ZnO Nanoparticle-Catalyzed Multicomponent Reaction for the Synthesis of 1,4-Diaryl Dihydropyridines

Full text of DOI:10.1080/00304948.2017.1320927

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: http://www.tandfonline.com/loi/uopp20
ZnO Nanoparticle-Catalyzed Multicomponent
Reaction for the Synthesis of 1,4-Diaryl
Dihydropyridines
Gagandeep Kour Reen, Monika Ahuja, Ashok Kumar, Rajesh Patidar &
Pratibha Sharma
To cite this article: Gagandeep Kour Reen, Monika Ahuja, Ashok Kumar, Rajesh Patidar &
Pratibha Sharma (2017) ZnO Nanoparticle-Catalyzed Multicomponent Reaction for the Synthesis
of 1,4-Diaryl Dihydropyridines, Organic Preparations and Procedures International, 49:3, 273-286,
DOI: 10.1080/00304948.2017.1320927
To link to this article: http://dx.doi.org/10.1080/00304948.2017.1320927
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Date: 01 June 2017, At: 12:49

Organic Preparations and Procedures International, 49:273–286, 2017
Copyright Ó Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2017.1320927
ZnO Nanoparticle-Catalyzed Multicomponent
Reaction for the Synthesis of 1,4-Diaryl
Dihydropyridines
Gagandeep Kour Reen,1 Monika Ahuja,1 Ashok Kumar,1 Rajesh
Patidar,2 and Pratibha Sharma1
1School of Chemical Sciences, Devi Ahilya University, Khandwa Road, Indore
(M.P.), 452001, India
2Central Salt and Marine Chemicals Research Institute, Gijubhai Badheka Marg,
Bhavnagar, Gujarat, 364002, India
Compounds in the 1,4-dihydropyridine (1,4-DHP) scaffold exhibit a wide range of pharma-
cological activities. The scaffold is the core of vasodilator, antitubercular, antiviral, anti-
tumorous, antidiabetic, analgesic, anti-inflammatory, hypnotic and anticonvulsant agents.1–5
Also, 1,4-DHPs are well known calcium channel blockers,6 cocaine dependent regulators7
and multidrug resistance (MDR) reversing agents.8 Cardiovascular agents like amlodipine,
nicardipine and nifedipine are effective antihypertensive drugs embracing the pyridine
nucleus.9,10 Pyridine based derivatives have broad applications in coordination chemistry,
luminescent sensor materials, non-linear optical materials and also as ligands.11–14 N-aryl
substituted DHPs were found to be prominent sirtuin activators and inhibitors,15 antidyslipi-
demic and antioxidant agents,16 and potential inhibitors of the leishmania parasite.17
In view of the extensive biological profile of 1,4-DHPs, several synthetic methodolo-
gies have been reported in the literature. The classical Hantzsch synthesis is a multicompo-
nent condensation of aldehydes with ethyl acetoacetate and ammonia.18 However, this
method requires long reaction times with low yields of products. Other commonly used
methods include cycloaddition reactions, iminoannulation, ring closing metathesis (RCM),
and coupling reactions of vinyl amides with alkenes or alkynes.19–22 Certain improvements
have been proposed to overcome the shortcomings of existing methods including use of
ionic liquids;23 silica supported acids,24 metal triflates,25 HY-zeolites,26 boronic acids,27
L-proline,28 TMSCl/piperazine,29 InCl3,30 and DBU,31 were used as catalysts. The use of
microwave,32 ultrasound radiation,33 and novel aqueous media34 have also been reported.
Recently, Yan35 and Liu36 reported a multicomponent reaction (MCR) pathway for the
synthesis of N-substituted DHPs (Scheme 1, A and B). The reaction required a long reaction
time (about 4h or longer). In continuation of our own studies37–41 it was thought worthwhile
to develop cost effective, environmentally-benign nanoparticles to catalyze formation of
Received August 27, 2016; in final form January 25, 2017.
Address correspondence to Pratibha Sharma, School of Chemical Sciences, Devi Ahilya
University, Khandwa Road, Indore, 452001, India. E-mail: drpratibhasharma@yahoo.com
Color versions of one or more of the figures in the article can be found online at
www.tandfonline.com/uopp.
273

