16 Letters in Drug Design & Discovery, 2010, Vol. 7, No. 1
Perveen et al.
(3H, t, J = 6.4 Hz, CH3); HREIMS, m/z: 192.2681 [M+, C12H16O2
(10 %) and administered intraperitoneally (i.p., 10ml/kg). Control
animals received appropriate vehicle.
requires 192.2570].
3.4.6. Ethyl-3, 5-dinitrobenzoate (5)
Yield 1.6 g (94 %); Rf = 0.6 (hexane/chloroform, 6:4); 1H-
NMR (CDCl3, 400 MHz) ꢀ: 8.21 (1H, d, J = 2.1 Hz, H-4), 8.02
(2H, d, J = 2.1 Hz, H-2, 6), 4.32 (2H, q, J = 6.9 Hz, CH2), 1.35 (3H,
t, J = 6.9 Hz, CH3); HREIMS, m/z: 240.0911 [M+, C9H8O6N2 re-
quires 240.1705].
3.3. Antidepressant Test in Mice (Forced Swim Test)
FST was performed as described by Porsolt et al., 1978 [30]
and Dar et al. 1997 [31]. The pre-test session was performed by
placing them in FST tank (glass tank; height = 25cm, diameter =
15cm filled with 10cm water at 250C) for 15min. Movement of
animals were noted carefully. Injured or ill animals e.g., those
showing symptoms of nose bleeding were discarded. After 24hrs,
mice received respective treatment and after 1 hr the animals were
placed in FST tank and immobility time was recorded in seconds
for 5 minutes. Mouse was considered immobile if it remained float-
ing with all four limbs motionless keeping its nose above the water.
Percent reduction in immobility time of the treated animals was
calculated as follows:
3.4.7. Ethyl-4-nitrobenzoate (6)
Yield 1.82 g (93 %); Rf = 0.62 (hexane/chloroform, 4:6);
1H-NMR (CDCl3, 400 MHz) ꢀ: 7.27 (2H, d, J = 7.5 Hz, H-3, 5),
7.25 (2H, d, J = 7.5 Hz, H-2, 6), 4.05 (2H, q, J = 6.8 Hz, CH2), 1.23
(3H, t, J = 6.8 Hz, CH3); HREIMS, m/z: 195.1502 [M+, C9H9O4N
requires 195.1735].
3.4.8. Ethyl Salicylate (7)
Yield 12.5 g (84 %); 1H-NMR (CD3OD, 400 MHz) ꢀ: 7.77 (1H,
dd, J = 8.1, 1.8 Hz, CH), 7.69 (1H, d, J = 8.0 Hz, CH), 7.46 (1H,
dd, J = 8.0, 7.8 Hz, CH), 6.89 (1H, dd, J = 8.1, 7.8 Hz, CH), 4.36
(2H, q, J = 6.9 Hz, CH2), 1.37 (3H, t, J = 6.9 Hz, CH3); HREIMS,
m/z: 166.1208 [M+, C9H10O3 requires 166.1754].
Percent reduction in immobility time = (Mean Immobility time
of test mice / Mean Immobility time of control x 100) – 100.
3.4. Preparation of esters 2-4
0.09 mole (12.24 g) of phenylacetic acid in different alcohols
(ethanol, isoamyl alcohol and n-butanol) containing sulfuric acid
(1ml) with activated Linde 4A molecular sieves (9.79 g). The reac-
tion was refluxed for 24 hrs and monitored by TLC. After comple-
tion of reaction, the reaction mixture was cooled and dried by the
addition of anhydrous sodium sulfate to absorb excess of sulfuric
acid and water that was formed during the reaction. The excess of
alcohol was removed by evaporation under reduced pressure and
affording esters of phenylacetic acid.
4. CONCLUSION
The result indicates that alcohol 1 and ester 3 having five car-
bon side chains demonstrate maximum antidepressant-like activity
whereas, esters with short alkyl side chain 2 and 4 causes a dra-
matic decline in it. Similarly, addition of nitro group (electron
withdrawing group) to the phenyl ring also has adverse effect on the
antidepressant-like activity. Addition of hydroxyl group at ortho
position of phenyl 7 elicit a complete loss of activity but displayed
depressant activity that may be related to its electron donating na-
ture which possibly activates the ring at 1, 4 and 6 positions.
3.4.1. Preparation of ethyl-3, 5-dinitrobenzoate (5), ethyl-4-
nitrobenzoate (6) and ethyl salicylate (7)
Ethyl-3,5-dinitrobenzoate, ethyl-4-nitrobenzoate and ethyl
salicylate were prepared using 3, 5-dinitrobenzoic, 4-nitrobenzoic
and salicylic acid respectively by the method mentioned above.
Thus research towards ester with long chain alkyl group ap-
pears important and may lead to the new antidepressants.
3.4.2. Preparation of 2-Phenylethyl Alcohol (1)
ACKNOWLEDGMENTS
Ethyl phenylacetate 2 (13.28 g) was dissolved in ethanol. So-
dium metal (0.021 g) was added by continuous stirring. After one hr
the reaction was completed (TLC analysis). Excess of ethanol was
removed under reduced pressure and then by vacuum distillation.
Dr. Shahnaz Perveen is thankful for the financial support from
Pakistan Science Foundation, for providing funding under “Re-
search Support Grants for Active Scientist and Technologist of
Pakistan”.
1
Yield 8.83 g (90 %); Rf = 0.70 (chloroform/methanol, 9:1); H-
NMR (CD3OD, 400 MHz) ꢀ: 7.10 (m, 5H), 3.52 (2H, t, J = 6.3 Hz,
CH2), 2.61 (2H, t, J = 6.3 Hz, CH2); HREIMS, m/z: 122.1640 [M+,
C8H10O requires 122.1664].
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3.4.3. Ethyl Phenylacetate (2)
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Yield 13.28 g (90 %); Rf = 0.75 (chloroform/methanol, 9:1);
1H-NMR (CD3OD, 400 MHz) ꢀ: 7.05 (m, 5H), 4.08 (2H, q, J = 6.9
Hz, CH2), 3.31 (2H, br s, CH2), 1.24 (3H, t, J = 6.9 Hz, CH3);
HREIMS, m/z: 164.1256 [M+, C10H12O2 requires 164.1043].
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3.4.4. Isoamyl Phenylacetate (3)
Yield 16.1 g (87 %); 1H-NMR (CD3OD, 400 MHz) ꢀ: 7.09-7.28
(m, 5H), 3.25 (2H, br s, CH2), 4.06 (2H, t, J = 6.1 Hz, CH2), 1.54
(2H, m, CH2), 1.88 (1H, m, CH), 0.89 (6H, d, J = 6.6 Hz, 2CH3);
HREIMS, m/z: 206.4167 [M+, C13H18O2 requires 206.2839].
3.4.5. n-Butyl Phenylacetate (4)
1
Yield 1.8 g (94 %); Rf = 0.7 (chloroform/methanol, 9:1); H-
NMR (CD3OD, 400 MHz) ꢀ: 7.08–7.30 (m, 5H), 4.12 (2H, t, J =
6.3 Hz, CH2), 3.23 (2H, s, CH2), 1.31-1.52 (4H, m, 2CH2), 0.90
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