Method for preparing glufosinate or its analogues

Abstract

The present invention relates to a process for preparing glufosinate or analogues and intermediates thereof, the process comprising the steps of: a) reacting a compound of formula (II), an alcohol of formula (III) and a compound of formula (V); b) hydrolyzing the product of the above reaction to obtain glufosinate or analogues thereof of formula (IV).

Description

Detailed Description of the Invention

[0001] [Field of the Invention] The present invention relates to processes for preparing glufosinate or its analogues and intermediates.

[0002] [Background of the invention] Glufosinate is a highly efficient, broad-spectrum, low-toxicity, non-selective (fungicidal) organophosphate herbicide with partial systemic action developed by Hoechst AG in the 1980s and can be used for the control of annual and perennial dicotyledonous and grassy weeds.

[0003] Existing processes for preparing glufosinate are complex and use limited raw materials, therefore, there is a need to develop new processes for preparing glufosinate or its analogues.

[0004] [Summary of the Invention] The present invention relates to a process for preparing glufosinate of formula (IV) or an analogue thereof, the process comprising: [ka] a) reacting a compound of formula (II), an alcohol of formula (III) and a compound of formula (V), [ka] b) subjecting the product obtained from the above reaction to hydrolysis to obtain glufosinate of formula (IV) or an analogue thereof; Including, Here, R 1 and R 2 are each independently 1 ~C 16 Alkyl, C 6 ~C 12 Aryl, C 3 ~C 10 Cycloalkyl, C 7 ~C 12 Alkaryl and C7 ~C 12 aralkyl, each group being unsubstituted or C 1 ~C 6 Alkyl, C 1 ~C 6 substituted with alkoxy, dialkyl, or dialkylamino; e.g., R 1 is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, hexyl, phenyl, benzyl, phenethyl, phenylpropyl, methylphenyl, ethylphenyl, and propylphenyl; R 2 is C 1 ~C 8 is alkyl; Hal 1 is a halogen, Hal 2 is a halogen, PG is hydrogen or an amino protecting group, where when PG is an amino protecting group, the process further comprises removing the amino protecting group; X is -OR 3 or -NR 3 R 4 where R 3 is C 1 ~C 16 Alkyl, C 6 ~C 16 Aryl, C 3 ~C 16 Cycloalkyl, C 7 ~C 16 Aralkyl or C 7 ~C 16 and alkaryl, where each of these groups is unsubstituted or C 1 ~C 6 Alkyl-substituted; R 4 is hydrogen or R 3 As defined in Provide a process. [Brief description of the drawings]

[0005] [Figure 1] FIG. 2 is a reaction flow diagram of Examples A1 to A3. [Diagram 2]FIG. 2 is a reaction flow diagram of Examples B1 to B3. [Diagram 3] FIG. 2 is a reaction flow diagram of Examples C1 to C2. [Figure 4] FIG. 2 is a reaction flow diagram of Examples D1 to D14.

[0006] [Detailed Description of the Invention] The present invention is described in more detail in the following paragraphs. Unless expressly indicated to the contrary, each aspect so described can be combined with any one or more of the other aspects. In particular, any preferred or advantageous feature can be combined with any one or more other preferred or advantageous features.

[0007] In the context of the present invention, the terms used are explained in accordance with the following definitions, unless the context indicates otherwise.

[0008] As used herein, the words "a," "an," "the," and "said" include the singular and plural referents of the object, unless the context clearly dictates otherwise.

[0009] As used herein, the terms "comprising" and "consisting" have the same meaning as "including," "having," or "containing" and are inclusive or open-ended and do not exclude other components, elements, or process steps not listed.

[0010] The recitation of numerical endpoints includes all numbers and fractions within the corresponding range, as well as the recited endpoints.

[0011] Unless otherwise specified, all terms (including technical and scientific terms) used in the process disclosing the present invention have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains.

[0012] definition As used herein, the term "microchannel reactor" refers to a continuous flow reactor in which the equivalent diameter of the reaction channel is less than 5 millimeters.

[0013] As used herein, the term "tubular reactor" refers to a continuous-flow reactor in which the reaction channels are not filled with packing material and have an effective diameter larger than that of the "microchannel reactor" described above.

[0014] As used herein, the term "tubular packed reactor" refers to a continuous flow reactor in which the reaction channels are packed with a packing material and have an equivalent diameter larger than that of the "microchannel reactor" described above.

[0015] As used herein, the term "residence time" refers to the time it takes for the reactants involved in a reaction to mix together in a reactor, react, and exit the reactor after the reaction. Residence time can be calculated by the following method: Residence time T s is calculated as follows:

number

[0016] In this disclosure, when ammonia gas is included as a reactant, the ammonia gas is not included as a reactant in the above calculation methods.

[0017] As used herein, the term "amino protecting group" refers to a group that can be attached to the nitrogen atom in an amino group to protect the amino group from participating in a reaction and can be easily removed in a subsequent reaction. Suitable amino protecting groups include, but are not limited to, the following protecting groups: -C(O)OR (wherein R is, for example, methyl, ethyl, tert-butyl, benzyl, phenylethyl, CH 2 =CH-CH 2 -, etc.); amide groups of the formula -C(O)-R', where R' is, for example, methyl, ethyl, phenyl, trifluoromethyl, etc.; 2 N-sulfonyl derivative radicals of -R'', where R'' is, for example, tolyl, phenyl, trifluoromethyl, 2,2,5,7,8-pentamethylchroman-6-yl-, 2,3,6-trimethyl-4-methoxybenzene, and the like.

[0018] Process for preparing compounds of formula (I) The present invention relates to a process for preparing a compound of formula (I) comprising: [ka] reacting a compound of formula (II) with an alcohol of formula (III) in a molar ratio of greater than 1:2; [ka] Including, Here, R 1 and R 2 are each independently 1 ~C 16 Alkyl, C 6 ~C 12 Aryl, C 3 ~C 10 Cycloalkyl, C 7 ~C 12 Alkaryl and C 7 ~C 12 aralkyl, each group being unsubstituted or C 1 ~C 6 Alkyl, C1 ~C 6 substituted with alkoxy, dialkyl, or dialkylamino; e.g., R 1 is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, hexyl, phenyl, benzyl, phenethyl, phenylpropyl, methylphenyl, ethylphenyl, and propylphenyl; R 2 is C 1 ~C 8 is alkyl; Hal 1 is a halogen Provide a process.

[0019] In a preferred embodiment, R 1 is C 1 ~C 16 alkyl, cyclohexyl, cyclopentyl, or phenyl, where each group is unsubstituted or 1 ~C 6 Alkyl, C 1 ~C 6 alkoxy, or dialkylamino; preferably phenyl or C 1 ~C 6 alkyl, for example, methyl, ethyl, propyl, butyl, amyl or hexyl; more preferably C 1 ~C 4 Alkyl, for example, methyl, ethyl, propyl, or butyl; most preferably, methyl.

[0020] In another preferred embodiment, R 2 is C 1 ~C 6 Alkyl, such as methyl, ethyl, propyl, butyl, amyl or hexyl; preferably C 1 ~C 4 Alkyl is, for example, methyl, ethyl, propyl, or butyl; more preferably, ethyl.

[0021] In yet another preferred embodiment, Hal 1 is fluorine, chlorine, bromine or iodine, preferably chlorine.

[0022] In a preferred embodiment, the compound of formula (II) is dichloromethylphosphine, dichloroethylphosphine, dichloropropylphosphine, dichlorobutylphosphine, dichlorocyclohexylphosphine, dichlorophenylphosphine, dichloro-4-methoxyphenylphosphine or dichloro-4-dimethylaminophenylphosphine.

[0023] In another preferred embodiment, the compound of formula (III) is methanol alcohol, ethanol, n-propanol, isopropanol or n-butanol, preferably ethanol, n-propanol, isopropanol or n-butanol, more preferably n-butanol or ethanol, and most preferably ethanol.

[0024] In yet another preferred embodiment, the molar ratio of the compound of formula (II) to the alcohol of formula (III) is 1: (0.1-1.9), preferably 1: (0.5-1.5), more preferably 1: (0.9-1.1). For example, the molar ratio of the compound of formula (II) to the alcohol of formula (III) is 1: 0.2, 1: 0.3, 1: 0.4, 1: 0.5, 1: 0.6, 1: 0.7, 1: 0.8, 1: 0.9, 1: 1, 1: 1.1, 1: 1.2, 1: 1.3; 1: 1.4, 1: 1.5, 1: 1.6, 1: 1.7, 1: 1.8 or 1: 1.9, most preferably 1: 1.

