MXPA99005361A

MXPA99005361A - Method for producing trifluoroacetoacetic acid anilides

Info

Publication number: MXPA99005361A
Application number: MXPA/A/1999/005361A
Authority: MX
Inventors: Lantzsch Reinhard; Steinbeck Karl; Kampfen Ulrich
Original assignee: Bayer Ag 51373 Leverkusen De
Priority date: 1996-12-19
Filing date: 1999-06-09
Publication date: 2000-02-02

Abstract

A novel method for producing trifluoroacetoacetic acid anilides of formula (I), wherein R1 has the meanings cited in the description, and trifluoroacetoacetic acid chloride is made to react with anilines of formula (III) optionally in the presence of an acid-binding agent and optionally in the presence of a diluent. The compounds of formula (I) are suitable as intermediate products in the production of uracil derivatives effectively used as herbicides.

Description

PROCEDURES FOR THE OBTAINING OF ANYLIDES OF THE TRIFLUORACETOACTIC ACID. Field of Invention The present invention relates to a novel process for the preparation of trifluoroacetoacetic acid anuides, which can be used as intermediates for the preparation of uracil derivatives with herbicidal activity. DESCRIPTION OF THE PRIOR ART It has already been disclosed that the arylamides of trifluoroacetoacetic acid can be prepared by reacting esters of trifluoroacetoacetic acid with arylamines (see DE-A 42 18 159, EP-A 0 598 436 and J. Het. Chem. 2 (1965), 124). However, the drawback of this method is that it can not be widely applied and that the desired products are obtained only with relatively low yields, since harmful side reactions occur. In this way, arylamine attacks the carbonyl group, which is contiguous with the trifluoromethyl group, considerably. The enamine formed in this case reacts easily with another molecule of arylamine so that bis-adducts are obtained.

This reaction can be represented by the Ref .: 30384 formulas below.

Ar-NH, CF, - C-CH, - COOR CF, - C = CH - COOR II OR NH-Ar Ar-NH, CF_C = CH - CO - NH - Ar NH - Ar Ar = aryl (for example) R = alkyl (for example methyl or ethyl). It is further known that arylamides of trifluoroacetoacetic acid can be prepared if they dissociate from the bis-adducts, of the structure given above, an arylamine molecule (cf. DE-A-42 18 159). The drawback of this method is that a step is required more than in the case of the methods described above. Furthermore, the yields are also unsatisfactory in this case for an industrial-scale implementation. Detailed description of the invention. It has now been found that trifluoroacetoacetic acid anvils of the formula are obtained wherein R1 means halogen or a residue of the formula -N SO- 3 where R 2 signifies hydrogen or optionally substituted alkyl and R 3 signifies optionally substituted alkyl, optionally substituted cycloalkyl or means substituted aryl if the trifluoroacetoacetyl chloride of the formula is reacted CF3- C-CH, -CO-CI (I!) with anilines of the formula wherein R1 has the meanings indicated above, optionally in the presence of an acid-accepting agent and, if appropriate, in the presence of a diluent at temperatures between -20 ° C and + 40 ° C. It should be regarded as extremely surprising that the trifluoroacetoacetic acid anilines of the formula (I) can be prepared in high yields according to the methods of the invention, in a reaction without problems. A reaction of this type is not expected above all because the trifluoroacetoacetyl chloride, necessary as the starting substance, is stable only for a short period of time even at low temperatures (see Chem. Abs. 1964, 2788 and following and GB-A 931 689). It is surprising that such anilines of the formula * III), in which R1 signifies a radical of the formula -NH-S02_R3 do not show a worthy reaction of the trifluoroacetyl chloride with the sulfonylamino group. The process according to the invention is characterized by a series of advantages. In this way, the necessary starting products are easily accessible and also in larger quantities. In addition the carrying out of the reaction and the isolation of the desired substances did not pose any kind of problems. It is especially favorable that the anilines of Trifluoroacetoacetic acid are obtained with high yields and with great purities. Otherwise, the procedure can be widely used. If the trifluoroacetoacetyl chloride and the 4-cyano-2-fluoro-methylsulfonyl-amino-aniline are used as starting materials, the development of the prori-imi pni-n according to the invention can be represented by means of the scheme of the following formulas: The trifluoroacetoacetyl chloride, which is necessary as starting material in carrying out the process according to the invention, of the formula (II) is known (cf. GB-A 931 689). The novel anilines which are also necessary as starting materials for carrying out the process according to the invention are generally defined by the formula (III). Compounds can preferably be used of the formula (III), wherein R 1 means fluorine, chlorine, bromine or a residue of the formula -N S02- J where R 2 signifies hydrogen or means alkyl having from 1 to 6 carbon atoms, optionally substituted by cyano, by halogen, by alkoxy with 1 to 4 carbon atoms, by alkyl with 1 to 4 carbon atoms, by alkylcarbonyl with 1 to 4 carbon atoms; carbon atoms, in the alkyl group or by alkylaminocarbonyl with 1 to 4 carbon atoms in the alkyl part and R3 means alkyl with 1 to 6 carbon atoms, optionally substituted by cyano, by halogen, by alkoxy with 1 to 4 atoms of carbon, by alkylthio with 1 to 4 carbon atoms, by alkylcarbonyl with 1 to 4 carbon atoms, by alkoxycarbonyl with 1 to 4 carbon, by alkylaminocarbonyl with 1 to 4 carbon atoms or by phenyl, means cycloalkyl with 3 to 6 carbon atoms optionally substituted one to three times, in the same or different ways, by halogen, by cyano and / or by alkyl with 1 to 4 carbon atoms, or optionally substituted phenyl of one to three times, d equal or differently by halogen, pocy, by alkyl having 1 to 4 carbon atoms or halogenalkyl having 1 to 2 carbon atoms and 1 to 5 carbon atom, by alkoxy with 1 to 4 carbon atoms and / haloalkoxy with 1 or 2 carbon atoms and 1 to 5 carbon atom. The anilines of the formula (III), in which R 1 means fluorine, chlorine, or a radical of the formula, can be used, especially preferably.

