Nanocrystalline and reusable ZnO catalyst for the assembly of densely functionalized 4H-chromenes in aqueous medium via one-pot three component reactions: A greener nOSE approach

Article abstract of DOI:10.1021/jo400763z

An ecofriendly, one-pot, three component ZnO nanoparticles-mediated synthesis of 4H-chromene in water under thermal condition has been described. The highly product-selective three component electrophilic reaction of 2-hydroxybenzaldehyde with an active methylene compound and another carbon-based varied nature of nucleophile has been developed by a reversible alkylation procedure using greener NOSE approach. Greenness of the process was well instituted, as water was used both as reaction media as well as medium for the synthesis of catalyst. In these reactions, the use of nano-ZnO as a catalyst was documented to be crucial for rendering the reactions possible in water media, while replacing nano-ZnO with other acids or bases resulted in the generation of too many side products. The catalyst can be efficiently recycled up to the sixth run, an essential point in the area of green chemistry. The methodology provides cleaner conversion, shorter reaction times, and high selectivity, which make the protocol globally putative. The crystal structures of 4H-chromene, easily produced by a chromatography-free highly product-selective reaction, were explored by means of single crystal X-ray diffraction analysis, and H-bonding arrangements of one signified compound prepared is presented. In optimized mild conditions, the isolated yields are 86-93%.

Full text of DOI:10.1021/jo400763z

Article
pubs.acs.org/joc
Nanocrystalline and Reusable ZnO Catalyst for the Assembly of
Densely Functionalized 4H‑Chromenes in Aqueous Medium via One-
Pot Three Component Reactions: A Greener “NOSE” Approach
Partha Pratim Ghosh and Asish R. Das*
Department of Chemistry, University of Calcutta, Kolkata-700009, India
S
* Supporting Information
ABSTRACT: An ecofriendly, one-pot, three component ZnO nanoparticles-mediated synthesis of 4H-chromene in water under
thermal condition has been described. The highly product-selective three component electrophilic reaction of 2-
hydroxybenzaldehyde with an active methylene compound and another carbon-based varied nature of nucleophile has been
developed by a reversible alkylation procedure using greener “NOSE” approach. Greenness of the process was well instituted, as
water was used both as reaction media as well as medium for the synthesis of catalyst. In these reactions, the use of nano-ZnO as
a catalyst was documented to be crucial for rendering the reactions possible in water media, while replacing nano-ZnO with other
acids or bases resulted in the generation of too many side products. The catalyst can be efficiently recycled up to the sixth run, an
essential point in the area of green chemistry. The methodology provides cleaner conversion, shorter reaction times, and high
selectivity, which make the protocol globally putative. The crystal structures of 4H-chromene, easily produced by a
chromatography-free highly product-selective reaction, were explored by means of single crystal X-ray diffraction analysis, and H-
bonding arrangements of one signified compound prepared is presented. In optimized mild conditions, the isolated yields are
86−93%.
efficient, and more ecofriendly, which institutes “green
chemistry” and produces most desirable products. The
emerging interest on the catalytic properties of transition
metal nanoparticles is due to their large surface area, distinctive
electronic, magnetic, optical, thermal and chemical properties.4
The definite intention to work with nanoparticles is their high
catalytic activity, recoverability, improved selectivity, criteria of
evolution and role in green chemistry.5 Hence, organic
synthesis catalyzed by metal/metal oxide nanoparticles has
received remarkable importance in recent years.
Chromenes and their structural analogues are of great
interest because they are frequently found in a number of
natural products and biologically active molecules like antibiotic
rhodomyrtone, a glycosidase inhibitor myrtucommulone-E and
HA14-1, apoptosis inducer (Figure 1).6 Their syntheses have
attracted wide attention for their biological properties, such as
anticonvulsant,7 antimicrobial,8 antitumor,9 anticoagulant,
diuretic, spasmolytic, and antianaphylactic activities.10 On the
other hand, 3-substituted coumarin, 3-substituted indole,
INTRODUCTION
■
In recent years, emergent awareness about ecological safety and
global warming has caused worldwide concern about the use of
renewable sources and reduction of waste. This has shifted the
paradigm toward the use of ecofriendly and green protocols in
all phases of chemical construction and can be appreciated by
creative research that widely addresses the issues of atom
economy, economy of steps, and avoidance of hazardous
chemicals.1 Development of efficient and environmentally
friendly synthetic methodologies for the synthesis of compound
libraries of medicinal scaffolds is as an attractive area of research
in both academic and pharmaceutical industry.2 Multicompo-
nent reactions (MCR) in water will be one of the most apt
approaches, which will meet the requirements of green
chemistry as well as for developing libraries of medicinal
scaffolds.3
Nanotechnology and related sciences offer the opportunity
to make products and processes green from the beginning. The
development of green processes and pollutant-free catalysts has
integrated great importance. Catalysis lies at the heart of
innumerable chemical protocols. Pioneering catalytic processes
based on such nanocatalysts will be simpler, economically
Received: April 18, 2013
© XXXX American Chemical Society
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Figure 1. Some biologically active chromenes, coumarins, indole and pyrazolones.
pyrazolone, β-naphthol, uracil derivatives are of much
significance due to their presence in plenty of natural and
medicinal scaffolds, namely, coumatetralyl,11 bromadialone,12
monatin,13 phenazone,14 propyphenazone,15 etc. (Figure 1),
possessing antibacterial, anti-HIV, anticancer, antioxidant and
antitubercular activities.
analysis confirmed the presence of zinc and oxygen element
only (Figure 2) in the nanosample. The weight % of Zn and O
is 73.80 and 26.20, and atomic % is 40.81 and 59.19,
respectively.
A molecular scaffold that accumulates chromene as well as
various bioactive nucleophiles like 3-substituted coumarin, 3-
substituted indole, pyrazolone, β-naphthol, and 6-amonouracil
moieties might integrate properties of both, and the synergism
of both the heterocyclic moieties in a single nucleus may result
in the formation of some worthwhile molecules from the
biological point of view. A literature survey suggested that there
are very few reports where chromene assimilates with indole,16
pyrazolone17 and 4-hydroxycoumarin18 moieties. However, the
reported methods suffer from many drawbacks like utilization
of hazardous chemicals, longer reaction time, unsatisfactory
yields and burdensome product isolation procedure. Moreover,
the striking disadvantage of almost all reported methods is that
the catalysts are consumed in the reaction. To overcome those
shortcomings, our interest goes in the growth of nanoparticle-
catalyzed organic synthesis enhancement (NOSE) chemistry,19
which enables us to report ZnO nanoparticles catalyzed
synthesis of highly functionalized chromene derivatives via
multicomponent reaction approach, commencing with 2-
hydroxybenzaldehyde, an active methylene compound and a
bioactive carbon-based nucleophile in water (Scheme 1). The
Figure 2. EDX analysis of nano-ZnO.
