The Journal of Organic Chemistry
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Figure 2. Calculated thermodynamic differences between intermediates along alternative pathways for the o-fluoranil−cyclohexene photoreaction
(B3LYP/6-311G**+).7
(15 g) with 10% EtOAc/hexanes as eluent yielded 1.2 g of pale yellow
solid, the dimer hydrate (4). Recrystallization from hexane gave 374
mg (31.5% yield) of white crystals of the hydrate, mp 129−130 °C. 1H
NMR (CD3CN): δ 6.23 (s, 2H), 2.38 (s, ∼4H). [This gem-diol binds
additional water that is not observed in the mass spectrum.] 19F NMR
(CD3CN): δ −139.2 (narrow “d”, 2F), −145.6 (s, 2F), −160.5 (br s,
1F), −160.8 (d, J = 20 Hz), 1F), −162.8 (t, J = 20 Hz), 1F), −163.4
(m, 1F). The two lowest field signals each integrated for 1F even with
allowance for long relaxation times, but actually represented 2F, as
shown below. 13C NMR (CD3CN, 19F-decoupled, 1H-coupled): δ
183.4, 149.1, 142.1, 138.9, 138.3, 138.2, 137.9, 127.8, 125.5, 103.0,
129.6, 127.3, 86.0, 65.1, 20.4. Anal. Calcd for C10H6F4O4: C, 45.13; H,
2.27; F, 28.55. Found: C, 45.19; H, 2.19; F, 28.80.
Methyl 5,6,7,8-Tetrafluoro-2,3-dihydrobenzo[b][1,4]dioxine-
2-carboxylate (7). o-Fluoranil (457 mg, 2.54 mmol) dissolved in
methyl acrylate (5 mL) was irradiated until the o-fluoranil got
consumed (1.5 h). After evaporation of the solvent, crude product was
chromatographed on 20 g of silica gel (200−400 mesh) using 3%
EtOAc/hexanes as eluent. The white crystalline adduct obtained
weighed 305 mg (45.2% yield). Mp: 87−88 °C. 1H NMR (CDCl3): δ
4.96 (m, 1H), 4.58 (dd, J = 11.7, 3.6 Hz, 1H), 4.40 (dd, J = 11.7, 2.7
Hz, 1H), 3.83 (s, 3H). 19F NMR (CDCl3): δ −164.0 (m, 2F), −168.4
(m, 1F), −168.9 (m, 1F). 13C NMR (CDCl3): δ 166.9, 137.2 (1JCF
=
101.0, 93.4. MS m/z: 378 (M+), 360 (M+ − H2O), 332 (M+
−
247 Hz, 2C), 135.9 (1JCF = 244 Hz, 2C), 129.7, 129.1, 71.5, 65.0, 52.8.
Anal. Calcd for C10H6F4O4: C, 45.13; H, 2.27; F, 28.55. Found: C,
44.89; H, 2.13; F, 28.83.
CH2O2), 294, 257, 210, 152, 124 (base), 93, 69. HRMS calcd for
C12H2O5F8 377.9774, found 377.9758; calcd for C12O4F8 359.9669,
found 359.9665.
2,3-Dichloro-5,6,7,8-tetrafluoro-2,3-dihydrobenzo[b][1,4]-
dioxine (9, 10). o-Fluoranil (460 mg, 2.55 mmol) dissolved in trans-
1,2-dichloroethylene (5 mL) was irradiated until it had reacted
completely (1.5 h). After evaporation of the solvent, the residue was
chromatographed on 20 g of silica gel using 1% EtOAc/hexanes as
eluent. The pale yellow oily product was a ∼8:1 trans/cis mixture of
adducts, 241 mg (34.0% yield). 1H NMR (CDCl3): trans (10), δ 6.29
(s, 2H); cis (9), 6.15 (s, 2H). 19F NMR (CDCl3): trans, δ −161.8 (m,
2F), −163.8 (m, 2F); cis, δ −161.4 (m, 2F), −164.2 (m, 2F). 13C
NMR (CDCl3, F-decoupled, 1H-coupled): trans, δ 137.9, 137.5, 124.7,
83.2 (JCH = 189 Hz); cis, 137.4, 137.3, 126.7, 84.1 (JCH = 182 Hz). MS
m/z: 276, 278, 280 (M+), 241, 243 (M+ − Cl), 206 (M+ − 2Cl), 193
(M+ − CHCl2, base). HRMS calcd for C8H2Cl2F4O2 275.9368, found
275.9370.
The hydrate (100 mg) was dissolved in methylene chloride (5 mL)
and stirred with P4O10 for 4 h. Filtration to remove the partially
hydrated P4O10 and evaporation gave anhydrous dimer. However, the
dimer absorbs water so voraciously that it became contaminated with
hydrate formed during the filtration. To obtain a spectrum of pure
dimer, hydrate was dissolved in CD3CN in an NMR tube, P4O10 was
added, and the mixture was allowed to stand overnight. 19F NMR
(CD3CN): δ −117.3 (m, 1F), −132.9 (d, J = 18.6 Hz, 1F), −133.2 (d,
J = 25 Hz, 1F), −141.1 (s, 1F), −160.0 (d, J = 18.9 Hz, 1F), −160.6
(d, J = 18.9 Hz, 1F), −162.0 to −162.3 (m, 2F). The four low field
resonances were derived from the two low field signals of the hydrate.
