Microwave assisted synthesis of unsaturated jasmone heterocyclic analogues as new fragrant substances

Article abstract of DOI:10.1016/j.ejmech.2008.07.028

Taking the rising interest in jasmone structure based fragrant compounds into account it has been decided to take up an attempt to synthesize the new heterocyclic derivatives of this 2,3-disubstituted cyclopentenone, which could be characterized by the ability of interaction with the same receptors with which jasmone affects. Obtained structures of unsaturated heterocyclic derivatives are based on pyrrolidinone, oxazolidinone, pyrazolidinone, pyrazolone and thiazolidinone systems with 2-double or 2-triple unsaturated five-carbon side chain. The rapid, highly yielding and ecofriendly microwave assisted organic syntheses (MAOS) have been used to obtain compounds mentioned above. Odor evaluation and relationships between their structure and osmic properties for all synthesized fragrant compounds have been studied. It has been shown that the majority of the obtained compounds have exhibited interesting, very intensive and fixative fragrant properties.

Full text of DOI:10.1016/j.ejmech.2008.07.028

European Journal of Medicinal Chemistry 44 (2009) 3032–3039
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Short communication
Microwave assisted synthesis of unsaturated jasmone heterocyclic
analogues as new fragrant substances
*
Anna Pawe1czyk, Lucjusz Zaprutko
´
Chair and Department of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Taking the rising interest in jasmone structure based fragrant compounds into account it has been
decided to take up an attempt to synthesize the new heterocyclic derivatives of this 2,3-disubstituted
cyclopentenone, which could be characterized by the ability of interaction with the same receptors with
which jasmone affects. Obtained structures of unsaturated heterocyclic derivatives are based on pyrro-
lidinone, oxazolidinone, pyrazolidinone, pyrazolone and thiazolidinone systems with 2-double or 2-
triple unsaturated five-carbon side chain. The rapid, highly yielding and ecofriendly microwave assisted
organic syntheses (MAOS) have been used to obtain compounds mentioned above. Odor evaluation and
relationships between their structure and osmic properties for all synthesized fragrant compounds have
been studied. It has been shown that the majority of the obtained compounds have exhibited interesting,
very intensive and fixative fragrant properties.
Received 16 April 2008
Received in revised form 14 July 2008
Accepted 17 July 2008
Available online 26 July 2008
Keywords:
Jasmone
Heterocyclic analogues
Microwave assisted synthesis
Fragrant compounds
Odor evaluation
Ó 2008 Elsevier Masson SAS. All rights reserved.
1. Introduction
a large scale using synthetic methods; however, the cost of their
production is still very high. Thus, the search for cheaper fragrances
Jasmine extract is mainly obtained from jasmine flowers of the
species Jasminum grandiflorum from the olive family (Oleaceae).
The extract of jasmine flowers contains over 250 components. The
number and diversity of these compounds are enormous. In
the jasmine absolute in addition to benzyl alcohol, benzyl acetate,
linalool, indole, methyl anthranilate, also ketonic compounds, such
as jasmone and methyl jasmonate have been discovered. Those
carbonyl compounds, called jasmonoids, are derived from poly-
unsaturated fatty acids as a result of biosynthesis, which probably
proceeds in the same way as the biosynthesis of prostaglandins in
higher organisms. Jasmone is a well-known component of plant
volatiles and is a very important substance determining the odor
of jasmine flowers. This compound can be obtained from the
natural extract or by using different synthetic methods [1,3]. From
the chemical point of view, it is a 2,3-disubstituted derivative of
and new structural analogues of natural fragrant substances is
continued and many structural jasmone analogues exhibiting
interesting odor have been described [2,6,7]. New heterocyclic
furanone analogues of jasmone compounds with oxygen atom
introduced into the five-membered ring have been also developed
[8].
Recently, we have reported [9] microwave synthesis of some
fragrant structural jasmone heteroanalogues containing saturated
alkyl side chain with five-carbon atoms (Fig. 2).
It has been shown that saturated jasmone derivatives 3, 4 and 7
represented interesting, very intensive and long-lasting fragrant
properties such as aniseed, coconut and vanilla. Flower jasmine
note, characteristic of standard note of cis-jasmone, together with
structural correlation was also kept. Pyrazolidinone 5 showed very
weak odor, while odor of pyrazolone 6 was not detected. Now, the
preparation of series succeeding jasmone heterocyclic analogues
with pyrrolidinone, oxazolidinone, pyrazolidinone, pyrazolone
and thiazolidinone cycles and 2-unsaturated alkyl side chain is
described. Their odor evaluations are also investigated. The rapid,
highly yielding and ecofriendly microwave assisted organic
syntheses (MAOS) were used to obtain fragrant jasmone hetero-
analogues. The majority of microwave assisted reactions was con-
ducted in solvent-free conditions with the use of solid support or in
polar, highly microwave absorbing solvents.
cyclopentenone with 2-pentenyl side chain in
a-position to
carbonyl function [2–5]. The natural jasmine extract contains two
geometrical isomers of jasmone: cis-jasmone 1 and trans-jasmone
2 (Fig. 1).
The jasmine fragrances, in particular jasmonoids, are invaluable
in perfumery industry. These compounds are also produced on
* Corresponding author. Tel.: þ48 61 8546 670; fax: þ48 61 8546 680.
E-mail addresses: apaw@ump.edu.pl (A. Pawe1czyk), zaprutko@ump.edu.pl
(L. Zaprutko).
High-speed synthesis with microwaves has attracted a consid-
erable amount of attention in recent years [10]. Microwave assisted
0223-5234/$ – see front matter Ó 2008 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2008.07.028

A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 44 (2009) 3032–3039
3033
case of the synthesis of saturated heterocyclic jasmone analogues
3–7, we have compared the results of some of the microwave
assisted syntheses with classical, thermally initiated reactions in
organic solvent. Necessary reaction times for the microwave reac-
tion proceedings were reduced significantly in comparison with the
respective times in conventional conditions. The most of the reac-
tions were more efficient, much faster and generally more advan-
tageous than the appropriate classical reactions.
O
O
CH3
CH3
CH3
CH3
cis-jasmone
1
trans-jasmone
2
Almost all jasmone analogues were prepared successfully from
acyclic compounds with the use of new or known from literature
sources MAOS methods. Among heterocyclic ketones which were
used as substrates, only 5-methyl-2-pyrrolidinone (8) was
purchased from Aldrich as commercial product. First, compounds
necessary to obtain the planned heterocyclic derivatives such as 4-
methyl-2-oxazolidinone (9) [9,13], 1-methyl-3-pyrazolidinone (10)
[9,14], respective C-alkyl derivatives of ethyl acetylacetate 11–13
[9,15] and 2-mercaptoacetic acid amides 14–16 [16] were synthe-
sized. The preparation of oxazolidinone 9 from appropriate ami-
noalcohol and dimethyl carbonate requires the removal of the
alcohol appearing from the reaction mixture and it was accom-
plished by using distillation process [13]. Microwave cyclo-
condensation of ethyl acrylate with methylhydrazine in ethanolic
solution [9] was conducted during 10 min and has been leading to
heterocyclic pyrazolidinone 10.
