METHOD FOR PREPARING A URACIL COMPOUND CONTAINING A CARBOXYLATE FRAGMENT

Abstract

The present invention relates to the field of herbicides, in particular to a preparation method for a 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl) benzoate compound of formula (I). The present invention constructs a uracil ring under an acidic condition, and the intermediate prepared by this method can be used to prepare a novel high-efficiency uracil herbicide of structural formula (I), which has stable chemical properties and better herbicidal activity. The synthesis route is simple, and has broad application prospects in agriculture. The present invention further provides intermediate compounds used in the method, as well as methods for producing the intermediate compounds.

##STR00001##

Claims

1. A method for preparing a uracil compound containing a carboxylate fragment with the following reaction scheme, comprising: ##STR01438## reacting the compound of formula (V) with a methylation reagent in the presence of a base in an organic solvent at 20 C. to the boiling point of the solvent to obtain a uracil compound of formula (I); wherein, R.sub.1 and R.sub.2 are each independently selected from hydrogen or methyl; or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a three-membered carbocycle; R.sub.3 is selected from C.sub.13 alkoxy-C.sub.13 alkyl, C.sub.13 halogenated alkoxy-C.sub.13 alkyl, C.sub.26 enyloxy-C.sub.13 alkyl, C.sub.26 halogenated enyloxy-C.sub.13 alkyl, C.sub.26 ynyloxy-C.sub.13 alkyl, or C.sub.26 halogenated ynyloxy-C.sub.13 alkyl; when R.sub.1 is selected from hydrogen and R.sub.2 is selected from methyl, the chiral carbon atom connected thereto is selected from either an R configuration or an S configuration, or a mixture of the two; and in the mixture, a ratio of R to S is 1:99 to 99:1.

2. The method as recited in claim 1, wherein the base is selected from 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, pyridine, 2-methylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU), 2,6-Lutidine, NaH, NaNH.sub.2, NaHCO.sub.3, Na.sub.2CO.sub.3, K.sub.2CO.sub.3, KHCO.sub.3, Cs.sub.2CO.sub.3, NaOH, LiOH, or KOH; the methylation reagent is selected from dimethyl sulfate, chloromethane, methyl bromide, methyl iodide, methyl p-toluenesulfonate,or methyl trifluoromethanesulfonate.

3. A method for preparing a uracil compound containing a carboxylate fragment of formula (V) with the following reaction scheme, comprising: ##STR01439## reacting the compound of formula (IV) with R.sub.4 3-(3,3-dimethylureido)-4,4,4-trifluorobut-2-enoate or 2-(dimethylamino)-4-(trifluoromethyl)-6H-1,3-oxazin-6-one in an organic solvent at 20 C. to the boiling point of the solvent in the presence of an acid to obtain a compound of formula (V); wherein, R.sub.1 and R.sub.2 are each independently selected from hydrogen or methyl; or RI and R.sub.2 together with the carbon atom to which they are attached form a three-membered carbocycle; R.sub.3 is selected from C.sub.13 alkoxy-C.sub.13 alkyl, C.sub.13 halogenated alkoxy-C.sub.13 alkyl, C.sub.26 enyloxy-C.sub.13 alkyl, C.sub.26 halogenated enyloxy-C.sub.13 alkyl, C.sub.26 ynyloxy-C.sub.13 alkyl, or C.sub.26 halogenated ynyloxy-C.sub.13 alkyl; when R.sub.1 is selected from hydrogen and R.sub.2 is selected from methyl, the chiral carbon atom connected thereto is selected from either an R configuration or an S configuration, or a mixture of the two; and in the mixture, a ratio of R to S is 1:99 to 99:1; R.sub.4 is selected from methyl or ethyl.

4. The method as recited in claim 3, wherein the acid is selected from formic acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, sulfuric acid, hydrochloric acid, phosphoric acid, or nitric acid.

5. A method for preparing an aniline compound containing a carboxylate fragment of formula (IV) with the following reaction scheme, comprising: ##STR01440## reacting the compound of formula (III) with a reductant in water or an organic solvent at 20 C. to the boiling point of the solvent to obtain a compound of formula (IV); wherein, R.sub.1 and R.sub.2 are each independently selected from hydrogen or methyl; or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a three-membered carbocycle; R.sub.3 is selected from C.sub.13 alkoxy-C.sub.13 alkyl, C.sub.13 halogenated alkoxy-C.sub.13 alkyl, C.sub.26 enyloxy-C.sub.13 alkyl, C.sub.26 halogenated enyloxy-C.sub.13 alkyl, C.sub.26 ynyloxy-C.sub.13 alkyl, or C.sub.26 halogenated ynyloxy-C.sub.13 alkyl; when R.sub.1 is selected from hydrogen and R.sub.2 is selected from methyl, the chiral carbon atom connected thereto is selected from either an R configuration or an S configuration, or a mixture of the two; and in the mixture, a ratio of R to S is 1:99 to 99:1.

6. The method as recited in claim 5, wherein the reductant is selected from hydrogen, metal hydride, semimetal hydride and its derivatives, reduced iron powder or reduced zinc powder.

