18 Sudarma et al.
Asian J. Chem.
GC-MS were recorded on GC-MS QP-2010 Ultra, Merk
stirring with a magnetic stirrer in an ice bath there was added,
drop by drop a nitrating mixture consisting of 0.5 mL 65 %
HNO3 and 0.5 mL H2SO4. A yellow solid immediately started
forming. After the addition the mixture was left stirring for 45
min and then it was poured in 30 mL of cold water. The solids
were filtered and washed with 2 × 5 mL of ethanol. The product
was recrystallized from 30 mL of ethanol and gave 0.86 g of
crystalline mass of “green-olive-yellow” kind of colour. GC-
MS analyses gave (84.37 %), M+• 223, calculated for C11H13NO4
Major fragments: 163 (M+• – CH3), 147 (M+• – OCH3), 135,
115, 107, 91, 77 (C6H6). 1H NMR (400 MHz, CDCl3): δ 7.83
(1H, s); 6.85 (1H, s);); 5.98 (1H, m); 5.14 (2H, m); 3.91(3H,
s, OCH3); 3.89 (3H, s, OCH3); 3.76 (2H, d, J 6.4 Hz).
Method (c): Nitration of methyl eugenol using nitration
of eugenol approaches: A round bottomed flask (50 mL) with
magnetic stirrer was charged methyl eugenol (1 g) and aceto-
nitrile (20 mL) then stirred for 5 min. Potassium hydrogen
sulphate (0.64 g) and ammonium nitrate (1.4 g) were added
and stirred at room temperature for 0.5 h and refluxed for 5 h.
Worked up as method Baghernejad et al. [14] to afford yellowish
to reddish oil. GC-MS analyses gave (11.40 %), M+• 223,
calculated for C11H13NO4 major fragments: 163 (M+• – CH3),
147 (M+• – OCH3), 135, 115, 107, 91, 77 (C6H6).
Shimadzu. GC Parameters were setup as follows, oven tempe-
rature (°C) = 60.0, oven equilibrium time (min) = 0.50; injec-
tion temperature (°C) = 280.0; interface temperature (°C) =
300.0; column length (m) = 30; column diameter (mm) = 0.25;
column pressure (kPa) = 100; column flow (mL/min) = 1.6;
linear velocity = 46.4; split ratio = 22; total flow (mL/min) =
40.2; program time (min) = 27.00. MS parameter, start m/z =
33.00 end m/z = 550.00; scan interval (s) = 0.50; scan speed
(amu/s) = 1000.
1
The original H NMR, spectra were generally recorded
in CDCl3 on a Bruker spectrometer at 400 MHz.
Preparation of extract and isolation of eugenol: Clove
bud (100 g) were air dried and extracted with dichloromethane
for 2 × 24 h. The extract was filtrated and evaporated with
rotary evaporator to afford yellowish oil (40.4 g, 40.4 %).
Column chromatography was employed to isolate eugenol
from the clove oil (10 g). Gradient elution starting with hexane
and increased by the following hexane/dichloromethane ratios:
4/1, 3/2, 1/1 and 0/100). Twenty fractions were collected from
elution. Fractions shown to be identical by thin layer chromato-
graphy were combined and evaporated in rotary evaporator.
Fractions containing eugenol were combined affording yellowish
oil (8.26 g) (82.6 %). This oil was identified as eugenol by gas
chromatography-mass spectrometry (GC-MS) analyses, M+•
164, calculated for C10H12O2 Major fragments: 149 (M+• – CH3),
131, 121, 103, 91, 77 (C6H6, base peak); 1H NMR (400.1 MHz,
CDCl3): δ 6.82 (1H, d, ArH), 6.67 (1H, d, ArH), 6.66 (1H, s,
ArH), 5.91(2H, m, -CH2-), 5.53 (2H, m, ArOH and -HC=),
5.05 (2H, m, =CH2), 3.81 (3H, s, ArOCH3).
RESULTS AND DISCUSSION
Eugenol as a starting material for synthesis of nitro-methyl
eugenol was extracted and isolated from clove bud of Syzygium
aromaticum. Extraction with dichloromethane gave a yellowish
clove oil (40.4 %) and this crude oil was fractionated by column
chromatography to give eugenol which was confirmed by GC-
MS and 1H NMR analysis. The GC-MS result showed eugenol
peak with the retention time of 12.407 min (Fig. 1).
Synthesis of methyl eugenol: A 100 mL three-neck flask
equipped with condenser and magnetic stirrer was charged
with eugenol (5 g) was then added NaOH (2 g in 20 mL of
distilled water) and stirred for 15 min. 4 mL of dimethyl sulfate
was added drop-wise and stirring for 0.5 h. The mixture was
refluxed at 103 °C for 1 h. Worked up was adapted as method
by Riyanto et al. [13] to afford yellowish oil. GC-MS) analyses,
M+• 178, calculated for C11H14O2 Major fragments: 163 (M+•-
1
Eugenol
1
CH3), 147 (M+• – OCH3), 135, 115, 107, 91, 77 (C6H6). H
NMR (400.1 MHz, CDCl3): δ 6.82 (1H, d, ArH), 6.67 (1H, d,
ArH), 6.66 (1H, s, ArH), 5.91(2H, m, -CH2-), 5.50 (1H, m,
-HC=), 5.05 (2H, m, =CH2), 3.81 (3H, s, ArOCH3), 3.77(3H,
s, ArOCH3).
6
5
4
20
3
15
2
5
10
25
30
Fig. 1. Chromatogram of isolated eugenol
Synthesis of 5-nitromethyl eugenol
Eugenol is a simple phenol which is potentially reactive
towards electrophilic aromatic substitution. This is because
the hydroxy group, (-OH), is a strongly activating, ortho- or
para- directing substituent. Protection of phenols is one of the
most common synthetic strategies utilized to mask hydroxyl
functionalities during multistep synthetic procedures. Proce-
dures of o-methylation are widely employed for the protection
and purification of various natural and synthetic products.
Eugenol could be easily methylated by dimethyl sulfate in
high yield [13]. The GC-MS result showed methyl eugenol
peak (86.58 %) with the retention time of 9.928 min (Fig. 2).
Nitration of benzene derivatives with electron donating
substituent such as methoxy leads to substitution at o- and
p-positions according to a statistical distribution. Structurally
the methyl eugenol is similar to dimethoxybenzene will effect
Method (a): Nitration of methyl eugenol using nitration
of benzene approaches: A 50 mL round bottomed flask with
magnetic stirrer was charged with 0.01 M (5 mL) H2SO4 and
0.5 g methyl eugenol was stirred for 5 min (solution A). 70 %
HNO3 (10 mL) was mixed with 0.01 M (10 mL) H2SO4
(solution B). The (solution B) was added slowly to the solution
A and stirred at room temperature for 1 h then refluxed for 20
min. Worked up as method Sudarma et al. [8] to afford yello-
wish oil (0.72 g). GC-MS analyses gave (5.97 %), M+• 223,
calculated for C11H13NO4 Major fragments: 163 (M+• – CH3),
147 (M+• – OCH3), 135, 115, 107, 91, 77 (C6H6).
Method (b): Nitration of methyl eugenol using nitration
of dimethoxybenzene approaches: In a 25 mL beaker there
were added methyl eugenol (1 g), acetic acid (4 mL) and