Synthesis and perfume characteristics of acetals containing an aromatic ring

Article abstract of DOI:10.1023/A:1014848929083

Aromatic acetals were prepared by condensation of 2-methyl-3-(4-R-phenyl)propanals (R = Me, i-Pr, i-Bu) with ethanol, methanol, ethylene glycol, 1,2-propanediol, methyl Cellosolve, and Cellosolve. The perfume characteristics of the acetals were studied.

Full text of DOI:10.1023/A:1014848929083

Russian Journal of Applied Chemistry, Vol. 74, No. 11, 2001, pp. 1888 1891. Translated from Zhurnal Prikladnoi Khimii, Vol. 74, No. 11,
2001, pp. 1829 1832.
Original Russian Text Copyright
2001 by Vyglazov, Chuiko, Izotova, Vintarskaya, Yudenko.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Synthesis and Perfume Characteristics of Acetals
Containing an Aromatic Ring
O. G. Vyglazov, V. A. Chuiko, L. V. Izotova, Zh. V. Vintarskaya, and R. Ya. Yudenko
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
Tereza-Inter Limited Liability Company, Moscow, Russia
Received March 15, 2001
Abstract Aromatic acetals were prepared by condensation of 2-methyl-3-(4-R-phenyl)propanals (R = Me,
i-Pr, i-Bu) with ethanol, methanol, ethylene glycol, 1,2-propanediol, methyl Cellosolve, and Cellosolve. The
perfume characteristics of the acetals were studied.
Thanks to active development of synthetic organic
chemistry, the set of available synthetic perfumes is
CHO
.
rapidly extended, with new classes of compounds
being involved. The use of new synthetic perfumes is
characterized by two features: (1) as a rule, substances
with interesting scent are discovered empirically;
(2) the perfume characteristics are studied for as many
structurally related compounds as possible, with the
aim to apply the developed processes to synthesis of
a wide set of perfumes.
III
Acetals are widely used are synthetic perfumes.
This mostly concernes diethyl, dimethyl, and ethylene
acetals, although derivatives of some other alcohols
(geraniol, isoamyl alcohol, 2-phenylethanol) are also
used [5]. To systematically study the structure scent
relationship in the series of acetals derived from I III,
we prepared the acetals with methanol, ethanol, ethyl-
ene glycol, 1,2-propanediol, and also with methyl
Cellosolve and Cellosolve (the two latter compounds
were not used previously for these purposes).
Such an approach inevitably sets a task of revealing
the structure scent relationship for perfumes, with the
aim to make a search for new perfumes purposeful.
At the same time, to find such a relationship, it is
necessary to prepare as many structural analogs as
possible.
The reaction is usually performed in the presence
of an acid catalyst; from the viewpoint of process
simplicity, it is convenient to use cation-exchange
resins, e.g., granulated KU-2 cation exchanger. The
reaction was performed in benzene in the presence of
FIBAN K-1 fibrous sulfonic cation exchanger as cata-
lyst. This resin was prepared by radiation-induced
grafting ot styrene (98%) 1,4-divinylbenzene (2%)
copolymer to a polypropylene thread, followed by
sulfonation with sulfuric acid.
Such studies were performed previously [1] but
became more active in the past years. For example,
the structure scent relationship was studied for the
series of 7-oxanorbornanes [2], monoterpene lactones
[3], and bicyclo[2.2.n]oximes [4].
In this work, starting from aldehydes in which the
carbonyl group is located in a side chain of an aromat-
ic ring, we prepared aromatic acetals and studied their
perfume characteristics. The initial compounds were
the aldehydes widely used in perfumery: jasmorange
[2-methyl-3-(4-methylphenyl)propanal, I], cyclamen-
aldehyde [2-methyl-3-(4-isopropylphenyl)propanal,
II], and lilial [2-methyl-3-(4-tert-butylphenyl)propan-
al, III]:
With this catalyst, owing to its developed surface
[6], the reaction time was reduced by a factor of 1.5 2
as compared to KU-2. Furthermore, the fibrous ion
exchanger did not noticeably lose its activity in re-
peated use, as demonstrated by the example of the
reaction of aldehydes I III with Cellosolve (Table 1).
CHO
CHO
The reaction progress was monitored by GLC. The
structure of the acetals was confirmed spectroscopi-
cally. In the H NMR spectra, a characteristic doublet
I
II
1
1070-4272/01/7411-1888$25.00 2001 MAIK Nauka/Interperiodica