274
Sharma et al.
polysubstituted pyridines. We now report an efficient, convenient, and neat protocol for
synthesizing 1,4-DHPs using zinc oxide nanoparticles (ZnO NPs) (Scheme 1, C) as the het-
erogenous support catalyst.
It is known that the surface of metal oxides possess both Lewis acid and base sites.42
ZnO is certainly one of the most powerful metal oxides.43–45
Scheme 1 Multicomponent (MCR) synthesis of substituted-1,4-DHPs.
We prepared a number of substituted-1,4-DHP derivatives. This was achieved
through a one pot three-component reaction among aldehydes, b-dicarbonyl compounds
and substituted aromatic amines in a solvent free medium.
Characterization of the synthesized ZnO nanoparticles was performed by XRD,
SEM, TEM, high resolution transmission electron microscopy (HRTEM), EDX, UV-visi-
ble spectroscopy and FTIR spectroscopy. Figure 1 shows the XRD pattern of the ZnO
NPs. An X-ray diffractogram depicted broadened peaks centered at 31.7ꢀ, 34.4ꢀ, 36.2ꢀ,
47.5ꢀ, 56.6ꢀ, 62.9ꢀ, 66.4ꢀ, 67.9ꢀ, 69.1ꢀ, 76.9ꢀ which were attributed to the presence of
(100), (002), (101), (102), (110), (013), (200), (112), (201), (202) indices, respectively.
All the diffraction peaks were indexed to the pure zincite hexagonal phase of ZnO (space
ꢀ
group P63mc), having lattice parameters a D 3.25 and c D 5.21A which are in accord
with the standard JCPDS card no. 96-900-4180. No characterization peaks for any other
phases of ZnO were observed, confirming the phase purity of the synthesized material.
The sharpness of the peaks indicated the crystalline nature of the catalyst. The average
crystallite size has been calculated using the Scherrer equation,
D D Kλ/bCosu

ZnO Nanoparticle-Catalyzed Multicomponent Reaction
275
Figure 1 XRD pattern of Zinc oxide nano particles.
where D is the crystallite size, K is ꢀthe particle shape factor whose value is 0.9, λ is wave-
length of Cu Ka radiations (1.54 A), b is the full width at half maximum (FWHM) of
selected peak and u is the Bragg’s angle. The average crystallite size determined by the
equation was found to be 21.3 nm.
The morphology of the catalyst was further determined by SEM and TEM
analysis (Figures 2 and 3). SEM images of the catalyst resulted in flower like
structures. The crystalline nature of the zinc oxide flowers was authenticated by
Figure 2 SEM images showing growth of flowerlike structure.

276
Sharma et al.
Figure 3 TEM and HRTEM images of ZnO NPs; (A,B) Growth of flowerlike structure (C) HRTEM
showing interplanar spacing of 0.45 nm.
the XRD pattern. The diameter of the flower like structure is found to be in the
range of 1–2 mm.
TEM images represent the growth of the flower like structure (Fig. 3A and 3B). The
HRTEM image displayed clear lattice fringes and reveal the single crystalline nature of
the sample. The measured lattice spacing is about 0.45 nm (Fig. 3C).
Figure 4 EDX spectrum of Zinc oxide nanoparticles.

