NH4OH(aq). After extraction with diethyl ether (5 ¥ 25 mL)
the combined organic extracts dried over MgSO4 and con-
centrated in vacuo (12.9 g, 69%). Iodomethane (4.55 mL,
73.0 mmol) was then slowly added to the resulting isobutyl
nicotinate (12.87 g, 71.8 mmol) in toluene (200 mL) under
inert atmosphere at room temperature. The reaction was then
refluxed at 45 ◦C for 24 h, with the resulting iodide salt
separating out in the bottom of the flask. Recrystallization with
acetonitrile and diethyl ether afforded a light yellow powder
that was dried in vacuo (21.2 g, 92%). The resulting IL (3.94 g,
12.3 mmol) was dissolved in water (100 mL) and then treated
with bis(trifluoromethanesulfonimide) lithium salt (5.17 g,
18.0 mmol) and stirred for 1 h. Extraction with CH2Cl2 (3 ¥
50 mL) followed by drying (MgSO4 anhyd.) and concentration
Synthesis of 3-(tert-butoxycarbonyl)-1-methylpyridinium
bis(trifluoromethanesulfonyl)imide, 1d
Thionyl chloride (9.67 g, 5.90 mL, 81.3 mmol) was added to a
mixture of nicotinic acid (5.00 g, 40.7 mmol) in 100 mL toluene
and refluxed for 24 h at 110 ◦C. The resulting white solid
was filtered, washed with diethyl ether (5 ¥ 50 mL), and dried
in vacuo. The resulting acyl chloride (10.0 g, 70.95 mmol) in
THF (150 mL) was treated with potassium tert-butoxide (8.98 g,
80.0 mmol) at -5 ◦C and stirred for 2 h. Solvent was then
removed in vacuo and the resulting white solid was dissolved in
CH2Cl2 (200 mL) and washed with saturated NaHCO3 followed
by water. The organics were dried over anhydrous MgSO4 and
concentrated in vacuo to afford tert-butyl nicotinate (6.5 g,
52%). Iodomethane (2.49 mL, 40.0 mmol) was slowly added to
a toluene (100 mL) suspension of tert-butyl nicotinate (6.04 g,
33.7 mmol) under inert atmosphere at room temperature.
The reaction was then refluxed at 45 ◦C for 24 h, with the
resulting iodide salt separating out in the bottom of the flask.
Recrystallization with acetonitrile and diethyl ether afforded a
light yellow powder that was dried in vacuo (3.28 g, 30%). The
resulting IL (3.94 g, 12.3 mmol) was dissolved in water (100
mL) and then treated with bis(trifluoromethanesulfonimide)
lithium salt (5.17 g, 18.0 mmol) and stirred for 1 h. Extraction
with CH2Cl2 (3 ¥ 50 mL) followed by drying (MgSO4) and
concentration in vacuo afforded the desired product (2.9 g,
1
in vacuo afforded the desired product (27.5 g, 91%). H NMR
(DMSO-d6): d 1.01 (d, J = 6.5 Hz, 6H), 2.077 (m, 1H),
4.20 (d, J = 6.5 Hz, 2H), 4.44 (s, 3H), 8.25 (m, 1H), 8.98
(d, J = 8.4 Hz, 1H), 9.18 (d, J = 6.0 Hz, 1H) 9.53 (s,
1H). 13C NMR (DMSO-d6): d 18.8, 27.4, 48.4, 72.1, 119.6 (q,
JC–F = 322 Hz), 128.0, 129.6, 144.9, 146.8, 149.0, 161.8. HRMS
(ESI, +ve) calcd for C11H16NO2 194.1176, found 194.1177,
HRMS (ESI, -ve) calcd for N(SO2CF3)2 279.9178, found
279.9167.
Synthesis of 3-(sec-butoxycarbonyl)-1-methylpyridinium
bis(trifluoromethanesulfonyl)imide, 1c
1
95%). H NMR (DMSO-d6): d 1.60 (s, 9H), 4.41 (s, 3H), 8.23
(m, 1H), 8.91 (d, J = 8.4 Hz, 1H), 9.15 (d, J = 6.0 Hz, 1H) 9.45
(s, 1H). 13C NMR (DMSO-d6): d 27.6, 48.3, 84.1, 119.5 (q, JC–F
= 322 Hz), 127.8, 130.7, 144.7, 146.7, 148.7, 160.7. HRMS (ESI,
+ve) calcd for C11H16NO2 194.1176, found 194.1179, HRMS
(ESI, -ve) calcd for N(SO2CF3)2 279.9178, found 279.9178.
