DE3707402A1 - Process for the preparation of hydroxyacetamides - Google Patents

Abstract

Hydroxyacetamides of the general formula (I) <IMAGE> in which R<1> represents an optionally substituted radical from the series comprising alkyl, alkenyl and alkynyl and R<2> represents an optionally substituted radical from the series comprising alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl and aralkyl, or together with R<1> represents alkanediyl (alkylene) which is optionally interrupted by an oxygen atom, can be prepared in a one-step process in good yields by reacting haloacetamides of the general formula (II) <IMAGE> in which R<1> and R<2> have the abovementioned meanings and X represents halogen, with formamide and water at temperatures between 50@C and 200@C, if appropriate in the presence of a catalyst. The hydroxyacetamides (I) can be used as intermediates for the preparation of known herbicides, for example heteroaryloxyacetamides.

Description

The invention relates to a new, one-step process for the preparation of known hydroxyacetic acid amides, which became known as intermediates for the production of th herbicides can be used.

It is known that one in a hydroxyacetic acid three step reaction sequence can be obtained by going to next reacting chloroacetyl chloride with suitable amines, the chloroacetic acid amides thus obtained in a second Step with alkali carboxylates to corresponding acyloxy converts acetic acid amides and this in a third Step ver to the desired hydroxyacetic acid amides soaps (see DE-OS 22 01 432 and DE-OS 29 04 490). The technical disadvantages of such multi-stage reactions are obvious.

It is also known that Hydroxyessigsäureethyl ester obtained when using ethyl chloroacetate  Reacts formamide and water (see Chem. Ber. 87 (1954), Pp. 537-546). A corresponding reaction of chlorine however, acetic acid amides are not known.

It has now been found that hydroxyacetic acid amides of the general formula (I)

in which

R1 for an optionally substituted radical the series alkyl, alkenyl and alkynyl and R² for an optionally substituted radical the series alkyl, alkenyl, alkynyl, cycloalkyl, Cycloalkenyl and aralkyl stands or together with R1 for optionally through an oxygen atom interrupted alkanediyl (alkylene),

easily obtained in a one-pot process, if you have haloacetamides of the general formula (II)

in which
R¹ and R² have the meanings given above and
X represents halogen,
with formamide and water, optionally in the presence of a catalyst, at temperatures between 50 ° C and 200 ° C.

With regard to the state of the art (Chem. Ber. 87 (1954), pp. 537-546) is surprising designate that Hydroxyessigsäureamide after inventing process according to the invention under a relatively mild reaction conditions can be obtained in good yields; although with similar substitution reactions that Chlorine atom in chloroacetic acid amides is known is less reactive than the chlorine atom in chlorine acetic acid esters (see, e.g., Amer. Chem. Soc. 47 (1925), P. 488 ff, especially p. 489), can be used in the invention milder reaction conditions (lower Excess formamide, lower reaction temperature, shorter reaction times) are used than with the previously known implementation of chloroacetic acid esters with Formamide / water to form hydroxyacetic acid esters to obtain comparable high yields of hydroxyacetic acid to obtain acid derivatives.

Advantages of the new method compared to the known ones Process for the preparation of hydroxyacetic acid amides are, for example, in the one-step process leadership and in the use of the inexpensive chemical Formamide.  

The invention preferably relates to the production of Compounds of formula (I) in which

R¹ stands for C₁-C₈-alkyl, which if necessary by Fluorine, chlorine, cyano, C₁-C₄ alkoxy or C₁-C₄ alkyl thio is substituted, in which further R¹ for C₂-C₈ alkenyl, which is optionally by Fluorine, chlorine or cyano is substituted, in which cher further R¹ is C₂-C₈ alkynyl, and R² stands for C₁-C₈-alkyl, which if necessary by Fluorine, chlorine, cyano, C₁-C₄ alkoxy or C₁-C₄ alkyl thio is substituted, in which R² further for C₂-C₈ alkenyl, which is optionally by Fluorine, chlorine or cyano is substituted, in which cher further R² for C₂-C₈-alkynyl, C₅- or C₆-Cyc loalkyl, C₅- or C₆-cycloalkenyl or benzyl stands, or together with R¹ for optionally C₂-C₈- interrupted by an oxygen atom Alkanediyl is.