7. A method for preparing a nitrobenzene compound containing a carboxylate fragment of formula (III) with the following reaction scheme, comprising: ##STR01441## reacting the compound of formula (II) with a substituted hydroxyacetate in the presence of a base in an organic solvent at 20 C. to the boiling point of the solvent to obtain a compound of formula (III); wherein, R.sub.1 and R.sub.2 are each independently selected from hydrogen or methyl; or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a three-membered carbocycle; R.sub.3 is selected from C.sub.13 alkoxy-C.sub.13 alkyl, C.sub.13 halogenated alkoxy-C.sub.13 alkyl, C.sub.26 enyloxy-C.sub.13 alkyl, C.sub.26 halogenated enyloxy-C.sub.13 alkyl, C.sub.26 ynyloxy-C.sub.13 alkyl, or C.sub.26 halogenated ynyloxy-C.sub.13 alkyl; when R.sub.1 is selected from hydrogen and R.sub.2 is selected from methyl, the chiral carbon atom connected thereto is selected from either an R configuration or an S configuration, or a mixture of the two; and in the mixture, a ratio of R to S is 1:99 to 99:1.

8. The method as recited in claim 7, wherein the base is selected from 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, pyridine, 2-methylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU), 2,6-Lutidine, NaH, NaNH.sub.2, NaHCO.sub.3, Na.sub.2CO.sub.3, K.sub.2CO.sub.3, KHCO.sub.3, Cs.sub.2CO.sub.3, NaOH, LiOH, or KOH.

9. The method as recited in claim 1, wherein the organic solvent is one or more of alcohol, alkane, chloroalkane, ether, ester, aromatic hydrocarbon, halogenated aromatic hydrocarbon, ketone, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, or dimethyl sulfoxide.

10. The method as recited in claim 9, wherein the organic solvent is one or more of methanol, ethanol, isopropanol, butanol, tert-butanol, cyclohexanol, ethylene glycol, pentane, n-hexane, cyclohexane, heptane, octane, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, petroleum ether, ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, 1,4-dioxane, ethyl acetate, butyl acetate, benzene, toluene, o-xylene, m-xylene, p-xylene, xylene, chlorobenzene, acetone, butanone, 4-methyl-2-pentanone, cyclohexanone, N-methylpyrrolidone, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, or dimethyl sulfoxide.

11. A uracil compound containing a carboxylate fragment of formula (V): ##STR01442## wherein R.sub.1 and R.sub.2 are each independently selected from hydrogen or methyl; or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a three-membered carbocycle; R.sub.3 is selected from C.sub.13 alkoxy-C.sub.13 alkyl, C.sub.13 halogenated alkoxy-C.sub.13 alkyl, C.sub.26 enyloxy-C.sub.13 alkyl, C.sub.26 halogenated enyloxy-C.sub.13 alkyl, C.sub.26 ynyloxy-C.sub.13 alkyl, or C.sub.26 halogenated ynyloxy-C.sub.13 alkyl; when R.sub.1 is selected from hydrogen and R.sub.2 is selected from methyl, the chiral carbon atom connected thereto is selected from either an R configuration or an S configuration, or a mixture of the two; and in the mixture, a ratio of R to S is 1:99 to 99:1.

12. An aniline compound containing a carboxylate fragment of formula (IV): ##STR01443## wherein, R.sub.1 and R.sub.2 are each independently selected from hydrogen or methyl; or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a three-membered carbocycle; R.sub.3 is selected from C.sub.13 alkoxy-C.sub.13 alkyl, C.sub.13 halogenated alkoxy-C.sub.13 alkyl, C.sub.26 enyloxy-C.sub.13 alkyl, C.sub.26 halogenated enyloxy-C.sub.13 alkyl, C.sub.26 ynyloxy-C.sub.13 alkyl, or C.sub.26 halogenated ynyloxy-C.sub.13 alkyl; when R.sub.1 is selected from hydrogen and R.sub.2 is selected from methyl, the chiral carbon atom connected thereto is selected from either an R configuration or an S configuration, or a mixture of the two; and in the mixture, a ratio of R to S is 1:99 to 99:1.

13. A nitrobenzene compound containing a carboxylate fragment of formula (III): ##STR01444## wherein, R.sub.1 and R.sub.2 are each independently selected from hydrogen or methyl; or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a three-membered carbocycle; R.sub.3 is selected from C.sub.13 alkoxy-C.sub.13 alkyl, C.sub.13 halogenated alkoxy-C.sub.13 alkyl, C.sub.26 enyloxy-C.sub.13 alkyl, C.sub.26 halogenated enyloxy-C.sub.13 alkyl, C.sub.26 ynyloxy-C.sub.13 alkyl, or C.sub.26 halogenated ynyloxy-C.sub.13 alkyl; when R.sub.1 is selected from hydrogen and R.sub.2 is selected from methyl, the chiral carbon atom connected thereto is selected from either an R configuration or an S configuration, or a mixture of the two; and in the mixture, a ratio of R to S is 1:99 to 99:1.

14. Use of a uracil compound containing a carboxylate fragment of formula (V) as claimed in claim 11 in the preparation of 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl) benzoate compound of formula (I).

15. Use of an aniline compound containing a carboxylate fragment of formula (IV) as claimed in claim 12 in the preparation of a uracil compound containing a carboxylate fragment of formula (V).

