DE3038598A1 - Alpha-hydroxy-carboxylic acid amide(s) prepn. - by reacting an alpha formyl:oxy-n benzyloxy-carboxylic acid amide with an alcohol - Google Patents

Abstract

The prepn. of alpha-hydroxy carboxylic acid amides of formula HO-CHR1-CONR2R3 (I) comprises reacting an alpha-oxy-carboxylic acid amide of formula RCOOCHR1-CONR2R3 (II) with an alcohol of formula R4OH (III), in the presence of catalytic amts. of alkali(ne earth) hydroxides or (hydrogen)carbonates. Reaction is at 20-150 deg.C. In the formulae R is H or opt. substd. Ph; R1 is H or alkyl; R2 and R3 are each opt. substd. alkyl, alkenyl, alkinyl, cycloalkyl, aralkyl, or aryl, or together with the N atom to which they are attached form an opt. partially unsatd.-opt. benzannellated mono or bicyclo opt. contg. further heteroatoms; R4 is alkyl. Alpha-oxy carboxylic acid amides of formula (II) are new. (I) are intermediates in the prepn. of herbicides. (I) are obtd. in very pure form and in good yields. The starting materials are cheaper to prepare and easier to saponify than the acetoxy-carboxylic acid amides used in a previous process. There are fewer side reactions.

Description

Process for the production of -hydroxy-carboxamides,

new intermediates therefor and processes for their production The invention relates to a new process for the preparation of some known «; Hydroxycarboxamides, new oQ-formyloxy and benzoyloxy carboxamides as intermediates therefor and a method for their production.

It has already become known that glycolic anilides are obtained if chloroacetic anilides are reacted with acetate to form acetoxyacetic anilides and the latter is saponified under alkaline conditions (cf. DE-OS 2 2ol 432). For the production of acetoxyacetic anilides are for example the corresponding chloroacetic anilides according to the prior art with a high excess of potassium acetate in thin acetic acid Heated under reflux for 20 hours.

After cooling, the acetoxyacetic anilides formed can then generally be used can be isolated by filtration. The disadvantages of this method are the high Expenditure of potassium acetate and the burden on the mother liquor with the excess Acetate and the potassium chloride formed as a by-product.

The saponification of Acetoxyessigsäureanilide is according to the state of Technique using 1 to 2 molar equivalents of alkali hydroxide in methanol carried out. In general, the glycolic anilides are neutralized, for example with dilute hydrochloric acid, deposited in crystalline form. Even here the mother liquor contains larger amounts of salts.

In addition, the yield and purity of the products thus obtained are not always completely satisfactory.

It has also become known that O (-Hydroxy-carboxylic acid amides obtained in good yields if one C (-Halogencarbonsäureamide with alkali or Alkaline earth acetates in the presence of quaternary ammonium salts and the resulting o (-Acetoxy-carboxamides deacylated with alcohols in the presence of basic catalysts (see.

DE-OS 2 9o4 490 / Le A 19 445). One disadvantage of this method is that in the deacylation stage there are generally strong bases such as sodium or potassium hydroxide can be used as catalysts and thereby to some extent an amide saponification also takes place.

It has now been found that i-hydroxycarboxamides of the formula I. in which R1 stands for hydrogen or alkyl and R2 and R3 are identical or different and individually stand for givenElls substituted radicals from the series alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, aryl or together with the nitrogen atom to which they are bonded, a Form optionally substituted, optionally partially unsaturated and optionally benzene-fused mono- or bicyclic, which optionally contains further heteroatoms, is obtained in very pure form and in good yields when l-oxycarboxamides of the formula II in which R1, R2 and R3 have the meanings given above, and R is hydrogen or optionally substituted phenyl, with alcohols of the formula III R4-OH (III) in which R4 is alkyl, in the presence of catalytic amounts of alkali or Alkaline earth hydroxides or hydrogen carbonates at temperatures between 20 and 150 ° C.

It can be described as surprising that the implementation of the oxycarboxamides of formula (II) with alcohols in the presence of catalytic amounts of alkali or Alkaline earth hydroxides or - (hydrog e (hydrogercarbonates practically quantitative pure hydroxycarboxamides of formula (I) results.

One advantage of the new method over known methods is in that formyloxycarboxamides can be used as starting materials, which are cheaper in comparison with corresponding acetoxycarboxamides can be prepared and saponified more easily, with minor side reactions Extent than with known processes.

