Green Synthesis of Spiropyranone 3-Aryl-4-Methylcoumarin Derivatives using Carbonyldiimidazole

Article abstract of DOI:10.14233/ajchem.2020.22376

A series of spiropyranone 3-aryl-4-methylcoumarin derivatives have been synthesized from monospiro-2-hydroxy acetophenone in a novel and efficient green method using imidazolyl intermediates and inorganic base. Imidazolyl intermediates were in turn genera

Full text of DOI:10.14233/ajchem.2020.22376

Asian Journal of Chemistry; Vol. 32, No. 1 (2020), 205-208
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2020.22376
Green Synthesis of Spiropyranone 3-Aryl-4-Methylcoumarin
Derivatives using Carbonyldiimidazole
1,*,
3
D. ASHOK
, E.V. L. MADHURI1,2 and M. SARASIJA
1Green and Medicinal Chemistry Lab, Department of Chemistry, Osmania University, Hyderabad-500007, India
2Department of Chemistry, Telangana University, Nizamabad-503344, India
3Department of Chemistry, Satavahana University, Karimnagar-505001, India
*Corresponding author: E-mail: ashokdou@gmail.com
Received: 4 August 2019;
Accepted: 28 October 2019;
Published online: 18 November 2019;
AJC-19699
A series of spiropyranone 3-aryl-4-methylcoumarin derivatives have been synthesized from monospiro-2-hydroxy acetophenone in a
novel and efficient green method using imidazolyl intermediates and inorganic base. Imidazolyl intermediates were in turn generated by
grinding the respective phenylacetic acid along with carbonyldiimidazole (CDI). Similarly, monospiro-2-hydroxy acetophenone derivatives
were prepared selectively by avoiding formation of bis derivatives following literature procedure. The titled compounds were purified by
preparative TLC technique and were characterized by IR, 1H NMR, 13C NMR as well as mass spectral methods.
Keywords: Spiropyranone coumarin, Carbonyl diimidazole, Green synthesis.
Kostanecki-Robinson reactions [21,22]. Besides these routes,
3-aryl coumarin derivatives were also prepared using reagents
such as DCC, DDQ, NaOH, POCl3 and Mukaiyama reagent
(2-chloro-1-methylpyridiniumiodide) [23-26]. Many of these
methods suffer limitations such as formation of complex mixture
of products, usage of excess reagents and longer reaction times.
Hence a relatively more sustainable reagent such as carbonyl-
diimidazole (CDI) gains more importance. Carboxylic acid
group in various anhydrous solvent such as chloroform, DMF,
THF, benzene, etc. can be activated to corresponding acid
imidazolyl group by treating with excess CDI, which can be
directly used for next step without further purification [27].
INTRODUCTION
Benzopyrone analogues known as coumarins are widely
known fused heterocyclic framework that served as the proto-
type scaffold for the synthesis of a wide variety of heterocyclic
systems in order to evaluate their biological activity. Moreover,
several synthetic coumarin derivatives have important pharma-
cological potential as they proved to be efficient inhibitors of
a variety of enzymes such as the human 5-lipoxygenase [1],
aromatase [2], horseradish peroxidase [3], hAChE/BACE1 [4]
and 17b-hydroxysteroid dehydrogenase type 3 [5].
2H-Chromen-2-one i.e. coumarins and their various deri-
vatives are widely known in many natural products and are
effective pharmacophores. Warfarin, a coumarin based compound
is a known cardiovascular agent. Similarly, novobiocin, another
coumarin based compound is an antimicrobial agent. Added
to this importance of coumarins in different fields is widely
known in literature [6-12].
EXPERIMENTAL
Phenylacetic acid, 4-chlorophenylacetic acid, 4-methyl-
phenylacetic acid, 4-methoxyphenylacetic acid, DABCO (1,4-
diazabicyclo[2.2.2]octane) and carbonyldiimidazole, were
obtained from Aldrich Chemical Co. All common chemicals
were of synthetic grade. Reactions were monitored by thin
layer chromatography (TLC) on silica gel plates (60 F254),
visualizing with ultraviolet light. 1H and 13C nuclear magnetic
resonance (NMR) spectra using CDCl3 as solvent were recorded
on Bruker Avance II 400 MHz spectrometer at the frequency
Based on the biological applications and various uses,
synthesis of coumarins gained lot of importance in medicinal
chemistry. Approaches to synthesize coumarins include proto-
type reactions such as Perkin reaction [13-15], Pechmann
reaction [16-18], Knoevenagel reaction [19], Wittig reaction [20],
This is an open access journal, and articles are distributed under the terms of the Attribution 4.0 International (CC BY 4.0) License. This
license lets others distribute, remix, tweak, and build upon your work, even commercially, as long as they credit the author for the original
creation. You must give appropriate credit, provide a link to the license, and indicate if changes were made.

