A new convenient synthesis of some novel 2,6-disubstituted-pyridine derivatives

Abstract

The versatile, hitherto unreported pyridine-2,6-bis-(3-oxo-3-propanenitrile) 2 was prepared by the Claisen condensation of pyridine-2,6-dicarboxylic acid ester 1 with acetonitrile in the presence of sodium hydride. Several new pyrazoles, isoxazoles, and pyrazolopyridazine derivatives have been synthesized by the reaction of pyridine-2,6-bis-(3-oxo-3-propanenitrile) 2 with bidentate nucleophilic reagents and hydrazonoyl chloride derivatives.

Synthesis of some new 2,6-bis pyridines incorporating with tetra-substituted pyrazole heterocycles

“…Firstly, We have prepared 2,6-bis(ethoxycarbonyl-acetyl)pyridine (2) by Claisen condensation of dimethyl pyridine-2,6-dicarboxylate ester (1) with the ethyl acetate using our procedure to synthesize pyridine-2,6-bis-(3-oxopropanenitrile) 11 with excellent yields (91%) that are more than the reported methods 16 (Scheme 1).…”

“…The corresponding pyrazolo [4,3-d]pyridazine derivative 10 was obtained by the reaction of 5a with an excess of hydrazine upon refluxing in ethanol for 5h (Scheme 4). Treatment of 2,6-bis(4-(ethoxycarbonyl)-3-acetyl-1-phenyl-1H-pyrazol-5-yl) (5a) with phenyl hydrazine in refluxing EtOH afforded a single product identified as 2,6-bis(4-(ethoxycarbonyl)-1-phenyl-3-(1-ethylidene-2-phenylhydrazino)-1H-pyrazol-5-yl)pyridine (11). The formation of compound 11 is assumed to proceed via condensation of the un-substituted nitrogen atom of phenyl hydrazine with the carbonyl function of the acetyl group and the reaction has stopped at this stage and didn't undergoes intramolecular cyclization may be due to the steric hindrance effect of the two terminals phenyl groups of the phenyl hydrazine (Scheme 4).…”

“…A mixture of compound 5a (0.6 g, 1 mmol) and phenyl hydrazine (0.22 g, 2 mmol), in EtOH (10 mL), was refluxed for 10h. The formed solid after cooling was filtered off, washed with EtOH, dried and finally recrystallized from EtOH to afford white powder of 2,6-bis(4-(ethoxycarbonyl)-1-phenyl-3-(1-ethylidene-2-phenylhydrazino)-1H-pyrazol-5-yl)pyridine (11 …”

“…7 On the other hand, various pyrazole derivatives were found to possess interesting pharmacological activities that include antirheumatic, anti-inflammatory, antipyretic and analgesic properties. [8][9][10] In view of these observations and in continuation of our interest in the synthesis of 2,6-disubstituted pyridines for different applications, [11][12][13][14][15] we considered it attractive to synthesize some poly substituted pyrazoles incorporated into the 2,6-pyridine moiety using 2,6-bis(ethoxycarbonyl-acetyl)pyridine (2) as starting material.…”

Catalyst Free Synthesis of Pyridine-2,6-bis(2-bromo-propane-1,3-dione) and Pyrdine-2,6-bis(<i>N</i>-arylthiazoline-2-thiones)

“…In view of these observations and our interest in the synthesis of biologically target pyridine-2,6-bis(functionalized heterocycles) [15]- [ 21], we describe herein a catalyst-free, three component one pot synthesis for new class of 2,6-bis(5-substituted-3-aryl-2-thiothiazol-4-yl)pyridine (4a-i) by reaction of primary amines, carbon disulfide, and 2-chloro-1,3-dicarbonyl compounds in water. This protocol and the work-up procedure were facile and we have obtained pure target compounds containing several potential centres for further modification.…”