Pyrrolidinones 17–19, oxazolidinones 20–22 and pyr-
azolidinones 23–25 were obtained as a result of N-alkylation
reaction of 8–10, according to the procedure described by Bogdal
et al. [16] with the use of appropriate alkyl bromide. Heterocyclic
pyrrolidinone 8 and oxazolidinone 9 under microwave irradiation
react remarkably fast (5 min) with alkyl halides, resulting respec-
tive N-alkyl derivatives with good yields. The yield of N-alkylated
pyrazolidinones 23–25, which have been obtained from 10, was
somewhat lower (25–33%) because apart from the main product,
dialkylated by-products were also formed in the reaction condi-
tions. Alkyl derivatives of ethyl acetylacetate 11–13 and 2-mer-
captoacetic acid amides 14–16 were cyclized under microwave
conditions. As a result of these processes, the 2-unsaturated in the
alkyl side chain heterocyclic analogues of jasmone 17–31 were
obtained.
Fig. 1. Isomers of natural jasmone.
chemistry is based on efficient heating of materials by ‘‘microwave
dielectric heating’’ effects and especially by two mechanisms:
dipolar polarization and ionic conduction. This phenomenon is
dependent on the ability of dielectric properties of reagents or
solvents to absorb microwave energy and convert it into heat [11].
Presently, most scientists agree that in the majority of cases the
reason for the observed rate enhancements are purely thermal/
kinetic effects, which are a consequence of high temperature that
can rapidly be attained when irradiating polar materials in
a microwave field. In addition to effects mentioned above, micro-
wave specific effects must also be considered e.g., superheating
effect of solvent at the atmospheric pressure, the selective heating
of selected reaction components, the molecular radiators forma-
tion, the elimination of wall effects caused by inverted temperature
gradients compared to classical heating [11,12]. The main benefits
of performing reaction under microwave irradiation conditions are
the significant rate enhancements and higher product yields that
can frequently be observed.
2. Results and discussion
2.1. Chemistry
The series of unsaturated heterocyclic analogues of jasmone
with 2-double and 2-triple unsaturated five-carbon side chain was
prepared. Obtained structures of unsaturated heterocyclic deriva-
tives are based on pyrrolidinone, oxazolidinone, pyrazolidinone,
pyrazolone and thiazolidinone systems, which contain one or two
heteroatoms in the five-membered ring, such as nitrogen, oxygen
or sulfur and also 2-trans-pentenyl, 2-cis-pentenyl and 2-pentynyl
side chain (Fig. 2).
Microwave assisted reactions were optimized and adjusted to
obtain planned products, and also introduction of different modi-
fications was indispensable in many cases, not only displacement of
conventional reaction to microwave conditions. Recently [9], in the
A majority of compounds used as factors supplying character-
istic for jasmine five-carbon chains were purchased as commercial
products. However, in order to obtain full structural analogy to
natural jasmone which contains 2-cis-pentenyl substituent, the
commercially not available 1-bromo-2-cis-penten was prepared.
This compound was synthesized from 2-cis-penten-1-ol on the way
of the substitution reaction of hydroxyl function by bromide atom
with the use of PBr3, in the mixture of petroleum ether and pyridine
[17,18].
O
O
O
O
O
R
R
R
R
R
N
N
HN
HN
6, 26-28
O
N
N
N
S
CH3
CH3
CH3
CH3
CH3
3, 17-19
4, 20-22
5, 23-25
7, 29-31
-n
3, 4, 5, 6, 7; R =
17, 20, 23, 26, 29; R =
18, 21, 24, 27, 30; R =
CH2CH2CH2CH2CH3
-trans-CH CH=CHCH CH
3
2
2
-cis-CH CH=CHCH CH
2
2
3
-CH C CCH2CH3
19, 22, 25, 28, 31; R =
2
Fig. 2. Structures of heterocyclic derivatives of jasmone.

3034
A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 44 (2009) 3032–3039
Microwave alkylation processes were performed for about
Purity of final compounds was determined with the use of thin layer
chromatography (TLC) method. The fundamental physico-chemical
properties, such as boiling or melting point and optical rotationwere
also measured. Optical rotation of pyrrolidinones, oxazolidinones
and thiazolidinones which can contain asymmetric carbon atom
was close to null. This indicates racemic structure of the products,
which is in agreement with racemic structure of substrates used.
5 min in solvent-free conditions usually with the use of equimolar
mixture of K2CO3/KOH as a solid support and catalytic amount of
tetrabutylammonium bromide (TBAB).
Pyrazolone analogues 26–28 were synthesized by the cyclo-
condensation reactions of obtained C-alkyl derivatives of ethyl
acetylacetates 11–13 with hydrazine hydrate in ethanolic solution
for about 10 min [9,19]. Respective alkyl derivatives of ethyl ace-
tylacetate such as ethyl 2-acetyl-4-heptenoates (11,12) and ethyl
2-acetyl-4-heptynoate (13) were prepared by C-alkylation of ethyl
acetylacetate with the use of 2-unsaturated alkyl bromides under
microwave irradiation and required solvent-free condition with the
use of K2CO3 as a solid support for 4 min. According to the literature
sources [20] pyrazolone compounds exhibit tautomerism ability.
The suggested structure of pyrazolone analogues was confirmed by
spectral data. The 1H NMR spectra shows the broad bands at 9.5–
11.2 ppm which correspond with two protons attached to nitrogen
atoms. Besides, two signals at the range 98–137 ppm, characteristic
to unsaturated carbon atoms, were observed in 13C NMR spectra.
This structure can be additionally confirmed by the optical rotation
measurement. The lack of optical activity for these compounds can
be a proof of the absence of asymmetric carbon atom in molecule of
pyrazolone analogues.