16. Use of a nitrobenzene compound containing a carboxylate fragment of formula (III) as claimed in claim 13 in the preparation of an aniline compound containing a carboxylate fragment of formula (IV).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0123] Hereinafter, the present invention will be described with reference to the following but not limiting examples. Any simple replacement or improvement made to the present invention by the person skilled in the art shall fall within the protection scope of the present invention.

[0124] Several methods for preparing compounds of the present invention are explained in detail in the following schemes and examples. The raw materials can be purchased from the market or prepared using methods known in the literature or as detailed in the explanation. The person skilled in the art should understand that the compounds of the present invention can also be synthesized using other synthesis routes. Although specific raw materials and conditions in the synthesis route have been explained below, they can be easily replaced with other similar raw materials and conditions, and various isomers of the compounds prepared by variants or variations of the preparation method of the present invention shall fall within the protection scope of the present invention. In addition, the preparation method described below can be further modified according to the disclosure of the present invention, using conventional chemical methods well-known to one skilled in the art, for example, protecting appropriate groups during the reaction process, and so on.

[0125] The method examples provided below are intended to promote further understanding of the preparation method of the present invention, and the specific substances, types, and conditions used are determined as further explanations of the present invention, not as limitations to the reasonable protection scope of the present invention. The raw materials and reagents used in the synthesis of the compounds described below can either be purchased from the market or easily prepared by one skilled in the art.

[0126] The analytical instrument described in the examples is as follows:

1. High Performance Liquid Chromatography (Hereinafter Referred to as HPLC)

Method A:

[0127] Using Agilent Technologies, 1260 Infinity II device [0128] Column: Agilent Eclipse Plus C.sub.18 3.5 m. 4.6*100 mm [0129] Mobile phase: A: water+0.1% phosphoric acid; B: acetonitrile, temperature: 30 C. [0130] Gradient: 5% B to 95% B within 15 minutes; 95% B 3 min [0131] Flow rate: 1 mL/min

Method B:

[0132] Using Agilent Technologies, 1260 Infinity II device [0133] Column: Agilent Eclipse Plus C.sub.18 3.5 m. 4.6*100 mm [0134] Mobile phase: A: water+0.1% phosphoric acid; B: methanol, temperature: 30 C. [0135] Gradient: 30% B to 95% B within 20 minutes; 95% B 3 min [0136] Flow rate: 1 mL/min

2. Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (Hereinafter Referred to as LC-MS): Using Waters, ACQUITY H-Class UPLC-SQ Detector 2 Device

[0137] Column: ACQUITY UPLC BEH C.sub.18 1.7 m, 2.1*50 mm Column [0138] Mobile phase: A: water+0.2% formic acid; b: acetonitrile, temperature: 30 C. [0139] Gradient: 10% B to 95% B within 5 min; 95% B 1 min [0140] Flow rate: 0.5 mL/min. [0141] MS method: ESI positive, negative, mass range (m/z): 100-800

3. Gas Chromatograph (Hereinafter Referred to as GC): Using Agilent Technologies, 7890B GC Device

[0142] Detector: FID [0143] Chromatographic column: HP-1 30 m*530 m*10.5 m [0144] Injection port temperature: 250 C. [0145] Split ratio: 40:1 [0146] Flow rate: 20 mL/min [0147] H.sub.2: 30 mL/min [0148] Air: 300 mL/min [0149] He: 25 mL/min [0150] Detector temperature: 280 C. [0151] Method: remain the temperature of 40 C. for 2 min, raise the temperature to 260 C. at a rate of 20 C./min, and remain the temperature o 260 C. for 5 min, a total time of 18 min

4. Gas Chromatography-Tandem Mass Spectrometry (Hereinafter Referred to as GC-MS): Using Agilent Technologies, 7890B GC System-5977A MSD Device

[0152] Column: Agilent Technologies, HP-5 MS UI 0.25 m, 30 m*0.250 mm [0153] Sample injector temperature: 250 C. [0154] Chromatographic column flow rate: helium 1 mL/min [0155] Method: remain the temperature of 40 C. for 2 min, raise the temperature to 280 C. at a rate of 20 C./min, remain the temperature of 280 C. for 5 min, a total time of 19 min [0156] MSD transmission line temperature: 280 C. [0157] EI ion source temperature: 230 C., MS quadrupole temperature: 150 C., scanning range: 30.00-400.00

[0158] In addition, the chemical shift value of proton nuclear magnetic resonance spectrum (hereinafter referred to as .sup.1H-NMR) recorded below is measured at 400 MHz (Bruker, AVANCE III HD 400M) in deuterated chloroform solvent using Me.sub.4Si (tetramethylsilane) as the standard substance. In the case of determination in deuterated dimethyl sulfoxide solvent, it is shown as (DMSO-d6) in the data of chemical shift value. It should be noted that the symbols in the chemical shift values of .sup.1H-NMR represent the following meanings.

[0159] s: singlet, d: doublet, dd: double doublet, dt: double triplet, td: triple doublet, ddd: double double doublet, t: triplet, q: quartet, sep: septet, m: multiplet, brs: broad singlet. In addition, in the presence of two or more stereoisomers, each chemical shift value is marked with and for signals that can be analyzed.

