Photocatalytic synthesis of 2-amino-4,6-diarylpyrimidines using nanoTiO2

Article abstract of DOI:10.1016/j.jphotochem.2020.112648

Photocatalytic synthesis of 2-amino-4,6-diarylpyrimidines was carried out by using nano TiO₂. The method follows a green route by avoiding the use of toxic organic solvents and tedious experimental conditions. Compared with conventional methods the present strategy offers excellent yield under UV irradiation for a period of 20 min in ethanolic medium. Only a small quantity of nanocatalyst (1 mol%) is sufficient to achieve the completion of the reaction. The nanocatalyst can be reused up to four reaction cycles without much loss in the activity.

Full text of DOI:10.1016/j.jphotochem.2020.112648

Journal Pre-proof
Photocatalytic synthesis of 2-amino-4,6-diarylpyrimidines using nanoTiO2
E.P. Aparna, Divya Mathew, Ashly Thomas, Rakesh N, K.S. Devaky
PII:
S1010-6030(20)30447-0
DOI:
https://doi.org/10.1016/j.jphotochem.2020.112648
JPC 112648
Reference:
To appear in:
Journal of Photochemistry & Photobiology, A: Chemistry
Received Date:
Revised Date:
Accepted Date:
15 November 2019
16 May 2020
19 May 2020
Please cite this article as: E.P. A, Mathew D, Thomas A, N R, K.S. D, Photocatalytic synthesis
of 2-amino-4,6-diarylpyrimidines using nanoTiO2, Journal of Photochemistry and amp;
Photobiology, A: Chemistry (2020), doi: https://doi.org/10.1016/j.jphotochem.2020.112648
This is a PDF file of an article that has undergone enhancements after acceptance, such as
the addition of a cover page and metadata, and formatting for readability, but it is not yet the
definitive version of record. This version will undergo additional copyediting, typesetting and
review before it is published in its final form, but we are providing this version to give early
visibility of the article. Please note that, during the production process, errors may be
discovered which could affect the content, and all legal disclaimers that apply to the journal
pertain.
© 2020 Published by Elsevier.

Photocatalytic synthesis of 2-amino-4,6-diarylpyrimidines using nanoTiO2
E. P Aparna, Divya Mathew, Ashly Thomas, Rakesh N and K. S. Devaky *
School of Chemical Sciences, Mahatma Gandhi University, Kottayam, Kerala 686560,
India,
*Corresponding author at: School of Chemical Sciences, Mahatma Gandhi University,
Priyadarshini Hills P. O., Kottayam-686 560, Kerala, India.
E-mail address: ksdevakyscs@yahoo.com (K.S. Devaky).
Graphical abstract
Synthesis of 2-amino-4,6-diarylpyrimidines were carried out by using reusable
nanophotocatalyst TiO2 at λmax of 365 nm in ethanolic medium. The method offers excellent
yield in 20 min at room temperature. The method follows a green route by avoiding the use of
toxic reagents and drastic reaction conditions.

Highlights
 2-Amino-4,6-diarylpyrimidines were synthesised photocatalytically using nano TiO2.
 The reaction could be completed with excellent yields within 20min.

Use of strong basic conditions, toxic organic solvents and tedious experimental
conditions could be avoided.
 The method is environmentally friendly by minimising waste production.
 The method follows a green route with low E-factor and high Eco-scale score.
Abstract
Photocatalytic synthesis of 2-amino-4,6-diarylpyrimidines was carried out by using
nano TiO2. The method follows a green route by avoiding the use of toxic organic solvents
and tedious experimental conditions. Compared with conventional methods the present
strategy offers excellent yield under UV irradiation for a period of 20 min in ethanolic
medium. Only a small quantity of nanocatalyst (1 mol%) is sufficient to achieve the
completion of the reaction. The nanocatalyst can be reused up to four reaction cycles without
much loss in the activity.
Keywords: photocatalytic synthesis, photocatalyst, nano TiO2, pyrimidine derivatives, green
synthesis.
1. Introduction
Pyrimidine and its derivatives have engrossed the scientists due to their remarkable
biological and therapeutic applications [1]. Many biologically and pharmacologically active
molecules contain pyrimidine core. The fundamental building blocks of nucleic acids are
pyrimidine bases like thymine, cytosine, and uracil and fused pyrimidine system (purine) in
adenine and guanine [2]. Pyrimidine ring is present in many drugs such as imatinib,
idoxuridine, trifluridine, zalcitabine and zidovudine, etc. [3, 4]. Many pyrimidine derivatives
exhibit antibacterial, antifungal, anti-inflammatory, anticancer, antiviral, anti-allergic,
antipyretic, analgesic, antioxidant activities [3, 5-10]. Due to their broad spectrum of
applications in medical as well as biological fields, synthesis of pyrimidine derivatives
received great attention.

