Characterisation of a by-product formed in the industrial production of γ-nonalactone

Article abstract of DOI:10.3184/174751916X14538088859488

Distillation residues from the industrial production of γ-nonalactone, which is accomplished by reaction of hexanol with methyl acrylate initiated by t-butyl peroxide, yielded a by-product which we deduced to be 4-(methoxycarbonylethyl)-γ-nonalactone. The possible pathway of formation of this by-product is discussed.

Full text of DOI:10.3184/174751916X14538088859488

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 MARCH, 141–143
RESEARCH PAPER 141
Characterisation of a by-product formed in the industrial production of
g-nonalactone
Haitao Chena, Dan Wanga, Yongguo Liua, Guoying Zhanga, Tianyi Wangb, Yang Wangb, Shaoxiang
Yanga, Baoguo Suna and Hongyu Tiana*
aBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Key Laboratory of Flavor Chemistry, Beijing Technology and Business
University, Beijing 100048, P.R. China
bAnhui Hyea Aromas Company, Qianshan County, Anhui Province 246300, P.R. China
Distillation residues from the industrial production of g-nonalactone, which is accomplished by reaction of hexanol with methyl acrylate
initiated by t-butyl peroxide, yielded a by-product which we deduced to be 4-(methoxycarbonylethyl)-g-nonalactone. The possible pathway
of formation of this by-product is discussed.
Keywords: 4-(methoxycarbonylethyl)-g-nonalactone, g-nonalactone, identification, industrial production
g-Lactones are well known naturally-occurring flavour
compounds and many are present as important aroma
components of various foods such as dairy products, fruits,
nuts and vegetables. Several representative compounds,
such as g-octalactone, g-nonalactone, g-decalactone, and
g-undecalactone, are widely used in various fragrance and
flavour formulations due to their low odour threshold values
and pleasant sweet, creamy and fruity aromas.1 Among the
commercialised g-lactones, synthetic products still account
for most of the market share due to their lower cost compared
to natural lactones, although natural products are preferred
by the more discerning consumers. Many synthetic routes for
g-lactones have been developed, such as lactonisation of olefinic
fatty acids catalysed by various Lewis or protonic acids.2–6
However, the methods suitable for industrial production are very
limited. In addition to hemi-synthesis of g-undecalactone from
undecylenic acid obtained by degradation of natural ricinoleic
acid, which is catalysed by acid usually with a relatively low
yield,7 the method developed by Nikishin and Vorob′ev8 is still
the commonest one for the industrial production of g-lactones,
which involves peroxide-catalysed addition of an aliphatic
alcohol to acrylic acid (or its ester) (Scheme 1).
in its production of g-lactones with methyl acrylate. The major
unknown component was found to account for about 51% of the
residue after g-nonalactone had been distilled off. Herein, we
will report the characterisation of this by-product and discuss
its possible route of formation.
Results and discussion
Structure determination of the by-product isolated from
distillation residues
The mass data of the by-product obtained by GC/EIMS did not
match with any data in the NIST library. Its molecular formula
was determined to be C13H22O4 by HR-ESI-MS, from which the
number of double-bond equivalents (DBE) in this molecule was
1
calculated to be three. 1D NMR spectra, including H NMR,
13C NMR and dept135 indicated that there were 2 ester carbonyl
groups (2 × DBE), 2 methyl groups (one was the end methyl of
a long-chain alkyl group and the other should be from a methyl
ester), 8 methylene groups and 1 quaternary carbon in this
compound. So the remaining double-bond equivalent must be
accounted for by a ring. Based on all these data, one possible
structure was postulated to be 4-(methoxycarbonylethyl)-g-
nonalactone as shown in Fig. 1.
The Anhui Hyea Aromas Company is one of the top 10
flavour and fragrance companies in China, and it focuses on
the production of lactones, including g- and d-lactones. The
production of g-lactones is based on the synthetic route shown
in Scheme 1. The average yields of these lactones are about
65% based on the amounts of the unrecovered alcohols, which
are not satisfying to the manufacturer. High costs confront the
manufacturer with strong competitive pressure in the market
and lowering costs becomes most urgent. Undoubtedly, one of
the most efficient ways to lower costs is by the analysis and
identification of by-products so that methods to avoid their
formation can be developed. Alternatively, a by-product can
sometimes have commercial value.
In order to confirm this structure, this by-product was
analysed further with 2D NMR methods, including H,H- and
H,C-correlation, and HMBC. All of the 2D NMR data agreed
well with the structure. All peaks in the 1H and 13C NMR spectra
were assigned as shown in Table 1 based on the information
obtained from 2D NMR spectra. Two ester carbonyl groups
were easily assigned based on the cross peak corresponding to
the methyl peak of d 51.7 in the HMBC spectrum, which led to
the identification of the two similar spin systems attached to the
ester carbonyl groups.
The possible route of formation of the by-product
It is well known that the reaction mechanism for the industrial
production of g-nonalactone is as shown in Scheme 2. In the
initiation step, abstraction of an a-hydrogen from hexanol by
We recently analysed and identified one by-product
provided by the manufacturer derived from the production
of g-nonalactone (so-called ‘aldehyde C18’). It was from the
distillation residue derived from the production of g-nonalactone,
in which the manufacturer replaced usually-used acrylic acid
O
COOR'
O
R = n-pentyl; R' = CH3
t
t
-BuO
OBu-
+
R
COOH
OH
R
R
O
O
Scheme 1
Fig. 1 The possible structure of the by-product.
* Correspondent. E-mail: tianhy@btbu.edu.cn

