DE1260468B - Process for the preparation of aminonitrophenols - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. CL:

C07d

German class: 12p-5

Number: 1260 468

File number: F 39484IV d / 12 ρ

Date of registration: April 13, 1963

Open date: February 8, 1968

The invention relates to a process for the preparation of aminonitrophenols in general Formula I.

Method of manufacture
of aminonitrophenols

NO,

in which R and R 'stand for identical or different alkyl groups or together with the nitrogen atom Be part of a 5-, 6- or 7-membered ring or a morpholino or thiomorpholino radical can, which is characterized in that 3-nitro-4-chlorophenol, whose hydrogen atom of the hydroxyl group is replaced by a methanesulfonyl, benzenesulfonyl or replaced p-toluenesulfonyl radical as a protective group is, with a secondary amine of the general formula

/ R

HN

where R and R 'are identical or different alkyl-NO.

O ₂ N

wherein the 3-chloro-4-nitrophenol, 5-chloro-2-nitrophenol or 3-chloro-2-nitrophenol at temperatures between 50 and 150 ⁰ C with a nitrogen base of the general formula. > .. ■

Applicant:

Paint factories Bayer Aktiengesellschaft,

5090 Leverkusen

Named as inventor:

Dr. Heinrich Pelster, 5090 Leverkusen;

Dr. Rudolf Heiss, 8501 Altenfurt

radicals or together with the nitrogen atom can also be part of a 5-, 6- or 7-membered ring or a morpholino or thiomorpholino radical, in the temperature range from 0 to 6O ⁰ C in dimethylformamide, acetonitrile, tetramethylene sulfone or their optionally alcoholic mixtures and then the Protective group is split off by heating with alkali hydroxide solution.

A separate older proposal relates to a process for the preparation of aminonitrophenols of the general type Formulas II, III and IV

NO ₂

OH

IV

this from 3-nitro-4-chlorophenol and amines of general formula

R '

R '

NH

NH

is implemented. .

It would have been conceivable, therefore, the aminonitrophenols of the general formula to prepare I in analogy. ,

In this reaction, however, there is generally no exchange of the chlorine for the amino group instead of. Only in a few cases, e.g. B. in the conversion of 3-nitro-4-chlorophenpl with dinajethylamine the desired product in traces. . *

809 S07 / 626

The preparation of the inventive Process required starting compounds is carried out by 3-nitro-4-chlorophenol in Presence of bases with halides of methanesulfo-, benzenesulfo- or p-toluenesulfonic acid, such as the Chlorides.

Then 1 mol of the compound protected on the hydroxyl group of the general Formula V

Cl

. V

wherein X is methanesulfonyl, benzenesulfonyl or p-toluenesulfonyl group, with 1 to 4 moles of an amine of the formula RR'NH at 0 to +60 ⁰ C, preferably at 15 to 26 ° C, in the stated solvents in order.

NO ₂

VI suctioned off, washed with water and then with ethanol. Yield: 1967 g (78% of theory), melting point 125 to 128 ^° C.

The methanesulfonic acid (3-nitro-4-chloro) -phenyl crystallized from ethanol as colorless crystals of melting point 127 to 128.5 ⁰ C.

B. 252 g (1 mol) of methanesulfonic acid (3-nitro-4-chloro) phenyl ester are suspended in 11% acetonitrile. 130 g (2.9 mol) of dimethylamine are then passed into the reaction mixture at 15 to 18 ° C. over the course of 7 hours, the mixture is stirred at room temperature overnight, the acetonitrile is distilled off in vacuo from the red solution, 200 ml of 40% sodium hydroxide solution, 500 ml of water and 500 ml of methanol were added and the mixture was refluxed for 1 hour. After cooling, the reaction mixture is adjusted to pH 6 with hydrochloric acid and the 3-nitro-4-dimethylaminophenol is extracted with ethyl acetate. After removing the solvent, a red oil is obtained, this is dissolved in 700 ml of ethanol and the hydrochloride of 3-nitro-4-dimethylaminophenol is precipitated therefrom by acidification with concentrated hydrochloric acid. It is then filtered off with suction and the hydrochloride is washed with ethyl acetate. Yield: 154 g (nearly colorless crystals), mp 19O ⁰ C (decomposition)..

To prepare the free base, 35 g

3 - nitro - 4 - dimethylaminophenol hydrochloride suspended in 500 ml of water, the mixture with sodium hydroxide solution adjusted to a pH of 6 to 7, extracted with ethyl acetate and the solvent distilled off in vacuo. Yield: 28 g of 3-nitro-4-dimethylaminophenol.

The compound is obtained as a dark red oil.

As amines of the general formula RR'NH, for example, dimethylamine, methylethylamine, methylpropylamine, Morpholine, piperidine, pyrrolidine, hexamethyleneimine and thiomorpholine are used will. Ethanol can be used as the alcohol.

The derivatives of the aminonitrophenols of the general formula VI thus obtained are extracted from the reaction mixture isolated. The group X is then re-saponified using customary methods cleaved.