For the identification of functional groups, bonding
information, study of strength and fraction of hydrogen
bonding, comparative FT-IR spectra (Figure 3) were recorded
between bulk ZnO and nano-ZnO. Broad band at 3408 and
3377 cm−1 are assigned to the O−H stretching mode of
hydroxyl groups of atmospheric moisture for both nano-ZnO
and bulk ZnO, respectively. The peaks at 1631 cm−1 of nano-
ZnO indicates the presence of CO residues, probably due to
Scheme 1. Synthesis of 4H-Chromene Derivatives
present work materializes as a part of our ongoing research
program involving water as the solvent and nano-ZnO as the
key catalyst in the synthesis of various biologically active
molecules.20
RESULTS AND DISCUSSION
■
ZnO nanoparticles were prepared through the “bottom up”
method.21 To characterize ZnO nanoparticles, EDX analysis
was performed to determine the elemental composition. EDX
Figure 3. FT-IR spectrum of nano-ZnO.
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atmospheric CO2, which was not observed in bulk ZnO. Hence,
as the size of the nanoparticles increases, the content of CO
residues in the sample decreases.
Figure 4 shows the XRD pattern of ZnO nanoparticles. The
observed peaks correspond to the Bragg angle for the (100),
The TGA and SDTA curve measures the compositional
changes associated with the calcinations processes and is shown
in Figure 6. Because of high thermal stability of nano-ZnO, no
change has been observed up to 600 °C.
Figure 4. Comparative XRD patterns of (a) bulk ZnO, (b) nano-ZnO,
(c) recovered after sixth cycle.
Figure 6. TGA and SDTA curve of nano-ZnO.
(002), (101), (102), (110), (103) and (112) planes of the
crystalline ZnO, which are consistent with standard JCPDS
reported values. Applying Sherrer’s formula, Dp = 0.941λ/βz
cos θ; where X-ray wavelength (λ) = 1.5406 Å and β is the
corresponding full width at half-maximum (fwhm) value of
characteristic peaks (100) and (101), and accordingly, (a) the
particle sizes of bulk ZnO is about 68 nm; (b) the synthesized
ZnO were found to lie between 10 and 12 nm; and (c) after
sixth run of recycling it is about 13−14 nm, conforming the
unchanged morphology. These sizes are consistent with those
measured from the TEM images, indicating the single crystal
nature of nanoparticles.
Figure 5a−c shows the TEM images of synthesized nano-
ZnO. The size of the particle of nano-ZnO is estimated through
TEM and found to be near about 10 nm. No impurities were
involved in the synthesized ZnO nanoparticles sample. The
synthesis of ZnO nanoparticles was carried out by aqueous
chemical method using zinc acetate dihydrate and potassium
hydroxide as source materials. The entire process was carried
out in deionized water for its intrinsic advantages, as it is
simple, cost-effective, environment-friendly and can be easily
scaled up for large scale synthesis; moreover, in this method
there is no need to use high pressure and toxic chemicals.
In order to confirm ZnO nanoparticles to be the crucial for
rendering the reactions possible in aqueous media, we carried
out a long screening test employing a series of catalysts and
solvents (Table 1). Initially, salicylaldehyde (1.0 mmol),
dimedone (1.0 mmol), and 4-hydroxycoumarin (1.0 mmol)
were refluxed in presence of H2O and ethanol as the solvent
without any catalyst; however, the reactions, even after 24 h,
failed to generate any product (Table 1, entries 1 and 2). Then
the reaction was carried out in water in the presence of p-
toluenesulphonic acid (PTSA) at 55 °C, and the product was
isolated in 41% yield (Table 1, entry 3). The reactions were
also restrained in aqueous media by using L-proline as the
catalyst (Table 1, entries 4), while the use of zeolite as a catalyst
in aqueous media provided a trace amount of the desired
product (Table 1, entry 5). Among the Lewis acid catalysts,
InCl3 was tested, but it did not promote the reaction well
(Table 1, entries 6). However, an improved yield was obtained
when we applied metal oxide like nano-MgO, nano-Al2O3 and
bulk ZnO as catalyst in water (Table 1, entries 7, 8and 9).
Interestingly, we observed that ZnO was most effective for the
selective formation of desired product. Again ZnO nano-
particles showed outstanding activity in the formation of
desired product than bulk ZnO in terms of reaction time and
Figure 5. TEM images of nano-ZnO at (a) 50, (b) 20, and (c) 10 nm scale, respectively, in aqueous media.
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4H-chromene derivatives (4) in good to excellent yields (85−
93%) (Table 2).
Table 1. Screening of Catalyst, Solvents, and Reaction
Conditions
a
To estimate the scope and generality of the protocol, 2-
hydroxy aromatic aldehydes, having both electron-withdrawing
and electron-donating groups, were reacted with an active
methylene compound like dimedone, 1,3-cyclohexanedione,
malononitrile and N,N-dimethylbarbituric acid and a carbon-
based nucleophile like 4-hydroxycoumarin, 4-aminocoumarin,
6-aminouracil, β-naphthol, indole and pyrazolone under
optimized reaction conditions, and the results are exhibited in
Table 2. The reactions were consistently carried out at the 1
mmol scale, and no change of product yield was observed when
scaled up to the 10 mmol scale. From the perspective of green
chemistry, it was positive to find that the final products could
be isolated by filtration because of their solubility difference of
the product from the starting materials, leading to separation of
product from the reaction mixture upon completion, thereby
facilitating easy isolation of solid product from the reaction
mixture simply by filtration. Since ZnO nanoparticles are often
recovered easily by simple workup, which prevents contami-
nation of products, they may be considered as promising safe
and reusable catalysts as well as being greener compared to
traditional catalysts. Furthermore, the purity of the products
was too high to require their preparation in an analytically pure
form by single recrystallization, thus avoiding extraction steps
and chromatographic separations. Therefore, we preferred
water as the reaction medium over unsafe organic solvents,
which decreases the chemical impurity, features easy workup
procedure, and minimizes large volumes of waste from the
discarded chromatographic static phases. The structure of the
final products were well characterized by using spectral (IR, 1H,
13C NMR and HRMS) and elemental analysis data . The
structural motif was fully established by single X-ray crystallo-
graphic analysis of one signified compound 4e (CCDC
926789) (Figure 7).22 The compound 4e crystallizes in the
b
conditions
yields
(%)
entry
catalysts
solvents
(°C)
time (h)
c
1
2
3
4
−
−
H2O
reflux
reflux
55
24
24
8
−
−
c
EtOH
TsOH (10 mol %) H2O
41
L-proline (10
mol %)
H2O
55
8
46
5
6
7
zeolite (10 mol %) H2O
55
55
55
8
8
8
trace
29
InCl3 (10 mol %)
H2O
H2O
nano-MgO (10
mol %)
51
8
9
nano-Al2O3(10
mol %)
H2O
55
55
55
55
55
55
55
55
8
8
55
68
92
81
87
77
56
31
bulk ZnO (10
mol %)
H2O
10 nano-ZnO (10
mol %)
H2O
45 min
45 min
45 min
45 min
45 min
45 min
11
12
13
14
15
nano-ZnO (5
mol %)
H2O
nano-ZnO (15
mol %)
H2O
nano-ZnO (10
mol %)
EtOH
CH3CN
CHCl3
nano-ZnO (10
mol %)
nano-ZnO (10
mol %)
a
All reactions were carried out with salicylaldehyde (1.0 mmol),
dimedone (1.0 mmol), and 4-hydroxycoumarin (1.0 mmol) in 5 mL of
solvent. Yield of isolated product. Reaction failed to provide any
b
c
product.
