A novel, facile, rapid, solvent free protocol for the one pot green synthesis of chromeno[2,3-d]pyrimidines using reusable nano ZnAl2O4 - A NOSE approach and photophysical studies

Article abstract of DOI:10.1039/c4ra16263c

The current protocol resulted in the preparation of an eco-friendly, highly stable, reusable nano ZnAl₂O₄ and for the first time this was used as an excellent catalyst for the pseudo four component synthesis of a library of fluorescent chromeno[2,3-d]pyrimidine derivatives. This novel protocol involved the grinding of salicylaldehydes, malononitrile and secondary amines in the presence of a catalytic amount of nano ZnAl₂O₄ at room temperature which was an extremely simple, facile, cost effective, solvent free protocol and also required just two minutes to achieve the products with excellent yields. The synthesized chromeno[2,3-d]pyrimidine derivatives showed significant absorption and emission properties and large Stoke's shift values due to their characteristic feature of an excited state intramolecular proton transfer (ESIPT) mechanism. Nano ZnAl₂O₄ exhibited better catalytic activity than that of the bulk due to its larger surface area of 63 m² g^-1, and was recycled 5 times without loss of activity.

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ARTICLE TYPE
A novel, facile, rapid, solvent free protocol for the one pot green
synthesis of chromeno[2,3ꢀd]pyrimidines using reusable nano ZnAl2O4 –
NOSE approach and their photophysical studies
Balijapalli Umamahesh, Triveni Rajashekhar Mandlimath and Kulathu I. Sathiyanarayanan*
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
The current protocol manifested the preparation of an ecoꢀfriendly, highly stable, reusable nano ZnAl2O4
and for the first time this was used as an excellent catalyst for the pseudo four component synthesis of
library of fluorescent chromeno[2,3ꢀd]pyrimidines derivatives. This novel protocol involved grinding of
10 salicylaldehydes, malononitrile and secondary amines in the presence of catalytic amount of nano
ZnAl2O4 at room temperature which was extremely simple, facile, cost effective, solvent free protocol
and also required just two minutes to achieve the products with excellent yields. The synthesized
chromeno[2,3ꢀd]pyrimidine derivatives showed significant absorption, emission properties and large
Stoke’s shift values due to their characteristic feature of excited state intramolecular proton transfer
15 (ESIPT) mechanism. Nano ZnAl2O4 exhibited better catalytic activity than that of the bulk due to its
larger surface area of 63 m2/g, and was recycled for 5 times without loss of activity.
Chromeno[2,3ꢀd]pyrimidine derivatives are the important class
of compounds constructed by the fusion of chromenes and
pyrimidines. These are the potential candidates, which exhibit in
vivo antitumor activity, cytotoxic activity against P388
50 lymphocytic leukemia by causing significant perturbation in cell
cycle kinetics, and also by being selectively active against a
number of human ovarian cell lines18. Chromeno[2,3ꢀd]
pyrimidines possess in vitro activity against both gram positive
and negative bacteria19. The derivatives with this moiety are also
55 active against fungi and their antimicrobial activities are higher
than that of 4Hꢀ chromenes19. In addition, these molecules exhibit
excellent photophysical properties but detailed study has not been
carried out so far20.
Chromeno[2,3ꢀd]pyrimidine moiety was reported by
60 O’Callaghan by the condensation of 2ꢀiminocoumarinꢀ3ꢀ
carboxamide with aldehyde, which involves multistep reaction
procedure21. LiClO4 has been used as catalyst for the synthesis of
chromeno[2,3ꢀd]pyrimidine derivatives but it requires 15 h of
stirring22. There are only few reports in the literature for the
65 synthesis of chromeno[2,3ꢀd]pyrimidines by the one pot tandem
condensation of salicylaldehydes, malononitrile and secondary
amines: high temperature solventꢀfree microwave assisted
synthesis23, expensive [Bmim]BF4 ionic liquid24, less active
heterogeneous catalyst25 and magnetic nanomaterial26 synthesis.
70 Homogeneous Lewis acid catalysts such as CuCl, ZnCl2 and
ZrOCl2.8H2O have been used for this synthesis. Even though this
protocol involves room temperature synthesis, it takes long time
to achieve the good yields and the catalysts are not reusable20.
Keeping the drawbacks of existing methods in our mind for the
75 synthesis of chromeno[2,3ꢀd]pyrimidines, we prepared ZnAl2O4
[journal], [year], [vol], 00–00 | 1
Introduction
The development of a facile, efficient protocol for the multiꢀ
component reactions (MCRs) which meet the credentials of green
20 chemistry aspects as well as cost effectiveness has gained a great
importance in synthetic as well as medicinal chemistry. MCRs
involving carbonꢀcarbon1, carbonꢀoxygen2 and carbonꢀnitrogen3
bond formation are very attractive as they allow synthesizing a
wide range of complicated medicinal scaffolds4. It is extremely
25 important to explicate a protocol which can construct such
complex molecules in a single step using reusable heterogeneous,
inexpensive catalyst in a simple solventꢀfree rapid procedure at
room temperature, with excellent yields. In recent years, nano
metal oxides have attracted much attention as excellent catalysts
30 for MCRs because of their high thermal5, chemical stability6,
large surface area7, high efficiency8 and ease of separation from
the reaction mixture9. Being cheap10 and environmentally
benign11, these nano metal oxides facilitate the reactions as they
possess active sites on their surface12 by bringing the reactants
35 close to each other, and thus accelerate the reaction rate13 and
also provide reusability14, high selectivity15 and excellent yields
in shorter duration16. Nanomaterials have been employed to
mimic the homogeneous catalysts for MCRs to carry out at room
temperature and thus these materials could be the alternative
40 catalysts for homogeneous catalysts17.
* Chemistry Division – School of Advanced Sciences VIT University,
Vellore – 632014, Tamil Nadu, India. Fax:+914162243092; Tel:
+914162244520; E-mail:sathiya_kuna@hotmail.com
† Electronic Supplementary Information (ESI) available: [NMR copies of
45 synthesized compoundes were included]. See DOI: 10.1039/b000000x/
This journal is © The Royal Society of Chemistry [year]

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nanoparticles and employed them as catalyst for MCRs. We
developed a new protocol for the pseudo four component
synthesis of chromeno [2,3ꢀd]pyrimidines using salicylaldehydes,
malononitrile and secondary amines. The protocol demonstrated
5
was a room temperature synthesis, rapid, solvent free,
environmentally benign and cost effective method. The catalysts
were chemically stable and also reused successfully for 5 cycles.
To the best of our knowledge, we report nano ZnAl2O4 for the
first time for the pseudo four component synthesis of library of
10 fluorescent chromeno[2,3ꢀd]pyrimidines synthesis.