[0160] The examples of representative compounds are as follows, and the synthesis methods of other compounds are similar, which will not be explained in detail here.

Example 1: Synthesis of 2-methoxyethyl 2-hydroxy-2-methylpropionate

##STR01070##

[0161] In a reaction flask, were placed 50 g (480.31 mmol) 2-hydroxyisobutyric acid, 300 g ethylene glycol monomethyl ether and 2.35 g (23.96 mmol) concentrated sulfuric acid (98%). The reaction mixture was heated to 125 C. and refluxed for 4 h. After the reaction was completed, the remaining ethylene glycol monomethyl ether was removed by reduced pressure distillation, and the residue was vacuum distilled. The fraction at the distillation head temperature of 100 C. was collected to give 58.40 g product 1a with a yield of 78% and a GC area normalized purity of 98.6%. .sup.1HNMR (400 MHz, DMSO-d.sub.6) 5.29 (s, 1H), 4.21-4.07 (m, 2H), 3.57-3.49 (m, 2H), 3.27 (s, 3H), 1.29 (s, 6H).

Example 2: Synthesis of 2-methoxyethyl 2-hydroxy-2-methylpropionate

##STR01071##

[0162] In a 500 mL four-necked flask, were placed 156.15 g (1.50 mol) 2-hydroxyisobutyric acid, 125.55 g (1.65 mol) ethylene glycol monomethyl ether, 1.43 g (7.5 mmol) p-toluenesulfonic acid monohydrate and 200 g toluene. The reaction mixture was heated and refluxed for 3-5 hours using a Dean-Stark apparatus for azeotropic removal of water until no new water was generated. The mixture was distilled at atmospheric pressure to remove toluene and the remaining ethylene glycol monomethyl ether, and then distilled at reduced pressure (0.099 Mpa). The colorless liquid fraction at the distillation head temperature of 100 C. was collected to give 231.06 g product 1a with a yield of 94.98% and a GC area normalized purity of 98.51%.

Example 3: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-4-fluoro-5-nitrobenzoate

##STR01072##

[0163] In the reaction flask, was placed 32.7 g (201.7 mmol) compound 1a, and cooled to 0 C. under ice bath. 19.9 g (252.1 mmol) pyridine was added, and 80 g dichloromethane solution of 40 g (168.1 mmol) compound II was added dropwise at 0-5 C. under nitrogen protection. After addition, the mixture returned to room temperature to react for 1 h. The reaction was quenched by methanol to detect the content of compound II. The formed methyl 2-chloro-4-fluoro-5-nitrobenzoate was analyzed by HPLC (Method A). The content of methyl 2-chloro-4-fluoro-5-nitrobenzoate was less than 1% as the end of the reaction. The reaction solution was added with 80 g water and stirred for 10 min, standing for layering. The organic phase was separated and the solvent was removed under reduced pressure to obtain 55.38 g light yellow oil as title compound III-179 with a yield of 90.59% and an HPLC area normalization purity of 91.7% (Method A). .sup.1HNMR (400 MHz, DMSO-d.sub.6) 8.53 (d, J=8.0 Hz, 1H), 8.12 (d, J=11.1 Hz, 1H), 4.27-4.14 (m, 2H), 3.56-3.48 (m, 2H), 3.22 (s, 3H), 1.66 (s, 6H).

Example 4: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-4-fluoro-5-nitrobenzoate

##STR01073##

[0164] In a 2 L four-necked flask, were placed 238.0 g (1 mol) compound II and 1000 g toluene. The reaction mixture was heated 80-90 C. while stirring. At this temperature, a mixed solution of 222.62 g (2.20 mol) triethylamine and 243.27 g (1.50 mol) compound 1a was added dropwise for 2 h, and the reaction was continued for 4-5 h after addition. The reaction was quenched by methanol to detect the content of compound II. The formed methyl 2-chloro-4-fluoro-5-nitrobenzoate was analyzed by HPLC (Method A). The content of methyl 2-chloro-4-fluoro-5-nitrobenzoate was less than 1% as the end of the reaction. The reaction solution was cooled to room temperature and added with 700 g ice water while stirring, standing for layering. The organic phase was distilled under reduced pressure to remove the solvent, and 361.21 g brown oil was obtained, which was compound III-179. The crude yield was 99.31%, and HPLC area normalization purity was 92.51% (Method A).

Example 5: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-4-fluoro-5-nitrobenzoate

##STR01074##

[0165] In a 1 L four-necked flask, were placed 101.19 g (1 mol) triethylamine, 3.05 g (0.025 mol) 4-dimethylaminopyridine, 121.64 g (0.75 mol) compound 1a and 200 g toluene. The mixture was heated to 80 C. while stirring. The mixture of 119.0 g (0.5 mol) compound II and 300 g toluene was added dropwise at 80 C. for 2 h, and the reaction was continued at 80 C. for 4 h after addition. The reaction was quenched by methanol to detect the content of compound II. The formed methyl 2-chloro-4-fluoro-5-nitrobenzoate was analyzed by HPLC (Method A). The content of methyl 2-chloro-4-fluoro-5-nitrobenzoate was less than 1% as the end of the reaction. The reaction solution was cooled to room temperature and added with 500 g ice water while stirring, standing for layering. The organic phase was distilled under reduced pressure to remove the solvent to give 173.06 g brown oil, which was compound III-179. The yield of crude product was 95.16%, and HPLC area normalization purity was 87.90% (Method A).

