Synthesis of meso-tetrakis (2-chloroquinolin-3-yl) porphyrins

meso -Tetrakis (-2-chloroquinolin-3-yl) porphyrins were synthesized from 2-chloroquinoline-3-carboxaldehydes and pyrrole in 1:1 ratio in propionic acid at 140 o C for 4 hours. Different substituted 2-chloroquinoline-3-carboxaldehydes were synthesized from corresponding N-aryl acetamides by Vilsmeier–Haack cyclization. The aldehydes were obtained in better yields, when acetamides, dimethyl formamide and POCl 3 were taken in 1:3: 7 molar ratios at 70-75 o C


Introduction
There is a particular interest for synthesis of porphyrins bearing heterocyclic moieties due to varied biological 1 , photophysical 2 and electronic properties 3 .The heteroaryl porphyrin with diverse substitutents is important for the studies of biomimetic and molecular recognition properties 4,5 .A good number of porphyrins containing nitrogen heterocycles have been prepared and their properties were studied.Substituted nitrogen heterocyclic porphyrins are of particular interest 6 as they provide sites for metal coordination, hydrogen bonding, alkylation and modulating electronic properties.Indeed, pyridine substituents have yielded a broad array of metal coordinated multi porphyrin architectures 7 and imidazole groups have yielded stacked multi porphyrin assembles 8 .Pyrimidine 9 , purine 10 or pyrazole 11 units have enabled molecular recognition and self-assembly studies of porphyrins with complementary molecules.Several quinoline derivatives have been found to possess useful biological activities such as bactericidal 12 , antitumor 13 , antimalarial 14 , antinflamatory 15 .The benzo and hetero fused quinolines are known to bind to DNA topoisomerase and display cytotoxic and antitumor activities 16 .[5,15-Bis(8-quinolyl)porphyrinato]zincII has been used for molecular recognition of carbohydrates 17 .The above applications of the meso-substituted heterocyclic porphyrins inspired us to synthesize the new meso-tetrakis (2-chloroquinolin-3-yl)porphyrins (2a-2d).Porphyrins themselves are having high applications in organic chemistry, so by substituting quinoline
Scheme 1 meso-Tetrakis(-2-chloroquinolin-3-yl) porphyrins (2a-2d) exhibit the phenomenon of atropisomerism, a typical feature of meso-(2-substituted-aryl)porphyrins 20 .This is due to a high rotational energy barrier caused by steric hindrance between the quinoline 2-chloro group and the porphyrin β-protons.Four distinct bands were observed by TLC for porphyrins 2a-2d.Attempts were made to separate these atropisomers by column chromatography (flash silica gel 230-400 mesh).TLC studies indicate that each one of the individual isomeric fractions of 2a-2d, becomes a mixture of atropisomers, on standing at ambient temperature.The 1 H NMR spectra show a complex resonances for the central porphyrin N-H and β-protons for porphyrins 2a-2d.Where as, the C 4 proton of the quinoline appears as a singlet around δ 8.60 ppm in all the porphyrins.UV-Vis spectra of quinoline porphyrins were recorded at 1x10 -5 mol concentrations in CHCl 3. Highly characteristic spectra were obtained for quinoline porphyrins 2a-d, in which the B band is prominent at 430 nm and Q bands are observed at 520, 600 and 661nm.The IR spectra contain a characteristic macrocyclic bending frequency of 970cm -1 for 2a-2d.

Experimental Section
General Procedures.UV-vis spectra were recorded on a SHIMADZU UV 160 A UV-vis-NIR spectrophotometer, using chloroform as solvent.IR spectra were recorded as KBr pellets using a SHIMADZU 8010 FTIR spectrophotometer. 1 H NMR spectra were recorded on a VARIAN FT 500 MHz instrument using CDCl 3 and DMSO-d 6 as solvent and TMS as internal reference.FAB-Mass spectra were recorded on a VG Micromass 7070H (F, or CI) auto spectrometer.The C, H, N analysis of the compounds was performed on a Carlo Erba Model EA 1108 CHNS-O elemental analyzer.Porphyrins were purified by flash column chromatography using 230-400 mesh silica gel (Aldrich).

Synthesis of meso-tetrakis(2-chloroquinolin-3-yl)porphyrin (2a).
2-Chloroquinoline-3carboxaldehyde (1a, 383 mg, 2 mmol) was dissolved in 50 ml of freshly distilled propionic acid and pyrrole (134 mg, 2 mmol) was added.The reaction mixture was stirred at 140 o C in open air for 4 h.Then the propionic acid was distilled off under reduced pressure and the residue was cooled to room temperature.30 ml of cold water was added to the residue and neutralized carefully with saturated sodium bicarbonate solution.The dark colored residue was filtered and dried.The crude product was purified by flash column chromatography using chloroform: methanol (95: 5) mixture as eluent.Four separate atropisomeric fractions were collected, which after concentration gave a dark purple solid 2a (58 mg, 12.1%).Identification and characterization of all the four fractions indicated that they contain the same compound.(m, aromatic C=C, C=N ring stretch), 973, 956 (m, porphyrin macrocyclic bend), 801, 785, 758 (s, aromatic C=C-H out-of plane bend).

Synthesis of meso-tetrakis(2-chloro-6-methylquinolin-3-yl)porphyrin (2c).
A mixture of 410 mg (2 mmol) of 2-chloro-6-methylquinoline-3-carboxaldehyde (1c) and 134 mg (2 mmol) of freshly distilled pyrrole was dissolved in 50 ml of propionic acid and heated at 140 o C for 4hrs with stirring.After the usual work up procedure was conducted as described above, the black residue obtained was subjected to column chromatography on flash silica gel using chloroform : methanol (97 : 3) mixture as eluent.Four separate purple colored atropisomeric fractions were collected, which after concentration gave a dark purple solid 2c (54 mg, 10.6%).Identification and characterization of all the four fractions indicated that they contain the same compound.