The invention particularly relates to the production of Compounds of formula (I) in which

R¹ for C₁-C₆-alkyl, C₃-C₄-alkenyl or C₃-C₄-alkynyl stands and R² for C₁-C₆-alkyl, C₃-C₄-alkenyl or C₃-C₄-alkynyl stands, or together with R¹ for trimethylene, tetra methylene or pentamethylene.

Examples of the compounds of the formula (I) which can be prepared according to the invention are:
Hydroxyacetic acid-dimethylamide, -diethylamide, -di-n-propylamide, -di-isopropylamide, -di-n-butylamide, -di-isobutylamide, -di-sec-butylamide, -N-methyl-N-ethylamide, - N-methyl-Nn-propylamide, -N-methyl-N-isopropylamide, -N-methyl-Nn-butylamide, -N-methyl-N-isobutylamide, -N-methyl-N-sec-butylamide, -N- ethyl-Nn-propylamide, -N-ethyl-N-isopropylamide, -N-ethyl-Nn-butylamide, -N-ethyl-N-iso-butylamide, -N-ethyl-N-sec-butylamide, -Nn-propyl- N-isopropylamide, -Nn-propyl-Nn-butylamide, -Nn-propyl-N-isobutylamide, -Nn-propyl-N-sec-butylamide, -N-isopropyl-Nn-butylamide, -diallylamide, -dicrotylamide, - dipropar gylamide, -N-methyl-N-allylamide, -N-ethyl-N-allylamide, -Nn-propyl-N-allylamide, -N-isopropyl-N-allylamide, -N-methyl-N-propargylamide, -N -ethyl-N-propargylamide, -Nn-propyl-N-propargylamide, -N-isopropyl-N-propargylamide, -N-methyl-N- (1-methyl-propargyl) -amide, -N-methyl-N-cyclopentylamide , -N-ethyl-N-cyclopentylamide, -N-methyl-N-cyclohexylamide, -N-methyl-N-cyclopentenylamide, -N-methyl-N-cyclohexenylamide , -pyrrolidide, -2-methylpyrrolidide, -piperidide, -2-methylpiperidide, -4-methylpiperidide, -2,4-dimethylpiperidide, -3-ethylpiperidide and -morpholide.

For example, dimethyl chloroacetic acid is used amide, formamide and water as starting materials, so can the reaction taking place in the process according to the invention can be outlined by the following formula scheme:  

The starting materials in the process according to the invention Haloacetic acid amides to be used are indicated by the Formula (II) generally defined. In this formula (II) are preferably

R¹ for C₁-C₈ alkyl, which is optionally by Fluorine, chlorine, cyano, C₁-C₄ alkoxy or C₁-C₄ alkyl thio is substituted for C₂-C₈ alkenyl, which optionally by fluorine, chlorine or cyano sub is substituted or for C₂-C₈ alkynyl, R² for C₁-C₈ alkyl, which is optionally by Fluorine, chlorine, cyano, C₁-C₄ alkoxy or C₁-C₄ alkyl thio is substituted for C₂-C₈ alkenyl, which optionally by fluorine, chlorine or cyano sub is substituted for C₂-C₈ alkynyl, C₅- or C₆- Cycloalkyl, C₅- or C₆-cycloalkenyl or benzyl, or together with R¹ for optionally by a Oxygen atom interrupted C₂-C₈-alkanediyl and X for chlorine, bromine or iodine.

Particularly preferred starting materials are those Compounds of formula (II) in which

R¹ for C₁-C₆-alkyl, C₃-C₄-alkenyl or C₃-C₄-alkynyl stands,  R² for C₁-C₆-alkyl, C₃-C₄-alkenyl or C₃-C₄-alkynyl stands, or together with R¹ for trimethylene, tetra methylene or pentamethylene, and X represents chlorine or bromine.