Synthesis of pyrimidine derivatives by traditional thermal methods and advanced
microwave assisted methods is well established [11-16]. But most of these methods make use
harmful organic solvents and tedious reaction conditions. Moreover, organic reactions
without the use of risky experimental conditions have gained much attention for the past few
years [17-21]. Currently the development of such approaches becomes the core part of
scientific research and the use of green protocols in the chemical reactions is very
important[22-25]. One such method includes the application of nanoparticles in synthesis as
catalyst [26]. Use of inorganic metal oxides in organic synthesis is rapidly growing due to
their ability in the enhancement of reaction rates, simplicity of operation and their availability
at low cost and reusability [27-29]. Metal oxides such as SiO2, Al2O3, ZnO etc. are normally
used in organic synthesis [30-32]. The catalytic activity of these kinds of metal oxides in
nanoform in organic synthesis was explored by many researchers in recent times [33-36].
There are several reports on the photocatalysed C-N coupling reactions. Ohtani et al. reported
the photocatalytic coupling of amine with aldehydes to imines in presence of nanoTiO2.
Palmisano and co-workers reported the photocatalytic cyclization of lysine in presence of
nanoTiO2 to pipecolinic acid. The intramolecular cyclization of the diaminodicarboxylic acid
and the hydrazone via C-N coupling in the presence of the photocatalyst nanoTiO2 has also
been reported by Kisch et al. [37-39]. But the investigations of photocatalytic activity of TiO2
nanoparticles in the synthesis of pyrimidine derivatives are rarely reported. The present work
is an attempt to exploit the photocatalytic activity of TiO2 nanoparticles in the synthesis of 2-
amino-4,6-diarylpyrimidines.
We have carried out the synthesis of a series of substituted pyrimidines by both
traditional thermal method as well as microwave assisted method. Then the photocatalytic
effect of TiO2 nanoparticles on the synthesis of pyrimidine derivatives was also explored.
This method offers high yield, short reaction time, reduced cost, easy work-up and mild
reaction procedure under environmentally friendly conditions avoiding toxic waste
production.
2. Experimental
2.1 Chemicals and instruments
All the substrates and reagents used including guanidine hydrochloride, aldehydes and
ketones were purchased from Spectrochem Chemicals Pvt. Ltd. India. All solvents used were
purchased from local suppliers and were purified before use by following the standard

procedures. The Fourier Transform infrared spectra (FT-IR) were recorded on a Perkin-Elmer
1
400 FT-IR spectrophotometer. H NMR and 13C NMR spectra of the samples were taken
using Bruker Avance DPX-300MHz FT-NMR spectrometer. Scanning electron microscopic
(SEM) analyses were performed on a JEOL-JSM-6390A SEM analyzer. The high resolution
mass spectra (HRMS) were recorded HRMS using XEVO G2 Q-TOF (Waters) mass
spectrometer. XRD analysis was conducted on a PANalytic X’PERT-PRO X-ray
spectrometer. Melting points were recorded on MPHT melting point apparatus and are
uncorrected.
2.2 Synthetic procedures
2.2.1. Synthesis of TiO2 nanopaticles
Titanium tetrabutoxide (1mL, 1.00 g/mL) was dissolved in ethanol (25 mL) and the
solution was added to distilled water (250 mL) at 40°C with constant stirring. The pH of the
solution was maintained at 1.5 with the addition of HCl. The obtained transparent colloidal
solution was stirred overnight [40]. The solvent was then rota evaporated. The obtained TiO2
nanopowder was collected, heated at 600 oC for 4 h, characterised by SEM, DLS & XRD and
used for further studies.
2.2.2. Synthesis of 2-amino 4,6-diarylpyrimidines catalysed by nanoTiO2
Initially chalcones were synthesised by reported procedure [41]. Guanidine (1 mmol)
was treated with the chalcone component (1mmol) in presence of TiO2 nanoparticles (1
mol%, 3.33 mg) in ethanol under UV irradiation at λmax 365 nm for 20 min. The catalyst was
then filtered off and the solution was poured into ice cold water (30 ml). The crude solid
product was collected by filtration and recrystallized from ethanol to afford the pure product.
3. Results and discussion
3.1 Synthesis and characterisation of TiO2 nanoparticles
TiO2 nanoparticles were synthesised according to the reported procedure and was
characterised and used as photocatalyst for the synthesis of the pyrimidine derivatives. The
synthesis was carried out by the hydrolysis and condensation of the precursor, titanium
tetrabutoxide [42]. At first titanium tetrabutoxide was dissolved in ethanol and the resulted
ethanolic solution was subsequently added to distilled water. In the aqueous medium
hydrolysis of the precursor took place and subsequent polymerisation resulted in the
formation of a three dimensional metal oxide network Ti(OH)4, which was then condensed on
calcination via the formation of oxo bridges between the Ti atoms and further olation leading