-N SO- where R 2 signifies hydrogen or means methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl substituted, where appropriate, by cyano, by fluorine, by chlorine, by methoxy, by ethoxy, by methylthio, for ethylthio, for acetyl, for propionyl, for methoxycarbonyl, for ethoxycarbonyl, for methylaminocarbonyl for ethylaminocarbonyl and R3 means methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, respectively substituted if necessary by cyano, by fluorine, by chlorine, by methoxy, by ethoxy, by methylthio, ethylthio, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, ethylcarbonyl or phenyl or cyclopropyl, cyclopentyl or cyclohexyl optionally substituted one to three times, in the same or in different ways by fluorine, by chlorine, by cyano, by methyl and / or by ethyl, means phenyl, optionally substituted one to three times, in the same or different way by fluorine, by chlorine, by cyano, by methyl, by ethyl , by trifluoromethyl, by methoxy, by ethoxy, by trifluoromethoxy and / or difluoromethoxy. The anilines of the formula (III) are known or can be prepared by methods known per se (cf. EP-A-0 648 772). Suitable acid acceptors in carrying out the process according to the invention are all customary inorganic or organic bases. Preference is given to using carbonates and bicarbonates of alkali metals or alkaline earth metals, such as sodium, potassium or calcium carbonate, sodium, potassium or calcium bicarbonate, as well as basic organic hydrogenated compounds, especially trimethylamine, triethylamine, tripropylamine, tributylane, ethyl-diisopropylamine, N, N-dimethyl- cyclohexylamine, ethyl-dicyclohexylamine, N, -dimethyl-aniline, N, N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2, -dimethyl-, 2,6-dimethyl- , 3,4-dimethyl- and 3, 5-dimethyl-pyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylamine-pyridine, N-methyl-piperidine, 1,4-diazabicyclo [2, 2, 2] -octane (DABCO), 1,5-diazabicyclo- [4, 3, 0] non-5-ene (DBN), or 1,8-diazabicyclo [5, 4, 0] -undec-7 -eno (DBU). Suitable diluents for carrying out the process according to the invention are all customary inert organic solvents. Aliphatic, alicyclic or aromatic hydrocarbons, if appropriate halogenated, may be used, for example benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetraeloride, ethers, such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, ethylene glycol dimethyl or diethyl ether, tert-butyl methyl ether or tere. -amil-methyl ether. Also nitriles, such as ecetonitrile, propionitrile or butyronitrile, and also also esters, such as methyl acetate or ethyl acetate. The reaction temperatures in carrying out the process according to the invention can vary within certain limits. In general, temperatures are worked between -20 ° C and + 40 ° C, preferably between -10 ° C and + 30 ° C. In carrying out the process according to the invention, the reaction is generally carried out under atmospheric pressure. However, it is also possible to work under higher pressure. In carrying out the process according to the invention, preference is given to working under protective gas, such as nitrogen or argon. In carrying out the process according to the invention, about 1 mole of the aniline of the formula (III) is used, generally 1 to 3 moles, preferably 1 to 1.9 moles of trifluoroacetoacetyl chloride of the formula (II) as well as from 1 to 3, preferably from 1 to 1.9 moles of acid accepting agents. In a preferred embodiment, the aniline of the formula (III) and the acid-accepting agent are placed in a diluent and then the trifluoroacetoacetyl chloride of the formula (II) is added dropwise. in a diluent. Working up is carried out by customary methods. In general, the process proceeds in such a way that the crystalline product formed is filtered off, washed and dried. Eventually the impurities present can still be removed according to usual methods (see the preparation examples).

