Microwave assisted synthesis of fragrant jasmone heterocyclic analogues

Article abstract of DOI:10.1016/j.ejmech.2005.09.012

cis-Jasmone, from jasmonoid group, is an important jasmine odor fragrance compound. The syntheses of new heterocyclic analogues of jasmone were described. Five analogues of this compound were prepared under microwave irradiation and the results of the microwave assisted syntheses were compared with classical, thermally initiated reactions in solvent. Microwave reactions were carried out successfully, and reaction times were significantly reduced to a few minutes. Three of five obtained analogues, pyrrolidinone, oxazolidinone and thiazolidinone demonstrated an interesting, specific odor which was compared with floral, typical jasmine odor of jasmone.

Full text of DOI:10.1016/j.ejmech.2005.09.012

European Journal of Medicinal Chemistry 41 (2006) 586–591
http://france.elsevier.com/direct/ejmech
Original article
Microwave assisted synthesis of fragrant
jasmone heterocyclic analogues
Anna Pawełczyk, Lucjusz Zaprutko *
Chair and Department of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland
Received 16 May 2005; received in revised form 1 September 2005; accepted 8 September 2005
Available online 24 March 2006
Abstract
cis-Jasmone, from jasmonoid group, is an important jasmine odor fragrance compound. The syntheses of new heterocyclic analogues of
jasmone were described. Five analogues of this compound were prepared under microwave irradiation and the results of the microwave assisted
syntheses were compared with classical, thermally initiated reactions in solvent. Microwave reactions were carried out successfully, and reaction
times were significantly reduced to a few minutes. Three of five obtained analogues, pyrrolidinone, oxazolidinone and thiazolidinone demon-
strated an interesting, specific odor which was compared with floral, typical jasmine odor of jasmone.
© 2006 Elsevier SAS. All rights reserved.
Keywords: cis-Jasmone; Heterocyclic analogues; Microwave synthesis; Fragrance compounds; Odor evaluation
1. Introduction
enzymes and stimulation of biosynthesis process. Besides, they
act as signal transducers in cellular response and regulate im-
portant vital functions, the growth for example [3–5] (Fig. 1).
cis-Jasmone (1) is one of the most important representatives
of jasmine fragrance which was isolated from jasmine absolute
[2]. Jasmine has a tonic effect on human organism, fosters bet-
ter concentrations and increases human ability to work. Jas-
mine is regarded as calming, antidepressant, antiseptic and
anti-inflammatory agent. This compound is produced on a
large scale by using synthetic methods; however, the manufac-
ture price is still very high [6]. Thus, research focused on find-
ing new, cheaper fragrance and structural analogues is to be
conducted. Many structural jasmone analogues which exhibit
interesting odor have been described in literature [3,7,8] but
according to our knowledge, odor of heterocyclic analogues,
containing heteroatom(s) in the ring have not been examined
yet. Now, the preparation of five jasmone heterocyclic analo-
gues with saturated chain and pyrrolidinone 7, oxazolidinone
8, pyrazolidinone 9, pyrazolinone 10a and thiazolidinone 11
cis-Jasmone (1) and methyl jasmonate (2), which belong to
jasmonoid group, are a well appreciated flower fragrances and
valuable perfume ingredient known since the ancient times.
Jasmine extract is mainly obtained from flowers of Jasminum
grandiflorum (Oleaceae) and contains a complex bouquet of
more than hundred volatiles comprising cis-jasmone at the
amount of 2–3%, together with methyl jasmonate, jasmolac-
tone, dihydrojasmone and trans-jasmone. All of these com-
pounds have to be considered as late metabolites of the same
lipid peroxidation process which begins with the conversion of
linolenic and linoleic acids. Jasmine oil is usually produced
from fresh flowers by means of the extraction process, known
as “enfleurage” [1–3]. cis-Jasmone has been found in the oils
of jonquil, orange flowers and also in different species of mint.