Results and discussion
40 Fig.3 TEM images and SAED pattern of nano ZnAl2O4.
Characterization of nano ZnAl2O4
Catalytic role and optimization of nano ZnAl2O4 on the
synthesis of chromeno[2,3ꢀd]pyrimidines
In the initial phase, we planned to study the catalytic role of nano
ZnAl2O4 on oneꢀpot pseudo four component reactions of
45 salicylaldehyde, malononitrile and secondary amine as shown in
Scheme 1. We focused our attention on designing and
generalizing the optimal conditions of the reaction. At first, in
order to carry out the synthesis of chromeno[2,3ꢀd]pyrimidine
derivatives in
a more efficient way, the reaction among
50 salicylaldehyde (2 mmol), malononitrile (1 mmol) and
morpholine (1 mmol) was selected as a model reaction at room
temperature (Scheme 2). Without catalyst, the reaction did not
proceed by grinding or stirring conditions and even with ethanol
as solvent. Very low yields were obtained by employing bulk
55 Al2O3 as a catalyst in ethanol. Then we attempted preliminary
screening tests of catalysts using bulk and nanoꢀAl2O3, ZnO,
ZnAl2O4, and these tests are summarized in Table 1. Significant
improvements in the yields were observed when the reaction
conditions were switched from bulk Al2O3 to nanoꢀAl2O3 under
60 same experimental conditions. But when we carried out the same
reaction in ethanol by using bulk ZnO as a catalyst, interestingly
yields were moderately increased with reduced reaction time.
Almost similar results were obtained using nano ZnO as a
catalyst. By keeping these interesting key properties in our mind,
65 i.e., significant yield improvement using nanoꢀ Al2O3 and
reduction in the time taken for the completion of reaction using
ZnO, it was of interest to design spinel ZnAl2O4 for employing as
a catalyst for these MCRs.
Fig.1 Powder X-ray diffraction pattern of fresh nano ZnAl2O4 (a) and after
15 5 cycles (b).
Fig 1a. shows that the synthesized fresh nano ZnAl2O4 was phase
pure, and was crystallized in face centered cubic phase with the
diffraction peaks at 2θ = 19.0, 31.3, 36.8, 44.8, 49.1, 55.6, 59.3,
65.3, 74.2 and 77.3 which were indexed based on ICDD data (#
20 821043). The average crystallite size of nano ZnAl2O4 was
calculated using full width half maximum values in Scherrer’s
formula and was found to be 20 nm which corroborates the TEM
result. Fig 1b affirms that the nano ZnAl2O4 was stable even after
5 cycles. BET surface area of the catalyst was 63 m2/g. FTIR
25 spectrum of the nano ZnAl2O4 is shown in Fig. 2. It gives the
bands at 662 cmꢀ1, 558 cmꢀ1 and 501 cmꢀ1 corresponding to
stretching and bending modes of AlꢀO of octahedral AlO6 units
respectively. The absence of stretching vibration bands of inverse
spinel units (AlO4) in the range 700ꢀ850 cmꢀ1 confirms ZnAl2O4
30 was purely normal spinel structure27. EDX spectrum (Fig. 2),
confirmed the presence of atoms Zn, Al and O in the catalyst.
TEM images (Fig. 3) affirmed that the particles exhibited oval
shape and found in the range 6ꢀ20 nm (the inset in Fig. 4).
Selected area electron diffraction pattern (SAED) indicated the
35 presence of pure and crystalline spinel ZnAl2O4.
R2
R3
N
R1
CHO
OH
NanoꢀZnAl2O4
2 min, rt
R1
N
+
R2
R3
+
N
N
N
H
R1
Grinding
O
N
Solvent free
1
4
3
2
HO
70 Scheme
1 Nano ZnAl2O4 catalyzed synthesis of chromeno[2,3-
d]pyrimidine derivatives under solvent free conditions.
In order to study the catalytic role of bulk ZnAl2O4, a
controlled experiment was carried out by adopting the above
model reaction conditions by stirring at room temperature using
75 appropriate 20 mol % catalysts (Table 1, entry 1). Under these
conditions, the reaction proceeded moderately with 66% yield
and took less reaction time compared to ZnO. With the same
standard conditions, when nano ZnAl2O4 was employed as a
catalyst, surprisingly 86 % of desired chromeno[2,3ꢀd]pyrimidine
80 4a was obtained within 30 min. This was because of the higher
Fig.2 FTIR spectrum of nano ZnAl2O4 (left) and EDX spectrum of nano
ZnAl2O4(right).
2
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surface area of nano ZnAl2O4 (63 m2/g) when compared to bulk
ZnAl2O4 (10.4 m2/g). In order to study the effect of quantity of
nano ZnAl2O4 on the reaction, we monitored the same reaction
resulted in a vigorous exothermic reaction within few seconds.
Realizing this catalytic enhancement of the MCRs reaction by
nanoꢀZnAl2O4 with this ‘NOSE’ approach, the desired
using 5, 10, 15, 20 and 25 mol % of nano ZnAl2O4 catalyst and 45 chromeno[2,3ꢀd]pyrimidine derivatives were obtained up to 97 %
5
found that the quantity of catalyst had a significant effect on the
formation of the desired product. The use of 5 mol % and 15 mol
% of nanoꢀ ZnAl2O4 resulted in low yields (Table 1, entries 6 and
8). Whereas, 86 % of the desired product 4a was obtained by
employing 20 mol % of nanoꢀZnAl2O4 at room temperature
yield in 2 min reaction time under solventꢀfree grinding
conditions.
Table 2 Effect of solvents on the synthesis of chromeno[2,3d]pyrimidines
Sl. No.
Solvent
Toluene
Chloroform
Dioxane
Tetrahyrofuron,
Ethanol
Yield (%) a, b
59, 61
1
2
3
4
5
6
7
10 (Table 1, entry 5).
60, 62
69, 68
66, 70
86, 86
81, 85
79, 80
Methanol
Acetonitrile
a. Under room temperature; b. under reflux conditions; Reaction
50 Conditions: Salicylaldehyde (2 mmol), malononitrile (1 mmol),
morpholine (1mmol) and nano ZnAl2O4 catalyst (20 mol %) in 10 ml
solvent
Scheme
2 Nano ZnAl2O4 catalyzed synthesis of chromeno[2,3-
d]pyrimidines using salicylaldehyde, malononitrile and morpholine.