temperature, and eventually we achieved satisfaction because
the reaction proceeded well, affording the desired product in
92% yield within 45 min (Table 1, entry 10). The reaction was
very clean because of the amphoteric nature of nano-ZnO;
besides, upon application of acids or bases, many unwanted
products in the reaction flask have been generated because of
the high acid−base sensitivity of starting materials, specifically
carbon-based nucleophiles.
triclinic P1 space group with one molecule in the asymmetric
̅
unit (Z = 2). While the molecule in the asymmetric unit as such
had no conventional functional groups to form H-bonding, the
coumarin groups present, however, were responsible for the
formation of weak intermolecular H-bonding along c-direction.
The inversion related molecule in the asymmetric unit forming
the heterochiral dimer synthon through C−H···O interaction is
shown in Figure 8. They formed channels with one molecule
above and one molecule below via C−H···O interaction and are
stabilized by aromatic C−H···π interactions.
Ascertaining nano-ZnO as the right catalyst for the
experiment, we then concentrated our attention on designing
and also generalizing the favorable conditions for the reaction.
We first attempted some screening tests with nano-ZnO. The
quantity of the catalyst had a large effect on the formation of
the desired product. The use of 5 mol % nano-ZnO diminished
the quantity of the yield, whereas the yield of the product also
decreased when we used 15 mol % nano-ZnO (Table 1, entries
11 and 12). Water (Table 1, entry 10) has shown its superiority
to other solvents tested [ethanol (Table 1, entry 13),
acetonitrile (Table 1, entry 14) and chloroform (Table 1,
entry 15)]. As a part of our program aimed in developing new
and environmentally benign synthetic methodologies with ZnO
nanoparticles, these optimized conditions were then applied for
all experiments: taking equimolar amounts of 2-hydroxy
benzaldehyde (1), active methylene compound (2) and a
carbon-based nucleophile (3) at 55 °C in the presence of 10
mol % nano-ZnO in aqueous media (Scheme 1). Typically, a
mixture of 2-hydroxy benzaldehyde (1.0 mmol), active
methylene compound (1.0 mmol) and a carbon-based
nucleophile (1.0 mmol) and 10 mol % nano-ZnO in 3 mL of
water was refluxed for 40−65 min, which afforded a library of
Presumably the reaction seems to proceed through following
mechanistic pathway as presented in Scheme 2. The ZnO
nanoparticles facilitate the Knoevenagel-type coupling through
Lewis acid sites (Zn2+) coordinated to the oxygen of carbonyl
groups of 2-hydroxybenzaldehyde. On the other hand, ZnO
nanoparticles can activate active methylene compounds so that
deprotonation of the C−H bond occurs in the presence of
Lewis basic sites (O2−) and form intermediate (I).
Subsequently, during the Michael addition step, nucleophilic
attack on intermediate (I) by the carbon-based nucleophile
afforded the desired product (4) via intermediate (II) paving
the way for its ring closure. Alternatively, there is another
possible reaction pathway for the reaction, via the formation of
intermediate (III) followed by its reaction with dimedone to
afford 4. Our efforts to isolate intermediate (III) from the two-
component reaction of 2-hydroxybenzaldehyde (1 equiv) and
4-hydroxycoumarin (1 equiv) in water in presence of nano-
ZnO did not fructify. These reactions, instead, led to (i)
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a
Table 2. Substrate Scopes for the Synthesis of 4H-Chromenes
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Table 2. continued
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Table 2. continued
a
2-Hydroxy benzaldehyde (1 mmol), active methylene compound (1 mmol), and a nucleophile (1 mmol) were stirred in 5 mL of water in the
b
presence of 10 mol % nano-ZnO. Isolated yield of the pure product.
(Figure 6) (Ar = 2-OHC6H4) with 50% unreacted 2-
hydroxybenzaldehyde. Similarly, the reaction of equimolar
amounts of dimedone (1 equiv) and 2-hydroxybenzaldehyde
(1 equiv) was performed with a view to getting intermediate
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medium using “NOSE” approach. ZnO nanoparticles were well
characterized by EDX, TEM, FT-IR and XRD techniques, and
their thermal stability was confirmed by TGA and SDTA curve.
This method offers several advantages including shorter
reaction time with excellent yields, a simple workup procedure,
ease of separation and recyclability of the catalyst, as well as the
ability to tolerate a wide variety of 2-hydroxy benzaldehyde,
active methylene compounds and carbon-based biologically
important nucleophile. Several green chemistry principles were
included, as (i) it is a one-pot multicomponent reaction offering
only water as the byproduct (ii) using commercially available
substrates with low cost and (iii) easy extension of the substrate
scope. Finally, one representative molecular structure was
investigated by means of X-ray diffraction analysis, which
confirms the presence of weak intermolecular H-bonding
forming a molecular channel.
Figure 7. ORTEP diagram of one signified compound 4e (CCDC
926789).
(I). Interestingly, this reaction resulted in the formation of (ii)
(Figure 6) along with unreacted 2-hydroxybenzaldehyde,
wherein intermediate (I) could not be detected even in traces.
These results indicate that both intermediates (III) and (I) in
the above reactions are very reactive toward the subsequent
reactions with dimedone and 4-hydroxycoumarin, respectively.
