Journal of Advanced Research (2014) 5, 209–218

Cairo University

Journal of Advanced Research

ORIGINAL ARTICLE

Pentafluorophenylammonium triflate (PFPAT)

catalyzed facile construction of substituted
chromeno[2,3-d]pyrimidinone derivatives and their
antimicrobial activity
Majid Ghashang a, Syed Sheik Mansoor b,*
, Krishnamoorthy Aswin b

a
Faculty of Sciences, Najafabad Branch, Islamic Azad University, Najafabad, Esfahan, Iran
b
Research Department of Chemistry, Bioactive Organic Molecule Synthetic Unit, C. Abdul Hakeem College, Melvisharam 632 509,
Tamil Nadu, India

A R T I C L E I N F O A B S T R A C T

Article history: A new, simple thermally efficient and solvent-free condensation of 2-amino-3-cyano-6-methyl-4-
Received 25 December 2012 phenyl-4H-pyran-5-ethylcarboxylate derivatives with coumarin-3-carboxylic acid employing
Received in revised form 27 February pentafluorophenylammonium triflate (PFPAT) as an inexpensive organocatalyst for the synthe-
2013 sis of a series of ethyl 4,5-dihydro 7-methyl-2-(2-oxo-2H-chromen-3-yl)-4-oxo-5-aryl-3H-chro-
Accepted 12 March 2013 meno[2,3-d]pyrimidine-6-carboxylate derivatives is described. This method has the advantages
Available online 20 March 2013 of high yields, a cleaner reaction, simple methodology, short reaction times, easy workup,
and greener conditions. All the compounds were evaluated for their in vitro antimicrobial activ-
Keywords: ity against different bacterial and fungal strains.
Pentafluorophenylammonium triflate ª 2013 Cairo University. Production and hosting by Elsevier B.V. All rights reserved.
Coumarin-3-carboxylic acid
Antimicrobial activity
Chromeno[2,3-d]pyrimidinones
2-Amino-3-cyano-6-methyl-4-phenyl-
4H-pyran-5-ethylcarboxylate

Introduction
* Corresponding author. Tel.: +91 9944 093020; fax: +91 4172
266487. Coumarins (2-oxo-2H-chromene) are the family of lactones
E-mail address: [email protected] (S.S. Mansoor). containing benzopyran skeletal framework. Coumarin deriva-
Peer review under responsibility of Cairo University. tives have been established as well-known naturally occurring
oxygen-heterocyclic compounds isolated from various plants
which occupy a special role in nature [1]. The plant extracts
containing coumarin-related heterocycles are employed as her-
Production and hosting by Elsevier
bal remedies in traditional systems of medicine. They belong to
2090-1232 ª 2013 Cairo University. Production and hosting by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jare.2013.03.003
210 M. Ghashang et al.

the flavonoid class of plant secondary metabolite. Coumarin

R1
derivatives constitute an important class of heterocyclic com-
O CHO O
pounds that have attracted significant attention in recent years ZrOCl2.8H2O CN
[2,3]. They have attracted intense interest because of their di- C2H5O (5 mol%) C2H5O
+ + CH2(CN)2
verse pharmacological properties. Cancer, a diverse group of Reflux H3C O NH2
H3C O R EtOH/H2O
diseases characterized by uncontrolled growth of abnormal 1

cells, is a major worldwide problem. It is a fatal disease stand- 4a-j

ing next to the cardiovascular disease in terms of morbidity
and mortality. A series of coumarin–chalcone hybrids have Scheme 1 2-Amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-
been synthesized and evaluated for their in vitro cytotoxicity ethylcarboxylate derivatives.
against a panel of four human cancer cell lines and normal
fibroblasts (NIH3T3) [4]. Tuberculosis (TB) is a common thol, aldehydes and cyclic 1,3-dicarbonyl compounds [20],
and often deadly infectious disease caused by various strains synthesis of xanthenes derivatives [21], and Biginelli reaction
of mycobacterium, usually Mycobacterium tuberculosis. Tuber- [22]. However, to the best of our knowledge, there are no exam-
culosis has been considered to be a disease of poverty for many ples on the use of PFPAT as catalyst for the synthesis of ethyl-
years with quite rare occurrence in the developed countries. A 4,5-dihydro 7-methyl-2-(2-oxo-2H-chromen-3-yl)-4-oxo-5-
new series of 4-(3-coumarinyl)-3-benzyl-4-thiazolin-2-one ben- aryl-3H-chromeno[2,3-d]pyrimidine-6-carboxylate derivatives.
zylidenehydrazones were synthesized, and they were evaluated Recently, we have reported the synthesis of biologically ac-
for anti-tuberculosis activity against M. tuberculosis H37Rv in tive heterocyclic molecules, such as 2-amino-4,6-diphenylpyri-
BACTEC 12B medium using the BACTEC 460 radiometric dine-3-carbonitrile derivatives [23], polyhydroquinoline
system [5]. Coumarin derivatives also used as anti-HIV [6], derivatives [24], 2-amino-6-(2-oxo-2Hchromen-3-yl)-4-arylnic-
antioxidant [7], dyslipidemic [8], anti-inflammatory agents [9], otinonitrile derivatives [25], and 2-arylbenzothiazole deriva-
and antimicrobial agents [10]. tives [26] by multi-component reactions. In continuation of
In view of the pharmaceutical importance of heterocyclic our research on the development of environmentally friendly
compounds containing coumarin moiety, many methods have procedures, we now describe the synthesis of ethyl-4,5-dihydro
been developed. Coumarin derivatives are synthesized using dif- 7-methyl-2-(2-oxo-2H-chromen-3-yl)-4-oxo-5-aryl-3H-chro-
ferent catalysts like nano-crystalline ZnO [11], heteropoly acids meno[2,3-d]pyrimidine-6-carboxylates using PFPAT as an effi-
[12] and tetrabutylammonium bromide [13]. Recently, chro- cient novel organocatalyst. These compounds were synthesized
meno pyrimidinone derivatives [14] and quinoxaline derivatives using 2-amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-ethyl-
containing the coumarin moiety [15] are reported. Various chro- carboxylates (Scheme 1).
meno pyrimidinones are prepared under solvent-free condition
at 120 C in the presence of 10 mol% of ionic liquid [14]. Experimental
Although these methods are quite satisfactory, many of
them employ considerable amounts of hazardous organic sol- Apparatus and analysis
vents, which are not environmentally friendly, for carrying out
the reactions and/or for extraction and purification (column
Chemicals were purchased from Merck, Fluka, and Aldrich
chromatography). Furthermore, these methods are not suit-
Chemical Companies. All yields refer to isolated products un-
able in terms of the recent trends in process chemistry, because
less otherwise stated. 1H NMR (500 MHz) and 13C NMR
of the use of metallic catalysts. Therefore, a method using a
(125 MHz) spectra were obtained using Bruker DRX-500
nonmetallic catalyst is desirable. Organo-catalysts have gained
Avance at ambient temperature, using TMS as internal stan-
interesting attraction in recent years due to economic and envi-
dard. FT-IR spectra were obtained as KBr disks on Shimadzu
ronmental considerations. These catalysts are generally inex-
spectrometer. Mass spectra were determined on a Varion –
pensive and easily available. They can conveniently be
Saturn 2000 GC/MS instrument. Elemental analysis was mea-
handled and removed from the reaction mixture, thus making
sured by means of Perkin Elmer 2400 CHN elemental analyzer
the experimental procedure simple and eco-friendly. The lead-
flowchart.
ing contenders for environmentally acceptable processes are
supported reagents.
Preparation of the catalyst (PFPAT)
PFPAT as an efficient organo-catalyst was applied in vari-
ous transformations. From the literatures, it was found that
PFPAT is a useful catalyst for multi-component reactions To a solution of 2,3,4,5,6-pentafluoroaniline (25 mmol) in tol-
(MCRs) [16–22], since it is low toxic catalyst, air and water uene (25 mL), CF3SO3H (25 mmol) was added at 0–5 C. The
compatible and has remarkable ability to suppress side reac- reaction mixture was stirred at the same temperature for
tions in acid-sensitive substrates. 30 min. After this time, the solvent was evaporated in vacuo,
Recently, Funatomi et al. reported the application of penta- and the crude product was collected and washed with hexane
fluorophenylammonium triflate (C6F5NH3OTf; PFPAT) as a to give the pure catalyst in 92% yield [16].
novel heterogeneous catalyst in organic transformation such
as esterification of carboxylic acids with alcohols [16], C-acyla- General procedure to synthesis of 2-amino-3-cyano-6-methyl-4-
tions of enol silyl ethers or ketene silyl (thio)acetals with acid phenyl-4H-pyran-5-ethylcarboxylate derivatives using
chlorides [17] and Mukaiyama aldol and Mannich reactions ZrOCl2Æ8H2O (5 mol%) as catalyst
using ketene silyl acetals with ketones and oxime ethers [18].
Further, PFPAT also used as the catalyst for acylation of alco- A mixture of ethyl acetoacetate (1 mmol), aldehydes (1 mmol),
hols, phenols, and amines [19], one-pot condensation of b-naph- malononitrile (1 mmol), and catalyst ZrOCl2Æ8H2O (5 mol%)
PFPAT catalyzed construction of chromeno[2,3-d]pyrimidinones 211