206 Ashok et al.
Asian J. Chem.
indicated. Proton chemical shifts (δ) are relative to tetramethyl-
silane (TMS) as internal standard and expressed in ppm. Coupling
constants (J) are given in hertz. Mass spectra were recorded on
GCMS-QP 1000, The IR spectra were recorded on Shimadzu
FTIR 8400S spectrophotometer. Melting points of synthesized
compounds were determined in Polmon make instrument
(model No. MP-96) and are uncorrected.
mixture was heated at this temperature for appropriate time.
To the reaction mixture water was added and solid obtained
was filtered. This filtrate was dissolved in ethyl acetate and
purified by preparative TLC (5 % ethylacetate in n-hexane) to
obtain desired coumarins (3a-l) in better yields.
6′-Methyl-7′-phenyl-8′H-spiro[cyclohexane-1,2′-
pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3a):Yield: 75 %,
Initial efforts for preparing coumarin from phenylacetic
acid were attempted using different reagents as well as various
bases in different solvents for standardization of reaction
conditions. Inspired by the results of Foroumadi et. al. [28],
the first trial was initiated using neat DABCO as coupling reagent.
Unfortunately, the yields were poor on targeted substrate which
forced to look for alternate methods. These results prompted
to try the synthesis of coumarins with acid imidazole in the
presence of different base and solvents as according to Hamilakis
et al. report [29].Activation of acid using carbonyldiimidazole
using 1 equiv. of DBU as base for 2 h as well as 4 h, did not
result in improvement of reaction yield. Increasing the amount
of DBU to 3 and 5 equiv. also did not help in further improve-
ment of yield. Based on reports of Kaushik et. al. [30], solvent
was changed from DCM to toluene. The reaction performed
at room temperature as well as 80 ºC in toluene with DBU as
a base did not help much in improvization of yield. Parallel
effort by changing the base to triethylamine, resulted in even
poor results. Use of K2CO3 as a base improved the yield to
around 45 %. Finally, a trial using acid imidazole in dry acetone
as solvent and K2CO3 as base under microwave irradiation
resulted in improved yield (Scheme-I). However, several trials
to purify the compound by column chromatography were un-
successful, as impurities got eluted along with desired product.
Finally, all the targeted compounds were purified by prepa-
rative TLC technique, which resulted in 72-76 % yield of pure
product. All the compounds were well characterized by IR,
1H NMR, 13C NMR and mass spectral studies.
White solid; m.f. C24H22O4; m.p.: 156-158 ºC; IR (KBr, νmax,
cm-1): 2952, 1718, 1693, 1622; 1H NMR (CDCl3, 400 MHz):
δ 8.21 (s, 1H, Ar-H), 7.47-7.37 (m, 3H, Ar-H), 7.29-7.27 (m,
2H, Ar-H), 6.91 (s, 2H, Ar-H), 2.77 (s, 2H, -CH2), 2.31 (s, 3H,
-CH3), 2.04-2.00 (m, 2H, -CH2), 1.78-1.66 (m, 3H, -CH2), 1.57-
1.52 (m, 5H, -CH2); 13C NMR (100 MHz, CDCl3): δ 191.23,
161.62, 160.31, 158.07, 147.83, 134.10, 130.05, 128.44,
125.53, 124.78, 117.95, 115.15, 105.33, 81.51, 47.98, 34.88,
24.99, 21.37, 16.71; MS (m/z): 375 [M+H]+ (100 %).