Hence information on the relative rates of formation as well as
further reactions of intermediate (III) and (I) with dimedone
and 4-hydroxycoumarin, respectively, could not be obtained
and compared. Consequently, whether the multicomponent
reactions occur through intermediate (I) or (III), it could not
be ascertained in the current study.
EXPERIMENTAL SECTION
■
Preparation of ZnO Nanoparticles. To a 50 mL 0.05 M solution
of zinc acetate dihydrate in deionized water, 25 mL 1 M aqueous
solution of KOH was added dropwise with a dropping funnel for 1 h at
60 °C under sonication. The sonication was carried out for another 1
h. Then the solution was centrifuged, the mother liquor was removed,
and the precipitate was washed five times with deionized water. Then
the precipitate was dried in air. It was characterized by TEM image and
X-ray diffraction study.
It is pertinent to mention that the reaction is highly product-
selective, affording only desired product (4); surprisingly, (i)−
(v) (Figure 9) were not observed in detectable amounts at all
applying this reaction.
General Procedure for the Synthesis of 4H-Chromene
Derivatives (4a−4v). A mixture of 2-hydroxybenzaldehyde 1 (1
mmol), an active methylene compound 2 (1 mmol), carbon-based
nucleophile 3 (1 mmol) and 10 mol % ZnO nanoparticles in 5 mL of
water was stirred at 55 °C for the stipulated time mentioned in Table
2. After completion of the reaction (indicated by TLC), the free-
flowing solid was filtered and washed with water (20 mL) to afford the
desired products as pale yellow solids. The product thus obtained was
recrystallized from ethanol to get pure compounds as white or pale
yellow crystals. The isolated compounds were well characterized by IR,
1H NMR, 13C NMR, HRMS, elemental analysis and an X-ray
It is important to emphasize that catalyst recyclability is an
essential aspect of green chemistry. The catalyst could be
recycled easily followed by washing with ethanol several times
to remove all the organic substances. It was then dried at room
temperature and was recycled six consecutive times with almost
unaltered catalytic activity. The recyclability chart of the
catalytic potential of the nano-ZnO is shown in Figure 10
(recovery amount 92% and yield, 89% after sixth run) (Table 2,
entry 1). The XRD pattern of the fresh nano-ZnO was
compared with the recovered one after the sixth cycle, and bulk
ZnO (Figure 4) and the TEM image of recovered nano-ZnO
after sixth cycle is presented in Figure 11.
crystallographic study.
9-(4-Hydroxy-2-oxo-2H-chromen-3-yl)-3,3-dimethyl-2,3,4,9-
tetrahydro-1H-xanthen-1-one (4a). Yield: (0.357g, 92%); White
crystalline solid; mp 232−234 °C; IR (KBr) 3317, 3192, 2952, 2921,
1674, 1632, 1582, 1486, 1453, 1369, 1275, 1234, 1184, 1036, 1014,
758 cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ 0.96 (s, 3H), 1.03 (s,
3H), 2.06−2.23 (m, 2H), 2.46−2.52 (m, 2H), 5.32 (s, 1H), 6.87−7.09
(m, 5H), 7.17 (t, J = 7.5 Hz, 1H), 7.40 (t, J = 7.5 Hz, 1H), 7.92 (d, J =
6 Hz, 1H); δC (75 MHz, DMSO-d6; Me4Si) δ 25.6, 26.4, 27.8, 30.6,
49.1, 114.4, 114.5, 115.4, 122.1, 122.6, 123.1, 126.22, 127.3, 129.9,
151.2, 158.9, 166.8, 196.1; HRMS (ESI-TOF) Calcd for C24H20O5
([M + H]+) 389.1344, found 389.1341. Anal. Calcd for C24H20O5: C
74.21; H 5.19%. Found: C 74.17; H 5.17%.
CONCLUSION
■
In conclusion, a highly product-selective and chromatography-
free three component reaction protocol has been developed for
the synthesis of densely functionalized 4H-chromene deriva-
tives, catalyzed by ZnO nanoparticles effectively in aqueous
Figure 8. The intermolecular H-bonds between the R-molecules and S-molecules. All hydrogens, except those participating in the H-bonding, have
been omitted for clarity. Symmetry codes: A x, y, −1 + x; B 2 − x, −y, −z; C 2 − x, −y, 1 − z.
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Scheme 2. Plausible Mechanism for the Formation of 4H-Chromene
Figure 9. Condensation products of aromatic aldehyde with 4-hydroxycoumarin/dimedone.
Figure 11. TEM image of recovered nano-ZnO after sixth cycle.
Figure 10. Recyclability chart of ZnO nanoparticles.
Pale yellow crystalline solid; mp 222−224 °C; IR (KBr) 3321, 3191,
2950, 1679, 1636, 1581, 1484, 1366, 1273, 1184, 1034, 1015, 758
cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ 0.90 (s, 3H), 1.02 (s, 3H),
2.10−2.19 (m, 2H), 2.32−2.49 (m, 2H), 5.09 (s, 1H), 7.08−7.13 (m,
9-(4-Hydroxy-2-oxo-2H-chromen-3-yl)-3,3-dimethyl-7-nitro-
2,3,4,9-tetrahydro-1H-xanthen-1-one (4b). Yield: (0.390g, 90%);
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2H), 7.35 (t, J = 7.5 Hz, 1H), 7.66 (s, 1H), 7.75−8.00 (m, 3H); δC (75
MHz, DMSO-d6; Me4Si) δ 26.9, 29.3,31.8, 32.1, 50.6, 103.1, 111.1,
112.8, 115.1, 115.6, 116.4, 120.4, 123.3, 124.6, 125.6, 127.2, 130.8,
139.8, 152.8, 168.8, 196.8; HRMS (ESI-TOF) Calcd for C24H19NO7
([M + H]+) 434.1195, found 434.1190. Anal. Calcd for C24H19NO7: C
66.51; H 4.42; N 3.23%. Found: C 66.49; H 4.44; N 3.21%.