in 5 mL of EtOH/H2O[50/50(v/v)] were refluxed for appropri- d: 14.9, 19.8, 40.6, 58.6, 60.6, 106.3, 119.9, 125.7, 128.4,
ated time. After the TLC indicates the disappearance of start- 129.2, 131.2, 144.8, 147.3, 167.6 ppm; MS (ESI): m/z 315
ing materials, the reaction was cooled to room temperature, (M+H)+. Anal. Calcd. for C17H18N2O4 (%): C, 64.97; H,
ethanol (20 mL) was added, and the insoluble material was fil- 5.73; N, 8.92. Found: C, 64.90; H, 5.70; N, 8.91.
tered to separate the catalyst. The filtrate was concentrated un-
der vacuum, and the crude residue was purified by 2-Amino-3-cyano-6-methyl-4-(4-nitrophenyl)-4H-pyran-5-
recrystallization. 2-Amino-3-cyano-6-methyl-4-phenyl-4H- ethylcarboxylate (4h)
pyran-5-ethylcarboxylate was obtained as crystals. The recov- IR (KBr, cm 1): 3430, 3338, 3209, 2202, 1668, 1644, 1489,
ered catalyst can be washed consequently with diluted acid 1203, 774. 1H NMR (500 MHz, CDCl3) d: 1.19 (t,
solution, water, and then acetone. After drying, it can be re- J = 7.4 Hz, 3H, CH3CH2), 2.31 (s, 3H, CH3), 4.14 (q,
used without noticeable loss of reactivity. The products were J = 7.3 Hz, 2H, CH3CH2), 4.92 (s, 1H, CH), 5.07 (s, 2H,
identified by IR, 1H NMR, 13C NMR, mass, elemental analy- NH2), 7.15 (d, J = 7.4 Hz, 2H, ArH), 7.44 (d, J = 7.4 Hz,
sis, and melting points. 2H ArH) ppm; 13C NMR (125 MHz, CDCl3) d: 15.2, 20.2,
39.3, 58.3, 59.7, 105.7, 119.3, 125.6, 128.1, 129.0, 131.0,
Spectral data for the selected synthesized compounds 144.1, 147.4, 167.0 ppm; MS (ESI): m/z 330 (M+H)+. Anal.
Calcd. for C16H15N3O5 (%): C, 58.35; H, 4.56; N, 12.76.
2-Amino-3-cyano-6-methyl-4-(4-N,N-dimethylaminophenyl)- Found: C, 58.30; H, 4.53; N, 12.75.
4H-pyran-5-ethylcarboxylate (4d)
(KBr, cm 1): 3413, 3342, 3214, 2217, 1662, 1638, 1484, 1203, General procedure for the synthesis of ethyl 4,5-dihydro-7-
785; 1H NMR (500 MHz, CDCl3) d: 1.20 (t, J = 7.2 Hz, 3H, methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-5-phenyl-3H-
CH3CH2), 2.66 (s, 6H, N(CH3)2), 2.28 (s, 3H, CH3), 4.11 (q, pyrano[2,3-d]pyrimidine-6-carboxylate by PFPAT
J = 7.2 Hz, 2H, CH3CH2), 4.94 (s, 1H, CH), 5.17 (s, 2H,
NH2), 7.11 (d, J = 7.2 Hz, 2H, ArH), 7.34 (d, J = 7.2 Hz, A mixture of 2-amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-
2H ArH) ppm; 13C NMR (125 MHz, CDCl3) d: 15.1, 19.2, ethylcarboxylate 4a–j (1 mmol), coumarin-3-carboxylic acid
39.8, 57.4, 59.8, 105.8, 120.3, 125.2, 128.3, 129.1, 131.1, (1 mmol) and PFPAT (5 mol%) were heated at 80 C for
144.8, 147.1, 166.5 ppm; MS (ESI): m/z 328 (M+H)+. Anal. about 5.5–7.0 h (Scheme 2). After completion of the reaction
Calcd. for C18H21N3O3 (%): C, 66.05; H, 6.42; N, 12.84. as indicated by TLC, 2 mL of water was added and stirred
Found: C, 66.00; H, 6.41; N, 12.85. at room temperature for 20 min. The precipitated product
was filtered, washed with water, dried and purified over col-
2-Amino-3-cyano-6-methyl-4-(4-fluorophenyl)-4H-pyran-5- umn chromatography using silica gel (230–400 mesh) with n-
ethylcarboxylate (4f) hexane and ethyl acetate (8:2) as eluent. The aqueous layer
IR (KBr, cm 1): 3428, 3329, 3205, 2216, 1667, 1636, 1483, containing catalyst was recovered, washed with acetone, dried
1219, 793. 1H NMR (500 MHz, CDCl3) d: 1.13 (t, and reused for subsequent reactions without loss in its activity
J = 7.0 Hz, 3H, CH3CH2), 2.26 (s, 3H, CH3), 4.06 (q, and product yield.
J = 7.0 Hz, 2H, CH3CH2), 4.90 (s, 1H, CH), 5.21 (s, 2H,
NH2), 7.10 (d, J = 7.4 Hz, 2H, ArH), 7.32 (d, J = 7.4 Hz, Recycling and reusing of the catalyst
2H ArH) ppm; 13C NMR (125 MHz, CDCl3) d: 14.5, 19.6,
39.4, 58.0, 60.4, 105.3, 120.3, 125.0, 129.1, 131.1, 144.7, The catalyst is soluble in water and could therefore be recycled
146.7, 167.5 ppm; MS (ESI): m/z 303 (M+H)+. Anal. Calcd. as the filtrate. The catalyst was recovered by evaporation of the
for C16H15FN2O3 (%): C, 63.57; H, 4.96; N, 9.27. Found: C, water, washed with hexane, dried at 50 C under vacuum for
63.50; H, 4.95; N, 9.28. 1 h, and reused in another reaction without appreciable reduc-
tion in the catalytic activity.
2-Amino-3-cyano-6-methyl-4-(4-methoxyphenyl)-4H-pyran-5-
ethylcarboxylate (4g) Spectral data for the synthesized compounds (6a–j)
IR (KBr, cm 1): 3429, 3337, 3219, 2220, 1675, 1644, 1488,
1219, 779. 1H NMR (500 MHz, CDCl3) d: 1.16 (t, Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-
J = 7.4 Hz, 3H, CH3CH2), 2.24 (s, 3H, CH3), 3.62 (s, 3H, 5-phenyl-3H-pyrano[2,3-d] pyrimidine-6-carboxylate (6a)
OCH3), 4.17 (q, J = 7.2 Hz, 2H, CH3CH2), 4.87 (s, 1H, IR (KBr, cm 1): 3311, 1714, 1677, 1638, 1600, 1208; 1H NMR
CH), 5.15 (s, 2H, NH2), 7.07 (d, J = 7.2 Hz, 2H, ArH), 7.34 (500 MHz, CDCl3) d: 1.18 (t, J = 7.4 Hz, 3H, CH3CH2), 2.22
(d, J = 7.2 Hz, 2H ArH) ppm; 13C NMR (125 MHz, CDCl3) (s, 3H, CH3), 4.12 (q, J = 7.2 Hz, 2H, CH3CH2), 4.53 (s, 1H,

