Solid-supported synthesis of bio-active carvacrol compounds using microwaves

Article abstract of DOI:10.1080/00397910802138785

The most abundant and potent natural products having a broad spectrum of biological activity against various pests are terpenoids, especially monoterpenoids. The chemical modification of natural monoterpenoids has been reported to result in modified biological activity. The present work emphasizes the structural modification of carvacrol, a phenolic monoterpenoid, through the synthesis of different ether and ester derivatives that are useful for structure-activity relationship studies to exploit the potent molecules. The carvacrol was reacted with alkyl halides and acid chlorides under microwaves using solid supports such as silica gel, alumina, and fly ash to give ethers and esters, respectively. The synthesis of dimeric ether and ester compounds using dihalides and acid dichlorides was conducted with novel reactions. Additional features of the methodology include very fast reactions, higher yields and purities of the products, and an ecofriendly approach. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802138785

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Solid-Supported Synthesis
of Bio-active Carvacrol
Compounds Using Microwaves
H. P. Narkhede a , U. B. More b , D. S. Dalal c & P. P.
Mahulikar c
a Smt. Padambai Kapoorchandji Kotecha Mahila
Mahavidyalaya , Bhusawal, India
b Rao Bahaddur Narayan Borawake College ,
Shrirampur, India
c School of Chemical Sciences, North Maharashtra
University , India
Published online: 11 Jul 2008.
To cite this article: H. P. Narkhede , U. B. More , D. S. Dalal & P. P. Mahulikar (2008)
Solid-Supported Synthesis of Bio-active Carvacrol Compounds Using Microwaves,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:14, 2413-2418, DOI: 10.1080/00397910802138785
To link to this article: http://dx.doi.org/10.1080/00397910802138785
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Synthetic Communications1, 38: 2413–2418, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802138785
Solid-Supported Synthesis of Bio-active
Carvacrol Compounds Using Microwaves
H. P. Narkhede,1 U. B. More,2 D. S. Dalal,3 and P. P. Mahulikar3
1Smt. Padambai Kapoorchandji Kotecha Mahila Mahavidyalaya,
Bhusawal, India
2Rao Bahaddur Narayan Borawake College, Shrirampur, India
3School of Chemical Sciences, North Maharashtra University, India
Abstract: The most abundant and potent natural products having a broad spectrum
of biological activity against various pests are terpenoids, especially monoterpenoids.
The chemical modification of natural monoterpenoids has been reported to result in
modified biological activity. The present work emphasizes the structural modification
of carvacrol, a phenolic monoterpenoid, through the synthesis of different ether and
ester derivatives that are useful for structure–activity relationship studies to exploit
the potent molecules. The carvacrol was reacted with alkyl halides and acid chlorides
under microwaves using solid supports such as silica gel, alumina, and fly ash to give
ethers and esters, respectively. The synthesis of dimeric ether and ester compounds
using dihalides and acid dichlorides was conducted with novel reactions. Additional
features of the methodology include very fast reactions, higher yields and purities of
the products, and an ecofriendly approach.
Keywords: Carvacrol; Esters; Ethers; Microwave Irradiation; Monoterpenoid;
Solid Supports
INTRODUCTION
The natural monoterpenoids play an important role in the enzyme
system of plants and are one of the most abundant and potent groups, with
Received August 28, 2007
Presented at the Joint International Conference on Advances in Organic
Chemistry and Chemical Biology, IICT, Hyderabad, Jan. 11–12, 2006.
This article is dedicated to Dipesh M. Kotecha, director, Shri. Saraswati Vidya
Prasarak Mandal Bhusawal, India.
Address correspondence to P. P. Mahulikar, School of Chemical Sciences,
North Maharashtra University, Jalgaon 425 001, M. S. India. E-mail:
mahulikarpp@rediffmail.com
2413