It has been found that microwave irradiation is also successfully
applicable to synthesis of the thiazolidinone compounds. Until
now, one pot synthesis in toluene solution has been a very popular
procedure that leads to thiazolidinone system [21]. Recently, we
have reported [9] microwave solvent less thiazolidinone synthesis
from pentylamine, acetaldehyde and ethyl 2-mercaptoacetate
resulted in good yields. The reaction time of this process was
significantly reduced from hours to 10 min relatively to conven-
tional heating. It has not managed to employ formula cited above to
synthesis of thiazolidinones with unsaturated side chain, because
appropriate unsaturated pentylamines induced great synthetic
difficulties. Thiazolidynone derivatives 29–31 were obtained as
a result of cyclocondensation of acetaldehyde with mono-alkylated
2-mercaptoacetamide derivatives 14–16. First, five-carbon chains
were introduced into acyclic amide of 2-mercaptoacetic acid by the
use of general N-alkylation process [16] and next the obtained
N-mono-substituted amides were reacted with acetaldehyde,
yielding final disubstituted thiazolidinones. Amide alkylation with
the use of appropriate alkyl bromide realized both in classical and
microwave conditions was processed very fast but not selective.
Many of the alkylated derivatives of 2-mercaptoacetamide were
found in the reaction mixture. The mono-alkylated derivatives
were separated using chromatography method. Microwave cyclo-
condensation process was carried in solvent-free conditions with
the use of montmorilonite K10-clay and catalytic amount of
p-toluenesufonic acid. General synthesis methods of all prepared
compounds were presented on Scheme 1.
2.2. Odor evaluation
‘‘Jasmine chemistry’’ is a very dynamically developing direction
of organic chemistry and research focused on finding cheaper
synthesis methods of jasmone [3] and other jasmine odor
compounds or new fragrance and structural analogues of natural
fragrant substances are to be conducted [2]. Lately [9], we have
examined fragrant properties of saturated structural jasmone het-
eroanalogues. The present investigation has shown fragrant prop-
erties of series of following new, unsaturated structural and
functional heterocyclic analogues of natural jasmone. Structural
similarity gets through introduction of one or two heteroatoms into
the five-membered cycle of jasmone molecule or its closest
analogues. It is known that usually heterocyclic analogues of
natural origin substances show interesting properties, which often
are similar to their mother substances but differently directed. It
also has been observed in the case of jasmone heteroanalogues. The
influence of the exchange of carbon(s) atom(s) on heteroatom(s)
e.g., N, O and S on olfactory properties of obtained analogues was
examined. Chemical modifications of 2-unsaturated side chain
were also in question. Organoleptic analysis of the odor and rela-
tionships between their structure and osmic properties for all
fragrant compounds were performed. Their odors were compared
with typical jasmine floral, warm and spicy odor of cis-jasmone.
Characteristics of the odor and odor durability of these heterocyclic
jasmone derivatives were presented in Table 1. It has been shown
that the majority of the obtained compounds were exhibited
interesting, very intensive and extremely durable odor, in some
cases considerably exceeding durability odor of jasmone, such as
aniseed, coconut and vanilla. In many cases, flower jasmine note,
characteristic for standard odor of cis-jasmone, together with
structural correlation was also kept. Pyrrolidinones (17–19), oxa-
zolidinones (20–22) and thiazolidinones (29–31) exhibited the
most interesting osmic properties, while pyrazolidinones (23–25)
and pyrazolones (26–28) showed very weak odor or were odorless.
This new group of obtained fragrances, despite close structural
correlation with jasmone, represents new, somewhat different odor
notes respectively to standard jasmone. Most probably the
heteroatoms which have been introduced into five-membered ring
are responsible for these interesting and specific olfactory proper-
ties. As a result of conduced sensory analysis it has been found that
most of the received compounds exhibited interesting fragrant
properties. Based on the group of obtained fragrant compounds it
takes attempts to coherence of their structural and osmic features,
the influence of exchanging one or two carbon atoms in five-
membered cycle on heteroatoms such as: N, O or S and also influ-
ence their amount and kinds of fragrant impressions. In the case of
compounds which contain two adjoining nitrogen atoms the odor
is very weak and not characteristic or has not been detected. It was
observed in pyrazolidinones (23–25) and pyrazolones (26–28). On
the other hand, the most intensive and durable odors were
exhibited by compounds including two different heteroatoms in
the ring, such as oxazolidinones (20–22) with nitrogen and oxygen
atoms and thiazolidinones (29–31) with nitrogen and sulfur atoms
in the ring. The pyrrolidinones, containing only one heteroatom,
exhibited quite interesting fragrant properties also. A similar odor-
structure correlation was observed in the case of saturated
heterocyclic derivatives of jasmone (3–7) [9]. Odor of selected
The obtained products were identified by some spectral
methods. The IR absorption bands at about 1600–1720 cmꢀ1 indi-
cate the presence 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 [Mþ] were detected in the mass spectra of
all synthesized compounds. The fragmentationwayexhibited by the
loss of one of the CH3 groups as the first fragment and subsequent
loss of the fragments of alkyl side chain. In the recorded spectra,
except characteristic signals for appropriate heterocyclic moiety,
signals of characteristic 2-unsaturated side chains were also
observed. Carbon signals for 2-pentenyl group CH]CH were
observed as well at the range of 120–140 ppm and in case of
2-pentynyl group C^C at the range of 70–85 ppm. Additionally,
proton signals at the range of 5.0–6.0 ppm for CH]CH were well
affirmed byappropriate carbon signals on 13C NMR spectra. All of the
prepared compounds were submitted sufficient spectral analysis.

A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 44 (2009) 3032–3039
3035
O
O
+
OCH2CH3
OCH3
NH2
H3CO
HO
CH2
+
NH2
NH
CH3
CH3
EtOH
CH3ONa
O
O
O
O
O
NH
O
CH3CH2O
NH
NH
NH2
N
SH
O
CH3
CH
9
8
CH3
CH3
10
3
RBr
TBAB
K2CO3
KOH
K2CO3
KOH
K2CO3
KOH
K2CO3
KOH
K2CO3
O
O
R
R
CH3CH2O
NH
SH
O
CH3
14-16
11-13
CH3CHO
K10
p-TsOH
NH2NH2
EtOH
O
O
O
O
O
R
N
R
R
N
R
R
O
N
HN
N
S
29-31
HN
26-28
N
CH3
CH3
CH3
CH3
23-25
CH3
20-22
17-19
11, 14, 17, 20, 23, 26, 29; R = -trans-CH2CH=CHCH2CH3
12, 15, 18, 21, 24, 27, 30; R = -cis-CH2CH=CHCH2CH3
CCH2CH3
13, 16, 19, 22, 25, 28, 31; R = -CH2C
Scheme 1. Microwave assisted synthesis of unsaturated heteroanalogues of jasmone.
compounds is more durable than odor durability of pattern jas-
mone after 24 h, but odor of pyrrolidinone 18 and oxazolidinone 21
is smelt after 6 days even.
decline or decrease of floral-jasmine odor participation. However,
a new spicy and burned note appeared.
