Efficient preparation of racemic γ-nonalactone

Full text of DOI:10.1080/00304948.2013.743759

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Organic Preparations and Procedures
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Efficient Preparation of Racemic γ-
Nonalactone
Song Tu a , Wan Dong a , Jing Yang a , Chen Zhang a & Youyu Shen a
a Department of Chemical and Biochemical Engineering, College of
Chemistry and Chemical Engineering, Xiamen University, Xiamen, P.
R. China
Version of record first published: 16 Jan 2013.
To cite this article: Song Tu , Wan Dong , Jing Yang , Chen Zhang & Youyu Shen (2013): Efficient
Preparation of Racemic γ-Nonalactone, Organic Preparations and Procedures International: The New
Journal for Organic Synthesis, 45:1, 72-74
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Organic Preparations and Procedures International, 45:72–74, 2013
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2013.743759
OPPI BRIEF
Efficient Preparation of Racemic γ -Nonalactone
Song Tu, Wan Dong, Jing Yang, Chen Zhang, and Youyu Shen
Department of Chemical and Biochemical Engineering, College of Chemistry
and Chemical Engineering, Xiamen University Xiamen, P. R. China
Lactones, also known as furanones, are widespread in the plant world1 and are responsible
for the odor of flowers, fruits and vegetables. γ -Lactones occur mainly in fruits such as
coconut, peach, mango, apricot, passionfruit, strawberry, etc.1 γ -Nonalactone, also named
coconut aldehyde, is a valuable lactone for perfumes. The formation of γ -lactones catalyzed
by lipase,2,3 by microbial action4 or via biosynthetic routes5 is well known. Lactones can also
be prepared by chemical methods.6–11 The general process for obtaining γ -lactones is the
cyclization of 3-alkenoic acids using 78% or 80% sulfuric acid.12 At present, γ -nonalactone
is mainly produced via free radical addition using acrylic acid (or methyl acrylate) and n-
hexanol as inexpensive and easily obtained starting materials.13–18 However, this method
requires high pressure,15,16,18 otherwise, the yield is low17 because the water (or methanol)
generated during the reaction is difficult to remove from the system. This article describes a
modified technique for the efficient preparation of γ -nonalactone in better than 75% yield
by the free radical addition of acrylic acid and n-hexanol.
In the present study, a Dean-Stark trap containing anhydrous sodium sulfate is used
because the low boiling points of acrylic acid and of the water generated make it difficult to
separate them at high temperature (about 180◦C). The anhydrous sodium sulfate (used as
desiccant) absorbs the water and acrylic acid is returned to the reaction flask with n-hexanol.
To the best of our knowledge, there is no previous report on the use of Dean-Stark trap
with an added desiccant via the free radical addition of alcohols to acrylic acid as starting
materials to yield γ -lactones.19
In order to minimize polymerization of acrylic acid and to increase the yield of γ -
nonalactone, it was necessary to use a large excess of n-hexanol. Increase in the molar ratio
of n-hexanol to acrylic acid from 5 to 8 led to an increase in the yield of γ -nonalactone from
46% to 69%. Although a higher yield could be reached by increasing the molar ratio to
more than 8, the cost-recovery of n-hexanol would be higher and would be a disadvantage
for industrial process. Prolonging the charge period (the time for adding the mixture of
Received June 3, 2012.
Address correspondence to Song Tu, Department of Chemical and Biochemical Engineering,
College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China.
E-mail: tusong@xmu.edu.cn
72

Efficient Preparation of Racemic γ -Nonalactone
CO2H
73
CO2H
OH
OCMe3
Me3CO
OH
C
C
H
OH
H
O
O
ZnBr2
(CH2)4CH3
CH3(CH2)4CH2OH
O
OH
OH
Scheme 1
acrylic acid, DTBP and n-hexanol to the flask) from 2.5 to 7 hrs also led to an increase in
the yield of γ -nonalactone from 40% to 67% while the yield of γ -nonalactone decreased
if the charge period was increased to 10 hrs. So the optimal molar ratio of n-hexanol to
acrylic acid and the optimal charge period were chosen to be 7 and 7 hours respectively.
Di-t-butyl peroxide (DTBP) was chosen as the initiator in this process. Increase in the
molar ratio of DTBP to acrylic acid from 0.109 to 0.272 resulted in an increase in the yield
of γ -nonalactone from 48% to 77% .When the molar ratio of DTBP to acrylic acid was
raised to more than 0.272, the yield of γ -nonalactone was nearly unchanged. The yield of
γ -nonalactone increased from 60% to 75% with the molar ratio of zinc bromide to acrylic
acid increased from 0.047 to 0.051. When the molar ratio of zinc bromide to acrylic acid
raised to more than 0.051, the yield of γ -nonalactone declined.19
In conclusion, γ -nonalactone was prepared efficiently via the free radical addition of
n-hexanol to acrylic acid in the presence of di-t-butyl peroxide and zinc bromide using a
Dean-Stark trap containing anhydrous sodium sulfate as a desiccant.
Experimental Section
Acrylic acid (purity: 98%), n-hexanol (purity: 98%), di-t-butyl peroxide (purity: 99%),
anhydrous zinc bromide (purity: 96%) and anhydrous sodium sulfate (Na2SO4) were all
purchased from Sinopharm Chemical Reagent Co., Ltd. Gas chromatography (GC) analyses
were performed on GC9560, using capillary columns [SE-30 dimethylpolysiloxane, 30 m ×
0.32 mm i.e., 0.33 μm film thickness]; detector and inlet temperature, 250◦C; temperature
program, 130◦C for 1 min, rising to 250◦C at a rate of 10◦C/min., then held for 15 mins;
carrier gas, nitrogen; injections, average 0.5 μL. Compounds were identified by comparison
1
of the retention times (Rf) with those of authentic samples. The H NMR and 13C NMR
spectra were recorded in CDCl3 on an AV 400 NMR spectrophotometer using TMS as
internal standard.
General Procedure for the Preparation of γ -Nonalactone
Anhydrous zinc bromide (3.05 g, 0.013 mol) and n-hexanol (139.08 g, 1.334 mol) were
added to a 500 ml round bottom flask fitted with a magnetic stirrer, a thermometer, an
addition funnel, a Dean-Stark trap containing anhydrous Na2SO4 (15.00 g) in it and a
condenser. After the reaction temperature had been raised to 180◦C, a mixture of acrylic
acid (18.68 g, 0.254 mol), di-t-butyl peroxide (DTBP, 10.19 g, 0.069 mol) and n-hexanol
(46.39 g, 0.445 mol) was added via the addition funnel over 7 h. During this process, a
mixture of n-hexanol, acrylic acid, water and other low boiling point substances collected
in the Dean-Stark trap. After 5 h, heating was stopped and the low boiling point substances

74
Tu et al.
were distilled off. Then γ -nonalactone (30.12 g, 76%) was obtained by distillation in vacuo,
bp. 136–140◦C/13 mmHg, lit.20 bp. 148–153◦C/13 mmHg. 1H NMR (400 MHz, CDCl3):
δ 4.53–4.44 (m, 1H), 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(m, 2H), 1.48–1.25(m, 6H), 0.92–0.86(m, 3H). 13C NMR (100 MHz, CDCl3): δ
177.39, 81.11, 35.52, 31.49, 28.86, 27.99, 24.89, 22.47, 13.94.
Acknowledgments
This work was supported by the Science and Technology Planning Project of Xiamen City,
P. R. China (No. 3502Z20113001) and the Fundamental Research Funds for the Central
Universities, P. R. China (No. 2011121019).
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