Jasmonoids exhibit not only characteristic fragrance properties
but they also play a key role as phytohormones in plants. These
compounds enable the plants to communicate with their sur-
roundings as well as generate defense responses against in-
sects. Jasmonoids are crucial in defense-related and develop-
mental processes occurring in plants e.g. the production of
* Corresponding author. Tel.: +48 61 8546 670; Fax: +48 61 4546 680.
Fig. 1. Structure of main jasmonoides.
E-mail address: zaprutko@amp.edu.pl (L. Zaprutko).
0223-5234/$ - see front matter © 2006 Elsevier SAS. All rights reserved.
doi:10.1016/j.ejmech.2005.09.012

A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 41 (2006) 586–591
587
rings are described. Their odor evaluations are presented also.
All of these compounds were obtained by using not only the
microwave assisted method but also the classical one. The use
of microwave irradiation to the synthesis of five-membered
heterocyclic compounds, which had a common structure know-
ing from many biologically important compounds, has become
very popular in the pharmaceutical field, due to the fact that it
is a new technology of drugs discovery and development. Mi-
crowave irradiation has been used to assist many organic
syntheses and it is known as a modern, highly yielding, envir-
onmental friendly and economical synthetic technique [9,10].
been carried out for 6–10 h [13], while the reaction under mi-
crowave irradiation required only 4 min [14]. The preparation
of oxazolidinone 4 from aminoalcohol and dimethyl carbonate
requires the removal of the alcohol appearing from the reaction
mixture. In the classical method it was accomplished by using
distillation method. It takes about 4 h at 100–140 °C [15] and
the final yield of oxazolidinone 4 was 78%. The application of
microwave irradiation was rather unsuccessful because reaction
time was not reduced significantly and even after 1 h under the
microwave irradiation the yield of final product was only 20%.
Heterocyclic compounds 3 and 4 under microwave irradia-
tion react remarkably fast with alkyl halide resulting respective
N-alkyl derivatives 7 and 8 with good yields. The yield of N-
alkylated pyrazolidinone 9, which had been obtained from 5,
was somewhat lower (38%) because apart from the main pro-
duct also by-products were formed in reaction conditions. Mi-
crowave alkylation reactions were performed in “solvent-free”
conditions with use of different solid supports: K2CO3,
K2CO3/KOH, SiO2/KOH. Optimal results were obtained in
the case of K2CO3/KOH mixture. The application of K2CO3
only required more time and was not always successful. The
addition of KOH is very advantageous to N-alkylation reaction
rate. Microwave reactions were carried out by simple mixing of
reagents, catalytic amount of TBAB as a phase transfer cata-
lyst, potassium carbonate and potassium hydroxide [16]. N-Al-
kylation in dry DMF solution was carried out at room tempera-
2. Results and discussion
2.1. Syntheses
Almost all jasmone analogues were prepared successfully
from acyclic compounds by connecting classical and micro-
wave assisted synthesis. Reactions were performed in two
steps: condensation and alkylation, except the thiazolidinone
analogue 11, which was obtained in one stage. Microwave re-
actions were carried out according to two optional procedures,
dependent on the type of reaction:
● N-alkylation and C-alkylation in “solvent-free” conditions;
● cyclocondensation in polar, high microwave absorbing sol-
vent solutions.
ture for 24–48
h [17]. The classical N-alkylation of
heterocyclic compounds bearing an acidic hydrogen atom at
tached to nitrogen is generally accomplished by the treatment
of these compounds with an appropriate base. An alternative is
to perform the reaction under phase transfer catalysis (PTC)
conditions. Classical N-alkylation is a time-consuming process
and results in a lower selectivity of reaction; while microwave
assisted alkylation on basic solid support is realized faster and
more efficiently.
