Efficient and convenient preparation of γ-nonalactone, with use of a Dean-Stark trap to remove methanol

Article abstract of DOI:10.1007/s11164-013-1066-7

We describe the development of an efficient and convenient process for preparation of γ-nonalactone. The synthesis was accomplished by free-radical addition of methyl acrylate and n-hexanol. A Dean-Stark trap filled with water and n-hexanol was used to remove the methanol generated during the process. Orthogonal experiments were performed to optimize the reaction conditions, and the desired product, γ-nonalactone, was produced in better than 70 % yield.

Full text of DOI:10.1007/s11164-013-1066-7

Res Chem Intermed
DOI 10.1007/s11164-013-1066-7
Efficient and convenient preparation of c-nonalactone,
with use of a Dean–Stark trap to remove methanol
Song Tu
Chen Zhang
•
Youyu Shen
Liyi Ye
•
Wan Dong
•
Jing Yang
•
•
Received: 10 December 2012 / Accepted: 17 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract We describe the development of an efficient and convenient process for
preparation of c-nonalactone. The synthesis was accomplished by free-radical
addition of methyl acrylate and n-hexanol. A Dean–Stark trap filled with water and
n-hexanol was used to remove the methanol generated during the process.
Orthogonal experiments were performed to optimize the reaction conditions, and
the desired product, c-nonalactone, was produced in better than 70 % yield.
Keywords Preparation Á c-Nonalactone Á Dean–Stark trap used to remove
methanol Á Orthogonal experiments
Introduction
Lactones, also known as furanones, are common in the plant world. They are
responsible for the odor of some flowers, fruits, and vegetables. c-Lactones mainly
occur in such fruits as coconut, peach, mango, apricot, passion fruit, and strawberry,
among others [1]. c-Nonalactone, also known as coconut aldehyde, is a valuable
lactone for perfumes. Production of c-lactones catalyzed by lipase [2, 3], by
microbial action [4], or via biosynthetic routes [5] has been extensively studied.
Lactones can also be prepared by chemical methods [6–11]. The general process for
obtaining c-lactones is cyclization of 3-alkenoic acids by use of 78–80 % sulfuric
S. Tu (&) Á Y. Shen Á J. Yang Á C. Zhang Á L. Ye (&)
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical
Engineering, Xiamen University, Xiamen 361005, People’s Republic of China
e-mail: tusong@xmu.edu.cn
L. Ye
e-mail: lyye@xmu.edu.cn
W. Dong
Linde Gas Xiamen Ltd., Xiamen 361021, People’s Republic of China
123

S. Tu et al.
acid [12]. Currently, c-nonalactone is mainly produced by free-radical addition of
acrylic acid (or methyl acrylate) and n-hexanol, which are inexpensive and
accessible starting materials [13–18]. However, this method requires high pressure
[
15, 16, 18]; otherwise, the yield would be low [17] because removal of the water
or methanol) generated during the process is an arduous task. We have previously
(
conducted a preliminary study on the preparation of c-nonalactone by free-radical
addition of acrylic acid and n-hexanol using a Dean–Stark trap with added
anhydrous Na SO4 as desiccant. The anhydrous Na SO absorbs the water
2
2
4
generated when acrylic acid is heated under reflux in the reaction flask with
n-hexanol [19, 20]. This process is, however, unsuitable for industrial manufacture.
In this study, a Dean–Stark trap containing water was used because of the
difficulty of separating the low-boiling-point substances methyl acrylate (bp 80 °C)
from the methanol generated (bp 65 °C) at high temperature (*180 °C). The water
absorbed the methanol, and the methyl acrylate was returned to the reaction flask
with n-hexanol. This article describes an efficient and convenient method of
preparing c-nonalactone in better than 70 % yield by free-radical addition of methyl
acrylate and n-hexanol. To the best of our knowledge, this study is the first to have
used a Dean–Stark trap filled with water and alcohol in the free-radical addition of
methyl acrylate and alcohol as starting materials to yield c-lactones.
Results and discussion
The mechanism proposed herein for the preparation of c-nonalactone by the free-
radical addition reaction is shown in Scheme 1 [21].
A Dean–Stark trap filled with water and n-hexanol was attached to a flask and
used to remove the methanol generated in the process. During the reaction, a
mixture of n-hexanol, methanol, and other low-boiling-point substances collected in
the Dean–Stark trap. Methanol dissolved in water, whereas the raw material methyl
acrylate and di-t-butyl peroxide (DTBP) were returned to the flask with n-hexanol.
As a result, methanol was efficiently removed from the system and the reaction
proceeded smoothly.
First, the effects of different Dean–Stark trap conditions were investigated. As
shown in Table 1, under the control condition in which no Dean–Stark trap was
fitted in the flask, the generated methanol could not be removed from the system and
led to a low yield of c-nonalactone (Table 1, entry 1). When the Dean–Stark trap
was filled with water, the yield of c-nonalactone was also low because part of the
mixture of water and methanol was returned to the flask, which negatively affected
OH
CO2CH3
CO H
2
OH
Me CO
3
OCMe3
C
C
H
OH
H
O
O
CH (CH ) CH OH
ZnBr2
O
(CH2)4CH3
3
2 4
2
+ CH OH
3
O
OH
Scheme 1 Possible mechanism of preparation of c-nonalactone by the free-radical addition reaction
1
23

