Electrolytic Partial Fluorination of Organic Compounds
J . Org. Chem., Vol. 64, No. 21, 1999 7939
Eth yl r-[(3,4-d ih yd r o-4-oxo-3-p h en yl-2-qu in a zolin yl)-
th io]a ceta te (3b):26 mp 117-118 °C (EtOH); 1H NMR δ 1.30
(t, 3H, J ) 7.25 Hz), 3.89 (s, 2H), 4.22 (q, 2H, J ) 7.25 Hz),
7.39 (m, 3H), 7.55 (m, 4H), 7.71 (ddd, 1H, J ) 8.58, 8.25, 1.65
Hz), 8.23 (dd, 1H, J ) 8.25, 1.65 Hz); MS m/e 340 (M+), 295
(M+ - OEt), 267 (M+ - COOEt), 253 (M+ - CH2COOEt), 221
(M+ - SCH2COOEt). Anal. Calcd for C18H16N2O3S: C, 63.51;
H, 4.74; N, 8.23. Found: C, 63.57; H, 4.74; N, 8.23.
149.79, 155.23 (d, J ) 3.6 Hz); MS m/e 143 (M+), 123 (M+
-
HF), 110 (M+ - CH2F), 79 (pyridine); HRMS m/e calcd for
C6H6FNS 143.0205, found 143.0206.
2-(Diflu or om eth ylth io)p yr id in e (6): 1H NMR δ 7.15 (dd,
1H, J ) 7.6, 5.0 Hz), 7.35 (d, 1H, J ) 8.6 Hz), 7.61 (m, 1H),
7.71 (t, 1H, J ) 56.4 Hz), 8.36 (d, 1H, J ) 4.6 Hz); 19F NMR δ
-19.71 (d, J ) 56.1 Hz); MS m/e 161 (M+), 141 (M+ - F), 111
(M+ - CF2), 79 (pyridine); HRMS m/e calcd for C6H5F2NS:
161.0111, found 161.0080.
2-(F lu or om eth ylth io)-6-flu or op yr id in e (7): 19F NMR δ
-112.39 (t, 1F, J ) 51.5 Hz), -44.53 (d, 1F, J ) 9.2 Hz); MS
m/e 161 (M+), 141 (M+ - HF), 97 (fluoropyridine); HRMS m/e
calcd for C6H5F2NS 161.0111, found 161.0082.
2-(Diflu or om eth ylth io)-6-flu or op yr id in e (8): 19F NMR
δ -42.77 (d, 1F, J ) 9.2 Hz) -20.53 (t, 2F, J ) 56.1 Hz); MS
m/e 179 (M+), 160 (M+ - F), 129 (M+ - CHF2), 97 (fluoropy-
ridine); HRMS m/e calcd for C6H4F3NS 179.0017, found
179.0012.
An od ic F lu or in a tion of Heter ocyclic Su lfid es. Typical
anodic fluorination was carried out as follows:
Electrolysis was carried out with platinum electrodes (3 ×
2 cm2) in 0.3 M fluoride salt/DME (20 mL) to which heterocyclic
sulfide 1, 2, or 3 (1 mmol) was added, using an undivided cell
or H-type divided cell with an anion-exchange membrane (IE-
DF 34-5 TOSOH) under nitrogen atmosphere at room tem-
perature. Constant current electrolysis (5 mA‚cm-2) was
applied until the starting sulfide was almost consumed
(monitored by TLC or GC). After the electrolysis, the resulting
electrolytic solution was passed through
a short column
1-Flu or o-1-[(3,4-dih ydr o-4-oxo-3-ph en yl-2-qu in azolin yl)-
th io]-2-p r op a n on e (9a ): mp 63 °C (hexane/i-PrOH); 1H NMR
δ 2.45 (d, 3H, J ) 3.63 Hz), 6.73 (d, 1H, J ) 48.83 Hz), 7.35
(m, 2H), 7.45 (dd, 1H, J ) 7.92, 7.26 Hz), 7.55 (m, 3H), 7.61
(d, 1H, J ) 7.92 Hz), 7.76 (dd, 1H, J ) 7.92, 7.26 Hz), 8.24 (d,
1H, J ) 7.26 Hz); 19F NMR δ -89.15 (dq, J ) 48.72, 3.68 Hz);
MS m/e 328 (M+), 286 (M+ - CH2dCdO), 253 (M+ - CHF-
chromatography on silica gel using ethyl acetate to remove
fluoride salts. The eluents were collected and evaporated under
reduced pressure, and the residue was further purified by
passing through a long column chromatography on silica gel
using hexane/ethyl acetate (10:1-3) as an eluent.