9-(4-Hydroxy-2-oxo-2H-chromen-3-yl)-6-methoxy-3,3-di-
methyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (4c). Yield:
(0.380g, 91%); White crystalline solid; mp 246−248 °C; IR (KBr)
3320, 3196, 2951, 1678, 1633, 1581, 1482, 1452, 1362, 1271, 1182,
1033, 1015, 757 cm−1;δH (300 MHz; DMSO-d6; Me4Si) δ 0.97 (s,
3H), 1.10 (s, 3H), 1.98−2.19 (m, 2H), 2.26−2.47 (m, 2H), 3.61 (s,
3H), 5.30 (s, 1H), 6.38−7.47 (m, 6H), 7.90 (s, 1H); δC (75 MHz,
DMSO-d6; Me4Si) δ 18.8, 25.2, 27.0, 28.2, 29.5, 31.9, 32.1, 50.7, 55.5,
56.7, 100.8, 110.7, 111.6, 117.9, 122.8, 123.4, 124.3, 129.5, 131.3,
131.9, 151.0, 158.4, 158.9, 165.0, 196.4; HRMS (ESI-TOF) Calcd for
C25H22O6([M + H]+) 419.1450, found 419.1448. Anal. Calcd for
C25H22O6: C, 71.76; H, 5.30; %. Found: C, 71.73; H, 5.28%.
9-(4-Hydroxy-2-oxo-2H-chromen-3-yl)-2,3,4,9-tetrahydro-
1H-xanthen-1-one (4d). Yield: (0.327g, 91%); White crystalline
solid; mp 207−209 °C; IR (KBr) 3320, 3199, 2955, 1671, 1633, 1581,
1481, 1451, 1361, 1277, 1181, 1036, 1017, 758 cm−1; δH (300 MHz;
DMSO-d6; Me4Si) δ 1.60−1.90 (m, 2H), 2.33 (s, 2H), 2.63 (s, 2H),
5.54 (s, 1H), 6.66 (d, J = 6.6 Hz,1H), 7.03−7.19 (m, 2H), 7.36−7.41
(m, 2H), 7.58 (d, J = 9 Hz, 2H), 7.74 (d, J = 9 Hz, 1H); δC (75 MHz,
DMSO-d6; Me4Si) δ 28.2, 29.3, 29.5, 31.6, 32.0,50.7, 100.1, 110.1,
110.3,111.2,115.6,122.5, 124.2, 126.1, 127.2, 128.1, 128.6, 129.2,133.2,
150.3, 165.0, 196.4; HRMS (ESI-TOF) Calcd for C22H16O5 ([M +
H]+) 361.1076, found 361.1071. Anal. Calcd for C22H16O5: C 73.33;
H 4.48%. Found: C 73.30; H 4.41%.
5-(4-Hydroxy-2-oxo-2H-chromen-3-yl)-1,3-dimethyl-1H-
chromeno[2,3-d]pyrimidine-2,4(3H,5H)-dione (4e). Yield:
(0.367g, 91%); White crystalline solid; mp 267−269 °C; IR (KBr)
3407, 3160, 3079, 1730, 1640, 1577, 1431, 1394, 1340, 1237, 1187,
1136, 1039, 757 cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ 3.43 (s,
3H), 3.61 (s, 3H), 5.37 (s, 1H), 7.10−7.61 (m, 6H), 8.00−8.04 (m,
2H); δC (75 MHz, DMSO-d6; Me4Si) δ 28.1, 28.6, 29.1, 29.5, 29.6,
36.2, 87.1, 108.9, 115.9, 116.2, 116.9,121.9, 123.8, 124.3, 125.5, 125.8,
126.1, 128.5, 131.7, 149.9, 150.9, 161.9, 165.4, 196.4; HRMS (ESI-
TOF) Calcd for C22H16N2O6 ([M + H]+) 405.1042, found 405.1046.
Anal. Calcd for C22H16N2O6: C 65.34; H 3.99, N 6.93%. Found: C
65.37; H 3.94, N 6.90%.
2′-Amino-4-hydroxy-2-oxo-2H,4′H-[3,4′-bichromene]-3′-
carbonitrile (4f). Yield: (0.332g, 87%); White crystalline solid; mp
200−202 °C; IR (KBr) 3440, 3366, 2181, 1668, 1618,1576, 1531,
1481, 1184, 1034, 751 cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ 5.30
(s, 1H), 5.79 (s, 2H), 6.80−7.19 (m, 4H), 7.27−7.59 (m, 2H), 7.62−
7.94 (m, 2H); δC (75 MHz, DMSO-d6; Me4Si) δ 30.5, 115.6, 116.0,
116.3,116.5, 121.1, 121.9, 123.6, 123.8, 124.2, 127.8, 128.1, 131.7,
132.2, 149.8, 152.8, 162.3; HRMS (ESI-TOF) Calcd for C19H12N2O4
([M + H]+) 333.0831, found 333.0827. Anal. Calcd for C19H12N2O4:
C, 68.67; H, 3.64; N, 8.43; O, 19.26%. Found: C, 68.63; H, 3.61; N,
8.48; O, 19.21%.
4.91 (s, 1H), 6.73−6.99 (m, 4H), 7.13−7.16 (m, 2H), 7.23−7.48 (m,
4H); δC (75 MHz, DMSO-d6; Me4Si) δ 26.4, 27.2, 33.3, 34.1, 36.6,
103.3, 106.2, 115.5, 120.7, 122.4, 125.9, 126.5, 127.9, 131.6, 134.9,
136.5, 146.0, 147.7, 149.3, 152.4, 162.0, 164.2, 164.5, 168.2; HRMS
(ESI-TOF) Calcd for C22H17NO4 ([M + H]+) 360.1191, found
360.1187. Anal. Calcd for C22H17NO4: C 73.53; H 4.77; N 3.90%.
Found:: C 73.56; H 4.72; N 3.88%.
9-(4-Amino-2-oxo-2H-chromen-3-yl)-2,3,4,9-tetrahydro-1H-
xanthen-1-one (4i). Yield: (0.366g, 91%); White crystalline solid;
mp 225−227 °C; IR (KBr) 3444, 3178, 1740, 1631, 1570, 1438, 1397,
1348, 1239, 1188, 1135, 1031, 758 cm−1; δH (300 MHz; DMSO-d6;
Me4Si) δ 3.13−3.16 (m, 3H), 3.21 (s, 3H), 5.30 (s, 1H), 6.91−7.88
(m, 6H), 8.10−8.18 (m, 2H); δC (75 MHz, DMSO-d6; Me4Si) δ 24.3,
25.1, 80.77, 108.25, 109.69, 110.74, 111.5, 111.9, 113.2, 114.2, 117.6,
121.6, 123.7, 126.9, 128.7, 130.9, 145.4, 149.0, 149.5, 150.7, 198.7;
HRMS (ESI-TOF) Calcd for C22H17N3O5 ([M + H]+) 404.1202,
found 404.1207. Anal. Calcd for C22H17N3O5: C 65.5; H 4.25; N
10.42%. Found: C 65.44; H 4.21 N 10.46%.