to the formation of TiO2 nanoparticles. The reported reaction mechanism is as shown
below[42, 43].
Ti(O(CH2)3CH3)4+4H2O
Ti(OH)4
2Ti(OH)4+4CH3(CH2)3OH (hydrolysis)
TiO2.xH2O+ (2-x)H2O (condensation)
The morphology of TiO2 nanoparticles was analysed by scanning electron microscopy
(SEM) and the average particle size was determined from dynamic light scattering (DLS)
studies (Figure 1).
Figure 1. SEM and DLS graphs of TiO2 nanocatalyst
From the DLS analysis the average particle size of the TiO2 nanoparticles was found to be
49.9 nm confirming the formation of nanoparticles. The band gap of TiO2 nanoparticle was
determined by UV spectrophotometric studies and was found to be 2.8 eV from the Tauc’s
plot. The X-ray diffraction pattern of the synthesized TiO2 nanoparticles is shown in Figure 1.
The peaks of 2θ values at 25.23, 38.38, 48.46, 54.41, 62.62 and 68.57 indicate (101), (004),
(200), (105), (211), (204) and (116) planes of anatase TiO2. In the spectrum there is only one
small peak at 2θ values of 27.48 (110 plane) indicate the presence of traces of rutile phase
[44, 45].

Figure 2. X-ray diffraction pattern of the synthesized TiO2 nanoparticles
3.2. Synthesis of 2-amino-4,6-diarylpyrimidine 3c catalysed by nanophotocatalyst TiO2
Chalcones 2 were prepared from substituted benzaldehydes and substituted
acetophenones according to the reported procedure [41]. The synthesised chalcone, guanidine
and 1 mol% of nanoTiO2 were stirred in ethanol under UV irradiation having λmax of 365 nm
at room temperature for 20 min to afford 2-amino-4,6-diarylpyrimidine (3) (Scheme 1). After
completion of the reaction, the nanocatalyst was removed by simple centrifugation and the
supernatant liquid containing the product was poured into crushed ice and the product, 2-
amino-4,6-diarylpyrimidine was precipitated out. The precipitated 2-amino-4,6-
diarylpyrimidine was separated in moderate to excellent yield and further purified by
recrystallisation from ethanol. By varying the substituents in chalcone moiety, a series of
pyrimidine derivatives were synthesised.
R2
R1
O
NH
UV, rt,
+
R1
R2
N
N
NH2
3
H2N NH2
stirring, 20 min
2
1
Scheme 1.Synthesis of 2-amino-4,6-diarylpyrimidines catalysed by nanophotocatalyst TiO2

In a typical reaction the 2-amino-4,6-diarylpyrimidine (3c) was synthesised from 3-
(4-methoxyphenyl)-1-phenylprop-2-en-1-one and guanidine in the presence of the
photocatalyst with a yield of 99%. The product was characterised using IR, NMR, HRMS
and single crystal X-ray diffraction techniques.
Characterisation of 4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine (3c): FT-IR: The
FT-IR spectral analysis shows broad absorption bands at 3320 and 3280 cm-1 corresponding
to N-H stretching. The HRMS showed a base peak at 278.1293 indicating the formation of
product (Figure 3).
Figure 3. HRMS of 4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine (3c)
1
NMR: In the H NMR (400 MHz, CDCl3) spectrum a singlet appeared at δ 5.17 ppm
corresponding to the two NH2 protons. The OCH3 protons resonated at δ 3.88 ppm as a
singlet. The C5 proton in the pyrimidine ring appeared as a singlet at δ 7.02 ppm. Peak at
6.99 ppm correspond to the protons ortho to the OCH3 group. The signals corresponding to
the remaining six aromatic protons appeared in the range δ 7.26 – 8.05 ppm confirming the
formation of the product (Figure 4).

