DD155613A1 - PROCESS FOR PREPARING N- (3-NITROPHENYL) -ETHYLENEDIAMINE HYDROCHLORIDE - Google Patents

Abstract

N- (3-Nitrophenyl) -a-ethylenediamine hydrochloride can be prepared industrially simply and safely by reacting 3-nitroaniline, aluminum chloride and liquid ethylenimine in the order stated and in equimolar amounts to form an inert organic solvent such as benzene or toluene at temperatures of 30 to 60 degrees C, preferably from 30 to 45 degrees C, is added and reacted, the reaction mixture after completion of the reaction with water, the precipitate separated, this with a mixture of water and a water-immiscible organic solvent such as Essigsaeureaethylester, heated to boiling and the precipitate formed after cooling separates.

Description

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Title of the invention:

Process for the preparation of N - (3 - Kitrophenyl) ethylenediamine hydrochloride

Field of application of the invention:

The invention relates to a process for the preparation of N - (3 - nitrophenyl) ethylenediamine hydrochloride of the formula

HO ₂

r \

ν / - NH - CH ₂ - CH ₂ - KE ₂ . HCl

which is a valuable intermediate for the synthesis of 3 - / B - (m-nitrophenyl-amino) -ethyl-7-amino-2-hydroxy-1-phenoxy-propane hydrochloride.

Characteristic of the known technical solution:

The preparation of N-phenylethyldylenediamine and its phenyl-substituted derivatives has been described in a number of ways. Thus, N-phenylethylenediamine is obtained by hydrogenation of anilinoacetonitrile over nickel / kieselguhr in an autoclave (US Pat. No. 2,067,291 / T933_7),

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by hydrogenation of K - phenyl - IT ¹ , ll'-dibenzyläthylendiaiain of palladium in acetic acid (DEP 550 762 / I93O_7), in addition to bis - (2-anilinoethyl) - amine by treating K - (2-chloroethyl) - aniline with two days liquid ammonia]! (Chem. Ber. £ 0, 979, 986 / ~ 1937_7), upon heating N- / 1-hydroxyethyl 7-IT-phenylguanidine hydrochloride

with conc. Hydrochloric acid to 180 ⁰ C (DEP 446 547), or by reaction of aniline with ß - Bromäthylphthalimid and subsequent cleavage of the thereby resulting N - (2-Anilinoäthyl) - phthalimide by heating with aqueous hydrochloric acid at 130 ⁰ C (Fourneau, de Lestrange, Soc. Chim. France 1947, 827-839).

Substituted phenyl-substituted derivatives of R-phenylethylenediamine can also be prepared by reacting 2-bromoethylanine hydrobromide with the double molar amount of aniline or substituted aniline (J. Med. Chem., 852-857, I966-7). K - (o-toluyl) ethylenediamine can be obtained from o-toluidine ui-d A'thanolamin. (J.Pharm.Soc. Japan £ ?, I3I8-1321, / ~ 1955_7) ·

H - (4-chlorophenyl) ethylenediamine is obtainable by reduction of 4-chloroanilinohydroxamic acid or of 4-chlorophenylacetonitrile with lithium aluminum hydride (Arch. Pharm. (Weinbeim) 303 , 933-938 / ~ 197Ο_7). N- (2-nitrophenyl) - and N- (4-keto-phenyl) -ethylenediamine are obtained by reacting 2- or 4-isotrochlorobenzene with ethylenediamine in the presence of CuCl ₂ (J.Org. Chem. 10, 283-285 / T945_7).

Most previously known processes for the preparation of substituted phenyl in the derivatives of IT-Phenyläthylendianins based in the last or one of the preceding Eeaktionsstufen on the implementation of aniline derivatives with haloalkyl with elimination of

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Hydrohalic acids or water. The reaction conditions required for this include long reaction times, higher reaction temperatures and, in some cases, also an excess of aniline derivative for capturing liberated acids. The reaction of ethylenediamine with nitrochlorobenzene derivatives is not generally applicable and only allows the preparation of 2- or 4-Nitrophenylätbylendiamin.