The following may be mentioned as examples of the starting materials of the formula (II):
Chloroacetic acid or bromoacetic acid-dimethylamide, -diethylamide, -di-n-propylamide, -di-isopropylamide, -di-n-butylamide, -di-isobutylamide, -di-sec-butylamide, -N-methyl-N -ethylamide, -N-methyl-Nn-propylamide, -N-methyl-N-isopropylamide, -N-methyl-Nn-butylamide, -N-methyl-N-isobutylamide, -N-methyl-N-sec-butylamide, -N-ethyl-Nn-propylamide, -N-ethyl-N-isopropylamide, -N-ethyl-Nn-butyl amide, -N-ethyl-N-isobutylamide, -N-ethyl-N-sec-butyl amide, - Nn-propyl-N-isopropylamide, -Nn-propyl-Nn-butylamide, -Nn-propyl-N-isobutylamide, -Nn-propyl-N-sec-butylamide, -N-isopropyl-Nn-butylamide, -diallylamide, -dicrotylamide, -dipropargylamide, -N-methyl-N-allylamide, -N-ethyl-N-allylamide, -Nn-propyl-N-allylamide, -N-iso propyl-N-allylamide, -N-methyl-N- propargylamide, -N-ethyl- N-propargylamide, -Nn-propyl-N-propargylamide, -N-isopropyl-N-propargylamide, -N-methyl-N- (1-methyl-propargyl) amide, -N- methyl-N-cyclopentylamide, -N-ethyl-N-cyclopentylamide, -N-methyl-N-cyclohexylamide, -N-methyl-N-cyclopentenylamide, -N-methy IN cyclohexenylamide, pyrrolidide, -2-methyl-pyrrolidide, -piperidide, -2-methyl-pipe ridid, -4-methyl-piperidide, -2,4-dimethyl-piperidide, -3-ethyl-piperidide and - morpholide.

The haloacetic acid amides of the general formula (II) are known connections.

The inventive method is preferably in Ge in the presence of a catalyst. As a cat In particular, substances are considered that are under the generic term phase transfer catalysts together can be grasped (see Angew. Chem. 86 (1974), Pp. 187-195; ibid. 89 (1977), pp. 521-533).

Examples of such catalysts are: Benzyl triethylammonium chloride, methyltricaprylammonium chloride, tetrabutylammonium bromide, tetrabutylammoniumhy drug sulfate, hexadecyl tributylphosphonium bromide, Te tramethylammonium bromide, tetraethylammonium bromide, Benzyl tributylammonium chloride, benzyl trimethylammo nium chloride, hexadecyl trimethyl ammonium chloride, methyl trioctylammonium bromide and tetrabutylammonium chloride.

The reaction temperature is in the invention Process generally between 50 ° C and 200 ° C, before preferably between 80 ° C and 160 ° C, especially between between 100 ° C and 140 ° C.

The inventive method can at normal pressure or slightly increased or decreased pressure will. Is preferably carried out at normal pressure.

To carry out the method according to the invention to 1 mol of haloacetamide of the formula (II) in generally between 1 and 5 moles, preferably between  2 and 2.5 moles of formamide and between 1 and 5 moles preferably between 2 and 2.5 moles of water and given if between 0.0001 and 0.1 mol, preferably between 0.001 and 0.01 moles of a catalyst.

To carry out the method according to the invention ver the reaction components in any order mixes and after completion of the implementation by conventional methods be worked up.

In a preferred embodiment of the fiction The first step in the process is formamide, water and the catalyst is mixed and heated to a temperature heated between 100 ° C and 120 ° C. Then it will Haloacetamide and the reaction mixture Schung is at 120 ° C to 140 ° C until the end of Um setting stirred. After cooling, use a non-polar or moderately polar solvents, such as. B. toluene, ver thins and the resulting crystalline ammonium chloride is separated by suction. The filtrate is with aqueous alkali metal hydroxide solution made alkaline and heated to 80 ° C to 100 ° C. Then fil is again and the filtrate by distillation with min worked up pressure, including the product of formula (I) as a higher boiling fraction.

