CN102863351A - New technique of paracetamol decoloration process - Google Patents

Abstract

The invention relates to a new technique of a paracetamol decoloration process, which can remove red impurities of cruse wet products. In the new technique, quartic-applied cruse wet products for acylation mother liquor and an acetic acid acylation process serves as an initial raw materials, first decoloration is carried out by using purified water, the quartic-applied cruse wet products and 302-P deprived red carbon, a press filter is used for pressing and filtering activated carbon after decoloration, a first decoloration solution enters another decoloration pot, second decoloration is carried out by using the first decoloration solution and 302 medicinal carbon, the press filter is used for pressing and filtering the activated carbon after decoloration, a second decoloration solution enters a crystallization pot for cooling and crystallization at the temperature of 25 DEG C, and centrifuging and drying are carried out. A product of the new technique of the decoloration process is pure white in appearance, and good in stability through observing a reversed sample, does not appear red in a 25%W/V (weight per volume) 60 DEG C 99.5% carbinol solution, and can reach the full pattern comparison standards of an acetic anhydride acylation process.

Description

Paracetamol decoloration process new technology

Paracetamol is antipyretic and analgesic; chemistry paracetamol by name; in 2000 in the past abroad take p-aminophenol as starting raw material; adopt the aceticanhydride acylation process; acylation reaction is 75 ℃, 2 hours; the acidylate mother liquor is partly applied mechanically; thick wet product outward appearance is that off-white color does not contain red impurity; decolor refined technology technology with classics is that the product that slightly wet are dissolved in the hot water; with obtaining the high-quality Paracetamol of redfree impurity behind the 1% medical active carbon decoloring; not aobvious red in 25%W/V60 ℃ of 99.5% methanol solution, total recovery 80%.Because the aceticanhydride acylation process can not produce red impurity, so BP, USP pharmacopeia just there is no need to record the test item of red impurity.Acetic acid acylation process from nineteen sixty by the development of Wuxi the first pharmaceutical factory, acylation reaction is 130 ℃, 10 hours, acidylate mother liquid recycle four times, the thick wet product outward appearance of production is grey or light brown, and the consumption of gac is increased to 10%, and total recovery brings up to 85%; Product is aobvious red in 10%W/V25 ℃ of 99.5% methanol solution, and Chinese Pharmacopoeia can not produce the test item that red impurity is worked out red impurity by the acetic acid acylation process, but each factory all arranges the inner quality standard of dispatching from the factory that detects red impurity.Began each factory concentrates the decolorizing and refining mother liquor with outer circulation concentrating under reduced pressure and cover four acidylate mother liquors recovery article from 1975; total recovery is brought up to 91-92% after participating in the decolorizing and refining of thick wet product of product batch number, and product has obvious redness in 10%W/V25 ℃ of 99.5% methanol solution.Because two kinds of products that acylation process is produced; after pressing the residual quantity of the red impurity of pharmacopoeia of each country standard detection; cause inner quality widely different; particularly because after Chinese Pharmacopoeia do not control the residual quantity of red impurity; many factories are increased to the acidylate mother liquor for four times more than 10 time from original applying mechanically; the outward appearance of thick wet product is that dark-brown is to avy blue; the consumption of gac is down to 8% from 10%; the residual quantity of red impurity increases more than 10 times; but still meet the Chinese Pharmacopoeia standard, do not think quality problems yet.The ability that the gac of supplying on the market now all has removing and adsorbs red impurity, 302 Medicinal Charcoal are greater than 772 charcoals and 767 charcoals, and the product through after the decolouring of 302 Medicinal Charcoal has obvious redness in 10%W/V25 ℃ of 99.5% methanol solution.

The present invention is a Paracetamol decoloration process new technology; can remove the red impurity in the crude product; new technology is take the thick wet product of acetic acid acylation process and acidylate mother liquid recycle four times as starting raw material; once decolour by purified water; cover four thick wet product and 302-P take off red charcoal; remove red impurity in the thick wet product 85 ℃ of PH slight alkalinitys; use pressure filter press filtration gac after the decolouring; one time destainer enters an other Decolouring pot; secondary decolourization is taken off a destainer to clarification at 100 ℃ of PH6-6.5 by destainer and 302 Medicinal Charcoal again; colourless; with pressure filter press filtration gac, it is ℃ centrifugal that secondary decolourization liquid enters crystallizing pan crystallisation by cooling to 25 after the decolouring; dry.Pure white and the reserved sample observing good stability of the product appearance of decoloration process new technology, aobvious red in 25%W/V60 ℃ of 99.5% methanol solution, reach the full pattern contrast standard of aceticanhydride acylation process product.Single batch of gac total amount of the technology of the present invention decolouring is identical with former decoloration process gac total amount, do not increase with charcoal amount cost, increase a Decolouring pot and a pressure filter in technical process, increase a press filtration gac on the operation sequence and increase by 30 minutes when producing platform.