The trifluoroacetoacetic acid rings preparable according to the invention of the formula (I) can be present in the "keto" form of the formula well as hydrate of the formula (la) (ia) well the tautomeric "enol" form of (I) of the formula in order to simplify, only the "keto" form will be indicated respectively. The trifluoroacetoacetic acid anhydrides prepared according to the invention of the formula (I) are valuable intermediate products for the synthesis of uracil with herbicidal properties. In this way, uracil derivatives of the formula can be prepared wherein R1 has the meanings indicated above and R4 signifies hydrogen, hydroxy, amino, means methyl, ethyl, n- or i-propyl, n-, or i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy substituted, where appropriate, by hydroxy, by cyano, by fluorine, by chlorine, by methoxy or by ethoxy, or means substituted propenyl, butenyl, propynyl butynyl respectively, if appropriate, by cyano, fluorine, chlorine or bromine, if they are reacted with anhydride of the acid Lrifluoroacetoacetic acid of the formula (l) wherein R1 has the meanings given above, with phosgene in the presence of an acid-accepting agent, such as pyridine or 4-dimethylaminopyridine, and in the presence of a diluent, such as toluene or tetrahydrofuran, at temperatures ranging from -20 ° C and + 150 ° C and the phenyloxazin-diones, obtained in this case, from the formula wherein R1 has the meanings indicated above, are reacted with amino-compounds of the formula H2N-R4 (VI ' wherein R 4 has the meanings given above, optionally in the presence of an acid-accepting agent and, if appropriate, in the presence of a diluent, such as ethanol, at temperatures between -50 ° C and + 80 ° C . The uracil derivatives of the formula (IV) and their Use as herbicides are known (see EP-A 0 40 382, EP-A 0 648 749 and WO 9532 952). The process according to the invention will be explained by means of the following examples: Preparation examples. Example 1, .3 (45 mmol) of 4-cyano-2-fluoro-5-methylsulfonylamino anilin and 4.28 g (54 mmol) of pyridine in 110 ml are added dropwise to a suspension. of methylene chloride, under an argon atmosphere, at 20 to 22 ° C, under stirring, over the course of 15 minutes, 40.4 g of a 35% solution of trifluoroacetoacetyl chloride (81 mmol) in methylene chloride. Once the addition is completed, it is finally rinsed in a drip funnel with 10 ml. of methylene chloride, which is added, dropwise, also to the reaction mixture. The progress of the reaction is monitored by thin layer chromatography. After a reaction time of 15 minutes, filtration separation is carried out by cooling at 0 ° C. precipitate formed, further washing with methylene chloride and drying. 15 g of a pulverulent substance are obtained which is combined with water. The mixture is extracted three times with ethyl acetate. The combined organic phases are concentrated by evaporation under reduced pressure, after drying over sodium sulfat. The remaining product is dried under vacuum. In this way, 12.2 g (73.8% of the theory) of N- (4-cyano-2-fluoro-5-methylsulfanylamino-phenyl) -4,4,4-trifluoro-3-oxo-bureairamide is obtained in the form of a solid substance with a melting point of 186 to 191? C. Example 2 A cooled mixture at 10 ° C, consisting of 169.5 g (1.1 mmoles) of 2,5-difluoro-4-cyano-aniline, 104.5 g of pyridine (1.32 mmoles) and 640 ml of sodium chloride, are added dropwise. methylene, under an argon atmosphere and under stirring over the course of 25 minutes, 7.13 g of a solution of trifluoroacetoacetyl chloride (1.43 mol, 35% solution) in methylene chloride. Once the addition is complete, the dropping funnel is finally rinsed with 20 ml of methylene chloride, which is also added dropwise to the mixture. the reaction. The progress of the reaction is monitored by thin layer chromatography. The further 1 hour of stirring at 22 ° C the reaction mixture is cooled to 0 ° C and stirred for 15 minutes at this temperature. The precipitate formed is separated by filtration, washed with methylene chloride and dried. 