Synthesis of biologically active carvacrol compounds using different solvents and supports

Article abstract of DOI:10.1080/00397910701354608

Natural monoterpenoids have been documented for their acute toxicity and repellent, antifeedent, reproduction inhibitory, and insecticidal actions. The present work aims to derive a variety of ether and ester compounds using polymer-supported reactions from the polymer-supported carvacrol anion was reacted with alkyl halides and acid chlorides to afford carvacryl ethers and esters, respectively. Furthermore, a special study on the effect of different solvents and supports revealed that Amberlite IRA 400 (chloride form) was found to be the best polymer support and acetone among the solvents. Copyright Taylor & Francis Group, LLC.

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Synthesis of Biologically Active Carvacrol
Compounds using Different Solvents and
Supports
a
a
a
a
U. B. More , H. P. Narkhede , D. S. Dalal & P. P. Mahulikar
a
School of Chemical Sciences, North Maharashtra University , Jalgaon, India
Published online: 22 Jun 2007.
To cite this article: U. B. More , H. P. Narkhede , D. S. Dalal & P. P. Mahulikar (2007) Synthesis of Biologically
Active Carvacrol Compounds using Different Solvents and Supports, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:12, 1957-1964
To link to this article: http://dx.doi.org/10.1080/00397910701354608
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Synthetic Communications , 37: 1957–1964, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701354608
Synthesis of Biologically Active Carvacrol
Compounds using Different Solvents and
Supports
U. B. More, H. P. Narkhede, D. S. Dalal, and P. P. Mahulikar
School of Chemical Sciences, North Maharashtra University, Jalgaon,
India
Abstract: Natural monoterpenoids have been documented for their acute toxicity and
repellent, antifeedent, reproduction inhibitory, and insecticidal actions. The present work
aims to derive a variety of ether and ester compounds using polymer-supported reactions
from the polymer-supported carvacrol anion was reacted with alkyl halides and acid
chlorides to afford carvacryl ethers and esters, respectively. Furthermore, a special study
on the effect of different solvents and supports revealed that Amberlite IRA 400
(chloride form) was found to be the best polymer support and acetone among the solvents.
Keywords: carvacrol, ethers, esters, polymer-supported reactions, solvents
INTRODUCTION
The natural monoterpenoids play an important role in the enzyme system of
plants and are one of the most abundant and potent groups that have biological
activity against various pests. Monoterpenoids are secondary metabolites of
plants that are generally considered as self-defence tactics against plant
[1–4]
enemies. The biological activity of monoterpenoids
against insects
nematodes, phytopathogenic fungi, and other pest species are believed to be
related to the nature and position of specific groups or substituents.
[1–9]
The chemical modification of natural monoterpenoids to various
ether and ester derivatives had been reported to result in modified biological
Received in India October 27, 2006
Address correspondence to P. P. Mahulikar, School of Chemical Sciences,
North Maharashtra University, Jalgaon 425 001 (M.S.), India. E-mail:
mahulikarpp@rediffmail.com
1
957

1
958
U. B. More et al.
activity. The routine synthetic methods suffer from some disadvantages such
as low yields, high-temperature conditions, longer reaction time, and
[10]
formation of by-products in addition to tedious reaction workup.
The polymer-supported methodology adopted in the work is very simple
because of ease of operation and workup and also has higher yield and purity
[6–9]
of products. Our work is more centered on the structural modification
i.e., derivatization of natural pest-controlling compounds, which are easily
(
degradable and less toxic and nontoxic). It is suggested that the activation
of compounds are dependent upon nature and position of the functional
groups rather than volatility and molecular size. Keeping in view the bioactiv-
ity of monoterpenoids, we report a simple and efficient method for the prep-
aration of alkyl and acyl derivatives of carvacrol in higher yields and purity
under mild reaction conditions.
Different polymer supports such as Amberlite IRA 400 (chloride form),
Amberlyst A 26 (hydroxide form), and Indion 820 (chloride form) were
used to support the carvacrol anion. The alkyl halides and acid chlorides
were added to the carvacrol-supported resin in different solvents such as
acetone, acetonitrile, ethanol, tetrahydrofuran, and dichloromethane. The
reaction mixture was stirred until the completion of the reaction. In general,
the reactions with acid chlorides were faster than alkyl halides. Isolation of
pure products by simple filtration and evaporation of solvent are important
features of this method (Scheme 1). The method is also inexpensive
because the resin (polymer support) could be used repeatedly.
EXPERIMENTAL
All chemicals were of analytical grade, and solvents were distilled before use.
Melting points and boiling points are uncorrected. Commercial Amberlite
Scheme 1. Synthesis of carvacrol ethers and esters. Solvent: acetone, acetonitrile,
ethanol, tetrahydrofuran, DCM.