1-F lu or o-1-[(2-p yr im id yl)th io]-2-p r op a n on e (4a ): yellow
oil; 1H NMR δ 2.46 (d, 3H, J ) 3.30 Hz), 6.85 (d, 1H, J ) 50.14
Hz), 7.14 (t, 1H, J ) 4.62 Hz), 8.59 (d, 2H, J ) 4.62 Hz); 19F
NMR δ -89.27 (dq, J ) 50.56, 3.68 Hz); 13C NMR (DEPT) δ
26.25 (CH3), 96.37 (dd, CHF, J ) 232, 4.9 Hz), 118.1, 157.25,
157.63 (3 CH), 167.37, 200.24 (2 C); MS m/e 186 (M+), 166 (M+
- HF), 143 (M+ - COCH3), 124 (M+ - CH3COF), 80 (pyrimi-
dine). Anal. Calcd for C7H7FN2OS: C, 45.15; H, 3.79; N, 15.04.
Found: C, 45.27; H, 3.82; N, 15.25.
COCH3), 221 (M+ - SCHFCOCH3); HRMS m/e calcd for C17H13
FN2O2S 328.0682, found 328.0675. Anal. Calcd for C17H13
-
-
FN2O2S: C, 62.18; H, 3.99; N, 8.53. Found: C, 61.69; H, 3.99;
N, 8.35.
Eth yl r-flu or o-r-[(3,4-d ih yd r o-4-oxo-3-p h en yl-2-qu in -
1
a zolin yl)th io]a ceta te (9b): mp 42 °C (hexane); H NMR δ
1.18 (t, 3H, J ) 7.26 Hz), 4.16 (q, 2H, J ) 7.26 Hz) 7.03 (d,
1H, J ) 50.49 Hz), 7.24 (m, 2H), 7.33 (dd, 1H, J ) 7.56, 7.26
Hz), 7.44 (m, 3H), 7.53 (d, 1H, J ) 7.91 Hz), 7.64 (dd, 1H, J )
7.92, 7.26 Hz), 8.12 (d, 1H, J ) 7.92 Hz); 19F NMR δ -88.73
(d, J ) 49.63 Hz); 13C NMR (DEPT) δ 13.78 (CH3), 62.66 (CH2),
90.32 (dd, CHF, J ) 233.2, 4.9 Hz), 126.29, 126.56, 127.04,
128.93, 129.06, 129.72, 130.04, 130.26, 134.74 (9 CH), 119.91,
146.79, 151.93, 161.26, 165.12, 165.52 (6 C); MS m/e 358 (M+),
313 (M+ - OEt), 285 (M+ - COOEt), 253 (M+ - CHFCOOEt),
221 (M+ - SCHFCOOEt); HRMS m/e calcd for C18H15FN2O3S
358.0787, found 358.0783. Anal. Calcd for C18H15FN2O3S: C,
60.33; H, 4.22; N, 7.82. Found: C, 59.88; H, 4.19; N, 7.74.
3,4-Dih yd r o-2-flu or o-4-oxo-3-p h en ylqu in a zolin e (10):
mp 164-165 °C (EtOH); 1H NMR δ 7.33 (m, 2H), 7.52 (m, 4H),
7.66 (d, 1H, J ) 8.25, 7.26 Hz), 8.29 (d, 1H, J ) 7.91 Hz); 19F
NMR δ 23.45 (s); MS m/e 240 (M+), 144 (M+ - F - Ph); HRMS
m/e calcd for C14H9FN2O 240.0699, found 240.0702. Anal. Calcd
for C14H9FN2O: C, 70.00; H, 3.78; N, 11.66. Found: C, 69.73;
H, 3.51; N, 11.55.