9-(2-Hydroxynaphthalen-1-yl)-3,3-dimethyl-2,3,4,9-tetrahy-
dro-1H-xanthen-1-one (4j). Yield: (0.344g, 93%); White crystalline
solid; 234−236 °C; IR (KBr) 3398, 3210, 2870, 1636, 1598, 1481,
1390, 1199, 1151, 1036, 758 cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ
0.85 (s, 3H), 0.99 (s, 3H), 2.03−2.24 (m, 2H), 2.41−2.57 (m, 2H),
5.64 (s, 1H), 6.44−6.48 (m, 2H), 6.63−6.66 (m, 4H), 6.77 (t, J = 7.5
Hz, 1H), 7.18−7.32 (d, J = 6 Hz, 1H) 7.62−7.67 (m, 2H), 8.02 (d, J =
6 Hz, 1H), 9.26 (s, 1H); δC (75 MHz, DMSO-d6; Me4Si) δ 26.9, 28.5,
29.4, 32.3, 50.6, 113.6, 116.9, 117.3, 118.3, 120.1, 123.8, 125.0, 127.1,
128.7, 129.8, 131.3, 132.2, 147.5, 153.6, 165.2, 197.6; HRMS (ESI-
TOF) Calcd for C25H22O3 ([M + H]+) 371.1602, found 371.1599.
Anal. Calcd for C25H22O3: C 81.06; H 5.99%. Found: C 81.03; H
5.94%.
9-(2-Hydroxynaphthalen-1-yl)-2,3,4,9-tetrahydro-1H-xanth-
en-1-one (4k). Yield: (0.311g, 91%); White crystalline solid; mp
211−213 °C; IR (KBr) 3392, 3238, 2970, 1627, 1598, 1487, 1398,
1196, 1154, 1048, 757 cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ
1.55−1.58 (m, 2H), 1.86−1.87 (m, 2H), 2.16 (d, J = 3 Hz, 2H), 5.64
(s, 1H), 7.11−7.25 (m, 2H), 7.33−7.49 (m, 2H), 7.56−7.60 (m, 2H),
7.73−7.75 (d, J = 6 Hz, 2H), 7.87 (d, J = 7.5 Hz, 2H); δC (75 MHz,
DMSO-d6; Me4Si) δ 29.4, 31.3, 32.4, 32.8, 50.6, 105.4, 106.4, 115.5,
118.0, 120.5, 121.0, 123.3, 123.7, 128.4, 130.9, 131.3, 135.0, 138.0,
146.6, 151.9, 162.2, 163.6, 164.3, 196.0; HRMS (ESI-TOF) Calcd for
C23H18O3 ([M + H]+) 343.1289, found 343.1286. Anal. Calcd for
C23H18O3: C 80.68; H 5.30%. Found: C 80.62; H 5.27%.
5-(2-Hydroxynaphthalen-1-yl)-1,3-dimethyl-1H-chromeno-
[2,3-d]pyrimidine-2,4(3H,5H)-dione (4l). Yield: (0.357g, 92%);
White crystalline solid; mp 192−194 °C; IR (KBr) 3418, 3222, 2978,
1628, 1592, 1488, 1392, 1192, 1157, 1041, 759 cm−1; δH (300 MHz;
DMSO-d6; Me4Si) δ 3.34 (s, 3H), 3.60 (s, 3H), 5.97 (s, 1H), 6.78−
7.14 (m, 5H), 7.19−7.36 (m, 2H), 7.50−7.69 (m, 3H), 9.83 (s, 1H);
δC (75 MHz, DMSO-d6; Me4Si) δ28.6, 30.7,89.4, 109.4, 115.8, 117.9,
121.0, 122.3, 122.7, 122.8, 123.5, 124.6, 125.8, 126.4, 127.7, 128.4,
128.8, 129.2, 129.8, 130.8, 131.9, 134.6, 149.2, 150.2, 153.3, 153.7,
164.6; HRMS (ESI-TOF) Calcd for C23H18N2O4 ([M + H]+)
387.1300, found 387.1306. Anal. Calcd for C23H18N2O4: C 71.49; H
4.70; N 7.25%. Found: C 71.46; H 4.66; N 7.29%.
2-Amino-4-(2-hydroxynaphthalen-1-yl)-4H-chromene-3-car-
bonitrile (4m). Yield: (0.292g, 93%); White crystalline solid; mp
212−214 °C; IR (KBr) 3360, 3228, 2987, 2214, 1627, 1599, 1479,
1393, 1191, 1169, 1037, 759 cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ
5.10 (s, 1H), 6.06 (s, 2H), 6.31 (s, 1H), 6.82 (s, 2H), 7.05 (s, 2H),
7.26−7.64 (m, 4H), 10.80 (s, 1H); δC (75 MHz, DMSO-d6; Me4Si) δ
30.2, 110.9, 118, 7, 119.0, 124.2, 124.4, 125.6, 125.8, 125.9, 126.1,
126.5, 126.8, 127.9, 128.3, 134.6, 138.5, 141.2, 143.6, 150.4; HRMS
(ESI-TOF) Calcd for C20H14N2O2 ([M + H]+) 315.1089, found
315.1092. Anal. Calcd for C20H14N2O2: C 76.42; H 4.49; N 8.91%.
Found: C 76.37; H 4.47; N 8.88%.
9-(4-Amino-2-oxo-2H-chromen-3-yl)-3,3-dimethyl-2,3,4,9-
tetrahydro-1H-xanthen-1-one (4g). Yield: (0.349g, 90%); White
crystalline solid; mp 254−256 °C; IR (KBr) 3401, 3162, 3078, 1732,
1641, 1571, 1435, 1398, 1341, 1231, 1139, 1032, 758 cm−1; δH (300
MHz; DMSO-d6; Me4Si) δ 0.98 (s, 3H), 1.05 (s, 3H), 2.05−2.26 (m,
2H), 2.41−2.57 (m, 2H), 5.13 (s, 1H), 6.94−7.14 (m, 4H), 7.25 (t, J =
7.5 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 8.08 (d, J = 6 Hz, 1H); δC (75
MHz, DMSO-d6; Me4Si) δ 27.1, 28.5, 29.4, 32.1, 50.8, 101.2, 110.2,
115.6, 116.5, 123.8, 124.3, 124.6, 127.5, 128.9, 150.7, 152.7, 166.3,
196.9; HRMS (ESI-TOF) Calcd for C24H21NO4 ([M + H]+)
388.1504, found 388.1501. Anal. Calcd for C24H21NO4: C 74.40; H
5.46; N 3.62%. Found: C 74.37; H 5.49 N 3.58%.