Efficient and convenient preparation of c-nonalactone
the reaction (Table 1, entry 2). However, when the Dean–Stark trap was filled with
water and n-hexanol in the bottom layer and top layer, respectively, c-nonalactone
was produced in higher yield for the reasons described above (Table 1, entry 3).
Our previous research on the preparation of c-nonalactone by free-radical
addition of acrylic acid and n-hexanol showed that the optimum reaction
temperature and molar ratio of n-hexanol to acrylic acid were 180 °C and 7,
respectively [19, 20]. Considering that the possible mechanisms in the preparation
of c-lactones by free-radical addition of acrylic acid or by free-radical addition of
methyl acrylate to fatty alcohol are similar, we set the molar ratio of n-hexanol to
methyl acrylate and the reaction temperature to 7 and 180 °C, respectively, in this
study.
Orthogonal experiments were performed to optimize the reaction conditions.
Four important conditions, feeding time (A), reaction time (B), molar ratio of DTBP
to methyl acrylate (C), and molar ratio of ZnBr to methyl acrylate (D), were
2
optimized by use of the orthogonal test schedule in Table 2. Each factor had three
levels.
The effects of the four factors in Table 2 were investigated by use of orthogonal
4
tests and variance analysis. An orthogonal table L (3 ) was used to array the factors,
9
and the results are listed in Table 3. The yield was used to evaluate the efficiency of
the synthetic process under different conditions (different factors and levels).
According to Table 3, the effects of the four factors on the yield of c-nonalactone
were in the order: A [ B [ C [ D. The results also showed that the differences
between the effect of feeding time and that of reaction time on yield were not
obvious. The molar ratio of DTBP to methyl acrylate (C) affected the yield of
c-nonalactone more clearly than the molar ratio of ZnBr to methyl acrylate (D).
2
The optimum reaction conditions were A2B2C3D1: feeding time = 7 h, reaction
time = 5 h, molar ratio of DTBP to methyl acrylate = 0.273, and molar ratio of
ZnBr2 to methyl acrylate = 0.035. Under these conditions, the yield of
c-nonalactone reached 70.1 %.
The results of the orthogonal experiments also indicated that the yield of
c-nonalactone decreased with increasing the molar ratio of zinc bromide to methyl
acrylate, because the presence of a large amount of ZnBr resulted in destruction of
2
free radicals [21]. This result is in agreement with our previous research findings
[
19, 20].
Table 1 Effects of different experimental Dean–Stark trap conditions
a
Entry
Dean–Stark trap
Yield (%)
1
2
3
None
47.7
49.2
59.3
Filled with water
Filled with n-hexanol (top) and water (bottom)
Reaction conditions: n(n-hexanol)/n(methyl acrylate) = 7, n(DTBP)/n(methyl acrylate) = 0.273,
n(ZnBr )/n(methyl acrylate) = 0.050, feeding time = 7 h, reaction time = 5 h, reaction temperature =
80 °C
2
1
a
Determined by gas chromatography (GC)
123