ZnO Nanoparticle-Catalyzed Multicomponent Reaction
277
Figure 5 UV-visible spectrum of Zinc oxide nanoparticles.
The chemical purity of the samples was tested by EDX studies. The EDX spectra
(Figure 4) ascertained the presence of zinc and oxygen as the only elements.
The UV-vis spectrum of the obtained nano-particles is depicted in Figure 5. Absorp-
tion at 369 nm was observed for the prepared ZnO NPs in 0.01M ethanolic solution. The
band gap energy for this wavelength was 3.36 eV. The observed value is close to the
electronic transition from the valence band to the conduction band (O2p!Zn3d) of ZnO
(band gap of 3.3 eV).46
The presence of a prominent peak at 364.07 cm¡1 in the FTIR spectrum (Figure 6)
showed the presence of Zn-O stretching vibration in the obtained ZnO NPs. The absence
of any other IR peak confirms the structural purity of the prepared sample.
The role of ZnO NPs was explored as the catalytic support under solvent free condi-
tions to synthesize our N-substituted-1,4-dihydropyridine derivatives. Optimization stud-
ies were carried out by reacting together benzaldehyde, ethyl acetoacetate and 4-bromo
aniline in the presence of a variable catalytic amount of ZnO (5 mol% to 20 mol%).
Figure 6 FTIR spectrum of Zinc oxide nanoparticles.

278
Sharma et al.
Table 1
Optimization of Catalyst Concentration for the Model Reactiona
Entry
Catalyst (mol%)
Timeb (min.)
Yieldc (%)
1.
2.
3.
4.
5.
6.
ZnO NPs (5)
ZnO NPs (10)
ZnO NPs (15)
ZnO NPs (20)
ZnO bulk (15)
ZnO bulk (20)
100
90
70
83
92
90
66
65
90
90
180
180
aReaction condition: The mixture of benzaldehyde (1 mmol), ethyl acetoacetate (2 mmol), and
4-bromo aniline (1 mmol) with different concentration of catalyst was heated at 80ꢀC.
bAll the reactions were monitored by TLC.
cIsolated yield.
Initially the reaction was carried out under ambient conditions using 5 mol% of catalyst
loading in solvent free media. It was observed that a very poor yield was obtained even
after the elapse of 6 hrs reaction time; no remarkable change took place on increasing the
reaction time up to 8 hrs. To our surprise, the use of 15 mol% of ZnO at 80ꢀC was found
to afford the corresponding diethyl-1-(4-bromophenyl)-2,6-dimethyl-4-phenyl-1,4-dihy-
dropyridine-3,5- dicarboxylate (Table 1, Entry 3) in 92% yield. The use of ZnO NPs in
comparison to bulk ZnO reduces the reaction time by a factor of two with higher yields
(Table 1, Entries 3 and 5). This may be attributed to the nanosize of the catalyst particles
with enhancement in the surface area.
In order to investigate the effect of solvent media we have carried out the reaction in
different solvents, including water (H2O), methanol, acetonitrile (ACN) and dimethyl
Figure 7 Graphical representation of solvent effect.

ZnO Nanoparticle-Catalyzed Multicomponent Reaction
279
formamide (DMF). It was observed that this three-component one pot reaction resulted in
the best outcome under neat reaction conditions (Figure 7).
With the optimized reaction conditions for the model system in hand, the scope and
limitations of the protocol were explored for reactions of structurally diverse substrates
(Table 2). The reaction can tolerate a variety of substituted aldehydes and anilines with
both electron-withdrawing and electron-donating groups. Steric hindrance exerted an
impact on the reaction time and yields. Among all the examined substituted anilines, para
Table 2
Synthesis of Substituted 1,4-dihydropyridines Using Zinc Oxide Nanoparticlesa,b
aReaction conditions: The mixture of aldehyde (1 mmol), ethyl acetoacetate (2 mmol), and ani-
line (1 mmol) with 15 mol% catalyst was heated at 80ꢀC.
bIsolated yield.

280
Sharma et al.
substituted compounds gave better yields in comparison to the meta substituted ones
(Table 2, Entries 4c-4f).
A plausible mechanistic pathway for the formation of final product 4 is depicted in
Scheme 2. The reaction may proceed through the formation of A by Knoevenagel conden-
sation between 1 and 2, which further undergoes Michael addition with enamine (B)
(formed by reacting together 1 and 3). In this mechanism the Lewis acid sites of the cata-
lyst (Zn2C) coordinate to the oxygen of carbonyl groups and Lewis basic sites (O2¡) help
Scheme 2 A plausible mechanistic pathway to the synthesis of 1,4-dihydropyridine (1,4-DHP).
in deprotonation of active methylene compounds. The Michael adduct (C) thus formed
undergoes dehydration and affords the final 1,4-DHP 4.
Recyclability and reusability of ZnO NPs were examined. After completion of the
reaction, the catalyst was filtered, washed with distilled water and methanol, dried and
activated at 150ꢀC for 4 h, and reused for subsequent experiments (up to four cycles)