The pyrazolone analogue 10a was synthesized from mono-
alkylated ethyl acetoacetate (6) and hydrazine hydrate in etha-
nolic solution. Classical reaction has been refluxed for 1–2 h
[12], while the application of microwave irradiation required
only 5–10 min (160 W). The 10a and 10b structures are tauto-
meric forms and according to the literature data [18], in polar
medium, the 10a structure is the more stable form. The sug-
gested structure of pyrazolinone analogue is confirmed by
The results of these microwave assisted reactions (MWA)
were compared with classical, thermally initiated ones
(Fig. 2).
Five heterocyclic derivatives of jasmone were obtained. The
structure and classical preparation of compounds 8 [11] and
odorless 10a [12] were described in the literature sources, but
in the case of compounds 7, 9 and 11 no data have been found.
Necessary reaction times for the microwave reactions pro-
ceeding were reduced significantly in comparison with the re-
spective times in conventional conditions. Microwave cyclo-
condensation of ethyl acrylate with methylhydrazine leading
to heterocyclic compound 5 was more efficient and much faster
than the appropriate reaction in conventional conditions, which
requires 24 h. Ethyl 2-acetylheptanoate (6) was prepared by C-
alkylation of ethyl acetoacetate. Classical C-alkylation has
Fig. 2. Formula picture.

588
A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 41 (2006) 586–591
Table 1
The results of heterocyclic jasmone analogues synthesis
Compound
Classical method
Temperature (°C) Time (h)
Microwave assisted method
Yield (%)
78
62
Temperature (°C) Power (W)
Time (min)
Yield (%)
–
4
5
6
7
8
9
10a
11
100–120
Reflux
Reflux
rt
rt
rt
4
24
–
–
–
5
4
4
4
4
5–10
5
78–80
100–105
100–105
100–105
100–105
80–82
60
160
400
450
450
450
160
160
72
83
90
54
38
58
85
6–10
24–48
24–48
24–48
1–2
56
Below 20
Below 20
Below 20
41
Reflux
60
15
58
rt: room temperature.
1
spectral data. The H-NMR spectra shows the broad singlet at
10.3 ppm which corresponds with two protons attached to ni-
trogen atoms. Besides, two signals at 100.79 and 136.33, char-
acteristic to unsaturated carbon atoms, were observed in 13C-
NMR spectra. The 10a structure can be additionally confirmed
by the optical rotation measurement. The lack of optical activ-
ity for this compound can be a proof of the absence of asym-
metrical carbon atoms in molecule of pyrazolone analogue.
It has been found that microwave irradiation is also applic-
able to synthesis of the thiazolidinone analogue 11. Until now,
one pot synthesis in toluene solution is a very popular proce-
dure that leads to thiazolidinone system [19]. In this paper,
microwave solventless thiazolidinone synthesis from pentyla-
mine, acetaldehyde and ethyl thioglycolate resulted in good
yields. The reaction time of this process was reduced signifi-
cantly from several dozen to 10 min in comparison with con-
ventional heating, but the main aim of the microwave techni-
que is to eliminate solvents, especially low polar solvents, and
replacing them with the more environmental friendly e.g. etha-
nol [20]. The obtained results and comparison of the main
parameters of syntheses for all compounds are presented in
Table 1.
The products were identified by some spectral methods. The
IR absorption bands at about 1600–1720 cm−1 indicate the pre-
sence of a carbonyl group, which is also confirmed on 13C-
NMR spectra as a signal at lower fields about 160–174 ppm.
The respective molecular ions [M+] were detected in the mass
spectra of all synthesized compounds. The fragmentation way
exhibited a loss of the one of CH3 groups as the first fragment
and subsequent loss of the alkyl side chain, which was cut step
by step. Optical rotation of final compounds 7, 8 and 11 with
asymmetric carbon atom were close to null. This indicates a
racemic structure of mentioned products, which is in agreement
with the racemic structure of substrates 3 and 4. (Scheme 1).
Scheme 1. Microwave synthesis of jasmone heterocyclic analogues.

