Facile aldolization catalyzed by ionic liquid [4-sulfbmpyrazine][BF 4]

Article abstract of DOI:10.14233/ajchem.2013.14396

The acidic functionalized ionic liquid 1-(4-sulfonic group)butyl-3- methylpyrazine tetrafluoroborate (abbreviated as [4-sulfbmpyrazine][BF ₄]) was employed as the catalyst of the condensation of aromatic aldehyde and diols. The optimized condition was as follows: aromatic aldehyde (0.20 mol), diols (0.30 mol) and [4-sulfbmpyrazine][BF₄] (0.60 g) were refluxed in cyclohexane (10.00 mL) for 1 h. A series of aromatic aldehydes were studied and afforded the corresponding acetals products with good yields which were from 70.3 to 96.9 %. The ionic liquid catalyst could be recycled for four times without significant loss of catalyst reactivity.

Full text of DOI:10.14233/ajchem.2013.14396

Asian Journal of Chemistry; Vol. 25, No. 12 (2013), 6643-6646
http://dx.doi.org/10.14233/ajchem.2013.14396
Facile Aldolization Catalyzed by Ionic Liquid [4-Sulfbmpyrazine][BF4]
*
JIANZHONG ZOU, FENGPING YI , LIRONG ZHANG and ZHEN WANG
School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, P.R. China
*Corresponding author: Tel: +86 21 60873280; E-mail: yifengping@sit.edu.cn; zlir2008@163.com
(Received: 3 August 2012;
Accepted: 27 May 2013)
AJC-13539
The acidic functionalized ionic liquid 1-(4-sulfonic group)butyl-3-methylpyrazine tetrafluoroborate (abbreviated as [4-sulfbmpyrazine][BF4])
was employed as the catalyst of the condensation of aromatic aldehyde and diols. The optimized condition was as follows: aromatic
aldehyde (0.20 mol), diols (0.30 mol) and [4-sulfbmpyrazine][BF4] (0.60 g) were refluxed in cyclohexane (10.00 mL) for 1 h. A series of
aromatic aldehydes were studied and afforded the corresponding acetals products with good yields which were from 70.3 to 96.9 %. The
ionic liquid catalyst could be recycled for four times without significant loss of catalyst reactivity.
Key Words: Aldolization, Ionic liquid, Aromatic aldehyde, Acetals.
INTRODUCTION
EXPERIMENTAL
The demand of flavours is greatly increasing with the rapid
development of chemical industry. Acetals are better than the
parent carbonyl compounds in spices and become new fast
developed flavours in recent years. Although aldehydes
species play an extremely important role in the flavour of food,
they can easily be oxidized and darken under the air, light and
heat, etc. Carbonyl compounds are feasible to form stable
acetals, most of which show the flavour of floral, woody and
mint. In addition, the acetals are usually used to be the
protected group of carbonyl compounds and reagent in the
organic synthesis1.
1H NMR spectra were recorded on a Bruker AVANCE III
500 MHz spectrometer with TMS as an internal. ESI-MS spectra
were recorded on a Micromass LCT KC317 spectrometer.
Reagents and chemicals were purchased from commercial
resource and used without further purification. All final prod-
ucts are known compounds; their physical and spectroscopic
data were compared with those reported in the literatures and
found to be identical.
Preparation of [4-sulfbmpyrazine][BF4] (Scheme-I):
2-Methylpyrazine ( 0.94 g, 0.01 mol) was dissolved in aceto-
nitrile, then added 1,4-butanesultone (2.72 g, 0.02 mol) and
the mixture was heated to reflux. On completion, the mixture
was cooled down to room temperature, filtered and the cake
was washed for three times with ethyl acetate, dried in vacuum
to give the intermediate 1 (1.92 g, yield is 83.5 %). And then
HBF4 (5.28 g, 0.06 mol) was dropped in the intermediate 1
(11.50 g, 0.05 mol) in the acetonitrile and heated at 60 ºC for
2 h. On completion, the solvent was removed and the residue
was washed with acetone to afford a brown liquid [4-sulfbm-
pyrazine][BF4] (14.66 g, yield is 92.4 %). Some spectra of
[4-sulfbmpyrazine][BF4]: 1H NMR (500 MHz, D2O) δ: 1.72-
1.79 (m, 2H, CH2), 2.11-2.15 (t, J = 7.6, 2H, CH2), 2.75 (s,
3H, CH3), 2.88-2.92 (t, J = 7.6, 2H, CH2), 4.62-4.68 (m, 2H,
CH2), 8.77 (s, 1H, CH=CH), 8.89 (s, 1H, CH=CH), 9.19 (s,
1H, CH=N); MS(ESI): m/e 231.1.
The traditional acetals syntheses meet many drawbacks,
such as long reaction time, more byproducts, low reaction
yields, deep colour of the products, corrosion of equipments
and large amount of acid waste. Recently much attention has
been paid to studies on acidic ionic liquid catalysts with
stability and high catalytic activities. Ionic liquids are consi-
dered as the green solvents and catalysts in terms of low vapour
pressure, high efficiency, easy separation of products and
recyclability2-7. In this paper, we reported that the acid-
functionalized ionic liquid 1-(4-sulfonic group) butyl-
3-methylpyrazine tetrafluoroborate (abbreviated as [4-
sulfbmpyrazine][BF4]) catalyzed the acetalization of aromatic
aldehydes and diols to afford acetals. The synthesis conditions
of acetals were optimized. It was found that the ionic liquid
showed excellent catalytic activity and was easily handled and
recycled for at least four times without significant loss of
activity.
Acetals were synthesized via the acetalization of carbonyl
compounds with diols (Scheme-II) catalyzed by [4-sulfbm-
pyrazine][BF4]. In the typical procedure, carbonyl compounds

