Synthesis of new 8-formyl-4-methyl-7-hydroxy coumarin derivatives

Article abstract of DOI:10.5012/jkcs.2012.56.4.459

8-Formyl-4-Methyl-7-Hydroxy Coumarin Derivatives were synthesized via Penchem condensation followed by Duffs reaction. Treatment of this with N,N-di substituted cyano acetamides in the presence of piperdine afforded New 8- Formyl-4-Methyl-7-Hydroxy Coumarin Derivatives (7a-o). Their structures were characterized by IR, ¹H and ¹³C NMR and Mass spectral and elemental analysis data.

Full text of DOI:10.5012/jkcs.2012.56.4.459

Journal of the Korean Chemical Society
2012, Vol. 56, No. 4
Printed in the Republic of Korea
http://dx.doi.org/10.5012/jkcs.2012.56.4.459
Synthesis of New 8-Formyl-4-methyl-7-hydroxy Coumarin Derivatives
D. M. Manidhar, K. Uma Maheswara Rao, N. Bakthavatchala Reddy,
Ch. Syama Sundar, and C. Suresh Reddy*
Department of Chemistry, S.V. University, Tirupati, A.P, India.
*E-mail: csrsvu@gmail.com
(Received January 13, 2012; Accepted June 13, 2012)
ABSTRACT. 8-Formyl-4-Methyl-7-Hydroxy Coumarin Derivatives were synthesized via Penchem condensation followed
by Duffs reaction. Treatment of this with N,N-di substituted cyano acetamides in the presence of piperdine afforded New 8-
1
Formyl-4-Methyl-7-Hydroxy Coumarin Derivatives (7a-o). Their structures were characterized by IR, H and 13C NMR and
Mass spectral and elemental analysis data.
Key words: N,N-di substituted cyano acetamides, Piperdine, Coumarin derivatives
INTRODUCTION
EXPERIMENTAL
Materials and Methods
Coumarin is a pleasanty fragrant benzopyrone com-
pound, found in many plants, notably in high concentra-
tion in the tonka bean (Dipteryx odorata), vanilla grass
(Anthoxanthum odoratum), sweet woodruff (Galium odo-
ratum), mullein (Verbascum spp.), sweet grass (Hiero-
chloe odorata), Cassia cinnamon (Cinnamomum aromaticum)
and sweet clover. Natural products with coumarin moiety
and have wide range of biological activity. They are used
as drugs, intermediates and pesticides.1 They are found to
have anti-coagulant, inflammatory microbial,2 oxidant,3
HIV, allergic, cancer,4 proliferative and viral5 properties.
4-methyl-7-hysroxy coumarin has similar structure of
Scopoletin, an alkaloid which is isolated from medicinal
plant (Gelsemium Seperiven) has an anti-cancer activity.
Recently 4-methyl-7-hydroxy coumarin has been reported to
have anti skin-cancer activity.6
Melting points were determined on Buchi-540 melting
point apparatus and are un-corrected. FT-IR spectra were
recorded as KBr pellet on Nicolet-380 FT-IR instrument
(Model Thermo Electron corporation-Spectrum one), 1H
and 13 C NMR (proton decoupled) spectra were recorded
on Varian 300 MHz spectrometer using DMSO-d6 and
CDCl3 as solvent. Mass spectra were recorded on Agilent
triple quadrapole mass spectrometer equipped with turbo
ion spray interface at 360 oC.
Synthesis of 4-Methyl-7-hydroxy Coumarin of 27
Concentrated sulfuric acid (20 mL) was added to a
100 mL round bottom flask and cooled to 0-5 oC in an ice
bath. A solution of resorcinol (0.001 mol) in ethyl ace-
toacetate (0.0015 mol) was added to sulfuric acid under
constant stirring at 0-5 oC. The reaction mass was stirred
over night at room temperature and poured in to crushed
ice under vigorous stirring. An off-white solid obtained was
filtered and recrystallised in ethanol. m.p: 180-182 oC; 1H
NMR (300MHz, CDCl3): δ 2.49 (s, 3H, C4-CH3), 6.31 (s,
1H, C3-H), 6.92 (d, 1H, C6-H, J=9.0 Hz), 6.94 (s, 1H, C8-
H), 7.57 (d, 1H, C5-H, J=9.0 Hz); IR (KBr, ν max): 3423
(-OH), 1733 (-CO), 1555 (-C=C-) cm-1.