SYNTHESIS AND PERFUME CHARACTERISTICS OF ACETALS
1889
at 4.3 4.8 ppm (J 5 8 Hz) corresponds to the
Table 1. Yield of acetals in reactions of aldehydes I III
with Cellosolve, as influenced by catalysis conditions
HC(OR) proton. The IR spectra exhibit a character-
2
istic acetal pattern consisting of five bands in the
1
Aldehyde conversion, %
range 1185 1030 cm .
Alde-
hyde
,
Catalyst
min
The synthesis conditions and yields of the target
products are given in Table 2, and the perfume char-
first run
second run
1
acteristics of the acetals, in Table 3.
I
FIBAN K-1
KU-2
130
180
95
90
93
65
Certain similarity of the scents of the initial alde-
hydes I III is undoubtedly due to their similar molec-
ular structure, not only topological but also steric.
It was suggested [7] that all these molecules have a
rolled-up conformation of the side chain (A, B),
which is stabilized owing to conjugation of the orbi-
tals of the aromatic ring and carbonyl group. This
factor is also responsible for the similar scent of these
aldehydes and of 7-hydroxy-3,7-dimethyloctanal (hy-
droxycitronellal, IV). As suggested in [7], the mole-
cule of IV in the vapor phase can take the rolled-up
conformation C owing to hydrogen bonding:
II
III
FIBAN K-1
KU-2
150
220
95
92
91
58
FIBAN K-1
KU-2
190
230
90
90
88
50
Table 2. Reaction time and yield of acetals from alde-
hydes I III
Conversion
%
Yield
Alde-
hyde
,
Alcohol used
min
I
Methanol
Ethanol
Ethylene glycol
Propylene glycol
Methyl Cellosolve 120
45
55
70
90
100
100
93
92
95
94
95
88
85
91
87
O
O
A
B
Cellosolve
130
95
.
.
H
.
.
O
O
II
Methanol
Ethanol
Ethylene glycol
Propylene glycol
Methyl Cellosolve 150
55
60
80
90
100
100
92
90
95
95
95
90
87
92
90
C
However, optimization of the molecular geometry
of I III in the MM-2 approximation [8] shows that
for each aldehyde the energies of the molecule in all
the possible conformations differ by no more than
Cellosolve
150
95
1
III Methanol
60
75
100
120
100
100
93
90
93
94
93
88
85
86
82
0.8 kJ mol . Thus, the rolled-up conformation
Ethanol
Ethylene glycol
Propylene glycol
Methyl Cellosolve 180
Cellosolve 190
affords no additional stabilization of the aldehyde
molecule. Furthermore, calculation shows that the
angle between the planes of the aromatic ring and
CHO group in I III in the rolled-up conformation is
41.3 , 43.2 , and 44.5 , respectively. Such orientation
excludes any overlap through space of the orbitals
of the two nonbonded molecular fragments. It should
be noted also that in conformation C of IV the dis-
tance between the hydroxyl hydrogen and carbonyl
oxygen is 4.87 , which is too long for hydrogen
bonding, especially in the gas phase when the mole-
cule acquires additional energy.
90
These data cast doubt on the conformational
approach to scent analysis. The obtained set of acetals
allows us to correlate variations of the scent with
variations of, e.g., the number of alkyl substituents,
with the conformation of the molecular core being
preserved.
1
The perfume characteristics of acetals, tested as 10% solutions
When considering the relationship between the
scent of the initial aldehydes and their molecular
structure, it should be noted that, in going from the
methyl to isopropyl and then tert-butyl substituent,
the scent changes from fresh fruit to fresh flower. In
the series of the corresponding dimethyl acetals, the
in purified 96% ethanol, were evaluated by the Tasting Council
(eight experts) at the Accredited Control and Analytical
Laboratory of Perfumes and Cosmetics, Tereza-Inter Limited
Liability Company (Accreditation Certificate of the State
Committee for Standards of the Russian Federation no. ROSS
RU.0001.512.312, July 6, 2000).
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 74 No. 11 2001