[0025] In another preferred embodiment, the reaction is carried out at a temperature in the range of -35°C to 50°C, preferably -30°C to 30°C, more preferably -20°C to 0°C, and most preferably -10°C to 0°C. For example, the reaction temperature can be -35°C, -34°C, -33°C, -32°C, -31°C, -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 22°C, 20°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, 39°C, 38 ℃, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C.

[0026] In another preferred embodiment, the reaction is carried out in a continuous flow reactor selected from a microchannel reactor, a tubular reactor, a tubular packed reactor, a stirred tank reactor, or any combination thereof. For example, the reactor consists of one or more microchannel continuous flow reactors, or the reactor consists of one or more microchannel continuous flow reactors and one or more tubular reactors.

[0027] In yet another preferred embodiment, the temperature in the continuous flow reactor is in the range of -35°C to 50°C, preferably -30°C to 30°C, more preferably -20°C to 30°C, and most preferably -10°C to 30°C. For example, the temperature can be -35°C, -34°C, -33°C, -32°C, -31°C, -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C. , 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C.

[0028] The flow rates of the compound of formula (II) and the alcohol of formula (III) are not limited and may vary depending on the dimensions of the device.

[0029] In a further preferred embodiment, when the continuous flow reactor comprises a microchannel reactor, the residence time of the compound of formula (II) and the alcohol of formula (III) in the continuous flow reactor is in the range of 0.1 seconds to 300 seconds, preferably 1 second to 30 seconds, more preferably 15 seconds to 28 seconds. For example, the dwell time can be set to 0.1 seconds, 0.2 seconds, 0.5 seconds, 0.8 seconds, 1 second, 1.2 seconds, 1.4 seconds, 1.6 seconds, 1.8 seconds, 2 seconds, 2.5 seconds, 3 seconds, 4 seconds, 5 seconds, 6 seconds, 7 seconds, 8 seconds, 9 seconds, 10 seconds, 11 seconds, 12 seconds, 13 seconds, 14 seconds, 15 seconds, 16 seconds, 17 seconds, 18 seconds, 19 seconds, 20 seconds, 21 seconds, 22 seconds, 23 seconds, 24 seconds, 25 seconds, 26 seconds, 27 seconds, 28 seconds, 29 seconds, 30 seconds, 31 seconds, 35 seconds, 40 seconds, 45 seconds, 50 seconds, 55 seconds, 60 seconds, 65 seconds, 70 seconds, 75 seconds, 80 seconds, 85 seconds, 90 seconds, , 95 seconds, 100 seconds, 105 seconds, 110 seconds, 115 seconds, 120 seconds, 125 seconds, 130 seconds, 135 seconds, 140 seconds, 145 seconds, 150 seconds, 155 seconds, 160 seconds, 165 seconds, 170 seconds, 175 seconds, 180 seconds, 185 seconds, 190 seconds, 195 seconds, 200 seconds, 205 seconds, 210 seconds, 215 seconds, 220 seconds, 225 seconds, 230 seconds, 235 seconds, 240 seconds, 245 seconds, 250 seconds, 255 seconds, 260 seconds, 265 seconds, 270 seconds, 275 seconds, 280 seconds, 285 seconds, 290 seconds, 295 seconds, or 300 seconds.

[0030] In another preferred embodiment, the reaction is carried out in a tank reactor.

[0031] In a more preferred embodiment, the tank reactor is a continuous tank reactor.

[0032] In yet another preferred embodiment, the temperature in the tank reactor is in the range of -35°C to 50°C, preferably -30°C to 30°C, more preferably -20°C to 30°C, and most preferably -18°C to 30°C. For example, the temperature may be -35°C, -34°C, -33°C, -32°C, -31°C, -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C. , 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C.

[0033] Process for preparing glufosinate or its analogues of formula (IV) The present invention further provides a process for preparing glufosinate or an analogue thereof of formula (IV), comprising: [ka] a) reacting a compound of formula (II), an alcohol of formula (III) and a compound of formula (V), [ka] b) subjecting the product obtained from the above reaction to hydrolysis to obtain glufosinate or an analogue thereof of formula (IV) Including, Here, R 1 , R 2 and Hal 1 are each as defined in the process for preparing a compound of formula (I); Hal 2 is a halogen, PG is hydrogen or an amino protecting group, and when PG is an amino protecting group, the process further comprises removing the amino protecting group; X is -OR 3 or -NR 3 R 4 where R 3 is C 1 ~C 16 Alkyl, C 6 ~C 16 Aryl, C 3 ~C 16 Cycloalkyl, C 7 ~C 16 Aralkyl or C 7 ~C 16 alkaryl, where each group is unsubstituted or C 1 ~C 6 Alkyl-substituted; R 4 is hydrogen or R 3 As defined in Provide a process.

[0034] R 1 , R 2 and Hal 1 With respect to, all groups, preferred groups, more preferred groups and most preferred groups defined in the preceding process for the compound of formula (I) apply to the process for preparing glufosinate or an analogue thereof of formula (IV) in the present invention.

[0035] In the present invention, the order of supplying the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) does not affect the effect achieved by the embodiment of the present invention when the three substances are reacted. In a preferred embodiment, step a) can be carried out by: mixing the compound of formula (II), the alcohol of formula (III), the compound of formula (V) and a solvent together; or mixing the compound of formula (II) and the alcohol of formula (III), and then mixing the obtained product with the compound of formula (V), preferably without the need for another solvent; or mixing the compound of formula (II) and the compound of formula (V), and then mixing the obtained product with the alcohol of formula (III).

[0036] In a further preferred embodiment, when all the reactions in step a) are carried out in a microchannel reactor, the reaction in step a) is carried out at a reaction temperature in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 30°C; or when the reaction in step a) is carried out in a reactor consisting of a microchannel reactor and a tubular reactor, or a tank reactor, the reaction in step a) is carried out at a reaction temperature in the range of -30°C to 50°C, preferably -20°C to 10°C, more preferably -15°C to 5°C. For example, the reaction temperatures can be -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C , 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C.