A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 41 (2006) 586–591
589
2.2. Odor evaluation
3. Experimental protocols
The MWA were carried out using a microwave reactor
“Plazmatronika RM 800” with maximum power of 800 W,
the inert magnetic stirrer and the temperature control with IR
method. The progress of reaction and purity of products were
controlled with TLC method on silica gel plates (60 F254 from
Merck). The spots on the plates were visualized with UV meth-
od or developed by the use of iodine or Dragendorff reagent.
Jasmine fragrance compounds are very expensive materials.
The discovery of structure–odor correlation was very helpful in
projecting cheaper and more easily available jasmine-odor
compounds. Characteristic jasmine odor of jasmonates is deter-
mined by the presence of three different groups around a five-
membered carbon cycle: a strongly polar functional group e.g.
carbonyl function, an alkyl side chain (five or six carbon
atoms) and a weakly polar functional group e.g. lower alkyl
[21]. The unsaturated cis-double bond, presents in the alkyl
side chain in position 2 in jasmone, play very important role
in fragrance properties; odor of trans-jasmone and dihydrojas-
mone is less floral than cis-jasmone. Present investigation
showed the influence of the exchange of carbon(s) atom(s) on
heteroatom(s) e.g. nitrogen, oxygen and sulfur on olfactory
properties of obtained analogues.
Characteristic odor and odor durability of five heterocyclic
analogues of jasmone were examined and the results are de-
monstrated in Table 2. The majority of obtained compounds
exhibit specific olfactory properties. Their odors were com-
pared with typical jasmine floral, warm and spicy odor of cis-
jasmone. The 8 and 11 analogues are the strongest smelling
compounds. The 7 and 8 analogues demonstrate strong, sweet
coconut note. Compounds 7 and 11 exhibited jasmone note in
the background.
1
The H- and 13C-NMR spectra were recorded on a Varian Ge-
mini NMR-spectrometer (respectively, 300 and 75 MHz) in
CDCl3 or DMSO solutions. Chemical shifts are given in ppm
relative to tetramethylsilane (TMS) used as internal standard.
Infrared (IR) spectra were performed on a “Specord 71-IR” as
a film for liquid samples and as KBr tablets for solid samples
and were expressed in cm−1 scale. Mass spectra were recorded
on an AMD 402 spectrometer. Melting points were determined
in an open capillary and were uncorrected. Products purifica-
tion processes were performed with use of column chromato-
graphy method on silica gel 60 (70–230 mesh) and appropriate
solvent mixtures as an eluent. Solid product was purified in the
crystallization process. Analytical data of C, H, N assay for all
new compounds were within less than 0.3% of the theoretical
values and are in the good agreement with the proposed struc-
tures. Among five-membered heterocyclic ketones which were
used as substrates, the racemic 5-methyl pyrrolidinone 3 was
purchased from Aldrich as commercial product.
The original jasmine character was significantly decreased
for 7 and 11 analogues. Odor of 8 and 9 analogues lacked of
jasmine note. Compound 9 showed only very weak, not very
characteristic odor. Compound 10a was odorless.
3.1. Classical syntheses
The classical syntheses were carried out according to the
methods described in literature or with the use of some mod-
ifications of these procedures. Oxazolidinone 4 was prepared
from racemic 2-amino-1-propanol and dimethyl carbonate in
the presence of catalytic amount of sodium methoxide [15].