To estimate the scope and generality of the NOSE protocol, 2ꢀ
hydroxy aromatic aldehydes having both electronꢀwithdrawing
55 and electronꢀdonating groups were allowed to react with an active
methylene compound malononitrile and secondary amine based
nucleophile like morpholine, piperidine, 1ꢀphenylpiperazine, 1ꢀ
benzylpiperazine, NꢀBenzhydrylpiperazine, pyrrolidine, diethyl
amine, nꢀethylaniline, and nꢀethyltoluidine under optimized
60 reaction conditions. The results are depicted in Table 4. The
reaction proceded smoothly with the substituted salicylaldehydes
i.e., 4a, 4b, 4c, 4d, 4e yielding 96, 94, 89, 93, 89 % respectively
except 4f which yielded only 72 %. Similarly, the reaction with
the cyclic secondary amines such as 4a, 4g, 4k, 4l, 4m gave
65 better yields of 96, 97, 85, 89, 90 % respectively when
compared to dialkyl substituted amines such as 4q, 4r giving 81,
Table 1 Screening of the catalyst for oneꢀpot synthesis of chromeno[2,3ꢀ
15 d]pyrimidines
Ent Nano catalyst
ry
Solvent i
Without solvent
a
Stirring
Grinding
Time Yield Time Yield Time Yield
(min)
720
(%)
10
(min)
720
720
720
360
(%)
ND
12, 29
10,32
68, 69
(min)
720
30
30
30
(%)
ND
10, 28
10, 27
71, 78
1
2
3
4
5
6
7
No catalyst
Al2O3(b, n)c
720 25, 45
Al2O3(b, n)d 720 30, 47
ZnO(b, n)
360 61, 63
ZnAl2O4(b, n) 60, 30 66, 86 30, 2 84, 93 30, 2 80, 96
ZnAl2O4(b,n) e 75, 30 10, 25 45, 30 25, 44 45, 30 5, 40
ZnAl2O4(b,n) f 60, 30 30, 50 30, 10 39, 70 30, 10 35, 60
8 ZnAl2O4(b,n) g 60, 30 55, 78 30, 5 77, 88 30, 5 79, 90
9 ZnAl2O4(b,n) h 60, 30 65, 84 30, 2 83, 89 30, 2 81, 95
Reaction Conditions: Salicylaldehyde (2 mmol), malononitrile (1 mmol),
morpholine (1 mmol) and catalyst (20 mol %) in 10 ml solvent; a. 20 mol
% catalyst loaded; b.bulk; c. acedic; d. basic; e. 5 mol % catalyst loaded;
f. 10 mol % catalyst loaded; g. 15 mol % catalyst loaded; h. 25 mol %
20 catalyst loaded; i. Ethanol used as solvent; n. nano.
CN
ZnAl2O4
R2
O
6
N
H
ZnAl2O4
H
N
3
R1
CN
ZnAl2O4
R2
CN
In order to achieve high yield in a shorter duration, we
performed the reactions in various solvents at room temperature
as well as under reflux conditions. A range of nonpolar to polar
solvents such as toluene, chloroform, dioxane, tetrahydrofuron,
25 ethanol, methanol and acetonitrile were used for these MCRs, but
there was no significant effect on the yields of product even after
few hours (Table 2). Unsatisfied with these results, we also tested
the influence of solventꢀfree conditions on the reaction rate and
yield by screening several conditions at room temperature in the
30 presence of ZnAl2O4 nanoparticles and found that the product
formation took place rapidly under solventꢀfree stirring
O
H
ZnAl2O4
R1
N
N
5
2
NH
ZnAl2O4
O
N
N
7
H
H
CO
ZnAl2O4
CHO
O
H
1
OH
ZnAl2O4
R2
R1
H
N
Recycled ZnAL2O4
H shift
N
H
conditions than in the presence of
a solvent (Table 1).
O
N
Satisfactory results were obtained with the use of liquid reactants
but moderate yields were achieved with solid reactants due to the
35 improper mixing of solid reactants, which in turn reduced the
feasibility to react each other due to heterogenity. To overcome
this drawback, a systematic procedure was followed. Mixture of
salicylaldehydes (2 mmol), malononitrile (1 mmol), and nano
ZnAl2O4 catalyst (20 mol %) in mortar was well ground with
40 pestle at room temperature for 60 sec. Then the secondary amine
(1 mmol) was added to the well ground reaction mixture which
4A
R1
R2
N
N
N
O
4
Scheme 3 Plausible mechanism for nano ZnAl2O4 catalyzed synthesis of
70 chromeno[2,3-d]pyrimidines.
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80 % respectively. No products were obtained with the use of 35 out the leaching of ions after each cycle, and it was found to be
alkylꢀaryl substituted amines. The reactions were consistently
carried out at 1 mmol scale, and no change of product yield was
observed when scaled up to 10 mmol scale under the same
reaction conditions.
nil. We made a comparison of our protocol with the reported
protocols (Table 3). It is understood that although there are few
solvent free, short duration protocols for the synthesis of
chromeno[2,3ꢀd]pyrimidine available in literature, they suffer
5
The plausible mechanism for the formation of chromeno[2,3ꢀ 40 from drawbacks such as, high temperature reactions, use of
d]pyrimidine was proposed according to the literature. Initially
the condensation of salicylaldehyde 1 and malononitrile 2 yielded
Knoevenagel product 5, which upon subsequent Pinner reaction
expensive and nonꢀreusable catalysts. Nano ZnAl2O4 took the
shortest duration to synthesize these derivatives with reusability.
Photophysical study of chromeno[2,3ꢀd]pyrimidines
10 formed cyclized product 6. The reaction was initiated by catalytic
nucleophilic attack of amines 3 on the cyano group of cyclized
product 6 to produce intermediate 7. Finally, intermediate 7
reacted with another molecule of salicylaldehyde 1 followed by
proton transfer of 4A to result in the product 4 with recyclable
15 nano catalyst (Scheme 3). We assumed that the nano ZnAl2O4
initiated both Knoevenagel condensation of salicylaldehyde with
malononitrile and nucleophilic attack of secondary amine as it
possess Lewis acidic Zn2+ and Al3+ sites7. It is known from the
previous report that the Lewis acid catalysts facilitate
20 chromeno[2,3ꢀd]pyrimidines synthesis and the zinc based catalyst
is more reactive20.
The spectral properties of the compounds such as absorption
45 (λmax), emission (λem), Stoke’s shift and molar extinction
coefficient (ε) were measured in tetrahydrofuran, and they are
summarized in Table 4. The absorption and fluorescence spectra
of all the products dissolved in tetrahydrofuran are shown in Fig.
5a and 5b respectively. All the compounds showed absorption
50 with maximum wavelength ranging from 285 to 360 nm. Most of
the derivatives displayed two absorption maxima except 4f, 4h
and 4i which showed single band. Highest energy absorption
band I in the region of 280–300 nm and lowest energy absorption
band II in the region of 315–360 nm were observed. The lowest
55 energy transition band II could be attributed to the transition from
singlet ground (S0) to the first excited state (S1) S0→S1. The
increase in conjugation and increased electron density associated
with salicylaldehyde groups and presence of alkyl groups in
Table 4 Photophysical properties of nanoꢀZnAl2O4 catalyzed chromeno
60 [2,3ꢀd]pyrimidine derivatives.