Example 6: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-4-fluoro-5-nitrobenzoate

##STR01075##

[0166] In a 1 L four-necked flask, were placed 119.0 g (0.5 mol) compound II and 300 g toluene. The mixture was heated to 80 C. while stirring, a mixture of 101.19 g (1 mol) triethylamine, 3.05 g (0.025 mol) 4-dimethylaminopyridine, 121.64 g (0.75 mol) compound 1a and 200 g toluene was added dropwise at 80 C. for 2 h, and then the reaction was continued at 80 C. for 4 h after addition. The reaction was quenched by methanol to detect the content of compound II. The formed methyl 2-chloro-4-fluoro-5-nitrobenzoate was analyzed by HPLC (Method A). The content of methyl 2-chloro-4-fluoro-5-nitrobenzoate was less than 1% as the end of the reaction. The reaction solution was cooled to room temperature and added with 500 g ice water while stirring, standing for layering. The organic phase was distilled under reduced pressure to remove the solvent to give 175.20 g brown oil, which was compound III-179. The yield of crude product was 96.34%, and HPLC area normalization purity was 92.00% (Method A).

Example 7: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 5-amino-2-chloro-4-fluorobenzoate

##STR01076##

[0167] 100 g compound III-179 was dissolved in 500 g methanol, which was added to a 1000 mL autoclave, then 3 g Pt/C (1%) was added. The gas in the autoclave was replaced 5 times with hydrogen. The reaction solution was heated to 45 C. and the hydrogen pressure in the autoclave was controlled at 2.0 MPa to react for 8 h. The raw material compound III-179 was detected by sampling until it disappeared, and then the insoluble matter was removed by filtration. The filtrate was distilled under reduced pressure to remove the solvent to give 87.72 g brown oil, which was title compound IV-179 with a yield of 95.6% and HPLC area normalization purity of 96.2% (Method A). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.30 (d, J=11.1 Hz, 1H), 7.24 (d, J=9.4 Hz, 1H), 4.23-4.18 (m, 2H), 3.54-3.49 (m, 2H), 3.22 (s, 3H), 1.60 (s, 6H).

Example 8: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 5-amino-2-chloro-4-fluorobenzoate

##STR01077##

[0168] In a 2 L autoclave, were place 361.21 g (0.93 mol) compound III-179 obtained in example 4 which was dissolved in 1000 g methanol and 3.6 g Pt/C (5%). The hydrogen pressure was 2.0 MPa. The reaction solution was heated to 60-70 C. for 5-6 h, and the content of compound III-179 detected by sampling and HPLC (Method A) was less than 0.5% as the end of the reaction. Pt/C was removed by filtration, and the filtrate was distilled under reduced pressure to obtain crude product. The crude product was added to 200 g 70% (w/w) isopropanol aqueous solution, heated to 60 C. and stirred for 0.5 h, slowly cooled to about 0 C. and remained the temperature of 0 C. for more than 2 h to precipitate crystals. The mixture was filtered, the filter cake was collected and dried to obtain 267.31 g yellow solid, which was the title compound IV-179. The two-step yield (calculated as compound II in example 4) was 80.10%, and HPLC area normalization purity (Method A) was 98.51%.

Example 9: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)-4-fluorobenzoate

##STR01078##

[0169] In a reaction flask, were placed 50 g (149.82 mmol) compound IV-179, 41.89 g (164.8 mmol) ethyl 3-(3,3-dimethylureido)-4,4,4-trifluorobut-2-enoate, and 250 g acetic acid. The mixture were heated to 110 C. to react for 4 h, and the raw material IV-179 disappeared by detection. After removing the remaining acetic acid by reduced pressure distillation, water and ethyl acetate were added for extraction. The organic phase was washed twice with water, and was distilled under reduced pressure to remove the solvent to give 71.6 g the title compound V-179, with a yield of 96.2% and HPLC area normalization purity of 92.7% (Method B). It is a light yellow solid with a melting point of 142.4 C.-143.3 C. .sup.1H NMR (400 MHz, DMSO-d6) 12.85 (s, 1H), 8.09 (d, J=7.7 Hz, 1H), 7.90 (d, J=9.5 Hz, 1H), 6.43 (s, 1H), 4.24-4.19 (m, 2H), 3.53-3.49 (m, 2H), 3.20 (s, 3H), 1.63 (s, 6H).

Example 10: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)-4-fluorobenzoate

##STR01079##

[0170] In a 100 mL four-necked flask, were placed 10.00 g (0.03 mol) compound IV-179, 30 g acetic acid, and 9.2 g (0.05 mol) ethyl 3-(3,3-dimethylureido)-4,4,4-trifluorobut-2-enoate. The mixture was heated to reflux for 4 h, and compound IV-179 disappeared or was less than 1% by HPLC detection (Method B). The reaction mixture was distilled under reduced pressure to remove acetic acid to give 14.09 g brown oil which was compound V-179, with a yield of 94.54% and HPLC area normalization purity of 92.51% (Method B).