[0037] In yet another preferred embodiment, the molar ratio of the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) is 1:(0.1-1.9):(0.1-2), preferably 1:(0.5-1.5):(0.5-1), more preferably 1:(0.9-1.1):(0.7-1), and most preferably 1:1:(0.7-0.9). For example, the molar ratio of the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) may be 1:0.1:0.1, 1:0.1:0.2, 1:0.1:0.3, 1:0.1:0.4, 1:0.1:0.5, 1:0.1:0.6, 1:0.1:0.7, 1:0.1:0.8, 1:0.1:0.9, 1:0.1:1, 1:0.1:1.1, 1:0.1:1.2, 1:0.1:1.3, 1:0.1:1.4, 1:0.1:1.5, 1:0.1:1.6, 1:0.1:1.7, 1: 0.1:1.8, 1:0.1:1.9, 1:0.1:2, 1:0.2:0.1, 1:0.2:0.2, 1:0.2:0.3, 1:0.2:0.4, 1:0.2:0.5, 1:0.2:0.6, 1:0.2:0.7, 1:0.2:0.8, 1:0.2:0.9, 1:0.2:1, 1:0.2:1.1, 1:0.2:1.2, 1:0.2:1.3, 1:0.2:1.4, 1:0.2:1.5, 1:0.2:1.6, 1:0.2:1.7, 1:0.2:1.8, 1:0.2:1.9 ,1:0.2:2,1:0.3:0.1,1:0.3:0.2,1:0.3:0.3,1:0.3:0.4,1:0.3:0.5,1:0.3:0.6,1:0.3:0.7,1:0.3:0.8,1:0.3:0.9,1:0.3:1,1:0.3:1.1,1:0.3:1.2,1:0.3:1.3,1:0.3:1.4,1:0.3:1.5,1:0.3:1.6,1:0.3:1.7,1:0.3:1.8,1:0.3:1.9,1:0.3:2,1:0.4:0 .1, 1:0.4:0.2, 1:0.4:0.3, 1:0.4:0.4, 1:0.4:0.5, 1:0.4:0.6, 1:0.4:0.7, 1:0.4:0.8, 1:0.4:0.9, 1:0.4:1, 1:0.4:1.1, 1:0.4:1.2, 1:0.4:1.3, 1:0.4:1.4, 1:0.4:1.5, 1:0.4:1.6, 1:0.4:1.7, 1:0.4:1.8, 1:0.4:1.9, 1:0.4:2, 1:0.5:0.1, 1:0.5:02, 1:0.5:0.3、1:0.5:0.4、1:0.5:0.5、1:0.5:0.6、1:0.5:0.7、1:0.5:0.8、1:0.5:0.9、1:0.5:1、1:0.5:1.1、1:0.5:1.2、1:0.5:1.3、1:0.5:1.4、1:0.5:1.5、1:0.5:1.6、1:0.5:1.7、1:0.5:1.8、1:0.5:1.9、1:0.5:2、1:0.6:0.1、1:0.6:0.2、1:0.6:0.3、1:0.6:0.4、1:0.6:0.5、1:0.6:0.6、1:0.6:0.7、1:0.6:0.8、1:0.6:0.9、1:0.6:1、1:0.6:1.1、1:0.6:1.2、1:0.6:1.3、1:0.6:1.4、1:0.6:1.5、1:0.6:1.6、1:0.6:1.7、1:0.6:1.8、1:0.6:1.9、1:0.6:2、1:0.7:0.1、1:0.7:0.2、1:0.7:0.3、1:0.7:0.4、1:0.7:0.5、1:0.7:0.6、1:0.7:0.7、1:0.7:0.8、1:0.7:0.9、1:0.7:1、1:0.7:1.1、1:0.7:1.2、1:0.7:1.3、1:0.7:1.4、1:0.7:1.5、1:0.7:1.6、1:0.7:1.7、1:0.7:1.8、1:0.7:1.9、1:0.7:2、1:0.8:0.1、1:0.8:0.2、1:0.8:0.3、1:0.8:0.4、1:0.8:0.5、1:0.8:0.6、1:0.8:0.7、1:0.8:0.8、1:0.8:0.9、1:0.8:1、1:0.8:1.1、1:0.8:1.2、1:0.8:1.3、1:0.8:1.4、1:0.8:1.5、1:0.8:1.6、1:0.8:1.7、1:0.8:1.8、1:0.8:1.9、1:0.8:2、1:0.9:0.1、1:0.9:0.2、1:0.9:0.3、1:0.9:0.4、1:0.9:0.5、1:0.9:0.6、1:0.9:0.7、1:0.9:0.8、1:0.9:0.9、1:0.9:1、1:0.9:1.1、1:0.9:1.2、1:0.9:1.3、1:0.9:1.4、1:0.9:1.5、1:0.9:1.6、1:0.9:1.7、1:0.9:1.8、1:0.9:1.9、1:0.9:2、1:1:0.1、1:1:0.2、1:1:0.3、1:1:0.4、1:1:0.5、1:1:0.6、1:1:0.7、1:1:0.8、1:1:0.9、1:1:1、1:1:1.1、1:1:1.2、1:1:1.3、1:1:1.4、1:1:1.5、1:1:1.6、1:1:1.7、1:1:1.8、1:1:1.9、1:1:2、1:1.1:0.1、1:1.1:0.2、1:1.1:0.3、1:1.1:0.4、1:1.1:0.5、1:1.1:0.6、1:1.1:0.7、1:1.1:0.8、1:1.1:0.9、1:1.1:1、1:1.1:1.1、1:1.1:1.2、1:1.1:1.3、1:1.1:1.4、1:1.1:1.5、1:1.1:1.6、1:1.1:1.7、1:1.1:1.8、1:1.1:1.9、1:1.1:2、1:1.2:0.1、1:1.2:0.2、1:1.2:0.3、1:1.2:0.4、1:1.2:0.5、1:1.2:0.6、1:1.2:0.7、1:1.2:0.8、1:1.2:0.9、1:1.2:1、1:1.2:1.1、1:1.2:1.2、1:1.2:1.3、1:1.2:1.4、1:1.2:1.5、1:1.2:1.6、1:1.2:1.7、1:1.2:1.8、1:1.2:1.9、1:1.2:2、1:1.3:0.1、1:1.3:0.2、1:1.3:0.3、1:1.3:0.4、1:1.3:0.5、1:1.3:0.6、1:1.3:0.7、1:1.3:0.8、1:1.3:0.9、1:1.3:1、1:1.3:1.1、1:1.3:1.2、1:1.3:1.3、1:1.3:1.4、1:1.3:1.5、1:1.3:1.6、1:1.3:1.7、1:1.3:1.8、1:1.3:1.9、1:1.3:2、1:1.4:0.1、1:1.4:0.2、1:1.4:0.3、1:1.4:0.4、1:1.4:0.5、1:1.4:0.6、1:1.4:0.7、1:1.4:0.8、1:1.4:0.9、1:1.4:1、1:1.4:1.1、1:1.4:1.2、1:1.4:1.3、1:1.4:1.4、1:1.4:1.5、1:1.4:1.6、1:1.4:1.7、1:1.4:1.8、1:1.4:1.9、1:1.4:2、1:1.5:0.1、1:1.5:0.2、1:1.5:0.3、1:1.5:0.4、1:1.5:0.5、1:1.5:0.6、1:1.5:0.7、1:1.5:0.8、1:1.5:0.9、1:1.5:1, 1:1.5:1.1, 1:1.5:1.2, 1:1.5:1.3, 1:1.5:1.4, 1:1.5:1.5, 1:1.5:1.6, 1:1.5:1.7, 1:1.5:1.8, 1:1.5:1.9, 1:1.5:2, 1:1.6:0.1, 1:1.6:0.2, 1:1.6:0.3, 1:1.6:0.4, 1:1.6:0.5, 1:1.6:0.6, 1:1.6:0.7, 1:1.6:0.8, 1:1.6:0.9, 1:1.6:1, 1:1.6:1.1, 1:1.6:1.2, 1:1.6:1.3, 1:1.6:1.4, 1:1.6:1.5, 1:1.6:1.6, 1:1.6:1.7, 1:1.6:1.8, 1:1.6:1.9, 1:1.6:2, 1:1.7:0.1, 1:1.7:0.2, 1:1.7:0.3, 1:1.7:0.4, 1:1.7:0.5, 1:1.7:0.6, 1:1.7:0.7, 1:1.7:0.8, 1:1.7:0.9, 1:1.7:1, 1:1.7:1.1, 1:1.7:1.2, 1:1.7:1.3, 1:1.7:1.4, 1:1.7:1.5, 1:1.7:1.6, 1:1. 7:1.7, 1:1.7:1.8, 1:1.7:1.9, 1:1.7:2, 1:1.8:0.1, 1:1.8:0.2, 1:1.8:0.3, 1:1.8:0.4, 1:1.8:0.5, 1:1.8:0.6, 1:1.8:0.7, 1:1.8:0.8, 1:1.8:0.9, 1:1.8:1, 1:1.8:1.1, 1:1.8:1.2, 1:1.8:1.3, 1:1.8:1.4, 1:1.8:1.5, 1:1.8:1.6, 1:1.8:1.7, 1:1.8:1.8, 1:1.8:1.9, 1:1.8:2, 1:1.9:0.1, 1:1.9:0.2, 1:1.9:0.3, 1:1.9:0.4, 1:1.9:0.5, 1:1.9:0.6, 1:1.9:0.7, 1:1.9:0.8, 1:1.9:0.9, 1:1.9:1, 1:1.9:1.1, 1:1.9:1.2, 1:1.9:1.3, 1:1.9:1.4, 1:1.9:1.5, 1:1.9:1.6, 1:1.9:1.7, 1:1.9:1.8, 1:1.9:1.9, 1:1.9:2, 1.1:1.1:1, 1.2:1.2:1 or 1.3:1.3:1.

[0038] In another preferred embodiment, Hal 2is fluorine, chlorine, bromine or iodine, preferably chlorine.

[0039] In a further preferred embodiment, PG is H, -C(O)-R 5 , -SO 2 -R 6 , -CHC(O)OR 7 Or -C(O)OR 8 where R 5 is C 6 ~C 16 Aryl, C 7 ~C 16 Aralkyl or C 7 ~C 16 Alkaryl, preferably C 6 ~C 12 Aryl, C 7 ~C 13 Aralkyl or C 7 ~C 13 R is alkaryl, more preferably phenyl, tolyl, benzyl or phenylethyl, most preferably phenyl; 6 is C 6 ~C 16 Aryl, C 7 ~C 16 Aralkyl or C 7 ~C 16 Alkaryl, preferably C 6 ~C 12 Aryl, C 7 ~C 13 Aralkyl or C 7 ~C 13 R is alkaryl, more preferably phenyl, tolyl, benzyl or phenylethyl, most preferably tolyl; 7 and R 8 are each independently 1 ~C 16 Alkyl, C 6 ~C 16 Aryl, C 3 ~C 16 Cycloalkyl, C 7 ~C 16 Aralkyl or C 7 ~C 16 Alkaryl, preferably C1 ~C 8 Alkyl, C 6 ~C 12 Aryl, C 3 ~C 10 Cycloalkyl, C 7 ~C 12 Aralkyl or C 7 ~C 12 It is alkaryl, more preferably methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, tolyl, ethylphenyl, cyclopropyl, cyclobutyl or cyclopentyl, most preferably methyl, ethyl, or an isomer of propyl or butyl.