R1
R1 O O
O PFPAT
CN HOOC (5 mol%) C2H5O NH
C2H5O
+
Solvent-free, H3C O N
H3C O NH2 O O 80 oC
O O
4a-j
6a-j

Scheme 2 Ethyl 4,5-dihydro 7-methyl-2-(2-oxo-2H-chromen-3-yl)-4-oxo-5-aryl-3H-chromeno[2,3-d]pyrimidine-6-carboxylate

derivatives.
212 M. Ghashang et al.

CH), 7.01–7.41 (m, 5H, ArH), 7.75–7.92 (m, 4H, ArH), 8.66 (s, ppm; 13C NMR (125 MHz, CDCl3) d: 16.6, 20.7, 26.7, 35.9,
1H, Coumarin H), 9.07 (s, 1H, NH) ppm; 13C NMR 36.8, 101.0, 114.2, 116.2, 117.5, 119.1, 121.2, 124.8, 126.0,
(125 MHz, CDCl3) d: 16.4, 20.1, 26.4, 36.0, 37.4, 100.7, 127.5, 129.0, 130.1, 134.7, 136.9, 153.6, 154.2, 156.9, 162.7,
113.5, 116.1, 118.0, 118.7, 121.3, 124.5, 126.4, 127.0, 129.3, 170.4 ppm; MS(ESI): m/z 491 (M+H)+; Anal. Calcd. for
130.8, 134.0, 136.8, 153.0, 154.2, 157.0, 163.7, 170.4 ppm; C26H19ClN2O6: C, 63.61; H, 3.87; N, 5.71%. Found: C,
MS(ESI): m/z 456 (M+H)+; Anal. Calcd. for C26H20N2O6: 63.58; H, 3.86; N, 5.73%.
C, 68.42; H, 4.38; N, 6.14%. Found: C, 68.31; H, 4.33; N,
6.14%. Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-
5-(4-fluorophenyl)-3H-pyrano[2,3-d]pyrimidine-6-carboxylate
Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)- (6f)
5-(3-hydroxyphenyl)-3H-pyrano[2,3-d pyrimidine-6- IR (KBr, cm 1): 3314, 1722, 1682, 1646, 1616, 1214; 1H NMR
carboxylate (6b) (500 MHz, CDCl3) d: 1.19 (t, J = 7.2 Hz, 3H, CH3CH2), 2.20
IR (KBr, cm 1): 3362, 3308, 1712, 1675, 1640, 1609, 1212; 1H (s, 3H, CH3), 4.17 (q, J = 7.2 Hz, 2H, CH3CH2), 4.55 (s, 1H,
NMR (500 MHz, CDCl3) d: 1.10 (t, J = 7.2 Hz, 3H, CH), 7.07–7.16 (m, 2H, ArH), 7.46–7.57 (m, 2H, ArH), 7.66–
CH3CH2), 2.18 (s, 3H, CH3), 4.22 (q, J = 7.2 Hz, 2H, 7.74 (m, 4H, ArH), 8.88 (s, 1H, Coumarin H), 9.10 (s, 1H, NH)
CH3CH2), 4.58 (s, 1H, CH), 7.09–7.49 (m, 4H, ArH), 7.71– ppm; 13C NMR (125 MHz, CDCl3) d: 15.9, 20.0, 26.4, 35.8,
7.90 (m, 4H, ArH), 8.70 (s, 1H, Coumarin H), 9.01 (s, 1H, 36.7, 101.2, 113.9, 116.4, 117.7, 118.6, 121.5, 124.0, 125.9,
NH), 9.66 (s, 1H, OH) ppm; 13C NMR (125 MHz, CDCl3) 127.8, 129.4, 130.1, 133.9, 136.5, 153.4, 154.6, 157.2, 163.5,
d: 15.9, 20.2, 26.3, 36.4, 37.3, 100.6, 114.0, 116.4, 117.7, 170.3 ppm; MS(ESI): m/z 475 (M+H)+; Anal. Calcd. for
118.8, 121.0, 124.3, 126.2, 127.2, 129.4, 130.4, 134.5, 136.8, C26H19FN2O6: C, 65.82; H, 4.01; N, 5.91%. Found: C,
153.2, 154.5, 156.9, 163.6, 170.3 ppm; MS(ESI): m/z 473 65.80; H, 4.00; N, 5.90%.
(M+H)+; Anal. Calcd. for C26H20N2O7: C, 66.10; H, 4.24;
N, 5.93%. Found: C, 66.01; H, 4.20; N, 5.90%. Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-
5-(4-methoxyphenyl)-3H-pyrano[2,3-d]pyrimidine-6-
Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)- carboxylate (6g)
5-(3-nitrophenyl)-3H-pyrano[2,3-d]pyrimidine-6-carboxylate IR (KBr, cm 1): 3310, 1711, 1668, 1652, 1603, 1205; 1H NMR
(6c) (500 MHz, CDCl3) d: 1.08 (t, J = 7.2 Hz, 3H, CH3CH2), 2.27
IR (KBr, cm 1): 3296, 1720, 1680, 1644, 1611, 1216; 1H NMR (s, 3H, CH3), 3.62 (s, 3H, OCH3), 4.10 (q, J = 7.1 Hz, 2H,
(500 MHz, CDCl3) d: 1.09 (t, J = 7.0 Hz, 3H, CH3CH2), 2.26 CH3CH2), 4.35 (s, 1H, CH), 7.12–7.30 (m, 2H, ArH), 7.43–
(s, 3H, CH3), 4.26 (q, J = 7.0 Hz, 2H, CH3CH2), 4.44 (s, 1H, 7.56 (m, 2H, ArH), 7.70–7.82 (m, 4H, ArH), 8.65 (s, 1H, Cou-
CH), 7.03–7.33 (m, 4H, ArH), 7.68–7.88 (m, 4H, ArH), 8.80 (s, marin H), 9.06 (s, 1H, NH) ppm; 13C NMR (125 MHz,