Coumarin has clinical medical value by itself, as an
edema modifier. Coumarin and other benzopyrones, such
as 5,6 benzopyrone, 1,2 benzopyrone, diosmin and others
stimulate macrophages and degrade extracellular albu-
men, allowing faster resorption of edematous fluids.
Coumarin itself has no anticoagulant activity but is
transformed into the natural anticoagulant called dicou-
marol by a number of fungi species. This occurs as the
result of the production of 4-hydroxycoumarin, then fur-
ther (in the presence of naturally occurring formaldehyde)
into the actual anticoagulant dicoumarol, a fermentation
product and mycotoxin. This substance was responsible
for the bleeding disease known historically as “sweet clo-
ver disease” in cattle eating moldy sweet clover silage.
Synthesis of 4-Methyl-7-hydroxy-8-formyl Coumarin 38
7-hydroxy-4-methyl-coumarin (2) (0.001 mol) was dis-
solved in glacial acetic acid (20 mL) and hexamethylene
tetramine (0.003 mol) was added to the reaction mixture.
Heated to 80-85 oC in a water bath for 6.0 hr. A hot mix-
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460
D. M. Manidhar, K. Uma Maheswara Rao, N. Bakthavatchala Reddy, Ch. Syama Sundar, and C. Suresh Reddy
ture of 5 mL water and 30 mL hydrochloric acid was added,
kept for 30 min. and cooled to room temperature. It was
extracted with diethyl ether. And on evaporation of ether,
a pale yellow solid was obtained. Yield: 22%; m.p. 176-
178 ºC; 1H NMR (300 MHz, CDCl3): δ 2.44 (s, 3H, C4-
CH3), 6.22 (s, 1H, C3-H), 6.90-6.93 (d, 1H, C6-H, J=9
Hz), 7.73-7.76 (d, 1H, C5-H, J=9 Hz), 10.63 (s, 1H, HCO),
12.28 (s, 1H, OH); IR (KBr, ν max): 3442(-OH), 1742
(-CO), 1644(-CHO), 1594(-C=C-) cm-1.
cooled to 0-5 oC and filtered the solid. Pale yellow to
orange red color solids were obtained. Yields varied from
50-60%.
SPECTRAL DATA
(E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-
8-yl)-N-(1-(4-methoxyphenyl)ethyl) acryl amide (7a)
IR (KBr cm-1): 3437 (-OH), 3275 (-NH), 2240 (-CN),
1729 (-CO, cyclic), 1624 (-CO), 1557 (-C=C-): 1H NMR
(DMSO-d6): δ 11.8 (s, -OH), 8.9 (s, H, -NH), 8.5 (s, H,
exocyclic CH=C), 6.9-7.2 (m, 4H, phenyl), 6.0-6.5 (m,
2H, coumarin ring), 5.0 (q, H, -CH-NH), 3.8 (s, 3H, -OCH3),
2.45 (s, 3H, -CH3), 1.5 (d, 3H, -CH3); 13C NMR (DMSO-
d6): δ 160.8 (C-2), 160 (C=O), 158.9 (C-1'), 155 (C-7), 153.4
(C-exocyclic), 153 (C-4), 146 (C-10), 133 (C-4'), 126.5
(C-3', C-5'), 125.2 (C-5), 118.2 (C-8), 115 (-CN), 114.0
(C-2', C-6', C-6), 112.5 (C-3), 112.0 (C-9), 103 (C-exo-
cyclic), 56.1 (-OCH3), 49.0 (C, -CH-NH ), 21.5 (C, -CH3),
19.5 (-CH3 of C-4); MS: m/z(M++1) 405.4; Anal. Calcd
for C23H20N2O5: C, 68.31; H, 4.98; N, 6.93; O, 19.78,
Found: C, 68.29; H, 4.89; N, 6.91; O,19.8.
Synthesis of N,N-di substituted cyano acetamide Deriva-
tives (6 a-o)9,10
General procedure:
Amine (0.001 moles) was dissolved in 10 ml ethanol,
0.0012 moles of ethyl cyano acetate was added and stirred
for 5.0 hr at reflux. Cooled the mass to 0-5 oC and filtered,
which were used directly in the next step. Yields were vari-
ed from 60-70%.