2414
H. P. Narkhede et al.
biological activity against various pests. Monoterpenoids are secondary
metabolites of plants that are generally considered to be self-defense
tactics against plant enemies. The biological activity of monoterpenoids[1–
5] against insect nematodes, phytopathogenic fungi, and other pest species
are believed to be related to the nature and position of specific groups or
substituents. The chemical modification of natural monoterpenoids[1–9] to
various ether and ester derivatives has been reported to result in modified
biological activity. The routine synthetic methods suffer from some disad-
vantages such as low yields, high temperature conditions, long reaction
times, and formation of by-products in addition to tedious reaction
workup.[10]
In continuation of our work on structural modification of monoter-
penoids[11–13] and microwave technique,[14] we report herein a simple,
rapid, efficient, and environmentally friendly synthesis of carvacrol
compounds Scheme 1. The present work includes microwave-mediated
alkylation, acylation, and dimerization of carvacrol using solid supports
such as silica gel, alumina, and fly ash (a waste generated by thermal
power stations by burning coal). Carvacrol was adsorbed on silica
gel, alumina, and fly ash using aqueous sodium hydroxide and irra-
diated with various alkyl halides, acid chlorides, a,x-dihaloalkanes, or
diacid chlorides to give the carvacryl ethers, esters, and dimeric
products.
EXPERIMENTAL
All chemicals were of analytical grade and solvents were distilled before
use. A microwave oven (model OM9918C, 2450 MHz, 900 W) was used
Scheme 1. Synthesis of carvacryl ethers and esters.

Bioactive Carvacrol Compounds
2415
to carry out the reactions. The fly ash (70–300 mesh) was collected from a
thermal power plant, Deepnagar, Bhusawal, Dist. Jalgaon, India and
used as such for the reactions. Silica gel (60–120 mesh) and alumina
(60–120 mesh) were of synthetic grade (S. D. Fine Chem. Ltd., Mumbai,
India). The reactions were monitored by silica-gel thin-layer chromato-
graphy (TLC) using petroleum ether–n-hexane (1:1). Melting points
and boiling points are uncorrected.
The reagents ratio is carvacrol 10 mmol, RX 10 mmol, XRX 5 mmol,
NaOH 0.4 g, adsorbent 1.5 g, H2O 5 ml; adsorbent is either silica gel, alu-
mina, or fly ash.
General Procedure for Synthesis of Carvacryl Ethers and Esters
(1a–m and 2a–d)
Carvacrol (10 mmol) was dissolved in an aqueous sodium hydroxide sol-
ution (5 mL, 2N). Then adsorbent (1.5 g) was added to this solution and
stirred well. The mixture was treated in a microwave oven for complete
removal of water. To this dry powder, alkyl halide or acid chloride
(10 mmol) or a,x-dibromoalkane or diacid chloride (5 mmol) was added
and irradiated under microwaves at 270 W at pulses of 30 s for 1–5 min.
After completion of reaction (monitored by TLC), the mixture was
cooled and extracted with petroleum ether (2 Â 25 mL). The extract was
treated with sodium bicarbonate, washed with water, and dried over
anhydrous sodium sulphate. The removal of the solvent afforded the pro-
ducts 1a–m and 2a–d (Scheme 1, Table 1).
Data
Compound 1a. 1H NMR (CDCl3, 300 MHZ, d ppm): 1.19 (d, 6H, gem 2
-CH3), 2.17 (s, 3H, Ar-CH3), 2.84 (septet, 1H, -CH), 3.37 (s, 3H, -OCH3),
6.63–6.70–7.02 (s, d, d, 3H, Ar-H); IR (neat): 744, 817, 1046, 1138, 1255,
1413, 1617, 2966 and 3009 cmÀ1
.
1
Compound 1g. H NMR (CDCl3, 300 MHZ, d ppm): 1.20 (d, 6H,
gem 2 -CH3), 2.16 (s, 3H, Ar-CH3), 2.78 (septet, 1H, -CH), 4.02 (s, 2H,
-OCH2), 6.64–6.71–7.01 (s, d, d, 3H, Ar-H), 10.15 (s, 1H, -COOH); IR
(neat): 766, 810, 1105, 1250, 1380, 1500, 1590, 1710, 2966, 3006 and
3450 cmÀ1
.
1
Compound 1i. H NMR (CDCl3, 300 MHZ, d ppm): 1.14 (d, 6H,
gem 2 -CH3), 2.19 (s, 3H, Ar-CH3), 2.87 (septet, 1H, -CH), 3.01 (m,
=
1H, -CH ), 3.30 (d, 2H, CH2), 3.48 (d, 2H, -OCH2), 6.63–6.70–7.02
=
(s, d, d, 3H, Ar-H); IR (neat): 763, 809, 1108, 1245, 1380, 1500, 1590,
1630, 2966 and 3009 cmÀ1
.