1H, Coumarin H), 9.05 (s, 1H, NH) ppm; 13C NMR CDCl3) d: 16.1, 20.1, 26.4, 36.1, 37.4, 100.5, 113.8, 115.8,
(125 MHz, CDCl3) d: 16.2, 20.0, 26.7, 36.1, 37.1, 100.2, 117.6, 118.7, 121.2, 124.2, 126.1, 127.3, 129.2, 130.1, 134.4,
113.7, 115.7, 117.6, 119.0, 121.4, 124.4, 126.7, 127.5, 128.6, 136.4, 153.7, 154.8, 157.3, 163.0, 170.2 ppm; MS(ESI): m/z
129.4, 130.6, 134.6, 136.8, 153.3, 154.5, 156.8, 162.9, 487 (M+H)+; Anal. Calcd. for C27H22N2O7: C, 66.67; H,
170.1 ppm; MS(ESI): m/z 502 (M+H)+; Anal. Calcd. for 4.53; N, 5.76%. Found: C, 65.70; H, 4.50; N, 5.75%.
C26H19N3O8: C, 62.27; H, 3.79; N, 8.38%. Found: C, 62.22;
H, 3.74; N, 8.35%. Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-
5-(4-nitrophenyl)-3H-pyrano[2,3-d]pyrimidine-6-carboxylate
Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)- (6h)
5-(N,N-dimethylaminophenyl)-3H-pyrano[2,3-d]pyrimidine-6- IR (KBr, cm 1): 3299, 1709, 1671, 1647, 1600, 1210; 1H NMR
carboxylate (6d) (500 MHz, CDCl3) d: 1.13 (t, J = 7.2 Hz, 3H, CH3CH2), 2.20
IR (KBr, cm 1): 3304, 1704, 1688, 1633, 1604, 1200; 1H NMR (s, 3H, CH3), 4.20 (q, J = 7.2 Hz, 2H, CH3CH2), 4.30 (s, 1H,
(500 MHz, CDCl3) d: 1.12 (t, J = 7.2 Hz, 3H, CH3CH2), 2.27 CH), 7.00–7.15 (m, 2H, ArH), 7.40–7.52 (m, 2H, ArH), 7.69–
(s, 3H, CH3), 2.74 (s, 6H, N(CH3)2), 4.19 (q, J = 7.4 Hz, 2H, 7.81 (m, 4H, ArH), 8.58 (s, 1H, Coumarin H), 9.21 (s, 1H, NH)
CH3CH2), 4.39 (s, 1H, CH), 7.08–7.17 (m, 2H, ArH), 7.34– ppm; 13C NMR (125 MHz, CDCl3) d: 16.7, 20.6, 26.6, 36.4,
7.48 (m, 2H, ArH), 7.74–7.82 (m, 4H, ArH), 8.77 (s, 1H, Cou- 37.6, 100.7, 113.3, 116.1, 118.0, 118.5, 121.4, 124.3, 125.8,
marin H), 9.24 (s, 1H, NH) ppm; 13C NMR (125 MHz, 127.0, 129.4, 130.1, 134.0, 136.2, 153.3, 154.3, 156.7, 162.6,
CDCl3) d: 15.5, 20.3, 26.5, 36.5, 37.3, 46.5, 100.4, 113.9, 170.6 ppm; MS(ESI): m/z 502 (M+H)+; Anal. Calcd. for
116.0, 118.1, 118.8, 122.0, 124.6, 126.3, 127.7, 129.5, 130.1, C26H19N3O8: C, 62.27; H, 3.79; N, 8.38%. Found: C, 62.29;
134.3, 136.5, 153.0, 154.3, 156.7, 163.0, 170.2 ppm; MS(ESI): H, 3.79; N, 8.36%.
m/z 500 (M+H)+; Anal. Calcd. for C28H25N3O6: C, 67.33;
H, 5.01; N, 8.42%. Found: C, 67.35; H, 5.00; N, 8.37%. Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-
5-(4-bromophenyl)-3H-pyrano[2,3-d]pyrimidine-6-carboxylate
Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)- (6i)
5-(4-chlorophenyl)-3H-pyrano[2,3-d]pyrimidine-6-carboxylate IR (KBr, cm 1): 3292, 1714, 1675, 1644, 1611, 1208; 1H NMR
(6e) (500 MHz, CDCl3) d: 1.12 (t, J = 7.1 Hz, 3H, CH3CH2), 2.16
IR (KBr, cm 1): 3294, 1716, 1677, 1640, 1609, 1206; 1H NMR (s, 3H, CH3), 4.16 (q, J = 7.2 Hz, 2H, CH3CH2), 4.56 (s, 1H,
(500 MHz, CDCl3) d: 1.16 (t, J = 7.1 Hz, 3H, CH3CH2), 2.19 CH), 7.16–7.26 (m, 2H, ArH), 7.46–7.58 (m, 2H, ArH), 7.72–
(s, 3H, CH3), 4.14 (q, J = 7.2 Hz, 2H, CH3CH2), 4.53 (s, 1H, 7.90 (m, 4H, ArH), 8.78 (s, 1H, Coumarin H), 9.09 (s, 1H, NH)
CH), 7.11–7.24 (m, 2H, ArH), 7.42–7.52 (m, 2H, ArH), 7.76– ppm; 13C NMR (125 MHz, CDCl3) d: 16.5, 20.5, 26.5, 35.7,
7.96 (m, 4H, ArH), 8.75 (s, 1H, Coumarin H), 9.12 (s, 1H, NH) 36.6, 101.1, 114.4, 116.4, 117.4, 119.4, 121.6, 124.6, 126.0,
PFPAT catalyzed construction of chromeno[2,3-d]pyrimidinones 213