Figure 4.1H NMR spectrum of 4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine (3c)
Figure 5.13C NMR spectrum of 4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine (3c)
13
The CNMR (100 MHz, CDCl3) spectrum also supports the structure of the product
from the following peaks at δ 165.99 ppm (C2), 161.69 ppm (C4), 103.58 ppm (C5), 165.65

ppm (C6) of the pyrimidine ring and 55.41 ppm (OCH3). The OCH3 substituted carbon
appeared at δ 163.48 ppm. The ortho- carbon of the OCH3 group resonated at δ 114.12 ppm.
The remaining nine aromatic carbons resonated in the range δ 127.10 – 137.88 ppm (Figure
5). The single crystal XRD data also confirms the structure of product (Figure 6).
Figure 6. ORTEP diagram of single crystal X-ray diffraction structure of 4-(4-
methoxyphenyl)-6-phenylpyrimidin-2-amine (3c)
3.3 Optimisation Studies
The synthesis of pyrimidine derivatives from 3-(4-methoxyphenyl)-1-phenylprop-2-
en-1-one and guanidine in ethanolic medium in presence of TiO2 nanophotocatalyst was
selected as the model reaction to study the catalytic activity of the nanoTiO2.The reaction
conditions were optimised on the basis of reaction time and the amount of nanocatalyst used.
Initially a mixture of equimolar quantities (1mmol) of 3-(4-methoxyphenyl)-1-phenylprop-2-
en-1-one and guanidine hydrochloride were reacted in presence of 1 mol% of TiO2
nanophotocatalyst at λmax of 365 nm. The progress of the reaction was monitored by thin
layer chromatography (TLC). After 20 min the reaction mixture was taken, the product was
isolated and the yield was found to be 99%.
3.3.1 Optimisation of catalyst concentration and time
Varying the amount of nanocatalyst from 0.2 mol% to 2.0 mol%, a series of
experiments was carried out using 3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one and

guanidine in ethanolic medium. The results are summarised in the Table 1. The yield of the
product formed increased with increasing the amount catalyst loading. The yield was 99%
when the amount of catalyst reached 1 mol% for a reaction time of 20 min. There was no
increase in the yield of the product with further increase in catalyst loading. The maximum
dispersion of nanocatalyst will be attained only at a particular concentration [46]. Further
increase in concentration may cause the agglomeration of nanoparticle.
The optimum reaction time for the synthesis was also investigated. The synthesis was
carried out by varying the reaction time from 10 to 30 min. The maximum yield of the
product was observed at 20 min with a catalyst concentration of 1 mol% (Table 1). Further
increase in time has no effect on product yield. A blank reaction was also carried out in the
absence of nanocatalyst TiO2 under the same conditions and no product formation was
observed in such case indicating the role of the nanocatalyst in the reaction. The reaction was
also conducted in the absence of UV light but in the presence of the catalyst nano TiO2. In
this case also no product was formation proving that the cyclisation is taking place in the
presence of UV irradiation.
By this photocatalytic method twenty one 2-amino-4,6-diarylpyrimidines (3a-3u)
were synthesised. All the products were obtained in moderate to excellent yields under mild
green reaction conditions (Table 2). All the products were characterised by IR, NMR and
HRMS analysis.
3.5. Regeneration and reusability
The regeneration and reusability of the catalyst after each step was checked by
separating the catalyst after completing the each reaction cycle by centrifugation. The
collected catalyst was then purified by washing with ethanol and kept at hot air oven for 1h at
100oC. The reusability of the spent nanocatalyst was investigated by carrying out the
synthesis of 2-amino-4,6-diarylpyrimidines under the same catalytic conditions described
above after regenerating the catalyst and compared with the fresh catalyst. The catalyst was
then analysed by SEM and DLS analysis, which confirms the nano size of catalyst up to the
fourth reaction cycle.
The catalyst regenerated could be used for four cycles of synthesis without much loss
in the catalytic activity and after the fourth cycle, reduction in catalytic activity reduced and
the yield of the product was decreased by 15 % (Table 3). After the fourth reaction cycle