2416
H. P. Narkhede et al.
Table 1. Carvacrol derivatives
Yield (%) on solid support
Bp=mp
(ꢀC)
Lit.[11,13,16]
bp=mp (ꢀC)
Compound
Silica gel
Alumina
Fly ash
1a
1b
1c
1d
1e
1f
91
93
89
90
87
89
76
87
82
84
93
90
90
87
80
85
88
92
94
90
91
89
90
79
87
84
85
94
91
90
88
83
89
87
92
93
90
92
88
89
78
86
80
84
93
90
89
86
82
86
85
201
229
233
177
237
200–203
228–230
233–235
176–178
236–238
216–218
182–183
77a
216–217
182
1g
1h
1i
77a
201
181
244
247
270
184
132
201
181
245
1j
1k
1l
247–248
268–270
184
1m
2a
2b
2c
2d
132
190
203
190
203
aMelting point.
1
Compound 1k. H NMR (CDCl3, 300 MHZ, d ppm): 1.22 (d, 6H,
gem 2 CH3), 2.17 (s, 3H, Ar-CH3), 2.30 (s, 3H, -COCH3), 2.83 (septet,
1H, -CH), 6.62–6.71–7.02 (s, d, d, 3H, Ar-H); IR (neat): 760, 800,
1100, 1233, 1500, 1600, 1750, 2990 and 3006 cmÀ1
.
1
Compound 1m. H NMR (CDCl3, 300 MHZ, d ppm): 1.23 (d, 6H,
gem 2 -CH3), 2.20 (s, 3H, Ar-CH3), 2.85 (septet, 1H, -CH), 7.00–7.62
(m, 3H and 5H, Ar-H); IR (neat): 760, 840, 1120, 1284, 1428, 1612,
1715, 2985 and 3007 cmÀ1
.
1
Compound 2b. H NMR (CDCl3, 300 MHZ, d ppm): 1.21 (d, 6H,
gem 2 CH3), 2.20 (m, 4H, -CH2CH2-), 2.18 (s, 3H, Ar-CH3), 2.80 (septet,
1H, -CH), 3.41 (m, 4H, -OCH2CH2O-), 6.63–6.70–7.02 (s, d, d, 6H,
Ar-H); IR (neat): 762, 843, 1120, 1285, 1428, 1612, 1715, 2985 and
3007 cmÀ1
.
CONCLUSION
The yields and purity of the products were excellent compared to those
obtained by conventional methods. The reactions were rapid, and the

Bioactive Carvacrol Compounds
2417
isolation of products was very simple. The synthesized compounds were
characterized by their physical constants, comparative TLC, and spectro-
scopic proton magnetic resonance (PMR) and infra-red (IR) techniques
with the products prepared by conventional routes.[11,15]
The derivatization or structural modification through such a simple,
rapid, and environmentally friendly approach to the synthesis of carva-
crol compounds will be helpful to develop potent pest management
agents.
ACKNOWLEDGMENT
H. P. Narkhede is thankful to UGC, New Delhi, for providing a teacher
fellowship under FIP Scheme of Xth UGC Plan.
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