2-Chloro-5-(chloromethyl)pyridine

beige moist crystals

18 g (0.1 mol) of 2-chloro-2-chloromethyl-4-cyanobutanal were addedDissolved in 50 ml of toluene, A solution of 33 g (1.1 eqiv)Solid phosgene toluene solution, The reaction was incubated at 50 ° C for 5 hours. Cooling crystallization, Acetamiprid intermediate 2-chloro-5-chloromethylpyridine, yield 97percent.Then methylated, esterified to synthesize acetamiprid original drug, Yield 95percent.Mix 9000g (about 50mol) of 2-chloro-2-chloromethyl-4-cyanobutyraldehyde and 32000ml of chlorobenzene, Dissolve 2870 g (about 9.66 mol) (CCl3)2CO3 with 14000 ml of chlorobenzene.Proportional to the use of the pump to drive the two materials simultaneously into the heating device, 0.1m2 continuous reactor equipped with reflux condenser and thermometer at the outletThe reactor outlet material temperature was controlled at 105°C.One-stage reactor outlet sampling, GC analysis, solvent peak deducted, Unreacted 2-chloro-2-chloromethyl-4-cyanobutyraldehyde 1.8percent, 2-chloro-5-chloromethylpyridine 87.5percent, (CCl3)2CO 31.6percent.After the material passes through the primary reactor, it is heated toA 0.15m2 secondary reactor equipped with a reflux condenser and thermometer at the outletControl and control the temperature between 105 ~ 110 °C.Secondary reactor outlet sampling, GC analysis, solvent peak deducted, Unreacted 2-chloro-2-chloromethyl-4-cyanobutanal 0.08percent, 2-chloro-5-chloromethylpyridine 92.1percent, (CCl3)2CO 31.1percent. Hydrogen chloride tail gas is absorbed by lye.After about 17 minutes, the material enters with mechanical stirring, reflux condenser, Thermometer 20000ml hydrolysis neutralizer with overflowA 10percent Na2CO3 solution was added to the bottle in proportion to control the pH to 7.5-8.Then divide the neutralized material into water, The aqueous layer was extracted twice with chlorobenzene, and the organic layer and the extract were combined and distilled after desolvation under reduced pressure.Collect fractions at 100 to 105 °C (750 mmHg vacuum), This gave 6763 g of 2-chloro-5-chloromethylpyridine. GC analysis, content 95.2percent, yield 79.5percent.Chloro-5-methylpyridine 350g, was added to a 500ml four-necked flask under stirring and heating 115-120 conditions, Into the chlorine reaction 5.5 hours, Control analysis of 2-chloro-5-dichloropyridine <3wtpercentAfter stopping the reaction cooling down, Analysis of feed solution 2-chloro-5-methyl pyridine, 2-Chloro-5-chloromethylpyridineAnd 2-chloro-5-dichloromethyl pyridine content, Chloro-5-chloromethylpyridine (calculated as 2-chloro-5-methylpyridine)The yield was 93.5percent.the above-obtained oil layer is mixed with 2-chloro-5-chloromethylpyridine of equal quality, 350 g of azobisisobutyronitrile, and chlorine, and the temperature of the mixture is maintained at 50-60° C., flowing through the ultraviolet light. In the tube reactor, the reaction was completed, 200 kg of water was washed, and the mixture was allowed to stand for delamination to obtain 105.6 kg of 2-chloro-5-chloromethylpyridine liquid having a purity of 99.6percent. The yield was 96.7percent (based on the conversion of 3-methylpyridine. ).Take the compound CCC 0.1mol, Dissolved in 20 ml of toluene, The oil bath was heated to 90 ° C, 6.6 g of catalyst N, N-dimethylformamide, A 40 ml portion of toluene solution containing 14.74 g (0.08 mol) of cyanuric chloride was added dropwise, Keep the temperature between 90-100 ° C, Dropping 2h, 100 for 30 minutes, Then cooled to 50 ° C, Add 10 ml of water, Then 10.7 g of an aqueous solution of 30percent NaOH was added dropwise at 20-50 ° C, The pH of the aqueous phase is about 8.0-10.0, Start filtering, The filter cake was rinsed with 10 ml of toluene, The separated filtrate was allowed to stand, The upper layer is toluene, De-dissolving, 18.4 g of a brown solid, GC internal standard detection containing CCMP 75.4percentYield 85.8percent.

2-Chloro-5-(chloromethyl)pyridine, is a building block used for the synthesis of various pharmaceutical compounds. It can also be used for the synthesis of new neonicotinoid compounds, having insecticidal activity.

Molecular Weight:162.01
XLogP3:2.2
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:160.9799046
Monoisotopic Mass:160.9799046
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:87.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes