MXPA99001055A - Process for preparing substituted valine amide derivatives - Google Patents
Process for preparing substituted valine amide derivativesInfo
- Publication number
- MXPA99001055A MXPA99001055A MXPA/A/1999/001055A MX9901055A MXPA99001055A MX PA99001055 A MXPA99001055 A MX PA99001055A MX 9901055 A MX9901055 A MX 9901055A MX PA99001055 A MXPA99001055 A MX PA99001055A
- Authority
- MX
- Mexico
- Prior art keywords
- process step
- process according
- reaction
- organic solvents
- allowed
- Prior art date
Links
- XDEHMKQLKPZERH-BYPYZUCNSA-N (2S)-2-amino-3-methylbutanamide Chemical class CC(C)[C@H](N)C(N)=O XDEHMKQLKPZERH-BYPYZUCNSA-N 0.000 title abstract description 7
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 42
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract description 18
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Natural products NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000003960 organic solvent Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 13
- NBEOBNPETXOCKI-UHFFFAOYSA-N propan-2-ylchloranuidyl formate Chemical compound CC(C)[Cl-]OC=O NBEOBNPETXOCKI-UHFFFAOYSA-N 0.000 claims description 13
- HVZJRWJGKQPSFL-UHFFFAOYSA-N 1,1-Dimethylpropyl methyl ether Chemical compound CCC(C)(C)OC HVZJRWJGKQPSFL-UHFFFAOYSA-N 0.000 claims description 11
- 229960004295 valine Drugs 0.000 claims description 11
- 239000011541 reaction mixture Substances 0.000 claims description 7
- VKJXAQYPOTYDLO-UHFFFAOYSA-N 4-Methylphenethylamine Chemical compound CC1=CC=C(CCN)C=C1 VKJXAQYPOTYDLO-UHFFFAOYSA-N 0.000 claims description 6
- 229940117803 Phenethylamine Drugs 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 230000000875 corresponding Effects 0.000 claims description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N MeOtBu Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- 230000003197 catalytic Effects 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 4
- 238000007792 addition Methods 0.000 claims description 3
- 230000005591 charge neutralization Effects 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 230000001264 neutralization Effects 0.000 claims description 3
- 238000006386 neutralization reaction Methods 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-Methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 2
- XXBDWLFCJWSEKW-UHFFFAOYSA-N Dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 claims description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N N,N-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- ZCKAMNXUHHNZLN-UHFFFAOYSA-N Chlorphentermine Chemical compound CC(C)(N)CC1=CC=C(Cl)C=C1 ZCKAMNXUHHNZLN-UHFFFAOYSA-N 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 229950007046 chlorphentermine Drugs 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 12
- 239000004474 valine Substances 0.000 abstract description 6
- AOGYCOYQMAVAFD-UHFFFAOYSA-N Chloroformic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- 238000003756 stirring Methods 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 235000011121 sodium hydroxide Nutrition 0.000 description 8
- 239000012065 filter cake Substances 0.000 description 6
- FZQMJOOSLXFQSU-UHFFFAOYSA-N 3-[3,5-bis[3-(dimethylamino)propyl]-1,3,5-triazinan-1-yl]-N,N-dimethylpropan-1-amine Chemical compound CN(C)CCCN1CN(CCCN(C)C)CN(CCCN(C)C)C1 FZQMJOOSLXFQSU-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000012265 solid product Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- -1 chloro, methyl Chemical group 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000000855 fungicidal Effects 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011068 load Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
Abstract
A process is disclosed for preparing valine amide derivatives by reacting valine with chloroformic acid esters and phenethyl amines in water.
Description
PROCEDURE FOR THE OBTAINING OF SUBSTITUTE DERIVATIVES OF VALINAMIDA
FIELD OF THE INVENTION
The invention relates to valinamide derivatives and to a process for obtaining them.
BACKGROUND OF THE INVENTION
Valinamide derivatives are known and have an excellent effect in the fight against pests. They can especially be used as fungicides, above all in the protection of plants (EP-472 996). It has now been found that the known derivatives of valinamide can be prepared more simply and with greater yield as well as with greater purity, and basically the use of organic solvents can be desisted.
DESCRIPTION OF THE INVENTION
The object of the application is therefore a process for obtaining compounds of the formula (I) REF .: 29253
wherein R1 means i-propyl and R2 means chloro, methyl, ethyl or methoxy, wherein a) an aqueous alkaline solution of L-valine is allowed to react with isopropyl chloroformate and the reaction product, obtained in this way , after neutralization, b) is allowed to react again, if appropriate, in the presence of organic solvents, in the presence of catalytic amounts of a tertiary amine with isopropyl chloroformate and then the product of the reaction, obtained in this way, in case given after combination with organic solvents, c) it is allowed to react with correspondingly substituted phenethylamine, if appropriate dissolved in organic solvents, using either at process step b) or at process step c) at least one organic solvent.
