I. Pravst, S. Stavber / Journal of Fluorine Chemistry 156 (2013) 276–282
281
13C NMR spectra on the same instrument at 76 MHz. Chemical shifts
are reported in parts per million using TMS as internal standard. 19
165 mg of crude reaction mixture. Purification by column
chromatography (SiO2, elution with EtOAc) afforded 115 mg
(66.8%) of 8b as white crystals; mp 38.0–40.0 8C; 1H NMR
F
NMR spectra were recorded on Varian EM 360L at 56.4 MHz or on
Varian INOVA 300 at 285 MHz and chemical shifts are reported in
parts per million using CCl3F as internal standard. IR spectra were
recorded on Perkin-Elmer 1310 spectrometer. Standard KBr pellet
procedures were used to obtain IR spectra of solids, while a film neat
material was used to obtain IR spectra of liquid products. Mass
spectra were obtained an Autospec Q instrument under electron
impact (EI) conditions at 70 eV or under ESI conditions. Elemental
analyses were carried on a Perkin-Elmer 2400 CHN analyzer.
Cesium fluoroxysulfate was prepared according to literature
[36], SelectfluorTM F-TEDA-BF4 (Appolo) was used as purchased,
while AccufluorTM NFTh (AlliedSignal, 50% w/w on Al2O3) was
crystallized from an MeCN/MeOH mixture in order to remove
alumina, dried in vacuo at 20 8C and used. 4-Alkyl-substituted
phenols were obtained from commercial sources, while 4-
alkylphenyl alkyl ethers 4 were prepared from alkyl halogenides
and corresponding 4-alkyl-substituted sodium phenolates follow-
ing Williams’s procedure [37]. Data for thus obtained compounds 4
were in agreement with data from literature while the new
compound 4ag was identified according to spectroscopic data.
(60 MHz, CCl4):
d 1.1 (d, J = 9.1 Hz, 6H), 2.5 (m, 1H), 5.92–6.33
(m, 2H), 7.02 (d, J = 15.0 Hz, 1H); 19F NMR (56.4 MHz, CCl4):
d-
105.03 (m); MS (EI, 70 eV): m/z 172 (M+, 90%), 157 (100), 152 (53),
129 (50), 91 (26), 69 (93); HRMS: calcd. for C9H10F2O m/z:
172.0700, measured m/z 172.0696; IR (KBr): n
1690 cmÀ1; analysis
calcd. for C9H10F2O: C 62.78%, H 5.85%; found: C 62.82, H 5.95.
4.5. 2,2-Difluoro-4-t-butylcyclhexa-3,5-dienone [19] (8c)
The reaction of 1 mmol (192 mg) of 4-t-butyl-i-propoxyben-
zene (4cd) with 2.2 mmol of AccufluorTM NFTh in MeOH gave
150 mg of crude reaction mixture. Purification by column
chromatography (SiO2, elution with EtOAc) afforded 118 mg
(63.4%) of 8c as white crystals; mp 53.4–55.2 8C; 1H NMR
(60 MHz, CCl4):
J = 12.0 Hz, 1H); 19F NMR (56.4 MHz, CCl4):
J = 6.5 Hz); IR (KBr):
1695 cmÀ1
d
1.22 (s, 9H), 6.02–6.22 (m, 2H), 7.2 (d,
d
-103.03 (d,
n
.
4.6. 4-Fluoro-4-methylcyclohexa-2,5-dienone [40] (6a)
4.2. 4-Methylphenyl 3-trifluoromethylbenzyl ether (4ag)
The reaction of 1 mmol (108 mg) of 4-methylphenol (4aa) with
1.1 mmol of SelectfluorTM F-TEDA-BF4 in MeCN gave 110 mg of
crude reaction mixture. Separation by preparative TLC (SiO2,
CH2Cl2/petroleum ether 4/1) afforded 41 mg of (31.7%) of 6a as
White crystals (from petroleum ether); mp 50.5–51.0 8C; 1H
NMR (300 MHz, CDCl3):
J = 9.0 Hz, 2H), 7.45–7.7 (m, 6H); 19F NMR (56.4 MHz, CCl4):
64.24 (s); MS (EI, 70 eV): m/z 266 (M+, 44%), 159 (100), 109 (20), 77
(15); IR (KBr):
(cmÀ1) 2950, 2890, 2850, 1890, 1610, 1585, 1515,
d 2.29 (s, 3H), 5.06 (s, 2H), 6.87 (d,
d
-
liquid; 1H NMR (60 MHz, CCl4):
J = 9.2 Hz, 2H), 6.8 (dd, J = 9.2 Hz, 6.2 Hz, 2H); 19F NMR (56.4 MHz,
CCl4): -147.52 (qt, J = 12.1 Hz, 6.2 Hz); IR (neat):
: 1670 cmÀ1
d 1.42 (d, J = 22.1 Hz, 3H), 6.1 (d,
n
d
n
.
1455, 1340, 1330, 1245, 1190, 1165, 1130, 1050, 925, 815, 800,
770, 740, 700, 665; analysis calcd. for C15H13F3O: C 67.66%, H
4.92%; found: C 67.81, H 4.74.