209.3 g of a crude product that is combined with water is obtained. The mixture formed is extracted several times with ethyl acetate.The aqueous phase is acidified strongly with concentrated hydrochloric acid and extracted again with ethyl acetate.The combined organic phases are washed with water and then dried over sodium sulfate. The remaining solution after filtration is concentrated by evaporation under reduced pressure, the remaining product is dried under vacuum, thereby obtaining 150.4 g (47.1% of theory) of the N- (4-cyano-2,5-diflurophenyl). ) -4,4,4-trifluoro-3-oxo-butyramide in the form of a white solid substance with a melting point of 176 to 181 ° C. From the mother liquors, a new formulation is isolated, indicated additional amount of product in the form of the hydrate of the compound of the formula (1-2) The total yield is 54% of the theory Example 3 In a manner analogous to that of Example 1, N- (4-cyano-2-fluoro-5-ethylsulfonylamino-phenyl) -4,4 is prepared from 4-cyano-2-fluoro-5-ethylsulphonylaminoaniline, 4-trifluoro-3-oxobutyramide with a melting point of 185 to 187 ° C. Application example A. Obtaining the compound of the formula 120 g of a 20% solution of phosgene in toluene are added dropwise at 40 ° C. under stirring to a mixture of 60 g (0.20 moles) of the N- (4-cyano) amide -2,5-difluoro-phenyl) -3-oxo-4,4,4-trifluoro-1-butanoic acid, 40 ml of pyridine, 4 g of 4-dimethylamino-pyridine and 1.5 liters of toluene. The reaction mixture is then stirred for a further 4 hours at 40 ° C. The excess phosgene is then removed by blowing with nitrogen. The remaining mixture is washed three times with water, it is dried over sodium sulfate and filtered. The solvent is carefully removed from the filtrate by vacuum distillation of the water tube. 63.7 g (77.5% of theory) of 3- (4-cyano-2, 5-difluoro-phenyl) -3,4-dihydro-6-trifluoromethyl-2H-1, 3-oxazin-2, 4 are obtained. -Diona in the form of a viscous mass, which crystallizes slowly. Obtaining the compound of the formula 7 ml of a 25% aqueous solution of ammonia (0.10 mole of NH 3) are added dropwise at room temperature (about 20 ° C), under stirring, to a mixture of 15.9 g (0.05 mole). of 3- (4-cyano-2, 5-difluorophenyl) -3,4-dihydro-6-trifluoromethyl-2H-1, 3-oxazin-2,4-dione and 100 ml of ethanol. The reaction mixture is stirred for 20 hours at room temperature. It is then concentrated by evaporation under vacuum of the water pump and the residue is taken up in ethyl acetate. The formed solution is washed with water, dried over sodium sulfate and filtered. The filtrate is concentrated by evaporation under reduced pressure, the residue is digested with a little isopropanol and the product crystalline formed is isolated by suction filtration 11.8 g (74% of the theory) of l- (4-cyano-2,5-difluoro-phenyl) -3,6-dihydro-2,6-dioxo-4 are obtained. -trifluoromethyl-1 (2H) -pyrimidine with a melting point of 234 ° C. 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 co or "property what-contained in the following:

