DE2110614A1 - Arylazobenzenesulfonyl chlorides and processes for their preparation - Google Patents

Description

LAWYERS

Our no. 16 998

Pharmacia Aktiebolag Uppsala / Sweden

Arylazobenzenesulfonylchloride and processes for their preparation;

The invention relates to arylazobenzenesulfonyl chlorides general formula

(D

in which R ₁ , R ₂ , R ₁ , R 1, and R ₅ each represent a hydrogen or halogen atom, an alkyl, aryl, aralkyl, nitro or cyanide radical or the remainder of the formulas RCOO; - (CH ₂ ) _n COOR ₆ ; -CO NR ₇ R ₈ ; -OSO ₂ R _g ; -OR ₁₀ or COR ₁₁ , where R, Rg, R ~, Rg, R «, R ₁₀ and R _{11 are} each an alkyl or aryl radical and η is an integer from 0 to 3, where at least one of the radicals R ₁ and R, which has the formula R-COO-, R ₁ J is not a hydrogen atom when R _{1 has} the meaning of R-COO- and at least two of the radicals R ₁ to R, - have the formula R-COO, and salts thereof .

_2_ 21106H

The Arylazobenzenesulfonylchloride can be used as reagents for the qualitative and quantitative determination of primary and secondary organic amines such as / and peptides. They can also be used as intermediates in the manufacture of pharmaceuticals.

The compounds according to the invention contain chlorosulfonyl groups, those in the presence of primary and secondary amines, preferably in the presence of acid-binding Means to easily biHen the appropriate sulfonamides. The compounds also contain azo groups, which are strong chromophores and both the compounds themselves and also give the reaction products with amines a strong parbiness. The compounds according to the invention also contain ester groups, which optionally follow on from the aforementioned reaction can be hydrolyzed with amines to the corresponding phenolic hydroxyl groups. In the alkaline mediuiri these hydroxyl groups are present as anions, which means that the reaction products mentioned above give their light absorption spectrum change especially in the visible wave range. This enables an accurate quantitative Determination of the reaction products with the amines.

It is essential that the compounds of the invention do not have any free phenolic hydroxyl groups, as SuIfony! chlorides are easily absorbed under the influence of bases Phenols react and form stable acylsulfonic acid esters as secondary products »which the use of the Making compounds as a reagent impossible.

109838/1836

The compounds according to the invention can contain groups which modify the light absorption spectra of the compounds and those of the reaction products physically convey chemical properties that are suitable for separating the mixtures that arise when several components, which react easily with the compounds according to the invention, in the sample to be analyzed, e.g. biological Origin.

Leave the arylazobenzenesulfonyl chlorides according to the invention by chlorinating a compound of the general formula

SOo OMe (II)

produce, in the R. to R_ each of the above Have meaning and Me denotes a hydrogen or metal atom or an organic salt residue. The chlorinating agents which can be used are, for example, phosphorus pentachloride, phosphorus oxychloride, phosgene and Thionyl chloride. It is extremely beneficial to use thionyl chloride in the presence of a tertiary formamide, for example Dimethylformamide, to be used. The reaction is preferably carried out in the presence of an inert organic solvent, for example a chlorinated hydrocarbon or a solvent of the benzene series, such as benzene, toluene, Xylene or chlorobenzene.

1 0 9.8 3.8 / 18 36.

The compounds of formula II can be derived from the compounds of general formula

= N - (/ V> - SO ₉ OMe (III)

t f

* in R. - R ^ have the same meaning as the corresponding groups R ₁ - R ₅ in formulas I and II, where if one or more of the groups R ^ - R ₁ - in formulas I and II are RCOO- , the corresponding group or

f I

the groups R ^ - R ₁ - -OH, and Me has the above meaning, by treating the compounds of the formula III with an aylating agent which contains the radical R, prepare. An acid chloride of the formula R-CO-X, in which X is a chlorine atom, or an acid anhydride of the formula R-COO-CO-R is preferred. When an acid chloride is used, the reaction is carried out in the presence of an acid binding agent. When an anhydride is used, the reaction is preferably W in the presence of catalytic amounts of a mineral acid or an organic base such as pyridine, performed.