Below be the production test example of the technology of the present invention:

1. once decolour and in 5000 liter stainless steel Decolouring pots, add purified water 3500 liters, be warmed up to 85-90 ℃, add 850 kilograms of cover four thick wet product, be raised to again 90 ℃ of liquid temperatures, after the product that slightly wet all dissolve, slowly add cold purified water 500 liters, liquid temperature is down to 85 ℃, add 302-P and take off 25 kilograms of red charcoals, 85 ℃ of PH slight alkalinity insulations 10 minutes, will pass into steam preheating in the pressure filter after 10 minutes in advance, namely with 0.2Mpa pressurized air Liqui-Char is passed through the pressure filter of individual layer filter cloth, the 302-P that press filtration falls to adsorb red impurity takes off red charcoal, and one time destainer enters in the another 5000 liter stainless steel Decolouring pots.

2. secondary decolourization: with a destainer in the another Decolouring pot, under agitation transfer PH to 6-6.5 with 50% dilute acetic acid solution, be warmed up to 90 ℃ and add 50 kilograms of 302 Medicinal Charcoal, be warmed up to again 100 ℃, be incubated 15 minutes, namely use 0.2Mpa steam with pressure filter and the multiple filter of Liqui-Char by filter cloth, filter paper after 10 minutes with passing into steam preheating in the pressure filter in advance, 302 Medicinal Charcoal are fallen in press filtration, and secondary decolourization liquid enters crystallizing pan.

3. crystallization: add in advance 5% sodium metabisulfite solution, 40 liters in crystallizing pan, under agitation enter secondary decolourization liquid, crystallisation by cooling to 25 is ℃ centrifugal, dry.

Claims (5)

1. Paracetamol decoloration process new technology; it is characterized in that thick wet product take acetic acid acylation process and acidylate mother liquid recycle four times are as starting raw material; once decolour by purified water; cover four thick wet product and 302-P take off red charcoal; remove red impurity in the thick wet product 85 ℃ of PH slight alkalinitys; use pressure filter press filtration gac after the decolouring; secondary decolourization is taken off a destainer to clarification at 100 ℃ of PH 6-6.5 by destainer and 302 Medicinal Charcoal again; colourless; use pressure filter press filtration gac after the decolouring; pure white and the reserved sample observing good stability of the product appearance of decoloration process new technology; in 25%W/V60 ℃ of 99.5% methanol solution, do not show red, reach the full pattern contrast standard of aceticanhydride acylation process product.

2. the thick wet product of acidylate mother liquid recycle four times must be thick wet product after the just centrifugal and washing as described in claim 1; without tart flavour, moisture at the PH of 3-4%, the aqueous solution at 6-6.5; product with the decolouring of this decoloration process new technology; can meet the quality standard described in the claim 1; the acidylate mother liquid recycle surpasses four times and thick wet product are placed the thick dry product that dried out in 1-2 days in air; product with the decolouring of this decoloration process new technology can not all meet the quality standard described in the claim 1.

As described in claim 1 once decolouring be to remove red impurity in the thick wet product at 85 ℃, PH slight alkalinity, bleaching temperature can not be above 85 ℃.

4. 302-P takes off red charcoal as described in claim 1, is to be initial former charcoal with 302 Medicinal Charcoal, makes after purified and physically activated again in reactor the strong 302-P of red impurity absorption power is taken off red charcoal.

5. not aobvious red in 60 ℃ of 99.5% methanol solution of 25%W/V described in claim 1, the 25%th, the weight and volume ratio of sample and methyl alcohol, can not all dissolve at 25 ℃ of samples, must in hot water bath, be heated to 60 ℃ of samples complete molten after, colorimetric cylinder on test-tube stand, is observed red degree and time in fine, as to keep away sunlight bright chamber.