ZnO Nanoparticle-Catalyzed Multicomponent Reaction
281
Table 3
Recyclability of the Zinc Oxide Nanocatalyst for the Synthesis of Diethyl-1-(4-bromo-
phenyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5- dicarboxylate 4b
Entry
Cycle
Yielda (%)
1.
2.
3.
4.
Cycle 1
Cycle 2
Cycle 3
Cycle 4
92
89
87
84
aIsolated Yield.
under similar reaction conditions. It was noticed that there was only a minor variation in
the yields of the product in these experiments (Table 3).
In conclusion, we have developed a simple, efficient and environmentally-benign
MCR methodology. ZnO NPs have been used as the heterogenous catalyst for the synthe-
sis of desired 1,4-diaryl dihydropyridines by reacting together aldehydes, b-dicarbonyl
compounds and a number of substituted anilines. This one pot synthesis of 1,4-DHPs
offer easy recovery and reusability of the catalyst. Furthermore, neat conditions, short
reaction time, high yields and easy work up are among the noteworthy advantages.
Experimental Section
All chemicals were purchased from Sigma Aldrich and Merck India, and used without
further purification. The reactions were performed in an aerobic atmosphere without any
specific precautions. UV-visible spectrum was recorded on Schimadzu UV-visible spec-
trophotometer in a wavelength range of 300–550 nm. Fourier Transform Infra Red (FT-
IR) spectra were recorded as ATR spectra and KBr pellets within the range of 4000–
1
350 cm¡1 using Frontier Perkin-Elmer FTIR SP 10 STD. The H and 13C NMR spectra
of the synthesized compounds were recorded at 400 MHz using Bruker Avance II 400
NMR spectrometer in chloroform (CDCl3) solvent, and the chemical shifts were
expressed in parts per million. Mass analysis was performed on quadrupole-time-of-flight
(Q-TOF) mass spectrometer (MICROMASS) using electrospray ionization (ESI) in posi-
tive mode. The XRD measurements were carried out on Bruker D8 Advance X-ray dif-
fractometer using Cu K-alpha radiations of 0.154 nm. Transmission Electron
Microscopic (TEM) images were recorded using Jeol (Jem-2100) electron microscope
operated at an acceleration voltage of 200 kV. Scanning Electron Microscopic (SEM)
images and their corresponding Electron Dispersive X-ray analysis (EDX) data were
recorded by Jeol microscope (JSM7100F). Elemental analyses were performed on
Thermo Scientific (Flash 2000) CHN Elemental Analyzer. Thin-layer chromatography
(TLC) was performed using precoated aluminium sheets with silica gel 60 F254.
Synthesis of Catalyst
Catalyst synthesis was achieved by the hydrothermal chemical precipitation method with
slight modifications.47 A 25 ml aqueous solution of zinc acetate di-hydrate (0.5 M) was
prepared at room temperature under constant stirring for 15 min. In another round bot-
tomed flask, a homogenous solution was prepared by dissolving 1.25 M of sodium
hydroxide in 25 ml of deionized (DI) water using a magnetic stirrer at room temperature

