1-hexyl-3-methylimidazolium chloride [C6mim][Cl] (20.37
g, 100 mmol) and sodium hydrogen sulphate (12 g, 100
mmol) that gave the desired [C6mim][HSO4] 1b in 94% yield
Standard Procedure Using a Focused Microwave Oven
for Esterification of Acids 2(a-d) and neo-Pentanol 3. A
mixture of [C4py][HSO4] 1c (3 equiv), acid 2 (1 equiv), and
neo-pentanol 3 (3 equiv) was placed in a cylindrical quartz
reactor (L ) 4 cm). The reactor was then introduced into a
Synthewave 402 Prolabo microwave reactor [fitted with a
stirring device and an IR temperature detector]. The stirred
homogeneous liquid mixture was irradiated at 25% power
level (75 W) for a reaction time ranging from 1.5 to 4.5 h.
at 80 °C (see Table 5). Then the mixture was allowed to
cool during 45 min. The upper ester layer was separated
carefully from the acidic catalyst [C4py][HSO4] 1c by
decantation. The bottom layer that contained the catalyst 1c
was washed with Et2O according to the procedure described
for “standard procedure for esterification reaction in oil bath”.
neo-Pentyl propanoate (4a): yield ) 95%. 1H NMR (300
MHz, CDCl3, TMS): δ 0.94 (s, 9H); 1.16 (t, 3H, J ) 7.6
Hz); 2.34 (q, 2H, J ) 7.6 Hz); 3.77 (s, 2H). 13C NMR (75
MHz, CDCl3, TMS): δ 9.25 (qt, J ) 128, 5.6 Hz); 26.46
(qm, J ) 128 Hz); 27.69 (tq, J ) 128, 4.5 Hz); 31.34 (m);
73.63 (tm, J ) 148 Hz); 174.60 (m, C-l, CdO). IR (KBr):
1734 cm-1. HRMS m/z: 144.1156 found (calcd for C8H16O2
requires 144.1150), M+.
1
(24.84 g). H NMR (300 MHz, CD3CN, TMS): δ 0.87 (t,
3H, J ) 7.1 Hz); 1.30 (m, 6H); 1.96 (m, 2H); 3.86 (s, 3H);
4.15 (t, 2H, J ) 7.3 Hz); 7.54 (m, 2H, H-4, H-5); 8.20 (br
s, 1H, HSO4); 8.89 (s, 1H, H-2). 13C NMR (75 MHz, CD3-
CN, TMS): δ 14.34 (q, J ) 123 Hz); 23.01; 26.32; 30.61;
31.68 (tm, J ) 122 Hz); 38.28 (q, J ) 144 Hz); 50.63 (t, J
) 123 Hz); 123.32; 124.73 (dm, J ) 202 Hz, C-4, C-5);
137.22 (dm, J ) 220 Hz, C-2). HRMS m/z: 431.2692 found
- +
(calcd for C20H9N4O4S+ [2C+, HSO4 ] requires 431.2692).
1-Butyl-pyridinium Hydrogen Sulphate [C4py][HSO4]
(1c). The acidic ionic liquid 1c was prepared according to
the method used for the synthesis of 1a from 1-butyl-pyrid-
inium bromide [C4py][Br] (20 g, 92.6 mmol) and sodium
hydrogen sulphate (22.23 g, 185.2 mmol) that gave the
desired [C6mim][HSO4] 1b in 96% yield (20.7 g). 1H NMR
(300 MHz, CD3CN, TMS): δ 0.92 (t, 3H J ) 7,3 Hz); 1.36
(m, 2H); 1.96 (m, 2H); 4.67 (t, J ) 7.5 Hz); 8.10 (t, J ) 7
Hz, 2H, H-2, H-6); 8.36 (br s, 1H HSO4); 8.56 (m, 1H, H-4);
9.00 (d, J ) 5.6 Hz, 2H, H-3, H-5). 13C NMR (75 MHz,
CD3CN, TMS): δ 12.31 (qm, J ) 125 Hz); 18.42 (tm, J )
127 Hz); 32.44 (tm, J ) 128 Hz); 60.89 (tm, J ) 145 Hz);
127.88 (dm, J ) 172 Hz, C-3, C-5); 144.21 (dm J ) 192
Hz, C-4); 145.13 (dm, J ) 172 Hz, C-2, C-6). HRMS m/z:
136.1127 found (calcd for C9H14N+, C+ requires 136.1126).