1890
VYGLAZOV et al.
Table 3. Scent characteristics of the synthesized acetals
Compound
Scent
2-Methyl-3-(4-methylphenyl)propanal dimethyl acetal Green, flower, with a bittery tint
2-Methyl-3-(4-isopropylphenyl)propanal dimethyl
Green, of cyclamen, with a bitter grassy note
acetal
2-Methyl-3-(4-tert-butylphenyl)propanal dimethyl
acetal
Strong, flower, with a cold note of cyclamen and lily of the val-
ley, light ozone
2-Methyl-3-(4-methylphenyl)propanal diethyl acetal Green, fresh watermelon, with a note of spice herbs
2-Methyl-3-(4-isopropylphenyl)propanal diethyl acetal Flower, of cyclamen, with a wood note
2-Methyl-3-(4-tert-butylphenyl)propanal diethyl acetal Flower, of cyclamen and lily of the valley, with a wood note
2-Methyl-3-(4-methylphenyl)propanal di(2-methoxy- Fresh, flower, of peony with a bright watermelon note
ethyl) acetal
2-Methyl-3-(4-isopropylphenyl)propanal di(2-methoxy- Fresh, of cyclamen, with a watermelon ozone note
ethyl) acetal
2-Methyl-3-(4-tert-butylphenyl)propanal di(2-methoxy- Flower, with notes of cyclamen, lily of the valley, and sweet
ethyl) acetal
lime blossom
2-Methyl-3-(4-methylphenyl)propanal di(2-ethoxy-
ethyl) acetal
Flower, grassy, with a fresh note of watermelon and heady anise
and wood tint
2-Methyl-3-(4-isopropylphenyl)propanal di(2-ethoxy- Flower, of cyclamen, with an anise ozone note
ethyl) acetal
2-Methyl-3-(4-tert-butylphenyl)propanal di(2-ethoxy- Flower, fresh, with a beewax and honey tint, with a light bittery
ethyl) acetal
note
2-Methyl-3-(4-methylphenyl)propanal ethylene acetal Flower-grassy with a tint of parsley, celery, and anise
2-Methyl-3-(4-isopropylphenyl)propanal ethylene
acetal
2-Methyl-3-(4-tert-butylphenyl)propanal ethylene
Flower, of cyclamen, with a fresh watermelon note
Flower, of cyclamen, with a sweet anise note
acetal
2-Methyl-3-(4-methylphenyl)propanal propylene acetal Grassy, heady, wood, with seaweed note
2-Methyl-3-(4-isopropylphenyl)propanal propylene
Fresh, flower, sweet, with a beewax tint
acetal
2-Methyl-3-(4-tert-butylphenyl)propanal propylene
Flower, of cyclamen, sweet, powdery
acetal
scent changes from green fruit watermelon through
flower-grassy with a bittery note to fresh flower with
an ozone note. With diethyl acetals, very gentle heady
and wood notes appear. With methoxy and ethoxy
groups introduced into the ethyl acetal moiety, the
scent changes more significantly: the fresh fruit
watermelon note is enhanced, ozone freshness compo-
nents disappear, and a sweet wood or honey note
appears. These trends are observed with derivatives of
all the three aldehydes. Smooth variation of the scent
of the initial aldehydes corresponds to smooth varia-
tion of the scent in the series of similar acetals with
linear alkyl or alkoxy groups.
melon note is added. In the series of propylene ace-
tals, a wood scent gives way to a fresh flower scent
subsequently acquiring a warm powdery tint.
The acetals obtained show promise as components
of fragrant and perfume formulations, because they
produce a fairly wide range of scents of various tints
and, in contrast to the initial aldehydes, are stable to
oxidation in ready perfumes and cosmetics.
EXPERIMENTAL
1
The H NMR spectra were taken with a Tesla BS-
567A spectrometer (CDCl , internal reference HMDS).
With compounds containing a cyclic acetal groups
(ethylene or propylene acetals), the trend is reverse.
In the series of ethylene acetals, the scent varies very
sharply with increasing size of the substituent in the
phenyl moiety: first a fairly pronounced sweet flower
3
The IR spectra were recorded on a Specord 75-IR
spectrometer (thin films). The GLC analysis of reac-
tion mixtures was performed with a Chrom-5 chroma-
tograph [flame-ionization detector, 2000 3-mm
note appears, then it is enhanced, and a fresh water- column, Chromaton N-AW-DMCS support (0.125
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 74 No. 11 2001