[0040] In a further preferred embodiment, X is -OR 3 where R 3 is C 1 ~C 8 Alkyl or C 7 ~C 10 Aralkyl, preferably C 1 ~C 6 Alkyl or C 7 ~C 9 It is aralkyl, more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl or benzyl.

[0041] In another preferred embodiment, X is -NR 3 R 4 where R 3 is C 1 ~C 8 Alkyl or C 7 ~C 10 Aralkyl, preferably C 1 ~C 6 Alkyl or C 7 ~C 9 R is aralkyl, more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl or benzyl, particularly preferably methyl, propyl, isopropyl or butyl; 4 is H or R 3 and is preferably H or methyl.

[0042] In a preferred embodiment, the hydrolysis is acid hydrolysis or base hydrolysis, where acid hydrolysis is preferably carried out with an inorganic or organic acid, and base hydrolysis is preferably carried out with an inorganic or organic base, where the inorganic acid is preferably hydrochloric acid or sulfuric acid.

[0043] In a further preferred embodiment, step a) is carried out in the absence of a solvent or in the presence of an inert solvent, wherein the inert solvent is preferably any one or more of a benzene solvent, an amide solvent, a hydrocarbon solvent, a halohydrocarbon solvent, a sulfone or sulfoxide solvent, an ether solvent or an ester solvent; preferably, the inert solvent is selected from any one or more of a chlorobenzene, a trimethylbenzene, a 1,4-dioxane, a 1,2-dichloroethane, a dimethylsulfoxide, N-methylpyrrolidone, N,N-dimethylformamide, a petroleum ether, a n-heptane, a tetrahydrofuran, a methyltetrahydrofuran, a benzene, a toluene, an ethyl acetate, and a butyl acetate.

[0044] In a preferred embodiment, a base is added at the start of, during and / or after the reaction of step a), preferably after the reaction of step a), wherein the base is preferably an organic base or ammonia, more preferably ammonia.

[0045] In another preferred embodiment, the organic base is an organic amine, such as triethylamine, a pyridine derivative having 1 to 3 substituents attached to one or more carbon atoms in the pyridine or heterocycle, or a piperidine derivative having 1 to 3 substituents attached to one or more carbon atoms in the piperidine or heterocycle.

[0046] In yet another preferred embodiment, step a) comprises: (i) simultaneously feeding the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) into a first reactor to react with each other in the presence of a solvent, and then feeding the resulting product and a base, preferably ammonia gas, together into a second reactor; or (ii) simultaneously feeding the compound of formula (II) and the alcohol of formula (III) into a first reactor to react with each other in the presence of a solvent or in the absence of another solvent, then feeding the resulting product and the compound of formula (V) into a second reactor, and finally feeding the resulting product and a base, preferably ammonia gas, together into a third reactor to react with each other; or (i) ii) the compound of formula (II) and the compound of formula (V) are simultaneously charged into a first reactor to react with each other in the presence of a solvent or in the absence of other solvents, then the resulting product and the alcohol of formula (III) are charged into a second reactor, and finally the resulting product and a base, preferably ammonia gas, are charged together into a third reactor to react with each other; or (iv) the compound of formula (II) and the alcohol of formula (III) are simultaneously charged into a first reactor to react with each other in the presence of a solvent or in the absence of other solvents, then the resulting product, the compound of formula (V) and a base, preferably ammonia gas, are charged together into a second reactor to react with each other.

[0047] In a preferred embodiment, the first reactor, the second reactor and / or the third reactor are each independently one or more reactors.

[0048] In another preferred embodiment, the first reactor, the second reactor, and / or the third reactor are each independently selected from a microchannel reactor, a tubular reactor, a tubular packed reactor, a stirred tank reactor, or any combination thereof. For example, the first reactor, the second reactor, and / or the third reactor are each independently comprised of one or more microchannel continuous flow reactors; or each independently comprised of one or more microchannel continuous flow reactors and one or more tubular reactors.

[0049] In a further preferred embodiment, step a) comprises: (i) simultaneously feeding the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) into a first microchannel reactor to react with each other in the presence of a solvent, and then feeding the resulting product and a base, preferably ammonia gas, together into a second microchannel reactor; or (ii) simultaneously feeding the compound of formula (II) and the alcohol of formula (III) into a first microchannel reactor to react with each other in the presence or absence of a solvent, then feeding the resulting product and the compound of formula (V) into a second microchannel reactor, and finally feeding the resulting product and a base, preferably ammonia gas, together into a third microchannel reactor to react with each other; or (iii) by simultaneously feeding the compound of formula (II) and the compound of formula (V) into a first microchannel reactor to react with each other in the presence or absence of a solvent, then feeding the resulting product and the alcohol of formula (III) into a second microchannel reactor, and finally feeding the resulting product and a base, preferably ammonia gas, together into a third microchannel reactor to react with each other; or (iv) by simultaneously feeding the compound of formula (II) and the alcohol of formula (III) into a first microchannel reactor to react with each other in the presence or absence of a solvent, then feeding the resulting product, the compound of formula (V) and a base, preferably ammonia gas, together into a tubular reactor to react with each other.

[0050] In yet another preferred embodiment, in embodiment (i), the temperature of the first microchannel reactor and / or the second microchannel reactor is each independently in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 30°C, and the temperatures are the same or different. For example, the reaction temperature can be -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, - It may be 4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C or 30°C.

[0051] In embodiment (ii), the temperature of the first microchannel reactor, the second microchannel reactor and / or the third microchannel reactor is each independently in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 30°C, and the temperatures are the same or different. For example, the reaction temperature can be -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -5°C, -6°C, -5 ... ℃, -3℃, -2℃, -1℃, 0℃, 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, 10℃, 11℃, 12℃, 13℃, 14℃, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃ or 30℃.

[0052] In embodiment (iii), the temperature of the first microchannel reactor, the second microchannel reactor and / or the third microchannel reactor is each independently in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 30°C, and the temperatures may be the same or different.

[0053] In embodiment (iv), the temperature of the first microchannel reactor is in the range of -30°C to 50°C, preferably -25°C to 5°C, more preferably -20°C to -10°C; and / or the temperature of the tubular reactor is in the range of -30°C to 50°C, preferably -25°C to 10°C, more preferably -20°C to 5°C.

[0054] In a preferred embodiment, in step a), if the reactors consist of only microchannel reactors, the total residence time in all the reactors is in the range of 0.1 s to 300 s, preferably 1 s to 50 s, more preferably 10 s to 40 s; or if the reactors consist of microchannel reactors and tubular reactors, the total residence time in all the reactors is in the range of 1 min to 20 min, preferably 5 min to 18 min, more preferably 9 min to 14 min. For example, the dwell time can be set to 0.1 seconds, 0.2 seconds, 0.5 seconds, 0.8 seconds, 1 second, 1.2 seconds, 1.4 seconds, 1.6 seconds, 1.8 seconds, 2 seconds, 2.5 seconds, 3 seconds, 4 seconds, 5 seconds, 6 seconds, 7 seconds, 8 seconds, 9 seconds, 10 seconds, 11 seconds, 12 seconds, 13 seconds, 14 seconds, 15 seconds, 16 seconds, 17 seconds, 18 seconds, 19 seconds, 20 seconds, 21 seconds, 22 seconds, 23 seconds, 24 seconds, 25 seconds, 26 seconds, 27 seconds, 28 seconds, 29 seconds, 30 seconds, 31 seconds, 35 seconds, 40 seconds, 45 seconds, 50 seconds, 55 seconds, 60 seconds, 65 seconds, 70 seconds, 75 seconds, 80 seconds, 85 seconds, 90 seconds, , 95 seconds, 100 seconds, 105 seconds, 110 seconds, 115 seconds, 120 seconds, 125 seconds, 130 seconds, 135 seconds, 140 seconds, 145 seconds, 150 seconds, 155 seconds, 160 seconds, 165 seconds, 170 seconds, 175 seconds, 180 seconds, 185 seconds, 190 seconds, 195 seconds, 200 seconds, 205 seconds, 210 seconds, 215 seconds, 220 seconds, 225 seconds, 230 seconds, 235 seconds, 240 seconds, 245 seconds, 250 seconds, 255 seconds, 260 seconds, 265 seconds, 270 seconds, 275 seconds, 280 seconds, 285 seconds, 290 seconds, 295 seconds, or 300 seconds.