7′-(4-Chlorophenyl)-6′-methyl-8′H-spiro[cyclohexane-
1,2′-pyrano[3,2-g]chromene]-4′,8′(3'H)-dione (3b): Yield:
75 %, White solid; m.f. C24H21O4Cl; m.p.: 152-154 ºC; IR (KBr,
1
ν
max, cm-1): 2952, 1714, 1694, 1624; H NMR (400 MHz,
CDCl3): δ 8.21 (s, 1H, Ar-H), 7.44-7.42 (d, 2H, J = 8.28 Hz,
Ar-H), 7.24-7.22 (d, 2H, J = 8.28 Hz, Ar-H), 6.91 (s, 1H, Ar-H),
2.78 (s, 2H, -CH2), 2.31 (s, 3H, -CH3), 2.02-1.99 (m, 2H, -CH2),
1.74-1.69 (m, 4H, -CH2), 1.55-1.51 (m, 4H, -CH2); 13C NMR
(100 MHz, CDCl3): δ 191.14, 161.78, 160.10, 158.00, 148.20,
134.39, 132.48, 131.54, 128.74, 124.86, 124.34, 118.04,
114.93, 105.40, 81.61, 47.96, 34.88, 24.97, 21.36, 16.72; MS
(m/z): 409 [M+H]+ (100 %).
6′-Methyl-7′-(p-tolyl)-8′H-spiro[cyclohexane-1,2′-
pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3c):Yield: 72 %,
White solid; m.f. C25H24O4; m.p.: 198-200 ºC ; IR (KBr, νmax
,
cm-1): 2952, 1713, 1695, 1623; 1H NMR (400 MHz, CDCl3):
δ 8.20 (s, 1H, Ar-H), 7.27-7.25 (d, 2H, J = 8.03Hz, Ar-H),
7.18-7.16 (d, 2H, J = 8.03Hz, Ar-H), 6.90 (s, 1H, Ar-H), 2.77
(s, 2H, -CH2), 2.40 (s, 3H, -CH3), 2.31 (s, 3H, -CH3), 2.03-
2.00 (m, 2H, -CH2), 1.75-1.65 (m, 4H, -CH2), 1.55-1.51 (m,
4H, -CH2); 13C NMR (100 MHz, CDCl3): δ 191.24, 161.53,
158.04, 147.59, 138.11, 131.08, 129.90, 129.15, 125.52, 124.71,
117.92, 115.24, 105.29, 81.47, 47.98, 34.88, 24.99, 21.37, 16.70;
MS (m/z): 389 [M+H]+ (100 %).
General procedure for synthesis of spiropyranone 3-
aryl-4-methylcoumarin (3a-l): Substituted phenylacetic acid
(1a-d) (1 mmol) and 1,1-carbonyldiimidazole (CDI, 1.2 mmol)
were grinded with the help of a glass rod for 3 min to generate
acid imidazole. To this a mixture of spirochromanone bearing
2-hydroxyacetophenone (2a-c) (1 mmol) and K2CO3 were
introduced into a CEM Discover Microwave reaction vessel
which is equipped with a magnetic stirrer. This vessel was
sealed and then placed into the cavity. A microwave irradiation
of 180 W was used and the temperature being ramped from
room temperature to desired 50 ºC temperature. The reaction
7′-(4-Methoxyphenyl)-6′-methyl-8′H-spiro[cyclo-
hexane-1,2′-pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3d):
Yield: 74 %, White solid; m.f. C25H24O5; m.p.: 204-206 ºC; IR
(KBr, νmax, cm-1): 2952, 1712, 1694, 1626; 1H NMR (400 MHz,
CDCl3): δ 8.20 (s, 1H, Ar-H), 7.23-7.20 (d, 2H, J = 8.78Hz,
Ar-H), 6.99-6.97 (d, 2H, J = 8.78Hz, Ar-H), 6.90 (s, 1H, Ar-
OH
O
O
O
O
O
OH
X
X
i. CDI, grinding
O
+
R
ii. K2CO3, MWI, 5 min
1a-l
1g:
O
O
R
2a-l
2a: X= CH2-CH2 2g: X= CH2-NBoc
2b: 2h:
3a-l
1a:
R=H
1b: R=Cl
1c:
R=CH3
1h: R=OCH3
1i:
X= CH2-CH2
X= CH2-NBoc
R=CH3
1d: R=OCH3 1j: R=Cl
1e: R=H 1k: R=CH3
1f: 1l:
R=H
2c: X= CH2-CH2 2i: X= CH2
2d: X= CH2-CH2 2j: X= CH2
X= CH2-NBoc
2f: X= CH2-NBoc 2l: X= CH2
2e:
2k:
X= CH2
R=Cl
R=OCH3
Scheme-I: Synthesis of spiropyranone 3-aryl-4-methylcoumarin derivatives

Vol. 32, No. 1 (2020)
Green Synthesis of Spiropyranone 3-Aryl-4-Methylcoumarin Derivatives using Carbonyldiimidazole 207
H), 3.85 (s, 3H, -OCH3), 2.77 (s, 2H, -CH2), 2.33 (s, 3H, -CH3),
2.03-2.00 (m, 2H, -CH2), 1.75-1.65 (m,3H, -CH2), 1.56-1.52
(m, 5H, -CH2); 13C NMR (100 MHz, CDCl3): δ 191.25, 161.50,
160.58, 159.47, 157.99, 147.53, 131.36, 126.21, 125.16, 124.70,
117.92, 115.28, 113.90, 105.27, 81.47, 55.30, 47.99, 34.88,
24.99, 21.37, 16.75; MS (m/z): 405 [M+H]+ (100 %).
