Synthesis and crystal structures of 2-methyl-4-aryl-5-oxo-5H-indeno [1,2-b] pyridine carboxylate derivatives
- Ramesh Pandian†1, 2,
- Edayadulla Naushad†3,
- Vinodhkumar Vijayakumar4,
- Günther H Peters5 and
- Ponnuswamy Mondikalipudur Nanjappagounder1Email author
© Pandian et al.; licensee Chemistry Central Ltd. 2014
Received: 20 February 2014
Accepted: 9 May 2014
Published: 29 May 2014
Hantzsch 1,4-dihydropyridines (Hantzsch1,4-DHP) have been extensively utilized as the analogs of nicotinamide adenine dinucleotide (NADH) coenzyme to study the mechanism and various redox processes. During the redox processes 1,4-DHP systems undergo transformation into the corresponding pyridine derivatives through oxidation. Consequently, the interest in this aromatization reaction, investigation of a wide range of 1, 4-DHPs continues to attract the attention of researchers. Herein, we report the preparation of pyridine derivatives and the crystal structures determined by X-ray crystallographic methods.
The crystal structures and conformational studies of two organic compounds, namely ethyl 2-methyl-4-phenyl-5-oxo-5H-indeno [1,2-b] pyridine-3-carboxylate (I) and ethyl 2-methyl-4-(4 chlorophenyl)-5-oxo-5H-indeno [1,2-b] pyridine-3-carboxylate (II) are reported. The terminal ethyl group of the compound I is disordered over two positions with the refined occupancies of 0.645 & 0.355 and C8 one dimensional zig-zag chain running along 101 direction through C-H…O type of intermolecular interactions. In the compound II, C-H…O interactions connect the molecules to form an R22 (16) dimer running along 011 direction.
The crystal structures ethyl 2-methyl-4-phenyl-5-oxo-5H-indeno [1,2-b] pyridine-3-carboxylate and ethyl 2-methyl-4-(4 chlorophenyl)-5-oxo-5H-indeno [1,2-b] pyridine-3-carboxylate have been investigated in detail. The terminal ethyl group of compound I is disordered. In compound II, the substitution of Cl atom in the phenyl ring alters the configuration of carboxylate group with respect to the pyridine indane ring.
Hantzsch 1,4-dihydropyridines (Hantzsch1,4-DHP) have been extensively utilized as the analogs of nicotinamide adenine dinucleotide (NADH) coenzyme to study the mechanism and the synthetic potential of various redox processes [1, 2]. Hantzsch 1,4-DHP based drugs such as nifedipine and niguldipine are widely used as calcium channel blockers for the treatment of cardiovascular disorders including angina, hypertension and cardiac arrhythmias . During the redox processes and in the course of drug metabolism , 1,4-DHP systems are oxidatively transformed into the corresponding pyridine derivatives. Consequently, this aromatization reaction continues to attract the attention of researchers to establish a general protocol applicable to a wide range of 1,4-dihydropyridines. A number of methods and reagents have been reported recently in the literature for this purpose [5–14].
Some of these methods suffer from disadvantages such as the use of strong or toxic oxidants, the requirement of severe conditions or need excess of the oxidants. Other drawbacks are the long reaction times, production of by-products, the lower yields of products and/or the requirement of tedious work-up procedures.
N-Bromosuccinimide (NBS) is a versatile reagent for the oxidation of primary and secondary alcohols, α-hydroxycarboxylic acids , α-hydroxycarboxylic esters , hydrazines and hydrazones . In addition, NBS is preferred for allylic bromination. While hydroxy acids like malic acid, tartaric acid, citric acid etc. are converted to aldehydes and ketones, polyhydric alcohols (glycol, glycerol and hexitols) are quantitatively decomposed to carbon dioxide and water  with NBS. NBS also promotes reactions of sterically hindered cresols via p-benzoquinone methide .
Preparation of 4a-b
To an alcoholic solution (50 mL) of indane-1,3-dione 2 (0.01 mol), appropriate aromatic aldehydes 1a-b (0.01 mol), ethyl acetoacetate 3 (0.01 mol), ammonium acetate (0.02 mol) and a drop of piperidine were added and the mixture was refluxed for 1 hr. The reaction mixture was concentrated to half of its original volume and allowed to cool in an ice-chest. The solid 4a-b thus separated was filtered, washed with ice cold aqueous ethanol and crystallized from petroleum ether (60–80°C)-chloroform (1: 1) (Scheme 1).
Preparation of 5a-b
Results and Discussion
The crystal data, experimental conditions and structure refinement parameters for the compounds (I) and (II)
Crystal system, space group
Unit cell dimensions
a = 7.5078(5) Å
a = 9.7750(8) Å; α = 113.199(2)˚
b = 21.0935(15) Å
b = 9.8262(4) Å; β = 102.572(3)˚
c = 11.5058(3) Å
c = 10.8687(5) Å; γ = 99.791(3)˚
β = 104.876(2)˚
Z, Calculated density
4, 1.295 g/cm3
2, 1.398 g/cm3
0.23 × 0.20 × 0.19 mm3
0.22 × 0.18 × 0.17 mm3
Theta range for data collection
1.93 to 30.48˚
2.15 to 30.99˚
−10 ≤ h ≤ 10, −30 ≤ k ≤ 30, −15 ≤ l ≤ 16
−13 ≤ h ≤ 14, −14 ≤ k ≤ 14, −15 ≤ l ≤ 15
[R (int) = 0.032]
[R (int) = 0.0261]
Full-matrix least-squares on F2
Goodness-of-fit on F2
Final R indices [I > 2σ (I)]
R1 = 0.0574, wR2 = 0.1494
R1 = 0.0464, wR2 = 0.1334
R indices (all data)
R1 = 0.1047, wR2 = 0.1819
R1 = 0.0638, wR2 = 0.1470
Largest diff. peak and hole
0.333 and −0.240 e.Å−3
0.393 and −0.332 e.Å−3
The geometry of the hydrogen bonds (Å, ˚)
C (20) -H (20)…O (1)i
C (14)-H (14A)…O (2)
C (5)-H (5)…O (3)ii
C (22)-H (22)…O (1)iii
C (16) -H (16A)…Cg(3)iv
The title compounds were synthesized, crystallized and the crystal structures have been determined by single-crystal X-ray diffraction methods. The terminal ethyl group of the compound I is disordered over two positions with the refined occupancies of 0.645 & 0.355. C-H…O intermolecular hydrogen bond builds up a one dimensional zig-zag chain running along 101 directions. In compound II, C-H…O hydrogen bonds connect the molecules to form a R22 (16) dimer chain running along 011 direction.
One of the authors NE is grateful to Mother Teresa Women’s University, Kodaikanal, Tamilnadu-India and DST-CURIE programme for their encouragement and providing facilities for doing this research work. NE also put forth his heartfelt thanks to his guide Dr. P. Ramesh (Late) for the encouragement and motivation of the research work. PR thanks Prof. Kyeong Kyu Kim, Laboratory of Structural Biology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440–746, South Korea and the National Research Foundation of Korea for the financial support in the form of postdoctoral fellowship (2012K2A4A1034867 and 2011–0030915).
Crystallographic data (excluding structure factors) for the structures of compounds (I) and (II) reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers, CCDC 996464 and CCDC 996465, respectively. Copies of the data can be obtained free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1 EZ, UK. (fax: +44-(0)1223-336033 or email: firstname.lastname@example.org).
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