The group RCO- is preferably an acetyl group. if the group RCO- is an acetyl group, becomes the hydroxy compound preferably reacted with acetic anhydride, optionally in the presence of acetic acid.

10 983: 8/1836

Me preferably means an alkali metal atom. The compounds of formula III are new compounds that by reacting a compound of the formula

"J-

react with 4-diazobenzenesulfonic acid in an alkaline medium leave, after which the reaction product of the formula III obtained is separated off, for example in the form of an alkali metal salt, if the solubility properties permit.

Jj-Diazobenzenesulfonic acid can be obtained by diazotizing Sulfanilic acid obtained.

example 1

a) Potassium 4- (4-hydroxyphenylazo} benzalsulfonate

A solution of 69 g of sulfamic acid, 27.6 g of potassium carbonate and 800 ml of water was cooled to 10 ° C., after which 29.6 g of sodium nitrite dissolved in 80 ml of water were added. The solution was poured into 80 ml of concentrated hydrochloric acid and 500 g of ice with vigorous stirring and left to stand ^{at 0 ° C. for 10 to 15 minutes.} A cooled solution of 37.6 g of phenol, 52 g of potassium hydroxide and 400 ml of water was prepared and then the diazonium salt mixture was added with vigorous stirring. After 5 minutes the device was

ORfQINAL INSPECTED 10 9838/18 36

mixed heated, the previously precipitated azo pigment went into solution. Then 30 ml of concentrated acetic acid were added added and the mixture cooled and filtered. 122 g of potassium salt were obtained, which is a small amount Contained sodium sais.

b) Potassium 4- (4-azetoxyphenylazo) benzene sulfonate

110 g of the above product, 500 ml of acetic anhydride, 500 ml of acetic acid and 2 ml of sulfuric acid were heated to the boil, the salt going into solution. Qa3 Product soon began to crystallize, whereupon the mixture was cooled, diluted with ether, filtered and washed with ether became. Yield; 121 g.

c) 4- (4-Acetopnenylazo) -benzenesulfonyl chloride

ο 119 g of the above product were at 5 C in 350 ml

ihionyl chloride _w ml / true a

added quickly to cool the mixture. The temperature rose to 33 ° C, the cooling bath was removed after which and the temperature to 43 ⁰ C increased. The mixture was poured into ice water, the precipitate was filtered off and carefully washed with water and cold petroleum ether. Yield: 108 »5 g, melting point 127 to 129 ° C

Example 2

a) Potassium 4- (ii-Hydroxy-3-carbomethoxyphenylazo) benzene sulfonate

The title compound was obtained from 0.1 mol of methyl alkylate and 4-diazobenzenesulfonic acid prepared according to Example la. Yield: 33 g.

ORIGINAL INSPECTED 109838/1836

21106H

b) Potassium-ii-d-acetoxy ^ -earbomethoxyphenylazo) -

benzenesulfonate

The above product was used together with 150 ml of acetic anhydride, 20 ml of acetic acid and 6 drops of sulfuric acid are heated until all components are dissolved had. The solution was then cooled. 400 ml of filter were added and the precipitate was filtered off. Yield: 33.2 g.

c) if- {J {-Azetoxy-t {-carboiBethoxyphenylazo) -benzene sulfonyl chloride

14.1 g of the above product were slurried in 33 ml of dimethylformamide. 10 ml of thionyl chloride was added with cooling. After 2 minutes the solution was poured into cold water. After filtering, washing with water and petroleum ether, the product weighed 11.6 g. Melting point after recrystallization: 139 - I ¹ IO ⁰ C.

