Organic compounds -- part of the class 532-570 series – Organic compounds – Sulfonic acids or salts thereof
Reexamination Certificate
2000-04-19
2001-08-07
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Sulfonic acids or salts thereof
C562S030000, C562S042000
Reexamination Certificate
active
06271415
ABSTRACT:
This application is the national phase and PCT/EP98/06453 filed Oct. 12, 1998 now WO99/20604.
BACKGROUND OF THE INVENTION
The present invention relates to novel S-(4-biphenyl)-thiosulphuric acids and salts thereof, to a process for their preparation starting from S-(4-biphenyl)-sulphinic acids and salts thereof and the preparation of 4-mercaptobiphenyls from the S-(4-biphenyl)-thiosulphuric acids and their salts.
4-Mercaptobiphenyls are important intermediates for preparing pharmaceutically and agiochemilcally active compounds (see, for example, BE-A 887 423, U.S. Pat. No. 3,912,757 and WO 96/25 936). Some processes for preparing 4-mercaptobiphenyls are already known; however, all of them are unsatisfactory.
Thus, biphenylsulphonyl chloride can be reduced using amalgamated zinc, metallic tin or tin(II) chloride (see, for example, J.A.C.S. 66, 1674 (1944), Chem. Ber. 13, 386 (1880) and Ann. Univ. Marie Curie-Sklodowska, Section Aa, Volume Date 1966 No. 21, 65 to 83 (1967)). In all of these processes, waste waters containing heavy metal salts are produced, the disposal of which involves great costs.
It is also possible to diazotize 4-aminodiphenyl, followed by reaction with potassium ethyl xanthate and hydrolysis of the resulting thioester (see DE-A 23 17 142, pp. 34 to 35). Here, water-soluble nickel chloride has to be employed which likewise passes into the waste water, where the disposal involves high costs.
The reaction of p-hydroxybiphenyl with dimethylthiocarbamoyl chloride followed by Newman-Kwart rearrangement and finally hydrolysis (see J. Het. Chem. 15, 281 (1978) and WO 96/25 936) affords 4-mercaptobiphenyl only in a yield of 39%.
When 4-bromobiphenyl is reacted with sodium methyl sulphide or sodium ethyl sulphide and the resulting thioether is cleaved, good yields of 4-mercaptobiphenyl (for example 96% of theory) are only obtained when handling of the carcinogenic hexamethylphosphoric triamide is accepted (see Tetrahedron Lett. 21, 3099 (1980)). The use of other solvents, for example dimethylformamide, results in considerably lower yields of 4-mercaptobiphenyl (for example 67% of theory—see Synthesis 9, 751 (1983)).
The reaction of 4-bromobiphenyl with elemental sulphur and the cleavage of the reaction product with lithium aluminium hydride to give 4-mercaptobiphenyl requires the use of lithium aluminium hydride, which is difficult to handle (see Tetrahedron Lett. 13, 1283 (1972).
Also known are reduction processes for preparing 4-mercaptobiphenyl starting from aromatic sulphonyl chlorides and aromatic disulphides. However, reduction with hydrogen and noble metal catalysts requires temperatures of up to 150° C. and pressures of up to 150 bar (see EP-A 2755), and reduction with red phosphorus and iodine necessarily leads to phosphoric acid and hydrogen chloride being produced (see Chem. Ber. 99, 375 (1966)) and requires red phosphorus, which is difficult to handle.
Finally, it is known that Bunte salts, i.e. salts of the type R-S-SO3M (R=organic radical, M=monovalent metal) in aqueous-acidic media generally hydrolyse to give thiols (see Angew. Chem. 79, 525 (1967)). However, in the present case disulphides were produced.
DESCRIPTION OF THE INVENTION
We have now found S-(4-biphenyl)-thiosulfuric acids and salts thereof corresponding to the formula (I)
in which
A represents hydrogen, an equivalent of a metal atom or optionally substituted ammonium and
R and R′ independently of one another each represent hydrogen, C
1
-C
6
-alkyl, C
1
-C
6
-alkoxy or halogen.
In the formula (I),
A preferably represents hydrogen, sodium, potassium, ½ calcium, ½ magnesium, ½ zinc, NH
4
or NH
4
substituted by 1 to 4 C
1
-C
6
-alkyl radicals and
R and R′ independently of one another each represent hydrogen, methyl, ethyl, methoxy, ethoxy, fluorine or chlorine.