Synthesis of 7a-o by Knoevengel Condensation of 3
& 6a-o11
General procedure:
8-formyl-4-methyl-7-hydroxy Coumarin (3) (0.001 mol)
was dissolved in 10mL ethanol containing N,N di sub-
stituted cyanoacetamide derivatives (6a-o) (0.001 mol)
and catalytic amount of piperidine. Refluxed for 2.0 hr,
(E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-
8-yl)-N-(1-phenylethyl) acrylamide (7b)
IR (KBr, cm-1): 3442 (-OH), 2257 (-CN), 3275 (-NH),
1
1742 (-CO), 1644 (cyclic -CO), 1594 (-C=C); H NMR
(DMSO-d6): δ 11.7 (s, H, -OH), 8.9 (s, H, -NH), 8.5 (s, H,
exocyclic CH=C), 6.5-7.4 (m, 5H, phenyl), 6.0-6.4 (m,
2H, coumarin ring), 6.23 (d, 1H, endocyclic), 5.0 (q, H, -CH-
NH), 2.5 (s, 3H, CH3), 1.5 (d, 3H, CH3); 13C NMR (DMSO-d6 :
δ 164.5 (C-4'), 160.7 (C-2), 159 (-CO), 155 (C-7), 153.5
(C, exocyclic ethylene), 152.5 (C-4), 146.8 (C-10), 128.7
(C-2', C-6'), 127 (C-3', C-5'), 126 (C-1'), 125 (C-5), 118
(C-8), 116 (-CN), 114.5 (C-6), 112.5 (C-3), 112 (C-9), 103
(C-exocyclic), 49 (-CH-NH-), 22 (-CH3), 21.5 (-CH3);
MS: m/z(M++1) 375.0; Anal. Calcd for C22H18N2O4: C,
70.58; H, 4.85; N, 7.48; O, 17.09 Found C, 70.55; H, 4.80;
N, 7.50; O, 17.0.
Scheme 1. Synthesis of 4-methyl-7-hydroxy-8-formyl coumarin.
Scheme 2. Synthesis of N,N-di substituted cyano acetamide deri-
vatives (6 a-o).
(E)-N-benzyl-2-cyano-3-(7-hydroxy-4-methyl-2-oxo-2H-
chromen-8-yl)acrylamide (7c)
IR (KBr, cm-1): 3430 (-OH), 3275 (-NH), 2230 (-CN),
1730.4 (-CO), 1674 (cyclic -CO), 1546 (-C=C) cm-1; 1H
NMR(DMSO-d6): δ 11.7 (s, H, -OH), 8.9 (s, H, -NH), 8.5
(s, H, exocyclic CH=C), 7.5 (d, H, coumarin ring), 6.8 (d,
H, coumarin ring), 7.2-7.4 (m, 5H, phenyl), 6.0 (s, H,
endocyclic), 4.5 (s, 2H, -CH2), 2.5 (s, 3H, CH3); 13C NMR
(DMSO-d6): δ 162.7 (C-2), 160 (-CO), 155 (C-7), 153.5
(C, ethylene), 152.5 (C-4), 146 (C-10), 134 (C-4'), 128.5
Scheme 3. Synthesis of 7a-o by Knoevengel condensation of 3
& 6a-o.
Journal of the Korean Chemical Society

Synthesis of New 8-Formyl-4-methyl-7-hydroxy Coumarin Derivatives
461
(C-2', C-6'), 126.5 (C-3', C-5'), 126 (C-1'), 125.2 (C-5),
118.2 (C-7), 115 (C, -CN), 114.5 (C-6), 112.5 (C-3), 112
(C-9), 103 (C-CN), 43.0 (C, -CH2), 19.5 (C, -CH3); MS:
m/z(M++1) 361.9; Anal. Calcd for C21H16N2O4: C, 69.99;
H, 4.48; N, 7.77; O, 17.76. Found C, 69.89; H, 4.44; N,
7.80; O, 17.66.