Taking structure–odor relationship into consideration, the
structural modifications in five-carbon, 2-unsaturated alkyl side
chain must be also pointed out. The introduction of double bond for
classic, low molecular weight ketones usually results in the
increase of intensity of odor which sometimes accompanied by
spicy note, but with increase of molecular weight, the spicy odor
character was vanished and floral note was appeared [22]. The
unsaturated cis-double bond, present in the alkyl side chain in
position 2 in natural cis-jasmone plays very important role in
fragrance properties; odor of trans-jasmone and dihydrojamone is
less floral than cis-jasmone [2]. The introduction of double bond
into heterocyclic jasmone analogues, both cis and trans, leads to the
increase of odor intensity relatively to their saturated hetero-
analogues. Presence of triple bond in the structure of compounds
resulted in the increase of spicy and diffusivity of odor and also in
3. Experimental protocols
3.1. General
The microwave assisted reactions were carried out using
a microwave reactor PLAZMATRONIKA RM 800 with operating
frequency 2.45 GHz, maximum power of microwave 800 W and
equipped with the inert magnetic stirrer, the temperature control
through IR sensor, the post-reaction cooling system, the module for
small-scale experiments (below 30 ml), the computer software
control system. 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 method or
developed by the use of iodine vapour or Dragendorff reagent.
The 1H and 13C NMR spectra were recorded on a Varian Gemini

3036
A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 44 (2009) 3032–3039
Table 1
Odor evaluation of 2-unsaturated jasmone heteroanalogues
Compound
Jasmone
Odor
Int.a
3
Odor durability
1 h
6 h
24 h
Remarks
Floral, warm, typical jasmine
þþþþþ
þþþþ
þ
Pyrrolidinones
17
18
19
Floral, aniseed, with lightly cucumber note, reminiscent of cis-jasmone
Floral, aniseed, reminiscent of cis-jasmone, very intensive
First note lightly acidic and burned, the next reminiscent of cis-jasmone
2
3
2
þþþþ
þþþþþ
þþþþ
þþþ
þþþþ
þþ
þþ
þþþ
þ
Smelt after 6 days
Smelt after 6 days
Oxazolidinones
20
21
22
Sweet with aniseed, coconut and vanilla note, the lack of jasmine character
Sweet with coconut, vanilla and caramel note, then jasmine-floral, very intensive
First note lightly acidic and burned, the next reminiscent of cis-jasmone
3
3
2
þþþþþ
þþþþþ
þþþ
þþþ
þþþþ
þþ
þþ
þþþ
þ
Pyrazolidinones
23–25
Very weak, not characteristic
Odorless
–
–
þ
–
–
–
–
Pyrazolones
26–28
–
Thiazolidinones
29
30
31
With significant floral-jasmine note, weak fatty, aniseed and pepper
With significant floral-jasmine note, spicy, aniseed and pepper
Lightly acidic, spicy, then reminiscent of cis-jasmone
3
3
2
þþþþþ
þþþþþ
þþ
þþþ
þþþþ
þþ
þþ
þþþ
þ
a
Int. – odor intensity respective to cis-jasmone; 1 – weak, 2 – moderate, 3 – strong.
NMR-spectrometer (resp. 300 and 75 MHz) in CDCl3 or DMSO
solutions. Chemical shifts are given in parts per million, relatively 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
3.2.1.1.1. 5-Methyl-1-(2-trans-pentenyl)-2-pyrrolidinone (17). To
the mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and
1.12 g of potassium hydroxide 0.49 g of 8 and subsequently 1.12 g of
1-bromo-2-trans-pentene were added. Reagents were irradiated in
the microwave reactor. The crude product was purified by a column
chromatography, using a mixture of chloroform and ethanol 10:1 as
an eluent, yielding 0.80 g (94%) of 17 as pale yellow oil (b.p. 262–
266 ꢁC). Rf ¼ 0.71 (chloroform:ethanol 10:1). MS, m/z (%): 167 (35)
[Mþ], 152 (28), 138 (82), 125 (9), 112 (57); 98 (92), 84 (100), 69 (97),
cmꢀ1 scale. Mass spectra were recorded on an AMD 402 spec-
20
trometer (70 eV, EI). The optical rotation [
a]
was measured on
D
a PERKIN–ELMER 242B polarimeter using 1 dm glass tube at
wavelength
l
¼ 598
m
m. Melting and boiling points were deter-
¨
mined with the use of certified apparatus BUCHI B-545 with warm-
up time 1 ꢁC/min. Melting points were automatically determined in
an open melting point capillary and were uncorrected. Boiling
points were determined with sample observation in an open
boiling point tubes with plunged capillaries. Product purification
processes were performed with the use of column chromatography
method on silica gel 60 (70–230 mesh) and appropriate solvent
mixtures as an eluent. Solid products were purified in the crystal-
lization process. Analytical data of C, H, N assays for all new
compounds were analyzed on a VARIO EL III elementary analyzer
and were within less than ꢂ0.3% of the theoretical values. The
results were in the good agreement with the proposed structures.
56 (49). IR (cmꢀ1): 1685 (
n
C]O). 1H NMR (CDCl3):
d
¼ 0.98 (t,
J ¼ 7.5 Hz, 3H, CH3-50), 1.19 (d, J ¼ 6.0 Hz, 3H, CH3), 1.56–1.62 (m, 2H,
CH2-4), 2.02–2.10 (m, 2H, CH2-40), 2.13–2.22 (m, 2H, CH2-3), 2.25–
2.41 (m, 1H, CH2-10), 3.41–3.50 (m, 1H, CH2-10), 3.64–3.74 (m, 1H,
CH-5), 5.27–5.37 (m, 1H, trans-CH]), 5.62–5.72 (m, 1H, trans-
CH]). 13C NMR (CDCl3):
d
¼ 13.32 (CH3), 22.04 (CH3-50), 25.26 (C-
40), 31.28 (C-3), 32.93 (C-4), 38.63 (C-5), 67.78 (C-10), 123.47/135.97
20
(trans-CH]CH), 170.20 (C]O). C10H17NO (167.2). [
a]
¼ w0ꢁ.
D
3.2.1.1.2. 5-Methyl-1-(2-cis-pentenyl)-2-pyrrolidinone (18). To
the mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and
1.12 g of potassium hydroxide 0.49 g of 8 and subsequently 1.12 g of
1-bromo-2-cis-pentene were added. Reagents were irradiated in
the microwave reactor. The crude product was purified by a column
chromatography, using a mixture of chloroform and ethanol 10:1 as
an eluent, yielding 0.65 g (78%) of 18 as pale yellow oil (b.p. 266–
270 ꢁC). Rf ¼ 0.76 (chloroform:ethanol 10:1). MS, m/z (%): 167 (34)
[Mþ], 152 (27), 138 (82), 125 (9), 112 (58), 98 (91), 84 (100), 69 (98),
3.2. Microwave assisted synthesis (MAOS)
Based on our earlier experiences [9], conditions of reactions
conducted have been optimized both in the view of microwave
power and reaction time as well as a composition of solid support.
