Design、Synthesis And Characterization Of The Heterocyclic Compound With Ethyl 2-(Chloro- Methyl)-4-methyl (4-bromomethyl)Quinoline- 3-carboxylate As A Skeleton

Quinoline and its derivatives as a very important class of heterocyclic compounds, widely present in natural products and exhibit a broader biological, pharmacological activity, especially planar polycyclic fused heterocyclic quinoline compound containing a heteroatom has good anti-tumor activity. Therefore, research has important implications for the synthesis and properties of fused heterocyclic polycyclic quinoline compounds, In this paper, ethyl 2-(chloromethyl)-4-methylquinoline-3-carboxylate and ethyl 4-(bromomethyl)-2-(chloro-methyl)quinoline-3-carboxylate as raw materials, we successful synthesis of a variety of novel heterocyclic compounds containing quinoline skeleton. This paper is divided into the following five sections:The first part, we based on a large number of the literature in recent years, then we conducted a literature review for quinoline and its derivatives’nature and their synthesis,and the properties and synthesis methods of quinoline and pyrrole, quinoline and Zhuo derivatives.The second part, with 2-chloromethyl-4-methylquinoline-3-carboxylate (1) as raw material, and aniline, a substituted aniline, ammonia, methylamine, ethylamine, bian amine (2a-m) in ethanol as solvent under reflux conditions by Williamson reaction and intramolecular ester exchange reaction has been successfully obtained 9-methyl-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-l-one derivatives (3a-m), and their structure by infrared spectroscopy, nuclear magnetic resonance spectroscopy, mass spectrometry and high-resolution mass spectrometry to characterize.The third part, with 2-chloromethyl-4-methylquinoline-3-carboxylate (1) as raw material, and phenol, substituted phenol, naphthol, hydroquinone, naphthol and naphthol (4a-q) in acetonitrile as solvent, potassium carbonate as catalyst under reflux conditions for a successful synthesis of 4-methyl-2-(phenoxymethyl)quinoline-3-carboxylic acid derivatives (5a-j),4-methyl-2-(naphthalenmethyl)quinoline-3-carboxylic acid derivatives(5k-1), 2,2’-((phenylenebis(oxy))bis(methylene))bis(4-methylquinoline-3-carboxylic acid) derivatives (5m-o),2,2’-((naphthalene-1,5-diylbis(oxy))bis(methylene))bis(4-methylquinoline-3-carboxylic acid) (5p), and 2,2’-(([1,1’-binaphthalene]-2,2’-diylbis(oxy))bis(methylene))bis (4-methylquinoline-3-carboxylic acid) (5q); compound 5a-1 in polyphosphoric acid (PPA) catalyzed by Friedel-Crafts intramolecular acylation successfully obtained 12-methylbenzo(naphthalene) [6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives (6a-1). Their structure through IR, NMR, MS and high resolution mass spectrometry to be confirmed.The fourth part, with 2-chloromethyl-4-methylquinoline-3-carboxylate (1) as raw material, with o-hydroxyacetophenone and substituted ortho-hydroxyacetophenone (7a-e) by the Williamson reaction and the condensation reactions "one-pot" successfully synthesized 4-methyl-2-(3-methylbenzofuran-2-yl)quinoline-3-carboxylic acid compounds (8a-e), their structure by IR, NMR, MS and high-resolution mass spectrometry characterization.The fifth part, with 2-chloromethyl-4-methylquinoline-3-carboxylate (1) as raw material, by NBS bromination, synthesized another compound of ethyl 4-(bromomethyl)-2-(chloromethyl)quinoline-3-carboxylate (9). And it as a raw material with phenol and substituted phenol (10a-k) through the "one-pot" successfully synthesized 2,4-bis(phenoxymethyl)quinoline-3-carboxylic acid derivatives (11a-k).Their structure after IR, NMR, MS, and high-resolution mass spectrometry spectra.