However, the saponification can also be carried out directly in the reaction mixture without isolating the intermediate stage perform and the aminonitrophenols of general formula I in yields of mostly 60 isolate up to 80% of theory. The new compounds are intermediate products for manufacture of esters of phosphoric acid.

35

example 1

OH

Example 2

OH

NO ₂

There are 126 g (0.5 mol) of 3-nitro-4-chlorophenyl methanesulfonate suspended in 400 ml of acetonitrile, slowly 128 g with cooling at 20 ° C (1.5 mol) of piperidine was added dropwise and: Stirred for 2 days at room temperature. Then as in Example 1 worked up. The S-nitro ^ piperidinophenol hydrochloride is obtained in the form of almost colorless crystals. Yield: 95 g (74% of theory).

The free base is obtained analogously to Example 1 as a dark red oil (60 g).

Example 3

OHN

OH

NO ₂

NO ₂

60

A. 1736 g (10 moles) of 4-chloro-3-nitrophenol become dissolved in a solution of 475 g of sodium hydroxide and 3.5.1 of water and 1145 g in IVa hours (10 mol) of methanesulfonyl chloride are added dropwise so that the reaction temperature does not rise above 55.degree. For this purpose, stirring is continued for 5 hours and the precipitate from methanesulfonic acid (3-nitro-4-chloro) phenyl ester 126 g (0.5 mol) of 3-nitro-4-chlorophenyl methanesulfonate are obtained analogously to the examples reacted in 400 ml of acetonitrile with 130 g (1.5 mol) of morpholine. Yield: 75 g of S-nitro- ^ morpholinophenol hydrochloride in almost colorless crystals (58% of theory).

The hydrochloride is suspended in 400 ml of water, heated to 70 ° C. and the mixture is washed with sodium hydroxide solution adjusted to a pH of 6 to 7. The free base precipitates in crystalline form on cooling. 62 g 3-Nitro-4-morpholinophenol are in the form of

orange-red crystals with a melting point of 161 to 162.5 ° C were obtained.

Example 4

NO ₂

Analogously to Example 2, 1 mol of methanesulfonic acid S-nitro ^ -chlorophenyl ester is used reacted in acetonitrile at 15 to 20 ° C with 3 mol of hexamethyleneimine, stirred for a few days at room temperature and worked up. The hydrochloride of 3-nitro-4-hexamethyleneiminophenol precipitates from the ether-ether mixture with hydrogen chloride gas in colorless crystals. Neutralization gives the free base in the form of a dark red oil.

20th

Methanesulfonic acid (3-nitro-4-chloro) phenyl ester is used analogously to Example 4 reacted with pyrrolidine. The hydrochloride of 3-nitro-4-pyrrolidinophenol is made by introducing hydrogen chloride gas into the ethereal-ethanolic solution of the crude product in Preserved form of colorless crystals. The free base is neutralized with sodium hydroxide in Obtained in the form of dark red crystals. The compound crystallizes from benzene in dark red Crystals with a melting point of 94.5 to 96 ° C.

Example 6

174 g (1 mol) of 4-chloro-3-nitrophenol are dissolved in a solution of 40 g (1 mol) of sodium hydroxide in 70 ml of water and 300 ml of ethanol at about 30 ° C in the course of 1 to 2 hours with 190 g of p- Toluenesulfochloride added. After the exothermic reaction has subsided, the mixture is subsequently stirred at 30 to 35 ^° C. for 1 hour and, after cooling to room temperature, filtered off with suction. The residue is washed with ethanol. 240 g (73% of theory) of p-toluenesulfonic acid (3-nitro-4-chloro) phenyl ester with a melting point of 82 ^° C. are obtained.

164 g (0.5 mol) of p-toluenesulfonic acid (3-nitro-4-chloro) phenyl ester are dissolved in 400 ml of acetonitrile and ^{slowly added dropwise at 15 to 20 °} C. to 131 g (1.5 mol) of morpholine. After stirring overnight at room temperature, it is saponified and worked up analogously to Example 1. The 3-nitro-4-morpholino-phenol is obtained as a hydrochloric acid salt (yield: 78% of theory), from which the free base (mp 161 to 162 ° C.) is obtained in the usual way.

Claims (1)

Claim: Process for the production of tertiary aminonitrophenols, characterized in that that 3-nitro-4-chlorophenol, whose hydrogen atom of the hydroxyl group by a methanesulfonyl, Benzenesulfonyl or p-toluenesulfonyl radical is replaced as a protective group with a secondary amine of the general formula HN / R can wherein R and R 'represent identical or different alkyl radicals or, together with the nitrogen atom, also form part of a 5-, 6- or 7-membered ring, or a morpholino or thiomorpholino be in the temperature range from 0 to 6O ⁰ C in dimethylformamide, acetonitrile, tetramethylene sulfone or their optionally alcoholic mixtures are reacted and then the protective group is split off by heating with alkali metal hydroxide solution. «0» 507/62 «IM O BundadruckereiBerHn