Efficient synthesis of the odourant, 2-nonen-4-olide

Article abstract of DOI:10.3184/174751912X13402955389383

A three-step synthesis of 2-nonen-4-olide starting from heptanal is reported. (E)-3-Nonenoic acid, prepared by Knoevenagel condensation of malonic acid and heptanal, was oxidised by performic acid, a process accompanied by lactonisation, to give 3-hydroxynonan-4-olide in 85% yield. This lactone when reacted with MsCl in the presence of Et3N gave, by elimination, 2-nonen-4-olide in 88% yield. The overall yield was 75%. The odour of the product was evaluated by GC-olfactory analysis and sniffing blotter confirming an oily, coconut-like, and rancid odour.

Full text of DOI:10.3184/174751912X13402955389383

JOURNAL OF CHEMICAL RESEARCH 2012
AUGUST, 495–496
RESEARCH PAPER 495
Efficient synthesis of the odourant, 2-nonen-4-olide
Yi-feng Dai, Hong-yu Tian*, Bao-guo Sun, Yu-mei Sun, Hai-tao Chen and Xiao-yu Liu
School of Food Chemistry, Beijing Key Laboratory of Flavour Chemistry, BeijingTechnology and Business University, Beijing 100048,
P. R. China
A three-step synthesis of 2-nonen-4-olide starting from heptanal is reported. (E)-3-Nonenoic acid, prepared by
Knoevenagel condensation of malonic acid and heptanal, was oxidised by performic acid, a process accompanied by
lactonisation, to give 3-hydroxynonan-4-olide in 85% yield. This lactone when reacted with MsCl in the presence of
Et N gave, by elimination, 2-nonen-4-olide in 88% yield. The overall yield was 75%. The odour of the product was
3
evaluated by GC-olfactory analysis and sniffing blotter confirming an oily, coconut-like, and rancid odour.
Keywords: 2-nonen-4-olide, (E)-3-nonenoic acid, dihydroxylation, coconut-like odour
2
-Nonen-4-olide occurs naturally in the volatile components
followed by elimination, in which laconisation was accom-
21,22
of various foods and plant extracts, such as stewed beef/
vegetable gravy, sunflower oil, Chinese white salted noodles,
watermelon, potato crisps, lard cured with spices and
aromatic herbs, mushrooms, French fries, primulaceae and
plished with dihydroxylation in one pot.
(E)-3-Nonenoate
1
2
3
had to be prepared instead of (E)-3-nonenoic acid as substrate
of Sharpless AD since that method is carried out under basic
conditions. However, for the preparation of racemic 2-nonen-
4-olide, we found that (E)-3-nonenoic acid 1 could be con-
verted directly to the intermediate 3-hydroxy nonan-4-olide
4
5
6
7
8
9
10
1,7,8
flue-cured tobacco. It was described to have a coconut-like,
9
or sweet odour by gas chromatography-olfactometry (GC-O)
analysis. It had been approved as a flavour compound by
Flavour and Extract Manufacturers’ Association (FEMA)
until 2005 and was included in FEMA GRAS (Generally
2
by oxidation using 30% H O in formic acid in 85% yield,
2 2
during which lactonisation took place with oxidation in
one pot, just like the Sharpless AD of (E)-3-nonenoate.
3-Hydoxynonan-4-olide 2 was easily transformed to 2-nonen-
1
1
Recognised as Safe) List 22 with FEMA No. 4188.
4
-olide 3 in high yield by an elimination of the corresponding
The synthesis of α,β-unsaturated γ-lactones, better known as
butenolides, has attracted much interest since they are a very
important functionality in many biologically important natural
mesylate. The overall yield was 75%, which is much higher
than that of the one-step route reported by Browne et al.
17
12–14
In their one-pot synthesis of 2-nonen-4-olide by a catalytic
addition-elimination of (E)-3-nonenoic acid using selenium
electrophiles, the yield was only 49% and the reagents were
much more expensive. In contrast, a cheap and environmen-
compounds.
There have been many successful examples
reported of their synthesis in recent years. For example, they
were obtained by ring-closing metathesis of acrylates,
catalytic addition–elimination reaction of (E)-3-butenoic acids
using selenium electrophiles, by photooxygenation of alkyl
substituted 2,3-dihydrofurans with singlet oxygen, or by the
reaction of lithiated 3-tosylpropanal dimethyl acetal with
carbonyl compounds followed by oxidation and elimination.
However, for the preparation of 2-nonen-4-olide, a simple,
efficient method still needs to be developed from the stand-
points of the availability of starting materials and catalysts,
atom economy, simplicity of operation and low cost.
1
5,16
by a
1
7
tally benign oxidant (H O ) was used in our route and the extra
2 2
1
8
elimination step took place smoothly in high yield.
The product synthesised was evaluated by sniffing blotter,
the 1% (w/w) sample solution in 1,2-propanediol showing an
oily, coconut-like and rancid odour. To avoid the disturbance
by a trace amount of impurity, the product was also evaluated
by GC-O, presenting a very similar odour to that by directly
smelling the sample on a blotter. Its characteristic odour is
very different to that of saturated nonan-4-olide, which has a
distinct coconut odour with a typical sweet creamy note.
1
9
Herein, an efficient sythesis of 2-nonen-4-olide 3 is reported
(
Scheme 1). 2-Nonen-4-olide 3 was obtained starting from
heptanal, via a three-step route which involved condensation
of malonic acid and heptanal, dihydroxylation and ring closure
Experimental
Malonic acid (AR) was purchased from Beijing Bailingwei Science
and Technology Company, and the other chemicals and solvents were
purchased from Beijing Huaxue Shiji Company. The NMR spectra
by HCO H, and elimination (Scheme 1). The odour of the
3
product was evaluated by GC-O ananlysis and sniffing blotter.
1
were obtained on a Bruker AV300 instrument ( H NMR at 300 MHz,
Results and discussion
Using a reported method, reaction of heptanal with malonic
13
C NMR at 75 MHz) using CDCl as solvent with TMS as internal
3
2
0
standard.
For GC-MS Chromatography an Agilent 6890N-5973i was used
under the following conditions: capillary column DB-5MS (30 m ×
acid in xylene catalysed by piperidine gave (E)-3-nonenoic
1
acid 1 in 82% yield. H NMR data indicated the formation of a
0
4
0
2
.25 mm × 0.25 µm); the oven temperature was programmed from
trace amount of the conjugated isomer, (E)-2-nonenoic acid.
The ratio of (E)-3-nonenoic acid to (E)-2-nonenoic acid
was 1:0.06. The product 1 containing a trace amount of (E)-2-
nonenoic acid was not purified further for the next step.
Optically active 2-nonen-4-olide has been obtained by Shar-
pless asymmetric dihydroxylation (AD) of (E)-3-nonenoate
−
1
0 to 280 °C at a rate of 20 °C min ; carrier gas, helium; flow rate,
−1
.8 mL min ; electron ionisation, 70 eV; ion source temperature,
30 °C.
GC-O analysis was carried out using an Agilent 6890N gas chro-
matograph installed with a capillary column DB-Wax (30 m × 0.25
mm × 0.25 µm, Agilent Technologies, Palo Alto, CA, USA), a FID
Scheme 1 Preparation of 2-nonen-4-olide.
*
Correspondent. E-mail: tianhy@btbu.edu.cn

