WO2000032564A1

WO2000032564A1 - Method of producing hydroxamic acid esters

Info

Publication number: WO2000032564A1
Application number: PCT/EP1999/009121
Authority: WO
Inventors: Paul Hanselmann; Stefan Hildbrand
Original assignee: Lonza Ag
Priority date: 1998-12-03
Filing date: 1999-11-25
Publication date: 2000-06-08
Also published as: AU1386300A

Abstract

The invention relates to hydroxamic acid esters of general formula (I), wherein R is C1-6 alkyl and R1 to R3 independently is hydrogen or C¿1-4? alkyl. Said esters are produced from the corresponding esters in a one-pot method by reacting them with a hydroxylammonium salt and then with a dialkyl sulfate or alkyl chloride. The inventive compounds are suitable as blocking agents for isocyanates.

Description

Process for the preparation of hydroxamic acid esters

The invention relates to a process for the preparation of hydroxamic acid esters of the general formula

wherein RC, _ _£ - alkyl and R ¹ to R ^{3 are} independently hydrogen or C, ^ - alkyl.

C, _ "- alkyl here and below are to be understood to mean all linear or branched primary, secondary or tertiary alkyl groups having 1 to n carbon atoms, that is to say C, _ ₆ - alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl , sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, neopentyl, hexyl or isohexyl.

It is known that some derivatives of hydroxylamine such as hydroxamic acid esters and oximes can be used as agents for the reversible blocking of isocyanates (WJ Mijs et al., J. Coatings Technol. 1978, 50, 58-64; E. Querat et al., Angew. Makromol. Chem. 1994, 219, 185-203). For this purpose, the methacrylic hydroxamic acid benzyl ester and the methacrylic hydroxamic acid allyl ester were used in particular. These compounds were prepared by reacting the commercially available alkyl methacrylates with hydroxylamine hydrochloride and then with an appropriate reactive halide (for example benzyl chloride). However, this process is less suitable for the production of simple hydroxamic acid alkyl esters, such as, for example, methacrylhydroxamic acid methyl ester.

The object of the present invention was therefore to provide a process for the preparation of the hydroxamic acid alkyl esters (I) defined above and in particular of the methyl methacrylate hydroxamic acid. According to the invention, this object is achieved by the method according to claim 1.

It has been found that hydroxamic acid esters have the general formula

wherein RC, _ ₆ -alkyl and R ¹ to R ³ independently of one another denote hydrogen or C, _^ , - alkyl from esters of the general formula

wherein R 'is C _M - alkyl, and R ¹ to R ³ have the meanings mentioned above, to isolate by reaction with a Hydroxylammomumsalz with the addition of an aqueous strong base and anschhessende Alkyherung of Hydroxamsäuresalzes thus obtained, without this, with a dialkyl sulfate of the general formula (RO) ₂ SO ₂ (III) or an alkyl chloride of the general formula R-Cl (IV), in which R in each case has the meaning given above, can be prepared in the presence of a base.

Hydroxylamine hydrochloride (= hydroxylammonium chloride) or hydroxylammonium sulfate is preferably used as the hydroxylammonium salt.

Dimethyl sulfate or diethyl sulfate is preferably used as the dialkyl sulfate (III).

The esters (II) used are preferably those in which R 'is methyl. Hydroxamic acid esters (I) are preferably prepared in which R ¹ , R ² and R ³ independently of one another are hydrogen or methyl. These include, in particular, acrylic hydroxamic acid esters, methacrylic hydroxamic acid esters, ice and trans-croton hydroxamic acid esters and 3,3-dimethylacrylhydroxamic acid esters.

Particular preference is given to the preparation of hydroxamic acid esters (I) in which R ¹ and R ^{2 are} hydrogen and R ^{3 is} methyl, namely methacrylhydroxamic acid esters.

An alkali metal hydroxide is preferably used as the strong base in the reaction of the ester (II) with the hydroxylammonium salt (for example hydroxylamine hydrochloride or hydroxylammonium sulfate). Sodium hydroxide is particularly preferred. The strong base is advantageously used in an approximately stoichiometric amount, ie approximately the sum of the molar amounts of ester (II) and hydroxylammonium salt.

An alkali carbonate is preferably used as the base in the alkylation of the hydroxamic acid salt with the dialkyl sulfate (III). Sodium carbonate is particularly preferred.

The dialkyl sulfate is advantageously used in a slight excess, for example in an amount of 1.0 to 1.5 mol per 1 mol of the hydroxamic acid salt.

Both reaction steps of the process according to the invention are advantageously carried out at relatively low temperatures, for example at 0-10 ° C.