[0055] In a further preferred embodiment, step b) is carried out by: increasing the temperature of the reaction product resulting from step a) to be in the range of 30° C. to 130° C., preferably 60° C. to 120° C., more preferably 90° C. to 100° C. for 1 to 24 hours, preferably 2 to 10 hours, more preferably 5 to 8 hours; and then hydrolyzing the product with an acid, preferably hydrochloric acid, at a temperature in the range of 50° C. to 120° C., preferably 80° C. to 120° C., more preferably 100° C. to 110° C. For example, the reaction product of step a) may be maintained at a temperature of 30° C., 35° C., 40° C., 45° C., 50° C., 55° C., 60° C., 65° C., 70° C., 75° C., 80° C., 85° C., 90° C., 95° C., 100° C., 105° C., 110° C., 115° C., 120° C., 125° C. or 130° C. For example, the reaction product of step a) may be maintained at these temperatures for 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours, 8.5 hours, 9 hours, 9.5 hours, 10 hours, 10.5 hours, 11 hours, 11.5 hours, 12 hours, 12.5 hours, 13 hours, 13.5 hours, 14 hours, 14.5 hours, 15 hours, 15.5 hours, 16 hours, 16.5 hours, 17 hours, 17.5 hours, 18 hours, 18.5 hours, 19 hours, 19.5 hours, 20 hours, 20.5 hours, 21 hours, 21.5 hours, 22 hours, 22.5 hours, 23 hours, 23.5 hours or 24 hours. For example, the hydrolysis temperature may be 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C, 110°C, 115°C or 120°C.

[0056] Process for preparing glufosinate or its analogues of formula (IV) The present invention further provides a process for preparing glufosinate or an analogue thereof of formula (IV), comprising: [ka] a) feeding a compound of formula (II), an alcohol of formula (III) and a compound of formula (V) into a reactor to obtain a mixture stream; [ka] b) reacting the mixture stream at a temperature in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 5°C; c) subjecting the product obtained from step b) to hydrolysis to obtain compound (IV) glufosinate or an analogue thereof. Including, Here, R 1 , R 2 and Hal 1 is as defined in the process for preparing a compound of formula (I); Hal 2 is a halogen, PG is hydrogen or an amino protecting group, and when PG is an amino protecting group, the process further comprises removing the amino protecting group; X is -OR 3 or -NR 3 R 4 where R 3 is C 1 ~C 16 Alkyl, C 6 ~C 16 Aryl, C 3 ~C 16 Cycloalkyl, C 7 ~C 16 Aralkyl or C 7 ~C 16 alkaryl, where each group is unsubstituted or C 1 ~C 6 Alkyl-substituted; R 4 is hydrogen or R 3 As defined in Provide a process.

[0057] R 1 , R 2 and Hal 1With respect to, all groups, preferred groups, more preferred groups and most preferred groups defined in the preceding process for the compound of formula (I) apply to the process for preparing glufosinate or an analogue thereof of formula (IV) in the present invention.

[0058] In the present invention, "feeding the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) into the reactor" includes feeding the three substances in any order, and feeding any two substances can be performed simultaneously or at a time difference, all of which do not affect the effect achieved by the embodiment of the present invention. In a preferred embodiment, step a) can be performed by: mixing the compound of formula (II), the alcohol of formula (III), the compound of formula (V) and a solvent together; or mixing the compound of formula (II) and the alcohol of formula (III), and then mixing the obtained product with the compound of formula (V), preferably without the need for another solvent; or mixing the compound of formula (II) and the compound of formula (V), and then mixing the obtained product with the alcohol of formula (III).

[0059] In a further preferred embodiment, when all the reactions in step a) are carried out in a microchannel reactor, the reaction in step a) is carried out at a reaction temperature in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 30°C; or when the reaction in step a) is carried out in a reactor consisting of a microchannel reactor and a tubular reactor, or a tank reactor, the reaction in step a) is carried out at a reaction temperature in the range of -30°C to 50°C, preferably -20°C to 10°C, more preferably -15°C to 5°C. For example, the reaction temperatures can be -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C , 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C.