127.3, 129.2, 130.3, 134.5, 136.7, 153.7, 154.5, 156.7, 162.9, CH3CN, CH3Cl, EtOH, and H2O were examined at reflux con-
170.7 ppm; MS(ESI): m/z 535.9 (M+H)+; Anal. Calcd. for dition (Table 1, Enries 1–4). The reaction without any solvent
C26H19BrN2O6: C, 58.32; H, 3.55; N, 5.23%. Found: C, at reflux was not very successful (Table 1, Entry 5). The model
58.28; H, 3.50; N, 5.21%. reaction was studied at various mixtures of EtOH/H2O sol-
vent. The EtOH/H2O[50/50(v/v)] is proven to be the most suit-
Ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)- able solvent for this condensation in terms of yield and
5-(4-methylphenyl)-3H-pyrano[2,3-d]pyrimidine-6-carboxylate reaction time (Table 1, Entry 7). We have studied the amount
(6j) of ZrOCl2Æ8H2O required for the reaction. It was found that
IR (KBr, cm 1): 3313, 1714, 1669, 1655, 1603, 1208; 1H NMR when decreasing the amount of the catalyst from 5 mol% to
(500 MHz, CDCl3) d: 1.09 (t, J = 7.2 Hz, 3H, CH3CH2), 2.22 3 mol%, the yield decreased from 95% to 77% (Table 1, Entry
(s, 3H, CH3), 2.29 (s, 3H, CH3), 4.14 (q, J = 7.1 Hz, 2H, 9). When increasing the amount of the catalyst from 5 mol%
CH3CH2), 4.38 (s, 1H, CH), 7.18–7.35 (m, 2H, ArH), 7.45– to 10 mol%, there is no change in the yield (Table 1, Entry
7.58 (m, 2H, ArH), 7.77–7.88 (m, 4H, ArH), 8.69 (s, 1H, Cou- 10). The use of 5 mol% of ZrOCl2Æ8H2O maintaining the yield
marin H), 9.14 (s, 1H, NH) ppm; 13C NMR (125 MHz, at 95%, so this amount is sufficient to promote the reaction. In
CDCl3) d: 16.3, 20.3, 26.6, 27.3, 36.3, 37.8, 100.7, 113.4, the presence of more than this amount of the catalyst, neither
115.4, 117.9, 118.8, 124.4, 126.2, 127.0, 129.5, 130.4, 134.6, the yield nor the reaction time was improved (Table 1, Entry
137.0, 154.0, 155.9, 157.5, 163.3, 170.5 ppm; MS(ESI): m/z 10). Encouraged by this successful three component reaction,
471 (M+H)+; Anal. Calcd. for C27H22N2O6: C, 68.93; H, synthesis of diverse 2-amino-3-cyano-6-methyl-4-phenyl-4H-
4.68; N, 5.95%. Found: C, 68.88; H, 4.65; N, 5.94%. pyran-5-ethylcarboxylate derivatives 4a–j was undertaken.
The aromatic aldehydes bearing electron-withdrawing and
Results and discussion electron donating groups were found to be equally effective
to produce 2-amino-4H-pyrans 4a–j in very good yields
The synthetic pathway of the title compounds was achieved via (Table 2).
2-amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-ethylcarb- After the synthesis of 2-amino-3-cyano-6-methyl-4-phenyl-
oxylates intermediates (4a–j). Considering the broad spectrum 4H-pyran-5-ethylcarboxylate derivatives, we have synthesized
of biological activities of 4H-pyrans, synthetic chemists have Ethyl 4,5-dihydro 7-methyl-2-(2-oxo-2H-chromen-3-yl)-
developed numerous protocols for their syntheses including 4-oxo-5-aryl-3H-chromeno[2,3-d]pyrimidine-6-carboxylate
two-step as well as one-pot three component synthesis, cata- derivatives. Initially, the reaction between compound 4a and
lyzed by Baker’s yeast [27], MgO [28], hexadecyldimethylben- coumarin-3-carboxylic acid was carried out under neat condi-
zyl ammonium bromide (HDMBAB) [29], phenylboronic tions at 80 C without and with different acid catalyst (phenyl-
acid [30], 2,2,2-trifluoroethanol [31], and silica gel-supported boronic acid, bismuth nitrate, silica perchloric acid, sulfamic
polyphosphoric acid (PPA–SiO2) [32]. However, these methods acid, PFPAT each 5 mol%) and observed maximum yield with
often suffer from one or the other kind of drawbacks and most PFPAT (Table 3).
of them give moderate yields even after prolonged reaction The solvents played an important role in the synthesis of
time. This has clearly indicated that there is still scope to devel- chromeno pyrimidine derivatives. Various reaction media were
op an efficient and eco-sustainable method for the synthesis of screened (1,4-dioxane, ethanol, acetonitrile, THF, methanol,
4H-pyrans. The intermediates were obtained by the three com- and t-BuOH) using the model reaction (Table 4, Entries 1–
ponent condensation of ethyl acetoacetate, aldehydes with 6). It was found that the best results were obtained with
malononitrile using ZrOCl2Æ8H2O as catalyst in aqueous 5 mol% of PFPAT under solvent-free condition (Table 4, En-
ethanol. try 7). The reaction was completed in 6 h, and the expected
In order to optimize the conditions, we studied the reaction product was obtained in 89% yield.
of ethyl acetoacetate, benzaldehyde with malononitrile and At these optimize conditions (solvent-free, 80 C, 5 mol%
ZrOCl2Æ8H2O (5 mol%) as a simple model reaction in various of PFPAT), we synthesized various chromeno pyrimidinones
conditions. The reaction was performed in various solvents to 6a–j (Table 5). After completion of the reaction, the catalyst
identify the best solvent condition. A range of solvents like was recovered by evaporating the aqueous layer, washed with

Table 1 Optimization of the reaction conditions on the synthesis of 4a: Effect of solvent and catalyst amount.a
Entry Solvent Amount of catalyst (mol%) Time (h) Yield (%)b
1 CH3CN 5 3 41
2 CHCl3 5 3 62
3 H2O 5 3 72
4 EtOH 5 3 68
5 None 5 3 31
6 EtOH/H2O[30/70(v/v)] 5 1.5 78
7 EtOH/H2O[50/50(v/v)] 5 1.5 95
8 EtOH/H2O[70/30(v/v)] 5 1.5 80
9 EtOH/H2O[50/50(v/v)] 3 1.5 77
10 EtOH/H2O[50/50(v/v)] 10 1.5 96
a
Reaction conditions: ethyl acetoacetate (1 mmol), benzaldehyde (1 mmol) and malononitrile (1 mmol) at reflux.
b
Isolated yield.
214 M. Ghashang et al.

Table 2 Preparation of various 2-amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-ethylcarboxylate derivatives.a

Entry R1 Product Time (h) Yield (%)b Mp (C)
Found Reported
1 H 4a 1.5 95 193–195 195–196 [28]
2 3-OH 4b 1.5 93 162–164 161–162 [28]
3 3-NO2 4c 1.0 90 182–184 182–183 [28]
4 4-N(CH3)2 4d 2.0 88 180–182 –
5 4-Cl 4e 1.5 87 170–172 172–174 [28]
6 4-F 4f 1.5 91 186–188 –
7 4-OCH3 4g 2.0 87 141–143 142–144 [28]
8 4-NO2 4h 2.5 89 182–184 180–182 [28]
9 4-Br 4i 1.5 90 172–174 –
10 4-CH3 4j 2.0 86 178–180 177–179 [28]
a
Reaction conditions: ethyl acetoacetate (1 mmol), aldehyde (1 mmol), and malononitrile (1 mmol) in the presence of ZrOCl2Æ8H2O (5 mol%)
in EtOH/H2O[50/50(v/v)] at reflux.
b
Isolated yield.

