Vol. 26, No. 2 (2014)
Synthesis and α-Chymotrypsin Activity of Derivatives of 7-Hydroxy-4-methyl-1-benzopyran-2-one 327
320-A spectrophotometer (wave number in cm-1) using KBr
pellets. Numbers of protons calculated by nuclear magnetic
resonance spectra also helped in identification of structures
and were recorded on a Bruker spectrometer operating at 300
MHz in CD3OD solution. Chemical shifts are quoted in ppm.
Mass spectra (EIMS) were given on JMS-HX-110 spectro-
meter. Resorcinol, ethylacetoacetate and the other electrophiles
(methyl iodide, ethyl iodide, isopropyl iodide, allyl iodide,
2-phenylethyliodide, 2-chlorobenzylchloride, 4-bromobenzyl-
bromide, 4-flurobenzyl chloride and 4-chlorobenzyl chloride)
were purchased from Sigma Aldrich and Alfa Aesar through
local suppliers. All the other employed solvents were of
analytical grade.
m.w. 190; IR (KBr, νmax, cm-1): 3535 (O-H stretching), 3401
(C-H aromatic stretching), 1729 (C=O stretching), 1616 (C=C
stretching of aromatic ring). 1H NMR (300 MHz, CD3OD δ/
ppm): 7.60 (d, J = 8.4 Hz, 1H, H-5), 6.80 (dd, J = 8.7, 2.5 Hz,
1H, H-6), 6.69 (d, J =2.5 Hz, 1H, H-8), 6.09 (s, 1H, H-3),
3.78 (s, 3H, OCH3-1), 2.41 (s, 3H, CH3-4). EI-MS: m/z 190
[M]+, 175 [C10H7O3]+, 159 [C10H7O2]+, 144 [C9H4O2]+, 108
[C6H4O2]+, 51 [C4H3]+.
7-Ethoxy-4-methyl-1-benzopyran-2-one (3b): Buff
amorphous powder; yield 76 %; m.p. 98-100 ºC; m.f.: C12H12O3;
m.w. 204; IR (KBr, νmax, cm-1): 3539 (O-H stretching), 3407
(C-H aromatic stretching), 1727 (C=O stretching), 1614 (C=C
stretching of aromatic ring). 1H NMR (300 MHz, CD3OD δ/
ppm): 7.68 (d, J = 8.7 Hz, 1H, H-5), 6.95 (dd, J = 8.7, 2.4 Hz,
1H, H-6), 6.87 (d, J =2.4 Hz, 1H, H-8), 6.15 (s, 1H, H-3),
4.11 (q, J = 6.9 Hz, 2H, CH2-1), 2.43 (s, 3H, CH3-4), 1.42 (t,
J = 6.9 Hz, 3H, CH3-2). EI-MS: m/z 204 [M]+, 189 [M-CH3]+,
175 [C10H7O3]+, 159 [C10H7O2]+, 144 [C9H4O2]+, 108 [C6H4O2]+,
51 [C4H3]+.
Procedure for the synthesis of 7-hydroxy-4-methyl-1-
benzopyran-2-one (1): Resorcinol (4.4 g; a) and ethylaceto-
acetate (5 mL; b) was taken in iodine flask. Reaction mixture
was shaken well until reaction mass become clear by keeping
the flask on water bath and temperature was maintained at
40 ºC. Then, cooled concentrated sulphuric acid (15 mL) was
added to the iodine flask and the reaction mixture was placed
for overnight. Next day, the chilled water was added in the
solution with continuous stirring. The reaction mixture was
reserved at room temperature for 0.5 h; dark yellow solid was
filtered and washed with distilled water to afford 7-hydroxy-
4-methyl-1-benzopyran-2-one (1) on drying.
7-Isopropoxy-4-methyl-1-benzopyran-2-one (3c): Off-
white amorphous powder; yield 78 %; m.p: 88-90 ºC; m.f.:
C13H14O3; m.w. 218; IR (KBr, νmax, cm-1): 3542 (O-H stretching),
3406 (C-H aromatic stretching), 1728 cm–1 (C=O stretching),
1613 (C=C stretching of aromatic ring). 1H-NMR (300 MHz,
CD3OD δ/ppm): 7.67 (d, J = 8.7 Hz, 1H, H-5), 6.92 (dd, J =
8.7, 2.4 Hz, 1H, H-6), 6.86 (d, J = 2.4 Hz, 1H, H-8), 6.13 (s,
1H , H-3), 4.72 (m, 1H, H-1), 2.43 (s, 3H, CH3-4), 1.34 (d, J =
6.0 Hz, 6H, H-2 & 3). EI-MS: m/z 218[M]+, 175 [C10H7O3]+,
159 [C10H7O2]+, 144 [C9H4O2]+, 108 [C6H4O2]+, 51 [C4H3]+.
