CZ20001460A3 - S- (4-Biphenyl) -thiosulfuric acids and their salts, process for their preparation and preparation of 4-mercaptobiphenyls - Google Patents

Abstract

S-(4-biphenyl)-thiosulfuric acids and their salts of the general formula I, where A represents hydrogen, the equivalent of a metal atom or optionally substituted ammonium and R and R' each, independently of one another, represents hydrogen, a C1-C6-alkyl group, a C1-C6-alkoxy group or halogen. A method for their preparation by reacting S-(4-biphenyl)-sulfinic acids and their salts with an aqueous solution of bisulfite at a pH of from 2 to 7. A method for the preparation of 4-mercaptobiphenyls by heating S-(4-biphenyl)-thiosulfuric acids and their salts in the presence of an aqueous solution of a strong acid and subsequent reduction of the biphenyl disulfide thus obtained.

Description

S- (4-biphenyl) -thiosulphuric acids and their salts, process for their preparation and preparation of 4-mercaptobiphenyls

Technical field

The invention relates to novel S- (4-biphenyl) -thiosulphuric acids and their salts, to a process for their preparation starting from S- (4-biphenyl) -sulfinic acids and their salts and to the preparation of 4-mercaptobiphenyls from S- (4-biphenyl) acids ) thiosulfate and their salts.

BACKGROUND OF THE INVENTION

4-mercaptobiphenyls are important intermediates for the preparation of pharmaceutically and agrochemically active compounds (see for example: BE-A 887 423, US-A 3 912 757 and WO 96/25 936). Some processes for preparing 4-mercaptobiphenyls are already known, but all are unsatisfactory.

Thus, biphenylsulfonyl chloride can be reduced using amalgamated zinc, metallic tin or stannous 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 You Give 1966 No.21, 65-83 (1967). In all of these processes, waste waters containing heavy metal salts are produced, the disposal of which is very costly.

It is also possible to diazotize 4-aminodiphenyl, after which it is reacted with potassium ethylxanthate and saponification of the resulting thioester (see DE-A 23 17 142, pp. 34 to 35).

• 9 9 «9 9

9 4

-9 9 9 9 4 5

4 4 9 4 5

9 9 4 4 4 5

4 4 4 4 4 4

9449444 44 »

9 9 9 9 9

9 9 9

Water-soluble nickel chloride has to be used here, which is similarly transferred to wastewater where disposal costs are high.

Reaction of p-hydroxybiphenyl with dimethylthiocarbomoyl chloride followed by a Newman-Kwart rearrangement and finally saponification (see J. Het. Chem. 15. 281 (1978) and WO 96/25 936) yields 4-mercaptobiphenyl in a yield of only 39%.

When 4-bromobiphenyl reacts with sodium methylsulfide or sodium ethylsulfide and the resulting thioether is cleaved, good yields of 4-mercaptobiphenyl (for example, 96% of theory) are obtained only when handling with carcinogenic hexamethylphosphoric triamide is accepted (see Tetrahedron Lett, 21, 3099 (1980)). The use of other solvents, such as dimethylformamide, results in significantly lower yields of 4-mercaptobiphenyl (e.g., 67% of theory - see Synthesis 9, 751 (1983)).

Reaction of 4-bromobiphenyl with elemental sulfur and cleavage of the reaction product with lithium aluminum hydride to give 4-mercaptobiphenyl requires the use of lithium aluminum hydride, which is difficult to handle (see Tetrahedron Lett, 13, 1283 (1972)).

Reduction processes for the preparation of 4-mercaptobiphenyl starting from aromatic sulfonyl chlorides and aromatic disulfides are also known. However, hydrogen reduction and noble metal catalysts require temperatures up to 150 ° C and pressures up to 15 MPa (see EP-A 2755), and red phosphorus and iodine reduction necessarily results in phosphoric acid and hydrogen chloride (see Chem. Ber. 99. 375). (1966) and requires red phosphorus,

9 9 »· · · · · difficult to handle.