8-yl) N,N-dimethylacrylamide (7g)
IR (KBr, cm-1): 3442 (-OH), (-CN), 1742 (-CO), 1644
(cyclic -CO), 1594 (-C=C); 1H NMR (DMSO-d6): 11.8 (s,
-OH), 8.3 (s, H, -ethylene), 6.2-7.5 (m, 3H coumarin ring),
3.02 (d, 6H, -N(CH3)2), 2.43 (s, 3H, -CH3); 13C NMR
(DMSO-d6): δ 160.5 (-CO), 159.7 (C-2), 155 (C-7), 153
(C, exocyclic ethylene), 152.5 (C-5), 146 (C-10), 125.2
(C-3), 118.2 (C-8), 115 (-CN), 114.0 (C-6), 112.5 (C-3),
112.0 (C-5), 107 (C, ethylene), 36.6 (2C, -N(CH3)2), 19.5
(C, -CH3); MS: m/z(M++1): 300.0; Anal. Calcd for
C16H14N2O4: C, 64.42; H, 4.73; N, 9.39; O, 21.45. Found;
C, 64.24; H, 4.69; N, 9.55; O, 21.59.
(E)-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)-
2-(piperidine-1-carbonyl) acrylonitrile (7d)
IR (KBr, cm-1): 3442 (-OH), 2240.3 (-CN), 1742 (-CO),
1644 (cyclic -CO), 1594 (-C=C); 1H NMR (DMSO-d6): δ
11.79 (s, -OH), 8.32 (s, H, exocyclic CH=C), 6.2-7.55 (m,
3H, coumarinring), 3.7 (m, 4H, piperidine), 2.5 (s, 3H, CH3),
1.6 (m, 2H piperidine), 1.53 (m, 4H, piperidine); 13C NMR
(DMSO-d6): δ 170.5 (CO), 160 (C-2), 155 (C-7), 153 (C,
ethylene), 152.7 (C-4), 146 (C-10), 125.2 (C-5), 118.2 (C-
8), 115 (CN), 114.0 (C-6), 112.5 (C-3), 112.0 (C-9), 106
(C, ethylene), 47.0 (2C, piperidine), 25.0 (2C, piperidine), 24.1
(C, piperidine), 19.5 (C, -CH3); MS: m/z (M++1) 339.3;
Anal. Calcd for C19H18N2O4: C, 67.44; H, 5.36; N, 8.28;
O, 18.91. Found; C, 67.40; H, 5.39; N, 8.31; O, 18.20.
(E)-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)-
2-(pyrrolidine-1-carbonyl)acrylo nitrile (7e)
(E)-2-cyanoN,N-diethyl-3-(7-hydroxy-4-methyl-2-oxo-
2H-chromen-8-yl) acrylamide (7h)
IR (KBr, cm-1): 3442 (-OH), 2254 (-CN), 1742 (-CO),
1644 (cyclic -CO), 1594 (-C=C); 1H NMR(CDCl3): δ 11.8
(s, -OH), 8.3 (s, H, ethylene), 6.24-7.55 (m, 3H coumarin
ring), 3.72 (q, 4H, -H2C-N-CH2), 2.4 (s, 3H, -CH3), 1.34
(t, 6H, - (CH3)2); 13C NMR (CDCl3): δ 160.5 (CO), 159.7
(C-2), 155 (C-7), 153 (C-4), 146 (C-10), 125.2 (C-5),
118.2 (C-8), 115 (CN), 114.6 (C-6), 112.5 (C-3), 112.0 (C-
9), 106 (C, ethylene), 40.8 (q, 2C, -CH2), 19.5 (C, -CH3),
12.5 (t, 2C, -(CH3)2); MS: m/z(M++1): 327.5; Anal. Calcd
for C18H18N2O4: C, 66.25; H, 5.56; N, 8.58; O, 19.61.
Found; C, 66.30; H, 5.64; N, 8.65; O, 19.16.
IR (KBr, cm-1): 3442 (-OH), 2246 (-CN), 1742 (-CO),
1644 (cyclic -CO), 1594 (-C=C); 1H NMR (DMSO-d6): δ
11.8 (s, -OH), 8.35 (s, H, exocyclic CH=C), 6.23-7.5 (3H,
coumarin), 3.25 (t, 4H, pyrrolidine), 2.43 (s, 3H, -CH3),
1.72 (t, 4H, pyrrolidine); 13C NMR (DMSO-d6): δ170.7 (-CO),
160, (C-2), 155 (C-7), 153 (C, expcyclic ethylene), 146
(C-10), 125.2 (C-5), 118.2 (C-8), 115 (-CN), 114.0 (C-6),
112.5 (C-3), 112.0 (C-9), 106 (C, ethylene), 45.7 (2C, pyrro-
lidine), 25.0 (2C, pyrrolidine), 19.5 (C, -CH3); MS: m/
z(M++1) 325.3; Anal. Calcd for C18H16N2O5: C, 66.66; H,
4.97; N, 8.64; O, 19.73. Found; C, 66.76; H, 5.02; N, 8.54;
O, 19.80.