Tests of the methacrylic hydroxamic acid methyl ester obtainable by the process according to the invention as a blocking agent for toluene diisocyanate showed better scratch resistance of the end product than the 3,5-dimethylpyrazole which is usually used. It was also found that no catalyst is required for the reaction of the isocyanate with methacrylic hydroxamic acid methyl ester and that deblocking is possible at a considerably lower temperature (80-90 ° C.). The blocked isocyanate also did not tend to yellowing. The following examples illustrate the implementation of the method according to the invention, without any limitation being seen therein.

example 1

Methyl methacrylate (N-methoxy-2-methylpropenamide)

500.6 g (5 mol) of methyl methacrylate were added at 0 ° C. to a solution of 347.6 g (5 mol) of hydroxylamine hydrochloride in 600 ml of water. With vigorous stirring and cooling, a solution of 400 g (10 mol) of sodium hydroxide in 1 l of water was added over the course of 2 hours in such a way that the temperature did not exceed 1.5 ° C. The clear yellowish solution thus obtained was stirred for a further 13 h at 0 ° C. and then 742 g (7 mol) of sodium carbonate (anhydrous) were added in portions over the course of Vi h. 756.8 g (6 mol) of dimethyl sulfate were added to the yellowish suspension formed in the course of 2 ^{l of} A h in such a way that the temperature did not exceed 4 ° C. The reaction mixture was then heated to 10 ° C. in the course of 4 h, stirred at this temperature for a further 18 h and then extracted with ethyl acetate (3 × 2.5 l). The aqueous phase was concentrated. Hydrochloric acid (approx. 260 g) from pH 10.8 to pH 9.0, filtered and extracted with dichloromethane (3 x 2.5 l). The two organic phases were each dried separately over sodium sulfate, filtered and evaporated on a rotary evaporator. The ethyl acetate gave, after stripping off the solvent residues under high vacuum 281 g of a yellowish oil, which according to Η NMR spectrum consisted of about 88% from the title compound and about 12% ₀ of the N, O-dimethylated product N-methyl-methacrylhydroxamsäuremethylester . Accordingly, a further 209 g of product were obtained as a light orange oil from the dichloromethane phase. The total yield was 490 g (85%) containing about 8% of the N, 0-dimethyl compound. The latter can be largely removed by extracting the reaction mixture with a very non-polar solvent (e.g. hexane / diethyl ether) before the ethyl acetate extraction. For characterization, a sample of approx. 1 g was distilled in the Kugelrohr at 60 ° C / 1 mbar with the addition of approx. 1% hydroquinone as stabilizer. The pure methacrylic hydroxamic acid methyl ester was obtained as a colorless oil. 'H NMR (400 MHz, CDC1 ₃ ) δ = 9.4 (s, 1H); 5.7 (s, 1H); 5.4 (s. 1H); 3.8 (s. 3H);

1.95 (s, 3H). IR (film) v [cm ^"1 ]: 3204 (br.), 2979, 2939, 2899, 1663s, 1624s, 1501s,

1441, 1062s, 940, 885, 598.

The by-product N-methoxy-2N-dimethylpropenamide, which could also be obtained in pure form by using an excess of dimethyl sulfate, showed the following data:

'H ΝMR (300 MHz, CDCI ₃ ) δ = 5.2 (s, 1H); 5.12 (s, 1H); 3.55 (s. 3H); 3.12 (s, 3H); 1.85 (s, 3H).

Example 2

Methyl methacrylate (N-methoxy-2-methylpropenamide)

1101.32 g (11 mol) of methyl methacrylate were added at 0 ° C. to a solution of 902.77 g (5.5 mol) of hydroxylammonium sulfate in 1500 ml of water. A solution of 880 g (22 mol) of sodium hydroxide in 2.45 l of water was added with vigorous stirring and cooling so that the temperature did not exceed 0.degree. The clear yellowish solution thus obtained was stirred at 0 ° C. for a further 4 h. 1399 g (13.2 mol) of sodium carbonate (anhydrous) were then added in portions. 1665 g (13.2 mol) of dimethyl sulfate were then added to the yellowish suspension formed in such a way that the temperature did not exceed +4.degree. A total of a further 0.6 l of water were added during this addition. The reaction mixture was then stirred at 10 ° C. for a further 12 h and then filtered. The filtrate was concentrated with 186 g. Hydrochloric acid adjusted to pH 9 and then extracted with ethyl acetate (6 x 4 1) and then with dichloromethane (3 x 4 1). The aqueous phase was then adjusted to pH 7 and extracted again with ethyl acetate (3 × 4 1). The combined organic phases were concentrated in vacuo and the residue (1028.8 g) obtained after stripping off the solvent residues in a fine vacuum was distilled at 50 ° C./0.5 mbar (oil bath temperature 60 ° C., initial heating to 30 ° C.) and immediately stabilized by adding 400 ppm of 2,6-di-tert-butyl-4-methylphenol. O

Yield: 1014.4 g (80%) of a colorless oil which, according to the 'H NMR spectrum, contains approximately 90.5% of the title compound and approximately 9.5% of the N, O-dimethylated product N-methyl- methyl methacrylate.