Finally, it is known that salts of the type R-S-SOgM (R = organic residue, M = monovalent metal) in aqueous acidic medium generally hydrolyse to form thiols (see Angew. Chem.

79, 525 (1967)). In the present case, however, disulfides were produced.

SUMMARY OF THE INVENTION

We have now found S- (4-biphenyl) -thiosulphuric acids and their salts corresponding to the general formula (I)

R '

R (I) wherein

A represents hydrogen, a metal atom equivalent or an optionally substituted ammonium; and

R and R 'are each independently C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy or halogen.

In formula (I), preferably represents hydrogen, nitrogen, potassium,

1/2 calcium, 1/2 magnesium, 1/2 zinc, NH4 or NH4 substituted with 1 to 4 C1-C6-alkyl radicals and • ttt tttt tttt

4 · tttt tttt ttttt ttttt tttt tttt ttt ttt

R and R 'each independently represent hydrogen, methyl, ethyl, methoxy, ethoxy, fluorine or chlorine.

Particularly preferably in formula (I)

A is hydrogen or sodium; and

R and R 'are hydrogen.

In addition, the present invention provides a process for the preparation of S- (4-biphenyl) -thiosulphuric acids and their salts of the general formula (I), characterized in that S- (4-biphenyl) -sulfinic acids or their salts of the general formula (II)

O-A (II) in which

A, R and R ', as defined in formula (I), are reacted with an aqueous bisulfite solution at a pH in the range of 2 to 7.

The preferred and particularly preferred meanings of A, R and R 'are the same in formula (II) as in formula (I).

S- (4-Biphenyl) -sulfinic acids and their salts 444 4 4 9 4 9 4 4

4 4 4 4 4 4

9 4 9 4 9 ···· 4 4 99 ·

9 9 4 4 4 4 4 9 9

The formula (II) needed as starting materials is known and can be prepared in a known manner or analogously (cf. Ann. Univ. Marie Curie-Sklodowska, Section Aa, Volume Date 1966, No. 9). 21, 49-64 (1967) The compound of formula (II) need not be used in pure form and may, if appropriate, contain, for example, up to 25% by weight of the appropriate biphenylsulfonic acid and / or salts thereof. (II) is preferably used in the form of its sodium salt.

The sodium salt of S- (4-biphenyl) -sulfinic acid is particularly preferred.

Suitable aqueous bisulfite solutions are especially aqueous alkali metal bisulfite solutions which are obtained, for example, by introducing sulfur dioxide or sulfuric acid into an aqueous solution of sodium hydroxide or an aqueous solution of sodium carbonate, or when sodium pyrosulfite (Na 2 S 2 O 4) is dissolved in water. In addition to the hydrogen sulphite ions, the aqueous hydrogen sulphite solution may additionally contain, for example, sulphite ions, sulfuric acid or dissolved sulfur dioxide. For example, the aqueous bisulfite solution may have a concentration of 10 to 50% by weight and preferably has a concentration of 25 to 45% by weight. With respect to 1 mole of the compound of formula (II) used, it is possible, for example, to use an amount of an aqueous bisulfite solution corresponding to 1 to 5 moles of bisulfite. This amount is preferably from 1.5 to 3 mol.

If, after combining the S- (4-biphenyl) sulfinic acid or sulfinate of formula (II) and the aqueous bisulfite solution, the reaction mixture has a pH outside the range of 2 to 7, it is still necessary to adjust the pH to the range 2 to 7.

Φ Φ φ φ φ φ φ φ φ φ

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Φ Φ «· φ <

Φ Φ Φ ·

Φ Φ Φ Φ φ φ φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ case by adding an aqueous hydrochloric acid solution.

