Microwave-assisted sinthesis of thymyl ethers and esters in aqueous medium

Article abstract of DOI:10.1023/B:RUGC.0000025504.59745.09

Various thymyl ethers and esters have been synthesized by reactions of thymol with alkyl halides and acid chlorides, respectively, in aqueous medium under environmentally benign conditions using microwave irradiation. The products are important as potent pest managing agents.

Full text of DOI:10.1023/B:RUGC.0000025504.59745.09

Russian Journal of General Chemistry, Vol. 74, No. 2, 2004, pp. 217 218. From Zhurnal Obshchei Khimii, Vol. 74, No. 2, 2004,
pp. 244 245.
Original English Text Copyright
2004 by More, Pawar, Dewang, Patil, Mahulikar.
Dedicated to Dr. P.P. Wadgaonkar,
National Chemical Laboratory, Pune, 411008 India
Microwave-assisted Sinthesis of Thymyl Ethers and Esters
in Aqueous Medium1
D. H. More, N. S. Pawar, P. M. Dewang, S. L. Patil, and P. P. Mahulikar
School of Chemical Sciences, North Maharashtra University, Jalgaon, India
Received March 10, 2003
Abstract Various thymyl ethers and esters have been synthesized by reactions of thymol with alkyl halides
and acid chlorides, respectively, in aqueous medium under environmentally benign conditions using micro-
wave irradiation. The products are important as potent pest managing agents.
Terpenoids constitute an abundant and potent group
of natural products, which plays an important role in
the enzyme system of plants and reflects conspicuous
biological activity against various pests. Mono-
terpenoids are secondary metabolites of plants and
are self-defence tactics against plant enemies. Their
better pest management efficiency have been noted.
Higher terpenoids exhibit medicinal properties [1, 2].
The biological activity of monoterpenoids is believed
to be related to the nature and position of functional
groups or substituents. Chemical modification of
natural forms of monoterpenoids may lead to im-
proved biological activity [3, 4].
and improved the yield and purity of the products
which showed a high pest management potency [7, 9].
EXPERIMENTAL
Analytically pure thymol, alkyl halides, and some
acid chlorides were commercial products. Cinnamoyl
chloride and malonyl, succinyl, glutaryl, and adipyl
dichlorides were prepared by the procedures described
in [10, 11]. The progress of reactions and the purity
of products were monitored by TLC on silica gel
Synthesis of thymyl ethers and esters in aqueous medium
under microwave irradiation
Microwave (MW) irradiation technique has opened
new prospects in synthetic organic chemistry not only
from the viewpoint of high reaction rates and ease of
experimental procedures but also due to high yields
of the products, their purity, and reaction selectivity
and cleanliness. It has been commonly employed as
thermal energy source in organic synthesis under
Microwave-induced Organic Reaction Enhancement
(MORE) chemistry [5, 6]. In continuation of our work
on structural modifications of monoterpenoids [7 9],
the merits of the title methodology and importance of
the products prompted us to undertake the present
study. Here we report on the synthesis of thymyl
ethers and esters (see table) by reactions of thymol
with alkyl halides and acid chlorides, respectively,
in aqueous medium under conditions of microwave
irradiation (Scheme 1). All the products have already
been prepared via conventional [7, 9] and polymer-
supported reactions [8]. The use of microwave irradia-
tion technique considerably reduced the reaction time
Comp.
no.
Reaction Yield,b
R or n
bp,a
C
time, min
%
I
II
III
IV
V
CH3
216 218
224 225
226 228
216 218
236 238
238 240
253 254
210 212
224 226
227 229
241 242
284 286
5
98
98
98
98
99
99
99
98
97
98
98
99
99
99
99
99
99
CH3CH2
CH3CH2CH2
(CH3)2CH
CH3(CH2)2CH2
CH2 CHCH2
4.5
4.5
4.5
4
5
5
5
4
5
2.5
2
2.5
2
3
3
3
VI
VII C6H5CH2
VIII HO2CCH2
IX
X
XI
XII C6H5CO
XIII C6H5CH=CHCO 220 222
XIV n = 1
XV n = 2
n = 1
n = 2
CH3CO
219 221
235 236
222 224
236 238
XVI n = 3
XVII n = 4
1
a
b
The original article was submitted in English.
Data of [8, 9].
Yield of the isolated product.
1070-3632/04/7402-0217 2004 MAIK Nauka/Interperiodica

