Electrolysis: processes – compositions used therein – and methods – Electrolytic synthesis – Preparing organic compound
Reexamination Certificate
2002-12-13
2004-10-26
Wong, Edna (Department: 1753)
Electrolysis: processes, compositions used therein, and methods
Electrolytic synthesis
Preparing organic compound
C205S435000, C205S453000
Reexamination Certificate
active
06808616
ABSTRACT:
The present invention relates to a new process for the preparation of p-amino-phenols, especially 5-aminosalicylic acid, by the direct electrochemical reduction of a sulfophenylazophenol derivative. The process is preferably conducted at low temperatures and preferably with the use of a specialized electrode.
p-Aminophenols are technologically important compounds, and especially 5-aminosalicylic acid (5-ASA) of formula
has many applications, for example, in electrophotography, for the preparation of colorants and pigments and, particularly recently, also as an active substance in medicine for the treatment of a number of diseases. Various processes for the preparation of these compounds and especially of 5-ASA have also long been known.
Of particular technological importance is the preparation of 5-ASA by the reduction of 5-azoaromatic derivatives of salicylic acid
Thus, EP-A-0 253 788 describes the preparation of 5-ASA in the following way, essentially:
Thus, salicylic acid is first reacted with the diazo salt of sulfanilic acid, and the 5-(para-sulfophenylazo)salicylic acid is then converted to 5-ASA by catalytic hydrogenation. The hydrogenation is done with hydrogen gas on a catalyst at elevated temperatures of above 50° C.
In this reaction, the fact that hydrogen gas must be employed is disadvantageous above all. Although hydrogenations with hydrogen gas are possible on an industrial scale, such processes are undesirable due to a danger of explosion, and extensive safety measures are required, which renders the process more expensive. Also, operation at elevated temperatures is not favorable for economic reasons. Moreover, the final product in the hydrogenation is relatively high in impurities and requires an enhanced expenditure for purification.
WO 86/03194 describes an electrochemical process for the preparation of various p-aminophenols and also of 5-ASA, for example. When interpreted for the production of 5-ASA, the process essentially proceeds according to the following reaction scheme:
The process must be performed at a temperature of above 50° C., and the preferred range of temperatures is at 70 to 100° C.
The process of WO 86/03194 has a drawback in that aniline, which is considered hazardous to health, is formed in the same proportion as p-aminophenol. Especially when the objective compound is intended for medical use, the aniline formed must be separated off to the extent that the strict legal limit values are met. This is difficult and involves high costs. Also, the process must be conducted at temperatures of clearly above 50° C., which is also undesirable for cost reasons. Further, it is evident from the Examples of the publication that the electrochemical reaction is incomplete, and the electrochemical reaction is followed by a completion of the reaction by the addition of sodium hydrosulfite. The added amounts of sodium hydrosulfite are too high to serve exclusively for the decolorization of the reaction product as stated in the publication. Rather, it is evident that another reasons for this addition is to complete the incompletely proceeded electrochemical reduction by a chemical reduction with sodium hydrosulfite.
Therefore, it has been the object of the present invention to provide a process for the preparation of p-aminophenols, especially 5-ASA, which does not have the drawbacks of the prior art and by which 5-ASA, for example, can be advantageously prepared inexpensively. In particular, the reaction shall also be conducted at low temperatures, since this reduces the formation of by-products.
This object is achieved by the subject matter of the claims.
The invention is based on the surprising finding that sulfonates of general formula
in which R
1
may be hydrogen, a C
1
-C
6
alkyl residue, a hydroxy, sulfonyl or amino group, or a halogen atom, the residue R
2
may be OR
5
or NHR
5
, wherein R
5
may represent hydrogen or a C
1
-C
4
alkyl group, and the residues R
1
may be the same or different, the residues R
3
and R
4
independently represent hydrogen atoms, C
1
-C
4
alkyl residues, halogen atoms, COOH groups, SO
3
H groups or NO
2
groups, or their salts, especially their alkali metal salts, can be reduced electro-chemically in a particularly advantageous way, which process can be operated at temperatures of below 50° C. The sulfanil products which are obtained as by-products have not been rated toxic, in contrast to the aniline products obtained in the process of WO 86/03194, and some of them are even employed therapeutically as antibacterial agents. Therefore, separation of the by-product to such a high extent as required when anilines are formed is not necessary in the process according to the invention, depending on the intended use. However, the products formed can always be said to be aniline-free.
According to the invention, in the electrochemical process for the preparation of a compound of formula I
it is preferred to use a compound of formula II in which at least three residues R
1
represent a hydrogen atom. Most preferably, all four residues R
1
represent a hydrogen atom. Also preferred are compounds of formula II in which the SO
2
R
2
group is in a para position with respect to the azo group. It is also particularly preferred that the residue R
2
represents an OH group. Thus, those compounds are particularly preferred in which all residues R
1
represent a hydrogen atom and the residue —SO
2
R
2
is an —SO
3
H group in a p-position with respect to the azo group.
Also particularly preferred are compounds in which the residue R
3
represents a hydrogen atom. Also preferred are compounds in which the residue R
4
represents a COOH group, which is in turn preferably in an ortho position with respect to the OH group. Salts of these compounds are also preferred.
Thus, as the most preferred compound of formula II, a compound of formula
or a salt thereof is employed in the process according to the invention.
The starting compounds of formula II can be prepared by per se known methods, as described in principle, for example, in EP-A-0 253 788. For the preparation of the above mentioned particularly preferred compounds of formula II, the starting compound is sulfanilic acid, while for the preparation of other compounds of formula II, the corresponding derivatives of sulfanilic acid or the corresponding p-aminophenols are employed.
The electrochemical reaction of the compound of formula II can be performed in a per se known manner. Preferably, the electrochemical reaction is performed in a device and with the use of electrodes as are described in EP-A-618 312, included herein by reference. It is also particularly preferred that the electro-chemical reaction is performed in a device and with the use of electrodes as are described in EP-A-778 360, included herein by reference. Unless explicitly stated otherwise in the present specification, the devices and process conditions as described in EP-A-618 312 und EP-A-778 360 are preferred for performing the electrochemical reduction of the compound of formula II to the compound of formula I.
The electrochemical reduction of the compound of formula II is preferably performed in solution, especially in an aqueous solution. Preferably, the pH value of the solution should be greater than 8, more preferably greater than 9.
In a so strongly alkaline solution, the compound of formula II will be present in an ionized form, so that the corresponding salts, especially the alkali metal salts may of course also be employed directly instead of the free acids. The pH value of the solution which is employed for the electrochemical reduction is preferably adjusted by the addition of an alkali metal hydroxide. Optionally, other compounds giving an alkaline reaction may also be employed.
It is particularly preferred to perform the electrochemical reduction according to the invention by using a three-dimensional cathode, especially a three-dimensional carbon cathode, which has a metal collector. Such cathodes are described in EP-A-618 312 and EP-A-778 360 and are also commercially available. A three-dimen
Dunlap Thoburn T.
Noveon IP Holdings Corp.
Wong Edna
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