DE3245503A1 - Process for the preparation of alkylhydroxylamines - Google Patents

Abstract

Alkylhydroxylamines are prepared by reacting hydroxylamine with chloroformic acid esters, alkylating the resulting N-hydroxycarbamate, and hydrolysing the alkylation product.

Description

Process for the preparation of alkyl hydroxylamines

The invention relates to a process for the preparation of alkyl hydroxylamines by reacting hydroxylamine with chloroformic acid esters, alkylating the resulting N-hydroxy-carbamic acid ester and saponification of the alkylation product.

A number of processes are available for the preparation of alkyl hydroxylamines known. There is one possibility of producing e.g. O, N-dimethyl-hydroxylamine in the stepwise alkylation and partial saponification of hydroxylamine disulfonic acid or their alkali salts (see e.g. DE-AS 11 16 232, French patent application 12 63,547, U.S. Patent 3,336,371 and Japanese Patent Application 55/129248). This method However, the isolation of the N, O-dimethylhydroxylamine is lengthy because of the many process steps difficult and the yields are only moderate. The process therefore has no economic one Meaning.

There is another possibility for the production of alkylhydroxylamines in the direct implementation of Hydroxylamine. Will be according to the state The technology used hydroxylamine as a starting material, so it is a selective one Direct alkylation of hydroxylamine cannot be achieved using hydroxylamine suitable to protect, then gradually introduce the desired alkyl groups and finally to split off the protective group again. One such method is, for example described in DE-OS 2 113 355, in Chem. Ber. 100, 3463-3465 (1967), in Przem. Chem. 57 (1978) 5, 241-244; CA 89: 108408r (1978) and in J. Chem. Soc. 1947, 963-969 and in J. Org. Chem. 24, 431-433 (1959).

For example, DE-OS 2 113 355 describes a process for the preparation of N, O-dialkylhydroxylamines described, in which the hydroxylamine is first converted to an ald or ketoxime, the oximes are doubly alkylated and the corresponding quaternary immonium salts stiffened. The process described in the DE-OS, however, has the disadvantage that the immonium salts have a strong tendency to decompose, so that this process is carried out on a larger scale Scale is problematic for safety reasons.

This also has no technical significance in Przem. Chem. 57 (1958) 5, 241-244 for the preparation of alkyl hydroxylamines via hydroxamic acids, since pure hydroxylamine hydrochloride is assumed, which makes the process much more expensive.

The in Chem. Ber. 100, 3463-3465 (1957) presented method goes of N-hydroxy-N'-phenylurea or from N-hydroxyurea, easily accessible from hydroxylamine by reaction with phenyl isocyanate or urethanes are. The ureas are alkylated in stages and give the desired alkyl hydroxylamines saponified. The saponification is preferably carried out with aniline, in which case equimolar Amounts of diphenylurea accumulate, or by heating with alkali. In both Cases prepares the work-up of the alkyl-hydroxylamines, especially in such with lower alkyl radicals, technical difficulties.

Another method about the protected hydroxylamines is from J.Chem.Soc. 1947, 963-969 and from J.Org.

Chem. 24, 431-433 (1959). The method of the cited references treads the path via the N-hydroxy-carbamic acid alkyl esters. This path is however so far limited to the corresponding ethyl ester.

The disadvantage of this process is that the ethyl N-hydroxycarbamate is extremely water-soluble, which is complex and not practicable in technology Requires extraction with ether. In addition, all of the procedures carried out by run out of a protected hydroxylamine, the additional disadvantage that you are in this Case of pure hydroxylammonium salts as the source of hydroxylamine. Through the Use of pure hydroxylamine or its salts are those mentioned above The process is not very economical, which is why it has been widely used in technology to date the procedures presented did not take place.

There has now been made a process for the preparation of alkylhydroxylamines of the formula where R1 represents a straight-chain or branched, optionally substituted aliphatic radical or an optionally substituted cycloaliphatic radical and R2 represents hydrogen, a straight-chain or branched, optionally substituted aliphatic radical or an optionally substituted cycloaliphatic radical, by reacting chloroformic acid esters with hydroxylamine, alkylation of the N-hydroxycarbamic acid ester formed and saponification of the alkylation product found, which is characterized in that the reaction is carried out with an ammonium salt-containing, technical-grade hydroxylamine salt solution and, as chloroformic acid esters, those of the formula ClCOOR (II), in which 3 R3 is a straight-chain or branched one, optionally substituted aliphatic radical having more than 2 carbon atoms, an optionally substituted cycloaliphatic radical or an optionally substituted aromatic radical is used.

2 Possible radicals R1 and R are, for example: straight-chain or branched ones Alkyl radicals with 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, n-hexyl, iso-hexyl or heptyl, preferably methyl, ethyl, n- or iso-propyl; Cycloalkyl radicals with 3 to 12 carbon atoms, preferably 5 to 6 carbon atoms, such as cyclopentyl, cyclohexyl or Methylcyclohexyl, preferably cyclopentyl or cyclohexyl.

