Distance Dependence of Through-Space 19F-19F Coupling
J. Am. Chem. Soc., Vol. 122, No. 17, 2000 4115
5,6-Difluoroacenaphtho-1,2-b-quinoxaline (3h). A solution of 0.10
g (0.9 mmol) of o-phenylenediamine in 17 mL of 95% ethanol was
added to a solution of 0.20 g (0.9 mmol) of 5,6-difluoroacenaphthene-
quinone (3a) in 34 mL of acetic acid. The resulting mixture was heated
in a bath of boiling water for 20 min and then was poured over ice.
bath. A 210-mL portion of polyphosphoric acid (PPA), previously
heated to 90 °C, was added to the molten carboxylic acid, and the
mixture was stirred vigorously by hand for 5 min. Then a second 210-
mL portion of preheated PPA was added with vigorous manual stirring
for an additional 5 min. After the reaction mixture was allowed to cool
to 60 °C, 800 g of crushed ice was added with manual stirring. Then
100 mL of aqueous 5% NaOH was added, and the mixture was
extracted with diethyl ether. The ether extract was washed with water
and rotary evaporated. The solid residue was sublimed under reduced
pressure and recrystallized from hexane to give 47.5 g (69% overall
1
Filtration gave 0.13 g (50%) of yellow 3h: mp 273-274.5 °C; H
NMR δ 8.37 (br d, J ) 7.8 Hz, 2 H), 8.17 (dd, ∑J ) 6.2 + 3.5 ) 9.7
Hz, 2 H), 7.77 (dd, ∑J ) 6.3 + 3.4 ) 9.7 Hz, 2 H), 7.47 (dd, J )
11.5, 7.3 Hz); 19F NMR δ 3.68; MS m/z (rel intensity) 290 (100). Anal.
Calcd for C18H8F2N2: C, 74.47; H, 2.78. Found: C, 74.51; H, 2.81.
4,5-Dicyano-1,8-difluoronaphthalene (1a). A mixture of 200 mg
(0.81 mmol) of 5,6-difluoroacenaphtho-1,2-furazan oxide (3g), 430 mg
(1.64 mmol) of triphenylphosphine, and 26 mL of benzene was stirred
magnetically and heated under reflux for 48 h. The reaction mixture
was concentrated by rotary evaporation and then filtered to give 330
mg of crude brown product. This material was sublimed under reduced
pressure at about 110 °C to give 0.13 g of cream-colored sublimate.
The sublimate was dissolved in the minimum amount of hot 95%
ethanol and then enough water was added to make the composition
40% water. This solution was cooled in a freezer and the resulting
crystals were collected to give 400 mg (24%) of 1a: mp 247.5-249
°C; 1H NMR δ 8.20 (ddd, J ) 8.3 Hz, ∑J ) 2.5 + 2.4 ) 4.9 Hz, 2 H),
7.42 (ddd, ∑J ) 5.2 + 5.1 ) 10.3 Hz, J ) 8.3 Hz, 2 H); 19F NMR
(DMSO-d6) δ 10.71; MS m/z (rel intensity) 214 (100). Anal. Calcd for
C12H4N2F2: C, 67.29; H, 1.89. Found: C, 67.08; H, 2.02.
1
from 4) of 5 as white crystals: mp 66.0-67.8 °C; H NMR δ 7.08-
7.04 (m, 2 H), 2.93 (br t, J ) 6.2 Hz, 2 H), 2.64 (br t, J ) 6.6 Hz, 2
H), 2.59 (s, 3 H), 2.14-2.05 (m, 2 H); 19F NMR δ -6.63; 13C NMR
δ 199.1 (d, J ) 3.2 Hz), 158.1 (d, J ) 242.8 Hz), 136.6 (d, J ) 3.4
Hz), 132.0 (d, J ) 3.2 Hz), 131.8 (d, J ) 16.5 Hz), 130.5 (d, J ) 7.5
Hz), 118.5 (d, J ) 21.9 Hz), 40.6 (s), 22.6 (s), 22.5 (d, J ) 5.3 Hz),
22.1 (s); MS m/z (rel intensity) 178 (54), 150 (100). Anal. Calcd for
C11H11FO: C, 74.14; H, 6.22. Found: C, 74.28; H, 6.24.