(E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-
8-yl) N,N-diisopropylacrylamide (7i)
IR (KBr, cm-1): 3442 (-OH), 2244 (-CN), 1742 (-CO),
1644 (cyclic -CO), 1594 (-C=C); 1H NMR (CDCl3): 11.8
(s, -OH), 8.35 (s, exocyclic ethylene), 6.23-7.55 (m, 3H,
coumarin ring), 4.0 (m, 2H, -CH-), 2.45 (s, 3H, -CH3),
1.27 (d, 12H, 4Me of isopropyl): 13C NMR (CDCl3): δ
160.5 (CO), 159.7 (C-2), 155 (C-7), 153 (C, exocyclic
ethylene), 152.7 (C-4), 146 (C-10), 125.2 (C-5), 118.2 (C-
8), 115 (CN), 114.6 (C-6), 112.5 (C-3), 112.0 (C-9), 107
(C, ethylene), 47.0 (2C, -CH), 19.5 (C - CH3), 21.5 (t, 4C,
-4CH3 of isopropyl); MS: m/z(M++1): 355.4; Anal. Calcd
for C20H22N2O4: C, 67.78; H, 6.26; N, 7.90; O, 18.06.
Found; C, 67.87; H, 6.30; N, 8.01; O, 18.14.
(E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-
8-yl) N-methylacrylamide (7f)
IR (KBr, cm-1): 3442 (-OH), 3225 (-NH), 2248 (-CN),
1
1742 (-CO), 1644 (cyclic -CO), 1594 (-C=C); H NMR
(DMSO-d6): 11.8 (s, OH), 8.4 (s, H, exocyclic ethylene),
8.1 (m, -NH), 6.22-7.5 (m, 3H, coumarin ring), 2.72 (d,
3H, -HN-CH3), 2.43 (s, 3H, -CH3); 13C NMR (DMSO-d6):
δ 160.5 (CO), 159.7 (C-2), 155 (C-7), 153.8 (C, exocyclic
ethylene), 153 (C-4), 146 (C-10), 125.2 (C-5), 118.2 (C-
8), 115 (CN), 114.5 (C-6), 112.5 (C-3), 112.0 (C-9), 104
(C, ethylene), 25.5 (-NH-CH3), 19.5 (C, -CH3); MS: m/
z(M++1): 285.3; Anal. Calcd for C15H12N2O4: C, 63.38;
H, 4.25; N, 9.85; O, 22.51. Found; C, 63.80; H, 4.19; N,
9.65; O, 22.39.
(E)-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)-
2-(1H-imidazole-1-carbonyl)acrylo nitrile (7j)
IR (KBr, cm-1): 3442 (-OH), 2254 (-CN), 1742 (-CO),
1644 (cyclic -CO), 1594 (-C=C), 1549 (-C=C, -C=N); 1H
NMR (DMSO-d6): 11.8 (s, OH), 8.35 (s, H exocyclic
ethylene), 6.23-7.55 (m, 3H coumarin ring), 8.14 (s, H,
imidazole), 7.4 (d, H, imidazole), 7.14 (d, H, imidazole),
2.45 (s, 3H, -CH3); 13C NMR(DMSO-d6): δ 189.7 (C, -CO),
162 (C, exocyclic ethylene), 160.5 (C-2), 155 (C-7), 153
(C-4), 136.7 (C, imidazole), 130.0 (C, imidazole), 146 (C-
(E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-
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D. M. Manidhar, K. Uma Maheswara Rao, N. Bakthavatchala Reddy, Ch. Syama Sundar, and C. Suresh Reddy
10), 125.2 (C-5), 117.5 (C, imidazole), 118.2 (C-8), 115 (-CN),
114.6 (C-6), 112.5 (C-3), 112.0 (C-9), 104 (C, ethylene),
19.5 (C, -CH3); MS: m/z(M++1): 322.3; Anal. Calcd for
C17H11N3O4: C, 63.55; H, 3.45; N, 13.08; O, 19.92.