[0060] In yet another preferred embodiment, the molar ratio of the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) is 1:(0.1-1.9):(0.1-2), preferably 1:(0.5-1.5):(0.5-1), more preferably 1:(0.9-1.1):(0.7-1), and most preferably 1:1:(0.7-0.9). For example, the molar ratio of the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) may be 1:0.1:0.1, 1:0.1:0.2, 1:0.1:0.3, 1:0.1:0.4, 1:0.1:0.5, 1:0.1:0.6, 1:0.1:0.7, 1:0.1:0.8, 1:0.1:0.9, 1:0.1:1, 1:0.1:1.1, 1:0.1:1.2, 1:0.1:1.3, 1:0.1:1.4, 1:0.1:1.5, 1:0.1:1.6, 1:0.1:1.7, 1: 0.1:1.8, 1:0.1:1.9, 1:0.1:2, 1:0.2:0.1, 1:0.2:0.2, 1:0.2:0.3, 1:0.2:0.4, 1:0.2:0.5, 1:0.2:0.6, 1:0.2:0.7, 1:0.2:0.8, 1:0.2:0.9, 1:0.2:1, 1:0.2:1.1, 1:0.2:1.2, 1:0.2:1.3, 1:0.2:1.4, 1:0.2:1.5, 1:0.2:1.6, 1:0.2:1.7, 1:0.2:1.8, 1:0.2:1.9 ,1:0.2:2,1:0.3:0.1,1:0.3:0.2,1:0.3:0.3,1:0.3:0.4,1:0.3:0.5,1:0.3:0.6,1:0.3:0.7,1:0.3:0.8,1:0.3:0.9,1:0.3:1,1:0.3:1.1,1:0.3:1.2,1:0.3:1.3,1:0.3:1.4,1:0.3:1.5,1:0.3:1.6,1:0.3:1.7,1:0.3:1.8,1:0.3:1.9,1:0.3:2,1:0.4:0 .1, 1:0.4:0.2, 1:0.4:0.3, 1:0.4:0.4, 1:0.4:0.5, 1:0.4:0.6, 1:0.4:0.7, 1:0.4:0.8, 1:0.4:0.9, 1:0.4:1, 1:0.4:1.1, 1:0.4:1.2, 1:0.4:1.3, 1:0.4:1.4, 1:0.4:1.5, 1:0.4:1.6, 1:0.4:1.7, 1:0.4:1.8, 1:0.4:1.9, 1:0.4:2, 1:0.5:0.1, 1:0.5:02, 1:0.5:0.3、1:0.5:0.4、1:0.5:0.5、1:0.5:0.6、1:0.5:0.7、1:0.5:0.8、1:0.5:0.9、1:0.5:1、1:0.5:1.1、1:0.5:1.2、1:0.5:1.3、1:0.5:1.4、1:0.5:1.5、1:0.5:1.6、1:0.5:1.7、1:0.5:1.8、1:0.5:1.9、1:0.5:2、1:0.6:0.1、1:0.6:0.2、1:0.6:0.3、1:0.6:0.4、1:0.6:0.5、1:0.6:0.6、1:0.6:0.7、1:0.6:0.8、1:0.6:0.9、1:0.6:1、1:0.6:1.1、1:0.6:1.2、1:0.6:1.3、1:0.6:1.4、1:0.6:1.5、1:0.6:1.6、1:0.6:1.7、1:0.6:1.8、1:0.6:1.9、1:0.6:2、1:0.7:0.1、1:0.7:0.2、1:0.7:0.3、1:0.7:0.4、1:0.7:0.5、1:0.7:0.6、1:0.7:0.7、1:0.7:0.8、1:0.7:0.9、1:0.7:1、1:0.7:1.1、1:0.7:1.2、1:0.7:1.3、1:0.7:1.4、1:0.7:1.5、1:0.7:1.6、1:0.7:1.7、1:0.7:1.8、1:0.7:1.9、1:0.7:2、1:0.8:0.1、1:0.8:0.2、1:0.8:0.3、1:0.8:0.4、1:0.8:0.5、1:0.8:0.6、1:0.8:0.7、1:0.8:0.8、1:0.8:0.9、1:0.8:1、1:0.8:1.1、1:0.8:1.2、1:0.8:1.3、1:0.8:1.4、1:0.8:1.5、1:0.8:1.6、1:0.8:1.7、1:0.8:1.8、1:0.8:1.9、1:0.8:2、1:0.9:0.1、1:0.9:0.2、1:0.9:0.3、1:0.9:0.4、1:0.9:0.5、1:0.9:0.6、1:0.9:0.7、1:0.9:0.8、1:0.9:0.9、1:0.9:1、1:0.9:1.1、1:0.9:1.2、1:0.9:1.3、1:0.9:1.4、1:0.9:1.5、1:0.9:1.6、1:0.9:1.7、1:0.9:1.8、1:0.9:1.9、1:0.9:2、1:1:0.1、1:1:0.2、1:1:0.3、1:1:0.4、1:1:0.5、1:1:0.6、1:1:0.7、1:1:0.8、1:1:0.9、1:1:1、1:1:1.1、1:1:1.2、1:1:1.3、1:1:1.4、1:1:1.5、1:1:1.6、1:1:1.7、1:1:1.8、1:1:1.9、1:1:2、1:1.1:0.1、1:1.1:0.2、1:1.1:0.3、1:1.1:0.4、1:1.1:0.5、1:1.1:0.6、1:1.1:0.7、1:1.1:0.8、1:1.1:0.9、1:1.1:1、1:1.1:1.1、1:1.1:1.2、1:1.1:1.3、1:1.1:1.4、1:1.1:1.5、1:1.1:1.6、1:1.1:1.7、1:1.1:1.8、1:1.1:1.9、1:1.1:2、1:1.2:0.1、1:1.2:0.2、1:1.2:0.3、1:1.2:0.4、1:1.2:0.5、1:1.2:0.6、1:1.2:0.7、1:1.2:0.8、1:1.2:0.9、1:1.2:1、1:1.2:1.1、1:1.2:1.2、1:1.2:1.3、1:1.2:1.4、1:1.2:1.5、1:1.2:1.6、1:1.2:1.7、1:1.2:1.8、1:1.2:1.9、1:1.2:2、1:1.3:0.1、1:1.3:0.2、1:1.3:0.3、1:1.3:0.4、1:1.3:0.5、1:1.3:0.6、1:1.3:0.7、1:1.3:0.8、1:1.3:0.9、1:1.3:1、1:1.3:1.1、1:1.3:1.2、1:1.3:1.3、1:1.3:1.4、1:1.3:1.5、1:1.3:1.6、1:1.3:1.7、1:1.3:1.8、1:1.3:1.9、1:1.3:2、1:1.4:0.1、1:1.4:0.2、1:1.4:0.3、1:1.4:0.4、1:1.4:0.5、1:1.4:0.6、1:1.4:0.7、1:1.4:0.8、1:1.4:0.9、1:1.4:1、1:1.4:1.1、1:1.4:1.2、1:1.4:1.3、1:1.4:1.4、1:1.4:1.5、1:1.4:1.6、1:1.4:1.7、1:1.4:1.8、1:1.4:1.9、1:1.4:2、1:1.5:0.1、1:1.5:0.2、1:1.5:0.3、1:1.5:0.4、1:1.5:0.5、1:1.5:0.6、1:1.5:0.7、1:1.5:0.8、1:1.5:0.9、1:1.5:1, 1:1.5:1.1, 1:1.5:1.2, 1:1.5:1.3, 1:1.5:1.4, 1:1.5:1.5, 1:1.5:1.6, 1:1.5:1.7, 1:1.5:1.8, 1:1.5:1.9, 1:1.5:2, 1:1.6:0.1, 1:1.6:0.2, 1:1.6:0.3, 1:1.6:0.4, 1:1.6:0.5, 1:1.6:0.6, 1:1.6:0.7, 1:1.6:0.8, 1:1.6:0.9, 1:1.6:1, 1:1.6:1.1, 1:1.6:1.2, 1:1.6:1.3, 1:1.6:1.4, 1:1.6:1.5, 1:1.6:1.6, 1:1.6:1.7, 1:1.6:1.8, 1:1.6:1.9, 1:1.6:2, 1:1.7:0.1, 1:1.7:0.2, 1:1.7:0.3, 1:1.7:0.4, 1:1.7:0.5, 1:1.7:0.6, 1:1.7:0.7, 1:1.7:0.8, 1:1.7:0.9, 1:1.7:1, 1:1.7:1.1, 1:1.7:1.2, 1:1.7:1.3, 1:1.7:1.4, 1:1.7:1.5, 1:1.7:1.6, 1:1. 7:1.7, 1:1.7:1.8, 1:1.7:1.9, 1:1.7:2, 1:1.8:0.1, 1:1.8:0.2, 1:1.8:0.3, 1:1.8:0.4, 1:1.8:0.5, 1:1.8:0.6, 1:1.8:0.7, 1:1.8:0.8, 1:1.8:0.9, 1:1.8:1, 1:1.8:1.1, 1:1.8:1.2, 1:1.8:1.3, 1:1.8:1.4, 1:1.8:1.5, 1:1.8:1.6, 1:1.8:1.7, 1:1.8:1.8, 1:1.8:1.9, 1:1.8:2, 1:1.9:0.1, 1:1.9:0.2, 1:1.9:0.3, 1:1.9:0.4, 1:1.9:0.5, 1:1.9:0.6, 1:1.9:0.7, 1:1.9:0.8, 1:1.9:0.9, 1:1.9:1, 1:1.9:1.1, 1:1.9:1.2, 1:1.9:1.3, 1:1.9:1.4, 1:1.9:1.5, 1:1.9:1.6, 1:1.9:1.7, 1:1.9:1.8, 1:1.9:1.9, 1:1.9:2, 1.1:1.1:1, 1.2:1.2:1 or 1.3:1.3:1.

[0061] In another preferred embodiment, Hal 2is fluorine, chlorine, bromine or iodine, preferably chlorine.

[0062] In a further preferred embodiment, PG is H, -C(O)-R 5 , -SO 2 -R 6 , -CHC(O)OR 7 Or -C(O)OR 8 where R 5 is C 6 ~C 16 Aryl, C 7 ~C 16 Aralkyl or C 7 ~C 16 Alkaryl, preferably C 6 ~C 12 Aryl, C 7 ~C 13 Aralkyl or C 7 ~C 13 R is alkaryl, more preferably phenyl, tolyl, benzyl or phenylethyl, most preferably phenyl; 6 is C 6 ~C 16 Aryl, C 7 ~C 16 Aralkyl or C 7 ~C 16 Alkaryl, preferably C 6 ~C 12 Aryl, C 7 ~C 13 Aralkyl or C 7 ~C 13 R is alkaryl, more preferably phenyl, tolyl, benzyl or phenylethyl, most preferably tolyl; 7 and R 8 are each independently 1 ~C 16 Alkyl, C 6 ~C 16 Aryl, C 3 ~C 16 Cycloalkyl, C 7 ~C 16 Aralkyl or C 7 ~C 16 Alkaryl, preferably C1 ~C 8 Alkyl, C 6 ~C 12 Aryl, C 3 ~C 10 Cycloalkyl, C 7 ~C 12 Aralkyl or C 7 ~C 12 It is alkaryl, more preferably methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, tolyl, ethylphenyl, cyclopropyl, cyclobutyl or cyclopentyl, most preferably methyl, ethyl, or all isomers of propyl or butyl.

[0063] In a further preferred embodiment, X is -OR 3 where R 3 is C 1 ~C 8 Alkyl or C 7 ~C 10 Aralkyl, preferably C 1 ~C 6 Alkyl or C 7 ~C 9 It is aralkyl, more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl or benzyl.

[0064] In another preferred embodiment, X is -NR 3 R 4 where R 3 is C 1 ~C 8 Alkyl or C 7 ~C 10 Aralkyl, preferably C 1 ~C 6 Alkyl or C 7 ~C 9 R is aralkyl, more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl or benzyl, particularly preferably methyl, propyl, isopropyl or butyl; 4 is H or R 3 and is preferably H or methyl.

[0065] In a preferred embodiment, the hydrolysis is acid hydrolysis or base hydrolysis, where acid hydrolysis is preferably carried out with an inorganic or organic acid, and base hydrolysis is preferably carried out with an inorganic or organic base, where the inorganic acid is preferably hydrochloric acid or sulfuric acid.

[0066] In a further preferred embodiment, step a) is carried out in the absence of a solvent or in the presence of an inert solvent, wherein the inert solvent is preferably any one or more of a benzene solvent, an amide solvent, a hydrocarbon solvent, a halohydrocarbon solvent, a sulfone or sulfoxide solvent, an ether solvent or an ester solvent; preferably, the inert solvent is selected from any one or more of a chlorobenzene, a trimethylbenzene, a 1,4-dioxane, a 1,2-dichloroethane, a dimethylsulfoxide, N-methylpyrrolidone, N,N-dimethylformamide, a petroleum ether, a n-heptane, a tetrahydrofuran, a methyltetrahydrofuran, a benzene, a toluene, an ethyl acetate, and a butyl acetate.

[0067] In a preferred embodiment, a base is added at the start of, during and / or after the reaction of step a), preferably after the reaction of step a), wherein the base is preferably an organic base or ammonia, more preferably ammonia.