Particularly preferably, in the formula (I)
A represents hydrogen or sodium and
R and R′ represent hydrogen.
Furthermore, we have found a process for preparing S-(4-biphenyl)-thiosulfuric acids and salts thereof of the formula (I) which is characterized in that S-(4-biphenyl)-sulfinic acids or salts thereof of the formula
in which
A, R and R′ are as defined in formula (I),
are reacted with an aqueous bisulfite solution at a pH in the range from 2 to 7.
The preferred and particularly preferred meanings of A, R and R′ are also stated in formula (II) as in formula (I).
Some of the S-(4-biphenyl)-sulfinic acids and salts thereof of the formula (II) required as starting materials are known and can be prepared in a known manner or analogously thereto (see Ann. Univ. Marie Curie-Sklodowska, Section Aa, Volume Date 1966, No. 21, 49 to 64 (1967). The compound of the formula (II) in question does not have to be employed in pure form. It may, if appropriate, contain, for example, up to 25% by weight of the corresponding biphenylsulfonic acid and/or salts thereof. The compound of the formula (II) in question is preferably employed in the form of its sodium salt.
Very particular preference is given to using the sodium salt of S-(4-biphenyl)-sulfinic acid. Suitable aqueous bisulfite solutions are, in particular, aqueous alkali metal bisulphite solutions as are obtained, for example, when sulfur dioxide or sulfurous acid is introduced in an aqueous sodium hydroxide solution or an aqueous sodium carbonate solution or when sodium disulfite (Na
2
S
2
O
5
) is dissolved in water. In addition to hydrogen sulfite ions, the aqueous bisulfite Solution may additionally contain, for example, sulphite ions, sulfurous acid or dissolved sulfur dioxide. The aqueous bisulfite solution may, for example, be 10 to 50% by weight strength, and it is preferably 25 to 45% by weight strength. Based on 1 mol of the compound of the formula (II) employed, it is possible to use, for example, an amount of aqueous bisulfite solution which corresponds to 1 to 5 mols of bisulfite. This amount is preferably from 1.5 to 3 mols.
If, after S-(4-biphenyl)-sulfinic acid or sulfinate of the formula (II) and aqueous bisulfite solution have been combined, the reaction mixture has a pH outside the range of 2 to 7, it is necessary to bring the pH into the range from 2 to 7, in the simplest case by addition of aqueous hydrochloric acid.
The reaction with the aqueous bisulfite solution is preferably carried out at a pH of from 3 to 5 which can, if appropriate, be established by addition of acid, for example by addition of aqueous hydrochloric acid. The more acidic the reaction and the longer the treatment in the more acidic medium, the higher the risk that the reaction will not stop at the stage of the S-(4-biphenyl)-thiosulfuric acids and salts thereof of the formula (II) but proceed to the formation of the corresponding bisdiphenyl disulfides of the formula (IV) (see further below). This may be desired (see further below).
If appropriate, water, for example in an amount of up to 5, preferably up to 3, parts by weight, based on one part by weight of the compound of the formula (II) used, may be added to the reaction with the aqueous bisulfite solution.
The reaction with the aqueous bisulfite solution can be carried out, for example, at temperatures in the range from 50 to 200° C. Preference is given to 120 to 170° C. If the reaction is to be carried out at temperatures above the boiling point (at atmospheric pressure) of the reaction mixture, the use of closed and pressure-tight reactors is required. In such cases, pressures of up to 12 bar, for example, may occur.
After the reaction has ended, the resulting salt of the S-(4-biphenyl)-thiosulfuric acid can be separated off, for example, in crude form by cooling the reaction mixture, for example to room temperature, and filtering off and, if appropriate, drying the precipitate which is then present. If desired, the product can be purified further, for example by extraction with boiling ethanol.
From the resulting salt of a S-(4-biphenyl)-thiosulfuric acid, generally the sodium salt, the corresponding S-(4-biphenyl)-thiosulfuric acid can be liberated by methods known per se.
Eymann Wolfgang
Fiege Helmut
Ullrich Friedrich-Wilhelm
Bayer Aktiengesellschaft
Eyl Diderico van
Gil Joseph C.
Vollano Jean F.
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