Found; C, 63.45; H, 3.40; N, 13.11; O, 20.05.
methyl-2-oxo-2H-chromen-8-yl) acrylamide (7n)
IR (KBr, cm-1): 3442 (-OH), 2254 (-CN), 1742 (-CO),
1644 (cyclic -CO), 1594 (-C=C), 1549 (-C=C); 1H NMR
(DMSO-d6): 11.8 (s, OH), 10.5 (s, -NH), 8.35 (s, H exo-
cyclic ethylene), 8.1 (d, H of C-3'), 6.23-7.55 (m, 3H cou-
marin ring), 6.53-6.8 (2H, of C-2', C-6'), 3.8 (s, 6H of
-OCH3), 2.4 (s, 3H, -CH3); 13C NMR(DMSO-d6): δ 169
(C-1'), 64 (C, -CO), 160.5 (C-2), 155 (C-7), 153.6 (C, exo-
cyclic ethylene), 154 (C-4, C-5'), 146 (C-10), 125.2 (C-5),
123 (C-3'), 118.2 (C-8), 117 (C-4'), 115 (-CN), 114.6 (C-
6), 112.5 (C-3), 112.0 (C-9), 106 (C-2'), 104 (C, ethylene), 100
(C-6'), 56 (2C, -OCH3), 19.5 (C, -CH3); MS: m/z (M++1):
407.4; Anal. Calcd for C22H18N2O6: C, 65.02; H, 4.46; N,
6.89; O, 23.62. Found; C, 65.07; H, 4.52; N, 6.79; O,
23.90.
(E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-
8-yl)-N-(2-hydroxyethyl)acrylamide (7k)
IR (KBr, cm-1): 3442 (-OH), 2254 (-CN), 1742 (-CO),
1594 (-C=C), 1549 (-C=C); 1H NMR (DMSO-d6): δ 11.8
(s, OH), 8.9 (t, -NH), 8.35 (s, H exocyclic ethylene), 6.23-
7.55 (m, 3H coumarin ring), 4.8 (s, -OH, aliphatic), 3.6 (t,
2H, -CH2-O), 3.4 (t, 2H, N-CH2-), 2.45 (s, 3H, -CH3); 13C
NMR (DMSO-d6): δ 161 (C-2), 159 (CO), 155 (C-7), 154
(C, exocyclic ethylene), 153 (C-4), 146.2 (C-10), 125.5
(C-5), 118.5 (C-8), 115 (-CN), 114.6 (C-6), 112.5 (C-3), 112.0
(C-9), 104 (C, ethylene), 61.0 (C-OH), 42 (-NH-C), 19.5
(C, -CH3); MS: m/z(M++1): 315.3; Anal. Calcd for
C16H14N2O5: C, 61.14; H, 4.49; N, 8.91; O, 25.45. Found;
C, 61.25; H, 4.50; N, 9.00; O, 25.55.
(E)-2-cyano-N-(4,5-dihydrothiazol-2-yl)-3-(7-hydroxy-4-
methyl-2-oxo-2H-chromen-8-yl) acrylamide (7o)
IR (KBr, cm-1): 3442 (-OH), 2254 (-CN), 1742 (-CO),
1644 (cyclic -CO), 1594 (-C=C), 1549 (-C=C), 750 (C-S);
1H NMR (DMSO-d6): 11.8 (s, OH), 8.45 (s, H exocyclic
ethylene), 8.0 (s, H, -NH), 6.23-7.55 (m, 3H coumarin
ring), 3.8 (t, 2H, -N-CH2-), 3.25 (t, 2H, -S-CH2), 2.45 (s,
3H, -CH3); 13C NMR (DMSO-d6): δ 169 (CO), 163.5 (-N-
C=N), 162 (C, exocyclic ethylene), 160.5 (C-2), 155 (C-
7), 153 (C-4), 146 (C-10), 125.2 (C-5), 118.2 (C-8), 115 (-CN),
114.6 (C-6), 112.5 (C-3), 112.0 (C-9), 106 (C, ethylene),
54 (=N-CH2), 24 (-S- CH2), 19.5 (C,-CH3); MS: m/z(M++1):
356.37; Anal. Calcd for C17H13N3O4S: C, 57.46; H, 3.69;
N, 11.82; O, 18.01; S, 9.02. Found; C, 58.02; H, 3.70; N,
11.90; O, 18.20; S, 9.10.