Diversity in salicylaldehydes
CHO
CHO
NO2
CHO
OH
CHO
Br
CHO
OH
CHO
OH
OH
OH
OH
OEt
1d
OMe
1c
1a
1b
1f
1e
Diversity in amines
O
N
H
N
H
3a
N
3g
H
N
N
3h
N
Fig. 4 Reusability of nano ZnAl2O4 for the synthesis of chromeno[2,3-
d]pyrimidines using salicylaldehyde, malononitrile and morpholine.
N
N
H
N
H
N
H
3d
N
H
3b
H
N
H
3i
3c
3f
3e
25
To examine the reusability of nano ZnAl2O4, the catalyst was
collected by filtration after every cycle and it was washed with
chloroform, tetrahydrofuran and acetone (each 5 mL) to remove
the organic compound and dried overnight in the oven at 60 °C
before it was used for the next cycle. To check the reusability of
Entr Aldeh Amin Produ Yield
Solution
Solid
ꢁ
y
yde
e
ct
(%)
state (cmꢀ1)
λabs(nm)
290, 320
300, 355
290, 325
295, 315
295, 330
295
295, 320
285
295
290, 330
295, 320
295, 320
280, 320
295, 320
295, 315
290, 320
295, 360
290, 330
ꢀ
λem(nm)
485 499
445 509, 554 10861
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
1a
1b
1c
1d
1f
1e
1a
1c
1d
1f
1a
1a
1a
1a
1c
1d
1c
1f
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
3c
3d
3e
3f
3f
3f
3g
3g
3h
3i
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
96
94
89
93
89
72
97
93
92
91
85
89
90
91
89
87
81
80
nd
nd
10631
401
476
493
490
496
503
498
500
ꢀ
5831
10737
10019
13490
11089
13206
12978
10142
11170
11290
11089
9973
11706
11007
6681
10101
ꢀ
30 ZnAl2O4 nano, we have chosen Nano ZnAl2O4 and was found to
be consistently active for 5 cycles (Fig. 4). AAS was used to find
Table 3 Comparison of the activity of the catalysts for the synthesis of
chromeno[2,3ꢀd]pyrimidine derivatives.
491
402 ,457 512
478
496
498
501
496
470
499
494
474
495
ꢀ
516
507
508
505
500
477
509
503
555
492
ꢀ
Sl.
No.
1
Catalyst
Solvent Temperature/reReaction Yield Refer
action condition time (%) ence
LiClO4
ꢀ
C2H5OH
ꢀ
RT/stirring
100 °C/
15 h 74 ꢀ 80 22
3ꢀ 6 min 86 ꢀ 96 20
2
Microwave oven
RT/stirring
CuCl, ZnCl2 CH2Cl2, 80 °C/reflux
3
4
[Bmim]BF4*
ꢀ
20 min 65 ꢀ 90 21
7 h
4 h
72
80
16
CH3OH
ꢀ
80 °C/reflux
RT
5
6
Aminopropyl
coated Fe3O4
Nano ZnAl2O4
7 min 87ꢀ 89 22
1a
1a
4s
4t
ꢀ
RT
2 min 72 ꢀ 97 presen
t work
ꢀ
ꢀ
ꢀ
ꢀ
Yields refer to isolated products after purification by recrystallization.
* 1ꢀButylꢀ3ꢀmethylimidazolium tetrafluoroborate
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Fig. 5 (a) UV-vis spectra (b) Fluorescence spectra of compounds 4a–r recorded in tetrahydrofuran solution (5 × 10−5M).
amine moiety in chromeno[2,3ꢀd]pyrimidines led to
bathochromic shift of the absorption maxima in compounds 4b,
4q and 4r.
of ESIPT mechanism.
5
The most notable feature was the exited state intramolecular
proton transfer (ESIPT) mechanism that occurred in all the
compounds studied, and emission was observed from the excited
10 state of the keto form with fluorescence excitation wavelength
(λex) of 330 nm, which is shown in Fig. 6. It can be understood
from Fig. 5b that the compounds are fluorescent in solution and
most of the compounds displayed almost similar emission spectra
in the range of 475–500 nm with the exception of 4b and 4c
15 which showed hypsochromic shift of the emission maxima. The
compound 4h showed two emission maxima ranges of 402 nm
and 457 nm which was 94 nm blue shifted when compared 4g.
The chromeno[2,3ꢀd]pyrimidines were strongly fluorescent in
solid state and the compounds showed strong, bright green
20 emission with a maximum range of 490ꢀ510 nm in the solid state.
The corresponding solid state fluorescence spectrum is given in
Fig. 7. The fluorescence maxima of the derivatives except 4g and
4r were bathochromically shifted in solid state when compared to
emission maxima in solution. In solid state, compounds 4b and
25 4q bathochromically shifted with the emission maxima of 554,
555 nm respectively and 4n was hypsochromically shifted with
the emission maxima of 477 nm when compared to 4a.
Interestingly, compound 4l showed high emission maxima in
solid state, and donorꢀacceptor type flurophores based on 4l were
30 synthesized and detailed photophysical studies are under
progress. The compound 4f was not fluorescent in solid state. The
Stoke’s shift value was calculated to be 10631 cmꢀ1 for molecule
4a. The higher Stoke’s shift and molar extinction coefficient
value suggested significant structural changes between the
35 ground and excited states. Further, the large emission shift from
absorption maximum may be due to the presence of –OH group
connected to quinoline ring at 4th position through intervening
π−conjugation probably inducing the exited state intramolecular
proton transfer character which would also be responsible for the
40 observed larger Stoke’s shift values as the characteristic features
Fig.
6 The energy diagram of ESIPT process showing tautomeric
structures of 4g with normal and ESIPT fluorescence.
45 Conclusion
In the current study, we successfully prepared the ZnAl2O4
nanoparticles with 6ꢀ20 nm size. We developed a simple grinding
method for the pseudo four component synthesis of
chromeno[2,3ꢀd]pyrimidines at room temperature. The
50 advantages of this method are: the catalyst nano ZnAl2O4 is nonꢀ
toxic, inexpensive and chemically highly stable, reusable without
loss of activity and the method is novel, facile, rapid, green,
solventꢀfree, and a cost effective. Workup is simple and yields are
high in short duration. No column chromatography is required.
55 The prepared new chromeno[2,3ꢀd]pyrimidines showed excellent
fluorescent properties which can be used in fluorescence based
sensor applications.