Example 11: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-(2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)-4-fluorobenzoate

##STR01080##

[0171] Refer to the synthesis method of compound V-179 in example 9 and example 10. In a 250 mL four-necked flask, were placed 16.70 g (0.05 mol) compound IV-179, 100 g acetic acid and 12.50 g (0.06 mol) 2-(dimethylamino)-4-(trifluoromethyl)-6H-1,3-oxazin-6-one. The mixture was heated to reflux for 4 h, and compound IV-179 disappeared or was less than 1% by HPLC detection (Method B). The reaction mixture was distilled under reduced pressure to remove acetic acid to give 22.75 g brown oil which was compound V-179, with a yield of 91.59% and HPLC area normalization purity of 75.51% (Method B).

[0172] Through the method of the present invention, the prepared compound of formula (V) can be subjected to the following reaction to prepare the herbicidal compound of formula (I):

##STR01081##

Example 12: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl) benzoate

##STR01082##

[0173] In a reaction flask, were placed 100 g (201.28 mmol) compound V-179, 58.42 g (422.7 mmol) potassium carbonate and 500 g N,N-dimethylformamide. The mixture was stirred at room temperature for 0.5 h, and 27.93 g (221.42 mmol) dimethyl sulfate was added dropwise slowly. After addition, the reaction continued until the material compound V-179 disappeared by detection. The reaction solution was poured into 500 g water, extracted with 1000 g ethyl acetate. The organic phase was washed twice with saturated brine and spin-dried to give 94.76 g title compound I-179, with a yield of 92% and HPLC area normalization purity of 93.7% (Method B). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.07 (d, J=7.7 Hz, 1H), 7.92 (d, J=9.5 Hz, 1H), 6.63 (s, 1H), 4.24-4.19 (m, 2H), 3.54-3.48 (m, 2H), 3.43 (s, 3H), 3.21 (s, 3H), 1.63 (s, 6H).

Example 13: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl) benzoate

##STR01083##

[0174] In a 250 mL four-necked flask, were placed 10 g (20 mmol) compound V-179, 50 g N,N-dimethylformamide and 3.5 g (25 mmol) potassium carbonate, and 3.5 g (25 mmol) iodomethane was added dropwise at room temperature. After addition, the mixture was stirred at room temperature for 3 h, and compound V-179 disappeared or was less than 1% by HPLC detection (Method B). The reaction mixture was distilled under reduced pressure to remove most of the solvent, and was added with 100 g water and 100 g ethyl acetate for extraction. The organic phase was distilled under reduced pressure to remove the solvent to give a light yellow semisolid, which was recrystallized with isopropanol to give 9.2 g white solid of compound I-179, with a yield of 90% and HPLC area normalized purity of 98.67% (Method B).

Example 14: Synthesis of 1-(2-methoxyethoxy)-2-methyl-1-oxopropan-2-yl 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl) benzoate

##STR01084##

[0175] In a 250 mL four-necked flask, were placed 10 g (20 mmol) compound V-179, 50 g N,N-dimethylformamide and 3.5 g (25 mmol) potassium carbonate, and 4.6 g (48 mmol) bromomethane was added dropwise under ice bath condition. After addition, the mixture was heated to room temperature and stirred for 7 h, and compound V-179 disappeared or was less than 1% by HPLC detection (Method B). The reaction mixture was distilled under reduced pressure to remove most of the solvent, and was added with 100 g water and 100 g ethyl acetate for extraction. The organic phase was distilled under reduced pressure to remove the solvent to give a light yellow semisolid, which was recrystallized with isopropanol to give 9.0 g white solid of compound I-179, with a yield of 88% and HPLC area normalized purity of 98.54% (Method B).

[0176] According to the method described above, 2-hydroxyisobutyric acid and ethylene glycol monomethyl ether in example 1 or example 2 can be replaced with corresponding R.sub.1, R.sub.2 substituted glycolic acid and R.sub.3OH to obtain other compounds of formula (I). For example, compound I-169 can be prepared by DL-lactic acid and 2-(methylthio) ethanol, which needs no further elaboration. The corresponding R.sub.1, R.sub.2 substituted glycolic acid and R.sub.3OH can be obtained by commercial purchase or can be easily prepared by one skilled in the art.