The valinamide derivatives obtainable according to this process can be perfectly processed and isolated and obtained in a compact form with a higher space / time yield. The process according to the invention or the individual steps of processes a) and b) are preferably carried out in water as sole solvent or diluent. The products of the steps of processes a) and b) can be isolated in this case and used for further reactions. Preferably, however, the process will be carried out without intermediate isolation by way of the process referred to in a single container, optionally with reflux of the mother liquor to another load or, where appropriate, with a continuous process pipeline. For the steps of processes a) and b), isopropyl chloroformate is preferably used. In this case, the ester is preferably added to the corresponding solutions or to the reaction mixtures, the ester being added preferably in molar excess, based on the valine or on the product of the reaction from process step a) and in total in quantities of 2 to 3 moles, based on 1 mole of valine.
Temperatures or addition reaction for the process step a) are in this case preferably between -20 and 80 ° C, especially between 10 and 50 ° C and for process step b) preferably -20 to 40 ° C, especially from 10 to 30 ° C. Preferably, the process steps a) and b) are carried out at room temperature, if appropriate under cooling of the reaction, which takes place exothermically. The process step a) is carried out by alkaline means, that is to say preferably in the presence of inorganic bases such as KOH and, especially, NaOH. The base is present in excess, especially in an amount of 1 to 3 moles, based on 1 mole of valine. The neutralization in process step a) is preferably carried out with inorganic acids such as sulfuric acid and, especially, hydrochloric acid, especially at a pH value of about 7. Process step b) is carried out in the presence of of catalytic amounts of a tertiary amine, preferably pyridine, methylpyridine, dimethylaminopyridine, triethylamine and / or especially dimethylbenzylamine (Desmorapid DB®). Catalytic amounts will be understood in the present application preferably amounts of 1/10, 000 to 1/100 moles of catalyst per mole of valine. It is of special significance for the process step c) or for the further processing that the phenethylamines be dissolved in a little organic solvent and only then be reacted with the reaction products from process step b). The solvents used are preferably ethyl acetate, methyl tert-butyl ether and especially tert-amyl methyl ether (TAME). In this case, the amounts of organic solvents used are preferably 50 to 800 ml and in particular 100 to 500 ml, based on 0.3 mol of the corresponding phenethylamine. The phenethylamines previously dissolved in this way are then preferably added to the reaction mixture from process step b), the amount of phenethylamine being equimolar or in slight excess with respect to valine. In order to improve the preparation of the final compounds, which are obtained from process step c), the reaction mixtures obtained from process step c), optionally under pressure, at temperatures of 40 to boiling temperature, will be heated. of the corresponding organic solvent, until an optimum separation between the organic phase and the aqueous phase is observed. The preparation of the organic phase is carried out according to usual methods. The products obtainable according to the process of the invention, which are essentially constituted by mixtures of defined isomers of the desired valinamide derivatives, can be used, without further purification, for example as fungicides in the protection of plants. The method according to the invention therefore has, in addition to the preferences indicated above, the advantage that the process can be carried out in water as solvent and diluent, preferably with 50 to 500 g, especially with 100 to 300 g of water, Obtaining the desired products with high yield and high purity. The following examples serve to explain the invention. The invention is not limited to the examples.
EXAMPLES
EXAMPLE 1
To a mixture consisting of 105 g of water and 63.6 g (0.716 mole) of 45% strength sodium hydroxide solution, at room temperature, 35.8 g (0.305 mole) of L-valine are added. Stir until a clear solution is present. Subsequently, 45.4 g are added dropwise over the course of 2 hours at room temperature.
(0.366 moles) of isopropyl chloroformate. Stirring is continued for 30 minutes, adjusted to a pH value of 7 with 37% hydrochloric acid. Then 0.4 g (0.003 mole) of Desmorapid DB® is added from the reaction mixture. Stirring is continued for 15 minutes and then 38.4 g (0.31 mole) of isopropyl chloroformate are added. Stirring continues for another hour. A solution of 44.6 g (0.31 mol) of p-methylphenethylamine (3) in 200 ml of TAME (ter-amyl-methyl ether) is dosed in two hours. Immediately a white solid product precipitates, however, the mixture remains agitable. It is then heated to 70 ° C, at this temperature the separation of the phases is carried out and the organic phase is further washed with 100 ml of water. It is left to cool at 40 ° C and at this temperature a separation is carried out by filtration. The filter cake is further washed with a little TAME and then dried. 78.4 g of the product are obtained (content: 96.3%). This corresponds to a yield of 77.3% of the theory. From organic mother liquors are obtained, after solvent removal,
. 1 g of a residue, in which the desired product is contained in 43.7% (yield: 15.7% of the theory).