Table 3 Preparation of ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-5-phenyl-3H-pyrano[2,3-d]pyrimidine-6-car-

boxylate: effect of catalyst.a
Entry Catalyst Amount of catalyst (mol%) Time (h) Yield (%)b
1 Phenylboronic acid 5 8 55
2 Bismuth nitrate 5 8 62
3 Silica perchloric acid 5 8 72
4 Sulfamic acid 5 8 68
5 PFPAT 5 6 89
6 None 0 8 Trace
7 PFPAT 10 6 89
8 PFPAT 3 6 84
9 PFPAT 2 6 75
a
Reaction conditions: 4a (1 mmol) and coumarin-3-carboxylic acid (1 mmol) at 80 C.
b
Isolated yield.

acetone, dried and reused for subsequent reactions without sig- was established. In the next step, the protonation of nitrile group
nificant loss in its activity. The catalyst was recycled for four of intermediate (b) following by a cyclo-addition reaction was
runs without loss of its activity (Table 5, Entry 1). All the syn- occurred to form the intermediate (c). In continue the addition
thesized compounds were confirmed by their analytical and reaction of pentafluorophenyl amine (PFPA) followed by ring-
spectroscopic data. opening of the (c) to the intermediate (d) and (e) followed by ring
To explain the formation of 6a as a model via the condensa- closure of intermediate (e) results in the formation of intermedi-
tion reaction, we have proposed a plausible reaction mechanism, ate (f) that convert to the (6a) as product by the de-protonation
which is illustrated in Scheme 3. Firstly, the protonation of cou- reaction. Interestingly, the formation of compound 6a, obtained
marin-3-carboxylic acid by PFPAT as a Brønsted acid was oc- from the condensation of coumarin-3-carboxylic acid with 4a,
curred to form a cation intermediate (a). In continue, the confirms the mechanism of the reaction which was rarely de-
formation of (b) resulting from the amidation of (a) with 4a scribed in the literature as Dimroth rearrangement [33,34].

Table 4 Preparation of ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-5-phenyl-3H-pyrano[2,3-d]pyrimidine-6-car-

boxylate: effect of solvent.a
Entry Solvent Amount of catalyst (mol%) Time (h) Yield (%)b
1 1,4-Dioxane 5.0 6.0 66
2 Ethanol 5.0 6.0 82
3 Acetonitrile 5.0 8.0 20
4 THF 5.0 8.0 25
5 Methanol 5.0 6.0 78
6 t-BuOH 5.0 6.0 25
7 None 5.0 6.0 89
a
Reaction conditions: 4a (1 mmol) and coumarin-3-carboxylic acid (1 mmol) in the presence of PFPAT (5 mol%); 80 C.
b
Isolated yields.
PFPAT catalyzed construction of chromeno[2,3-d]pyrimidinones 215

Table 5 Preparation of various ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2-oxo-2H-chromen-3-yl)-5-phenyl-3H-pyrano[2,3-d]pyrimidine-

6-carboxylate derivatives.a
Entry R1 Product Time (h) Yield (%)b Mp (C)
1 H 6a 6.0 89 (87, 85, 84)c 272–274
2 3-OH 6b 6.0 85 234–236
3 3-NO2 6c 6.0 84 268–270
4 4-N(CH3)2 6d 5.5 82 280–282
5 4-Cl 6e 5.5 87 218–220
6 4-F 6f 5.5 86 286–288
7 4-OCH3 6g 7.0 84 220–222
8 4-NO2 6h 5.0 86 266–268
9 4-Br 6i 5.5 87 244–246
10 4-CH3 6j 6.0 85 234–236
a
Reaction conditions: 4a–j (1 mmol) and coumarin-3-carboxylic acid (1 mmol) in the presence of PFPAT (5 mol%) at 80 C.
b
Isolated yield.
c
Reusability of catalyst.

H O
O O
CN
C2H5O
HO PFPAT HO
+
-PFPA H3C O NH2
O O O O
a 4a

heat
heat - H2O
O PFPAT CN
NH O -PFPAT
- H2O O
C2H5O -PFPA
O N
C2H5O O H
H3C O O
N H3C O
H b
c
O O

NH2
F F
PFPA = Nu
F F
O O
F
NH
C2H5O Nu
O NH heat
O H3C O N
C2H5O Nu H
O O
H3C O N e
H
O O
d - Nu

O
O
O O C2H5O
Nu NH
C2H5O NH H3C O
-PFPAT N
H
H3C O N O
f O
O O

6a

Scheme 3 Proposed mechanism for the formation of 6a.

216 M. Ghashang et al.

Table 6 In vitro antibacterial activity of compounds 6a–j.

Compounds MIC in lg/mL and zone of inhibition in mm
E. coli P. aeruginosa K. pneumonia S. aureus
6a 12.5(15–18) 12.5(15–18) 12.5(15–18) 12.5(16–18)
6b 6.25(16–19) 6.25(19–21) 6.25(15–18) 6.25(16–18)
6c 12.5(14–17) 12.5(15–18) 12.5(15–18) 12.5(16–18)
6d 12.5(12–15) 12.5(12–15) 12.5(15–18) 12.5(15–18)
6e 6.25(16–18) 6.25(15–18) 6.25(15–18) 6.25(16–18)
6f 6.25(16–18) 6.25(15–18) 6.25(15–18) 6.25(16–18)
6g 25(8–11) 25(9–12) 25(8–11) 25(9–12)
6h 25(8–11) 25(9–12) 25(8–11) 25(9–12)
6i 6.25(18–20) 6.25(16–18) 6.25(16–18) 6.25(16–18)
6j 6.25(18–20) 6.25(15–18) 6.25(16–18) 6.25(18–20)
Ciprofloxacin 6.25(30–35) 6.25(26–32) 6.25(21–25) 6.25(25–28)