9-(4-Amino-2-oxo-2H-chromen-3-yl)-2,3,4,9-tetrahydro-1H-
xanthen-1-one (4h). Yield: (0.357g, 91%); White crystalline solid;
mp 232−234 °C; IR (KBr) 3389, 3170, 3098, 1741, 1641, 1579, 1436,
1390, 1346, 1238, 1137, 1039, 758 cm−1; δH (300 MHz; DMSO-d6;
Me4Si) δ 1.99−2.06 (m, 2H), 2.18−2.19 (m, 2H), 2.31−2.42 (m, 2H),
9-(1H-Indol-3-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanth-
en-1-one (4n). Yield: (0.312g, 91%); Pale yellow crystalline solid; mp
117−119 oC; IR (KBr) 3444, 3330, 3087, 2954, 2910, 1705, 1633,
1587,1484, 1410, 1365, 1199, 1148, 1087, 755 cm−1;δH δH (300 MHz;
J
dx.doi.org/10.1021/jo400763z | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
DMSO-d6; Me4Si) δ 0.82 (s, 3H), 0.95 (s, 3H), 1.93−2.25 (m, 2H),
2.38−2.46 (m, 2H), 5.06 (s, 1H), 6.25 (s, 1H), 6.49−7.36 (m, 8H),
10.48 (s, 1H); δC (75 MHz, DMSO-d6; Me4Si) δ 26.5, 26.9, 27.7, 28.7,
28.8, 31.5, 50.4, 111.0, 112.2, 114.9, 115.9, 118.2, 119.5, 120.6, 122.5,
123.4, 124.3, 125.2, 125.6, 126.4, 126.8, 126.9, 136.3, 136.5, 149.0,
154.1, 163.7, 195.8; HRMS (ESI-TOF) Calcd for C23H21NO2 ([M +
H]+) 344.1606, found 344.1602. Anal. Calcd for C23H21NO2: C 80.44;
H 6.16; N 4.08%. Found: C 80.49; H 6.15; N 4.04%.
125.2, 127.7, 129.4, 131.7, 133.3, 135.5, 138.7, 157.6, 196.6; HRMS
(ESI-TOF) Calcd for C17H14N2O3 ([M + H]+) 295.1038, found
295.1044. Anal. Calcd for C17H14N2O3: C 69.38; H 4.79; N 9.52%.
Found: C 69.32; H 4.76; N 9.57%.
6-Amino-5-(3,3-dimethyl-1-oxo-2,3,4,9-tetrahydro-1H-
xanthen-9-yl)pyrimidine-2,4(1H,3H)-dione (4u). Yield: (0.303g,
86%); White crystalline solid; mp >300 °C; IR (KBr) 3366, 3204,
2999, 2913, 1713, 1645, 1596, 1497, 1384, 1368, 1298, 969, 754 cm−1;
δH (300 MHz; DMSO-d6; Me4Si) δ 0.90 (s, 3H), 0.96 (s, 3H), 1.99−
2.15 (m, 2H), 2.34−2.41 (m, 2H), 4.56 (s, 1H), 6.18 (s, 2H), 6.79−
6.99 (m, 4H), 9.75 (s, 1H), 9.86 (s, 1H); δC (75 MHz, DMSO-d6;
Me4Si) δ 25.1, 27.1, 29.6, 33.6, 106.1, 116.6, 115.4, 118.6, 120.4, 123.1,
126.5, 127.7, 128.9, 131.1, 135.6, 139.6, 151.9, 163.6, 197.2; HRMS
(ESI-TOF) Calcd for C19H19N3O4 ([M + H]+) 354.1409, found
354.1413. Anal. Calcd for C19H19N3O4: C 64.58; H 5.42; N 11.89%.
Found: C 64.57; H 5.37 N 11.93%.
5-(6-Amino-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3-
dimethyl-1H-chromeno[2,3-d]pyrimidine-2,4(3H,5H)-dione
(4v). Yield: (0.313g, 85%); White crystalline solid; mp >300 °C IR
(KBr) 3466, 3236, 2991, 2944, 1703, 1656, 1567, 1491, 1386, 1293,
1066, 759 cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ 3.22 (s, 3H), 3.45
(s, 3H), 5.51 (s, 1H), 6.97−7.18 (m, 4H), 7.36 (t, J = 7.5 Hz, 1H),
7.37−7.85 (m, 2H); δC (75 MHz, DMSO-d6; Me4Si) δ 20.4, 27.6,
28.6, 36.9, 114.9, 116.7, 118.4, 120.1, 123.8, 125.0, 127.6, 129.3, 130.0,
147.7, 153.7, 166.9, 197.9; HRMS (ESI-TOF) Calcd for C17H15N5O5
([M + H]+) 370.1107, found 370.1104. Anal. Calcd for C17H15N5O5:
C 55.28; H 4.09 N 18.96%. Found: C 55.28; H 4.09 N 18.96%.
5-(1H-Indol-3-yl)-1,3-dimethyl-1H-chromeno[2,3-d]-
pyrimidine-2,4(3H,5H)-dione (4o). Yield: (0.326g, 92%); White
crystalline solid; mp 178−180 °C; IR (KBr) 3400, 3346, 3081, 2881,
1712, 1634, 1549, 1498, 1423, 1386, 1146, 1091, 756 cm−1; δH (300
MHz; DMSO-d6; Me4Si) δ 3.00−3.11 (m, 3H), 3.30 (m, 3H), 5.24 (s,
1H), 6.45−6.53 (m, 2H), 6.55−6.71 (m, 2H), 6.73−7.34 (m, 4H),
10.72 (s, 1H); δC (75 MHz, DMSO-d6; Me4Si) δ 28.2, 29.4, 30.2,
111.8, 118.4, 118.5, 118.9, 119.4, 121.1, 123.9, 126.9, 127.3, 129.7,
137.0, 154.8, 163.4; HRMS (ESI-TOF) Calcd for C21H17N3O3 ([M +
H]+) 360.1303, found 360.1299. Anal. Calcd for C21H17N3O3: C
70.18; H 4.77; N 11.69%. Found: C 70.15; H 4.79; N 11.64%.
2-Amino-4-(1H-indol-3-yl)-4H-chromene-3-carbonitrile (4p).