The reaction with the aqueous bisulfite solution is preferably carried out at a pH of from 3 to 5, which, if necessary, can be adjusted by the addition of an acid, for example by the addition of an aqueous hydrochloric acid solution. The more acidic the reaction and the longer the treatment in the acidic environment, the higher the risk that the reaction will not stop at the acid stage

S- (4-biphenyl) -thiosulfates and their salts of formula (II), but will continue to form the corresponding bisdiphenyldisulfides of formula (IV) (see below). This may be desirable (see text 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 formula (II) used, may be added to the reaction with an aqueous bisulfite solution.

The reaction with the aqueous bisulfite solution can be carried out, for example, at temperatures ranging from 50 to 200 ° C. Preferred is 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, it is necessary to use closed and pressure-tight reactors. In these cases pressures up to 1.2 MPa may occur.

Upon completion of the reaction, the resulting S- (4-biphenyl) -thiosulphuric acid salt may be separated, for example, in crude form by cooling the reaction mixture, for example, to room temperature and filtering and, if appropriate, drying the precipitate which is then present. If desired, the product can be further purified, for example, by extraction using 9 9 · · · 9 9

9 9 9 99

9

9 · 9 9 * ι>

of boiling ethanol.

From the resulting S- (4-biphenyl) -thiosulphuric acid salt, generally the sodium salt, the corresponding S- (4-biphenyl) -thiosulphuric acid can be liberated using known methods. Preferably, the respective thiosulphuric acid is liberated from the salt of the thiosulphuric acid by reaction on an acidic ion exchanger.

Of the free S- (4-biphenyl) -thiosulphuric acids, any salts of the respective S- (4-biphenyl) -thiosulphuric acid can be prepared by neutralization with an appropriate base.

A process for the preparation of 4-mercaptobiphenyls (III) has also been found with the general formula

(III) in which:

R and R 'are as defined in formula (I), which is characterized in that S- (4-biphenyl) -thiosulphuric acids and their salts, respectively, correspond to those of formula (I). of formula (I), heat in the presence of an aqueous solution of a strong acid and the resulting bisdiphenyldisulfide of formula IV

• · ♦

in which • 9 9 · 9

9 9

9 9

R and R 'are defined as in formula (I), reduced.

Suitable aqueous solutions of strong acids are, for example, sulfuric acid at concentrations of, for example, 0.05 to 30%, preferably 1 to 30% by weight. For example, the amount of acid may be selected such that the pH of the resulting reaction mixture is in the range of 0 to 2. Temperatures for treatment with an aqueous strong acid solution may be, for example, in the range of 50 to 200 ° C, preferably in the range of 80 to 170 ° C.

The prepared bisdiphenyldisulfide can be isolated from the reaction mixture by cooling the reaction mixture to, for example, room temperature and filtering and optionally drying the obtained precipitate.

The reduction of the bidiphenyldisulphide of the formula (IV) to the corresponding 4-mercaptobiphenyl of the formula (III) can, for example, be carried out according to known methods such as sodium borohydride reduction (see DE-A 44 20 777), catalytic reduction with molybdenum sulfide catalyst at high pressures. (see J. Org. Che. 24, 1598 (1959)) or by catalytic reduction with palladium, Raney cobalt or Raney nickel catalysts at high pressures in a liquid, two-phase system (see DE-A 17 68 421 and JP-A (Japanese Published Specification) 60 199 871).

However, this reduction is preferably carried out as a catalytic reduction by metal catalysts of the 8th subgroup φφ φ φ

Φ Μ

ΦΦ ΦΦ

Φ Φ Φ ·

Φ Φ Φ ·

Φ Φ Φ ·

Φ ΦΦΦΦ

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9999 of the periodic system of elements or Raney-type catalysts in an alcoholic solution and in the presence of alkaline compounds, for example at temperatures ranging from 20 to 200 ° C and pressures up to 5 MPa. These reductions form part of the subject-matter of another patent application, which was submitted simultaneously by the same applicant.