218
MORE et al.
dried over sodium sulfate. Removal of the solvent
Scheme 1.
ArOCOR
afforded products XI XIII (see table).
ArOR
XI XIII
I VIII
Diesters XIV XVII were synthesized as described
above for compounds IX and X using 0.05 mol of
thymol, 0.025 mol of the corresponding acid dihalide,
and 20 ml of 1% aqueous NaOH (see table).
RX
RCOCl
2 min
4 min
OH
REFERENCES
ArOH
X(CH2)nX
ClCO(CH2)nCOCl
n = 1, 2
n = 1 4
2 min
4 min
1. Agarwal, O.P., Chemistry of Organic Natural Prod-
ucts, Meerut (India): GOEL, 1987, vol. 1, p. 408.
XIV XVII
ArO(CH2)nOAr
2. Banthorpe, D.V. and Charlwood, B.V., Chemistry of
Terpenes and Terpenoids, New York, 1972, pp. 337
411.
IX, X
using authentic samples [7 9]. The boiling points
were determined by the open capilary technique and
were not corrected. The reactions were carried out in
a Kenstar OM 9918 C micriwave oven at 2450 MHz.
3. Coats, J.R., Karr, L.L., and Drewas, C.D., Naturally
Occurring Pest Bioregulators, Hedin, P.H., Ed.,
Washington: Am. Chem. Soc., 1991, ACS Symposium
Series, vol. 449, p. 305.
Thymyl ethers I VIII (general procedure).
A mixture of 2.5 mmol of thymol, 10 ml of a 1% so-
lution of NaOH, and 2.5 mmol of the corresponding
alkyl halide was placed in a 100-ml beaker and
irradiated for 4 5 min at a power level of 3. Volatile
alkyl halides were added in small portions after
irradiation for every 1 min. The product was extracted
into benzene or ether (2 20 ml), and the extract was
washed with water and dried over sodium sulfate.
Removal of the solvent afforded thymyl ethers I VIII
(see table).
4. Tsao, R., Lee, S., Rice, P.J., Jensen, C., and
Coats, J.R., Synthesis and Chemistry of Agroche-
micals. Vol. IV, Baker, D.R., Fenyes, J.G., and
Basarab, G.S., Eds., Washington: Am. Chem. Soc.,
1995, ACS Symposium Series, vol. 584, p. 312.
5. Caddick, S., Tetrahedron, 1995, vol. 38, p. 10403.
6. Bose, A., Banik, B., Lavlinskaia, N., and Jayara-
man, M., Chemtech, 1997, vol. 27, pp. 9, 18 24.
7. Kumbhar, P.P. and Dewang, P.M., Pestology, 1999,
vol. 23, p. 27.
8. Kumbhar, P.P., Kapadi, U.R., Hundiwale, D.G.,
Attarde, S.B., Dewang, P.M., and Pawar, N.S., Org.
Prep. Proced. Int., 2000, vol. 32, no. 6, p. 600.
Diethers IX and X were prepared in a similar way
using 0.05 mol of thymol and 0.025 mol of dihalo-
alkane (n = 1, 2) in 20 ml of 1% aqueous NaOH.
9. Kumbhar, P.P. and Dewang, P.M., J. Sci. Ind. Res.,
Thymyl esters XI XIII were synthesized as
described above for ethers I VIII using equimolar
amounts (0.025 mol) of thymol and the corresponding
acid chloride. Volatile acid chlorides were added in
small portions after irradiation for every 1 min. The
organic extract was washed first with a solution of
sodium hydrogen carbonate and then with water and
2001, vol. 60, p. 645.
10. Vogel, A.I., Vogel’s Textbook of Practical Organic
Chemistry, London: Longman Scientific and Tech-
nical, 1989, 5th ed.
11. Kumbhar, P.P., Cand. Sci. Dissertation, Kolhapur,
1993.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 2 2004