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method7. 1:2 molar ratio of aqueous solution of zinc nitrate
(Zn(NO3)2. 6H2O) and aluminium nitrate (Al(NO3)3.9H2O) were
added drop wise to 25% starch solution followed by 1:1 ratio of
45 acrylamide and N, N’ꢀ methylenebisacrylamide under constant
stirring and heating. A pinch of ammonium peroxodisulphate was
added to the above homogeneous solution when the temperature
reached 80 °C. The resulted gel was heated overnight at 80 °C,
and the obtained black mass was calcined at 300 °C, 500 °C and
50 700 °C for 6 h with intermittent grinding. For comparison of
activity of catalysts, we prepared bulk ZnAl2O4 by our previous
method7.
General procedure for the synthesis of chromeno[2,3ꢀ
d]pyrimidine derivatives
55 In a typical synthesis, 20 mol % of nano ZnAl2O4 was placed in a
mortar. To this, salicylaldehyde (1) (2 mmol) was introduced,
followed by malononitrile (2) (1 mmol). The entire mixture was
well ground at room temperature for 60 sec. A vigorous
exothermic reaction took place when the secondary amine (3) (1
60 mmol) was added to the well ground reaction mixture. Grinding
of the mixture for another 60 sec led to the formation of desired
products. Completion of the reaction was monitored by TLC. The
catalyst was separated using Whatman filter paper by dissolving
the reaction mixture in tetrahydrofuran. The solvent was removed
65 by evaporation, and the crude solid product was purified by a
recrystallization procedure in tetrahydrofuron and ethanol. In
order to reuse the catalyst for the next cycle, the catalyst was
washed with chloroform, tetrahydrofuron and acetone (each 5
mL), which was later dried overnight at 60 °C and reused for the
70 next cycle.
Fig. 7 Fluorescence spectra of compounds 4a–r recorded in solid state.
Experimental Section
General information
5
Zinc nitrate (Zn(NO3)2.6H2O) and Aluminium nitrate
(Al(NO3)3.9H2O) were purchased from Himedia. Acrylamide
(C3H5NO). N, N’ꢀ methylenebisacrylamide (C7H10N2O2) and
ammonium peroxodisulphate were purchased from Sigma
Aldrich. Starch was purchased from SD fine Chemicals. Organic
10 chemicals were purchased from Sigma Aldrich, Merck and
Himedia. Purity of all the chemicals was greater than 99%. The
phase formation of nano ZnAl2O4 was inferred by Bruker D8
Advanced powder Xꢀray diffractometer using Cu Kα (λ = 1.5406
Å) radiation. The diffraction angle 2θ measurements were
15 obtained in the range of 10° ꢀ 70° at room temperature. The
catalyst was further characterized by Fourier Transformed
Infrared Spectra (FTIR) on Shimadzu IR affinity – 1 FTIR
spectrometer by KBr disk method. BET surface area of the nano
ZnAl2O4 was found from Nitrogen adsorption desorption
20 isotherms on Micromeritics ASAP 2020 V3.00 H instrument.
Elemental analysis of the nano ZnAl2O4 was performed by Field
Emission Scanning Electron Microscope coupled with Energy
Dispersive Xꢀray Analysis (FESEMꢀEDX) on JEOL JSM 7001F
with BRUKERꢀ QUNTAX Version 1.8.2). Transmission Electron
25 microscopic (TEM) images of the catalyst were received on
JEOL 3010 instrument with UHR pole piece to find out
morphology and particle size. Concentration of leached metal
ions of the catalyst after every cycle of the reaction was tested by
Atomic Absorption Spectroscopic technique using Varian AA240
2ꢀ(4ꢀmorpholinoꢀ5Hꢀchromeno[2,3ꢀd]pyrimidinꢀ2ꢀ
yl)phenol(4a)
°
Yellow solid; Melting point: 197ꢀ199 C: IR (KBr): 3375, 3024,
2949, 2779, 1753, 1708, 1560, 1388, 1246, 1209, 1161, 1118,
75 1008, 920, 767, 671 cmꢀ1: H1NMR (400 MHz, CDCl3)TM ppm:
3.46ꢀ3.43 (t, J =6.0 Hz, 4H), 3.74ꢀ3.72 (t, J =8.0 Hz, 4H), 3.94 (s,
2H), 6.87ꢀ6.83 (t, J =8.0 Hz, 2H), 7.13ꢀ7.07 (m, 2H), 7.24ꢀ7.20 (t,
J =8.0 Hz, 2H), 7.33ꢀ7.29 (q, J =4.0 Hz, 2H), 8.20ꢀ8.18 (d, J =2.0
Hz, 1H), 13.03 (s, 1H); C13NMR (100 MHz, CDCl3)TM ppm:
80 24.6, 48.0, 65.9, 97.6, 116.3, 117.3, 118.0, 118.8, 119.8, 124.5,
128.1, 128.6, 129.0, 132.9, 149.7, 159.7, 160.5, 163.1, 164.0;
HRMS for C27H21N Calculated [M+] m/z 361.1426, Found
361.1420.
1ꢀ(11ꢀmorpholinoꢀ12Hꢀbenzo[5,6]chromeno[2,3ꢀd]pyrimidinꢀ
85 9ꢀyl)naphthalenꢀ2ꢀol (4b)
1
30 instrument. H and 13C NMR spectra were taken on Bruker 300
°
Brown solid; Melting point: 180ꢀ182 C: IR (KBr): 3377, 3051,
MHz using CDCl3 and DMSOꢀd6 as the solvent with TMS as an
internal standard. Melting points were measured on Guna
capillary based melting point apparatus and were not corrected.
HRMS values were obtained on Joel GC Mate II GCꢀ Mass
35 Spectrometer. FTIR spectra of the synthesized organic
compounds were recorded using a Jascoꢀ4100 spectrometer
instrument. UVꢀVisible spectra were taken using Hitachi Uꢀ2910
spectrophotometer. Fluorescence spectra in solution and solid
2970, 2845, 1737, 1622, 1588, 1537, 1425, 1404, 1365, 1228,
1111, 925, 821, 746, 518 cmꢀ1: H1NMR (400 MHz, CDCl3)TM
ppm: 3.65 (s, 4H), 3.88 (s, 4H), 4.36 (s, 2H), 7.24ꢀ7.22 (d, J =8.0
90 Hz, 1H), 7.36ꢀ7.32 (t, J =8.0 Hz, 1H), 7.43ꢀ7.41 (d, J =8.0 Hz,
1H), 7.59ꢀ7.48 (m, 3H), 7.70ꢀ7.66 (t, J =8.0 Hz, 1H), 7.84ꢀ7.82
(d, J =8.0 Hz, 1H), 7.98ꢀ7.89 (m, 5H), 8.08ꢀ8.06 (d, J =8.0 Hz,
1H), 9.00ꢀ8.98 (d, J =8.0 Hz, 1H), 12.96 (s, 1H); HRMS for
C27H21N Calculated [M+] m/z 461.1739, Found 461.1741.
were measured using Hitachi Fꢀ7000 fluorescence spectrometer
.