56 (49). IR (cmꢀ1): 1685 (
n
C]O). 1H NMR (CDCl3):
d
¼ 0.99 (t,
J ¼ 7.5 Hz, 3H, CH3-50),1.20 (d, J ¼ 6,3 Hz, 3H, CH3), 1.55–1.64 (m, 2H,
CH2-4), 2.02–2.11 (m, 2H, CH2-40), 2.13–2.27 (m, 2H, CH2-3), 2.32–
2.49 (m, 1H, CH2-10), 3.59–3.73 (m, superimposed bands: 1H (CH-5)
and 1H (CH2-10)), 5.21–5.37 (m, 1H, cis-CH]), 5.51–5.72 (m, 1H, cis-
3.2.1. Synthesis of pyrrolidinone, oxazolidinone and pyrazolidinone
heteroanalogues of jasmone
3.2.1.1. General procedure for N-alkylation of compounds 8–10. To
the pulverized mixture of 0.5 mmol of TBAB, 20 mmol of potassium
carbonate and 20 mmol of potassium hydroxide, 5 mmol of
respective azole (8, 9 or 10) and subsequently 7.5 mmol of appro-
priate 2-unsaturated pentyl bromide were added. Reagents, in
a calibrated flask (transparent to microwave irradiation) with
condenser, were irradiated for 4 min with 450 W power of micro-
waves. The crude product was extracted two times with the use of
20 ml of methylene chloride and the obtained organic solution was
filtered and concentrated in vacuo. The residued crude oil was
purified by a column chromatography, with the use of appropriate
eluent, yielding pure product.
CH]). 13C NMR (CDCl3):
d
¼ 13.60 (CH3), 22.18 (CH3-50), 25.28 (C-
40), 31.52 (C-3), 32.97 (C-4), 38.57 (C-5), 67.72 (C-10), 123.39/134.12
20
(cis-CH]CH), 171.20 (C]O). C10H17NO (167.2). [
a
]
¼ w0ꢁ.
D
3.2.1.1.3. 5-Methyl-1-(2-pentynyl)-2-pyrrolidinone (19). To the
mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and 1.12 g
of potassium hydroxide, 0.49 g of 8 and subsequently 1.10 g of 1-
bromo-2-pentyne were added. Reagents were irradiated in the
microwave reactor. The crude product was purified by a column
chromatography, using a mixture of chloroform and ethanol 10:1 as
an eluent, yielding 0.72 g (87%) of 19 as pale yellow oil (b.p. 281–
285 ꢁC). Rf ¼ 0.66 (chloroform:ethanol 10:1). MS, m/z (%): 165 (32)

A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 44 (2009) 3032–3039
3037
[Mþ], 150 (58), 136 (6), 124 (19), 112 (25), 98 (27), 84 (100), 70 (23),
Rf ¼ 0.66 (chloroform:ethanol 10:1). MS, m/z (%): 168 (16) [Mþ], 153
55 (46), 41 (51). IR (cmꢀ1): 1685 (
n
C]O). 1H NMR (CDCl3):
d
¼ 1.12
(1), 139 (10), 126 (1), 113 (100), 99 (23), 85 (7), 69 (20), 57 (47). IR
(t, J ¼ 7.5 Hz, 3H, CH3-50), 1.25 (d, J ¼ 6.6 Hz, 3H, CH3), 1.45–1.58 (m,
1H, CH2-40), 2.13–2.25 (m, superimposed bands: 2H (CH2-4) and 1H
(CH2-40)); 2.52–2.74 (m, 2H, CH2-3), 3.80–3.87 (m, 2H, CH2-10),
(cmꢀ1): 1660 (
n
C]O). 1H NMR (CDCl3):
d
¼ 0.90 (t, J ¼ 6.9 Hz, 3H,
CH3-50), 1.87–1.99 (m, 2H, CH2-40), 2.58–2.67 (m, 2H, CH2-4), 3.30 (s,
3H, CH3), 3.45–3.54 (m, 2H, CH2-10), 3.79–3.88 (m, 2H, CH2-5), 5.22–
5.29 (m, 1H, trans-CH]), 5.58–5.64 (m, 1H, trans-CH]). 13C NMR
4.04–4.16 (m, 1H, CH-5). 13C NMR (CDCl3):
d
¼ 12.52 (CH3), 13.77
(CH3-50), 19.64 (C-40), 22.02 (C-3), 31.39 (C-4), 38.36 (C-5), 67.97
(CDCl3):
d
¼ 13.98 (CH3-50), 22.47 (C-40), 43.20 (CH3), 50.54 (C-5),
(C-10), 74.07/84.89 (C^C), 170.10 (C]O). C10H15NO (165.1).
58.97 (C-4), 65.18 (C-10), 121.68/136.57 (trans-CH]CH), 167.64
20
20
[
a]
¼ w0ꢁ.
(C]O). C9H16N2O (168.1). [
a]
¼ w0ꢁ.
D
D
3.2.1.1.4. 4-Methyl-3-(2-trans-pentenyl)-2-oxazolidinone (20). To
3.2.1.1.8. 1-Methyl-2-(2-cis-pentenyl)-3-pyrazolidinone (24). To
the mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and
1.12 g of potassium hydroxide, 0.50 g of 10 and subsequently 1.12 g
of 1-bromo-2-cis-pentene were added. Reagents were irradiated in
the microwave reactor. The crude product was purified by a column
chromatography, using a mixture of chloroform and ethanol 10:1 as
an eluent, yielding 0.25 g (30%) of 24 as yellow oil (b.p. 219–225 ꢁC).