3 The remainder R3 can be, for example, a straight-chain or branched one Alkyl radical with more than 2 carbon atoms, preferably 3 to 10 carbon atoms, such as n-propyl, n-butyl, iso-butyl, tert-butyl, pentyl, hexyl or heptyl, are preferred n-Butyl, a cycloalkyl radical with 3 to 12 carbon atoms, preferably 3 to 6 carbon atoms, such as Cyclopentyl or cyclohexyl, and an aromatic radical with 6 to 10 carbon atoms, such as phenyl or naphthyl.

Possible substituents of the radicals R1 to R3 are, for example, which behave inertly under the given reaction conditions. For example are mentioned: alkyl radicals having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms, such as Methyl, ethyl, propyl, butyl, pentyl, hexyl or heptyl, halogens such as fluorine, chlorine or bromine, or the nitro group.

For example, are used as chloroformic acid esters in the inventive Processes can be used, called: n-butyl chloroformate, n-propyl chloroformate and phenyl chloroformate, preferably n-butyl chloroformate and n-propyl chloroformate.

Approximately 0.5 to 2, preferably 0.6 to 0.9, mol of chloroformic acid the process according to the invention is used per mole of hydroxylamine 4n.

As a technical hydroxylamine salt solution, e.g. a solution is used which was produced by the so-called modified Raschig process (cf. Ullmann, Vol. 13, pp. 169-172, Verlag Chemie Weinheim, New York 1977, 4th ed.).

The resulting crude hydroxylamine salt solution is acidic (approx. pH 0 to pH 5, preferably pH 0 to pH 1) and contains the molar ammonium sulfate Excess based on hydroxylammonium sulfate. For example, contains the raw solution in addition to about 1 mole of hydroxylammonium sulfate, 2 to 4 moles of ammonium sulfate.

The inventive reaction of hydroxylamine with chloroformic acid ester is usually at temperatures of about 10 to 1200C, preferably 40 to 80 "C, and in a pH range from approx. 3 to 7, preferably 5 to 6, particularly preferred at pH 6 carried out. The N-hydroxycarbamic acid ester almost separates out completely from the reaction mixture. The remainder of the N-hydroxycarbamic acid ester can then be isolated by simple extraction with a suitable solvent will. The following solvents can be used: methylene chloride, chlorobenzene, Diethyl ether, diisopropyl ether and di-sec-butyl ether, preferably methylene chloride. The solvents can be used for the extraction either individually or as a mixture with one another in- are set. The amount of solvent is not critical and can easily be determined by preliminary tests.

The alkylation of the N-hydroxycarbamic acid esters is carried out according to the known Methods such as those described in J. Chem.

Soc. 1947, 963-969. The Alkylation with the usual alkylating agents such as dialkyl sulfates, called dimethyl sulfate and diethyl sulfate, or the alkyl halides, may be mentioned Methyl iodide, methyl bromide and ethyl bromide.

Usually, about 0.8 to about 0.8 to be used per alkyl group to be introduced 4, preferably 1 to 2, particularly preferably 1.1 equivalents of alkylating agent in the process according to the invention. In general, the alkylation is at at a temperature of about 0 to 1200C, preferably at 20 to 80C. The alkylation is preferably carried out in an aqueous medium in the presence of an alkali, such as sodium hydroxide, carried out. It can be useful to use a phase transfer catalyst, such as Tetrabutylammonium bromide and / or zephirol (benzyldodecyldimethylammonium chloride) add to the alkylation mixture.

The subsequent saponification of the alkylation product is generally under aqueous-acidic conditions with mineral acids, preferably with concentrated ones. Hydrochloric acid. The reaction temperatures are about 80 to 1500C, preferably 100 to 1200C (see e.g. J. Amer. Chem. Soc. 20 (1898), 38-51; J. Chem.

Soc. 1947-969). The saponification of the alkylation product is long carried out until no more gas evolution can be observed. After distilling off of all volatile components are obtained in practically quantitative yield and in very high high purity the desired alkylhydroxylamines in the form of the corresponding salts.

Since the inventive method the alkyl hydroxylamines in very gives good yields and very high purities and since technical hydroxylammonium salt is used, how it arises with the modified Raschig process, can turn out, designed the process is particularly economical. It is particularly surprising that from of the technical raw hydroxylamine salt solution, the hydroxylamine selectively in addition to the high Excess ammonia can be reacted with the chloroformic acid esters.

Both 0-monoalkylhydroxylamines as well as O, N-dialkyl-hydroxylamines are produced. Have alkyl hydroxylamines great importance as intermediate products for active ingredients in the crop protection sector and in the field of veterinary and human medicine (see e.g. DE-AS 1 028 986 and DE-AS 1 210 793).

The process according to the invention is illustrated by the following examples explained without, however, limiting it to the scope of these examples.