142 JOURNAL OF CHEMICAL RESEARCH 2016
Table 1 The assignment of peaks in 1H and 13C NMR spectra of the by-product
Chemical shift d
13C NMR
13.8
Compound
Assignment
1H NMR
0.93
H–C9
H–C8
H–C7
–CH2CH2COOCH3
H–C2
22.3
22.9
28.3
28.7
1.27–1.40
1.27–1.40
2.38–2.50
2.63
O
COOCH3
O
4
1
2
H–C3
H–C6
–CH2CH2COOCH3
H–C5
–CH2CH2COOCH3
C4
30.6
31.8
33.2
38.1
51.7
87.6
2.08–2.15, 2.00–2.08
1.27–1.40
2.00–2.08
1.60–1.74
3.72
3
6
5
7
8
CH3
9
–CH2CH2COOCH3
C1
173.2
176.3
Initiation:
t
-BuO
2 t-BuO
OBu-t
t
-BuO
H
R = n-pentyl
R
OH
R
OH
1
Propagation:
H
OH
COOCH3
HO
R
H
R
OH
COOCH3
R
OH
R
OH
R
COOCH3
-CH3OH
1
2
1
R
O
O
Scheme 2
H
OH
t-BuO
R
COOCH3
COOCH3
COOCH3
OH
HO
H
rearrangement
COOCH3
OH
R
R
COOCH3
R
COOCH3
2
3
4
R = n-pentyl
RCH2OH
O
COOCH3
OH
-CH3OH
COOCH3
O
R
COOCH3
R
Scheme 3
t-BuO• produces radical intermediate 1. In the propagation
step, the addition of radical intermediate 1 to methyl acrylate
gives a new radical intermediate 2, which then abstracts an
a-hydrogen from the starting material, hexanol to give methyl
4-hydroxy-nonanoate and regenerates a radical intermediate 1
(Scheme 2).
The proposed pathway of formation of the by-product is
as shown in Scheme 3. This postulation involved a radical