4.7. 4-Fluoro-4-i-propylcyclohexa-2,5-dienone [21] (6b)
The reaction of 1 mmol (136 mg) of 4-i-propylphenol (4ba)
with 1.1 mmol of SelectfluorTM F-TEDA-BF4 in MeCN gave 125 mg of
crude reaction mixture. Separation by preparative TLC (SiO2,
CH2Cl2/petroleum ether 4/1) afforded 64 mg of (42%) of 6b as
4.3. Fluorination of 4-alkyl-substituted phenols and aromatic ethers
with CFS (1), SelectfluorTM F-TEDA-BF4 (2) or AccufluorTM NFTh (3);
general procedure
liquid; 1H NMR (60 MHz, CCl4):
1H), 6.2 (d, J = 12.3 Hz, 2H), 6.95 (dd, J = 12.3 Hz, 9.1 Hz, 2H); 19F
NMR (56.4 MHz, CCl4):
-153.32 (m); MS (EI, 70 eV): m/z 154 (M+,
31%), 139 (100), 112 (80), 109 (17), 91 (27) IR (neat):
: 1670 cmÀ1
d 1.05 (d, J = 9.1 Hz, 6H), 2.13 (m,
To a solution of substrate 4 (1 mmol) in 10 mL of solvent (MeCN
or MeOH) was added reagents 1, 2, or 3 (1.1 mmol). The reaction
mixture was further-stirred under reflux for 2 h. The solvent was
distilled off under reduced pressure. The crude reaction mixture was
dissolved in 50 mL of CH2Cl2, insoluble reaction products filtered off,
filtrate washed with water (30 mL), the organic layer dried over
Na2SO4, and solvent evaporated. The crude reaction mixture was
analyzed by 1H and 19F NMR spectroscopy. Relative distribution of
d
n
.
4.8. 4-Fluoro-4-t-butylcyclohexa-2,5-dienone [23] (6c)
The reaction of 1 mmol (206 mg) of 4-t-butyl-t-butoxybenzene
(4ce) with 1.1 mmol of CFS in MeCN gave 175 mg of crude reaction
mixture. Separation by preparative TLC (SiO2, CH2Cl2/petroleum
ether 4/1) afforded 49 mg of (29%) of 6c as yellow crystals; mp
fluorinated productsandtheiroverallyield wasdeterminedfrom19
F
NMR of crude reaction mixtures using octafluoronaphthalene (OFN)
asinternalstandard. Productswereidentifiedbycomparisonoftheir
NMR spectroscopic data with those known from literature,
independently prepared products or they were transformed to
known compounds. 2-Fluoro-4-alkyl substituted phenols or alkoxy
benzenes (5, Scheme 1) were thus transformed with an excess of
reagents [19,20,24] to 2,2-difluoro-4-alkyl-3,5-cyclohexadienones
(unknown compounds 8b or 8c [19]) or hydrolyzed [38] to 2-fluoro-
4-methylphenol (4aa) [39]. 4-Fluoro-4-alkyl-2,5-cyclohexadie-
nones 6a [40], 6b [21], and 6c [23] were isolated from crude
mixtures using preparative TLC (SiO2, CH2Cl2/petroleum ether 4/1)
and identified according to their spectroscopic data, while 4-fluoro
alkoxy benzene derivatives were hydrolyzed to 4-fluorophenol (9)
or compared to independently prepared compounds [36].
63.3–63.5 8C; 1H NMR (60 MHz, CCl4):
6.3 (d, J = 13.1 Hz, 2H), 7.0 (dd, J = 17.1 Hz, 13 Hz, 2H); 19F NMR
(56.4 MHz, CCl4):
-165.33 (m); MS (EI, 70 eV): m/z 168 (M+, 21%),
153 (75), 135 (65), 125 (35), 109 (17), 91 (12), 57 (100) IR (neat):
1675 cmÀ1
d 1.12 (d, J = 19.2 Hz, 9H),
d
n:
.
4.9. N-(3-fluoro-4-hydroxyphenethyl)acetamide (12a)
The reaction of 1 mmol (180 mg) of N-acetyl tyramin (11a) with
1.1 mmol of AccufluorTM NFTH in MeOH gave 170 mg of crude
reaction mixture. Separation by preparative TLC (SiO2, CH2Cl2)
afforded 122.5 mg (62%) of 12a as white crystals; mp 113.2–
114.3 8C; 1H NMR (300 MHz, CDCl3):
J = 6.9 Hz, 2H), 3.22 (m, 2H), 6.00 (bs, 1H), 6.72–7.03 (m, 3H), 8.40
(bs, 1H); 13C NMR (76 MHz, CDCl3):
23.5, 34.5, 41.0, 116.0 (d,
J = 18.1 Hz), 117.9 (d, J = 3.0 Hz), 124.5 (d, J = 3.2 Hz), 130.7 (d,
J = 5.7 Hz), 143.2 (d, J = 13.0 Hz), 151.5 (d, J = 240.8 Hz), 170.2; 19
NMR (285 MHz, CDCl3): - 137.8 (dd, J = 11.7 Hz, 9.1 Hz); MS (ESI):
d 1.98 (s, 3H), 2.71 (t,
4.4. 2,2-Difluoro-4-i-propylcyclhexa-3,5-dienone (8b)
d
The reaction of 1 mmol (178 mg) of 4-i-propyl-i-propoxyben-
zene (4bd) with 2.2 mmol of AccufluorTM NFTh in MeCN gave
F
d