Thionyl chloride (9.67 g, 5.90 mL, 81.30 mmol) was added to
a mixture of nicotinic acid (5.00 g, 40.65 mmol) in 100 mL
toluene and refluxed for 24 h at 110 ◦C. The resulting white solid
was filtered, washed with diethyl ether (5 ¥ 50 mL), and dried
in vacuo. The resulting acyl chloride (5.75 g, 40.7 mmol) was
dissolved in CH2Cl2 (200 mL) and treated with 2-butanol (6.03 g,
7.46 mL, 81.3 mmol) followed by the addition of triethylamine
(8.22 g, 11.32 mL, 81.3 mmol) and 4-dimethylaminopyridine
Synthesis of 3-(carboxy)-1-methylpyridinium
bis(trifluoromethanesulfonyl)imide, 1e
◦
(0.366 g, 3.0◦mmol) at -78 C. The reaction flask was allowed
Iodomethane (5.70 g, 40 mmol) was added to nicotinic acid
(4.29 g, 34.8 mmol) in dry THF (200 mL) and refluxed at
45 ◦C for 5 d. Removal of the solvent in vacuo afforded a
white solid (5.12 g, 56%). The resulting IL (4.06 g, 15.4 mmol)
was dissolved in water (100 mL) and treated with lithium
bis(trifluoromethanesulfonimide) (8.61 g, 30.0 mmol) and
stirred for 1 h. The reaction was then extracted with ethyl
acetate (3 ¥ 50 mL). The combined organic extracts were then
washed with water (3 ¥ 50 mL), dried over anhydrous MgSO4
and concentrated in vacuo to afford the product (0.29 g, 33%).
1H NMR (DMSO-d6): d 4.41 (s, 3H), 8.23 (m, 1H), 8.93 (d,
J = 8.1 Hz, 1H), 9.14 (d, J = 6.0 Hz, 1H) 9.51 (s, 1H). 13C
NMR (DMSO-d6): d 48.3, 119.7 (q, JC–F = 322 Hz), 128.0,
130.9, 145.1, 147.1, 148.6, 163.3. HRMS (ESI, +ve) calcd for
C7H8NO2 138.0550, found 138.0549, HRMS (ESI, -ve) calcd
for N(SO2CF3)2 279.9178, found 279.9181.
to stir at 50 C for 24 h after which the organics were washed
with saturated NaHCO3 followed by H2O. The organic layer was
dried over MgSO4 and concentrated in vacuo to afford sec-butyl
nicotinate (3.7 g, 51%). Iodomethane (0.62 mL, 10 mmol) was
then slowly added to sec-butyl nicotinate (1.50 g, 8.37 mmol)
suspended in toluene (50 mL) under inert atmosphere at room
◦
temperature. The reaction was then refluxed at 45 C for 24 h,
with the resulting iodide salt separating out in the bottom of
the flask. Recrystallization with acetonitrile and diethyl ether af-
forded a light yellow powder that was dried in vacuo (3.2 g, 50%).
The resulting IL (3.94 g, 12.3 mmol) was dissolved in water (100
mL) and then treated with bis(trifluoromethanesulfonimide)
lithium salt (5.17 g, 18.0 mmol) and stirred for 1 h. Extraction
with CH2Cl2 (3 ¥ 50 mL) followed by drying (MgSO4) and
concentration in vacuo afforded the desired product (4.16 g,
1
97%). H NMR (DMSO-d6): d 0.95 (t, J = 7.5 Hz, 3H), 1.35
(d, J = 6.3 Hz, 3H), 1.73 (m, 2H), 4.43 (s, 3H), 5.11 (sextet,
J = 6.0 Hz, 1H), 8.24 (m, 1H), 8.96 (d, J = 8.1 Hz, 1H),
9.17 (d, J = 6.3 Hz, 1H) 9.52 (s, 1H). 13C NMR (DMSO-d6):
d 9.4, 19.0, 28.2, 48.3, 75.2, 119.6 (q, JC–F = 322 Hz), 128.0,
130.0, 144.8, 146.8, 148.9, 161.3. HRMS (ESI, +ve) calcd for
C11H16NO2 194.1176, found 194.1171, HRMS (ESI, -ve) calcd
for N(SO2CF3)2 279.9178, found 279.9163.
General procedure for Sonogashira reactions in
3-(alkoxycarbonyl)-1-methylpyridinium
bis(trifluoromethanesulfonyl)imides (1a–d)
The arene (3.0 mmol) was sonicated in the biodegradable IL
(1a–d where indicated) (4.0 g) for 10 min under a nitrogen
atmosphere to facilitate dissolution of the arene in the ionic
654 | Green Chem., 2010, 12, 650–655
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The Royal Society of Chemistry 2010
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