JOURNAL OF CHEMICAL RESEARCH 2016 143
160–170 °C for 8 h while distilling off t-BuOH and methanol which
were produced during the reaction. After the addition, the reaction
mixture was kept stirring at 160–170 °C for 1 h. The reaction mixture
was submitted to a distillation process, in which the first cut was the
excess hexanol for recycling and the second cut contained the crude
product which was purified for further fractionation. Some residues
usually remained after g-nonalactone was distilled out in the second
cut.
intermediate 3, which could be formed via a rearrangement
of the radical intermediate 2 and/or a-hydrogen abstraction
of the intermediate methyl 4-hydroxynonanoate by a butyloxy
radical. The addition of the radical intermediate 3 to methyl
acrylate gave a new radical intermediate 4 which abstracted
an a-hydrogen from hexanol to produce methyl 4-hydroxy-4-
methoxycarbonylethyl nonanoate, intramolecular esterification
of which, gave 4-(methoxycarbonylethyl)-g-nonalactone.
This by-product was found to occur in the distillation
residues in the production of g-nonalactone when methyl
acrylate replaced acrylic acid. Earlier we had tried to help the
manufacturer characterise the components of the residue derived
from the industrial production of g-undecalactone through the
reaction of octanol with acrylic acid. However, the separation
of the residue by column chromatography failed to give any
useful results. A component similar to 4-methoxycarbonylethyl
g-nonalactone might, by analogy, also occur in the distillation
residue as an acid form (as shown in Fig. 1, R = n-heptyl, R′ =
H). The reason that we did not find this component was due to
the strong polarity of the acid which would have been retained
by the silica column. It is important to the manufacturer to
characterise the components of such residues since they are
usually produced in a relatively large amounts equal to about
25% of the g-lactone products. This work is under way in our
laboratory.
Purification of the sample
The sample was subjected to silica-gel column chromatography (silica
gel, petroleum ether-diethyl ether, 4:1) to separate a major component,
which was obtained as a light yellow oil in about 20% yield.
Spectroscopic data of the by-product: 1H NMR (CDCl3) d 0.93
(t, J = 6.6 Hz, 3H), 1.27–1.40 (m, 6H), 1.60–1.74 (m, 2H), 2.00–2.08
(m, 3H), 2.08–2.15 (m, 1H), 2.38–2.50 (m, 2H), 2.63 (t, J = 9 Hz,
2H), 3.72 (s, 3H); 13C NMR (CDCl3) d 13.8, 22.3, 22.9, 28.3, 28.7,
30.6, 31.8, 33.2, 38.1, 51.7, 87.6, 173.2, 176.3; GC/MS (EI) m/z (%) 41
(17), 43 (22), 55 (36), 56 (11), 95 (17), 111 (100), 143 (75), 155 (94),
171 (94), 211 (14); HR-ESI-MS, m/z 265.14065 [M + Na+] (calcd. for
C13H22NaO4, 265.14103).
Electronic Supplementary Information
The NMR spectra of the by-product are available through:
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
Financial support from the National Natural Science
Foundation of China (No. 31271932 and 31571886), the
National Key Technology R&D Program (2011BAD23B01)
and the Importation and Development of High-Caliber Talents
Project of Beijing Municipal Institutions (CIT&TCD20140306)
is gratefully acknowledged.
Experimental
The reagents were purchased from the Beijing Huaxue Shiji Company.
NMR spectra were obtained on a Bruker AV 300 spectrometer
(1H NMR at 300 MHz, 13C NMR at 75 MHz) or an AV 600
spectrometer (1H NMR at 600 MHz, 13C NMR at 150 MHz) in CDCl3
using TMS as an internal standard. Chemical shifts (d) are given
in ppm and coupling constants (J) in Hz. The high resolution mass
spectrum was obtained on a Bruker Apex IV FTMS.
A sample provided by the Anhui Hyea Aromas Company was the
residue derived from the production of g-nonalactone, in which the
major component to be analysed was isolated.
Received 1 December 2015; accepted 4 January 2016
Paper 1503751 doi: 10.3184/174751916X14538088859488
Published online: 8 February 2016
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