If, for example, formyloxy-acetic acid piperidide and ethanol are used as starting materials, the course of the reaction can be outlined using the following formula: The t-oxycarboxamides to be used as starting compounds are defined by formula (ti). Preferably, R1 is hydrogen or methyl, R2 and R3, which can be the same or different, individually for C1-C1O-alkyl, cyano-C1-C5alkYl, C1-C4-alkoxy-C1-C4-alkyl, C3-C1O- Alkenyl, C3-C1o-alkynyl, C3-C12-cycloalkyl, phenyl-C1-C3-alkyl, phenyl or naphthyl, the latter radicals optionally being replaced by halogen, C1-C4-alkyl, trifluoromethyl, nitro, C1-C4-alkoxy, and / or cyano are substituted, or the two radicals R2 and R3 together with the nitrogen atom to which they are bonded form an optionally substituted by C1-C5-alkyl, optionally partially unsaturated and / or optionally benzannellated monocycle or bicyclic with up to 15 carbon atoms or a saturated monocycle which is optionally substituted by C1-C5-alkyl and contains a further oxygen atom or sulfur atom and has up to 10 carbon atoms and R is preferably hydrogen or phenyl.

Those compounds are particularly preferred as starting materials of the formula (II), in which R1 is hydrogen, R2 and R3, which are identical or different can be, individually for C1-C5-alkyl, cyanoethyl, 2-methoxyethyl, allyl, 2-butenyl, 3-methyl-2-butenyl, propargyl, 1-methyl-2-propynyl, 1,1-dimethyl-2-propynyl, Cyclopentyl, cyclohexyl, benzyl, phenyl, which is optionally replaced by methyl, methoxy, Nitro, trifluoromethyl, fluorine, chlorine and / or bromine is substituted, or together with the nitrogen atom to which they are attached, for optionally through C1-C3-alkyl substituted radicals from the series pyrrolidyl, piperidyl, morpholinyl, Perhydroazepinyl, Indolinyl, perhydroindolyl, 1,2,3,4-tetrahydroquinolyl and isoquinolyl, perhydroquinolyl and -isoquinolyl and R is hydrogen.

Examples of the oxycarboxamides of the formula (II) are: Formyloxyacetic acid and benzoyloxyacetic acid dimethylamide, diethylamide, dipropylamide, -N-methyl-isopropylamide, -N-methyl-isobutylamide, -N-methyl-sec.-butylamide, -N-methyl-cyanoethylamide, -bis- (2-methoxy-ethyl) -amide, -diallylamide, -dipropargylamide, -N-methyl-propargylamide, -N-methyl- (1-methylpropargyl) -amide, -N-methyl-cyclopentylamide, -N-methyl-cyclohexylamide, -N-methyl-anilide, -N-methyl- (2-methyl-phenyl) -amide, -N-methyl- (3-methyl-phenyl) -amide, -N-methyl- (4-methyl-phenyl) -amide, -N-methyl- (3, 5-dimethyl-phenyl) -amide, -N-methyl- (2-nitro-phenyl) -amid, N-methyl- (3-nitro-phenyl) -amid, -N-methyl- (4-nitro-phenyl) -amide, -N-methyl- (2-methyl-5-nitro-phenyl) -amid, -N-methyl- (3-chlorophenyl) -amid, -N-ethyl-anilide, -N-propyl-anilide, -N-isopropyl-anilide, -N-butyl-anilide, -N-isobutyl-anilide, -N-met hyl-benzylamide, -N-ethyl-benzylamide, -N-propyl-benzylamide, -N-butyl-benzylamide, -pyrrolidide, -2-methyl-pyrrolidide, -morpholide, -piperidide, -2-methyl-piperidide, -4-methyl-piperidide, -2,4-dimethyl-piperidide, -2,4,6-trimethylpiperidide, -2-ethyl-piperidide, -4-ethyl-piperidide, -2, 4-diethyl-piperidide, -2-methyl-4-ethyl-piperidide, -2-ethyl-4-methyl-piperidide, -2-methyl-5-ethyl-piperidide, -2-ethyl-5-methyl-piperidide, -indolinide, -2-methyl-indolinide, -perhydroindolide, -2-methyl-perhydroindolinide, 2,2 - dimethyl-perhydroindolinide, -1,2,3,4-tetrahydroquinolide, -2-methyl-1,2,3,4-tetrahydroquinolide, -perhydroquinolide, -2-methyl-perhydroquinolide, -4-methyl-perhydroquinolide, -1,2,34 tetrahydroisoquinolide and perhydroisoquinolide.

The f-oxycarboxamides of the formula (11) have not yet been described in the literature. These compounds are obtained if one-halo-carboxamides of the formula are used in which R1, R2 and R3 have the meanings given above and Hal is chlorine or bromine, with compounds of the formula V R-CO-OM (V) in which R has the meaning given above and M is an alkali metal or an alkaline earth metal equivalent , in the presence of a quaternary ammonium salt and, if necessary, using a diluent at Tem --- perata-rentzmnandNw-2o ------ t If, for example, bromoacetic acid piperidide and potassium formate are used as starting materials, the course of the reaction can be sketched using the following equation: The> t-halocarboxamides to be used here as starting materials are defined by formula (II). The preferred or particularly preferred meanings of the radicals R1, R2 and R3 and of Hal are the same as for the compounds of the formula (II).