6644 Zou et al.
Asian J. Chem.
SO3
TABLE-2
RESULTS OF THE L9(34 ) ORTHOGONAL EXPERIMENT
OF ALDOLIZATION AND RANGE ANALYSIS
N
N
N
+
S
O
N
O
Yield
(%)
O
Entry
A
B
C
D
SO3H
BF4
1
A1
A1
B1
B2
B3
B1
B2
B3
B1
B2
B3
C1
C2
C3
C2
C3
C1
C3
C1
C2
D1
D2
D3
D3
D1
D2
D2
D3
D1
36.8
54.6
48.7
53.3
87.4
68.5
54.5
59.7
82.5
–
HBF4
N
N
2
3
A1
4
A2
1
5
A2
Scheme-I: Synthesis of [4-sulfbmpyrazine][BF4]
6
A2
7
A3
8
A3
O
O
9
A3
O
H
ionic liquid
HO CH
K1
140.10
209.20
196.70
46.70
69.73
65.57
23.03
144.60 165.00 206.70
201.70 190.40 177.60
199.70 190.60 161.70
2
R
H O
2
R
HO CH
–
K2
2
–
K3
–
k1
48.20
67.23
66.57
19.03
55.00
63.47
63.53
8.53
68.90
59.20
53.90
15.00
O
O
–
k2
k3
CH3
CH2OH
CH3
–
O
ionic liquid
H
HOH2C
R
H2O
R
–
Range
Primary-secondary
Optimal solution
ABDC
A2B2C3D1
Scheme-2: Synthesis of acetals
(0.20 mol), cyclohexane 10.00 mL, diols (0.30 mol) and the
[4-sulfbmpyrazine][BF4] (0.60 g, 0.20 mol) were mixed
together in a three necked round bottomed flask equipped with
a magnetic stirrer and thermometer. Here a Dean-Stark appa-
ratus was used to remove the water continuously from the
reaction mixture. The mixture was refluxed for the specified
time. On completion, the catalyst was recovered by centrifu-
gation, washing with acetone and drying in an oven at 80 ºC
for ca. 1 h.
conditions of synthesis of acetal were:the dosage of benzaldehyde
(0.20 mol), diol (0.30 mol), cyclohexane (10.00 mL), catalyst
(0.60 g), reaction time (1 h). The reaction gave the desired
product in 88.3 % yield under the optimized conditions.
To recover the catalyst [4-sulfbmpyrazine][BF4], the
residue after extraction was washed with acetone and dried
under vacuum to give regenerated [4-sulfbmpyrazine][BF4].
In order to demonstrate the repeatability of functionalized ionic
liquid [4-sulfbmpyrazine][BF4], the recycle of catalyst [4-
sulfbmpyrazine][BF4] was also investigated by using the prepa-
ration of benzaldehyde ethylene glycol acetal (a) as a model.
The recovered [4-sulfbmpyrazine][BF4] was employed in the
same aldolization, The yield of benzaldehyde ethylene glycol
acetal was fluctuated at 88.3-86.4 % in the first four cycles
(Fig. 1). Then it became less activity in the next run.
RESULTS AND DISCUSSION
The synthesis of acetal was optimized by the orthogonal
test method with the reaction of benzaldehyde with glycol as
the representative reaction (Scheme-III) and the orthogonal
experimental program was shown in Table-1. Four factors were
the dosage of diol (A), the dosage of cyclohexane (B), the
dosage of catalyst (C) and reaction time (D), respectively.
Orthogonal experimental results and analysis were shown in
Table-2.
100
87.6
86.4
88.3 87.2
80
60
40
20
0
O
65.5
O
ionic liquid
H
HO CH2
HO CH2
H2O
50.2
O
Scheme-III: Synthesis of benzaldehyde ethylene glycol acetal
TABLE-1
FACTOR LEVEL OF THE SYNTHESIS OF
BENZALDEHYDE ETHYLENE GLYCOL ACETAL
Factor
Dosage of
diol (A)
(mol)
Dosage of
cyclohexane
(B) (mL)
Dosage of
catalyst
(C) (g)
Reaction
time (D)
(h)
Level
1
2
3
4
5
6
1
2
3
0.20
0.30
0.40
5
0.20
0.40
0.60
1
2
3
10
15
Reaction cycles
Fig. 1. Recyclability of regenerated [4-sulfbmpyrazine][BF4]
The orthogonal test analysis showed that the best combi-
nation of factors wasA2B2C3D1. And, the longer reaction time,
the more byproducts. Therefore, the optimized reaction
Furthermore, in order to test the generality of [4-
sulfbmpyrazine][BF4] as catalyst for the aldolization, reactions
of a variety of aromatic aldehydes with diols were carried out