95 2ꢀmethoxyꢀ6ꢀ(9ꢀmethoxyꢀ4ꢀmorpholinoꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol (4c)
40 Synthesis of ZnAl2O4
Nano ZnAl2O4 was synthesized by modifying our previous
| Journal Name, [year], [vol], 00–00
6
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°
Pale yellow solid; Melting point: 198ꢀ200 C: IR (KBr): 3311,
150.6, 160.4, 162.0, 164.4, 165.2; HRMS for C27H21N Calculated
[M+] m/z 359.1634, Found 359.1632.
3023, 2848, 1737, 1546, 1435, 1369, 1273, 1240, 1203, 1078,
1016, 742, 737, 665 cmꢀ1: H1NMR (400 MHz, CDCl3)TM ppm:
3.50ꢀ3.49 (m, 4H), 3.91ꢀ3.89 (m, 4H), 3.94ꢀ3.93 (m, 8H), 6.79ꢀ
6.77 (d, J =8.0 Hz, 1H), 6.88ꢀ6.84 (t, J =8.0 Hz, 1H), 6.98ꢀ6.96
(d, J =8.0 Hz, 1H), 7.07ꢀ7.03 (t, J =8.0 Hz, 1H), 8.10ꢀ8.08 (d, J
=8.0 Hz, 1H), 13.67 (s, 1H); C13NMR (100 MHz, CDCl3)TM ppm:
25.7, 30.9, 48.7, 56.0, 56.1, 66.6, 97.8, 110.7, 114.1, 117.9,
118.5, 119.8, 119.9, 121.1, 124.3, 140.0, 148.2 ,148.7, 150.7,
2ꢀmethoxyꢀ6ꢀ(9ꢀmethoxyꢀ4ꢀ(piperidinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol(4h)
5
°
60 Pale yellow solid; Melting point: 181ꢀ183 C: IR (KBr): 3345,
3043, 2931, 2841, 1570, 1541, 1438, 1394, 1365, 1276, 1234,
1099, 1062, 954, 740, 682 cmꢀ1: H1NMR (400 MHz, CDCl3)TM
ppm: 1.71 (m, 2H), 1.76 (m, 4H), 3.42 (m, 4H), 3.91 (s, 2H),
3.93 (s, 6H), 6.78ꢀ6.76 (d, J =8.0 Hz, 1H), 6.86ꢀ6.81 (m, 2H),
65 6.97ꢀ6.95 (d, J =8.0 Hz, 1H), 7.05ꢀ7.01 (t, J =8.0 Hz, 1H), 8.11ꢀ
8.09 (d, J =8.0 Hz, 1H), 14.00 (s, 1H); C13NMR (100 MHz,
CDCl3)TM ppm: 24.3, 25.7, 25.9, 49.5, 56.0, 56.0, 97.5, 110.5,
113.8, 117.7, 118.7, 119.8, 120.5, 121.1, 124.1, 140.2, 148.1,
148.7, 150.7, 162.2, 164.5, 164.9; HRMS for C27H21N Calculated
10 162.4, 164.4; HRMS for C27H21N Calculated [M+] m/z 421.1638,
Found 421.1640.
2ꢀethoxyꢀ6ꢀ(9ꢀethoxyꢀ4ꢀmorpholinoꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol (4d)
°
Yellow solid; Melting point: 120ꢀ122 C: IR (KBr): 3247, 3037,
15 2978, 2922, 2893, 284, 2183, 1714, 1649, 1579, 1544, 1438, 70 [M+] m/z 419.1845, Found 419.1849.
1394, 1271, 1238, 1111, 1008, 732 cmꢀ1: H1NMR (400 MHz,
2ꢀethoxyꢀ6ꢀ(9ꢀethoxyꢀ4ꢀ(piperidinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol(4i)
CDCl3)TM ppm: 1.42ꢀ1.38 (t, J =8.0 Hz, 3H), 3.51 (s, 2H), 3.81
(s, 2H), 4.05ꢀ4.00 (m, 6H), 7.09ꢀ6.75 (m, 6H), 7.86ꢀ7.84 (d, J
=8.0 Hz, 1H), 13.35 (s, 1H); C13NMR (100 MHz, CDCl3)TM ppm:
20 14.6, 14.8, 24.8, 38.8, 39.0, 39.2, 39.4, 39.7, 39.9, 40.1, 48.1,
97.5, 111.8, 116.0, 117.9, 118.1, 120.0, 120.7, 124.3, 139.1,
146.6, 147.7, 150.4, 160.8, 163.31, 163.8; HRMS for C27H21N
Calculated [M+] m/z 449.1951, Found 449.1958
°
Yellow solid; Melting point: 100ꢀ102 C: IR (KBr): 3273, 3041,
2976, 2929, 2848, 1722, 1588, 1544, 1471, 1440, 1387, 1273,
75 1219, 1199, 1070, 1020, 897, 777 cmꢀ1: H1NMR (400 MHz,
CDCl3)TM ppm: 1.70 (t, 6H), 3.49 (m, 4H), 3.81 (m, 4H), 3.95 (s,
4H), 3.99 (s, 2H), 6.94ꢀ6.83 (m, 3H), 7.00ꢀ6.98 (d, J =8.0 Hz,
1H), 7.12ꢀ7.05 (m, 2H), 8.90ꢀ8.88 (d, J =8.0 Hz, 1H), 13.52 (s,
1H); C13NMR (100 MHz, CDCl3)TM ppm: 23.8, 24.9, 25.4, 48.7,
80 55.7, 55.7, 97.1, 114.8, 117.8, 118.1, 120.0, 120.0, 120.8, 124.3,
139.1, 147.4, 148.5, 150.3, 160.7, 164.1; HRMS for C27H21N
Calculated [M+] m/z 447.2158, Found 447.2157.
4ꢀbromoꢀ2ꢀ(7ꢀbromoꢀ4ꢀmorpholinoꢀ5Hꢀchromeno[2,3ꢀ
25 d]pyrimidinꢀ2ꢀyl)phenol(4e)
°
Yellow solid; Melting point: 194ꢀ196 C: IR (KBr): 3333, 3015,
2970, 2850, 1737, 1541, 1477, 1417, 1352, 1273, 1244, 1116,
1068, 956, 867, 731, 626 cmꢀ1: H1NMR (400 MHz, CDCl3)TM
ppm: 3.52 (m, 4H), 3.82 (m, 4H), 4.03 (s, 2H), 6.88ꢀ6.86 (d, J
30 =8.0 Hz, 1H), 7.15ꢀ7.13 (d, J =8.0 Hz, 1H), 7.48ꢀ7.41 (m, 2H),
7.56 (s, 1H), 8.31ꢀ8.30 (d, J =4.0 Hz, 1H), 13.08 (s, 1H);
C13NMR (100 MHz, CDCl3)TM ppm: 24.5, 48.0, 65.9, 97.5,
109.9, 116.1, 118.4, 119.7, 122.3, 130.4, 130.7, 131.4, 135.1,
148.9, 158.9, 159.4, 162.8, 163.9; HRMS for C27H21N Calculated
35 [M+] m/z 516.9637, Found 516.9639.