The compounds of the formula (IV) are already known (cf. DE-OS 2 9o4 49O).

The carboxylic acid salts to be used as starting materials are defined by formula (V).

Preferably, M is sodium or potassium and R is hydrogen or phenyl, especially for hydrogen.

Examples are sodium and potassium formate, as well as sodium and Called potassium benzoate.

The process for the preparation of the new -oxycarboxamides of the formula (II) is preferably carried out using diluents. as practically all inert organic solvents can be used. For this include in particular aliphatic and aromatic, optionally chlorinated hydrocarbons such as hexane, heptane, cyclohexane, benzene, toluene, xylene, Chloroform, carbon tetrachloride, chlorobenzene and o-dichlorobenzene, ethers such as dipropyl and dibutyl ether, glycol dimethyl ether and diglycol dimethyl ether, tetrahydrofuran and dioxane, ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, Esters such as methyl acetate and ethyl acetate, amides such as dimethylformamide and Dimethylacetamide and nitriles such as acetonitrile and propionitrile.

Quaternary ammonium salts are used as catalysts, preferably Tetraalkylammonium salts, the alkyl radicals containing 1 to 4 carbon atoms, or trialkylbenzylammonium salts, where the alkyl radicals have 1 to 2 carbon atoms contain. Examples are tetrabutylammonium chloride and trimethylbenzylammonium chloride called.

The reaction temperatures are used in the process for preparing the Compounds of the formula (II) in general between 20 and 200 ° C., preferably Maintained between Sun and 15c ° C. The reactions are generally carried out under normal pressure carried out.

Per mole of -halocarboxamide of the formula (IV) one uses from 0.9 to 1.5 mol, preferably 0.95 to 1.2 mol of carboxylic acid salt of the formula (V), and 1 to 20 mmol, preferably 2 to 15 mmol, ammonium salt catalyst.

The components are generally in one of the specified diluents heated to the required reaction temperature until the end of the reaction. To Cooling to room temperature is filtered and the filtrate will the solvent is carefully distilled off. The crude products remaining in the residue are optionally purified by recrystallization.

The α-oxycarboxamides of the formula obtained in this way (II) are used for the preparation of corresponding O (-hydroxy-carboxamides of Formula (I) reacted with alcohols.

The alcohols to be used here are defined by formula (III). Preferably therein R stands for C1-C4-alkyl, in particular for methyl.

Examples include methanol, ethanol, n- and iso-propanol.

The inventive method for the preparation of compounds of Formula (I) is made using catalytic amounts of alkali or alkaline earth hydroxides or - (hydrogen) carbonates carried out. Examples are sodium hydroxide, Potassium hydroxide, magnesium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, Called sodium hydrogen carbonate and potassium hydrogen carbonate.

The reaction temperatures are generally between 2O and 15o0C, preferably kept between Sun and 12o0C. The implementations are also generally carried out at normal pressure.

The alcohols of formula (III) are preferably used for dilution of the reaction mixture in high excess set. In general use between 100 and 100 ml, preferably between 150 and 300 ml, of alcohol per mole of oxycarboxamide of the formula (II).

In general, the starting materials of the formulas (II) and (III) as well as the catalysts combined at room temperature and the reaction mixtures heated to boiling, the ester formed as a by-product and the excess Alcohol can be distilled off. The products of the formula (I) remain in the distillation residue and are optionally purified by recrystallization.

In general, the hydroxy-carboxamides fall according to the invention Processes in high purity and can continue without further purification processes are processed.

The hydroxy-carboxamides which can be prepared according to the invention can used as intermediate products in the manufacture of herbicides (see European Patent application EP 5501).

Preparation examples A) Compounds of the formula (I): Example A-1 A mixture of 174 g (0.9 mol) of formyloxyacetic acid-N-methyl-anilide, 2 g of sodium hydrogen carbonate and 200 ml of methanol is refluxed for 3 hours. Then a mixture of methyl formate and methanol is distilled off at a bath temperature of 90 to 1000C under normal pressure. 149 g (100% of theory) of hydroxyacetic acid-N-methyl-anilide with a melting point of 48-50 ° C. are obtained as the distillation residue.

