Catalyst – solid sorbent – or support therefor: product or process – Solid sorbent – Free carbon containing
Reexamination Certificate
1999-07-30
2001-08-21
Kumar, Shailendra (Department: 1621)
Catalyst, solid sorbent, or support therefor: product or process
Solid sorbent
Free carbon containing
C502S416000, C502S180000
Reexamination Certificate
active
06277783
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to an improved method for the purification of N-acetyl-para-aminophenol (APAP), also known as acetaminophen. APAP is a well-known over-the-counter analgesic and anti-pyretic agent.
2. Description of Related Art
The following prior art references are disclosed in accordance with the terms of 37 CFR 1.56, 1.97 and 1.98.
U.S. Pat. No. 3,042,719, issued Jul. 3, 1962 to Hahn et al., discloses the purification of crude discolored APAP by acidifying an aqueous solution of the APAP with a mineral acid, filtering the solution while hot, and cooling the filtrate while adding an alkaline reducing sulfite, e.g., sodium hydrosulfite (sodium dithionite). A “decolorizing” carbon may be added to the hot solution.
U.S. Pat. No. 3,113,150, issued Dec. 3, 1963 to Young, teaches the preparation of “pure” APAP by adding acetic anhydride to a mixture of p-aminophenol and water, cooling the reaction mixture to precipitate the APAP, filtering to remove excess acetic acid, neutralizing the wet APAP with ammonium hydroxide, and agitating the resulting solution with carbon black.
U.S. Pat. No. 3,748,358, issued Jul. 24, 1973 to Baron, discloses the purification of APAP by treating it in aqueous solution with carbon which has been preliminarily treated with an acidic solution.
U.S. Pat. No. 3,781,354, issued Dec. 25, 1973 to Kosak, teaches the purification of APAP by treating it in hot aqueous solution with ferric chloride and adsorbing the colored by-product on activated carbon.
U.S. Pat. No. 4,524,217, issued Jun. 18, 1985 to Davenport et al., teaches an integrated process for the production of APAP comprising acetylating phenol by a Friedel-Crafts reaction, or subjecting phenyl acetate to a Fries rearrangement to produce 4-hydroxyacetophenone (4-HAP), reacting the 4-HAP with hydroxylamine or a hydroxylamine salt to form 4-HAP oxime, and subjecting the latter oxime to a Beckmann rearrangement to form APAP.
ADDITIONAL BACKGROUND INFORMATION
In the manufacture of APAP by any of the known methods, it has been found that there is a tendency for color bodies and color body precursors to form which cause the crude product to have or to develop subsequently an undesirably colored appearance. Because of this, various methods have been developed for the purification of APAP, which remove color bodies in addition to other impurities, such that the purified product has a substantially pure white appearance. These methods often include the addition to a hot aqueous solution of APAP containing color bodies of an adsorbent carbon, which is a well-known decolorizing agent. Some of these methods are described in the disclosures of several of the previously cited references.
It has been found that a disadvantage of decolorizing APAP by contacting a hot aqueous solution of the crude APAP with an adsorbent carbon is that certain impurities appear for the first time or increase as a result of such treatment, which impurities were not present previously, i.e., in the crude APAP before purification. In view of the fact that the main use for APAP is as a pharmaceutical, the presence of these impurities must be kept to a very low practical maximum, either by preventing their formation, or removing the bulk of them subsequent to the carbon treatment.
SUMMARY OF THE INVENTION
In accordance with this invention, a crude APAP containing undesirable color bodies or their precursors is subjected to a purification treatment comprising the steps of forming a hot aqueous solution of the crude APAP, and subsequently contacting said hot solution with an acid washed adsorbent carbon which, prior to said contact, has been pretreated with an aqueous solution of a reducing sulfite. It has been found that the treatment of the acid washed carbon with the aqueous reducing sulfite solution substantially reduces the formation of certain impurities which are observed to form during the treatment of the hot APAP solution with carbon which has not been treated with the aqueous reducing sulfite solution. The impurities formed during the treatment of APAP with carbon which has not been sulfite treated are different from other impurities present in the crude APAP before carbon treatment, which other impurities do not increase as a result of the carbon treatment, as indicated by liquid chromatographic analysis.
DESCRIPTION OF PREFERRED EMBODIMENTS
The aqueous solution of APAP containing color bodies which is subjected to carbon treatment will in most cases contain at least about 4 wt. % of APAP and the solution will be at least hot enough to dissolve the APAP substantially completely, e.g., at least about 70° C. and up to the boiling point of the solution. The method of the invention is useful in the preparation of a relatively pure decolorized APAP regardless of the manufacturing process used to produce the APAP, since such method accomplishes the reduction of impurities, formed during treatment of the APAP with acid washed carbon which has not been pretreated with reducing sulfite, no matter which manufacturing process is used. Thus, the APAP may be produced, for example, by the process illustrated in the examples of previously cited U.S. Pat. No. 4,524,217 as summed up in the foregoing description of the disclosure of that patent, or by the previously developed process of acetylating para-aminophenol with acetic anhydride, as described, for example, in previously cited U.S. Pat. No. 3,113,150.
The acid washed adsorbent carbon of this invention defines an art-recognized group of materials and is a commodity of commerce. Such a carbon has a relatively large surface area available for the adsorption of impurities and is preferably one of the class of materials known as activated carbon or activated charcoal. The feature of the carbon being “acid washed” is well-known in the art and may be accomplished as described, for example, in previously cited U.S. Pat. No. 3,748,858.
The reducing sulfite used to pretreat the acid washed carbon may be any water soluble reducing sulfite such as alkali metal and ammonium reducing sulfites, e.g., sodium, potassium, and ammonium dithionites, metabisulfites, sulfites, and bisulfites. Preferably the sulfite reducing agent is a dithionite, and most preferably sodium dithionite. In pretreating the acid washed carbon with reducing sulfite, the carbon is shaken with a sufficient quantity of an aqueous solution of the sulfite containing, for example, about 0.1 to 5 wt. % of the sulfite, to completely wet the carbon. The carbon may then be allowed to stand in such wetted condition, e.g., submerged in the solution, for a period of at least ½ hour, preferably at least 1 hour. In some cases, it may be desirable to allow the wetted carbon to stand for at least 24 hours or longer.
After pretreatment with a reducing sulfite, the carbon is contacted with the hot aqueous APAP solution. The amount of carbon used is not critical but is generally such that the weight ratio of APAP to carbon (APAP:carbon) is at least about 2:1 and may be as high as about 200:1. The APAP solution is then agitated with the pretreated carbon, preferably under reflux, for a period of at least about 1 min. The solution is then filtered to remove the carbon and cooled to crystallize out the APAP. In some cases, it may be advantageous to conduct an initial crystallization of the APAP from hot aqueous solution without any carbon treatment, followed by a second crystallization from a hot aqueous solution which has been subjected to a carbon treatment using a reducing sulfite pretreated acid washed carbon in accordance with this invention. It may also be advantageous for the purpose of reducing the impurities to the lowest feasible level, to dissolve some reducing sulfite, e.g., from about 0.05 to about 0.5 wt. %, (based on the total solution mixture including the reducing sulfite) in the hot aqueous APAP solution which is subjected to carbon treatment. The latter reducing sulfite may be the same or different from the reducing sulfite used to pretreat the carbon, and is preferably s
Fruchey Olan Stanley
Wheeler Larry O.
Zey Edward G.
BASF Corporation
Kumar Shailendra
Maurer Barbara V.
LandOfFree
Method for the purification of acetaminophen does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for the purification of acetaminophen, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for the purification of acetaminophen will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2541504