282
Sharma et al.
for 15 min. Afterwards the zinc acetate solution was added dropwise to the sodium
hydroxide solution under constant and vigorous stirring for approximately 10 min. The
solution was left under continuous stirring at room temperature for two hours; this yielded
Zn(OH)2 in the form of a white precipitate. The precipitate was filtered and washed with
DI water and ethanol. The precipitate was dried at about 80ꢀC in air followed by manual
grinding to a fine powder. Finally, the product was calcined in a muffle furnace at 300ꢀC
for 12 h. The yield obtained was 1.5g.
General Procedure for the Synthesis of Compounds 4a-j: Diethyl 2,6-dimethyl-1,
4-diphenyl-1,4-dihydropyridine-3,5-dicarboxylate (4a)
In a 50 ml round bottomed flask ethyl acetoacetate (0.25 ml, 2 mmol) 1a, benzal-
dehyde (0.1 ml, 1 mmol) 2a and a catalytic amount (15 mol%) of ZnO NPs were
taken, followed by the addition of aniline (0.09 ml, 1mmol) 3a at room tempera-
ture with stirring and heating at 80ꢀC. The reaction progress was monitored by
TLC (on aluminium sheets precoated with silica) using n-hexane/ethyl acetate
(4:1) as the eluting system. After the completion of the reaction the mixture was
cooled to room temperature and dissolved in 5 ml of methanol. The catalyst was
separated out by filtration and the solvent was removed by rotary evaporator. Fur-
ther purification of the product was achieved by column chromatography over sil-
ica gel using n-hexane/EtOAc (8:2, v/v) as the eluting system, yielding the pure
product 4a. Reddish brown semi solid; IR (ῡ, cm¡1) 3052, 2951, 2853, 1710,
1
1589, 1493, 1437, 1279, 1211, 1075, 750, 692; H NMR (400 MHz, CDCl3)d: 1.28
(t, J D 7.2 Hz, 6H), 1.81 (s, 6H), 4.18 (q, JD7.2 Hz, 4H), 4.92 (s, 1H), 7.31–7.22
(m, 5H), 7.48–7.36 (m, 5H); 13C NMR (100 MHz, CDCl3)d: 13.7, 14.5, 44.2, 59.8,
102.1, 115.8, 120.4, 126.3, 128.8, 129.1, 129.9, 142.3, 144.8, 155.2, 167.4; ESI
MS, m/z [MCH]C 406.120.
Anal. Calcd. for C25H27NO4: C, 74.05; H, 6.71; N, 3.45. Found C, 73.93; H, 6.62; N:
3.51.
Diethyl
1-(4-bromophenyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicar-
boxylate (4b)
Yellowish brown semi solid; IR (ῡ, cm¡1): 3060, 2962, 2856, 1712, 1587, 1488, 1452,
1267, 1202, 1069, 823, 758, 659; 1H NMR (400 MHz, CDCl3): d 1.27 (t,
JD7.7 Hz, 6H), 2.06 (s, 6H) 4.21 (q, JD7.7 Hz, 4H) 5.27 (s, 1H), 7.18 (d, JD8.2 Hz, 2H),
7.34–7.23 (m, 5H), 7.49 (d, JD8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 13.92, 18.4,
42.6, 59.8, 106.0, 116.4, 121.3, 126.1, 128.6, 132.5, 140.7, 146.1, 156.5, 167.7; ESI MS
m/z [MCH]C 485.233.
Anal. Calcd. for C25H26BrNO4: C, 61.99; H, 5.41; N, 2.89. Found C, 61.89; H, 5.32;
N, 3.02.
Diethyl
1-(4-chlorophenyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicar-
boxylate (4c)
Reddish brown oil; IR (ῡ, cm¡1) 3073, 2955, 2849, 1708, 1592, 1484, 1440, 1275, 1210,
1076, 749, 698; 1H NMR (400 MHz, CDCl3): d 1.29 (t, JD7.2 Hz, 6H), 1.82 (s, 6H), 4.19
(q, JD7.2 Hz, 4H), 5.05 (s, 1H), 7.18 (d, JD8.2 Hz, 2H), 7.38–7.24 (m, 5H), 7.58 (d,
JD8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 13.6, 14.2, 42.8, 59.5, 103.4, 118.4,
124.2, 125.1, 128.5, 129.2, 129.9, 140.3, 143.9, 154.2, 165.2; ESI MS m/z [MCH]C
440.156.