7-Allyoxy-4-methyl-1-benzopyran-2-one (3d): Creamy
white amorphous powder; yield 78 %; m.p. 154-157 ºC; m.f.:
C13H12O3; m.w. 216; IR (KBr, νmax, cm-1): 3503 (O-H stretching),
3410 (C-H aromatic stretching), 1729 (C=O stretching), 1617
(C=C stretching of aromatic ring). 1H NMR (300 MHz, CD3OD
δ/ppm): 7.66 (d, J = 9.0 Hz, 1H, H-5), 6.96 (dd, J = 9.0, 2.4,
1H, H-6), 6.90 (d, J =2.4 Hz, 1H, H-8), 6.15 (s, 1H, H-3),
6.11-6.02 (m, 1H, H-2), 5.44 (dd, J =1.5, 17.1 Hz, Hb-3), 5.27
(dd , J = 1.5, 10.5 Hz, Ha-3), 4.66 (d, J = 5.4 Hz, H-1), 2.43 (s,
3H, CH3-4). EI-MS: m/z 216[M]+, 175 [C10H7O3]+, 159
[C10H7O2]+, 144 [C9H4O2]+, 108 [C6H4O2]+, 51 [C4H3]+.
7-(2-Phenylethoxy)-4-methyl-1-benzopyran-2-one (3e):
Buff amorphous powder; yield 64 %; m.p. 96-98 ºC; m.f.:
C18H16O3; m.w. 280; IR (KBr, νmax, cm-1): 3510 (O-H stretching),
3418 (C-H aromatic stretching), 1723 (C=O stretching), 1613
(C=C stretching of aromatic ring). 1H NMR (300 MHz, CD3OD
δ/ppm): 7.64 (d, J = 8.7 Hz, 1H, H-5), 7.32-7.17 (m, 5H, H-2
to 6'), 6.94 (dd, J = 9.0 Hz, 2.4, 1H, H-6), 6.88 (d, J =2.4 Hz,
1H, H-8), 6.14 (s, 1H, H-3), 4.28 (t, J = 6.9 Hz, 2H, H-8'),
3.12 (t, J = 6.6 Hz, 2H, H-7'), 2.42 (s, 3H, CH3-4), EIMS: m/z
280 [M]+, 175 [C10H7O3]+, 159 [C10H7O2]+, 144 [C9H4O2]+, 108
[C6H4O2]+, 91 [C7H7]+, 51 [C4H3]+.
General procedure for the synthesis of O-substituted
derivatives 2a-i: Compound (1) (2.80 mmol, 0.5 g) was taken
in round bottom flask and N,N-dimethyl formamide (around
5 mL) and sodium hydride (2.80 mmol; 0.01g,) were added in
it at room temperature. The reaction mixture was stirred for
15 min and then the electrophiles (2.80 mmol; 2a-i) were added
into the mixture. The reaction mass was further stirred and
monitoring through TLC. After completion of the reaction,
the reaction mixture was quenched with cold water (150 mL).
The received solid was filtered, washed with water and dried to
yield the corresponding O-substituted derivatives of 7-hydroxy-
4-methyl-1-benzopyran-2-one (3a-i).
General procedure for the synthesis of compounds 3j-l:
Compound 1 (2.8 mmol; 0.5 g) and 20 mL of 5 % sodium
hydroxide solution was taken in the round bottom flask. The
mixture was stirred till solution become clear and then the
corresponding electrophiles (2.80 mmol; 2j-l) were added into
the reaction mixture with constant stirring at room temperature
until precipitates were formed. Precipitates were filtered,
washed with distilled water and dried to yield the corresponding
derivatives (3j-l).
Characterization of the synthesized compounds
7-Hydroxy-4-methyl-1-benzopyran-2-one (1): Dark
yellow amorphous powder; yield 92 %; m.p. 188-190 ºC; m.f.:
C10H8O3; m.w. 176; IR (KBr, νmax, cm-1): 3550 (O-H stretching),
3418 (C-H aromatic stretching), 1717 (C=O stretching), 1629
(C=C stretching of aromatic ring); 1H NMR (300 MHz, CD3OD
δ/ppm): 7.58 (d, J = 8.7 Hz, 1H, H-5), 6.82 (dd, J = 8.7, 2.4
Hz, 1H, H-6), 6.70 (d, J =2.4 Hz,1H, H-8), 6.09 (s, 1H, H-3),
2.41 (d, J = 0.9 Hz, 3H, CH3-4) . EI-MS: m/z 176 [M]+, 159
[C10H7O2]+, 144 [C9H4O2]+, 108 [C6H4O2]+, 51 [C4H3]+.
7-(2-Chlorobenzyloxy)-4-methyl-1-benzopyran-2-one
(3f): Creamy white amorphous powder; yield 70 %; m.p. 135-
137 ºC; m.f.: C17H13O3Cl; m.w. 300; IR (KBr, νmax, cm-1): 3515
(O-H stretching), 3416 (C-H aromatic stretching), 1719 (C=O
stretching), 1611 (C=C stretching of aromatic ring). 1H NMR
(300 MHz, CD3OD δ/ppm): 7.72 (d, J = 8.7 Hz, 1H, H-5),
7.58-7.32 (m, 4H, H-3' to 6'), 7.05 (dd, J = 8.7, 2.7 Hz, 1H, H-
6), 6.98 (d, J =2.4 Hz, 1H, H-8), 6.17 (s, 1H, H-3), 5.27 (s,
7-Methoxy-4-methyl-1-benzopyran-2-one (3a): White
amorphous powder; yield 58 %; m.p. 88-90 ºC; m.f.: C11H10O3;