1,2,3,4,5a,6,7,13b-Octafluoro-5a,13b-dihydrobenzo[5,6]-
[1,4]dioxino[2,3-a]phenazine (5). Dimer hydrate (330 mg, 0.873
mmol) was dissolved in 10 mL of a 1:1 MeOH/HOAc mixture and a
solution of o-phenylenediamine (91 mg, 0.84 mmol) in methanol (5
mL) was added. The reaction mixture was refluxed for 2 h. After
cooling, it was diluted with water (45 mL) and extracted with CH2Cl2
(3 × 15 mL). Organic layer was washed with saturated NaHCO3
solution (45 mL), then dried over Na2SO4. The crude product was
chromatographed on 15 g of silica gel using 1% EtOAc/hexanes as
eluent. Recrystallization from hexanes gave 213 mg (58.7% yield) of
In an NMR tube were placed 20 mg of o-fluoranil and 0.5 mL of cis-
1,2-dichloroethylene. After irradiation for 30 min, the solution yielded
a ∼10:1 cis/trans mixture of the adducts described above.
2,3,4,5-Tetrafluoro-6-hydroxyphenyl Benzoate (12). o-Fluo-
ranil (425 mg, 2.36 mmol) dissolved in benzaldehyde (5 mL) was
irradiated until the quinone was gone (1.5 h). Unreacted benzaldehyde
was distilled under vacuum and the product was dissolved in
methylene chloride (25 mL). The solution was stirred with saturated
aqueous sodium bisulfite (50 mL) in two portions to remove residual
aldehyde, then washed with water (25 mL). Crude product was
chromatographed on 20 g of silica gel using 3% EtOAc/hexanes as
eluent. The solid that precipitated upon concentration was collected
by filtration and recrystallized from hexanes. Yield: 102 mg (15.1%).
Mp: 166−167 °C. 1H NMR (CDCl3): δ 8.21 (m, 2H), 7.70 (m, 1H),
7.52 (m, 2H), 5.48 (s, 1H). 19F NMR (CDCl3): δ −154.3 (dd, J =
21.7, 5.9 Hz, 1F), −160.2 (t, J = 21.7 Hz, 1F), −163.5 (dd, J = 21.7,
5.93 Hz, 1F), −168.6 (m, 1F). 13C NMR (CD3CN): δ 164.3, 142.3
(1JCF = 245 Hz), 140.5 (1JCF = 244 Hz), 139.3 (1JCF = 244 Hz), 136.8,
135.7 (1JCF = 245 Hz), 135.7, 131.4, 130.1, 128.7, 125.8. Anal. Calcd
for C13H6F4O3: 54.56; H, 2.11; F, 26.55. Found: C, 54.30; H, 1.99; F,
26.82.
1
the phenazine, mp 105−107 °C. H NMR (CDCl3): δ 8.25 (s, 2H),
7.95 (s, 2H). 19F NMR (CDCl3): δ −126.0 (s, 1F), −133.5 (s, 1F),
−146.0 (s, 1F), −149.8 (s, 1F), −159.7 (s, 1F), −160.1 (s, 1F),
−162.1 (s, 1F) −162.4 (s, 2F). 13C NMR (CDCl3, 19F-decoupled, 1H-
coupled): δ 143.2, 142.7, 140.9, 140.6, 140.3, 138.7, 137.9, 137.8,
137.2, 137.0, 133.2 (dd, JCH = 163, 9.2 Hz), 132.4 (dd, JCH = 163, 8.7
Hz), 130.2 (dm, JCH = 166 Hz), 129.7 (dm, JCH = 167 Hz), 125.6,
125.4, 101.7, 100.7. Anal. Calcd for C18H4F8N2O2: C, 50.02; H, 0.93;
N, 6.48. Found: C, 49.84; H, 0.90; N, 6.58.
5,6,7,8-Tetrafluoro-2,3-dihydrobenzo[b][1,4]dioxin-2-yl Ace-
tate (6). A solution of o-fluoranil (436 mg, 2.42 mmol) in vinyl acetate
(5 mL) was irradiated until the quinone was completely consumed
(0.5 h). Solvent was evaporated, and the crude product was
chromatographed on 20 g of silica gel (200−400) using 4% EtOAc/
hexanes as eluent. Pale yellow oily adduct was obtained, 260 mg
(40.4% yield). 1H NMR (CDCl3): δ 6.55 (s, 1H), 4.40 (d, J = 12 Hz,
1H), 4.17 (d, J = 12 Hz, 1H), 2.11 (s, 3H). 19F NMR (CDCl3): δ
−163.3 (d, J = 25 Hz, 1F), −164.1 (d, J = 25 Hz, 1F), −167.8 (m, 1F),
−168.1 (m, 1F). 13C NMR (CDCl3): δ 168.8, 137.4 (1JCF = 247 Hz),
137.1 (1JCF = 247 Hz), 136.3 (1JCF ∼ 245 Hz), 136.0 (1JCF = 244 Hz),
2-(1-Ethoxyethoxy)-3,4,5,6-tetrafluorophenol (13). A solution
of o-fluoranil (460 mg, 2.55 mmol) in diethyl ether (20 mL) was
irradiated until the quinone was consumed (30 min). The acetal
product, which contained a comparable amount of tetrafluorocatechol
(14), was too unstable to isolate on silica gel or florisil. 19F NMR
(C2H5OC2H5): δ −158.2 (d, J = 18.6 Hz, 1F), −164.7 (d, J = 18.9
Hz), 1F), −166.2 (m, 1F, merged with catechol signal), −172.7 (m,
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dx.doi.org/10.1021/jo300506e | J. Org. Chem. 2012, 77, 5017−5021