[0068] In another preferred embodiment, the organic base is an organic amine, such as triethylamine, a pyridine derivative having 1 to 3 substituents attached to one or more carbon atoms in the pyridine or heterocycle, or a piperidine derivative having 1 to 3 substituents attached to one or more carbon atoms in the piperidine or heterocycle.

[0069] In yet another preferred embodiment, step a) comprises: (i) simultaneously feeding the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) into a first reactor to react with each other in the presence of a solvent, and then feeding the resulting product and a base, preferably ammonia gas, together into a second reactor; or (ii) simultaneously feeding the compound of formula (II) and the alcohol of formula (III) into a first reactor to react with each other in the presence of a solvent or in the absence of another solvent, then feeding the resulting product and the compound of formula (V) into a second reactor, and finally feeding the resulting product and a base, preferably ammonia gas, together into a third reactor to react with each other; or (i) ii) the compound of formula (II) and the compound of formula (V) are simultaneously charged into a first reactor to react with each other in the presence of a solvent or in the absence of other solvents, then the resulting product and the alcohol of formula (III) are charged into a second reactor, and finally the resulting product and a base, preferably ammonia gas, are charged together into a third reactor to react with each other; or (iv) the compound of formula (II) and the alcohol of formula (III) are simultaneously charged into a first reactor to react with each other in the presence of a solvent or in the absence of other solvents, then the resulting product, the compound of formula (V) and a base, preferably ammonia gas, are charged together into a second reactor to react with each other.

[0070] In a preferred embodiment, the first reactor, the second reactor and / or the third reactor are each independently one or more reactors.

[0071] In another preferred embodiment, the first reactor, the second reactor, and / or the third reactor are each independently selected from a microchannel reactor, a tubular reactor, a tubular packed reactor, a stirred tank reactor, or any combination thereof. For example, the first reactor, the second reactor, and / or the third reactor are each independently comprised of one or more microchannel continuous flow reactors; or each independently comprised of one or more microchannel continuous flow reactors and one or more tubular reactors.

[0072] In a further preferred embodiment, step a) comprises: (i) simultaneously feeding the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) into a first microchannel reactor to react with each other in the presence of a solvent, and then feeding the resulting product and a base, preferably ammonia gas, together into a second microchannel reactor; or (ii) simultaneously feeding the compound of formula (II) and the alcohol of formula (III) into a first microchannel reactor to react with each other in the presence or absence of a solvent, then feeding the resulting product and the compound of formula (V) into a second microchannel reactor, and finally feeding the resulting product and a base, preferably ammonia gas, together into a third microchannel reactor to react with each other; or (iii) by simultaneously feeding the compound of formula (II) and the compound of formula (V) into a first microchannel reactor to react with each other in the presence or absence of a solvent, then feeding the resulting product and the alcohol of formula (III) into a second microchannel reactor, and finally feeding the resulting product and a base, preferably ammonia gas, together into a third microchannel reactor to react with each other; or (iv) by simultaneously feeding the compound of formula (II) and the alcohol of formula (III) into a first microchannel reactor to react with each other in the presence or absence of a solvent, then feeding the resulting product, the compound of formula (V) and a base, preferably ammonia gas, together into a tubular reactor to react with each other.

[0073] In yet another preferred embodiment, in embodiment (i), the temperature of the first microchannel reactor and / or the second microchannel reactor is each independently in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 30°C, and the temperatures may be the same or different. For example, the reaction temperature may be -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -5°C, -6°C, -5°C, -7°C, -8 ... ℃, -3℃, -2℃, -1℃, 0℃, 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, 10℃, 11℃, 12℃, 13℃, 14℃, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃ or 30℃.

[0074] In embodiment (ii), the temperature of the first microchannel reactor, the second microchannel reactor and / or the third microchannel reactor is each independently in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 30°C, and the temperatures are the same or different. For example, the reaction temperature can be -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -18°C, -17°C, -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -5°C, -6°C, -5 ... ℃, -3℃, -2℃, -1℃, 0℃, 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, 10℃, 11℃, 12℃, 13℃, 14℃, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃ or 30℃.

[0075] In embodiment (iii), the temperature of the first microchannel reactor, the second microchannel reactor and / or the third microchannel reactor is each independently in the range of -30°C to 50°C, preferably -10°C to 30°C, more preferably -5°C to 30°C, and the temperatures may be the same or different.

[0076] In embodiment (iv), the temperature of the first microchannel reactor is in the range of -30°C to 50°C, preferably -25°C to 5°C, more preferably -20°C to -10°C; and / or the temperature of the tubular reactor is in the range of -30°C to 50°C, preferably -25°C to 10°C, more preferably -20°C to 5°C.

[0077] In a preferred embodiment, in step a), when the reactors consist of microchannel reactors, the total residence time in all reactors is in the range of 0.1 seconds to 300 seconds, preferably 1 second to 30 seconds, more preferably 2 seconds to 8 seconds. For example, the dwell time can be set to 0.1 seconds, 0.2 seconds, 0.5 seconds, 0.8 seconds, 1 second, 1.2 seconds, 1.4 seconds, 1.6 seconds, 1.8 seconds, 2 seconds, 2.5 seconds, 3 seconds, 4 seconds, 5 seconds, 6 seconds, 7 seconds, 8 seconds, 9 seconds, 10 seconds, 11 seconds, 12 seconds, 13 seconds, 14 seconds, 15 seconds, 16 seconds, 17 seconds, 18 seconds, 19 seconds, 20 seconds, 21 seconds, 22 seconds, 23 seconds, 24 seconds, 25 seconds, 26 seconds, 27 seconds, 28 seconds, 29 seconds, 30 seconds, 31 seconds, 35 seconds, 40 seconds, 45 seconds, 50 seconds, 55 seconds, 60 seconds, 65 seconds, 70 seconds, 75 seconds, 80 seconds, 85 seconds, 90 seconds, , 95 seconds, 100 seconds, 105 seconds, 110 seconds, 115 seconds, 120 seconds, 125 seconds, 130 seconds, 135 seconds, 140 seconds, 145 seconds, 150 seconds, 155 seconds, 160 seconds, 165 seconds, 170 seconds, 175 seconds, 180 seconds, 185 seconds, 190 seconds, 195 seconds, 200 seconds, 205 seconds, 210 seconds, 215 seconds, 220 seconds, 225 seconds, 230 seconds, 235 seconds, 240 seconds, 245 seconds, 250 seconds, 255 seconds, 260 seconds, 265 seconds, 270 seconds, 275 seconds, 280 seconds, 285 seconds, 290 seconds, 295 seconds, or 300 seconds.

[0078] In a further preferred embodiment, step b) is carried out by: increasing the temperature of the reaction product resulting from step a) to be in the range of 30° C. to 130° C., preferably 60° C. to 120° C., more preferably 90° C. to 100° C. for 1 to 24 hours, preferably 2 to 10 hours, more preferably 5 to 8 hours; and then hydrolyzing the product with an acid, preferably hydrochloric acid, at a temperature in the range of 50° C. to 120° C., preferably 80° C. to 120° C., more preferably 100° C. to 110° C. For example, the reaction product of step a) may be maintained at a temperature of 30° C., 35° C., 40° C., 45° C., 50° C., 55° C., 60° C., 65° C., 70° C., 75° C., 80° C., 85° C., 90° C., 95° C., 100° C., 105° C., 110° C., 115° C., 120° C., 125° C. or 130° C. For example, the reaction product of step a) may be maintained at these temperatures for 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours, 8.5 hours, 9 hours, 9.5 hours, 10 hours, 10.5 hours, 11 hours, 11.5 hours, 12 hours, 12.5 hours, 13 hours, 13.5 hours, 14 hours, 14.5 hours, 15 hours, 15.5 hours, 16 hours, 16.5 hours, 17 hours, 17.5 hours, 18 hours, 18.5 hours, 19 hours, 19.5 hours, 20 hours, 20.5 hours, 21 hours, 21.5 hours, 22 hours, 22.5 hours, 23 hours, 23.5 hours or 24 hours. For example, the hydrolysis temperature may be 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C, 110°C, 115°C or 120°C.

[0079] In the process of the present invention, the glufosinate of formula (IV) or an analogue thereof may be in the L-configuration or the D-configuration, or a mixture of the L- and D-configurations.

[0080] [Example] To further describe and illustrate the present invention, reference is made to the following examples, which are intended to assist those skilled in the art in better understanding and practicing the present invention, but are not intended to limit the scope of the invention.

[0081] The absolute yields of the reaction solutions in the following examples were all calculated from the mass percentage of L-glufosinate in the reaction solutions obtained from liquid chromatography.