(E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-
8-yl)acrylamide(7l)
IR (KBr, cm-1): 3442 (-OH), 3225 (-NH), 2254 (-CN),
1742 (-CO), 1644 (cyclic -CO), 1594 (-C=C), 1549 (-C=C);
1H NMR(DMSO-d6): 11.8 (s, OH), 8.35 (s, H exocyclic
ethylene), 7.66 (s, 2H, -NH2), 6.23-7.55 (m, 3H coumarin
ring), 2.45 (s, 3H, -CH3); 13C NMR (DMSO-d6): δ 1647
(CO), 154 (C, exocyclic ethylene), 160.5 (C-2), 155 (C-7),
153 (C-4), 146 (C-10), 125.2 (C-5), 118.2 (C-8), 115 (-CN),
114.6 (C-6), 112.5 (C-3), 112.0 (C-9), 106 (C, ethylene),
19.5 (C, -CH3); MS: m/z(M++1): 271.24; Anal. Calcd for
C14H10N2O4: C, 62.22; H, 3.73; N, 10.37; O, 23.68.
Found; C, 62.45; H, 3.54; N, 10.27; O, 23.70.
RESULTS AND DISCUSSION
(E)-N-benzhydryl-2-cyano-3-(7-hydroxy-4-methyl-2-
oxo-2H-chromen-8-yl)acrylamide (7m)
In this paper we reported that synthesis of some novel
coumarin derivatives (7a-o) Resorcinol (1) reacts with
ethyl acetoacetate in sulfuric acid and gives 7-hydroxy-4-
methyl coumarin (2). The structure of 2 was established
IR (KBr, cm-1): 3442 (-OH), 2254 (-CN), 1742 (-CO),
1644 (cyclic -CO), 1594 (-C=C), 1549 (-C=C); 1H NMR
(DMSO-d6): 11.8 (s, OH), 8.35 (s, H exocyclic ethylene),
8.0 (s, H, -NH), 6.23-7.55 (m, 3H coumarin ring), 7.22-
7.44 (m, 10H, benzhydril), 6.16 (s, H,-CH), 2.45 (s, 3H, -CH3);
13C NMR(DMSO-d6): δ 161 (C-2), 160 (C, exocyclic ethy-
lene), 159 (CO), 155 (C-7), 153 (C-4), 146 (C-10), 141.2
(C-4', C-4''), 128 (C-5', C-5'', C-3', C-3''), 129.2 (C-6', C-
6'', C-2', C-2''), 126.2 (C-1', C-1''), 125.2 (C-5), 118.2 (C-
8), 115 (-CN), 114.6 (C-6), 112.5 (C-3), 112.0 (C-9), 104
(C, ethylene), 52.5 (C, -CH of benzhydril), 19.5 (C, -CH3);
MS: m/z(M++1): 437.5; Anal. Calcd for C27H20N2O4: C,
74.30; H, 4.62; N, 6.42; O, 14.66. Found; C, 74.25; H,
4.66; N, 4.56; O, 14.56.
1
by IR, H NMR and MS studies. It showed strong IR
absorption bands at 3423, 1733, 1555 cm-1 due to enol,
coumarin carbonyl and alkene groups respectively. In its
1H NMR spectrum three singlets at δ 2.49, 6.31 and 6.94
were assigned to a methyl group, olefinic proton and an
aromatic proton respectively. Two aromatic protons of cou-
marin moiety appeared as doublets at 6.92, 7.57. Reflux-
ing of (2) and hexamethylene tetramine in glacial acetic
acid for 6 hours afforded 8-formyl-4-methyl-7-hydroxy
Coumarin (3). The structure of (3) was established on the
basis of IR, 1H NMR and MS data. Presence of a singlet
peak in its 1H NMR spectrum at 10.63 confirms the formyl
(E)-2-cyano-N-(2,4-dimethoxybenzyl)-3-(7-hydroxy-4-
Journal of the Korean Chemical Society

Synthesis of New 8-Formyl-4-methyl-7-hydroxy Coumarin Derivatives
463
Table 1. Synthesis of 7a-o
Acknowledgments. The authors express their grateful
thanks to Prof. C.D. Reddy, Department of Chemistry, Sri
Venkateswara University, Tirupati, for his helpful discus-
sions.
Compound
R1
R2
(CH3O)-C6H5-CH(CH3)-
C6H5-CH(CH3)-
C6H5-CH2
-(CH2)5-
7a
7b
7c
7d
7e
7f
H
H
H
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CH3
CH3
7g
7h
7i
CH3
C2H5
C2H5
CH3-CH-CH3
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7j
-(CH=CH-N=CH)-
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2012, Vol. 56, No. 4