Synthesis of Carvacrol Compounds
1959
IRA 400 (chloride form) and Indion 820 (chloride form) were activated by
treating with dil. HCl solution, and Amberlyst A26 (hydroxide form) was
activated by treating with dil. NaOH.
General Procedure for Supporting Carvacrol Anion on Polymer
Support
Carvacrol (15 g, 100 mmol) was dissolved in 100 ml of an aqueous solution
of sodium hydroxide (4 g, 100 mmol). The activated resin (100 g) was
packed in a column (2 cm in diameter and 45 cm long) and was eluted
slowly dropwise (about 1.5 ml/min) with the solution of sodium salt of
carvacrol. Thereafter the resin was washed with distilled water until
chloride ions and excess of carvacrol anion were completely removed. It
was then washed with ethanol followed by acetone and dried in vacuo at
[10]
5
08C for 4 h. The exchange capacities
of carvacrol anion–supported
resins were determined by passing a 1N NaCl (100 ml) solution through
supported resin (1 g) packed in a small column. The carvacrol in the
eluent was titrated against 0.01N HCl using methyl orange as an indicator.
The exchange capacities of Amberlite IRA 400 (chloride form), Amberlyst
A26 (hydroxide form), and Indion 820 (chloride form) were found to be
1 mmol, 1.5 mmol and 1.2 mmol anion of carvacrol per gram of dry resin,
respectively.
Synthesis of Carvacryl Ethers
Carvacrol-supported Amberlite IRA 400 (10 g, 10 mmol), Amberlyst A26
(7 g, 10.50 mmol) or Indion 820 (8.5 g, 10.30 mmol) was taken separately
in dry solvent (acetone, acetonitrile, tetrahydrofuran, dichloromethane, or
ethanol) (25 ml), and alkyl halide (10 mmol) was added. The reaction
mixture was stirred for 30–40 min depending upon reactivity of alkyl
halides. The progress of reaction was monitored by silica-gel thin-layer
chromatography (TLC) (hexane–pet. ether, 1:1). Then resin was filtered
and washed with solvent (3 Â 5 ml). The solvent, on evaporation, gave the
products as listed in Tables 1–3.
1
a. H NMR (CDCl , 300 MHz): d 1.19 (d, 6H, gem 2 CH ), 2.17 (s, 3H,
1
Ar-CH ), 2.84 (septet, 1H, CH), 3.37 (s, 3H, -OCH ) 6.63–6.70–7.02 (s, d, d,
3
3
3
3
3
3
H, Ar-H);IR (neat): 744, 817, 1046, 1138, 1255, 1413, 1617, 2966, and
2
1
009 cm
.
1
1
septet, 1H, CH), 4.02 (s, 2H, -OCH ), 6.64–6.71–701 (s, d, d, 3H, Ar-H),
g. H NMR: d 1.20 (d, 6H, gem 2 CH ), 2.16 (s, 3H, Ar- CH ), 2.78
3 3
(
2
1
1
0.15 (s, 1H, -COOH); IR (neat): 766, 810, 1105, 1250, 1380, 1500, 1590,
2
1
710, 2966, 3006, and 3450 cm
.

2
Table 1. Yield (%) using Amberlite IRA 400, Cl form, as support
Solvent
DCM
[
2,11,12]
Entry
R
Time (min)
Ethanol
Acetone
Acetonitrile
THF
Bp [Lit. bp]
(8C)
1
1
1
1
1
1
1
1
2
2
2
a
b
c
d
e
f
-CH
-CH
3
35
35
30
30
30
35
20
30
10
10
10
82
78
76
78
80
84
84
79
78
80
91
92
94
78
86
88
90
94
86
93
92
92
78
80
70
70
73
80
87
78
70
80
82
88
92
93
85
90
88
88
83
82
89
87
74
83
81
80
82
85
85
88
90
84
90
201 [200–203]
229 [228–230]
231–233 [233–235]
176–177 [176–178]
237 [236–238]
216–217 [216–218]
180–182 [182–183]
77 [77]
2
CH
3
-CH CH CH
2
2
3
2
-CH (CH
-CH CH
3 2
)
2
2
CH
CH
3
-CH(CH )CH CH
2
3
3
g
h
a
b
c
-CH COOH
2,4 Dinitrophenyl-
-COCH3
2
244 [245]
-COCH
-COC
2
CH
3
247 [247–248]
270 [268–270]
6
H
5