massive agglomeration of nanoparticles had taken place which was proved by SEM and DLS
studies.
After the fourth cycle, DLS and SEM analyses of the recycled catalyst were carried
out and were compared with the freshly prepared catalyst (Figures 7 & 8). Formation of
aggregates of catalyst with recycling was supported by the SEM images. Similarly DLS
studies reveal that the catalyst tends to form agglomerates with recycling. This was confirmed
from the increase of average particle size of catalyst to 273.6 nm after the fourth cycle.
These results confirmed the large agglomeration of nanoparticles which was the reason for
decreased catalytic activity.
Figure 7. DLS studies nanocatalysts indicating the size (nm) of TiO2 NPs (a) before reaction
average particle size = 49.9 nm (b) after fourth cycle average particle size = 273.6
nm

Figure 8. SEM images of TiO2 nanocatalyst showing the morphology of NPs (a) before
reaction (b) after fourth cycle
The advantages of the present method includes high yield, ease of purification, shorter
reaction periods, mild reaction conditions, etc. indicating that the method follows a green
synthetic protocol.
A plausible mechanism for the photocatalysed reaction is shown in Figure 9. The UV
light energy promotes the electronic transition in TiO2 from valence band to the conduction
band. The interaction of this electron with guanidine hydrochloride I provides a radical anion
II. This radical anion II is then added to chalcone molecule forming the radical anion III
which undergoes intramolecular cyclisation affording the 2-amino-4,6-diarylpyrimidine
product.
To confirm the formation of radical intermediates, the reaction was performed in the
presence of a radical scavenger 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO). No product
formation was observed in presence of the radical scavenger proving the formation of radical
intermediates.

Figure 9. Plausible mechanism for the synthesis of 2-amino-4,6-diarylpyrimidine by
nanophotocatalyst TiO2
The E-factor and Eco-scale score calculations of the present study were carried out,
these are the parameters which determine the greenness of an organic synthesis [47]. In order
to calculate these parameters, synthesis of pyrimidine derivatives from 3-(4-methoxyphenyl)-
1-phenylprop-2-en-1-one and guanidine hydrochloride was selected as model reaction. The
E-factor of the present study was observed as 0.012 and Eco-scale score was 83.5 [47-48].
The lower E-factor value (i.e, ~ 0) indicates less the waste generation and more green the
procedure. Similarly high Eco-scale score (i.e, ~ 100) indicates the ideal behaviour of the
reaction [48]. The advantages of the present method includes high yield, ease of purification,
short reaction time, mild reaction conditions, low E-factor, high Eco-scale score etc. These
factors indicate that the present method follows a green synthetic protocol.
3.4. Advantages of the present method: a comparison with conventional and microwave
assisted method
The present photocatalytic synthesis method was compared with conventional and
microwave assisted synthesis on the basis of reaction conditions, time taken for the reaction
and product yield. The conventional and microwave assisted method completed with the aid

of strong basic medium, which could be avoided in nanocatalysed synthesis. Similarly
conventional and microwave assisted synthesis used drastic reaction conditions such as high
temperature. But in nanocatalysed synthesis only room temperature was sufficient for the
completion of the reaction. The time required for conventional synthesis was 3 h which
could be reduced to 20 min in microwave assisted method. But with this time under mild
reaction conditions an increased yield was observed in nanocatalysed synthesis. The E-factor
and Eco-scale score for conventional synthesis were calculated to be 0.23 and 66. Similarly
for microwave assisted syntheses the values were estimated to be 0.17 and 61. The results
prove the more greenness of present photocatalysed synthesis over conventional and
microwave assisted synthesis.
4. Conclusion
2-Amino-4,6-diarylpyrimidines could be synthesised in presence of the photocatalyst
nanoTiO2 in ethanolic medium. The nanocatalysed synthesis avoids the use of tedious
reaction conditions and high yields of the product could be achieved. Other major advantages
of the present method include short reaction time, low cost and easy work-up. The method is
also environment friendly by avoiding the harmful reaction conditions, toxic waste
production, etc. The catalyst could be recycled and reused.
Acknowledgments
The authors gratefully acknowledge the financial support received from University Grants
Commission, India, by awarding junior and senior research fellowships to E.P. Aparna.
References
[1] T.P. Selvam, C.R. James, P.V. Dniandev, S.K. Valzita, A mini review of pyrimidine and
fused pyrimidine marketed drugs, Res. Pharm., 2 (2012).
[2] I.M. Lagoja, Pyrimidine as constituent of natural biologically active compounds, Chem.
Biodivers., 2 (2005) 1-50.
[3] R. Capdeville, E. Buchdunger, J. Zimmermann, A. Matter, Glivec (STI571, imatinib), a
rationally developed, targeted anticancer drug, Nat. Rev. Drug Discover,, 1 (2002) 493-502.
[4] K.N. Mohana, B.N.P. Kumar, L. Mallesha, Synthesis and biological activity of some
pyrimidine derivatives, Drug Invent. today, 5 (2013) 216-222.
[5] B. Grahner, S. Winiwarter, W. Lanzner, C.E. Mueller, Synthesis and structure-activity
relationships of deazaxanthines: analogs of potent A1-and A2-adenosine receptor antagonists,
J. Med.Chem., 37 (1994) 1526-1534.