White solid; m.f. C23H20O4; m.p.: 168-170 ºC; IR (KBr, νmax,
cm-1): 2954, 1716, 1691, 1620; 1H NMR (400 MHz, CDCl3):
δ 8.23 (s, 1H, Ar-H), 7.48-7.38 (m, 3H, Ar-H), 7.29-7.27 (m,
2H,Ar-H), 6.87 (s, 1H, Ar-H), 2.90 (s, 2H, -CH2), 2.32 (s, 3H,
-CH3), 2.14-2.09 (m, 2H, -CH2), 1.94-1.90 (m, 2H, -CH2), 1.76-
1.69 (m, 4H, -CH2); 13C NMR (100 MHz, CDCl3): δ 191.21,
162.29, 160.30, 157.92, 147.80, 134.07, 130.05, 128.44, 125.58,
125.04, 118.08, 115.22, 105.51, 91.25, 46.92, 37.62, 23.87,
16.71; MS (m/z): 361 [M+H]+ (100 %).
6′-Methyl-7′-phenyl-1-pivaloyl-8′H-spiro[piperidine-
4,2′-pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3e): Yield:
73 %, White solid; m.f. C28H29NO5; m.p.: 208-210 ºC; IR (KBr,
1
ν
max, cm-1): 2965, 1719, 1683, 1611; H NMR (400 MHz,
7′-(4-Chlorophenyl)-6′-methyl-8′H-spiro[cyclopentane-
1,2′-pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3j):Yield: 72
CDCl3): δ 8.23 (s, 1H,Ar-H), 7.48-7.40 (m, 3H,Ar-H), 7.29-7.27
(m, 2H, Ar-H), 6.93 (s, 1H, Ar-H), 3.89 (bs, 2H, -NCH2), 3.25
(bs, 2H, -NCH2), 2.79 (s, 2H, -CH2), 2.32 (s, 3H, -CH3), 2.06-
2.02 (m, 2H, -CH2), 1.71-1.63 (m, 2H, -CH2), 1.47 (s, 9H,
-C(CH3)3); 13C NMR (100 MHz, CDCl3): δ 190.13, 160.91,
160.10, 158.19, 154.62, 147.61, 133.94, 130.01, 128.46, 125.90,
124.97, 117.79, 115.64, 105.36, 79.97, 79.32, 47.84, 28.39,
16.71; MS (m/z): 460 [M+H]+ (100 %).
%, White solid; m.f. C23H19O4Cl; m.p.: 198-200 ºC; IR (KBr,
1
ν
max, cm-1): 2956, 1716, 1691, 1618; H NMR (400 MHz,
CDCl3): δ 8.23 (s, 1H, Ar-H), 7.44-7.42 (d, 2H, J = 8.28 Hz,
Ar-H), 7.24-7.22 (d, 2H, J = 8.28 Hz, Ar-H), 6.87 (s, 1H, Ar-H),
2.90 (s, 2H, -CH2), 2.32 (s, 3H, -CH3), 2.13-2.09 (m, 2H, -CH2),
1.94-1.88 (m, 2H, -CH2), 1.78-1.69 (m, 4H, -CH2); 13C NMR
(100 MHz, CDCl3): δ 191.12, 162.44, 160.10, 157.84, 148.19,
134.39, 132.44, 131.54, 128.73, 125.12, 124.38, 118.15,
114.99, 105.57, 91.33, 46.89, 37.62, 29.69, 23.86, 16.72; MS
(m/z): 395 [M+H]+ (100 %).