1-Fluoro-4,5-dimethylnaphthalene (6). A solution of 38.2 g (0.214
mol) of 5-fluoro-8-methyl-1-tetralone (5) in 350 mL of anhydrous
diethyl ether was added slowly to 107 mL (0.322 mol) of a magnetically
stirred 3 M ether solution of methylmagnesium bromide. The usual
workup, followed by sublimation of the crude product under reduced
pressure and recrystallization from hexane, gave 35.9 g (86%) of
5-fluoro-1,8-dimethyl-1-tetralol as white crystals: mp 99-100.5 °C;
1H NMR δ 6.89 (dd, J ) 8.2 Hz, 6.3 Hz, 1 H), 6.74 (br dd, ∑J ) 17.4
Hz, 1 H), 2.81-2.74 (m, 1 H), 2.62-2.56 (m, 1 H), 2.53 (s, 3 H), 2.12
(br s, 1 H), 1.95-1.70 (m, 4 H), 1.52 (s, 3H); 19F NMR δ 6.39; 13C
NMR δ 158.7 (d, J ) 241.1 Hz), 142.1 (d, J ) 3.0 Hz), 132.6 (d, J )
3.3 Hz), 130.5 (d, J ) 7.9 Hz), 124.3 (d, J ) 16.3 Hz), 112.6 (d, J )
21.8 Hz), 72.2 (d, J ) 3.0 Hz), 42.4 (s), 27.6 (s), 23.1 (d, J ) 5.5 Hz),
21.5 (s), 19.6 (s); MS m/z (rel intensity) 194 (5), 176 (80), 161 (100).
Anal. Calcd for C12H15FO: C, 74.20; H, 7.78. Found: C, 74.13; H,
7.65.
4,5-Difluoro-1,8-naphthalic Anhydride (1b). A magnetically stirred
mixture of 0.40 g (1.9 mmol) of 5,6-difluoroacenaphthenequinone (3a),
1.42 g (5.4 mmol) of Na2Cr2O7, and 31 mL of acetic acid was heated
in an oil bath at 80 °C for 12 h. Then the reaction mixture was cooled
to room temperature and diluted with 150 mL of water. The crude
product was collected by filtration, air-dried, and recrystallized from a
mixture of toluene and hexane to give 0.17 g (39%) of 1b as yellow
needles: mp 216-217.5 °C; 1H NMR δ 8.69 (ddd, J ) 8.3 Hz, ∑J )
2.5 + 2.3 ) 4.8 Hz, 2 H), 7.53 (ddd, J ) 8.4 Hz, ∑J ) 5.5 + 4.9 )
10.4 Hz, 2 H); 19F NMR (DMSO-d6) δ 10.04; MS m/z (rel intensity)
234 (92), 190 (100). Anal. Calcd for C12H4F2O3: C, 61.55; H, 1.73.
Found: C, 61.74; H, 1.93.
A magnetically stirred mixture of 4.85 g (25 mmol) of 5-fluoro-
1,8-dimethyl-1-tetralol, 0.4 g of Pd/C, and 6.13 g (63 mmol) of maleic
anhydride was heated under nitrogen for 10 h at 140 °C. The reaction
mixture was extracted with hot hexane, and the hexane extract was
filtered and rotary evaporated. The residue was sublimed under reduced
pressure to give 2.98 g (69%) of 6 as white needles: mp 70.5-72.5
3-(2′-Fluoro-5′-methylbenzoyl)propionic Acid (4). A magnetically
stirred mixture of 30 g (0.30 mol) of succinic anhydride, 80 g (0.60
mol) of AlCl3, and 150 mL of 1,1,2,2-tetrachloroethane was maintained
at 25-28 °C during the dropwise addition over 45 min of 33 g (0.30
mol) of p-fluorotoluene. The resulting dark red mixture was stirred for
an additional 4 h, and then was poured into a mixture of 40 mL of
concentrated HCl, 35 g of ice, and 100 mL of water. Extraction with
CH2Cl2 followed by recrystallization from toluene gave 45.5 g (72%)
1
°C; H NMR δ 7.98 (d, J ) 8.1 Hz, 1 H), 7.35 (dd, J ) 8.1, 7.1 Hz,
1 H), 7.29 (br d, J ) 6.8 Hz), 7.13 (br dd, ∑J ) 14.0 Hz, 1 H), 6.96
(dd, J ) 9.9, 7.9 Hz, 1 H), 2.91 (s, 3 H), 2.86 (s, 3 H); 19F NMR δ
-10.74; 13C NMR δ 157.8 (d, J ) 248.4 Hz), 135.5 (d, J ) 2.7 Hz),
133.9 (d J ) 3.2 Hz), 131.1 (d, J ) 4.3 Hz), 130.2 (s), 128.2 (d, J )
8.6 Hz), 125.4 (s), 125.4 (d, J ) 14.5 Hz), 119.4 (d, J ) 8.7 Hz),
108.2 (d J ) 19.9 Hz), 25.5 (s), 25.4 (s); MS m/z (rel intensity) 174
(100), 159 (84). Anal. Calcd for C12H11F: C, 82.72; H, 6.36. Found:
C, 82.85; 6.38.