4
96 JOURNAL OF CHEMICAL RESEARCH 2012
1
and a sniffing port (Sniffer 9000, Brechbühler Scientific Analytical
Solutions INC, Switzerland). The conditions were the same as those
in GC analysis. The column effluent was divided (ratio 1:1) between
the FID detector and the sniffing port through one “Y” shape glass
splitter. The effluent to the sniffing port was enclosed with a stream of
humidified air of 16 mL min and transferred to the glass detection
cone by one length of capillary column at the temperature of 220 °C.
Sniffings were carried out by a panel composed of three judges.
H NMR δ 0.89 (t, J = 6.9 Hz, 3H, Me), 1.31–1.33 (m, 4H, H-3′,4′),
1.46 (m, 2H, 2′), 1.65–1.77(m, 2H, H-1′), 5.03(m, 1H, H-4), 6.11 (dd,
13
J = 5.7, 1.5 Hz, 1H, H-2), 7.45(d, J = 5.7, 2.0 Hz, 1H, H-3); C NMR
δ 13.5 (C-5′), 22.0 (C-4′), 24.2 (C-2′), 31.0 ((C-3′), 32.7 (C-1′), 83.1
(C (4), 120.9 (C-2), 156.2 (C-3), 172.9 (C-1) (cf. ref. 17); GC/MS (EI)
−
1
+
m/z 154 (4, M ), 125 (72), 84 (100), 83(19), 55(15).
Financial support from the National Natural Science Founda-
tion of P. R. China (No. 31071610), Beijing Natural Science
Foundation Program and Scientific Research Key Program
of Beijing Municipal Commission of Education (KZ2011
10011015), the National Key Technology R&D Program
(2011BAD23B01) and PHR (IHLB) (No. PHR201008244 and
PHR20090504) is gratefully acknowledged.
Synthesis of (E)-3-nonenoic acid 1 from heptanal and malonic acid
To a refluxing mixture of malonic acid (15.6 g, 0.15 mol), piperidine
(
0.05 mL, 0.5 mmol) and xylene (100 mL), heptanal (5.7 g, 0.05 mol)
was slowly added during a period of 40 min. The reaction apparatus
was equipped with a Dean–Stark trap for the continuous removal of
water during the reaction. When no more water was separated, the
reaction was stopped. The reaction mixture was cooled to room tem-
perature and filtered to remove the unreacted malonic acid. Xylene
was removed under reduced pressure. The residue was distilled under
vacuum to give (E)-3-nonenoic acid 1 as a colourless oil (6.4 g, 82.0%
Received 24 May 2012; accepted 12 June 2012
Paper 1201332 doi: 10.3184/174751912X13402955389383
Published online: 8 August 2012
20
1
yield): b.p. 94–96 °C (0.4 KPa) [lit. b.p. 104–106 °C (1.5 mm)]. H
NMR δ 0.88 (t, J = 6.9 Hz, 3H, Me-9), 1.20–1.45 (m, 6H, H-6,7,8),
2
2
3
1
.02 (q, J = 6.2 Hz, 2H, H-5), 3.07 (d, J = 6.4 Hz, 2H, H-2), 5.54 (m,
H, H-3,4); C NMR δ 13.9 (C-9), 22.4 (C-8), 28.7 (C-6), 31.2 (C-7),
2.3 (C-5), 37.7 (C-2), 120.5 (C-4), 135.4 (C-3), 178.9 (C-1) (cf. ref.
7).
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