COMPARATIVE EXAMPLE 2
To the mixture consisting of 105 g of water and 63.6 g (0.716 mole) of 45% sodium hydroxide solution, at room temperature, 35.8 g (0.305 mole) of L-valine are added. Stir until a clear solution is present. Subsequently, 45.4 g (0.366 mol) of isopropyl chloroformate are heated dropwise over the course of 2 hours at room temperature. Stirring is continued for 30 minutes. A pH value of 7 is adjusted with 37% hydrochloric acid. Then 0.4 g (0.003 mole) of Desmorapid DB® is added to the reaction mixture. The mixture is stirred for a further 15 minutes and then 38.4 g (0.31 mol) of isopropyl chloroformate are added. It is stirred for another hour.
44.6 g (0.31 mol) of p-methylphenethylamine (3) are dosed in two hours. It is stirred for another hour. During this time the suspension formed becomes very thick, however, it remains justly agitable. The mixture is then separated by suction filtration at room temperature and the filter cake is further washed with 500 ml of water. After drying, 99.5 g of a solid product are obtained, which contains the desired product in 65.1%. This corresponds to a 66.3% yield of the theory.
EXAMPLE 3
.8 g (0.305 mole) of L-valine are dissolved, at room temperature, in a mixture consisting of 105 g of water and 63.6 g (0.716 mole) of 45% sodium hydroxide solution. Stir until a clear solution is present. Subsequently, 45.4 g (0.366 mol) of isopropyl chloroformate (98.9%) are added dropwise over the course of 2 hours. The mixture is stirred for a further 30 minutes and adjusted to a pH value of 7, by adding 2.9 g of 37% hydrochloric acid. 650 ml of TAME and 0.4 g of Desmorapid DB are added to the reaction mixture. Stirring is continued for another 15 minutes and then combined, over the course of one hour, with 38.4 g (0.31 mole) of isopropyl chloroformate (98.9%). Stirring is continued for 1 hour and a solution consisting of 44.6 g (0.31 mol) of p-methylphenethylamine (93.9%) in 130 ml of TAME is now dosed in 2 hours. Stir for an additional 1 hour and add 100 ml of sodium hydroxide solution (1N) to the suspension. The phases are separated at 55 ° C. The organic phase it is extracted at 55 ° C once with 50 ml of water and then cooled to 0 ° C. The mixture is stirred for a further 30 minutes and the solid product is filtered off by vacuum suction. The filter cake is further washed with a little TAME and dried in the vacuum drying cabinet. The filtrate is concentrated in the rotary evaporator. 75.1 g of a filter cake having an active product content of 99.7% (76.6% of the theory) are obtained. The residue of concentrated mother liquors for evaporation (17.2 g) has an active product content of 56.6%.
EXAMPLE 4 35.8 g (0.305 mole) of L-valine are dissolved at room temperature in a mixture consisting of 105 g of water and 63.6 g (0.716 mole) of 45% sodium hydroxide solution. Stir until a clear solution is present. Subsequently, 45.4 g (0.366 mol) of isopropyl chloroformate (98.9%) are added dropwise over the course of 2 hours. Stirring is continued for 30 minutes and a pH value of 7 is adjusted by the addition of 3 g of 37% hydrochloric acid. 650 ml of TAME, 15.3 g of the residue of the mother liquors from Example 3 and 0.4 g of Desmorapid DB® are added to the reaction medium. Stirring is continued for another 15 minutes and then combined, over the course of 1 hour, with 38.4 g (0.31 mole) of isopropyl chloroformate (98.9%). It is stirred for a further hour and then a solution consisting of 44.6 g (0.31 mol) of p-methylphenethylamine (93.9%) in 130 ml of TAME is dosed in 2 hours. Stirring is continued for 1 hour and 100 ml of sodium hydroxide lye (1N) is added to the suspension. The phases are separated at 55 ° C. The organic phase is extracted at 55 ° C once with 100 ml of water and then cooled to 0 ° C. The mixture is stirred for a further 30 minutes and the solid product is filtered off by vacuum suction. The filter cake is further washed with a little TAME and dried in the vacuum drying cabinet. The filtrate is concentrated by evaporation in the rotary evaporator. 92.8 g of a filter cake having an active product content of 97.4% (92.5% of the theory) are obtained.