1
of 4 as white crystals: mp 111-112.5 °C; H NMR δ 7.68 (dd, J )
6.9, 2.2 Hz, 1 H), 7.31 (ddd, J ) 8.0, 5.0, 2.5 Hz, 1 H), 7.02 (dd, J )
11.0, 8.4 Hz, 1 H), 3.29 (dd, J ) 6.4, 3.3 Hz, 2H), 2.34 (s, 3 H); 19F
NMR δ -0.69; 13C NMR δ 196.2 (d, J ) 4.2 Hz), 179.1 (s), 160.5 (d,
J ) 252.5 Hz), 135.4 (d, J ) 8.9 Hz), 134.0 (d, J ) 3.3 Hz), 130.6 (d,
J ) 2.1 Hz), 124.3 (d, J ) 13.1 Hz), 116.4 (d, J ) 24.0 Hz), 37.9 (d,
J ) 8.9 Hz), 28.1 (d, J ) 1.9 Hz), 20.4 (s); MS m/z (rel intensity) 210
(9), 137 (100). Anal. Calcd for C11H11FO3: C, 62.85; H, 5.27. Found:
C, 62.66; H, 5.26.
1-Bromo-8-fluoro-4,5-dimethylnaphthalene (7). A solution of 3.76
g (21.6 mmol) of 1-fluoro-4,5-dimethylnaphthalene (6) and 5.96 g (33.5
mmol) of N-bromosuccinimide in 26 mL of DMF was stirred magneti-
cally and heated for 8 h at 65 °C under nitrogen in the dark. Then 70
mL of water was added and the mixture was extracted with hexane.
The hexane extract was dried over anhydrous Na2SO4 and filtered
through alumina and silica gel, and the filtrate was rotary evaporated.
The residue was recrystallized from hexane to give 2.90 g (53%) of 7
as white crystals: mp 77.8-78.8 °C; 1H NMR δ 7.55 (d, J ) 7.7 Hz,
1 H), 7.10 (dd, J ) 7.6, 5.7 Hz, 1 H), 6.98 (dd, J ) 12.6, 8.1 Hz, 1 H),
6.96 (d, J ) 7.7 Hz, 1 H), 2.76 (s, 3 H), 2.75 (s, 3 H); 19F NMR δ
2.03; 13C NMR δ 157.1 (J ) 255.0 Hz), 136.2 (s), 135.3 (d, J ) 3.3
Hz), 132.5 (s), 131.7 (d, J ) 4.5 Hz), 130.4 (d, J ) 1.6 Hz), 129.5 (d,
J ) 8.7 Hz), 123.3 (d J ) 7.8 Hz), 113.1 (s), 111.2 (d, J ) 23.0 Hz),
26.1 (s), 25.8 (s); MS m/z (rel intensity) 254 (97), 252 (100). Anal.
Calcd for C12H10BrF: C, 56.94; H, 3.98. Found: C, 57.04; H, 4.12.
1,8-Difluoro-4,5-dimethylnaphthalene (1c). A solution of 1.19 g
(4.7 mmol) of 1-bromo-8-fluoro-4,5-dimethylnaphthalene (7) in 10 mL
of anhydrous diethyl ether was stirred magnetically and maintained at
0 °C under nitrogen while 2.26 mL (5.7 mmol) of a 2.5 M solution of
n-BuLi in hexane was added dropwise. After 30 min, the reaction
mixture was cooled to -78 °C, and a solution of 1.78 g (5.7 mmol) of
5-Fluoro-8-methyl-1-tetralone (5). Standard Wolff-Kishner meth-
odology was used, starting with 81.5 g (0.39 mol) of 3-(2′-fluoro-5′-
methylbenzoyl)propionic acid (4), 77.2 g (1.17 mol) of 85% KOH
pellets, 55.8 mL of aqueous 85% hydrazine hydrate, and 558 mL of
diethylene glycol, to produce a crude sample of 4-(2′-fluoro-5′-methyl)-
butyric acid. A small portion was purified by distillation under reduced
pressure followed by recrystallization from hexane to give 4-(2′-fluoro-
5′-methyl)butyric acid as white crystals: mp 48.5-50 °C; 1H NMR δ
11.81 (br s, 1 H), 6.97-6.84 (m, 3 H), 2.65 (t, J ) 7.5 Hz, 2 H), 2.38
(t, J ) 7.5 Hz, 2 H), 2.27 (s, 3H), 1.94 (pentet, J ) 7.5 Hz, 2 H); 19F
NMR δ -10.86; 13C NMR δ 180.2 (s), 159.3 (d, J ) 242.1 Hz), 133.3
(d, J ) 3.3 Hz), 131.1 (d, J ) 5.0 Hz), 128.1 (d, J ) 7.7 Hz), 127.4
(d, J ) 15.8 Hz), 114.8 (d, J ) 22.1 Hz), 33.3 (s), 28.1 (d, J ) 1.9
Hz), 24.9 (s), 20.5 (s); MS m/z (rel intensity) 196 (38), 136 (100). Anal.
Calcd for C11H13FO2: C, 67.33; H, 6.68. Found: C, 67.37; H, 6.59.
The crude 4-(2′-fluoro-5′-methyl)butyric acid described in the
preceding paragraph was heated in a 1000-mL beaker in a boiling water