Pyrazolidinone 5 was prepared from ethyl acrylate and excess
of methylhydrazine in ethanolic solution [22,23]. Ethyl 2-acet-
ylheptanoate 6 was prepared by C-alkylation of ethyl acetoace-
tate using pentyl bromide in the presence of sodium ethoxide in
ethanolic solution [13]. Analogues 7–9 were prepared by N-
alkylation of appropriate heterocyclic compounds 3–5 using
pentyl bromide in dry dimethylformamide in the presence of
potassium carbonate in room temperature [16]. Pyrazolinone
10a was synthesized from 6 and hydrazine hydrate in ethanolic
solution [12]. Thiazolidinone 11 was prepared from pentyla-
mine, acetaldehyde and ethyl thioglycolate in one pot synthesis
We tried confronting the number and the kind of heteroa-
toms introduced into the cycle with fragrance properties of ob-
tained compounds. In the case of compounds which contain
two adjoin nitrogen atoms the odor is very weak (9) or has
not been detected (10a). On the other hand, the most intensive
odor has been observed for analogues comprising two different
heteroatoms in five-membered ring (8, 11) or only one heteroa-
tom (7). The 8 and 11 analogues have been characterized as the
most tenacious fragrances which exhibited high odor durabil-
ity. After 24 h the odor of these compounds is the more tena-
cious than odor of cis-jasmone.
In conclusion, the introduction of heteroatoms into the five-
membered ring was undesirable for both, the jasmine odor and
its intensity, but odor durability of the analogues 7, 8 and 11
was increased in comparison with cis-jasmone odor durability.
Table 2
Odor evaluation of jasmone analogue
Compound
Odor
Odor durability
After 1 h
++++
++++
+
After 6 h
+++
++++
–
After 24 h
7
8
9
Medium-intensive, sweet, reminiscent of jasmone with coconut note
Medium-intensive, tenacious, sweet, coconut, lack of jasmine odor
Weak, not characteristic
++
+++
–
10a
11
Odorless
–
–
–
+++
Intensive, strong, spicy, tenacious, with sulfuric note, weak jasmone
note in the background
++++
++++
cis-Jasmone
Intensive, floral, warm, typical jasmine
+++++
++++
+

590
A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 41 (2006) 586–591
according to the well known method used to form thiazolidi-
none ring [24].
hexane 1:1 as an eluent, yielding 0.46 g (54%) of 8 as colorless
oil. IR (film): ν = 1720. MS: m/z (rel. int. %) = 171 (6.5) [M+],
156 (46.3), 142 (36.4), 128 (6.6), 114 (100.0), 100 (8.1), 86
1
3.2. Microwave assisted syntheses
(21.3), 70 (49.5). H-NMR (CDCl3): δ = 0.90 (t, J = 6.9 Hz,
3H, CH3 in pentyl), 1.27 (d, J = 5.8 Hz, 3H, CH3), 1.30–1.39
(m, 4H, 2 × CH2), 1.47–1.60 (m, 2H, CH2), 3.00–3.09 (m, 1H,
N–CH2), 3.36–3.46 (m, 1H, N–CH2), 3.79–3.92 (m, 2H, H-5),
4.39 (t, J = 7.7 Hz, 1H, H-4). 13C-NMR (CDCl3): δ = 13.90
(CH3 in pentyl), 18.08 (CH3), 22.27/26.99/28.79 (3 × CH2),
41.49 (C-4), 50.71 (N–CH2), 68.80 (C-5), 158.12 (C=O).
[α]D20 = ~0°.
3.2.1. 1-Methyl-3-pyrazolidinone (5)
One gram (10 mmol) of ethyl acrylate and 0.69 g (15 mmol)
of methyl hydrazine was dissolved in 20 ml of ethanol. The
mixture was refluxed under microwave conditions with
160 W power of microwaves for 5 min. After concentration
in vacuo, the crude product was obtained as orange oil, which
was purified by a column chromatography using a mixture of
chloroform and ethanol 10:1 as an eluent, yielding 0.72 g
(72%) of pale yellow oil. Results of spectral and elemental
analysis were in agreement with the literature data [23].