[0177] Some of the compounds of formula (I) prepared are shown in Table 4

##STR01085##

TABLE-US-00004 TABLE 4 Structure of some compounds with general formula (I) NO. R.sub.1 R.sub.2 R.sub.3 I-1 H H [01086] I-2 H H [01087] I-3 H H [01088] I-4 H H [01089] I-5 H H [01090] I-6 H H [01091] I-7 H H [01092] I-8 H H [01093] I-9 H H [01094] I-10 H H [01095] I-11 H H [01096] I-12 H H [01097] I-13 H H [01098] I-14 H H [01099] I-15 H H [01100] I-16 H H [01101] I-17 H H [01102] I-18 H H [01103] I-19 H H [01104] I-20 H H [01105] I-21 H H [01106] I-22 H H [01107] I-23 H H [01108] I-24 H H [01109] I-25 H H [01110] I-26 H H [01111] I-27 H H [01112] I-28 H H [01113] I-29 H H [01114] I-30 H H [01115] I-31 H H [01116] I-32 H H [01117] I-33 H H [01118] I-34 H H [01119] I-35 H H [01120] I-36 H H [01121] I-37 H H [01122] I-38 H H [01123] I-39 H H [01124] I-40 H H [01125] I-41 H H [01126] I-42 H H [01127] I-43 H H [01128] I-44 H H [01129] I-45 H [01130] [01131] I-46 H [01132] [01133] I-47 H [01134] [01135] I-48 H [01136] [01137] I-49 H [01138] [01139] I-50 H [01140] [01141] I-51 H [01142] [01143] I-52 H [01144] [01145] I-53 H [01146] [01147] I-54 H [01148] [01149] I-55 H [01150] [01151] I-56 H [01152] [01153] I-57 H [01154] [01155] I-58 H [01156] [01157] I-59 H [01158] [01159] I-60 H [01160] [01161] I-61 H [01162] [01163] I-62 H [01164] [01165] I-63 H [01166] [01167] I-64 H [01168] [01169] I-65 H [01170] [01171] I-66 H [01172] [01173] I-67 H [01174] [01175] I-68 H [01176] [01177] I-69 H [01178] [01179] I-70 H [01180] [01181] I-71 H [01182] [01183] I-72 H [01184] [01185] I-73 H [01186] [01187] I-74 H [01188] [01189] I-75 H [01190] [01191] I-76 H [01192] [01193] I-77 H [01194] [01195] I-78 H [01196] [01197] I-79 H [01198] [01199] I-80 H [01200] [01201] I-81 H [01202] [01203] I-82 H [01204] [01205] I-83 H [01206] [01207] I-84 H [01208] [01209] I-85 H [01210] [01211] I-86 H [01212] [01213] I-87 H [01214] [01215] I-88 H [01216] [01217] I-89 H [01218] [01219] I-90 H [01220] [01221] I-91 H [01222] [01223] I-92 H [01224] [01225] I-93 H [01226] [01227] I-94 H [01228] [01229] I-95 H [01230] [01231] I-96 H [01232] [01233] I-97 H [01234] [01235] I-98 H [01236] [01237] I-99 H [01238] [01239] I-100 H [01240] [01241] I-101 H [01242] [01243] I-102 H [01244] [01245] I-103 H [01246] [01247] I-104 H [01248] [01249] I-105 H [01250] [01251] I-106 H [01252] [01253] I-107 H [01254] [01255] I-108 H [01256] [01257] I-109 H [01258] [01259] I-110 H [01260] [01261] I-111 H [01262] [01263] I-112 H [01264] [01265] I-113 H [01266] [01267] I-114 H [01268] [01269] I-115 H [01270] [01271] I-116 H [01272] [01273] I-117 H [01274] [01275] I-118 H [01276] [01277] I-119 H [01278] [01279] I-120 H [01280] [01281] I-121 H [01282] [01283] I-122 H [01284] [01285] I-123 H [01286] [01287] I-124 H [01288] [01289] I-125 H [01290] [01291] I-126 H [01292] [01293] I-127 H [01294] [01295] I-128 H [01296] [01297] I-129 H [01298] [01299] I-130 H [01300] [01301] I-131 H [01302] [01303] I-132 H [01304] [01305] I-133 H CH.sub.3 [01306] I-134 H CH.sub.3 [01307] I-135 H CH.sub.3 [01308] I-136 H CH.sub.3 [01309] I-137 H CH.sub.3 [01310] I-138 H CH.sub.3 [01311] I-139 H CH.sub.3 [01312] I-140 H CH.sub.3 [01313] I-141 H CH.sub.3 [01314] I-142 H CH.sub.3 [01315] I-143 H CH.sub.3 [01316] I-144 H CH.sub.3 [01317] I-145 H CH.sub.3 [01318] I-146 H CH.sub.3 [01319] I-147 H CH.sub.3 [01320] I-148 H CH.sub.3 [01321] I-149 H CH.sub.3 [01322] I-150 H CH.sub.3 [01323] I-151 H CH.sub.3 [01324] I-152 H CH.sub.3 [01325] I-153 H CH.sub.3 [01326] I-154 H CH.sub.3 [01327] I-155 H CH.sub.3 [01328] I-156 H CH.sub.3 [01329] I-157 