7′-(4-Chlorophenyl)-6′-methyl-1-pivaloyl-8′H-spiro-
[piperidine-4,2′-pyrano[3,2-g]chromene]-4′,8′(3′H)-dione
(3f): Yield: 74 %, White solid; m.f. C28H28NO5Cl; m.p.: 196-
198 ºC; IR (KBr, νmax, cm-1): 2962, 1718, 1681, 1612; 1H NMR
(400 MHz, CDCl3): δ 8.23 (s, 1H, Ar-H), 7.45-7.42 (d, 2H, J =
8.53 Hz, Ar-H), 7.24-7.22 (d, 2H, J = 8.53 Hz, Ar-H), 6.93 (s,
1H, Ar-H), 3.89 (bs, 2H, -NCH2), 3.25 (bs, 2H, -NCH2), 2.79
(s, 2H, -CH2), 2.32 (s, 3H, -CH3), 2.05-2.02 (m, 2H, -CH2),
1.71-1.63 (m, 2H, -CH2), 1.47 (s, 9H, -C(CH3)3); 13C NMR
(100 MHz, CDCl3): δ 190.05, 161.06, 159.89, 158.11, 154.61,
148.00, 134.48, 132.30, 131.50, 128.76, 125.05, 124.72,
117.87, 115.41, 105.43, 79.99, 79.40, 47.81, 28.39, 16.73;
MS (m/z): 494 [M+H]+ (100 %).
6′-Methyl-7′-(p-tolyl)-8′H-spiro[cyclopentane-1,2′-
pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3k):Yield: 73 %,
White solid; m.f. C24H22O4; m.p.: 156-158 ºC; IR (KBr, νmax
,
cm-1): 2956, 1716, 1693, 1612; 1H NMR (400 MHz, CDCl3):
δ 8.21 (s, 1H, Ar-H), 7.27-7.25 (d, 2H, Ar-H), 7.18-7.16 (d, J
= 8.03 Hz, 2H, Ar-H), 6.86 (s, 1H, Ar-H), 2.89 (2H, s, -CH2),
2.40 (s, 3H, -CH3), 2.32 (s, 3H, -CH3), 2.13-2.08 (m, 2H, -CH2),
1.94-1.90 (m, 2H, -CH2), 1.77-1.66 (m, 4H, -CH2); 13C NMR
(100 MHz, CDCl3): δ 191.23, 162.21, 157.88, 138.14, 131.05,
129.90, 129.15, 128.44, 124.97, 118.04, 115.31, 105.46, 91.22,
46.93, 37.62, 34.88, 29.69, 23.87, 21.31, 16.71; MS (m/z): 375
[M+H]+ (100 %).
6′-Methyl-1-pivaloyl-7′-(p-tolyl)-8′H-spiro[piperidine-
4,2′-pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3g): Yield:
72 %, White solid; m.f. C29H31NO5; m.p.: 186-188 ºC; IR (KBr,
7′-(4-Methoxyphenyl)-6′-methyl-8′H-spiro[cyclopen-
tane-1,2′-pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3l):
Yield: 74 %, White solid; m.f. C24H22O5; m.p.: 146-148 ºC; IR
1
ν
max, cm-1): 2964, 1717, 1684, 1613; H NMR (400 MHz,
CDCl3): δ 8.22 (s, 1H, Ar-H), 7.27 (d, 2H, J = 8.0 Hz, Ar-H),
7.18-7.16 (d, 2H, J = 8.03Hz, Ar-H), 6.92 (s, 1H, Ar-H), 3.91
(bs, 2H, -N-CH2), 3.26 (bs, 2H, -N-CH2), 2.79 (s, 2H, -CH2),
2.40 (s, 3H, -CH3), 2.32 (s, 3H, -CH3), 2.06-2.02 (m, 2H, -CH2),
1.69-1.62 (m, 2H, -CH2), 1.47 (s, 9H, -C(CH3)3); 13C NMR
(100 MHz, CDCl3): δ 190.17, 160.83, 160.26, 158.15, 154.63,
147.39, 138.23, 129.87, 129.17, 125.89, 124.90, 117.75,
115.73, 105.32, 79.97, 79.28, 47.85, 34.13, 28.39, 21.31,
16.71; MS (m/z): 474 [M+H]+ (100 %).
