CH380743A - Process for the preparation of haloaminobenzoic acids or their functional derivatives - Google Patents

Description

  

  



  Process for the preparation of haloaminobenzoic acids or their functional derivatives
It is known that halo-nitro-benzoic acids or their esters with the usual reducing agents, such as iron / hydrochloric acid, zinc / hydrochloric acid, tin (II) chloride, ammonium sulfide, or by catalytic reduction with Raney nickel in the corresponding halogen can convert amino-benzoic acids or their esters. However, these methods have significant disadvantages.

   They are either easy to carry out or give poor yields, which are due to the fact that the reduction of the nitro group simultaneously eliminates the halogen bound in the nucleus, resulting in mixtures of amino and halogenoamino-benzoic acids that are difficult to separate. In the case of catalytic reduction with Raney nickel or mixed nickel catalysts, the reaction can stop at intermediate stages so that nitroso or hydroxylamino compounds and their secondary products, such as azo and hydrazo compounds, are obtained.



   It has now been found that the halonitrobenzoic acids or their functional derivatives can be converted practically quantitatively into the corresponding haloamino-benzoic acids or their derivatives if the respective nitro compound is used in the form of a 10 to 25% solution treated in a lower alcohol or ether and in the presence of a nickel-alumina catalyst at 40 to 150 "and under a hydrogen pressure of 80 to 120 atmospheres. Functional derivatives of the halo-nitro-benzoic acids are their salts, their esters or their amides. It is Z. B. also possible to use their hydrohalides in esters of basic alcohols.



   The hydrogenation products are worked up, for. B. in the usual way by evaporating the solvent and purifying the residue either by distillation, recrystallization or by reprecipitation.



   example 1
100 g of 4-chloro-2-nitro-benzoic acid are dissolved in 500 cm3 of methanol and neutralized with sodium hydroxide solution (19 g of NaOH, in 50 cm3 of water). The 4-chloro-2-nitro-benzoic acid first dissolves in methanol.



  When sodium hydroxide is added, only part of the salt formed dissolves in methanol, the other part precipitates and remains suspended in the methanol. The reaction mixture obtained in this way is placed in a 2-1 autoclave and mixed with 5 to 10 g of nickel alumina catalyst with a nickel content of 50 / w. Then hydrogen (100 atmospheres) is injected and heated to 80 to 100 C. After the pressure has been approved, work is done. After the catalyst has been filtered off, the mixture is concentrated, the residue is taken up in water and 4-chloro-2-aminobenzoic acid is precipitated with dilute mineral acid or acetic acid. The raw acid has a yellowish tinge, but can be recrystallized to a pure white substance or reprecipitated.



   Yield: 75 g (88axa of theory); F. 240.



   Example 2
500 g of methyl 2-chloro-4-nitro-benzoate are dissolved in 4 l of methanol and catalytically reduced with 40 to 50 g of nickel-alumina catalyst with a nickel content of 400 / o as in Example 1 in a 10-1 autoclave. After the catalyst has been filtered off, some of the methanol is evaporated.



  On cooling, methyl 2-chloro-4-aminobenzoate crystallizes out in long needles. The ester can be recrystallized from methanol.



   Yield: 420 g (95 "/. D. Th.); F. 106 C.



   Example 3
200 g of 2-chloro-4-nitro-benzoic acid (diethyl aminoethyl) amide hydrochloride are dissolved in 2 l of ethanol and 30 to 40 g of nickel-alumina catalyst with a nickel content of 60 / a are added. The hydrogenation conditions are: 100 atm at 40 to 45 C for six hours. After the catalyst has been filtered off, the ethanol is evaporated and the residue is taken up with 80 cm3 of warm water.



  The aqueous solution is treated with activated charcoal and then cooled with ice. The resulting crystal slurry is suctioned off and washed with acetone.



  After drying, the 2-chloro-4-amino benzoic acid (diethylaminoethyl) amino hydrochloride is obtained in the form of its dihydrate.



   Yield: 163 g (80% of theory); F. 51 C.



   Example 4
200 g of ethyl 2-bromo-4-nitro-benzoate are dissolved in 600 cm3 of methanol, 15 g of nickel alumina catalyst with a nickel content of 60% are added and the mixture is reduced under the conditions given in Example 1. Working up is carried out as in Example 2. The ethyl 2-bromo-4-aminobenzoate is obtained.



   Yield: 150 g (85 / o of theory); F. 83 C.



   Example 5
200 g of 2-chloro-4-nitro-benzoic acid-s-diethylamino-ethyl ester are dissolved in 1 l of di-n-propyl ether, treated with 30 g of nickel-alumina catalyst with a nickel content of 50 "/ o and at 40% After the catalyst has been filtered off, the propyl ether is stripped off and the residue is brought to pH 6 to 7. The aqueous solution is concentrated until crystallization occurs on cooling the 2-chloro-4-amino benzoic acid-ss-diethyl-aminoethyl ester hydrochloride (chloroprocaine hydrochloride).



   Yield: 155 g (75 of theory); F. 171 C.

 

Claims (1)

PATENT CLAIM Process for the production of halo-aminobenzoic acids or their functional derivatives by catalytic reduction of the halo-nitrobenzoic acids or their functional derivatives, characterized in that the halo-nitrobenzoic acids or their functional derivatives in the form of a 10 to 25 / o solution in a lower alcohol or Ether is used, a nickel-alumina catalyst is used as the catalyst and the reduction is carried out at 40 to 150 C and under a hydrogen pressure of 80 to 120 atmospheres.