Biological evaluations well. A control was also prepared for the plates in the same
way using DMSO as a solvent. The Petri dishes were prepared
All the compounds were screened for their antibacterial and in triplicate and maintained a 37 C for 3–4 days. Antibacterial
antifungal activity. Compounds 6a–j with various substituents activity was determined by measuring the diameter of inhibi-
in the aromatic ring will be useful in understanding the influ- tion zone. Activity of each compound was compared with cip-
ence of steric and electronic effects on the biological activity. rofloxacin as standard. Zone of inhibition was determined for
6a–j. The results are summarized in Table 6. The MIC values
Antibacterial activity were evaluated at concentration range, 6.25–25 lg/mL. The
figures in the table show the MIC values in lg/mL and the cor-
The newly synthesized compounds were screened for their responding zone of inhibition in mm. From the activity report
in vitro antibacterial activity against Escherichia coli (E. coli), (Table 6) it was notified that most of the compounds showed
Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumonia moderate activity against all the bacterial strains.
(K. pneumonia), and Staphylococcus aureus (S. aureus) bacte-
rial stains by serial plate dilution method. Serial dilutions of Antifungal activity
the drug in Muller Hinton broth were taken in tubes, and their
pH was adjusted to 5.0 using phosphate buffer. A standardized Newly prepared compounds were also screened for their anti-
suspension of the test bacterium was inoculated and incubated fungal activity against Aspergillus flavus (A. flavus), Rhizopus
for 16–18 h at 37 C. The minimum inhibitory concentration schipperae (R. schipperae), Aspergillus niger (A. niger) and Can-
(MIC) was noted by seeing the lowest concentration of the dida albicans (C. albicans) in DMSO by serial plate dilution
drug at which there was no visible growth. method. Sabourauds agar media were prepared by dissolving
A number of antibacterial disks were placed on the agar for peptone (1 g). D glucose (4 g) and agar (2 g) in distilled water
the sole purpose of producing zones of inhibition in the bacte- (100 mL) and adjusting the pH to 5.7. Normal saline was used
rial lawn. Twenty milliliters of agar media was poured into to make a suspension of sore of fungal strains for lawning. A
each Petri dish. Excess of suspension was decanted, and plates loopful of particular fungal strain was transferred to 3 mL sal-
were dried by placing in an incubator at 37 C for an hour. ine to get a suspension of corresponding species. Twenty mil-
Using a punch, wells were made on these seeds agar plates, liliters of agar media was poured into each Petri dish. Excess
and minimum inhibitory concentrations of the test compounds of suspension was decanted, and plates were dried by placing
in dimethyl sulfoxide (DMSO) were added into each labeled in an incubator at 37 C for 1 h. Using a punch, wells were

Table 7 In vitro antifungal activity of compounds 6a–j.

Compounds MIC in lg/mL and zone of inhibition in mm
A. flavus R. schipperae A. niger C. albicans
6a 12.5(16–20) 12.5(18–22) 12.5(20–22) 12.5(20–22)
6b 6.25(16–20) 6.25(18–22) 6.25(20–22) 6.25(18–20)
6c 12.5(15–18) 12.5(18–22) 12.5(20–22) 12.5(18–20)
6d 12.5(10–12) 12.5(12–16) 12.5(16–18) 12.5(18–18)
6e 6.25(12–16) 6.25(12–16) 6.25(16–18) 6.25(16–18)
6f 6.25(10–14) 6.25(12–14) 6.25(12–15) 6.25(14–16)
6g 25(10–12) 25(8–11) 25(10–12) 25(10–12)
6h 25(10–12) 25(9–12) 25(10–12) 25(10–12)
6i 6.25(15–16) 6.25(18–22) 6.25(18–22) 6.25(18–20)
6j 6.25(14–18) 6.25(16–14) 6.25(16–18) 6.25(16–18)
Amphoterecin-B 6.25(22–26) 6.25(30–34) 6.25(27–30) 6.25(28–32)
PFPAT catalyzed construction of chromeno[2,3-d]pyrimidinones 217

made on these seeded agar plates. Minimum inhibitory con- oxo calanolide A analogues as anti-HIV-1 agents. J Med Chem
centrations of the test compounds in DMSO were added into 2008;51(5):1432–46.
each labeled well. A control was also prepared for the plates [7] Kontogiorgis CA, Hadjipavlou LD. Synthesis and biological
in the same way using solvent DMSO. The Petri dishes were evaluation of novel coumarin derivatives with a 7-azomethine
linkage. Bioorg Med Chem Lett 2004;14:611–4.
prepared in triplicate and maintained at 37 C for 3–4 days.
[8] Sashidhara KV, Rosaiah JN, Kumar A, Bhatia G, Khanna AK.
Antifungal activity was determined by measuring the diameter Synthesis of novel benzocoumarin derivatives as lipid lowering
of inhibition zone. Activity of each compound was compared agents. Bioorg Med Chem Lett 2010;20:3065–9.
with Amphoterecin-B as standard. Zones of inhibition were [9] Bansala Y, Ratraa S, Bansala G, Singhb I, Aboul-Eneinc HY.
determined for 6a–j. The results are summarized in Table 7. Design and synthesis of coumarin substituted oxathiadiazolone
The MIC values were evaluated at concentration range, derivatives having anti-inflammatory activity possibly through
6.25–25 lg/mL. The figures in the table show the MIC values p38 MAP kinase inhibition. J Iran Chem Soc 2009;6(3):504–9.
in lg/mL and the corresponding zone of inhibition in mm. [10] Olayinka OA, Obinn CN. Microwave-assisted synthesis and
All the newly synthesized compounds showed moderate activ- evaluation of antimicrobial activity of 3-(3-(s-aryl and s-
ity against all the fungal strains. heteroaromatic)acryloyl)-2H-chromen-2-one derivatives. J
Heterocycl Chem 2010;47:179–87.
[11] Ghosh PP, Das AR. Nano crystalline ZnO: a competent and
Conclusions reusable catalyst for one pot synthesis of novel benzylamino
coumarin derivatives in aqueous media. Tetrahedron Lett
Various derivatives of ethyl 4,5-dihydro-7-methyl-4-oxo-2-(2- 2012;53:3140–3.
oxo-2H-chromen-3-yl)-5-phenyl-3H-pyrano[2,3-d] pyrimidine- [12] Khoobi M, Ramazani A, Foroumadi AR, Hamadi H, Hojjati Z,
6-carboxylate (6a–j) were synthesized from the reaction of Shafiee A. Efficient microwave-assisted synthesis of 3-
benzothiazolo and 3-benzothiazolino coumarin derivatives
2-amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-ethylcarboxy-
catalyzed by heteropoly acids. J Iran Chem Soc
lates (4a–j) with coumarin-3-carboxylic acid in the presence of 2011;8(4):1036–42.
PFPAT as reusable and inexpensive Brønsted acidic catalyst [13] Khurana JM, Kumar S. Tetrabutylammonium bromide
under solvent-free condition. All the synthesized compounds (TBAB): a neutral and efficient catalyst for the synthesis of
were screened for their in vitro antimicrobial activity. The new- biscoumarin and 3,4-dihydropyrano[c]chromene derivatives in
ly synthesized compounds showed moderate activity against all water and solvent-free conditions. Tetrahedron Lett
the bacterial and fungal strains. 2009;50:4125–7.
[14] Banothu J, Bavanthula R. Brønsted acidic ionic liquid catalyzed
Conflict of interest highly efficient synthesis of chromeno pyrimidinone derivatives
and their antimicrobial activity. Chin Chem Lett
2012;23:1015–8.
The authors have declared no conflict of interest. [15] Zhou J-F, Gong G-X, An L-T, Liu Y, Zhu F-X, Zhu Y-L. An
efficient synthesis of quinoxalines under catalyst-free and
microwave-irradiation conditions. Synlett 2008;20:3163–6.
[16] Funatomi T, Wakasugi K, Misaki T, Tanabe Y.
Acknowledgements Pentafluorophenylammonium triflate (PFPAT): an efficient,
practical, and cost-effective catalyst for esterification, thio
The authors Mansoor and Aswin are thankful to the Manage- esterification, trans esterification, and macrolactone formation.
ment of C. Abdul Hakeem College, Melvisharam 632 509 Green Chem 2006;8:1022–7.
(TN), India for the facilities and support. [17] Iida A, Osada J, Nagase R, Misaki T, Tanabe Y. Mild and
efficient pentafluoro phenylammonium triflate (PFPAT)-
catalyzed C-acylations of enol silyl ethers or ketene silyl
References (thio)acetals with acid chlorides. Org Lett 2007;9:1859–62.
[18] Nagase R, Osada J, Tamagaki H, Tanabe Y.
[1] Curir P, Galeotti F, Marcello D, Barile E, Lanzotti V. Pavietin, Pentafluorophenylammonium trifluoromethanesulfonamide:
a coumarin from Aesculus pavia with antifungal activity. J Nat mild, powerful, and robust catalyst for Mukaiyama aldol and
Prod 2007;70(10):1668–71. Mannich reactions between ketene silyl acetals and ketones or
[2] Al-Amiery AA, Al-Bayati RIH, Saour KY, Radi MF. oxime ethers. Adv Synth Catal 2010;352:1128–34.
Cytotoxicity, antioxidant and antimicrobial activities of novel [19] Khaksar S, Zakeri H. Pentafluorophenylammonium triflate as a
2-quinolone derivatives derived from coumarin. Res Chem mild and new organocatalyst for acylation of alcohols, phenols,
Intermed 2012;38:559–69. and amines under solvent-free condition. Comb Chem High
[3] Zhan W-H, Hua J-L, Jin Y-H, Teng X, Tian H. The synthesis Throughput Screen 2012;15(7):576–9.
and characterization of novel coumarin-containing cyanine dyes [20] Khaksar S, Behzadi N. Pentafluorophenylammonium triflate
via ‘‘Click’’ chemistry. Res Chem Intermed 2008;34:229–39. (PFPAT): an efficient, practical, and cost-effective catalyst for
[4] Sashidhara KV, Kumar A, Kumar M, Sarkar J, Sinha S. one-pot condensation of b-naphthol, aldehydes and cyclic 1,3-
Synthesis and in vitro evaluation of novel coumarin–chalcone dicarbonyl compounds. Comb Chem High Throughput Screen
hybrids as potential anticancer agents. Bioorg Med Chem Lett 2012;15(10):845–8.
2010;20:7205–11. [21] Khaksar S, Behzadi N. Mild and highly efficient method for
[5] Gursoy A, Karali N. Synthesis, characterization and primary synthesis of 14-aryl(alkyl)-14H-dibenzo[a, j]xanthenes and 1,8-
antituberculosis activity evaluation of 4-(3-coumarinyl)-3- dioxooctahydroxanthene derivatives using pentafluorophenyl
benzyl-4-thiazolin-2-one benzylidenehydrazones. Turk J Chem ammonium triflate as a novel organocatalyst. Chin J Catal
2003;27:545–51. 2012;33(6):982–5.
[6] Ma T, Liu L, Xue H, Li L, Han C, Wang L, et al. Chemical [22] Khaksar S, Vahdat SM, Moghaddamnejad RN.
library and structure–activity relationships of 11-demethyl-12- Pentafluorophenylammonium triflate: an efficient, practical,
218 M. Ghashang et al.