1
(KBr, νmax, cm-1): 2956, 1712, 1614; H NMR (400 MHz,
CDCl3): δ 8.21 (s, 1H, Ar-H), 7.23-7.21 (d, 2H, J = 8.53 Hz,
Ar-H), 6.99-6.97 (d, 2H, J = 8.53 Hz, Ar-H), 6.86 (s, 1H, Ar-
H), 3.85 (s, 3H, -OCH3), 2.89 (s, 2H, -CH2), 2.33 (s, 3H, -CH3),
2.11-2.08 (m, 2H, -CH2), 1.96-1.89 (m, 2H, -CH2), 1.77-1.68
(m, 4H, -CH2); 13C NMR (100 MHz, CDCl3): δ 191.24, 162.17,
160.57, 159.47, 157.82, 147.51, 131.35, 129.30, 126.17, 124.95,
118.03, 115.34, 113.89, 105.44, 91.21, 55.29, 46.92, 37.60,
23.86, 16.75; MS (m/z): 391 [M+H]+ (100%).
7′-(4-Methoxyphenyl)-6′-methyl-1-pivaloyl-8′H-
spiro[piperidine-4,2′-pyrano[3,2-g]chromene]-4′,8′(3′H)-
dione (3h): Yield: 72 %, White solid; m.f. C29H31NO6; m.p.:
202-204 ºC; IR (KBr, νmax, cm-1): 2964, 1719, 1684, 1615; 1H
NMR (400 MHz, CDCl3): δ 8.22 (s, 1H, Ar-H), 7.23-7.20 (d,
2H, J = 8.78 Hz, Ar-H), 6.99-6.97 (d, 2H, J = 8.78 Hz, Ar-H),
6.92 (s, 1H, Ar-H), 3.85 (bs, 5H, -OCH3, -N-CH2), 3.25 (bs,
2H, -NCH2), 2.79 (s, 2H, -CH2), 2.33 (s, 3H, -CH3), 2.05-2.02
(m, 2H, -CH2), 1.70-1.63 (m, 2H, -CH2), 1.47 (s, 9H, -C(CH3)3);
13C NMR (100 MHz, CDCl3): δ 190.15, 161.83, 160.30,
158.51, 155.63, 147.96, 138.58, 129.90, 129.00, 126.89, 125.90,
118.75, 115.83, 106.32, 81.23, 79.89, 47.85, 34.13, 28.39,
25.56, 21.31, 16.71; MS (m/z): 490 [M+H]+ (100 %).
RESULTS AND DISCUSSION
Compounds 3a-l were synthesized both in conventional
and green methods using different solvents and reagents. The
comparison of temperature required, yield and time taken for
completion of the reaction are given in Table-1.
Characterization of compound 3i: The structures of syn-
thesized spiropyranone coumarin derivatives were established
on the basis of IR, 1H NMR, 13C NMR and mass spectral data.
In the IR spectrum (KBr) of compound 3i, the characteristic
absorption peaks appeared at 1716 cm-1 corresponds to CH2-
C=O, 1691 cm-1 corresponds to -O-C=O of coumarin ring func-
tional group. 1H NMR spectrum (400 MHz, CDCl3) of compound
3i showed multiplet at δ 7.27-7.48 ppm representing the newly
6′-Methyl-7′-phenyl-8′H-spiro[cyclopentane-1,2′-
pyrano[3,2-g]chromene]-4′,8′(3′H)-dione (3i):Yield: 76 %,

208 Ashok et al.
Asian J. Chem.
5. K. Harada, H. Kubo,Y. Tomigahara, K. Nishioka, J. Takahashi, M. Momose,
S. Inoue and A. Kojima, Bioorg. Med. Chem. Lett., 20, 272 (2010);
https://doi.org/10.1016/j.bmcl.2009.10.111.