Eth yl r-flu or o-r-[(2-p yr im id yl)th io]a ceta te (4b): color-
1
less oil; H NMR δ 1.25 (t, 3H, J ) 7.26 Hz), 4.26 (q, 2H, J )
7.26 Hz), 7.01 (d, 1H, J ) 50.55 Hz), 7.07 (t, 1H, J ) 4.95 Hz),
8.52 (d, 2H, J ) 4.95 Hz); 19F NMR δ -88.61 (d, J ) 50.55
Hz); 13C NMR (DEPT) δ 13.55 (CH3), 62.34 (CH2), 90.67 (dd,
CHF, J ) 229.5, 4.9 Hz), 118.21 (CH), 157.55 (2 CH), 165.51,
166.95 (2 C); MS m/e 216 (M+), 196 (M+ - HF), 171 (M+
-
OEt), 143 (M+ - COOEt,), 124 (M+ - F - COOEt), 80
(pyrimidine). Anal. Calcd for C8H9FN2O2S: C, 44.44; H, 4.20;
N, 12.96. Found: C, 44.15; H, 4.09; N, 12.62.
r-F lu or o-r-[(2-p yr im id yl)th io]a ceton itr ile (4c): mp 90-
1
91 °C (hexane/i-PrOH); H NMR δ 7.21 (t, 1H, J ) 4.95 Hz),
7.41 (d, 1H, J ) 48.83 Hz), 8.65 (d, 2H, J ) 4.62 Hz); 19F NMR
δ -84.26 (d, J ) 48.71 Hz); MS m/e 169 (M+), 149 (M+ - HF),
142 (M+ - HCN), 111 (M+ - CHFCN), 80 (pyrimidine). Anal.
Calcd for C6H4FN3S: C, 42.60; H, 2.38; N, 24.84. Found: C,
42.73; H, 2.40; N, 24.74.
1
2-(F lu or om eth ylth io)p yr im id in e (4d ): colorless oil; H
NMR δ 6.14 (d, 2H, J ) 51.14 Hz), 7.08 (t, 1H, J ) 4.95 Hz),
8.61 (d, 2H, J ) 4.95 Hz); 19F NMR δ -114.26 (t, J ) 51.47
Ηz); 13C NMR (DEPT) δ 83.36 (dt, CH2F, J ) 216, 7.3 Hz),
117.81, 157.07, 157.68 (3CH), 168.80 (C); MS m/e 144 (M+),
124 (M+ - HF), 111 (M+ - CH2F), 80 (pyrimidine); HRMS m/e
calcd for C5H5FN2S 144.0157, found 144.0144. 2-(Diflu or o-
m eth ylth io)p yr im id in e (4d′): 19F NMR δ -22.49 (d, J ) 56.1
Hz); MS m/e 162 (M+), 112 (M+ - CF2), 80 (pyrimidine); HRMS
m/e calcd for C6H4F2N2S 162.0063, found 162.0038.
Ack n ow led gm en t. One of the authors, K.M.D., is
deeply indebted to the UNESCO and the J apanese
Ministry of Education, Science and Culture (Monbusho)
for granting him a research fellowship (1997-1998). We
also grateful to Dr. K. Momota of Morita Chemical
Industries Co. Ltd. For his generous gifts of Et4NF‚nHF
(n ) 3, 4).
2-(F lu or om eth ylth io)p yr id in e (5): 1H NMR δ 6.15 (d,
2H, J ) 51.5 Hz), 7.11 (dd, 1H, J ) 7.4, 4.8 Hz), 7.28 (d, 1H,
J ) 8.3 Hz), 8.51 (d, 1H, J ) 4.3 Hz); 19F NMR δ -111.00 (t, J
) 51.5 Hz); 13C NMR δ 83.40 (d, J ) 214.9 Hz), 121.02, 122.84,
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
spectra of 4d , 9a ,b, and a mixture of 5 and 6 and 19FNMR
spectra of a mixture of 5 and 6. This material is available free
(26) Srivastav, K. S. L. Ind. J . Pharm. 1970, 32, 97.
J O9909857