U. Hanefeld and S. K. Karmee
acid were purchased from Acros Organics and Sigma–Aldrich. Chol-
ine hydroxide was purchased from Acros Organics. Freshly distilled
benzaldehyde and 1-methylimidazole were used for the reactions.
1H and 13C NMR spectra were recorded on Bruker Avance 400 (400
and 100 MHz, respectively) or Varian Unity Inova 300 (300 and
75 MHz, respectively) instruments. All reactions were carried out
under N2 by using standard Schlenk techniques. Thin-layer chroma-
tography (TLC) was performed by using precoated silica gel SIL G/
UV 254 plates. The water contents in the ILs were determined by
applying Karl–Fischer titrations with a 756/831 KF Coulometer, ac-
cording to the manufacturer’s instructions.
Table 2. All of the products were characterised by using 1H and
13C NMR spectroscopy and the analytical data are in accordance
with the literature.[42–44]
Recycling of choline hydroxide: Choline hydroxide (4 mmol,
484 mg) was added to a stirred solution of benzaldehyde (1 mmol,
106 mg) in acetone (68 mmol, 5 mL) under N2 at 08C. The reaction
was stirred for 30 min. After the reaction, the organic layer was
separated and choline hydroxide was washed with dry diethyl
ether (2ꢁ2 mL) under N2 at 08C. Fresh benzaldehyde (1 mmol,
106 mg) and acetone (68 mmol, 5 mL) were added to the IL phase
for the second run of the reaction. The third run was performed as
described for the second run. The combined organic layers ob-
tained after each run were evaporated separately, and the crude
products were purified by using column chromatography with pe-
troleum ether/ethyl acetate (85:15) as the eluent. The isolated
yields of 4-hydroxy-4-phenylbutan-2-one and 4-phenylbut-3-en-2-
one are presented in Figure 5.
Separation of the formed products was carried out by using HPLC
using the following instrument and method: pump: Waters 590;
UV detector: Waters 486, flow rate: 1 mLminÀ1. A Chromolith
Speed ROD, RP-18e, 50–4.6 mm, column was used for this purpose
with H2O/CH3CN (90:10) as the mobile phase. The formed aldol (4-
hydroxy-4-phenylbutan-2-one) and dehydrated product (4-phenyl-
but-3-en-2-one) were quantified by using 1,2,3-trimethoxybenzene
as an internal standard. The retention times of 4-hydroxy-4-phenyl-
butan-2-one, benzaldehyde, 1,2,3-trimethoxybenzene, and 4-phe-
nylbut-3-en-2-one were 3.4, 4.3, 9.9 and 20.2 min. All analyses were
performed by diluting 20 mL of sample in 980 mL of HPLC eluent
H2O/CH3CN (90:10).
Acknowledgements
A senior research fellowship of the Technische Universiteit Delft
to S.K.K. is gratefully acknowledged. We are grateful to Maarten
Gorseling and Remco van Oosten for technical assistance.
Preparation of ILs: ILs used for this study, namely, [Hmim][BF4][14]
(3483 ppm H2O), [Hmim][TFA][15] (1777 ppm H2O), [NMP][HSO4][16,17]
(1669 ppm H2O), [HSO3-BMIm][HSO4][18] (513 ppm H2O), [TOBSA]-
[HSO4][19] (606 ppm H2O), and [TMG][Lac][20] (1126 ppm H2O), were
prepared and characterised according to reported methods.[14–20]
Choline hydroxide had a water content of 451 ppm.
Keywords: aldol reaction · ionic liquids · organocatalysis ·
sustainable chemistry
[2] T. Welton, Green Chem. 2008, 10, 483–483.
[6] P. Wasserscheid, T. Welton, Ionic Liquids in Synthesis, Wiley-VCH, Wein-
heim, 2008.
General procedure for the screening of acidic and basic ILs for the
aldol reaction: The required IL catalyst (5 mmol) was added to a
stirred solution of benzaldehyde (1 mmol, 106 mg), acetone
(27 mmol, 2 mL), and dry diethyl ether (29 mmol; 3 mL) under N2
in a dry 50 mL thermostated Schlenk flask. The reaction was stirred
at room temperature for the required time (Table 1).
Choline hydroxide, [TOBSA][HSO4]-, and [HSO3-BMIm][HSO4]-cata-
lysed synthesis of 4-hydroxy-4-phenylbutan-2-one: The IL (4 mmol)
was added to a stirred solution of benzaldehyde (1 mmol, 106 mg)
in acetone (68 mmol, 5 mL) under N2 at 08C in a dry 50 mL ther-
mostated Schlenk flask. The reaction was stirred for 30 min (choline
hydroxide) and 25 h ([TOBSA][HSO4] and [HSO3-BMIm][HSO4]). All
analyses were performed by using HPLC by diluting 20 mL of the
sample in 980 mL of HPLC eluent (90:10=H2O/CH3CN, Figures 2, 3,
and 4).
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General procedure for the synthesis of b-hydroxy ketone by using
NaOH, KOH, and Ca(OH)2: Ca(OH)2, KOH, or NaOH (4 mmol) was
added to a stirred solution of benzaldehyde (1 mmol, 106 mg) and
acetone (68 mmol, 5 mL) under N2 at 08C in a dry 25 mL thermo-
static Schlenk flask. The reaction was stirred for 30 min. The con-
version and selectivity were determined by HPLC, as described
earlier.
General procedure for the synthesis of b-hydroxy ketones by using
choline hydroxide as
a catalyst: Choline hydroxide (4 mmol,
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Tichit, B. Coq, Chem. Commun. 2004, 1096–1097.
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484 mg) was added to the stirred solution of aldehyde (1 mmol,
5 mL) in ketone (68 mmol, 7.94 mL) under N2 at 08C. The reaction
was stirred for the required time (Table 2). After the reaction, the
solvent was evaporated in vacuo and the residue was extracted
with diethyl ether (3ꢁ10 mL). The combined organic layers were
evaporated and the crude product was purified by using column
chromatography with petroleum ether/ethyl acetate (85:15) as the
eluent. The isolated yield of the b-hydroxy ketones is given in
1122
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ChemSusChem 2011, 4, 1118 – 1123