It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, it is claimed as property what is contained in the following
Claims (8)
1. Process for obtaining compounds of the formula (I) wherein R 1 signifies i-propyl, and R 2 signifies chlorine, methyl, ethyl or methoxy, characterized in that a) an alkaline aqueous solution of L-valine is allowed to react with isopropyl chloroformate and the reaction product, obtained in this way , after neutralization, b) is allowed to react again, if appropriate, in the presence of organic solvents, in the presence of catalytic amounts of a tertiary amine with isopropyl chloroformate and then the product of the reaction, obtained in this way, in case given after combination with organic solvents, c) it is allowed to react with correspondingly substituted phenethylamine, if appropriate dissolved in organic solvents, using either at process step b) or at process step c) at least one organic solvent.
2. Process according to claim 1, characterized in that the addition or reaction temperature of process step a) is at -20 to 80 ° C, that of process step b) at -20 to 40 ° C and that of the process step c) at 0 to 30 ° C.
3. Process according to claim 1, characterized in that pyridine, methylpyridine, dimethylaminopyridine, triethylamine and / or dimethylbenzylamine are used as catalytically acting ter-amine in process step b).
4. Process according to claim 1, characterized in that ethyl acetate, methyl tert-butyl ether or tert-amyl methyl ether are used as organic solvents.
5. Process according to claim 1, characterized in that the amounts of organic solvent are from 50 to 800 ml, based on 0.3 mol of the corresponding phenethylamine.
6. Process according to claim 1, characterized in that in the process step c) the reaction mixture is heated, after the addition of the phenethylamine, at 40 ° C to the boiling temperature of the corresponding organic solvent.
7. The product mixtures obtainable according to the method of claim 1.
8. Process according to claim 1, characterized in that p-methylphenethylamine is used in process step c).
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19631270.1 | 1996-08-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA99001055A true MXPA99001055A (en) | 2000-01-01 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5783734A (en) | Process for preparing N-methyl-N'-nitroguanidine | |
| US6077969A (en) | Process for preparing substituted valine amide derivatives | |
| CA1038879A (en) | PROCESS FOR MAKING A C1-C7 ALIPHATIC HYDROCARBYL ESTER OF AN N-(2,6-DI(C1-C7ALKYL)PHENYL.alpha.-AMINOCARBOXYLIC ACID | |
| CA1299584C (en) | Process for producing 1,6-di(n -cyano-n -guanidino) hexane | |
| MXPA99001055A (en) | Process for preparing substituted valine amide derivatives | |
| US5696283A (en) | Preparation of methyl isoproylideneaminooxyacetoxyacetate | |
| KR102548504B1 (en) | Method for manufacturing of guanidino-benzoate sulfonic acid compound | |
| US4275216A (en) | Process for preparing 4(5)-hydroxymethyl 5(4)-lower alkyl imidazoles | |
| US4001284A (en) | Process for the manufacture of 5-sulfamoyl-anthranilic acids | |
| US5488170A (en) | Process for producing 3-methyl-1-phenylphospholene oxide | |
| US5912354A (en) | Process for preparing 4-amino-1,2,4-triazolin-5-ones | |
| US4612385A (en) | Process for the preparation of phenyl N-(2-biphenylylsulfonyl) carbamate | |
| JP4430400B2 (en) | Method for producing 2-anilino-4,6-dimethylpyrimidine | |
| GB2101130A (en) | Process for preparing N-carbamoylbenzoic acid sulfimide derivatives | |
| SU1057494A1 (en) | Process for preparing 4,4-bis-(4-nitrophenylthio)-arylene | |
| JP3537489B2 (en) | Method for producing N-long-chain acylamino acids and salts thereof, intermediate amidonitrile, and method for producing the same | |
| JP2695035B2 (en) | Method for producing 2- (methylthio) barbituric acid | |
| JPH026459A (en) | Production of 4-quanidinomethyl-cyclohexane carboxylic acid | |
| US4235819A (en) | Process for isolating 1-(alkoxyphenyl)-5-(phenyl)biguanide compounds from a crude, acid reaction mixture thereof | |
| HU202481B (en) | Process for producing n-phenyl-n-(methoxyacetyl)-dl-alanine methyl ester derivatives | |
| JPH0139427B2 (en) | ||
| JPH02244A (en) | Production of aminophenol ether | |
| HUT64736A (en) | Method for producing thyramine derivatives | |
| JPS59130850A (en) | Manufacture of n,n'-diformylhydrazine | |
| JPH06504766A (en) | Method for producing solid betaines |