Claims

1- Procedure for obtaining trifluoroacetoacetic acid anuides of the formula OR) wherein R1 means halogen or a residue of the formula .R¿ - N so2-R > where R <2> is hydrogen or optionally substituted alkyl, and R <3> represents optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted name, characterized in that the trifluoroacetoacetyl chloride of the formula is reacted CF-C-CH -CO-CI _ ,. OR with aniline of the formula wherein R1 has the meanings given above, if appropriate in the presence of an acid-accepting agent and, if appropriate, in the presence of a diluent at temperatures between -20 ° C and + 40 ° C.

2- Process according to claim 1, characterized in that anilines of the formula (III) are used as starting materials, in which R 1 means fluorine, chlorine, bromine or a radical of the formula - SO-R where R 2 signifies hydrogen or means alkyl having from 1 to 6 carbon atoms, optionally substituted, by cyano, by halogen, by alkoxy with 1 to 4 carbon atoms, by alkylthio with 1 to 4 carbon atoms, by alkylcarbonyl with 1 to 4 atoms of carbon, in the alkyl group or by alkylaminocarbonyl with 1 to 4 carbon atoms in the alkyl part and R3 means alkyl with 1 to 6 carbon atoms, optionally substituted by cyano, by halogen, by alkoxy with 1 to 4 carbon atoms , by alkylthio with 1 to 4 carbon atoms, by alkylcarbonyl with 1 to 4 carbon atoms, by alkoxycarbonyl with 1 to 4 carbon atoms, by alkylaminocarbonyl with 1 to 4 carbon atoms or by phenyl, means cycloalkyl with 3 to 4 carbon atoms. to 6 carbon atoms optionally substituted one to three times, in the same or different forms, by halogen, by cyano and / or by alkyl having 1 to 4 carbon atoms, or by phenyl, optionally substituted by one to three times, in the same or different ways by halogen, by cyano, by alkyl with 1 to 4 carbon atoms by halogenalkyl with 1 or 2 carbon atoms and 1 to 5 carbon atoms, by alkoxy with 1 to 4 atoms of carbon and / or halogenoalkoxy with 1 or 2 atoms d e carbon and 1 to 5 carbon atoms.

3- Process according to claim 1, characterized in that anilines of the formula (III) are used as starting materials, in which R 1 means fluorine, chlorine, or a radical of the formula - S02- J where R 2 signifies hydrogen or means methyl, ethyl, n-i-propyl, n-, i-, s- or t-butyl substituted, where appropriate, by cyano, by fluorine, by chlorine, by methoxy, by ethoxy, by methylthio etiitol, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl and R3 means methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl substituted respectively in case given by cyano, by fluorine, by chlorine, by methoxy, by ethoxy, by methylthio, by ethylthio, by acetyl, by propinyl, by methoxycarbonyl, by ethoxycarbonyl, by methylaminocarbonyl, by ethylaminocarbonyl or by phenyl or means cyclopropyl, cyclopentyl or cyclohexyl If necessary, they can be replaced one to three times, in the same or different ways, by fluorine, chlorine, procyano, methyl and / or ethyl, phenyl, optionally substituted one to three times, equal or in different ways by fluorine, by chlorine, by cyano, by methyl, by ethyl by trifluoromethyl, by methoxy, by ethoxy, by trifluoromethoxy and / or difluoromethoxy.

4-process according to claim 1, characterized in that l aniline of the formula is used as starting materials

5- Process according to claim 1, characterized in that the aniline of the formula is used as starting material

6- Process according to claim 1, characterized in that the aniline of the formula is used as the starting material

7- Procedure for obtaining uracil derivatives of the formula wherein R1 has the meanings indicated in claim 1 and R4 means hydrogen, hydroxy, amino, means methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy substituted respectively by hydroxy, cyano, fluorine, chlorine, methoxy or ethoxy, or means propenyl, butenyl, propynyl or butynyl substituted, where appropriate, by cyano, fluorine, chlorine or bromine, characterized in that if they are reacted in anhydrous form, trifluoroacetoacetic acid of the formula wherein R1 has the meanings indicated above, with phosgene in the presence of an acid-accepting agent, and in the presence of a diluent, at temperatures between -20 ° C and + 150 ° C and the phenyloxazindiones, obtained in this case, from the formula wherein R1 has the meanings indicated above, are reacted with amino-compounds of the formula H2N R ": vi) in which R 4 has the meanings given above, if appropriate in the presence of an acid-accepting agent and, if appropriate, in the presence of a diluent, at temperatures between -50 ° C and + 80 ° C. R E S U M E N According to a process, trifluoroacetoacetic acid of the formula (I) can be prepared wherein R1 has the meanings indicated in the description, if the trifluoroacetoacetyl chloride is reacted with anilines of the formula (III) if appropriate in the presence of an acid-binding agent and, if appropriate, in the presence of a diluent. The compounds of the formula (I) are suitable as intermediates for the preparation of uracil derivative of herbicidal effect.