4ꢀbromoꢀ2ꢀ(7ꢀbromoꢀ4ꢀ(piperidinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol(4j)
85 Yellow solid; Melting point: 226 °C: IR (KBr): 3310, 3062,
2937, 2848, 2320, 1541, 1438, 1421, 1367, 1348, 1213, 1182,
1060, 971, 817, 744, 665, 623 cmꢀ1: H1NMR (400 MHz,
CDCl3)TM ppm: 1.71 (m, 6H), 3.48 (s, 4H), 4.00 (s, 2H), 6.88ꢀ
6.86 (d, J =8.0 Hz, 1H), 7.15ꢀ7.13 (d, J =8.0 Hz, 1H), 7.48ꢀ7.42
90 (m, 2H), 7.58 (s, 1H), 8.31ꢀ8.30 (d, J =4.0 Hz, 1H), 13.28 (s,
1H); C13NMR (100 MHz, CDCl3)TM ppm: 23.7, 24.6, 25.4, 48.7,
78.5, 78.9, 79.2, 97.2, 116.0, 118.4, 119.7, 119.8, 122.6, 130.4,
130.7, 131.4, 135.1, 149.1, 158.9, 159.3, 162.9, 164.1; HRMS for
C27H21N Calculated [M+] m/z 514.9844, Found 514.9848.
4ꢀnitroꢀ2ꢀ(7ꢀnitroꢀ4ꢀ(piperidinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol(4f)
°
Yellow solid; Melting point: 262ꢀ264 C: IR (KBr): 3346, 3071,
2927, 2858, 2677, 1708, 1602, 1517, 1336, 1244, 1182, 1064,
40 842, 742, 688 cmꢀ1: H1NMR (400 MHz, CDCl3)TM ppm: 1.76 (s,
6H), 2.51 (s, 2H), 3.53 (s, 4H), 4.10 (s, 2H), 7.03ꢀ7.00 (t, J =8.0
Hz, 1H), 7.35ꢀ7.33 (d, J =8.0 Hz, 1H), 7.98ꢀ7.97 (d, J =8.0 Hz,
1H), 8.26ꢀ8.10 (m, 3H), 9.10 (s, 1H), 14.19 (s, 1H); HRMS for
C27H21N Calculated [M+] m/z 449.1335, Found 449.1333.
95 2ꢀ(4ꢀ(4ꢀphenylpiperazinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀd]pyrimidinꢀ
2ꢀyl)phenol(4k)
°
Yellow solid; Melting point: 212ꢀ214 C: IR (KBr): 3337, 3031,
2885, 2833, 2731, 1737, 1597, 1577, 1490, 1429, 1365, 1247,
1180, 1012, 950, 815, 758, 695 cmꢀ1: H1NMR (400 MHz,
100 CDCl3)TM ppm: 3.41 (s, 4H), 3.71 (s, 4H), 4.03 (s, 2H), 6.93ꢀ
6.86 (m, 3H), 7.01ꢀ6.99 (d, J =8.0 Hz, 2H), 7.16ꢀ7.12 (m, 2H),
7.36ꢀ7.25 (m, 5H), 8.38ꢀ8.36 (d, J = 8.0 Hz, 1H), 13.13 (s, 1H);
C13NMR (100 MHz, CDCl3)TM ppm: 25.0, 47.6, 48.5, 97.3,
115.7, 116.3, 117.1, 118.0, 118.3, 118.9, 119.6, 124.1, 127.8,
45 2ꢀ(4ꢀ(piperidinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀd]pyrimidinꢀ2ꢀ
yl)phenol(4g)
°
Yellow solid; Melting point: 166ꢀ168 C: IR (KBr): 3373, 3045,
2926, 2852, 2229, 1722, 1602, 1588, 1446, 1257, 1186, 1051,
970, 758, 690, 582 cmꢀ1: H1NMR (400 MHz, CDCl3)TM ppm:
50 1.78ꢀ1.75 (m, 6H), 3.45ꢀ3.42 (t, J =6.0 Hz, 4H), 3.92 (s, 2H), 105 128.4, 128.6, 128.7, 132.4, 149.8, 150.4, 159.8, 161.1, 163.5,
6.93ꢀ6.89 (t, J =8.0 Hz, 1H), 6.98ꢀ6.96 (d, J =8.0 Hz, 1H), 7.12ꢀ
7.08 (t, J =8.0 Hz, 1H), 7.26ꢀ7.18 (m, 3H), 8.36ꢀ8.32 (t, J =8.0
Hz, 1H), 8.43ꢀ8.41 (d, J =8.0 Hz, 1H), 13.45 (s, 1H); C13NMR
(100 MHz, CDCl3)TM ppm: 24.3, 25.6, 25.9, 49.5, 97.5, 117.1,
55 117.5, 118.6, 118.8, 119.5, 124.4, 128.2, 128.5, 129.2, 132.8,
164.2; HRMS for C27H21N Calculated [M+] m/z 436.1899, Found
436.1896.
2ꢀ(4ꢀ(4ꢀbenzylpiperazinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀd]pyrimidinꢀ
2ꢀyl)phenol(4l)
°
110 White solid; Melting point: 136ꢀ138 C: IR (KBr): 3357, 3012,
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2926, 2808, 2736, 1708, 1579, 1529, 1436, 1253, 997, 835, 748,
Calculated [M+] m/z 433.2002, Found 433.2010.