Example 3

Ί- ( H- acetoxy-2-earbomethoxyphenylazo) -benzenesulfonyl chloride

The title compound was obtained from methyl 3-hydroxybeiuGoat and ^ -diazobenzenesulfonic acid by combining the two Compounds, acetylation and chlorination according to Example 1 manufactured. Melting point after recrystallization 97 ~ 99 ° C.

example

a) Sodium 4- (2-benzenesulfonyloxy-14-hydroxyphenylazo) benzenesulfonate

From 0.1 mol of sodium sulfanilate, 150 ml of water, 7 Ί g

109838/1 836

-8- 21106U

NaNOp in 20 ml of water, 20 ml of concentrated hydrochloric acid and 120 g of ice were prepared according to Example 1 4-diazobenzenesulfonic acid. It became a cold solution of 2.5 S (0> 1 mol) 3 * benzenesulfonyloxyphenol and 8.7 g Sodium hydroxide prepared in 100 ml of water, whereupon the diazonium mixture was added with vigorous stirring. After about 5 minutes the mixture was washed with hydrochloric acid acidified. The acidic mixture was heated until all components had dissolved. The solution was allowed to cool slowly and crystallization occurred.

b) Sodium 4- (4-acetoxy-2-benzenesulfonyloxyphenylazo) benzenesulfonate

The above product, 120 ml of acetic anhydride d and 3 ml of pyridine were heated to the boil, the salt going into solution. The product crystallized on cooling the end. Thereafter, ether was added, the product was filtered off and washed with ether. Yield: 48.1 g.

c) 4- (4-acetoxy-2-benzenesulfonyloxypheny lazo) benzenesulfonyl chloride

46 ζ of the above product, 160 ml of methylene chloride, 4.2 ml of dimethylformamide and 11.5 ml of thionyl chloride were allowed to boil for 2 hours. The reaction mixture was poured into ice water and petroleum ether was added. The substance was filtered off and washed with water. Yield: 40 g, melting point after recrystallization 131-133 ° C.

10983 8/1836 originally inspected

-9- 21106 H.

Example 5

a) Sodium 4- (2-hydroxy-4-phenylphenylazo) - i

benzenesulfonate |

The title compound was prepared from 0.2 mol of p-phenylphenol and ¹ 4-diazobenzenesulfonic acid according to Example 4a).

Yield: 72 g.

b) Sodium 4- (2-acetoxy-5-phenylphenylazo) benzene sulfonate

70 g of the above product were ^{aylated according to Example 1} Ib). Yield: 64 g.

c) 4- (2-acetoxy-5-phenylphenylazo) -benzenesulfonyl chloride

62 g of the above product, 100 ml of benzene, 12 ml of dimethylformamide and 36 ml of thionyl chloride were left Simmer for 15 minutes. The solution was then cooled and poured into ice water. Petroleum ether was added and the product was filtered. Yield: 54 g, melting point after recrystallization 146 - 148 ° C.

Example 6

a) Potassium - ^ - ^ - hydroxy ^ -chlorphenylaio ^ benzene sulfonate

and A solution of 34.6 g (0.2 mole) sulfanilic acid / 13 g Potassium hydroxide in 300 ml of water was cooled to 0 ° C,

whereupon 14.8 g of sodium nitrite dissolved in 40 ml of water, j

were added «The solution was added slowly and under j

vigorous stirring in 40 ml concentrated sales acid and \

ORIGINAL INSFEC 109 838/1836

21106U

240 g of ice poured. Kan left the reaction mixture 15 Standing in the cold for minutes