6. F. Borges, F. Roleira, N. Milhazes, L. Santana and E. Uriarte, Curr.
Med. Chem., 12, 887 (2005);
https://doi.org/10.2174/0929867053507315.
7. P.Anand, B. Singh and N. Singh, Bioorg. Med. Chem., 20, 1175 (2012);
https://doi.org/10.1016/j.bmc.2011.12.042.
8. I.S. Vinyarov and M.G. Bogdanov, Eur. J. Med. Chem., 78, 198 (2014);
https://doi.org/10.1016/j.ejmech.2014.03.053.
9. C. Mattsson, P. Svensson and C. Sonesson, Eur. J. Med. Chem., 73, 177
(2014);
https://doi.org/10.1016/j.ejmech.2013.11.035.
10. F. Belluti, G. Fontana, L. dal Bo, N. Carenini, C. Giommarelli and F.
Zunino, Bioorg. Med. Chem., 18, 3543 (2010);
TABLE-1
OPTIMIZATION OF REACTION
CONDITIONS FOR COUMARIN SYNTHESIS
Temp.
(°C)
180
Rt
Rt
Rt
Rt
Rt
80
Rt
Time
(h)
1.5
2
4
2
2
4
4
Yield
(%)
Reagent
Base
Solvent
DABCO
CDI
CDI
CDI
CDI
CDI
CDI
CDI
CDI
CDI
CDI
–
–
35
36
36
37
37
37
40
23
45
57
75
DBU 1eq
DBU 1eq
DBU 3eq
DBU 5eq
DBU 1eq
DBU 1eq
TEA
K2CO3
K2CO3
K2CO3
DCM
DCM
DCM
DCM
Toluene
Toluene
DCM
DCM
Dry acetone
6
4
3
Rt
Rt
MWI
https://doi.org/10.1016/j.bmc.2010.03.069.
11. M.J. Matos, D. Viña, F.J. Borges, L. Santana and E. Uriarte, Bioorg.
Med. Chem. Lett., 20, 5157 (2010);
5 min
https://doi.org/10.1016/j.bmcl.2010.07.013.
12. D. Bogdal, J. Chem. Res. (S), 468 (1998);
https://doi.org/10.1039/A801724G.
13. M. Trkovnik and Z. Ivezic, J. Heterocycl. Chem., 37, 137 (2009);
https://doi.org/10.1002/jhet.5570370123.
14. S.H. Mashraqui, D. Vashi and H.D. Mistry, Synth. Commun., 34, 3129
(2004);
https://doi.org/10.1081/SCC-200028575.
15. M.J. Matos, D. Viña, C. Picciau, F. Orallo, L. Santana and E. Uriarte,
Bioorg. Med. Chem. Lett., 19, 3268 (2009);
attached phenyl ring.A singlet corresponding to methyl group
appeared at δ 2.32 ppm. 13C NMR spectrum (100 MHz, CDCl3)
of compound 3i exhibited characteristic peak of newly formed
lactone carbon at δ 162 ppm, carbonyl carbon of chromanone
ring appears at δ 191 ppm. ESI mass spectrum of compound
3i exhibited a base peak at m/z 361 [M+H]+.
Conclusion
https://doi.org/10.1016/j.bmcl.2009.04.085.
A series of novel spiropyranone coumarin derivatives 3a-l
were successfully synthesized by microware irradiation method
to obtain better yields and shorter time compared to conven-
tional method. The derivatives were synthesized using carbonyl-
diimidazole (CDI) and corresponding acid, while K2CO3 was
used as base. The purification of compounds was done using
preparative TLC method. All the compounds were charact-
erized by spectral analysis.
16. M. M. Potdar, S.S. Mohile and M.M. Salunkhe, Tetrahedron Lett., 42,
9285 (2001);
https://doi.org/10.1016/S0040-4039(01)02041-X.
17. Y. Ming and D.W. Boykin, Heterocycles, 26, 3229 (1987);
https://doi.org/10.3987/R-1987-12-3229.
18. L. Santana, H. González-Díaz, E. Quezada, E. Uriarte, M. Yáñez, D. Viña
and F.J. Orallo, Med. Chem., 51, 6740 (2008);
https://doi.org/10.1021/jm800656v.
19. R.S. Mali and S.G. Tilve, Synth. Commun., 20, 1781 (1990);
https://doi.org/10.1080/00397919008053103.