N- (3-nitrophenyl) -ethylenediamine is so far only by reaction of 3-nitroaniline with ß-BromäthyIphthalimid and splitting of the thus formed N- (3-Nitroanilinoäthyl) phthalimide was prepared by heating with hydrochloric acid to I30 ⁰ C (Eourneau, de Lestrange, Bull. Soc. Chim. France, IW , 837-838)

 This method has several disadvantages.

Thus, the double molar amount of aniline derivative is to be used according to this method. Another disadvantage of the method is that the required for the reaction ß-Bromäthylphthalimid with greater energy and time must be prepared only from phthalimide and 1.2-dibromoethane. Finally, the process still involves the removal of the Phtbalimidrestes by heating with hydrochloric acid or hydrazine hydrate.

It is also known that N-Pbenyläthylendianin by \ introducing Ätbylenimin gas into a mixture of aniline and anhydrous aluminum chloride in tetralin or diphenyl at 180 ⁰ C (Coleman, Callen, J. Am. Chem. Soc. 68, 2006

or by heating ethylenimine with aniline and aniline hydrochloride (Doklady, Akad. SSSR, J5 <J, 489, 490 / 1948_7).

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The method described by Coleman and Callen of the reaction of aliphatic amines or aniline with Athylenimin in the presence of anhydrous AlCl-. has not yet been extended to the reaction with substituted aromatic amines.

According to the current state of knowledge of the literature 180 ⁰ C are required for the implementation of primary amines with Äthyleniinin under the conditions elaborated by Coleman and Callen. Furthermore, this method works with an excess of amine and gaseous A'thylenimin. The high reaction temperature means high energy gieaufwand, involves the risk of the formation of decomposition products in itself and leads to low yields. With the use of gaseous A'thylenimin a greater expenditure on equipment, disturbances in the reaction process and dangers are connected.

Nitrophenyläthylendiaminderivate, for example, the NO-pbenyl) - ethylenediamine can not be prepared by this method. It is known, that can take place during the heating of nitrobenzene with anhydrous AlCl., To about 200 ⁰ C explosions (3p. Dtscb. Former. Ges. 2 ^ _t 3522/189237, former. Ing. Techn. 48, 729 / T976J7 ).

Aniline derivative is formed even at temperatures of about 100 ⁰ C in toluene reacts with nitrobenzene AlCIo, wherein a next hydrogen chloride (Chem. 3. %%, I65O / ~ 1920_7). Personal observations and nitroaniline derivatives, for example, 3-nitroaniline, with AlCl in toluene at temperatures below 100 ⁰ C to form a dark decomposition products react.

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In addition, the addition compound of 3-kitroaniline with AlClO tends to form at temperatures above 45 ⁰ C a tough soil body ·

A common method for preparing a pure Aminbydrocblorids known is that the amine by suitable measures, such as recrystallization or distillation, purified, the so purified amine dissolves in an organic solvent and initiates hydrochloric acid until the acidic reaction or with a solution of hydrogen chloride in an organic solvent. This method is impractical for the preparation of pure K (3-keto-phenyl) -ethylenediamine hydrochloride, because of the low solubility of N- (3-nitrophenyl) -ethylenediamine in solvents suitable for its synthesis, benzene or toluene Extract solvent solvent and clean. Moreover, the purification of N- (3-nitrophenyl) ethylenediamine by distillation is practically impossible because of the high boiling point and the resulting decomposition.

Object of the invention:

The invention makes it possible to produce N- (3-nitrophenyl) ethylenediamine hydrochloride by a technically simple and safe process in good yields from 3-nitroaniline, AlCl 2 and ethyleneimine, which was previously not possible in this way and against its production According to the state of the art, this prior art prejudice already existed above.

