2.39 (s, 3
H), 3.70 (s, 3 H), 3.85 (s, 3 H), 6.51 (d, 1 H, J ) 2.4 Hz), 6.83
(dd, 1 H, J ) 2.4 Hz, J ) 8.7 Hz), 7.02 (d, 2 H, J ) 8.9 Hz), 7.22
(d, 2 H, J ) 8.9 Hz), 7.55 (d, 1 H, J ) 8.7 Hz); GCMS (m/ z) 268
(M+, 100), 253 (M+ - CH3, 98). Anal. Calcd for C16H16N2O2
(268.32): C, 71.62; H, 6.01; N, 10.44. Found: C, 71.49; H, 5.92;
N, 10.70.
Oxid a tion of 2 w ith Lea d (IV) Aceta te. Into 2 (0.5 mmol)
dissolved in CH2Cl2 (3 mL) was added dropwise by syringe, a

Notes
1-(4-Me t h oxyp h e n yl)-2-p h e n yl-6-m e t h oxyb e n zim id -
J . Org. Chem., Vol. 61, No. 11, 1996 3905
Ack n ow led gm en t. The authors are grateful to the
Ministry of Education, Science, and Culture of J apan
for financial support [Priority Areas (No. 236) 05235102]
and to the SC-NMR Laboratory of Okayama University
for the use of the facilities of 19F NMR analysis.
a zole (20): Colorless crystals (60%); mp 151-152 °C; IR (CHCl3)
1
3048, 2968, 2844 cm-1; H NMR (200 MHz, CDCl3) δ 3.78 (s, 3
H), 3.87 (s, 3 H), 6.64 (d, 1 H, J ) 2.2 Hz), 6.95 (dd, 1 H, J ) 2.2
Hz, J ) 8.8 Hz), 7.00 (d, 2 H, J ) 8.8 Hz), 7.22 (d, 2 H, J ) 8.8
Hz), 7.24-7.32 (m, 3 H), 7.51-7.58 (m, 2 H), 7.74 (d, 1 H, J 2
)
8.8 Hz); GCMS (m/ z) 330 (M+, 100) 315 (M+ - CH3, 70). Anal.
Calcd for C21H18N2O2 (330.39): C, 76.34; H, 5.49; N, 8.48.
Found: C, 76.06; H, 5.38; N, 8.17.
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