20. R.S. Mali and P.P. Joshi, Synth. Commun., 31, 2753 (2001);
https://doi.org/10.1081/SCC-100105321.
21. A.K. Prasad, H.N. Pati, A. Azim, S. Trikha and Poonam, Bioorg. Med.
Chem., 7, 1973 (1999);
https://doi.org/10.1016/S0968-0896(99)00109-1.
22. H.M.F. Madkour, Heterocycles, 36, 947 (1993);
https://doi.org/10.3987/COM-92-6079.
23. N. Hans, M. Singhi, V. Sharma and S.K. Grover, Indian J. Chem., 35B,
1159 (1996).
24. D.V. Kadnikov and R.C. Larock, J. Organomet. Chem., 687, 425 (2003);
https://doi.org/10.1016/S0022-328X(03)00786-1.
25. P. Bäuerle and M.S. Schiedel, Process for the Parallel Synthesis of
Atleast Two Organic Dyes and Substituted Coumarin Derivatives and
Arylboronic Acid Propanediol Esters, WO Patent 2001068635A2
(2001).
ACKNOWLEDGEMENTS
This work was supported by University Grants Commission
(UGC) as UGC-MRP, Project sanction letter No.: F. 43-211/
2014 (SR), New Delhi and is gratefully acknowledged. The
authors thank Central Facilities For Research and Development
(CFRD) and Indian Institute of Chemical Technology (IICT),
Hyderabad, India for providing the spectral analytical facilities.
One of the authors, D. Ashok is thankful to BSR.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests
regarding the publication of this article.
26. D. Olmedo, R. Sancho, L.M. Bedoya, J.L. López-Pérez, E.D. Olmo,
E. Muñoz, J. Alcamí, M.P. Gupta and A.S. Feliciano, Molecules, 17,
9245 (2012);
https://doi.org/10.3390/molecules17089245.
27. M. Roberct, E. Angrooan and D.G. Gerhared, Can. J. Chem., 66, 1701
(1988);
REFERENCES
1. E.L. Grimm, C. Brideau, N. Chauret, C. Chan, D. Delorme,Y. Ducharme,
D. Ethier, J.P. Falgueyret, R.W. Friesen, J. Guay, P. Hamel, D. Riendeau,
C. Soucy-Breau, P. Tagari and Y. Girard, Bioorg. Med. Chem. Lett., 16,
2528 (2006);
https://doi.org/10.1139/v88-275.
https://doi.org/10.1016/j.bmcl.2006.01.085.
28. S. Rahmani-Nezhad, L. Khosravani, M. Saeedi, L. Firoozpour, K. Divsalar,
Y. Pourshojaei,Y. Sarrafi, H. Nadri,A. Moradi, M. Mahdavi, A, Shafiee
and A. Foroumadi, Synth. Commun., 45, 741 (2015);
https://doi.org/10.1080/00397911.2014.979947.
29. M. Roussaki, C.A. Kontogiorgis, D. Hadjipavlou-Litina, S. Hamilakis
and A. Detsi, Bioorg. Med. Chem. Lett., 20, 3889 (2010);
https://doi.org/10.1016/j.bmcl.2010.05.022.
2. F. Leonetti, A. Favia, A. Rao, R. Aliano, A. Paluszcak, R. W. Hartmann
and A. Carotti, J. Med. Chem., 47, 6792 (2004);
https://doi.org/10.1021/jm049535j.
3. L.M. Kabeya,A.A. de Marchi,A. Kanashiro, N.P. Lopes, C.H.T.P. de Silva,
M.T. Pupo and Y.M. Lucisano-Valim, Bioorg. Med. Chem., 15, 1516
(2007);
https://doi.org/10.1016/j.bmc.2006.10.068.
30. S.K. Verma, R. Ghorpade, A. Pratap and M.P. Kaushik, Tetrahedron
Lett., 53, 2373 (2012);
4. L. Piazzi, A. Cavalli, F. Colizzi, F. Belluti, M. Bartolini, F. Mancini,
M. Recanatini, V. Andrisano and A. Rampa, Bioorg. Med. Chem. Lett.,
18, 423 (2008);
https://doi.org/10.1016/j.tetlet.2012.01.125.
https://doi.org/10.1016/j.bmcl.2007.09.100.