Standard Experimental Procedure for Esterification
of Propanoic Acid 2a with neo-Pentanol 3 in an Oil Bath
with 1a: [C4mim][HSO4], 1c: [C4py][HSO4], or with 1a
Modified with Concentrated H2SO4. Reuse of the Acidic
Catalyst. Into a glass reactor fitted with a reflux condenser
and a thermometer were added 3 equiv of the acidic TSIL
(1a: [C4mim][HSO4] or 1c: [C4py][HSO4] or 1a modified with
5% of concentrated H2SO4). Then neo-pentanol 3 (1 equiv)
and propanoic acid 2a (1 equiv) were successively placed
in the catalyst media. The outlet of the reflux condenser was
connected to a constant pressure of dry nitrogen, and the
reactor was kept in a thermostated oil bath at 80 °C (variation
(10 °C). The esterification reaction was typically allowed
to proceed for a reaction time ranging from 1.5 to 24 h (see
Tables 2, 3, and 4). Reaction progress was conveniently
monitored by 1H NMR spectroscopy [in (CD3)2SO or (CD3)2-
CO with TMS as internal reference] on a BRUKER ARX
200 spectrometer and also by TLC on precoated plates of
silica gel 60F 254 (Merck). At the end of the esterification,
the upper layer which contains the desired ester 4 was
separated carefully from the acidic catalyst by decantation.
The bottom layer was reused in a further run after washing
twice with Et2O (10 mL/g of catalyst) under vigorous
magnetic stirring at 25 °C for 30 min. The washing layer
was separated by decantation and concentrated by rotary
evaporation, and the resulting distillate was controlled by
1H NMR spectroscopy. The catalyst in the reactor was dried
under high vacuum (10-2 Torr) at 60 °C for 6 h and was
controlled by mass balance and eventually by 1H NMR spec-
troscopy. This control experiment was realized at each run.
neo-Pentyl cyclohexylcarboxylate (4b): yield ) 90%. 1H
NMR (300 MHz, CDCl3, TMS): δ 0.93 (s, 9H); 1.24-1.94
(m, 10H); 2.32 (m, 1H); 3.76 (s, 2H). 13C NMR (75 MHz,
CDCl3, TMS): δ 25.4 (m, C-3, C-5); 25.76 (m, C-4); 26.48
(m, C-1); 29.11 (m, C-2, C-6) 31.44 (m); 43.4 (dm, J ) 127
Hz); 73.37 (tm, J ) 146 Hz); 176.1 (m, C-1, CdO). IR
(KBr): 1732 cm-1. HRMS m/z: 198.1621 found (calcd for
C12H22O2 requires 198.1620), M+.
neo-Pentyl 10-undecenoate (4c): yield ) 89%. 1H NMR
(300 MHz, CDCl3, TMS): δ 0.93 (s, 9H); 1.30-1.37 (m, 10
H); 1.61-1.63 (m, 2H); 2.02-2.05 (m, 2H); 2.30-2.35 (m,
2H); 3.77 (s, 2H); 4.90-5.02 (m, 1H, dCH); 5.73-5.87 (m,
2H, dCH2). 13C NMR (75 MHz, CDCl3, TMS): δ 25.06 (m);
26.46 (m); 28.91 (m); 29.07 (m); 29.19 (m); 29.29 (m); 31.29
(m); 33.80 (m); 34.43 (m, C-2); 73.57 (tm, J ) 146 Hz);
114.17 (tm, J ) 155 Hz); 139.10 (dm, J ) 151 Hz); 174.02
(m, C-1, CdO). IR (KBr): 1737 cm-1. HRMS m/z: 239.2014
found (calcd for C15H27O2 requires 239.2011), [M-CH3]+.
1
neo-Pentyl phenylacetate (4d): yield ) 40%. H NMR
(300 MHz, CDCl3, TMS): δ 0.87 (s, 9H; 3.62 (s, 2H); 3.77-
(s, 2H); 7.28 (m, 5H, Ar). 13C NMR (75 MHz, CDCl3,
TMS): δ 26.32 (qm, J ) 123 Hz); 31.34 (m); 41.57 (tm, J
) 129 Hz); 74.05 (tm, J ) 146 Hz); 126.99 (dm, J ) 170
Hz, C-4′); 128.52 (dm, J ) 161 Hz, C-2′, C-6′); 129.3 (dm,
J ) 166 Hz, C-3′, C-5′); 134.22 (m, C-1′); 174.60 (m, C-1,
CdO). IR (KBr): 1732 cm-1. HRMS m/z: 206.1313 found
(calcd for C13H18O2 requires 206.1307), M+.
Acknowledgment
We thank Merck Eurolab Prolabo (Fr.) for providing the
Synthewave 402 apparatus. We also thank Professor Jack
Hamelin for fruitful discussions and Dr. Pierre Gue´not
(CRMPO) for the mass spectrometry measurements.
Received for review April 8, 2005.
OP058002X
748
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Vol. 9, No. 6, 2005 / Organic Process Research & Development