Example 3

Methyl methacrylate (N-methoxy-2-methylpropenamide)

In an autoclave, 3.75 g (37 mmol) of methyl methacrylate (stabilized with 600 ppm of 2,6-di-tert.) Were added to a solution of 3.04 g (18.5 mmol) of hydroxylammomium sulfate in 5 ml of water at 0 ° C. -butyl-4-methylphenol) added. A solution of 2.96 g (74 mmol) of sodium hydroxide in 8 ml of water was then added with vigorous stirring so that the temperature did not exceed 2 ° C. The clear yellowish solution thus obtained was stirred at 0 ° C. for a further 6 h. Then 1.29 g (4 mmol) of tetrabutylammonium bromide were added. The autoclave was then sealed and 18.7 g (0.37 mol) of methyl chloride were introduced at 0 ° C. The reaction mixture was then heated to 40 ° C. (oil bath temperature), the pressure in the autoclave rising to 5-6 bar. After stirring at 40 ° C. for 17 h, the reaction mixture was cooled to room temperature and the autoclave was depressurized. The pH was adjusted to 8.5 by adding 1.9 g sodium hydroxide (30% in water). The mixture was then filtered and the filtrate was separated into two phases. The aqueous phase was extracted with ethyl acetate (5 x 20 ml). The solvent was distilled off from the combined organic phases in vacuo at low temperature (<30 ° C.). The residue was filtered and the separated solid was washed with ethyl acetate. The filtrate was concentrated on a rotary evaporator and freed from solvent residues in a fine vacuum.

Yield: 3.36 g (approx. 78%>) of a slightly orange product as a mixture of methyl methacrylate hydroxamate and N-methoxy-2, N-dimethylpropenamide in a ratio of 7.5: 1 (GC). Example 4

Methyl methacrylate hydroxamic acid (N-ethoxy-2-methylpropenamide)

20.0 g (0.20 mol) of methyl methacrylate were added to a solution of 13.9 g (0.20 mol) of hydroxylamine hydrochloride in 30 ml of water at 0 ° C. A solution of 16 g (0.40 mol) of sodium hydroxide in 50 ml of water was then added with vigorous stirring so that the temperature did not exceed 1.5 ° C. The clear yellowish solution was stirred at 0 ° C overnight. Then 29.7 g (0.28 mol) of sodium carbonate (anhydrous) were added in portions. 37.0 g (0.24 mol) of diethyl sulfate were then added to the white-yellowish suspension obtained in such a way that the temperature did not exceed +4 ° C. The reaction mixture was warmed to 10 ° C, stirred at 10 ° C for 24 hours and then filtered. The filtrate was extracted with dichloromethane (3x150ml). After drying over sodium sulfate and distilling off the solvent on a rotary evaporator and stripping off solvent residues in a fine vacuum (4 h), 18.12 g of slightly yellowish product which was still contaminated with diethyl sulfate were obtained. The dialkylated product could not be detected in Η NMR (<3%).

'H NMR (400 MHz, CDC1 ₃ ) δ = 5.7 (s, 1H); 5.35 (s, 1H); 4.0 (q, 2H);

1.95 (s, 3H); 1.28 (t, 3H).

Claims

claims

1. Process for the preparation of hydroxamic acid esters of the general formula

wherein RC, ^ - alkyl and R ¹ to R ³ independently of one another are hydrogen or C, ^ - alkyl, characterized in that an ester of the general formula

wherein R 'is _C] _ ₆ - alkyl, and R ¹ to R ³ have the abovementioned meanings, is reacted first with the addition of an aqueous strong base with a hydroxylammonium salt and the hydroxamic thus obtained without isolating it in the presence of a base with a dialkyl sulfate of general formula (RO) ₂ SO ₂ (III) or an alkyl chloride of the general formula R-Cl (IV), in which R in each case has the meaning given above, is alkylated.

2. The method according to claim 1, characterized in that hydroxylamine hydrochloride or hydroxylammonium sulfate is used as the hydroxylammonium salt.

3. The method according to claim 1 or 2, characterized in that the dialkyl sulfate (III) used is dimethyl sulfate or diethyl sulfate.

4. The method according to any one of claims 1 to 3, characterized in that R 'is methyl.

5. The method according to any one of claims 1 to 4, characterized in that R ¹ , R ² and R ^{3 are} independently hydrogen or methyl.

6. The method according to claims 3 and 5, characterized in that R ¹ and R ^{2 are} hydrogen and R ^{3 is} methyl.

7. The method according to any one of claims 1 to 6, characterized in that an alkali metal hydroxide is used as the strong base.

8. The method according to any one of claims 1 to 7, characterized in that the alkylation with the dialkyl sulfate (III) is carried out in the presence of an alkali carbonate.