Those which can be produced by the method according to the invention Hydroxyacetic acid amides of formula (I) can as Zwi Products for the production of herbicidally active O-phosphoryl-oxyacetamiden (see. DE-OS 26 47 568) or  Heteroaryloxyacetamides can be used (cf. EP-A-5 501 / US 4,509,971; EP-A-18 497 / US 4,645,525; EP-A-94 541 / US 4,585,471; EP-A-100 045 / US 4,540,430; EP-A-100 044 / US 4,549,899; EP-A-148 501; EP-A-161 602; EP-A-192 117; EP-A-195 237; further DE-OS's 30 38 599, 30 38 608, 30 38 635 and 30 38 652).

Manufacturing examples Example 1

53.3 g (0.30 mol) of chloroacetic acid dipropylamide dropwise to a heated to 100 ° C to 120 ° C. and stirred mixture of 27 g (0.60 mol) formamide, 12 ml (0.66 mol) of water and 0.5 g of benzyl triethylammo given nium chloride. The reaction mixture then becomes two stirred at 120 ° C to 140 ° C for three hours, after which thanks to thin layer chromatographic control no starting material is detectable. After cooling the reaction mixture is diluted with 100 ml of toluene and the crystalline ammonium chloride is removed by Suction separated. The filtrate is washed with potassium hydroxide solution made alkaline and another hour at 80 ° C to 90 ° C heated. The mixture is filtered and the filtrate is distilled under reduced pressure.

39.4 g (73% of theory in the case of a gas chroma graphically determined content of 88.5%) hydroxyacetic acid Acid dipropylamide with a boiling point of 98 ° C (1 mbar).

In an analogous manner (i.e. the same molar ratio of the off starting materials, reaction time of 2 to 3 hours, however lower reaction temperatures: 120 to 125 ° C) were the compounds mentioned in the following examples produced (with the yields not optimized were):  

Example 2

Hydroxyacetic acid diethylamide

Yield: 77% of theory Boiling point: 114 ° C (16 mbar).

Example 3

Hydroxyacetic acid diallylamide

Yield: 60% of theory Boiling point: 85 ° C (1.3 mbar).

Example 4

Hydroxyacetic acid hexamethyleneimide

Yield: 83% of theory Boiling point: 108 ° C (1 mbar).  

Example 5

Hydroxyacetic acid-N-methyl-N-n-butylamide

Yield: 84% of theory Boiling point: 78 ° C (0.2 mbar).

Example 6

Hydroxyacetic acid-N-morpholide

Yield: 63% of theory Melting point: 78 ° C.

Claims (5)

1. Process for the preparation of hydroxyacetic acid amides of the general formula (I) in which R1 represents an optionally substituted radical from the series alkyl, alkenyl and alkynyl and R2 represents an optionally substituted radical from the series alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl and aralkyl or together with R1 represents alkanediyl (alkylene) which is optionally interrupted by an oxygen atom stands, characterized in that haloacetic acid amides of the general formula (II) in which
R¹ and R² have the meanings given above and
X represents halogen,
with formamide and water, optionally in the presence of a catalyst, at temperatures between 50 ° C and 200 ° C. 2. The method according to claim 1, characterized in that that one at temperatures between 80 ° C and 160 ° C. is working. 3. The method according to claim 2, characterized in that one at temperatures between 100 ° C and 140 ° C. is working. 4. The method according to claim 1, characterized in that as a catalyst a phase transfer Catalyst selected from the group consisting of from the compounds benzyl-triethylammonium chloride, methyltricaprylammonium chloride, tetra butylammonium bromide, tetrabutylammonium hydrogen sulfate, hexadecyl-tributylphosphonium bromide, Tetramethylammonium bromide, tetraethylammonium bromide, benzyl tributylammonium chloride, benzyl trimethylammonium chloride, hexadecyl trimethyl ammonium chloride, methyl trioctyl ammonium bromide and Tetrabutylammonium chloride. 5. The method according to claim 4, characterized in that as phase transfer catalyst benzyl triethyl ammonium chloride is used.