In the process for preparing 4-mercaptobiphenyls of formula (III) from diphenylsulfinic acids and their salts of formula (II) according to the present invention, it is not necessary to isolate the resulting S- (4-biphenyl) thiosulphuric acids and their salts of formula (I). In reaction with an aqueous bisulfite solution to prepare the bisdiphenyldisulfides of formula (IV), it is possible to adjust the appropriate pH during or after the reaction and / or to use sufficiently long reaction times to proceed directly to the corresponding bisdiphenyldisulfide of formula (IV) without isolation of S- (4). (biphenyl) -thiosulfate or salts thereof of formula (I).

The bisdiphenyldisulfide of formula (IV) need not be used in pure form for reduction, especially when the reduction is to be carried out in the preferred manner described above. For example, it is possible to mix the wet filter cake obtained with alcohol, the alkali compound and the catalyst, and then carry out the hydrogenation.

The S- (4-biphenyl) thiosulphuric acids and their salts of formula (II) required for the preparation of the 4-mercaptobiphenyls of formula (III) of the present invention may also be prepared in situ by reaction of the corresponding diphenyl-4-sulphonyl chloride of formula 9 9

9

9999 • 99

9 9 9 9

-ΙΛ · · · · · ·

- ΙΟ ** * · tt tt tt tt tt tt tt tt tt • tt tt tt tt tt

R R 'in which

R and R 'are defined as in formula (I) at a pH in the range of 6 to 10 with an aqueous bisulfite solution at 40 to 80 ° C, followed by addition of SO 2 and heating to 70 to 180 ° C. The bisdiphenyldisulphides of formula (IV) are obtained directly without the isolation phase of the respective S- (4-biphenyl) -sulfinic acids or their salts of formula (II) and without isolation of the corresponding S- (4-biphenyl) -thiosulphuric acids or their salts of formula (I) ) ·

In this method, the pH during the reaction with the aqueous bisulfite solution is preferably from 7.5 to 9 and the temperature after SO 2 introduction is preferably from 90 to 160 ° C. If the reaction is carried out above the boiling point of the reaction mixture (at atmospheric pressure), sealed and pressure-tight reaction vessels must be used.

The present invention provides a process for preparing 4-mercaptobiphenyls of formula (III) via the corresponding novel S- (4-biphenyl) -thiosulphuric acids or salts thereof of formula (I), which has a number of advantages. No waste water containing heavy metals is produced, the 4-mercaptobiphenyls of formula (III) are obtained with high yields, no special precautions are required for handling carcinogenic solvents, and no reagents are used that are difficult to handle, are not produced -

AND

11 φ φ φ vedlejší φ φ φ φ φ--φ φ φ φ φ φ φ φ φ žádné žádné žádné žádné žádné žádné žádné žádné žádné žádné žádné žádné žádné ♦ žádné ♦ ♦ ♦ ♦ ♦ ♦♦ ♦ ♦ The sum of these positive effects is particularly surprising because Angew. Chem. 79, 525 (1967) discloses acid hydrolysis of the Bunte salts as a generally suitable method for preparing thiols. That is not the case here. Under the conditions described, bisdiphenyldisulfides were formed. These substances had to be reductively cleaved to obtain mercaptan. It is particularly surprising that, despite many steps, biphenylsulfonyl chlorides can be converted in this way via S- (4-biphenyl) thiosulphuric acids to 4-mercaptobiphenyl in high yields.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

Preparation of a compound of formula (I) from a compound of formula (II).

