CN101643385A - Method for preparing 3,5-dichlorobenzyl chloride - Google Patents

Abstract

The invention discloses a method for preparing 3,5-dichlorobenzyl chloride. The method comprises the following steps: adding a reducing agent and zinc chloride in a kettle; after carrying out vacuum replacement, dripping THF in the kettle; after evenly stirring, adding 3,5-dichlorobenzoic acid in the kettle to perform a reducing reaction; maintaining reflux, filtering, washing and drying crystal after ethyl acetate is added to obtain a reduction product 3,5-dichlorobenzyl alcohol; adding DMF into the 3,5-dichlorobenzyl alcohol; after SOCl2 is dripped to perform a chlorination reaction, heatingand refluxing the reactant; cooling, crystallizing and recrystallizing feed liquid to prepare the final product 3,5-dichlorobenzyl chloride. The preparation method has reasonable process route, and is advanced and practicable. The prepared 3,5-dichlorobenzyl chloride has high purity and good quality.

Description

3, the preparation method of 5-dichlorobenzyl chloride

Technical field

The present invention relates to a kind of 3, the preparation method of 5-dichlorobenzyl chloride.

Background technology

3, the 5-dichlorobenzyl chloride is a medicine intermediate, is widely used in pharmaceutical industry, has bigger industrial prospect and social benefit.

Summary of the invention

It is a kind of 3 that purpose of the present invention just provides, the preparation method of 5-dichlorobenzyl chloride, and for reaching above purpose, the technical solution used in the present invention is:

1) reduction:

Add KBH in the there-necked flask ₄With anhydrous ZnCl ₂Vacuumize then and with twice of nitrogen replacement, be added drop-wise to THF in the flask slowly down in stirring, ice-water bath will be controlled and add to speed well,. take by weighing 3, the 5-dichlorobenzoic acid is dissolved in it among anhydrous THF, then this drips of solution is added in the reaction flask, add the back feed liquid and be the canescence pasty state. treat out to change the oil bath heating into after the venting body relaxes, temperature maintenance is added 27g KBH behind 70 ℃ of backflow 1h ₄, with than fast speeds backflow 2h, have this moment a large amount of zinc powders to generate again, the feed liquid gray stops heating, slowly drips water, added postcooling to room temperature, added the ethyl acetate vigorous stirring again, filtered,, filter cake washs with ethyl acetate, decompression pours into the solvent evaporate to dryness of trying one's best in the culture dish with not solidified liquid while hot, stirs to be cured as white fine crystals down very soon, get product 3 after drying, the 5-Dichlorbenzyl Alcohol, GC purity is 99%.

2) chlorination:

Add 3 in the dry reaction bottle that has device for absorbing tail gas, the 5-Dichlorbenzyl Alcohol adds DMF again, stirs to drip SOCl down _2c, gas to be produced is heated to faint backflow 1h gradually with oil bath after relaxing, feed liquid is poured in the frozen water that is stirring, had a large amount of light yellow solids to separate out, filter the back filter cake to wash three times, after drying solid crude product, with crude product with dehydrated alcohol and normal hexane mixed solvent heating for dissolving, frozen recrystallization again, filter, crystal dries with the absolute ethanol washing that is chilled to below-10 ℃, get white crystal 3, the 5-dichlorobenzyl chloride, yield 73%, GC purity is 99.3.

Embodiment

In 2000 milliliters there-necked flask, add 98g KBH ₄With the anhydrous ZnCl of 134g ₂Vacuumize then and with twice of nitrogen replacement, in stirring down 250mlTHF is added drop-wise in the flask slowly, ice-water bath will be controlled and add to speed well, with the harm heat release and produce gas and material is gone out .. take by weighing 181 grams 3, the 5-dichlorobenzoic acid is dissolved in it among anhydrous THF of 300ml, then this drips of solution is added in the reaction flask, treats out to change the oil bath heating into after the venting body relaxes, temperature maintenance is in about 70 ℃, about 30min that refluxes suitably accelerates return velocity. behind 1h, add 17g KBH ₄Again with than fast speeds backflow 1h, TLC steams the overwhelming majority when tracking to no obvious raw material spot THF. stops heating, slowly drip 200ml water, have a large amount of gases and heat generation this moment. added postcooling to room temperature, add 300ml ethyl acetate vigorous stirring again, filter, filter cake washs with the 400ml ethyl acetate, drying, 60 ℃ of decompressions pour into the solvent evaporate to dryness of trying one's best in the culture dish with not solidified liquid while hot, stir and be cured as white fine crystals down very soon, get product 3 after drying, the 5-Dichlorbenzyl Alcohol, GC purity is 99%.

Add 47.6g3 in the 250ml dry reaction bottle that has device for absorbing tail gas, the 5-Dichlorbenzyl Alcohol adds 1mlDMF again, stirs to drip 10.7ml SOCl down _2cEmit a large amount of HCl gases, and obviously lower the temperature because of heat absorption, after gas to be produced relaxes, after being heated to 110 ℃ ~ 150 ℃ backflow 1h gradually with oil bath, so feed liquid is poured in the frozen water that 150ml stirring, there are a large amount of light yellow solids to separate out, filter the back filter cake with 60ml washing three times, get solid crude product after drying, crude product with 5: 1 dehydrated alcohols and normal hexane mixed solvent heating for dissolving, is refrigerated to-10 ℃ of recrystallizations again, filters, crystal is with 30 milliliters of absolute ethanol washings that are chilled to below-10 ℃, dry, get white crystal and get white crystal 3, the 5-dichlorobenzyl chloride, yield 73%, GC purity are 99.3.

Claims (1)

1, a kind of 3, the preparation method of 5-dichlorobenzyl chloride is characterized in that being prepared from by following steps:

1) reduction:

Add KBH in the there-necked flask ₄With anhydrous ZnCl ₂Vacuumize then and with twice of nitrogen replacement, be added drop-wise to THF in the flask slowly down in stirring, ice-water bath will be controlled and add to speed well,. take by weighing 3, the 5-dichlorobenzoic acid is dissolved in it among anhydrous THF, then this drips of solution is added in the reaction flask, add the back feed liquid and be the canescence pasty state. treat out to change the oil bath heating into after the venting body relaxes, temperature maintenance is added 27g KBH behind 70 ℃ of backflow 1h ₄, with than fast speeds backflow 2h, have this moment a large amount of zinc powders to generate again, the feed liquid gray stops heating, slowly drips water, added postcooling to room temperature, added the ethyl acetate vigorous stirring again, filtered,, filter cake washs with ethyl acetate, decompression pours into the solvent evaporate to dryness of trying one's best in the culture dish with not solidified liquid while hot, stirs to be cured as white fine crystals down very soon, get product 3 after drying, the 5-Dichlorbenzyl Alcohol, GC purity is 99%.

2) chlorination:

Add 3 in the dry reaction bottle that has device for absorbing tail gas, the 5-Dichlorbenzyl Alcohol adds DMF again, stirs to drip SOCl down _2c, gas to be produced is heated to faint backflow 1h gradually with oil bath after relaxing, feed liquid is poured in the frozen water that is stirring, had a large amount of light yellow solids to separate out, filter the back filter cake to wash three times, after drying solid crude product, with crude product with dehydrated alcohol and normal hexane mixed solvent heating for dissolving, frozen recrystallization again, filter, crystal dries with the absolute ethanol washing that is chilled to below-10 ℃, get white crystal 3, the 5-dichlorobenzyl chloride, yield 73%, GC purity is 99.3.