695. cmꢀ1: H1NMR (400 MHz, CDCl3)TM ppm: 2.58 (s, 4H), 3.54
(s, 4H), 3.58 (s, 2H), 3.99 (s, 2H), 6.95ꢀ6.92 (t, J =6.0 Hz, 2H),
7.20ꢀ7.14 (m, 2H), 7.30ꢀ7.27 (t, J =6.0 Hz, 2H), 7.39ꢀ7.34 (m,
6H), 7.28ꢀ7.26 (d, J = 8.0 Hz, 1H), 13.16 (s, 1H); C13NMR (100
MHz, CDCl3)TM ppm: 24.7, 25.1, 47.7, 52.4, 61.9, 66.9, 97.4,
116.3, 117.3, 118.1, 118.8, 119.9, 124.5, 127.0, 128.1, 128.2,
128.6, 128.9, 129.0, 132.8, 137.8, 149.8, 159.7, 160.5, 163.2,
163.9; HRMS for C27H21N Calculated [M+] m/z 450.2056, Found
2ꢀ(4ꢀ(diethylamino)ꢀ9ꢀmethoxyꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)ꢀ6ꢀmethoxyphenol(4q)
°
Yellow solid; Melting point: 170ꢀ172 C: IR (KBr): 3377, 3045,
5
60 2977, 2322, 2212, 1726, 1637, 1595, 1489, 1371, 1255, 1197,
1149, 1118, 1049, 923, 752, 615 cmꢀ1: H1NMR (400 MHz,
CDCl3)TM ppm: 1.77ꢀ1.72 (m, 6H), 3.42 (s, 4H), 3.93 (s, 8H),
6.82ꢀ6.79 (d, J =8.0 Hz, 1H), 6.87ꢀ6.85 (t, J =4.0 Hz, 2H), 6.97ꢀ
6.95 (d, J =8.0 Hz, 1H), 7.06ꢀ7.04 (t, J =8.0 Hz, 1H), 8.12ꢀ8.10
65 (d, J = 8.0 Hz, 1H), 14.0 (s, 1H); C13NMR (100 MHz, CDCl3)TM
ppm: 24.3, 25.7, 25.9, 29.7, 49.6, 56.0, 56.1, 97.5, 110.5, 113.8,
117.7, 118.7, 119.8, 120.5, 121.1, 124.1, 140.2, 148.2, 148.7,
150.7, 162.2, 164.6, 165.0; HRMS for C27H21N Calculated [M+]
m/z 407.1845, Found 407.1847.
10 450.2054.
2ꢀ(4ꢀ(4ꢀbenzhydrylpiperazinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol(4m)
°
Pale yellow solid; Melting point: 198ꢀ200 C: IR (KBr): 3367,
3024, 2954, 2877, 2841, 2382, 1735, 1597, 1546, 1489, 1429,
15 1384, 1284, 1217, 1138, 997, 956, 742 cmꢀ1: H1NMR (400 MHz,
CDCl3)TM ppm: 3.59 (s, 8H), 3.96 (s, 2H), 4.40 (s, 1H), 6.93ꢀ
6.89 (t, J = 8.0 Hz, 2H), 7.38ꢀ7.12 (m, 12H), 7.51ꢀ7.49 (m, 4H),
7.26ꢀ7.24 (d, J = 8.0 Hz, 1H), 13.16 (s, 1H); C13NMR (100 MHz,
CDCl3)TM ppm: 24.7, 47.7, 51.4, 74.9, 97.4, 116.3, 117.3, 118.0,
20 118.8, 119.9, 124.57, 126.9, 127.6, 128.1, 128.6, 129.0, 132.9,
142.6, 149.7, 159.7, 160.5, 163.2, 163.9; HRMS for C27H21N
Calculated [M+] m/z 526.2369, Found 526.2369.
70 4ꢀbromoꢀ2ꢀ(7ꢀbromoꢀ4ꢀ(diethylamino)ꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol(4r)
°
Yellow solid; Melting point: 180ꢀ182 C: IR (KBr): 3329, 3059,
2964, 2864, 1737, 1595, 1539, 1481, 1421, 1377, 1257, 1214,
1103, 966, 812, 731, 628, 538 cmꢀ1: H1NMR (400 MHz,
75 CDCl3)TM ppm: 1.96 (s, 6H), 3.79 (s, 4H), 4.03 (s, 2H), 6.87ꢀ
6.85 (d, J =8.0 Hz, 1H), 7.10ꢀ7.08 (d, J =8.0 Hz, 1H), 7.49ꢀ7.39
(m, 3H), 8.28 (s, 1H), 13.54 (s, 1H); C13NMR (100 MHz,
CDCl3)TM ppm: 24.6, 48.0, 65.9, 97.6, 116.3, 117.3, 118.0, 118.8,
119.8, 124.6, 128.1, 128.6, 129.0, 132.9, 149.7, 159.7, 160.5,
2ꢀ(4ꢀ(pyrrolidinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀd]pyrimidinꢀ2ꢀ
yl)phenol(4n)
°
25 Yellow solid; Melting point: 186ꢀ188 C: IR (KBr): 3317, 3043, 80 163.1, 164.0; HRMS for C27H21N Calculated [M+] m/z 502.9844,
2968, 2870, 1602, 1543, 1448, 1436, 1390, 1259, 1134, 958, 839,
748 cmꢀ1: H1NMR (400 MHz, CDCl3)TM ppm: 1.94 (m, 4H), 3.80
(s, 4H), 4.32 (s, 2H), 6.92ꢀ6.88 (t, J =8.0 Hz, 2H), 7.14ꢀ7.12 (d, J
=8.0 Hz, 2H), 7.29ꢀ7.25 (m, 2H), 8.37ꢀ8.33 (t, J =8.0 Hz, 1H),
30 8.30ꢀ8.28 (d, J =8.0 Hz, 1H), 13.53 (s, 1H); C13NMR (100 MHz,
CDCl3)TM ppm: 24.3, 24.9, 46.0, 49.3, 91.8, 116.1, 117.2, 118.2,
118.5, 119.8, 124.2, 128.0, 128.5, 129.2, 132.5, 149.5, 159.9 ;
HRMS for C27H21N Calculated [M+] m/z 345.1477, Found
345.1478.
Found 502.9856.
Acknowledgements
Balijapalli Umamahesh and Triveni Rajashekhar Mandlimath
thank CSIR for providing Senior Research Fellowship. The DSTꢀ
85 FIST NMR facility at VIT University and VIT management are
duly acknowledged.
Notes and references
35 2ꢀmethoxyꢀ6ꢀ(9ꢀmethoxyꢀ4ꢀ(pyrrolidinꢀ1ꢀyl)ꢀ5Hꢀ
chromeno[2,3ꢀd]pyrimidinꢀ2ꢀyl)phenol(4o)
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Yellow solid; Melting point: 158ꢀ160 C: IR (KBr): 3369, 3051,
2968, 1737, 1548, 1536, 1435, 1396, 1240, 1211, 1138, 983, 777
cmꢀ1: H1NMR (400 MHz, CDCl3)TM ppm: 3.72 (s, 6H), 3.83ꢀ3.79
40 (m, 8H), 4.18 (s, 2H), 6.70ꢀ7.11 (m, 5H), 7.80ꢀ7.78 (d, J =8.0
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45 2ꢀethoxyꢀ6ꢀ(9ꢀethoxyꢀ4ꢀ(pyrrolidinꢀ1ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀ
d]pyrimidinꢀ2ꢀyl)phenol(4p)
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1112, 1060, 929, 773, 675 cmꢀ1: H1NMR (400 MHz, CDCl3)TM
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7.11ꢀ7.10 (d, J =4.0 Hz, 1H), 7.31ꢀ7.27 (t, J =8.0 Hz, 2H),
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77.5, 110.9, 116.9, 119.2, 121.7, 122.5, 124.6, 125.5, 126.7,
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