and cost-effective organocatalyst for the Biginelli reaction. [29] Jin T-S, Wang A-Q, Shi F, Han L-S, Liu L-B, Li T-S.
Monatsh Chem 2012;143:1671–4. Hexadecyldimethyl benzyl ammonium bromide: an efficient
[23] Mansoor SS, Aswin K, Logaiya K, Sudhan SPN. [Bmim]BF4 catalyst for a clean one-pot synthesis of tetrahydrobenzopyran
ionic liquid: an efficient reaction medium for the one-pot multi- derivatives in water. ARKIVOC 2006(xiv):78–86.
component synthesis of 2-amino-4,6 diphenyl pyridine-3- [30] Nemouchi S, Boulcina R, Carboni B, Debache A.
carbonitrile derivatives. J Saudi Chem Soc 2012, http:// Phenylboronic acid as an efficient and convenient catalyst for
dx.doi.org/10.1016/j.jscs.2012.07.011. a three-component synthesis of tetrahydrobenzo[b]pyrans. C R
[24] Mansoor SS, Aswin K, Logaiya K, Sudhan SPN. An efficient Chimie 2012;15:394–7.
one-pot multi component synthesis of polyhydroquinoline [31] Khaksar S, Rouhollahpour A, Talesh SM. A facile and efficient
derivatives through Hantzsch reaction catalysed by gadolinium synthesis of 2-amino-3-cyano-4H-chromenes and
triflate. Arab J Chem 2012, http://dx.doi.org/10.1016/ tetrahydrobenzo[b]pyrans using 2,2,2-trifluoroethanol as a
j.arabjc.2012.10.017. metal-free and reusable medium. J Fluorine Chem
[25] Ghashang M, Aswin K, Mansoor SS. An eco-friendly catalytic 2012;141:11–5.
route for one-pot synthesis of 2-amino-6-(2-oxo-2Hchromen-3- [32] Davoodnia A, Allameh S, Fazil S, Tavakoli-Hoseini N. One-pot
yl)-4-arylnicotinonitrile derivatives by silica supported synthesis of 2-amino-3-cyano-4-arylsubstituted
perchloric acid (HClO4–SiO2) under solvent-free conditions. tetrahydrobenzo[b]pyrans catalysed by silica gel-supported
Res Chem Intermed 2014;40:1135–45. polyphosphoric acid (PPA–SiO2) as an efficient and reusable
[26] Ghashang M. Bismuth nitrate as an efficient catalyst for the catalyst. Chem Pap 2011;65(5):714–20.
preparation of 2-arylbenzothiazole derivatives. Res Chem [33] Foucourt A, Dubouilh-Benard C, Chosson E, Corbière C,
Intermed 2013, doi:10.1007/s11164-013-1072-9. Buquet C, Iannelli M, Leblond B, Marsais F, Besson T.
[27] Pratap UR, Jawale DV, Netankar PD, Mane RA. Baker’s yeast Microwave-accelerated Dimroth rearrangement for the
catalyzed one-pot three-component synthesis of synthesis of 4-anilino-6-nitroquinazolines. Application to an
polyfunctionalized 4H-pyrans. Tetrahedron Lett efficient synthesis of a microtubule destabilizing agent.
2011;52:5817–9. Tetrahedron 2010;66:4495–502.
[28] Kumar D, Reddy VB, Sharad S, Dube U, Kapur S. A facile one- [34] Dimroth O. Ueber intramolekulare Umlagerungen.
pot green synthesis and antibacterial activity of 2-amino-4H- Umlagerungen in der Reihe des 1, 2, 3-triazols. Justus Liebigs
pyrans and 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromenes. Annalen der Chemie 1909;364:183–226.
Eur J Med Chem 2009;44:3805–9.