Rf ¼ 0.70 (chloroform:ethanol 10:1). MS, m/z (%): 168 (10) [Mþ], 153
(5), 139 (13), 126 (2), 113 (70), 99 (100), 85 (9), 69 (22), 57 (41). IR
the mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and
1.12 g of potassium hydroxide 0.50 g of 9 and subsequently 1.12 g of
1-bromo-2-trans-pentene were added. Reagents were irradiated in
the microwave reactor. The crude product was purified by a column
chromatography, using a mixture of hexane and ethyl acetate 1:1 as
an eluent, yielding 0.73 g (85%) of 20 as colorless oil (b.p. 294–
299 ꢁC). Rf ¼ 0.67 (hexane:ethyl acetate 1:1). MS, m/z (%): 169 (26)
[Mþ], 154 (11), 140 (84), 127 (2), 114 (78), 100 (6), 86 (17), 70 (23), 69
(36), 56 (36), 41 (100). IR (cmꢀ1): 1685 (
d
n
C]O). 1H NMR (CDCl3):
(cmꢀ1): 1670 (
n
C]O). 1H NMR (CDCl3):
d
¼ 1.10 (t, J ¼ 6.9 Hz, 3H,
¼ 0.99 (t, J ¼ 7.5 Hz, 3H, CH3-50), 1.25 (d, J ¼ 6.0 Hz, 3H, CH3), 2.01–
CH3-50), 2.17–2.23 (m, 2H, CH2-40), 2.62–2.68 (m, 2H, CH2-4), 3.32
(s, 3H, CH3), 3.40–3.51 (m, 2H, CH2-10), 3.81–3.92 (m, 2H, CH2-5),
5.25–5.31 (m,1H, cis-CH]), 5.59–5.65 (m,1H, trans-CH]). 13C NMR
2.16 (m, 2H, CH2-40), 3.52–3.60 (m, 1H, CH2-10), 3.79–3.93 (m,
superimposed bands: 1H (CH2-10) and 2H (CH2-5)), 4.40 (t,
J ¼ 7.7 Hz, 1H, CH-4), 5.32–5.42 (m, 1H, trans-CH]), 5.58–5.79 (m,
(CDCl3):
d
¼ 13.86 (CH3-50), 22.52 (C-40), 43.45 (CH3), 50.87 (C-5),
1H, trans-CH]). 13C NMR (CDCl3):
d
¼ 12.81 (CH3), 17.46 (CH3-50),
59.03 (C-4), 65.23 (C-10),121.88/136.67 (cis-CH]CH),167.87 (C]O).
20
24.62 (C-40), 43.15 (C-4), 49.89 (C-10), 68.34 (C-5), 121.94/136.03
C9H16N2O (168.1). [
a]
¼ w0ꢁ.
D
20
(trans-CH]CH), 157.16 (C]O). C9H15NO2 (169.0). [
a]
¼ w0ꢁ.
3.2.1.1.9. 1-Methyl-2-(2-pentynyl)-3-pyrazolidinone (25). To the
mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and 1.12 g
of potassium hydroxide 0.50 g of 10 and subsequently 1.10 g of 1-
bromo-2-pentyne were added. Reagents were irradiated in the
microwave reactor. The crude product was purified by a column
chromatography, using a mixture of chloroform and ethanol 10:1 as
an eluent, yielding 0.20 g (25%) of 25 as yellow oil (b.p. 234–
240 ꢁC). Rf ¼ 0.63 (chloroform:ethanol 10:1). MS, m/z (%): 166 (2)
[Mþ], 151(3), 137 (6), 125 (3), 113 (100), 99 (11), 81 (41), 67 (25). IR
D
3.2.1.1.5. 4-Methyl-3-(2-cis-pentenyl)-2-oxazolidinone (21). To
the mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and
1.12 g of potassium hydroxide 0.50 g of 9 and subsequently 1.12 g of
1-bromo-2-cis-pentene were added. Reagents were irradiated in
the microwave reactor. The crude product was purified by a column
chromatography, using a mixture of hexane and ethyl acetate 1:1 as
an eluent, yielding 0.61 g (73%) of 21 as colorless oil (b.p. 297–
302 ꢁC). Rf ¼ 0.76 (hexane:ethyl acetate 1:1). MS, m/z (%): 169 (28)
[Mþ], 154 (14), 140 (85), 127 (3), 114 (100), 100 (9), 86 (25), 70 (41),
(cmꢀ1): 1680 (
n
C]O). 1H NMR (CDCl3): 0.92 (t, J ¼ 7.0 Hz, 3H, CH3-
69 (70), 56 (60). IR (cmꢀ1): 1685 (
n
C]O). 1H NMR (CDCl3):
d
¼ 1.00
50), 1.85–1.97 (m, 2H, CH2-40), 2.54–2.65 (m, 2H, CH2-4), 3.33 (s, 3H,
CH3), 3.81–3.92 (m, superimposed bands: 2H (CH2-10) and 2H (CH2-
(t, J ¼ 7.5 Hz, 3H, CH3-50), 1.26 (d, J ¼ 6.0 Hz, 3H, CH3), 2.01–2.19 (m,
2H, CH2-40), 3.72–3.90 (m, superimposed bands: 1H (CH2-10) and
2H (CH2-5)), 4.01–4.12 (m, 1H, CH2-10), 4.39 (t, J ¼ 7.5 Hz, 1H, CH-4),
5.28–5.42 (m, 1H, cis-CH]), 5.57–5.78 (m, 1H, cis-CH]). 13C NMR
5)). 13C NMR (CDCl3):
50.91 (C-5), 60.23 (C-4), 65.76 (C-10), 75.62/77.31 (CH^CH), 168.03
(C]O). C9H14N2O (166.1). [
d
¼ 13.89 (CH3-50), 22.63 (C-40), 43.53 (CH3),
20
a]
¼ w0ꢁ.
D
(CDCl3):
d
¼ 13.82 (CH3), 17.83 (CH3-50), 24.86 (C-40), 43.45 (C-4),
50.27 (C-10), 68.65 (C-5),122.31/135.85 (cis-CH]CH),157.74 (C]O).
3.2.2. Synthesis of pyrazolone heteroanalogues of jasmone
Compounds 11–13, necessary to obtain pyrazolone hetero-
analogues, were prepared according to the method described
earlier [9].
20
C9H15NO2 (169.1). [
a]
¼ w0ꢁ.
D
3.2.1.1.6. 4-Methyl-3-(2-pentynyl)-2-oxazolidinone (22). To the
mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and 1.12 g
of potassium hydroxide, 0.50 g of 9 and subsequently 1.10 g of 1-
bromo-2-pentyne were added. Reagents were irradiated in the
microwave reactor. The crude product was purified by a column
chromatography, using a mixture of hexane and ethyl acetate 1:1 as
an eluent, yielding 0.67 g (80%) of 22 as colorless oil (b.p. 310–
315 ꢁC). Rf ¼ 0.62 (hexane:ethyl acetate 1:1). MS, m/z (%):167 (20)
[Mþ],152 (9), 138 (1), 126 (27), 114 (11), 100 (8), 86 (100), 70 (21), 67
3.2.2.1. General procedure for cyclocondensation to pyrazolone
cycles. To the solution of 5 mmol of ethyl 2-alkyl acetylacetate (11,
12 or 13) in 20 ml of anhydrous ethanol, 10 mmol of 99% hydrazine
hydrate was added. Reagents, in a calibrated flask with condenser,
were irradiated for 10 min with 160 W power of microwaves. The
obtained solution was concentrated in vacuo, yielding crude
product, which was purified by crystallization from benzene.