It should also be emphasized that the reactants can be used in an equimolar ratio, which is important in the interest of a high yield.

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to look that under these conditions, pure N- (3-i7itrophenyl) - ethylenediamine hydrochloride is obtained in good yield, because Coleman and Callen have used amine and AlClO over & thylenimine in excess to avoid the formation of larger amounts difficult to separate polyamines.

The inventive method of working up the reaction mixture allows at the same time the removal of by-products of the reaction and the production of the Hydrocblorids with little time and material cost by using liberated by hydrolysis of AlCIo liberated hydrogen chloride for salt formation. Most of the unreacted in the reaction 3-nitroaniline can be recovered by concentration of the organic solvent and re-used after recrystallization in the study.

The process gives pure N- (3-nitrophenyl) ethylhexylB-diamine hydrochloride in good yield without additional purification operations.

Explanation of the nature of the invention

The invention has for its object to develop a technically simple and safe process for the preparation of N - (3-nitrophenyl) - ethylenediamine hydrochloride, which avoids the disadvantages of the previously known methods.

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According to the present invention, this is achieved in that 3-nitroaniline, aluminum chloride, and liquid ethyleneimine in the order indicated and in the equimolar amount relative to an inert organic solvent such as toluene or benzene at temperatures from 30 to 60 ⁰ C, preferably 30 to 4- 5 ⁰ C, is added and reacted, added to the reaction mixture after the reaction with water, separating the precipitate, heats it with a mixture of 7 / ater and a water-immiscible organic solvent such as ethyl acetate, to boiling and, after cooling, separates resulting precipitate.

Embodiment:

N - Q-nitrophenyl) - ethylenediamine hydrochloride

240 g (1.8 mol) of anhydrous aluminum chloride are added with stirring to a slurry of 247.8 g (1.8 mol) of 3-nitroaniline in 1.2 l of dry toluene, the temperature being optionally by cooling at a maximum of 35 ° C is being held. After stirring for one hour at 35 ⁰ C is allowed to the reaction mixture while maintaining this temperature 77.4 g (1.8 Hol) A'thylenimin is added dropwise and the mixture is stirred for a further 6 hours. After standing overnight, the mixture is stirred for 1 hour at 60 ⁰ C and then added 900 ml of water. To dissolve product adhering to the reaction vessel, the mixture is heated to boiling, then slowly cooled and sucked through a frit. The frit residue is heated to boiling point in a mixture of 900 ml of ethyl acetate and 3OO ml of water until solution has occurred. After cooling, it is sucked through a frit and the residue washed successively with in each case 150 ml of ethyl acetate and ethanol.

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After drying, 248 g (63.6 % of theory) of N- (3-nitrophenyl) ethylenedianine hydrochloride are obtained with the Scbmp. 246-252 ⁰ C. The product is ozentig by the analytical assay 99p ^.

Concentration of the toluene and ethyl acetate solution gives most of the unreacted 3-methaniline (60 g), so that the yield of Ii - (3-keto-phenyl) -ethylenediamine hydrochloride, based on reacted 3-nitroaniline, 83.9 % of theory.

Claims (1)

- 9 - 226461 Pat entanspruch: Verfabren for the preparation of N - (3-nitrophenyl) ethylenediamine hydrochloride durcb reaction of 3-nitroaniline with ethenylimine, dadurcb characterized in that the reactants 3-nitroaniline, anhydrous aluminum chloride and liquid etbylenimine in the specified order of friction and in equimolar ratio to an inert organic solvent , as toluene or benzene at temperatures of 30 to 60 ° C, preferably 30 to 45 ⁰ C, is added and reacted, the reaction mixture after the reaction with Y / asser added, the precipitate separated, this with a mixture of water and a with 7 / aer immiscible organic solvent, such as ethyl acetate, heated to boiling and the entsterenden after cooling down precipitate separates.