3.2.5. 1-Methyl-2-pentyl-3-pyrazolidinone (9)
0.50 g (5 mmol) of 5 was N-alkylated as described above
for compound 7. The residued orange oil was purified by a
column chromatography, using a mixture of chloroform and
ethanol 10:1 as an eluent, yielding 0.32 g (38%) of 9 as yellow
oil. IR (KBr): ν = 1680. MS: m/z (rel. int. %) = 170 (100.0)
[M+], 155 (1.7), 141 (2.6), 127 (2.4), 113 (54.8), 99 (23.8),
3.2.2. Ethyl 2-acetylheptanoate (6)
0.65 g (5 mmol) of ethyl acetoacetate and subsequently
0.8 ml (6 mmol) of pentyl bromide were added to pulverized
mixture of 0.16 g (0.5 mmol) of tetrabutylammonium bromide
(TBAB), 3.59 g (26 mmol) of potassium carbonate and 0.39 g
(7 mmol) of potassium hydroxide. Reagents, in a flask with
condenser, were irradiated for 4 min with 450 W power of
microwaves. The product was extracted with ether and the ob-
tained organic solution was concentrated in vacuo. The resi-
dued yellow oil was purified by a column chromatography,
using a mixture of hexane and ether 6:1 as an eluent, yielding
0.83 g (83%) of colorless oil. All analytical data were in agree-
ment with the literature results [11].
1
85 (8.6), 70 (25.2), 57 (70.5). H-NMR (CDCl3): δ = 0.91 (t,
J = 6.9 Hz, 3H, CH3 in pentyl), 1.27–1.39 (m, 4H, 2 × CH2),
1.65–1.78 (m, 2H, CH2), 2.57 (m, 2H, H-4), 3.28 (s, 3H,
N–CH3), 3.47–3.56 (m, 2H, N–CH2), 3.79–3.88 (m, 2H, H-5).
13C-NMR (CDCl3): δ = 13.87 (CH3 in pentyl), 22.36/26.85/
28.66 (3 × CH2), 43.20 (CH3), 50.54 (C-5), 51.95 (N–CH2),
63.81 (C-4), 168.78 (C=O). [α]D20 = ~0°.
3.2.6. 3-Methyl-4-pentyl-5-pyrazolinone (10a)
0.50 g (10 mmol) of hydrazine hydrate was added to the
solution of 1.00 g (5 mmol) of 6 in ethanol. Reagents, in a
flask with condenser, were irradiated for 10 min with 160 W
power of microwaves. The obtained solution was concentrated
in vacuo, yielding 0.49 g (58%) of white crystals. The crude
product was purified by a crystallization from benzene, m.p.
198–200 °C (Ref. [12]: m.p. 186–187 °C). IR (film):
ν = 1600, MS: m/z (rel. int. %) = 168 (18.9) [M+], 153 (1.0),
139 (0.5), 125 (0.5), 111 (100.0), 97 (1.5), 83 (1.1), 68 (2.0),
3.2.3. 5-Methyl-1-pentyl-2-pyrrolidinone (7)
0.49 g (5 mmol) of 3 and subsequently 0.9 ml (7.5 mmol) of
pentyl bromide were added to pulverized mixture of 0.16 g
(0.5 mmol) of TBAB, 2.76 g (20 mmol) of potassium carbo-
nate and 1.12 g (20 mmol) of potassium hydroxide. Reagents,
in a flask with condenser, were irradiated for 4 min with
450 W power of microwaves. The crude product was extracted
with chloroform and the obtained organic solution was filtered
and concentrated in vacuo. The residued yellow oil was puri-
fied by column chromatography, using a mixture of chloroform
and ethanol 10:1 as an eluent, yielding 0.76 g (90%) of 7 as
pale yellow oil. IR (film): ν = 1680. MS: m/z (rel. int. %) = 169
(15.8) [M+], 154 (13.4), 140 (12.2), 126 (6.1), 112 (100.0), 98
(15.9), 84 (39.6), 67 (5.8), 55 (25.3), 41 (26.6). 1H-NMR
(CDCl3): δ = 0.91 (t, J = 7.0 Hz, 3H, CH3 in pentyl), 1.21 (d,
J = 6.3 Hz, 3H, CH3), 1.26–1.39 (m, 4H, 2 × CH2), 1.41–1.63
(m, 2H, CH2), 2.13–2.28 (m, 2H, H-4), 2.31–2.40 (m, 2H, H-
3), 2.89–2.96 (m, 1H, N–CH2), 3.52–3.62 (m, 1H, N–CH2),
3.67–3.76 (m, 1H, H-5). 13C-NMR (CDCl3): δ = 13.49 (CH3
in pentyl), 19.27 (CH3), 21.89/26.29/26.58 (3 × CH2), 26.59
(C-3), 29.83 (C-4), 39.42 (C-5), 57.73 (N–CH2), 174.12
(C=O). [α]D20 = ~0°.