SYNTHESIS AND PERFUME CHARACTERISTICS OF ACETALS
1891
0.160 mm), Reoplex-400 stationary phase, pro- on the substituent in the phenyl ring. In the series of
1
grammed heating from 100 to 180 C (4 deg min ),
nitrogen carrier gas].
diols, the scent changes more sharply.
ACKNOWLEDGMENTS
To prepare acetals, the catalyst (2 wt % relative to
aldehyde) was added to a solution of 0.10 mol of
aldehyde I III and 0.11 mol of dihydric alcohol in
70 ml of benzene. The mixture was refluxed until the
release of water ceased and the reaction was complete
(monitored by GLC). The catalyst was separated by
decanting, washed with benzene (2 5 ml), and re-
used; the wash solutions were combined with the reac-
tion solutions. The solvent was distilled off. When
necessary (if the acetal purity was less than 98%), the
product was purified by chromatography (alumina,
eluent hexane diethyl ether with gradually increasing
content of ether).
The authors are grateful to A.A. Shunkevich for
submitting samples of FIBAN K-1 sulfonic cation
exchanger.
REFERENCES
1. Ohloff, G., Helv. Chim. Acta, 1992, vol. 75, no. 7,
pp. 2041 2108.
2. Weyerstahl, P. and Brendel, J., Lieb. Ann., 1990,
no. 10, pp. 1029 1036.
3. Tadeba, H. and Mihara, S. Agr. Biol. Chem., 1990,
vol. 54, no. 9, pp. 2271 2276.
Monohydric alcohols were taken in a double
amount. With dimethyl acetals, the released water was
bound with a stoichiometric amount of triethyl ortho-
formate.
4. Buchbauer, G., Spreitzer, H., and Kotlan, U., Z. Natur-
forsch. (b), 1991, vol. 46, no. 9, pp. 1272 1274.
5. Voitkevich, S.A., 865 dushistykh veshchestv dlya par-
fyumerii i bytovoi khimii (865 Fragrants for Perfumery
and Domestic Chemicals), Moscow: Pishchevaya
Prom st., 1994.
CONCLUSIONS
6. Polyanskii, N.G., Kataliz ionitami (Catalysis with
Ion Exchangers), Moscow: Khimiya, 1973.
(1) A series of 2-methyl-3-(4-R-phenyl)propanal
(R = Me, i-Pr, t-Bu) acetals was prepared; these com-
pounds have pleasant scent and can be used as per-
fumes.
7. Voitkevich, S.A. and Kheifets, A.A., Ot drevnikh bla-
govonii k sovremennym parfyumerii i kosmetike (From
Ancient Fragrances to Modern Perfumes and Cosmet-
ics), Moscow: Pishchevaya Prom st., 1997.
(2) In the series of acetals with the same monohy-
dric alcohols, the scent changes smoothly depending
8. Burkert, U. and Allinger, N.L., Molecular Mechanics,
Washington, DC: Am. Chem. Soc., 1982.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 74 No. 11 2001