[6] G.B. Evans, R.H. Furneaux, G.J. Gainsford, J.C. Hanson, G.A. Kicska, A.A. Sauve, V.L.
Schramm, P.C. Tyler, 8-Aza-immucillins as transition-state analogue inhibitors of purine
nucleoside phosphorylase and nucleoside hydrolases, J. Med.Chem., 46 (2003) 155-160.
[7] Y. Sato, Y. Shimoji, H. Fujita, H. Nishino, H. Mizuno, S. Kobayashi, S. Kumakura,
Studies on cardiovascular agents. 6. Synthesis and coronary vasodilating and antihypertensive
activities of 1, 2, 4-triazolo [1, 5-a] pyrimidines fused to heterocyclic systems, J. Med.Chem.,
23 (1980) 927-937.
[8] A. Abdelal, M. Gineinah, S. Kheira, Synthesis and antibacterial activity of 2-(4-(4-
fluorophenyl) piperazin-1-yl) 4-substituted-4, 7-dihydro-7-oxo-1, 2, 4-triazolo (1, 5-a)
pyrimidine-6-carboxylic acids and its analogs, Med. Chem. Res., 9 (1999) 277-290.
[9] S.M. Sondhi, S. Jain, A.D. Dwivedi, R. Shukla, R. Raghubir, Synthesis of condensed
pyrimidines and their evaluation for anti-inflammatory and analgesic activities, Bioorg. Med.
Chem, 22 (2005) 6158-6166.
[10] M. Amir, S. Javed, H. Kumar, Pyrimidine as antiinflammatory agent: a review, Ind. J.
Pharm. Sci., 69 (2007) 337-343.
[11] A. Nefzi, J.M. Ostresh, R.A. Houghten, The current status of heterocyclic combinatorial
libraries, Chem. Rev., 97 (1997) 449-472.
[12] V. Krchňák, Solid-Phase Synthesis of Nitrogenous Heterocycles, Springer2017.
[13] P.H. Toy, Y. Lam, Solid-phase organic synthesis: concepts, strategies, and applications,
John Wiley & Sons2012.
[14] A. Kumar, S. Sinha, P.M. Chauhan, Syntheses of novel antimycobacterial combinatorial
libraries of structurally diverse substituted pyrimidines by three-component solid-phase
reactions, Bioorg. Med. Chem. Lett., 12 (2002) 667-669.
[15] R.S. Varma, Solvent-free organic syntheses. using supported reagents and microwave
irradiation, Green chem., 1 (1999) 43-55.
[16] M. Kidwai, B. Dave, K. Bhushan, P. Misra, R. Saxena, R. Gupta, R. Gulati, M. Singh,
Deacylation of cephalosporins by lipase catalysis and microwave assisted transformation on a
solid support, Biocatal. Biotransform., 20 (2002) 377-379.
[17] M.B. Gawande, R.K. Pandey, R.V. Jayaram, Role of mixed metal oxides in catalysis
science—versatile applications in organic synthesis, Catal. Sci. Technol., 2 (2012) 1113-
1125.
[18] M.B. Gawande, S.N. Shelke, R. Zboril, R.S. Varma, Microwave-assisted chemistry:
synthetic applications for rapid assembly of nanomaterials and organics, Acc. Chem. Res., 47
(2014) 1338-1348.
[19] G.M. Ziarani, S. Faramarzi, N. Lashgari, A. Badiei, A simple and clean method for
multicomponent synthesis of spiro [indole-tetrahydropyrano (2, 3-d) pyrimidine] derivatives
using SBA-Pr-SO 3 H as catalyst under solvent-free conditions, J. Iran. Chem. Soc., 11
(2014) 701-709.
[20] M. A Bodaghifard, Z. Faraki, A. R Karimi, Mild synthesis of mono-, bis-and tris 1, 2-
dihydrobenzo [4, 5] imidazo [1, 2-a] pyrimidine derivatives using alkyl disulfamic acid
functionalized magnetic nanoparticles, Curr. Org. Chem., 20 (2016) 1648-1654.
[21] M.A. Bodaghifard, M. Hamidinasab, N. Ahadi, Recent Advances in the Preparation and
Application of Organic–inorganic Hybrid Magnetic Nanocatalysts on Multicomponent
Reactions, Curr. Org. Chem., 22 (2018) 234-267.
[22] A. Nacci, N. Cioffi, Nano-Catalysts and Nano-Technologies for Green Organic
Synthesis, Molecular Diversity Preservation International, 2011.
[23] M. Gawande, Sustainable nanocatalysts for organic synthetic transformations, Org.
Chem. Curr. Res, 3 (2014) 1000-1137.
[24] G.M. Ziarani, N. Lashgari, S. Faramarzi, A. Badiei, Efficient Synthesis of
Spironaphthopyrano [2, 3-d] pyrimidine-5, 3’-indolines under Solvent-free Conditions