2
Table 2. Yield (%) using Amberlyst A 26, OH form, as support
Solvent
DCM
Entry
R
Time (min)
Ethanol
Acetone
Acetonitrile
THF
1
1
1
1
1
1
1
1
2
2
2
a
b
c
d
e
f
-CH
-CH
3
2
35
35
30
30
35
35
20
30
10
10
15
78
79
84
80
80
80
88
78
85
86
92
87
88
92
87
94
88
95
88
94
94
96
76
74
80
76
84
78
85
76
83
82
89
84
86
88
86
92
85
93
82
91
90
94
80
80
86
84
89
83
90
81
89
89
90
CH
3
-CH CH CH
2
2
3
2
-CH (CH
-CH CH
-CH(CH
-CH COOH
3 2
)
2
2
CH
CH
CH
3
3
)CH
2
3
g
h
a
b
c
2
2,4 Dinitrophenyl-
-COCH
-COCH CH
3
2
3
6 5
-COC H

2
Table 3. Yield (%) using Indion 820, Cl form, as support
Solvent
DCM
Entry
R
Time (min)
Ethanol
Acetone
Acetonitrile
THF
1
1
1
1
1
1
1
1
2
2
2
a
b
c
d
e
f
-CH
-CH
3
2
35
35
30
35
30
35
20
30
10
10
15
86
88
84
82
74
78
85
84
87
85
84
90
92
94
90
78
84
92
88
94
90
93
79
80
78
77
70
70
79
76
78
79
76
87
90
89
86
76
82
88
87
91
87
90
82
84
80
81
72
74
81
80
83
81
80
CH
3
-CH CH CH
2
2
3
2
-CH (CH
-CH CH
3 2
)
2
2
CH
CH
3
-CH(CH )CH CH
3
2
3
g
h
a
b
c
-CH COOH
2,4 Dinitrophenyl-
-COCH3
2
-COCH
-COC
2
CH
3
6
H
5

Synthesis of Carvacrol Compounds
Synthesis of Carvacryl Esters
1963
Carvacryl esters (Tables 1–3) were prepared by this procedure using acid
chlorides instead of alkyl halides. The acid chloride (10 mmol) was added
slowly dropwise in the solution of polymer-supported carvacrol anion
(10 mmol) in dry solvent (25 ml) with constant stirring at room temperature.
Depending on reactivity of the acid chlorides, these reactions were completed
within 10–20 min.
The yields and purity of the products were excellent compared to those
obtained by conventional methods. The reactions were rapid, and the
isolation of products was very simple. The resin could be used repeatedly
by regeneration of activity. The synthesized compounds were character-
[
11,12]
ized
(
by their physical constants, comparative TLC, and spectroscopic
PMR and IR) techniques with the products prepared by conventional routes.
The derivatization or structural modification through such a simple, rapid,
and environmentally friendly approach in the synthesis of pesticides will be
helpful to develop potent pest-management agents.
1
a. H NMR (CDCl , 300 MHz): d 1.22 (d, 6H, gem 2 CH ), 2.17 (s, 3H,
2
Ar-CH ), 2.30 (s, 3H, COCH ), 2.83 (septet, 1H, CH), 6.62–6.71–7.02 (s, d,
3
3
3
3
d, 3H, Ar-H); IR (neat): 760, 800, 1100, 1233, 1500, 1600, 1750, 2990, and
2
1
3
006 cm
.
1
c. H NMR: d 1.23 (d, 6H, gem 2 CH ), 2.20 (s, 3H, Ar- CH ), 2.85
2
septet, 1H, CH), 7.00–7.62 (m, 3H and 5H, Ar-H); IR (neat): 760, 840,
3
3
(
2
1
1
120, 1284, 1428, 1612, 1715, 2985, and 3007 cm
.
CONCLUSION
In the present investigation, Amberlite IRA 400 (chloride form) was found
to be a better support, followed by Indion 820 (chloride form) and
Amberlyst A26 (hydroxide form). Among the solvents, acetone was found
to be the best solvent on the basis of reaction period and yield as
compared to other solvents in the given order: Acetone . acetonitrile .
tetrahydrofuran . ethanol . dichloromethane.
ACKNOWLEDGMENT
U. B. More and H. P. Narkhede are thankful to University Grants Commission
(UGC), New Delhi, for providing a teacher fellowship under the Faculty
Improvement Programme (FIP) the Scheme of Xth UGC Plan. This paper
was first presented at the Joint International Conference: Advances in
Organic Chemistry and Chemical Biology, IICT, Hyderabad, Jan. 11–12,

1
964
U. B. More et al.
2006. It is dedicated to Prof. R. K. Padalkar, Balwant College, Vita (Dist.
Sangli), on his 60th birthday.
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