Example 1 N-Methoxy-N-methyl-carbamic acid butyl ester The mixture was heated 600 ml of a technical raw solution from hydroxylamine production with a content of approx. 1 mole of hydroxylammonium sulfate and approx. 2.5 moles of ammonium sulfate per liter of solution 1 hour at 1000C. It was then cooled to 60 ° C. and washed with a 20% strength aqueous Sodium hydroxide solution adjusted the solution to a pH value of 6. At 600C one dripped within 15 min. 1 mol = 136.5 g of A 130 ml of butyl chloroformate added, with the pH value of 6 was kept. The mixture was stirred for 5 hours and cooled to room temperature and extracted once with 300 ml of methylene chloride. The extract was made over sodium sulfate dried and evaporated. 125 g of a pink oil were obtained which, according to gas chromatography after silylation was about 90% N-hydroxycarbamic acid butyl ester. The raw booty was 84%. The crude N-hydroxycarbamic acid butyl ester was placed in 300 ml of water. To this was added 1 ml of zephirol (benzyldodecyldimethylammonium chloride), dosed within of 2 hours at room temperature 2.1 mol = 264.6 g - 200 ml of dimethyl sulfate and then a solution of 2.3 mol = 92 g of sodium hydroxide at room temperature within 2 hours to 800 ml of water. The mixture was then stirred for 6 hours at room temperature, extracted once with 500 ml of methylene chloride. The extract was dried over sodium sulfate. The methylene chloride was first distilled off at normal pressure, then was at 13 Torr fractionally distilled. 105 g of a colorless one were obtained liquid of boiling point 770C / 13 Torr, which, according to gas chromatography, is 99.8% of N-methoxy-N-methyl-carbamic acid butyl ester duration. The yield was 65% of theory.

O, N-Dimethyl-hydroxylamine One put into 20 ml of concentrated hydrochloric acid 0.05 mol = 8.1 g of N-methoxy-N-methyl-carbamic acid butyl ester and heated the Mixture at 1000C until no more gas evolution could be observed. Afterward the volatile components were drawn off on a rotary evaporator and obtained in quantitative yield of the O, N-dimethyl-hydroxylamine hydrochloride in the form of a colorless, crystalline product with a melting point of 106-1080C.

Example 2 N-Ethoxy-N-ethyl-carbamic acid butyl ester The procedure the reaction was carried out as described in Example 1. It was used instead of the dimethyl sulfate Diethyl sulfate and obtained the N-ethoxy-N-ethyl-carbamic acid butyl ester in 62% yield as a colorless liquid with a boiling point of 900C / 10 Torr.

O, N-diethyl-hydroxylamine As described in example 1, the saponification of the butyl carbamic acid ester was carried out. One received in practical quantitative yield of O, N-diethyl-hydroxylamine chloride in the form of a colorless crystalline Product with a melting point of 121-123 ° C.

Example 3 N-ethoxycarbamic acid butyl ester The mixture was placed in 100 ml of water 0.25 mol = 33.3 g of N-hydroxycarbamic acid butyl ester and added 1 ml of zephirol (benzyldodecyldimethylammonium chloride) added. 0.26 mol = 40 g = was metered in at room temperature over the course of 2 hours 34 ml of diethyl sulfate and then at room temperature within 2 hours a solution of 0.29 mol = 11.6 g of sodium hydroxide in 100 ml of water.

The mixture was then stirred for a further 5 hours and extracted with 300 ml of methylene chloride and the extract dried over sodium sulfate. After removing the solvent 31 g of A 77% butyl N-ethoxycarbamate were obtained in the form of a colorless Oil.

N-ethoxy-hydroxylamine The saponification of the N-ethoxy-carbamic acid butyl ester analogously to Example 1 gave the N-ethyl-hydroxylamine in practically quantitative yields in the form of a colorless crystalline product with a melting point of 124-5 ° C.

Claims (6)

Process for the preparation of alkyl-hydroxylamines of the formula where R1 represents a straight-chain or branched, optionally substituted aliphatic radical or an optionally substituted cycloaliphatic radical and R2 represents hydrogen, a straight-chain or branched, optionally substituted aliphatic radical or an optionally substituted cycloaliphatic radical, by reaction of chloroformic acid esters with hydroxylamine, alkylation of the resulting N-hydroxycarbamic acid ester and stiffening of the alkylation product, characterized in that the reaction is carried out with an ammonium salt-containing, technical hydroxylamine salt solution and the chloroformic acid ester is those of the formula ClCOOR3 where R3 is a straight-chain or branched, optionally substituted aliphatic radical with more than represents two carbon atoms, an optionally substituted cycloaliphatic radical or an optionally substituted aromatic radical, is used. 2) Method according to claim 1, characterized in that one Hydroxylamine salt solution uses the ammonium salt in excess, based on the Hydroxylamine salt. 3) Process according to claims 1 and 2, characterized in that a hydroxylamine salt solution is used which, in addition to 1 mole of hydroxylammonium sulfate still contains about 2 to 4 moles of ammonium sulfate. 4) Process according to Claims 1 to 3, characterized in that as the chloroformic acid ester, phenyl chloroformate, n-butyl chloroformate or n-propyl chloroformate is used. 5) Process according to Claims 1 to 4, characterized in that the reaction of chloroformic acid ester with the technical hydroxylamine salt solution carried out in a pH range of 3 to 7. 6) Process according to Claims 1 to 5, characterized in that the reaction of chloroformic acid ester with the technical hydroxylamine salt solution carried out in a pH range of 5 to 6.5.