2 - Chloro - 5 - (trifluoromethyl) Pyridine Synthesis

2-chloro-5-(trifluoromethyl) pyridine is a key raw material and intermediate in pharmaceutical and agrochemical industry. Based on broad information collection, author compared and studied on the old synthesis process, and proposed the better process that started from benzyl chloride, then according to the sequence of " synthesis of benzylamine, synthesis of N-benzyl-N-(l-propenyl)-acetamine (NBNA), synthesis of 2-chloro-5-methylpridine(CMP) ,2-chloro-5-trichloromethylpyridine(CTP),2-chloro-5-trifluropyridine(CTFP) " five steps to get the final product, CTFP. In this paper, issues such as clean production, operational and safety are fully considered.Advantage of proposed process is that benzyl chloride is a common and cheap raw material, and the by-product of synthesis of 2-chloro-5-methylpyridine is still benzyl chloride, it's easy to recovery and recycle, and to lower the cost. And no solvents involved in the synthesis of NBMA, CTP, CTEP, it's easy to keep whole production line in clean condition.Author studied and optimized the condition used in the synthesis of 2-chloro-5-(trifluoromethyl) pyridine in each step including: 1. synthesis of benzylamine: benzyl/NH3.H2O=l: 2.5 (g/g)? under temperature of 80℃, reaction maintains about 6 hours ; CuSO4 and KI are added as catalyst, dosage is catalyst/benzyl=l% (g / g); product's purity is 88%, yield is about 70.0% 2. synthesis of N-benzyl-N-(l-propenyl)-acetamine:Dosage:benzylamine:CH3CHO:KOH=l:1.05:0.54(mol/mol/mol), (KOH was added twice 1.5 hours ; dosage of synthesis of NBNA is C10H13N: triethylamine:acetic anhydride=l:5:l(mol/mol/mol), the temperature for adding anhydride is 5℃, and takes about 20 minutes; the synthesis temperature for NBNA is 25 ℃, whole reaction takes 3 hours, CH3CHO must be freshly distilled one.3. synthesis of 2-chloro-5-methylpridine (CMP) dosage: NBNA:POC13:DMF= 1:2.2:1.2(mol/mol/mol),NBNA : benzylchloride =1: 4(mol/V), the dropping temperature is 5℃, takes 3 hours; the feeding temperature of NNAA is 0-5℃, which takes 2 hours, cyclization was under 100℃.4.synthesis of 2-chloro-5-(trichloromethyl) pyridine (CTCMP);warm up the vessel temperature to 80℃, then start to add POC13, it's a exothermic reaction and keep temperature until 160℃, and reaction takes 16 hours, stirring speed is 100-120v/min catalyst: triethanolamine / benzoyl peroxide /POC13/CMP = 1:1:3:100 (weight) 5.synthesis of 2-chloro-5-(trifluoromethyl) pyridine (CTFP):HF/cat/CTCMP=200: 0.03: l(g/g/mol) reaction takes 6 hours and under 180℃, SbC15 was added as catalyst Assay is about 95.0%, and yield is about 80.5%.