3.2.2.1.1. 5-Methyl-4-(2-trans-pentenyl)-1,2-dihydro-3-pyrazolone
(26). To the solution of 0.99 g of 11 in 20 ml of anhydrous ethanol,
0.50 g of 99% hydrazine hydrate was added. Reagents were irradiated
in the microwave reactor. The crude product was isolated and
crystallized from benzene yielding 0.50þg (60%) of white crystals
(m.p.178–182 ꢁC). MS, m/z (%): 166 (9) [M ],151 (3),137 (23),124 (2),
(45), 56 (16), 42 (84). IR (cmꢀ1): 1685 ( C]O).1H NMR (CDCl3):
n
d
¼ 1.12 (t, J ¼ 7.5 Hz, 3H, CH3-50), 1.28 (d, J ¼ 6.6 Hz, 3H, CH3), 2.14–
2.24 (m, 2H, CH2-40), 3.73–3.80 (m, 2H, CH2-5), 3.84–3.94 (m, 1H,
CH2-10), 4.19–4.28 (m, 1H, CH2-10), 4.45 (t, J ¼ 7.5 Hz, 1H, CH-4). 13C
NMR (CDCl3):
d
¼ 12.60 (CH3), 13.79 (CH3-50), 21.38 (C-40), 43.24
(C-4), 62.09 (C-10), 73.37 (C-5), 75.67/77.42 (C^C), 163.82 (C]O).
20
C9H13NO2 (167.1). [
a]
¼ w0ꢁ.
D
3.2.1.1.7. 1-Methyl-2-(2-trans-pentenyl)-3-pyrazolidinone (23). To
the mixture of 0.16 g of TBAB, 2.76 g of potassium carbonate and
1.12 g of potassium hydroxide, 0.50 g of 10 and subsequently 1.12 g of
1-bromo-2-trans-pentene were added. Reagents were irradiated in
the microwave reactor. The crude product was purified by a column
chromatography, using a mixture of chloroform and ethanol 10:1 as
an eluent, yielding 0.28 g (33%) of 23 as yellow oil (b.p. 228–234 ꢁC).
111 (100), 97 (4), 82 (5), 69 (13), 53 (7), 41 (16). IR (cmꢀ1): 1600 (
n
C]O). 1H NMR (DMSO):
d
¼ 0.85 (t, J ¼ 6.8 Hz, 3H, CH3-50), 2.02 (s,
3H, CH3), 2.01–2.09 (m, 2H, CH2-40), 3.25–3.30 (m, 2H, CH2-10), 5.30–
5.38 (m, 2H, trans-CH]CH), 9.21 (br s, 1H, NH), 10.99 (br s, 1H, NH).
13C NMR (DMSO):
d
¼ 9.91 (CH3), 14.04 (CH3-50), 22.02 (C-40), 24.80
(C-20), 98.73 (C-4), 127.84/130.71 (trans-CH]CH), 136.52 (C-5),
20
159.15 (C]O). C9H14N2O (166.1). [
a]
¼ w0ꢁ.
D

3038
A. Pawełczyk, L. Zaprutko / European Journal of Medicinal Chemistry 44 (2009) 3032–3039
3.2.2.1.2. 5-Methyl-4-(2-cis-pentenyl)-1,2-dihydro-3-pyrazolone
pale yellow oil (b.p. 270–275 ꢁC). Rf ¼ 0.65 (hexane:ethyl acetate
1:1). MS, m/z (%): 185 (7) [Mþ], 170 (10), 156 (12), 143 (4), 130 (7),
(27). To the solution of 0.99 g of 12 in 20 ml of anhydrous ethanol,
0.50 g of 99% hydrazine hydrate was added. Reagents were irradi-
ated in the microwave reactor. The crude product was isolated and
crystallized from benzene yielding 0.42 g þ(51%) of white crystals
(m.p. 180–183 ꢁC). MS, m/z (%): 166 (9) [M ] 151 (2), 137 (23), 124
(3), 111 (100), 97 (4), 82 (4), 69 (12), 53 (7), 41 (15). IR (cmꢀ1): 1600
116 (9), 101 (5), 84 (13), 69 (100), 56 (11). IR (cmꢀ1): 1680 (
n C]O).
1H NMR (CDCl3):
d
¼ 0.90 (t, J ¼ 7.1 Hz, 3H, CH3-50), 1.63 (d,
J ¼ 6.2 Hz, 3H, CH3), 2.00–2.08 (m, 2H, CH2-40), 3.50–3.58 (m, 2H,
CH2-10), 3.67–3.77 (m, 2H, CH2-5), 4.94 (q, J ¼ 6.0 Hz, 1H, CH-2),
5.28–5.39 (m, 1H, cis-CH]), 5.47–5.69 (m, 1H, cis-CH]). 13C NMR
(
n
C]O). 1H NMR (DMSO):
d
¼ 0.91 (t, J ¼ 7.4 Hz, 3H, CH3-50), 2.01 (s,
(CDCl3):
d
¼ 13.49 (CH3-50), 22.00 (CH3), 23.83 (C-40), 46.21 (C-2),
3H, CH3), 1.91–2.20 (m, 2H, CH2-40), 2.89–2.94 (m, 2H, CH2-10),
49.60 (C-5), 58.18 (C-10), 127.80/130.61 (cis-CH]CH), 173.63 (C]O).
20
5.27–5.42 (m, 2H, cis-CH]CH), 10.24 (br s, 1H, NH), 10.96 (br s, 1H,
C9H15NOS (185.1). [
a]
¼ w0ꢁ.
D
NH). 13C NMR (DMSO):
d
¼ 9.95 (CH3), 14.02 (CH3-50), 19.09 (C-40),
3.2.3.1.3. 2-Methyl-3-(2-pentynyl)-4-thiazolidinone (31). To the
prepared dry mixture of 0.32 g of 16, 2 g of K10-clay and p-tolue-
nesulfonic acid, 0.44 g of acetaldehyde was added. Reagents were
irradiated in the microwave reactor. The crude product was purified
by a column chromatography yielding 0.22 g (60%) of 31 as pale
yellow oil (b.p. 319–325 ꢁC). Rf ¼ 0.50 (hexane:ethyl acetate 1:1).
MS, m/z (%): 183 (29) [Mþ], 168 (62), 154 (15), 142 (20), 130 (8), 117
24.78 (C-20), 98.74 (C-4), 127.63/130.48 (cis-CH]CH), 136.53 (C-5),
20
159.16 (C]O). C9H14N2O (166.1). [
a
]
¼ w0ꢁ.