ZnO Nanoparticle-Catalyzed Multicomponent Reaction
283
Anal. Calcd. for C25H26ClNO4: C, 68.25; H, 5.96; N, 3.18. Found C, 68.14; H, 5.82;
N, 3.06.
Diethyl 2,6-dimethyl-4-phenyl-1-p-tolyl-1,4-dihydropyridine-3,5-dicarboxylate (4d)
Dark brown semi solid; IR (ῡ, cm¡1) 3048, 2950, 2847, 1709, 1586, 1498, 1443, 1336,
1278, 1209, 1079, 729, 704; 1H NMR (400 MHz, CDCl3): d 1.27 (t, JD7.6 Hz, 6H), 1.81 (s,
6H), 2.36 (s, 3H), 4.17 (q, JD7.6 Hz, 4H), 5.10 (s, 1H), 6.92 (d, JD8.4 Hz, 2H), 7.01 (d,
JD8.4 Hz, 2H), 7.32–7.20 (m, 5H); 13C NMR (100 MHz, CDCl3): d 13.9, 14.5, 24.2, 61.2,
106.2, 116.2, 126.2, 128.1, 128.8, 129.0, 130.0, 140.8, 146.7, 156.6, 167.9; ESI MS m/z
[MCH]C 419.338.
Anal. Calcd. for C26H29NO4: C, 74.44; H, 6.97; N, 3.34. Found C, 74.31; H, 6.82; N,
3.48.
Diethyl
1-(3-chlorophenyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicar-
boxylate (4e)
Reddish brown oil; IR (ῡ, cm¡1) 3069, 2953, 2847, 1710, 1590, 1481, 1441, 1276, 1208,
1074, 746, 696; 1H NMR (400 MHz, CDCl3): d 1.26 (t, JD7.1 Hz, 6H), 1.79 (s, 6H), 4.16
(q, JD7.1 Hz, 4H), 5.09 (s, 1H), 7.20–7.06 (m, 4H), 7.40–7.29 (m, 5H); 13C NMR
(100 MHz, CDCl3): d 13.4, 13.9, 44.2, 61.1, 100.3, 101.9, 105.5, 109.4, 125.9, 128.6,
129.2, 131.4, 142.9, 153.8, 162.3, 165.8; ESI MS m/z [MCH]C 440.156.
Anal. Calcd. for C25H26ClNO4: C, 68.25; H, 5.96; N, 3.18. Found C, 68.13; H, 5.82;
N, 3.28.
Diethyl 2,6-dimethyl-4-phenyl-1-m-tolyl-1,4-dihydropyridine-3,5-dicarboxylate (4f)
Reddish brown viscous oil; IR (ῡ, cm¡1) 3053, 2954, 2847, 1707, 1588, 1497, 1439, 1337,
1277, 1207, 1074, 732, 706; 1H NMR (400 MHz, CDCl3): d 1.24(t, JD7.2 Hz, 6H), 1.79(s,
6H), 2.38 (s, 3H), 4.15 (q, JD7.2 Hz, 4H), 4.99 (s, 1H), 6.89–6.80 (m, 4H), 7.30–7.19 (m,
5H); 13C NMR (100 MHz, CDCl3): d 13.6, 14.1, 23.7, 44.2, 61.5, 102.5, 116.3, 120.4,
125.9, 128.4, 129.1, 138.9, 141.5, 142.9, 154.6, 167.2; ESI MS m/z [MCH]C 420.214.
Anal. Calcd. for C26H29NO4: C, 74.44; H, 6.97; N, 3.34. Found C, 74.34; H, 6.85; N,
3.26.
Diethyl 1-(4-methoxyphenyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5 dicar-
boxylate (4g)36
Dark yellow oil; IR (ῡ, cm¡1) 3389, 3059, 2936, 2845, 1710, 1591, 1491, 1435, 1219, 1062,
832, 740; 1H NMR (400 MHz, CDCl3): d 1.27 (t, JD7.1 Hz, 6H), 1.91 (s, 6H), 3.84 (s, 3H),
4.16 (q, JD7.1 Hz, 4H), 5.12 (s, 1H), 6.89 (d, JD8.6 Hz, 2H), 6.99 (d, JD8.6 Hz, 2H), 7.39–
7.21 (m, 5H); 13C NMR (100 MHz, CCl3): d 13.5, 14.2, 43.6, 55.6, 61.0, 102.9, 116.2, 117.5,
126.1, 128.5, 129.4, 133.6, 144.1, 148.2, 154.9, 167.5; ESI MS m/z [MCH]C 436.211.
Anal. Calcd. for C23H23NO5: C, 71.70; H, 6.71; N, 3.22. Found C, 71.58; H, 6.65; N,
3.39.
Diethyl 4-(4-chlorophenyl)-1-(4-methoxyphenyl-)2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (4h)36
Dark yellow oil; IR (ῡ, cm¡1): 3063, 2947, 2836, 1708, 1598, 1501, 1454, 1254, 1088,
1
760, 697. H NMR (400 MHz, CDCl3): d 1.26 (t, JD7.1 Hz, 6H), 1.69 (s, 6H), 3.87 (s,
3H), 4.14 (q, JD7.1 Hz, 4H), 5.08 (s, 1H), 6.75 (d, JD8.7 Hz, 2H), 6.92 (d, JD8.7 Hz,
2H), 7.52 (d, JD8.8 Hz, 2H), 8.12 (d, JD8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): d