Vol. 25, No. 12 (2013)
Facile Aldolization Catalyzed by Ionic Liquid [4-Sulfbmpyrazine][BF4] 6645
TABLE-3
SYNTHESIS OF RAMIFICATION OF ALDOLIZATION CATALYZED BY [4-SULFBMPYRAZINE][BF4]
Entry
1
Aromatic aldehydes
Diols
Product
Yield (%)
88.3
O
Benzaldehyde
Ethanediol
O
(a)
O
2
3
Phenylacetaldehyde
Ethanediol
Ethanediol
78.9
82.6
O
(b)
Cl
O
o-Chlorobenzaldehyde
O
(c)
O
4
Cyclamen aldehyde
Ethanediol
O
86.4
(d)
(e)
O
H3CO
5
6
p-Methoxybenzaldehyde
Ethanediol
Ethanediol
76.8
70.3
O
O
Cuminaldehyde
O
(f)
O
O N
2
7
8
m-Nitrobenzaldehyde
o-Chlorobenzaldehyde
Neopentyl glycol
Neopentyl glycol
85.7
87.6
O
(g)
Cl
O
O
(h)
O
H CO
3
9
p-Methoxybenzaldehyde
p-Formyl-benzonitrile
Neopentyl glycol
Neopentyl glycol
87.7
85.6
O
(i)
O
NC
10
O
(j)
O
O
O
O
11
12
Piperonyl aldehyde
Benzaldehyde
Neopentyl glycol
Neopentyl glycol
88.0
96.9
(k)
(l)
O
O
under the optimized conditions established above and the
results were shown in Table-3. The results demonstrated that
the functionalized ionic liquid [4-sulfbmpyrazine][BF4]
exhibited high catalytic reactivity in the synthesis of acetals.
Benzaldehyde ethylene glycol acetal8 (a): 1H NMR (500
MHz, CDCl3) δ: 7.53-7.52 (m, 2H), 7.42-7.39 (m, 3H), 5.84
(s, 1H), 4.15 (t, J = 7.0 Hz, 2H), 4.05 (t, J = 7.0 Hz, 2H).
4.0 Hz, 1H), 4.00 (t, J = 4.5 Hz, 2H), 3.90 (t, J = 4.5 Hz, 2H),
2.93-2.87 (m, 2H), 2.39 (dd, J = 13.5 Hz, J = 4.5 Hz, 1H),
1.25 (d, J = 7.0 Hz, 6H), 0.90 (d, J = 7.0 Hz 3H).
p-Methoxybenzaldehyde ethylene glycol acetal12 (e):
1H NMR (500 MHz, CDCl3) δ: 7.65 (d, J = 10.0 Hz, 2H), 6.89
(d, J = 10.0 Hz, 2H), 6.21 (s, 1H), 3.97 (t, J = 7.0 Hz, 2H),
3.85 (t, J = 7.0 Hz, 2H), 3.61 (s, 3H).
1
1
Phenylacetaldehyde ethylene glycol acetal9 (b): H
Cuminaldehyde ethylene glycol acetal13 (f): H NMR
NMR (500 MHz, CDCl3) δ: 7.34-7.24 (m, 5H), 5.10 (t, J = 4.5
Hz, 1H), 3.97 (t, J = 7.0 Hz, 2H), 3.86 (t, J = 7.0 Hz, 2H), 2.30
(d, J = 5.0 Hz, 2H).
(500 MHz, CDCl3) δ: 7.43-7.41 (m, 2H), 7.27-7.25 (m, 2H),
5.81 (s, 1H), 4.14 (t, J = 7.0 Hz, 2H), 4.04 (t, J = 7.0 Hz, 2H),
2.84 (dd, J = 14.0 Hz, J = 7.0 Hz, 1H), 1.26 (d, J = 7.0 Hz, 6H).
m-Nitrobenzaldehyde neopentyl glycol acetal14 (g): m.p.
49-50 ºC; 1H NMR (500 MHz, CDCl3) δ: 8.22 (t, J = 10.0 Hz,
2H), 7.07 (t, J = 7.5 Hz, 2H), 5.29 (s, 1H), 3.81 (d, J = 10.0
Hz, 2H), 3.69 (d, J = 10.0 Hz, 2H), 1.31 (s, 3H), 0.85 (s, 3H).
o-Chlorobenzaldehyde neopentyl glycol acetal15 (h): 1H
NMR (500 MHz, CDCl3) δ: 7.77 (d, J = 10.0 Hz, 1H), 7.30-
o-Chlorobenzaldehyde ethylene glycol acetal10 (c): 1H
NMR (500 MHz, CDCl3) δ: 7.63-7.61 (m, 1H), 7.40-7.38 (m,
1H), 7.31-7.29 (m, 2H), 7.62 (s, 1H), 4.17 (t, J = 7.0 Hz, 2H),
4.08 (t, J = 7.0 Hz, 2H).
1
Cyclamen aldehyde ethylene glycol acetal11 (d): H
NMR (500 MHz, CDCl3) δ: 7.16-7.11 (m, 4H), 4.77 (d, J =