1
55 (3.2), 41 (5.5). H-NMR (DMSO): δ = 0.85 (t, J = 7.0 Hz,
3H, CH3 in pentyl), 1.25–1.33 (m, 4H, 2 × CH2), 1.34–1.43
(m, 2H, CH2), 2.03 (s, 3H, CH3), 2.17 (t, J = 7.4 Hz, 2H,
H-1′), 10.31 (br s, 2H, NH). 13C-NMR (DMSO): δ = 9.87
(CH3), 14.03 (CH3 in pentyl), 21.33/22.03/29.57 (3 × CH2),
31.00 (C-1′), 100.79 (C-4), 136.33 (C-3), 159.82 (C=O).
[α]D20 = ~0°.
3.2.7. 2-Methyl-3-pentyl-4-thiazolidinone (11)
0.96 g (11 mmol) of n-pentylamine was cooled to 0 °C, and
mixed with 0.53 g (12 mmol) of acetaldehyde. The mixture
was stirred at room temperature under condenser. After 1 h
0.60 g (5 mmol) of ethyl thioglycolate (or thioglycolic acid)
was added. Reagents, were irradiated for 5 min with 160 W
power of microwaves in a flask with condenser. The obtained
product was dissolved in ethyl acetate, and solution was
washed successively with diluted hydrochloric acid and water,
it was subsequently dried with MgSO4 and concentrated in va-
cuo. The residued yellow oil was purified by a column chro-
matography, using a mixture of ethyl acetate and hexane 1:1 as
3.2.4. 4-Methyl-3-pentyl-2-oxazolidinone (8)
0.50 g (5 mmol) of 4 was N-alkylated as described above
for compound 7. The residued pale yellow oil was purified by
a column chromatography, using a mixture of ethyl acetate and

A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 41 (2006) 586–591
591
[2] D.H. Pybus, C.S. Sell, in: The Chemistry of Fragrances, RSC, Cam-
an eluent, yielding 0.79 g (85%) of 11 as pale yellow oil. IR
(film): ν = 1680. MS: m/z (rel. int. %) = 187 (51.9) [M+], 172
(100.0), 158 (2.7), 144 (3.4), 130 (13.6), 116 (6.5), 102 (61.0),
74 (12.0), 56 (15.2). 1H-NMR (CDCl3): δ = 0.90 (t, J = 7.0 Hz,
3H, CH3 in pentyl), 1.24–1.38 (m, 4H, 2 × CH2), 1.48–1.60
(m, 2H, CH2), 1.54 (d, J = 6.0 Hz, 3H, CH3), 2.97–3.07 (m,
1H, N–CH2), 3.52–3.60 (m, 1H, N–CH2), 3.61–3.70 (m, 2H,
H-5), 4.76 (q, J = 6.1 Hz, 1H, H-2). 13C-NMR (CDCl3):
δ = 13.96 (CH3 in pentyl), 23.17 (CH3), 22.32/26.86/28.93
(3 × CH2), 32.39 (C-2), 42.21 (C-5), 56.41 (N–CH2), 170.36
(C=O). [α]D20 = ~0°.
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