A Novel Synthetic Process Of 2,3-dichloro-5-Trifluoromethylpyridine

2,3-chloro-5-trifluromethylpyridine is a key intermediate for agrochemicals and pharmaceuticals. The known synthetic routes have such problems as poor yield, harsh reaction conditions and high cost. Therefore, it is important and necessary to develop a new synthetic procedure of the title product.In this thesis, a novel synthesis of 2,3-dichloro-5-trifluoromethylpyridine was developed, starting from benzylamine and propionaldehyde and comprising five steps such as condensation, acylation, cyclization, chlorination and fluorination giving four intermediates such as N-propylidene benzylamine, 2-chloro-N-benzyl-N-propen-1-ylacetamide, 2,3-dichloro-5-methyl pyridine and 2,3-dichloro-5-trichloromethyl pyridine respectively.In the procedure, Na3PO4 was firstly used as the catalyst and dehydrant in the condensation reaction, giving N-propylidene benzylamine in 96.7% purity and 90.3% yield; Using chloroacetyl chloride as acylating agent and triethylamine as catalyst, gave 2-chloro-N-benzyl-N-propen-1-ylacetamide in 93.0% purity and 85.6% yield; Using environmental friendly solid phosgene to replace phosphorus oxychloride in the cyclization step, 2,3-dichloro-5-methyl pyridine was obtained in 98.6% purity and 57.4% yield; By chlorination with chlorine gas under UV light,2,3-dichloro-5-trichloromethyl pyridine was obtained in 91.8% purity and 84.7% yield. Instead of HF, HF pyridine solution was firstly used in the fluorinating step in the presence of Sc(OTf)3 as the catalyst,giving 2,3-dichloro-5-trifluromethyl pyridine in 97.4% purity and 70.9% yield.In conclusion, the novel synthetic method of 2,3-dichloro-5-trifluoromethylpyridine using benzylamine and propionaldehyde as starting materials through 5 steps has such advantages as cheap and readily available raw materials, simple operations and warm reacting conditions, which is valuable for industrial application.