Catalyzed by SBA-Pr-SO 3 H as a Nanoporous Acid Catalyst, Acta Chim. Slov., 61 (2014)
574-579.
[25] T. Raj, H. Sharma, A. Singh, T. Aree, N. Kaur, N. Singh, D.O. Jang, “Solvent-Less”
Mechanochemical Approach to the Synthesis of Pyrimidine Derivatives, ACS Sustain. Chem.
Eng., 5 (2017) 1468-1475.
[26] L.L. Chng, N. Erathodiyil, J.Y. Ying, Nanostructured catalysts for organic
transformations, Acc. Chem. Res., 46 (2013) 1825-1837.
[27] A. Yamaguchi, F. Uejo, T. Yoda, T. Uchida, Y. Tanamura, T. Yamashita, N. Teramae,
Self-assembly of a silica–surfactant nanocomposite in a porous alumina membrane, Nat.
Mater., 3 (2004) 337-341.
[28] P. Claus, A. Brückner, C. Mohr, H. Hofmeister, Supported gold nanoparticles from
quantum dot to mesoscopic size scale: effect of electronic and structural properties on
catalytic hydrogenation of conjugated functional groups, J.Am. Chem. Soc., 122 (2000)
11430-11439.
[29] K. Hemalatha, G. Madhumitha, A. Kajbafvala, N. Anupama, R. Sompalle, S.M. Roopan,
Function of nanocatalyst in chemistry of organic compounds revolution: an overview, J.
Nanomater., 2013 (2013) 1-23.
[30] M. Mihara, Y. Ishino, S. Minakata, M. Komatsu, Solvent-free synthesis of cyclic ethers
from dihalo compounds in the presence of alumina, Synlett., 2002 (2002) 1526-1528.
[31] L. Ghule, A. Patil, K. Sapnar, S. Dhole, K. Garadkar, Photocatalytic degradation of
methyl orange using ZnO nanorods, Toxicol. Environ. Chem., 93 (2011) 623-634.
[32] S. Abdolmohammadi, ZnO nanoparticles-catalyzed cyclocondensation reaction of
arylmethylidenepyruvic acids with 6-aminouracils, Comb. Chem. High T Scr., 16 (2013) 32-
36.
[33] S. Abdolmohammadi, M. Afsharpour, Facile one-pot synthesis of pyrido [2, 3-d]
pyrimidine derivatives over ZrO2 nanoparticles catalyst, Chin.Chem. Lett., 23 (2012) 257-
260.
[34] S. Abdolmohammadi, S. Balalaie, A clean procedure for synthesis of pyrido [d]
pyrimidine derivatives under solvent-free conditions catalyzed by ZrO2 nanoparticles, Comb.
Chem. High T Scr., 15 (2012) 395-399.
[35] J. Deng, L.-P. Mo, F.-Y. Zhao, Z.-H. Zhang, S.-X. Liu, One-pot, three-component
synthesis of a library of spirooxindole-pyrimidines catalyzed by magnetic nanoparticle
supported dodecyl benzenesulfonic acid in aqueous media, ACS. Comb. Sci., 14 (2012) 335-
341.
[36] J. Deng, L.-P. Mo, F.-Y. Zhao, L.-L. Hou, L. Yang, Z.-H. Zhang, Sulfonic acid
supported on hydroxyapatite-encapsulated-γ-Fe 2 O 3 nanocrystallites as a magnetically
separable catalyst for one-pot reductive amination of carbonyl compounds, Green Chem., 13
(2011) 2576-2584.
[37] H. Kisch, Semiconductor photocatalysis for organic synthesis, Adv. Photochem., (2001)
93-143.
[38] G. Palmisano, V. Augugliaro, M. Pagliaro, L. Palmisano, Photocatalysis: a promising
route for 21st century organic chemistry, Chem. Comm., (2007) 3425-3437.
[39] D. Friedmann, A. Hakki, H. Kim, W. Choi, D. Bahnemann, Heterogeneous
photocatalytic organic synthesis: state-of-the-art and future perspectives, Green Chem., 18
(2016) 5391-5411.
[40] S.H. Kim, S.-Y. Kwak, T. Suzuki, Photocatalytic degradation of flexible PVC/TiO2
nanohybrid as an eco-friendly alternative to the current waste landfill and dioxin-emitting
incineration of post-use PVC, Polymer, 47 (2006) 3005-3016.
[41] A.H. Shntaif, Green synthesis of chalcones under microwave irradiation, Int.
J.Chem.Tech. Res., 9 (2016) 36-39.