Ea found a cold solution of 25.7 g (0.2 mol) of o-chlorophenol and 26 g of potassium hydroxide made in 200 ml of water, and the diazonium compound was added with vigorous stirring. After about 5 minutes the mixture became with Hydrochloric acid acidified and heated until all substances had gone into solution. When cooling down the product crystallized out. Yield: 71 g *

b) Potassium 4- ( ¹ i-acetoxy-3-chlorophenylazo) benzene sulfonate

71 g of the above product, 142 ml of acetic anhydride and 3.5 ml of pyridine were refluxed for 10 minutes. After cooling, ether was added, the product filtered off and washed with ether. Yield: 76.7 g

c) 4- (4-acetoxy-3-chlorophenylazo) -ben8olsulfonylchloride

75 g of the above product, 266 ml of benzene, 9 ml of dimethylformamide and 23.4 ml of thionyl chloride were refluxed for 1 hour. The reaction mixture was poured into ice water and petroleum ether was added. The substance crystallized out, was filtered off and washed with water, yield; 63.5 ß, melting point after recrystallization 128 - 130 ⁰ C.

Example 7
4 ~ (4-Acetoxy-3-acetylphenylazo) -benzene-ulfonyl chloride

The title compound was prepared from 0.2 mole of o-hydroxyacetophenone and 4-diazobenzenesulfonic acid by combining the two Compounds, acetylation and chlorination according to Example 6

ORiQINAL INSPECTED

109838/1838

-H- 21106U

manufactured. After treating the chlorination sea mixture with Ice water, the product was taken up in chloroform, the solution dried and evaporated. Yield: 23> 5 6 * Melting point after recrystallization 111-113 ° C.

Example 8

a) Potassium 4- (4 ~ acetoxy-3 ~ nitrophenylazo) benzene sulfonate

46 ε potassium 4- (4-hydroxy-3-nitrophenylazo) benzene sulfonate were acylated according to Example 6b). Yield: 40.7 g.

b) 4- (4-acetoxy-3-nitrophenylazo) -benzenesulfonyl chloride

39 g of the above compound were chlorinated according to Example 6c). Yield 29.5 g "melting point after recrystallization from 154 to 155.5 ⁰ C.

Example 9

4- (iJ-Acetoxy-S-dimethylcarbamoy / pheny lazo) -benzenesulfonyl chloride

The title compound was obtained from N, N-dimethyl-2-hydroxybenzamide and 4-diazobenzenesulfonic acid by combining the two compounds, acetylating and chlorinating according to Example 5 produced. Melting point after recrystallization 91 - 93 ° C.

109838/1836

Claims (5)

Patent claims: 1. Arylazobenzolsulfony! Chloride of the general formula ^R 2 V y N = N - / '' VSO Cl (I) in which R., R ₃ , R 1, R ^ and R_ each represent a hydrogen or halogen atom, an alkyl, aryl, aralkyl, nitro or cyanide radical or the remainder of the formulas RCOO; - (CHg) _n COOR ₆ ; -CO NR ₇ R ₈ ; -OSO ₃ R _g ; -0R _1Q or COR ₁₁ , where R, Rg, R ^, Rg> Rq * Rq and R .. each denotes an alkyl or aryl radical and H denotes an integer from 0 to 3, where at least one of the radicals R ₁ and R- has the formula R-COO-, R ₁ . means no hydrogen atom if R has the meaning of R-COO- and at most two of the radicals R ^ to R, - have the formula R-COO-, and their salts. 2. A method for preparing one of the compounds of claim 1, characterized in that one Compound of formula 109838/18 36 21106 H. 'R in which R ^, R, R, R. and R above meaning and Me denotes a hydrogen or metal atom or an organic salt residue, chlorinated. 3. The method according to claim 2, characterized in that thionyl chloride is used as the chlorinating agent . k. Process according to Claim 2 or 3 _S, characterized in that the chlorination is carried out in the presence of dimethylformamide. 5. Use of one of the compounds of claim 1 as a reagent for qualitative and quantitative determination of primary and secondary amines and as an intermediate in the manufacture of pharmaceuticals. par Fhamaoia Aktl «boltg Upptala / Sohw «d« n (D ».H.j! Wolff) Rtehtiarmtlt 10 9 8 3 8/1836