H CH.sub.3 [01330] I-158 H CH.sub.3 [01331] I-159 H CH.sub.3 [01332] I-160 H CH.sub.3 [01333] I-161 H CH.sub.3 [01334] I-162 H CH.sub.3 [01335] I-163 H CH.sub.3 [01336] I-164 H CH.sub.3 [01337] I-165 H CH.sub.3 [01338] I-166 H CH.sub.3 [01339] I-167 H CH.sub.3 [01340] I-168 H CH.sub.3 [01341] I-169 H CH.sub.3 [01342] I-170 H CH.sub.3 [01343] I-171 H CH.sub.3 [01344] I-172 H CH.sub.3 [01345] I-173 H CH.sub.3 [01346] I-174 H CH.sub.3 [01347] I-175 H CH.sub.3 [01348] I-176 H CH.sub.3 [01349] I-177 CH.sub.3 CH.sub.3 [01350] I-178 CH.sub.3 CH.sub.3 [01351] I-179 CH.sub.3 CH.sub.3 [01352] I-180 CH.sub.3 CH.sub.3 [01353] I-181 CH.sub.3 CH.sub.3 [01354] I-182 CH.sub.3 CH.sub.3 [01355] I-183 CH.sub.3 CH.sub.3 [01356] I-184 CH.sub.3 CH.sub.3 [01357] I-185 CH.sub.3 CH.sub.3 [01358] I-186 CH.sub.3 CH.sub.3 [01359] I-187 CH.sub.3 CH.sub.3 [01360] I-188 CH.sub.3 CH.sub.3 [01361] I-189 CH.sub.3 CH.sub.3 [01362] I-190 CH.sub.3 CH.sub.3 [01363] I-191 CH.sub.3 CH.sub.3 [01364] I-192 CH.sub.3 CH.sub.3 [01365] I-193 CH.sub.3 CH.sub.3 [01366] I-194 CH.sub.3 CH.sub.3 [01367] I-195 CH.sub.3 CH.sub.3 [01368] I-196 CH.sub.3 CH.sub.3 [01369] I-197 CH.sub.3 CH.sub.3 [01370] I-198 CH.sub.3 CH.sub.3 [01371] I-199 CH.sub.3 CH.sub.3 [01372] I-200 CH.sub.3 CH.sub.3 [01373] I-201 CH.sub.3 CH.sub.3 [01374] I-202 CH.sub.3 CH.sub.3 [01375] I-203 CH.sub.3 CH.sub.3 [01376] I-204 CH.sub.3 CH.sub.3 [01377] I-205 CH.sub.3 CH.sub.3 [01378] I-206 CH.sub.3 CH.sub.3 [01379] I-207 CH.sub.3 CH.sub.3 [01380] I-208 CH.sub.3 CH.sub.3 [01381] I-209 CH.sub.3 CH.sub.3 [01382] I-210 CH.sub.3 CH.sub.3 [01383] I-211 CH.sub.3 CH.sub.3 [01384] I-212 CH.sub.3 CH.sub.3 [01385] I-213 CH.sub.3 CH.sub.3 [01386] I-214 CH.sub.3 CH.sub.3 [01387] I-215 CH.sub.3 CH.sub.3 [01388] I-216 CH.sub.3 CH.sub.3 [01389] I-217 CH.sub.3 CH.sub.3 [01390] I-218 CH.sub.3 CH.sub.3 [01391] I-219 CH.sub.3 CH.sub.3 [01392] I-220 CH.sub.3 CH.sub.3 [01393] I-221 CH.sub.2CH.sub.2 [01394] I-222 CH.sub.2CH.sub.2 [01395] I-223 CH.sub.2CH.sub.2 [01396] I-224 CH.sub.2CH.sub.2 [01397] I-225 CH.sub.2CH.sub.2 [01398] I-226 CH.sub.2CH.sub.2 [01399] I-227 CH.sub.2CH.sub.2 [01400] I-228 CH.sub.2CH.sub.2 [01401] I-229 CH.sub.2CH.sub.2 [01402] I-230 CH.sub.2CH.sub.2 [01403] I-231 CH.sub.2CH.sub.2 [01404] I-232 CH.sub.2CH.sub.2 [01405] I-233 CH.sub.2CH.sub.2 [01406] I-234 CH.sub.2CH.sub.2 [01407] I-235 CH.sub.2CH.sub.2 [01408] I-236 CH.sub.2CH.sub.2 [01409] I-237 CH.sub.2CH.sub.2 [01410] I-238 CH.sub.2CH.sub.2 [01411] I-239 CH.sub.2CH.sub.2 [01412] I-240 CH.sub.2CH.sub.2 [01413] I-241 CH.sub.2CH.sub.2 [01414] I-242 CH.sub.2CH.sub.2 [01415] I-243 CH.sub.2CH.sub.2 [01416] I-244 CH.sub.2CH.sub.2 [01417] I-245 CH.sub.2CH.sub.2 [01418] I-246 CH.sub.2CH.sub.2 [01419] I-247 CH.sub.2CH.sub.2 [01420] I-248 CH.sub.2CH.sub.2 [01421] I-249 CH.sub.2CH.sub.2 [01422] I-250 CH.sub.2CH.sub.2 [01423] I-251 CH.sub.2CH.sub.2 [01424] I-252 CH.sub.2CH.sub.2 [01425] I-253 CH.sub.2CH.sub.2 [01426] I-254 CH.sub.2CH.sub.2 [01427] I-255 CH.sub.2CH.sub.2 [01428] I-256 CH.sub.2CH.sub.2 [01429] I-257 CH.sub.2CH.sub.2 [01430] I-258 CH.sub.2CH.sub.2 [01431] I-259 CH.sub.2CH.sub.2 [01432] I-260 CH.sub.2CH.sub.2 [01433] I-261 CH.sub.2CH.sub.2 [01434] I-262 CH.sub.2CH.sub.2 [01435] I-263 CH.sub.2CH.sub.2 [01436] I-264 CH.sub.2CH.sub.2 [01437]

[0178] The above-mentioned examples are only preferred examples of the present invention. It should be pointed out that for one skilled in the art. some changes and improvements can be made without deviating from the idea of the present invention, which should be within the protection scope of the present invention.