D
3.2.2.1.3. 5-Methyl-4-(2-pentynyl)-1,2-dihydro-3-pyrazolone
(28). To the solution of 0.98 g of 13 in 20 ml of anhydrous ethanol,
0.50 g of 99% hydrazine hydrate was added. Reagents were irradi-
ated in the microwave reactor. The crude product was isolated and
crystallized from benzene yielding 0.44 g (þ54%) of white crystals
(m.p. 189–194 ꢁC). MS, m/z (%): 164 (93) [M ], 149 (45), 135 (100),
123 (21), 111 (23), 97 (11), 77 (21), 67 (28), 55 (7), 41 (38). IR (cmꢀ1):
(16), 100 (20), 86 (100), 67 (77). IR (cmꢀ1): 1680 ( C]O). 1H NMR
n
(CDCl3):
d
¼ 1.10 (t, J ¼ 7.0 Hz, 3H, CH3-50), 1.60 (d, J ¼ 6.0 Hz, 3H,
CH3), 2.09–2.16 (m, 2H, CH2-40), 3.64–3.75 (m, 2H, CH2-5), 3.83–
1600 (
n
C]O). 1H NMR (DMSO):
d
¼ 1.02 (t, J ¼ 7.5 Hz, 3H, CH3-50),
3.94 (m, 2H, CH2-10), 4.93 (q, J ¼ 6.2 Hz, 1H, CH-2). 13C NMR (CDCl3):
2.09 (s, 3H, CH3), 2.02–2.15 (m, 2H, CH2-40), 3.37 (m, 2H, CH2-10),
d
¼ 13.49 (CH3-50), 22.00 (CH3), 23.83 (C-40), 46.57 (C-2), 48.96
9.53 (br s, 1H, NH), 11.15 (br s, 1H, NH). 13C NMR (DMSO):
(CH3), 11.20 (C-40), 11.78 (C-20), 14.20 (CH3-50), 78.02/80.35 (C^C),
d
¼ 10.10
(C-5), 64.19 (C-10), 74.81/86.71 (C^C), 174.43 (C]O). C9H13NOS
20
(183.2). [
a
]
¼ w0ꢁ.
D
96.40 (C-4), 102.38 (C-5), 158.55 (C]O). C9H12N2O (164.1).
20
[
a
]
¼ w0ꢁ.
D
3.3. Test of odor evaluation
3.2.3. Synthesis of thiazolidinone heteroanalogues of jasmone
Compounds 14–16, necessary to obtain thiazolidinone hetero-
analogues, were prepared by using the general N-alkylation
method [16].
Fragrant properties of the obtained compounds were performed
according to the Polish Standard Methodology PN-ISO 5496, which
is in accordance with the International Standard ISO 5496:1992(E).
Direct sniffing strips methodology was employed to the odor
analysis. Tests of odor evaluation were performed using 10% (v/v for
fluids and w/v for solid) ethanol solutions of samples 17–31. Three
drops of prepared solution were absorbed on a Whatman smelling
blotter (thin strip of highly absorbent paper) and take care of it so
that they did not touch. When the ethanol evaporated, the strips
with the sample were performed for organoleptic analyses by non-
training assessors. The evaluating panel is a group of persons
recognized to have normal olfaction sensitivity. Odor-assessors
were over 18 years old and both sex. The odor was evaluated by
sniffing the air under the testing strip gently moving them few
centimeters in front of the nose, to such manner so that it did not
touch the nose. The odor characteristic and intensity of each sample
were compared with the sample of cis-jasmone (commercial
product of Aldrich) similar solution. Durability of the scents was
studied after 1, 6 and 24 h. In the case of highest odor durability
samples 18 and 21, which smelt after 6 days even, additionally the
odor durability was determined after next 24 h to their odor
decline. The testing strips were held on a special holder stand in
well ventilated work-room. The test of odor evaluation was
repeated to confirm the results.
3.2.3.1. General procedure for cyclocondensation to thiazolidinone
cycles. In 10 ml of methylene chloride, 2 mmol of appropriate
N-mono-substituted 2-mercaptoacetamide (14, 15 or 16) and
catalytic amount of p-toluenesulfonic acid were dissolved. To the
obtained solution, 2 g montmorilonite K10-clay was added and
mixed. After evaporation of solvent, to the dry mixture 10 mmol of
acetaldehyde was added. Reagents, in a calibrated flask (trans-
parent to microwave irradiation) with condenser, were irradiated
for 5 min with 200 W power of microwaves. The crude product was
extracted two times with the use of 20 ml of methylene chloride
and the obtained organic solution was filtered and concentrated in
vacuo. The residued crude oil was purified by a column chroma-
tography, with the use of mixture of hexane and ethyl acetate 1:1 as
an eluent, yielding pure product.
3.2.3.1.1. 2-Methyl-3-(2-trans-pentenyl)-4-thiazolidinone (29). To
the prepared dry mixture of 0.32 g of 14, 2 g of K10-clay and
p-toluenesulfonic acid, 0.44 g of acetaldehyde was added. Reagents
were irradiated in the microwave reactor. The crude product was
purified by a column chromatography yielding 0.23 g (65%) of 29 as
pale yellow oil (b.p. 278–283 ꢁC). Rf ¼ 0.59 (hexane:ethyl acetate
1:1). MS, m/z (%): 185 (9) [Mþ], 170 (6), 156 (10), 143 (2), 130 (2), 116
(3), 101 (3), 84 (10), 69 (100), 56 (14). IR (cmꢀ1): 1680 ( C]O). 1H
n
Acknowledgement
NMR (CDCl3):
d
¼ 0.88 (t, J ¼ 7.0 Hz, 3H, CH3-50), 1.61 (d, J ¼ 6.0 Hz,
This study was partially supported by Polish State Committee for
Scientific Research (Grant No. 2 PO5F 031 29).
3H, CH3), 2.01–2.12 (m, 2H, CH2-40), 3.51–3.62 (m, 2H, CH2-10), 3.70–
3.81(m, 2H, CH2-5), 4.92 (q, J ¼ 6.2 Hz, 1H, CH-2), 5.32–5.42 (m, 1H,
trans-CH]), 5.58–5.79 (m, 1H, trans-CH]). 13C NMR (CDCl3):
¼ 13.54 (CH3-50), 22.25 (CH3), 23.87 (C-40), 46.25 (C-2), 49.63 (C-5),
References
d
58.21 (C-10),127.84/130.71 (trans-CH]CH),173.63 (C]O). C9H15NOS
20
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