Yield: (0.259g, 90%); White crystalline solid; mp 154−156 °C; IR
(KBr); 3456, 3356, 2198, 1656, 1599, 1580, 1528 and 1409, 753 cm−1;
δH (300 MHz; DMSO-d6; Me4Si) δ 5.78 (s, 1H), 6.69−7.22 (m, 3H),
7.33−7.36 (m, 2H), 7.42−7.54 (m, 2H), 7.91−8.24 (m, 3H); δC (75
MHz, DMSO-d6; Me4Si) δ 28.6, 49.6, 104.5, 115.6, 115.9, 116.7,
117.3, 124.5, 128.7, 129.3, 133.8, 146.5, 152.4, 153.7; HRMS (ESI-
TOF) Calcd for C18H13N3O ([M + H]+) 288.1092, found 288.1091.
Anal. Calcd for C18H13N3O: C 75.25; H 4.56; N 14.63%. Found: C
75.21; H 4.52; N 14.59%.
4-(3,3-Dimethyl-1-oxo-2,3,4,9-tetrahydro-1H-xanthen-9-yl)-
5-methyl-2-phenyl-1H-pyrazol-3(2H)-one (4q). Yield: (0.352g,
88%); Pale yellow crystalline solid; mp 242−244 °C; IR (KBr) 3080,
3061, 2988, 1659, 1598, 1490, 1387, 1198, 1039, 758 cm−1; δH (300
MHz; DMSO-d6; Me4Si) δ 0.87 (s, 3H), 1.01 (s, 3H), 2.06−2.34 (m,
4H), 2.46 (s, 3H), 5.03 (s, 1H), 6.72−6.93 (m, 4H), 7.07−7.26 (m,
2H), 7.61−8.02 (m, 3H), 10.83 (s, 1H); δC (75 MHz, DMSO-d6;
Me4Si) δ 26.4, 27.1, 32.5, 33.0, 53.0, 106.4, 111.3, 114.3, 115.4, 117.5,
118.3, 120.8, 123.8, 125.6, 126.1, 128.5, 131,1, 135.3, 145.7, 146.9,
151.9, 162.6, 196.7; HRMS (ESI-TOF) Calcd for C25H24N2O3 ([M +
H]+) 401.1801, found 401.1798. Anal. Calcd for C25H24N2O3: C
74.98; H 6.04; N 7.04%. Found: C 74.94; H 6.07; N 7.09%.
5-Methyl-4-(1-oxo-2,3,4,9-tetrahydro-1H-xanthen-9-yl)-2-
phenyl-1H-pyrazol-3(2H)-one (4r). Yield: (0.357g, 90%); White
crystalline solid; mp 253−255 °C; IR (KBr) 3036, 3010, 1676, 1502,
1465, 1388, 1337, 1254, 1179, 1012, 762 cm−1; δH (300 MHz; DMSO-
d6; Me4Si) δ 2.09−2.12 (m, 2H), 2.27 (s, 3H), 3.64−3.93(m4H), 5.20
(s, 1H), 7.00−7.38 (m, 2H), 7.61−7.76 (m, 2H; δC (75 MHz, DMSO-
d6; Me4Si) δ 17.6, 25.7, 27.6, 29.5, 33.6, 39.2, 105.8, 106.4, 115.8,
119.7, 123.3, 124.4, 125.8, 127.0, 128.0, 131.6, 140.7, 144.4, 152.6,
165.6, 197.1; HRMS (ESI-TOF) Calcd for C23H20N2O3 ([M + H]+)
373.1507, found 373.1515. Anal. Calcd for C23H20N2O3: C 74.18; H
5.41; N 7.52%. Found: C 74.17; H 5.37; N 7.57%.
4-(3,3-Dimethyl-1-oxo-2,3,4,9-tetrahydro-1H-xanthen-9-yl)-
5-methyl-3H-pyrazol-3-one (4s). Yield: (0.289g, 90%); White
crystalline solid; mp 165−167 °C; IR (KBr) 3455, 2190, 1666,
1609, 1548, 1487, 1405, 1022, 757 cm−1; δH (300 MHz; DMSO-d6;
Me4Si) δ 0.90 (s, 3H), 1.02 (s, 3H), 2.01−2.19 (m, 2H), 2.32−2.47
(m, 2H), 2.49 (s, 3H), 5.63 (s, 1H), 7.02−7.14 (m, 2H), 7.32−7.48
(m, 2H); δC (75 MHz, DMSO-d6; Me4Si) δ 25.6, 26.4, 27.8, 30.6, 49.0,
114.4, 115.4, 122.6, 126.2, 127.3, 129.9, 132.2, 151.8, 168.8, 196.1;
HRMS (ESI-TOF) Calcd for C19H18N2O3 ([M + H]+) 323.1351,
found 323.1348. Anal. Calcd for C19H18N2O3: C 70.79; H 5.63; N
8.69%. Found: C 70.79; H 5.60; N 8.65%.
ASSOCIATED CONTENT
■
S
* Supporting Information
ORTEP drawings of compounds 4e, H and 13C NMR spectra
of all compounds, and X-ray data for compounds 4e in CIF
format. These materials are available free of charge via the
Internet at http://pubs.acs.org.
1
AUTHOR INFORMATION
Corresponding Author
*E-mail: ardchem@caluniv.ac.in, ardas66@rediffmail.com. Tel.:
+913323501014, +919433120265. Fax: +913323519754.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support from U.G.C.
and University of Calcutta. P.P.G. thanks U.G.C., New Delhi,
India, for the grant of his Senior Research Fellowship.
Crystallography was performed at the DST-FIST, India-funded
Single Crystal Diffractometer Facility at the Department of
Chemistry, University of Calcutta. We also gratefully acknowl-
edge the TEQIP and Indian Association for the Cultivation of
Science for instrument facilities, and thanks are also extended to
Mr. Dibyendu Mondal for his various cooperation.
REFERENCES
■
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(2) (a) Organic Reactions in Water: Principles, Strategies and
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5-Methyl-4-(1-oxo-2,3,4,9-tetrahydro-1H-xanthen-9-yl)-3H-
pyrazol-3-one (4t). Yield: (0.344g, 89%); White crystalline solid; mp
188−190 °C; IR (KBr) 3455, 2988, 2198, 1656, 1622, 1576, 1466,
1456, 1021, 757 cm−1; δH (300 MHz; DMSO-d6; Me4Si) δ 2.57−2.58
(m, 2H), 2.69 (s, 3H), 3.21−3.26 (m, 2H), 3.66 (s, 2H), 5.02 (s, 1H),
7.91−7.93 (m, 1H), 8.04−8.06 (m, 1H), 8.12−8.43 (m, 2H); δC (75
MHz, DMSO-d6; Me4Si) δ 25.7, 26.9, 27.3, 41.0, 49.5, 108.8, 120.4,
K
dx.doi.org/10.1021/jo400763z | J. Org. Chem. XXXX, XXX, XXX−XXX

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L
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