The content of the methyl formate solution distilled over is measured on a sample determined by acid-base titration after alkaline hydrolysis. From the distillate are then added by heating with an equimolar amount of sodium hydroxide 52 g (85% of Theory) obtained sodium formate. The dry sodium formate can be used for production Use of formyloxyacetic acid-N-methyl-anilide (see. Example B-1).

Analogously to Example A-1, for example, those in the following Compounds of the formula (I) listed in Table A are prepared.

Table A: Compounds of the formula (I) At- 2 yield melting point match R1 -N (% of (OC) resp. No. \ R3 theory) refractive index; A-2 H -N (CH2-CH = CH22 99 nD5: 1,4854 H3C A-3 H -NHCH3 97 i: 1,4747 CH3 A-4 H -N 3 98 D 1,500 A-5 H -N (CH3) 2 99 41 cH CH3 A-6 CH3 \) 85 95-96 B) Compounds of the formula (II) EXAMPLE B-1 A suspension of 183.5 g (1 mol) of chloroacetic acid-N-methyl-anilide, 74.8 g (1.1 mol) of sodium formate (powder), 2 g of tetrabutylammonium bromide and 400 ml of methyl isobutyl ketone is refluxed for 10 hours Heated to boiling and then cooled to room temperature. The precipitated sodium chloride is filtered off with suction and washed with a little methyl isobutyl ketone. After distilling off the solvent in vacuo, the filtrate gives 200 g of formyloxyacetic acid N-methylanilide as a crude product with a melting point of 50 ° C., and after its recrystallization from diisopropyl ether 171 g of pure product (89% of theory) with a melting point of 550 ° C.

The compounds of the formula (II) listed in Table B below can be prepared analogously to Example B-1: TABLE B: Compounds of the formula (11) At- / R2 yield melting point game R R1 -N \ 3 (% of (° C) resp. No. The orie) refractive index; B-2 HH -N (CH2-CH = CH2) 2 99 25 , 4805 HC 3 B-3 HH - ß -CH3 98 57 CH3 B-4 HH-6 81 nD25: 1.4942 25th B-5 HH-N (cH3) 2 99 nu: 1.4591 CH3 B-6 H CH3 -N <95 72-73

Claims (10)

Process for the preparation of i-hydroxycarboxamides of the formula I. in which R1 represents hydrogen or alkyl and R2 and R3 are identical or different and individually represent optionally substituted radicals from the series alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, aryl or together with the nitrogen atom to which they are bonded, a optionally substituted, optionally partially unsaturated and optionally benzene-fused mono- or bicyclic, which optionally contains further heteroatoms, characterized in that i-oxycarboxamides of the formula II in which R11, R2 and R3 have the meaning given above, and R is hydrogen or optionally substituted phenyl, with alcohols of the formula III R4-oH (III) R -OH (III) in which 4 R4 is alkyl, in the presence catalytic amounts of alkali or alkaline earth hydroxides or (hydrogen) carbonates at temperatures between 20 and 1500C. 2. The method according to claim 1, characterized in that at Temperatures between 50 and 1200C will work. 3. The method according to claim 1, characterized in that one pro Moles of O & -oxycarboxamide of the formula (II) between 100 and 500 ml of alcohol Formula (III) is used. 4. The method according to claim 1, characterized in that there is alsO & -Oxy-carboxamide of the formula (II) formyloxyacetic acid-N-methylanilide (B-1) is used. 5. Process for the preparation of i-oxycarboxamides of the formula II in which R, R1, R2 and R3 have the meaning given above, characterized in that i-halocarboxamides of the formula IV in which R1, R2 and R3 have the meaning given above and Hal is chlorine or bromine, with compounds of the formula V R-CO-OM (V) in which R has the meaning given above and M is an alkali metal or an alkaline earth metal equivalent , in the presence of a quaternary ammonium salt and optionally using a diluent at temperatures between 20 and 2000C. 6. The method according to claim 5, characterized in that at Temperatures between 50 and 1500C will work. 7. The method according to claim 5, characterized in that one pro Moles of O & -halocarboxamide of the formula (IV) 0.9-1.5 moles of carboxylic acid salt of formula (V) and 1-20 mmol of the quaternary ammonium salt is used. 8. The method according to claim 5, characterized in that chloroacetic acid-N-methylanilide Reacts with sodium formate. 9. & -oxy-carboxamides of the formula II in which R, R1, R2 and R3 have the meaning given above. 10. Formyloxyacetic acid N-methylanilide (B-1); Formyloxyacetic acid-N, N-diallylamide (B-2); Formyloxyacetic acid 2,4,6-trimethylpiperidide (B-3); Formyloxyacetic acid-N, N-hexamethylene amide (B-4); Formyloxyacetic acid-N, N-dimethylamide (B-5); Ot-formyloxypropionic acid-N-methylanilide (B-6) according to claim 9.