140 g of diphenylsulfinic acid sodium salt (66.8% by weight, in addition to 10.5% by weight of diphenylsulphonic acid sodium salt) were mixed into 200 ml of water with 210 ml of aqueous bisulfite solution (concentration 39% by weight). The pH was adjusted to 4 using 37% aqueous hydrochloric acid. The mixture was heated in an autoclave to 150 ° C and then stirred at 150 ° C and a pressure between 0.41 MPa and 0.43 MPa for 2 hours. hours. After cooling to room temperature, the resulting suspension was filtered off with suction and the isolated solid was dried. 126.4 g of crude S- (4-biphenyl) -thiosulphuric acid as the sodium salt were obtained in a yield of 78% of theory. In addition to acid 9 9 99 9 9 9 9 9 9 9

999 9,999 99,999 9

-, _Ο ♦ · · ♦ · · 9 9 9 9

The entrained biphenylsulfonic acid was detected as a by-product using HPLC unreacted sulfinic acid, but no bis-diphenyldisulfide was detected. The recovered solid was extracted with boiling ethanol. Upon cooling the extract, the sodium salt of S- (4-biphenyl) thiosulphuric acid precipitated as the monohydrate. The isolated product had IR absorption bands characteristic of the Bunte salts. The following results (calculation / found) were obtained by elemental analysis:

C 47.1 / 47.4; H 3.6 / 3.6; 0 20.9 / 20.0; S 20.9 / 20.9;

At 7.5 / 8.0.

Example 2

Preparation of a compound of formula (IV) from a compound of formula (I).

100 ml of a 10% by weight aqueous sulfuric acid solution was metered in and heated to 100 ° C and then 17 g of the crude material of Example 1 was added. After a short time at pH 0 a white solid precipitated out of solution. slightly cloudy. After stirring at 100 ° C for 30 minutes, the batch was cooled to room temperature and then filtered with suction. The isolated solid was dried at 50 ° C and 0.01 MPa to obtain 8.2 g of bisdiphenyldisulfide with a content of 86.3% by weight (HPLC). S- (4-Biphenyl) -thiosulphuric acid was no longer detectable.

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9 9

9 9 9

99999 9

9 9

9

Example 3

Preparation of a compound of formula (IV) from a compound of formula (V).

440 ml of an aqueous bisulfite solution (concentration 39% by weight) and 550 ml of water were metered in with 125 ml of an aqueous solution of sodium hydroxide (concentration 45% by weight) and mixed with 2.2 g of triethylbenzylammonium chloride. The mixture was heated to 60 ° C. 289.5 g of diphenyl-4-sulfonyl chloride (96% by weight) was introduced over one hour while the pH was maintained at 8 by the addition of 45% by weight aqueous sodium hydroxide solution. PH control was also performed during 3 hours of further stirring. In an enameled autoclave, the reaction mixture was then mixed with 80 mL of sulfur dioxide and heated at 130 ° C for 3 hours. The batch was stirred at 130 ° C and a pressure between 0.44 and 0.69 MPa for 6 hours. During this time, the S- (4-biphenyl) -thiosulphuric acid phase took place. The mixture was then cooled to room temperature and degassed and the resulting suspension was filtered off with suction. The filter cake was dried to obtain 237.4 bisdiphenyldisulfide having a content of 78.3% by weight. This corresponds to a yield of 91.2% of theory.

Example 4

Preparation of a compound of formula (III) from a compound of formula (IV).

314 g of bisdiphenyldisulphide (obtained according to Example 3) were suspended as a wet filter cake with 1 liter of ethanol and mixed with 44 g of sodium hydroxide and 24.7 g of hydride

99 99

9

9

9

9 9 9 9 9 • 99 99 · 9 9 ·· ·· sodium. The resulting mixture was stirred at 70 ° C for 6 hours and the resulting suspension was then filtered with suction at 70 ° C. The filter residue was washed with 250 mL of ethanol. The filtrate and washings were combined and adjusted to pH 1 using 900 mL of 7 wt% aqueous hydrochloric acid. The precipitated product was filtered off with suction, washed with 500 ml of water and dried. 174.2 g of a white powder with a melting point of 111-113 ° C were obtained. The 4-mercaptobiphenyl content in the powder was 98.3% by weight (determined by iodometry). This corresponds to a yield of 83.6% of theory, based on the diphenyl-4-sulfonyl chloride used.