6646 Zou et al.
Asian J. Chem.
7.37 (m, 3H), 5.77 (s, 1H), 3.71-3.81 (m, 4H), 1.34 (s, 3H),
0.83 (s, 3H).
ACKNOWLEDGEMENTS
p-Methoxybenzaldehyde neopentyl glycol acetal16 (i):
The authors are thankful for the financial support from
the Key Project of Shanghai Educational Committee Founda-
tion (No. 11ZZ180), the Project of Local University Ability
Building of Shanghai Scientific and Technological Committee
(No. 11520502600) and the Science Foundation of Shanghai
Institute of Technology (No. YJ2012-29). The authors also
gratefully thank the Project of Shanghai Council for the Pro-
motion of the Transformation of Scientific and Technological
Achievements (No. LM201247) for financial support.
1
m.p. 60-61 ºC; H NMR (500 MHz, CDCl3) δ: 7.45 (d, J =
10.0 Hz, 2H), 6.91 (d, J = 10.0 Hz, 2H), 5.37 (s, 1H), 3.83 (s,
3H), 3.77 (d, J = 10.0 Hz, 2H), 3.65 (d, J = 10.0 Hz, 2H), 1.32
(s, 3H), 0.82 (s, 3H).
p-Formyl-benzonitrile neopentyl glycol acetal17 (j):
m.p. 106-109 ºC; 1H NMR (500 MHz, CDCl3) δ: 7.68 (d, J =
10.0 Hz, 2H), 7.63 (d, J = 10.0 Hz, 2H), 5.44 (s, 1H), 3.79 (d,
J = 15.0 Hz, 2H), 3.67 (d, J = 10.0 Hz, 2H), 1.29 (s, 3H), 0.84
(s, 3H).
Piperonyl aldehyde neopentyl glycol acetal18 (k): m.p.
44-45 ºC; 1H NMR (500 MHz, CDCl3) δ: 7.05 (s, 1H), 6.98
(d, J = 10.0 Hz, 1H), 6.81 (d, J = 5.0 Hz, 1H), 5.97 (s, 2H),
5.33 (s, 1H), 3.76 (d, J = 15.0 Hz, 2H), 3.64 (d, J = 10.0 Hz,
2H), 1.31 (s, 3H), 0.81 (s, 3H).
Benzaldehyde neopentyl glycol acetal19 (l): m.p. 32-33
ºC; 1H NMR (500 MHz, CDCl3) δ: 7.54 (t, J = 10.0 Hz, 3H),
7.38 (d, J = 15.0 Hz, 2H), 5.43 (s, 1H), 3.80 (d, J = 10.0 Hz,
2H), 3.68 (d, J = 10.0 Hz, 2H), 1.34 (s, 3H), 0.83 (s, 3H).
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