284
Sharma et al.
13.9, 14.4, 42.2, 55.5, 61.2, 104.5, 115.3, 120.5, 128.3, 130.8, 131.4, 133.4, 144.3, 153.2,
158.9, 167.4; ESI MS m/z [MCH]C 470.129.
Anal. Calcd. for C24H24ClNO4: C, 66.45; H, 6.01; N, 2.98. Found C, 66.30; H, 5.96;
N, 3.10.
Dimethyl 4-(4-chlorophenyl)-2,6-dimethyl-1-p-tolyl-1,4-dihydropyridine-3,5-dicar-
boxylate (4i)
Orange red semi solid; IR (ῡ, cm¡1) 3061, 2979, 2946, 2839, 1711, 1594, 1499, 1451,
1339, 1221, 1084, 745, 693; H NMR (400 MHz, CDCl3): d 1.75 (s, 6H), 2.34 (s, 6H),
1
3.70 (s, 3H), 5.12 (s, 1H), 6.99 (d, JD8.4 Hz, 2H), 7.05 (d, JD8.4 Hz, 2H), 7.49 (d,
JD8.8 Hz, 2H), 8.08 (d, JD8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 14.1, 23.8,
41.9, 51.8, 104.2, 117.7, 128.6, 129.7, 130.4, 131.6, 137.6, 141.2, 144.8, 153.5, 167.7;
ESI MS m/z [MCH]C 426.141.
Anal. Calcd. for C24H24ClNO4: C, 67.68; H, 5.68; N, 3.29. Found C, 67.55; H, 5.72;
N, 3.35.
Dimethyl 1-(3-bromophenyl)-4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (4j)
Reddish Brown semi solid; IR (ῡ, cm¡1) 3076, 2956, 2848, 1710, 1589, 1486, 1439, 1272,
1211, 1079, 782, 732, 670; 1H NMR (400 MHz, CDCl3): d 1.78 (s, 6H), 3.72 (s, 6H), 5.18
(s, 1H), 7.16–7.02 (m, 4H), 7.49 (d, JD8.8 Hz, 2H), 8.10 (d, JD8.8 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d 12.6, 42.9, 52.4, 104.4, 115.5, 116.1, 120.9, 124.3, 127.6, 130.2,
131.2, 131.9, 139.8, 143.9, 152.6, 165.9; ESI MS m/z [MCH]C 491.033.
Anal. Calcd. for C23H21BrClNO4: C, 56.29; H, 4.31; N, 2.85. Found C, 56.12; H,
4.23; N, 2.94.
Acknowledgments
The authors are thankful to Sophisticated Analytical Instrumentation Facility (SAIF),
Punjab University, Chandigarh (for spectral study), Central Salt and Marine Chemical
Research Institute (CSMCRI) Bhavnagar (for SEM, TEM and EDX studies), UGC-DAE
Consortium for Scientific Research, DAVV, Indore (for powder XRD). All the authors
have no conflict of interest.
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