Example 5

Preparation of a compound of formula (III) from a compound of formula (IV).

270 g of bisdiphenyldisulphide were prepared as in Example 3 and, as a wet filter cake, suspended in 800 ml of ethanol and mixed with 44 g of sodium hydroxide and 5.5 g of Raney nickel. In the autoclave, the mixture was heated to 80 ° C and then hydrogen was applied at 1 MPa. After 4 hours the hydrogen uptake was stopped. The batch was cooled and degassed. After filtration with suction at 60 ° C, the mother liquor was acidified with 840 ml of a 5.4% by weight aqueous hydrochloric acid solution and the product precipitated. The product was filtered off with suction, washed with 250 ml of water and dried. 178.8 g of a white powder with a melting point of 110 to 112 ° C were obtained. The 4-mercaptodiphenyl content was 91.8% by weight (iodometrically determined). This corresponds to a yield of 80.1% of theory, based on the diphenyl-4-sulfonyl chloride used.

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PATENT CLAIMS

Claims (10)

S- (4-biphenyl) -thiosulphuric acids and their salts, of general formula (I), s-so ₃ -a (I), R R 'in which A is hydrogen, a metal atom equivalent or optionally substituted ammonium; R and R 'are each independently hydrogen, C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy or halogen. Acids and salts according to claim 1, characterized in that in formula (I) A represents hydrogen, sodium, potassium, 1/2 calcium, 1/2 magnesium, 1/2 zinc, NH 4 or NH 4, which is substituted with 1 to 4 C 1 -C 8 -alkyl residues and R and R 'each independently represent hydrogen, methyl, ethyl, methoxy, ethoxy, fluorine or chlorine. Process for the preparation of S- (4-biphenyl) thiosulphuric acids and their salts according to claim 1, characterized in that the acids S- (4-Biphenyl) -sulfinic acids or salts thereof of formula II O-A (Π) in which A, R and R 'are as defined in claim (I), reacted with an aqueous bisulfite solution at a pH in the range of 2 to 7. The process according to claim 3, characterized in that 1 to 5 moles of bisulfite per mole of the compound of formula (II) are used and the reaction with aqueous bisulfite solution is carried out at temperatures ranging from 50 to 200 ° C. 5. A process for the preparation of 4-mercaptobiphenyls of general formula (III) SH R in which R and R 'are defined as in claim 1, - 17 · <· 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 characterized in that the acids S- (4-Biphenyl) -thiosulphate and their salts, corresponding to the compounds of claim 1, obtained by reacting S- (4-biphenyl) -sulfinic acids or their salts of formula (II) from claim 3 with an aqueous bisulfite solution at pH 2 to 7, are heated in the presence of an aqueous solution of a strong acid and the resulting bisdiphenyldisulfide of formula (IV) wherein: R and R 'are as defined in claim 1, are reduced. The process according to claim 5, wherein the aqueous solution of the strong acid used is an aqueous solution of sulfuric acid at a concentration of 0.05 to 30% by weight and the pH of the reaction mixture is maintained in the range of 0 to 2. The process according to claims 5 and 6, characterized in that the heating in the presence of an aqueous solution of a strong acid is carried out in a temperature range of 50 to 200 ° C. 8. Method according to claims 5 to 7, ΦΦ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující vyznačující Raney cobalt or Raney nickel. Process according to claims 5 to 8, characterized in that S- (4-biphenyl) -thiosulphuric acids and their salts of the general formula (I) are not isolated. Process according to claims 5 to 9, characterized in that the acids S- (4-Biphenyl) -thiosulfates and their salts of formula (II) are prepared in situ by reaction of the corresponding diphenyl-4-sulfonyl chloride of formula (V) R and R 'are as defined in claim 1, at a pH ranging from 6 to 10 with an aqueous bisulfite solution at 40 to 80 ° C, followed by addition of SO 2 and heating to 70 to 180 ° C.