S. Tu et al.
Table 2 Factors and levels selected for orthogonal experiments
Factor A
feeding time (h) )
Factor B
(reaction time (h))
Factor C (n(DTBP)/
n(methyl acrylate))
Factor D (n(ZnBr
(methyl acrylate))
2
)/n
a
(
Level 1
Level 2
Level 3
a
6
7
8
4
5
6
0.164
0.217
0.273
0.035
0.047
0.050
Time at which the mixture of acrylic acid, DTBP, and n-hexanol was added to the flask
4
(3 ) orthogonal experiments
Table 3 Results of L
9
a
No.
A
B
C
D
Yield (%)
1
2
3
4
5
6
7
8
1
1
2
1
1
57.3
63.3
63.4
62.0
70.1
65.8
61.4
60.9
64.9
1
1
2
2
2
3
3
3
2
3
2
3
3
1
2
3
2
3
1
3
1
2
1
3
2
2
1
3
9
3
2
1
b
K
1
K
2
K
3
61.3
66.0
62.4
4.7
60.2
64.8
64.7
4.6
61.3
63.4
65.0
3.7
64.1
63.5
62.1
2.0
c
R
Reaction conditions: n(n-hexanol)/n(methyl acrylate) = 7, reaction temperature = 180 °C
a
Determined by GC
b
Average of the sum of experimental results
c
i i min
R = K ,max - K ,
Conclusion
In summary, c-nonalactone was prepared efficiently by free-radical addition of
n-hexanol to methyl acrylate in the presence of DTBP and zinc bromide using a
Dean–Stark trap containing water to absorb the methanol generated.
Experimental
Methyl acrylate (purity, 98 %), n-hexanol (purity, 98 %), DTBP (purity, 99 %), and
anhydrous zinc bromide (purity, 96 %) were all purchased from Sinopharm
Chemical Reagent. GC was performed with a GC9560 system using capillary
columns (SE-30 dimethylpolysiloxane, 30 m 9 0.32 mm i.d., 0.33 lm film thick-
ness) and under the following conditions: detector and inlet temperature, 250 °C;
1
23

Efficient and convenient preparation of c-nonalactone
temperature program, 130 °C for 1 min, rising to 250 °C at 10 °/min, and then held
for 15 min; carrier gas, nitrogen; and average injection volume, 0.5 ll. Compounds
were identified by comparing their retention times (R ) with those of authentic
f
1
samples. H NMR and C NMR spectra were recorded in CDCl on an AV 400
13
3
NMR spectrophotometer using TMS as internal standard.
General procedure for preparation of c-nonalactone
Anhydrous zinc bromide (2.10 g, 0.009 mol) and n-hexanol (139.02 g, 1.334 mol)
were added to a 500-ml round-bottomed flask fitted with a magnetic stirrer, an
injector pump, a Dean–Stark trap containing water (15 ml) and n-hexanol (10 ml), a
condenser, and a thermometer. After the reaction temperature had increased to
1
80 °C, methyl acrylate (22.29 g, 0.254 mol), DTBP (10.19 g, 0.069 mol), and
n-hexanol (46.29 g, 0.444 mol) were added via the injector pump over 7 h. During
this process, a mixture of n-hexanol, methanol, and other low-boiling-point
substances collected in the Dean–Stark trap. After 5 h, heating was stopped and the
low-boiling-point substances were removed by distillation. c-Nonalactone was
obtained in 70.1 % yield by vacuum distillation. bp, 136–140 °C/13 mmHg; lit.
1
[
22] bp, 148–153 °C/13 mmHg. H NMR (400 MHz, CDCl ) d 4.53–4.44 (m, 1H),
3
2
.52 (dd, J = 9.5, 6.9 Hz, 2H), 2.33–2.25 (m, 1H), 1.87–1.77 (m, 1H), 1.75–1.52
1
m, 2H), 1.48–1.25 (m, 6H), 0.92–0.86 (m, 3H); C NMR (100 MHz, CDCl3)
3
(
d 177.39, 81.11, 35.52, 31.49, 28.86, 27.99, 24.89, 22.47, 13.94.
Acknowledgments This work was supported by a National Nature Science Foundation of China Grant
(No. 21106119), the Fundamental Research Funds for the Central Universities, P.R. China (No.
2
3
011121019), and the Science and Technology Planning Project of Xiamen City, P.R. China (No.
502Z20113001).
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