[42] S. Mahshid, M. Askari, M.S. Ghamsari, Synthesis of TiO2 nanoparticles by hydrolysis
and peptization of titanium isopropoxide solution, J. Mater. Process. Technol., 189 (2007)
296-300.
[43] C. Sanchez, J. Livage, M. Henry, F. Babonneau, Chemical modification of alkoxide
precursors, J. Non-Cryst. Solids, 100 (1988) 65-76.
[44] K. Thamaphat, P. Limsuwan, B. Ngotawornchai, Phase characterization of TiO2 powder
by XRD and TEM, J. Nat. Sci., 42 (2008) 357-361.
[45] H. Ijadpanah-Saravy, M. Safari, A. Khodadadi-Darban, A. Rezaei, Synthesis of titanium dioxide
nanoparticles for photocatalytic degradation of cyanide in wastewater, Anal. Lett., 47 (2014) 1772-
1782.
[46] V. Subbaramaiah, V.C. Srivastava, I.D. Mall, Optimization of reaction parameters and
kinetic modeling of catalytic wet peroxidation of picoline by Cu/SBA-15, Ind. Eng. Chem.
Res., 52 (2013) 9021-9029.
[47] R.A. Sheldon, E factors, green chemistry and catalysis: an odyssey, Chem.Comm.,
(2008) 3352-3365.
[48] M. Tobiszewski, M. Marc, A. Gałuszka, J. Namiesnik, Green chemistry metrics with
special reference to green analytical chemistry, Molecules, 20 (2015) 10928-10946.

Table 1.Optimisation studies of nanophotocatalysed synthesis of 3c
Yield (%)
Entry
Mol % of TiO2nanocatalyst
10 min
23
20 min
40
25 min
42
30 min
42
1
2
3
4
5
6
7
0.2
0.4
0.8
1.0
1.2
1.5
2.0
38
48
50
50
67
75
78
78
81
99
99
99
81
99
99
99
81
99
99
99
81
98
99
99

Table 2. Yields of 2-amino-4,6-diarylpyrimidines (3a-3u) synthesis catalysed by
photocatalyst TiO2 for 20 min.
Yield (%)
Photocatalysed
Compound
R1
R2
synthesis
(20min)
H
H
H
H
62
74
99
3a
3b
3c
CH3
OCH3
NO2
H
H
81
72
62
83
71
79
3d
3e
3f
Cl
NMe2
H
H
CN
H
3g
3h
3i
Cl
Cl
CH3
OCH3
NO2
Cl
84
3j
Cl
Cl
83
76
36
72
83
75
3k
3l
Cl
NMe2
Cl
3m
3n
3o
3p
Cl
CN
H
NO2
NO2
CH3
OCH3
NO2
NO2
NO2
NO2
NO2
NO2
85
71
82
32
79
3q
3r
3s
3t
Cl
NMe2
CN
3u

Table 3. Catalytic recyclability check up to fourth cycle
No of cycles
Yield (%)
1
2
3
4
5
99
98
92
91
84