[0082] The following reactions were carried out in all examples. [ka]

[0083] Examples A1 to A3: Preparation of L-glufosinate hydrochloride (delivered via microchannel) A chlorobenzene solution containing methyldichlorophosphine (hereinafter referred to as "MDP") at a concentration of 10 wt.% and a chlorobenzene / ethanol solution containing H3 at a concentration of 10 wt.% were prepared.

[0084] A schematic diagram of the reaction process is shown in Figure 1. The above MDP solution was passed through the microchannel reactor at the flow rate shown in Table 1 below, and the temperature was reduced to the temperature shown in T1 in Table 1. Then the MDP solution and the H3 solution were simultaneously fed into another microchannel reactor and reacted at a temperature of T2, with a residence time of t. The raw material stream coming out of the previous microchannel reactor together with ammonia gas was fed into the subsequent microchannel reactor (the reaction temperature was T3); then the temperature of the reaction liquid flowing out of the microchannel reactor was raised to 90°C, the temperature was maintained for 8 hours, and then the reaction liquid was hydrolyzed with hydrochloric acid at a temperature of 100°C, thereby obtaining L-glufosinate hydrochloride.

[0085] [Table 1]

[0086] Examples B1 to B3: Preparation of L-glufosinate hydrochloride (delivered via microchannel) [ka] The reactions carried out in Examples B1 to B3 included those described above.

[0087] A chlorobenzene solution containing 10 wt.% MDP, a chlorobenzene solution containing 10 wt.% H3, and a chlorobenzene solution containing 10 wt.% ethanol were prepared.

[0088] A schematic diagram of the reaction process is shown in FIG. 2. The above MDP solution was passed through the microchannel reactor at the flow rate shown in Table 2 below, and the temperature was reduced to the temperature shown in T1 in the table. Then the MDP solution and the ethanol solution were simultaneously fed into another microchannel reactor and reacted at the temperature T1, the reaction conditions were shown in Table 2 below, and the residence time was t1, and MCP was produced. The obtained MCP reaction solution and the above H3 solution were fed into the first microchannel reactor of another set of two microchannel reactors connected in series (the reaction temperature is T2) at the flow rate listed in Table 2 below, and the residence time was t2; the raw material stream coming out of the first microchannel reactor together with ammonia gas was fed into the second microchannel reactor (the reaction temperature is T3), and the reaction conditions were shown in the table below. Then, the temperature of the reaction solution flowing out of the microchannel reactor was increased to 90° C., the temperature was maintained for 8 hours, and then the reaction solution was hydrolyzed with hydrochloric acid at a temperature of 100° C., thereby obtaining L-glufosinate hydrochloride. Thereafter, the temperature of the reaction liquid flowing out of the microchannel reactor was increased to 90°C and maintained at that temperature for 8 hours, and then the reaction liquid was hydrolyzed with hydrochloric acid at a temperature of 100°C, thereby obtaining L-glufosinate hydrochloride.

[0089] [Table 2]

[0090] Examples C1 to C2: Preparation of L-glufosinate hydrochloride (delivered via microchannel) A chlorobenzene solution containing 10 wt.% MDP, a chlorobenzene solution containing 10 wt.% H3, and a chlorobenzene solution containing 10 wt.% ethanol were prepared.

[0091] A schematic diagram of the reaction process is shown in Figure 3. The above MDP solution was passed through a microchannel reactor at a flow rate shown in Table 3 below, and then the MDP solution and the H3 solution were simultaneously fed into another microchannel reactor and reacted at a temperature of T1, the reaction conditions were shown in Table 3 below, and the residence time was t1. The resulting reaction solution and the above ethanol solution were fed into the first microchannel reactor of another set of two serially connected microchannel reactors (the reaction temperature was T2) at a flow rate listed in Table 3 below, and the residence time was t2; the raw material stream coming out of the first microchannel reactor together with ammonia gas was fed into the second microchannel reactor. Then, the temperature of the reaction solution flowing out of the microchannel reactor was raised to 90°C, the temperature was maintained for 8 hours, and then the reaction solution was hydrolyzed with hydrochloric acid at a temperature of 100°C, thereby obtaining L-glufosinate hydrochloride.

[0092] [Table 3]

[0093] Examples D1 to D14: Preparation of L-glufosinate hydrochloride (delivered by microchannel and tubular reactors) A chlorobenzene solution of MDP, a chlorobenzene solution of H3, and a chlorobenzene solution of ethanol were prepared, each having the concentrations shown in Table 4 below.

[0094] The schematic diagram of the reaction process is shown in Figure 4. The above MDP solution and ethanol solution were pre-cooled by passing them through a microchannel reactor at the flow rate shown in Table 4 below, respectively, and then they were simultaneously introduced into another microchannel reactor to react with each other (at temperature T1), with a residence time of t1; the obtained reaction liquid was passed through a tubular reactor at the flow rate shown in Table 4 below (at temperature T2) to react with the above H3 solution and ammonia gas, with a residence time of t2; then, the temperature of the reaction liquid flowing out of the tubular reactor was raised to 90°C, the temperature was maintained for 8 hours, and then the reaction liquid was hydrolyzed with hydrochloric acid at a temperature of 100°C, thereby obtaining L-glufosinate hydrochloride.

[0095] [Table 4]

[0096] Except for using the same moles of triethylamine to replace ammonia gas in Example D11, the reaction of Example D11 was carried out in the same manner as that of Example D5 in Table 4 above, where the flow rates of reactants, equivalent ratios of reactants, concentration ratios of reactants, reaction temperatures, residence times and yields are shown in Table 5.

[0097] [Table 5]

[0098] The reactions of Examples D12 to D14 were carried out in the same manner as that of Example D5 in Table 4 above, except that in Examples D12 to D14, the alcohols listed in Table 6 were used to replace ethanol, where the flow rate of H3, the equivalent ratio of reactants, the reaction temperature, the residence time and the yields are shown in Table 6 below.

[0099] [Table 6]

[0100] Example E: Preparation of L-Glufosinate Hydrochloride (Tank Reactor) 155 g of a 10 wt. % solution of MDP in chlorobenzene, 200 g of a 10 wt. % solution of H3 in chlorobenzene, and 61.12 g of a 10 wt. % solution of ethanol in chlorobenzene were prepared.

[0101] 61.12 g of the above ethanol solution was added to a tank-type reactor and cooled to -15°C, and 155 g of the above DMP solution was slowly added dropwise, and the reaction solution was stirred for 5 minutes after the addition. Then, 200 g of the above H3 solution and 32.2 g of triethylamine were added dropwise, and the resulting mixture was heated to 90°C to carry out the rearrangement reaction for about 2 hours. The resulting mixture was then desolvated under reduced pressure and hydrolyzed with concentrated hydrochloric acid to obtain L-glufosinate hydrochloride. The absolute yield of the reaction solution as the product was 65.4%.

[0102] The above description is illustrative rather than limiting. Modifications and variations of the above disclosed embodiments are obvious to those skilled in the art and are indeed within the scope of the present disclosure. Therefore, the scope of legal protection of the present disclosure can only be determined through a study of the claims attached hereto.

[0103] The above description of the embodiments is provided for purposes of illustration and description. It is not intended to enumerate or limit the disclosure. Individual elements or features of a particular embodiment are generally not limited to a particular embodiment, are interchangeable where applicable, and can be used in selected embodiments even if not specifically shown or described. They can also be varied in many ways. Such changes should not be considered as a departure from the disclosure, and all such modifications are intended to be included within the scope of the disclosure.

[0104] The exemplary embodiments are provided so that the present disclosure will be detailed and the scope thereof will be fully conveyed to those skilled in the art. In order to fully understand the embodiments of the present disclosure, many specific details, such as examples of specific components, devices, and methods, are described. It will be apparent to those skilled in the art that specific details need not be applied, and the exemplary embodiments can be embodied in many different forms, none of which should be construed as limiting the scope of the present disclosure. In some exemplary embodiments, well-known processes, well-known device structures, and well-known technologies are not described in detail.

[0105] The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting. The terms "comprises," "including," and "having" are inclusive and thus specify the presence of features, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or combinations thereof. Unless expressly identified as a sequence of execution, the process steps, procedures, and operations described herein should not be construed as necessarily requiring performance in the particular sequence described or illustrated. It should also be understood that additional or alternative steps may be used.

Claims

1. A process for preparing glufosinate of formula (IV) or an analogue thereof, comprising: 【Chemistry 1】 The process comprises: a) reacting a compound of formula (II), an alcohol of formula (III) and a compound of formula (V); 【Chemistry 2】 b) subjecting the product obtained from the above reaction to hydrolysis to obtain glufosinate of formula (IV) or an analogue thereof; Including, Here, R １ and R ２ are each independently １ ~C １６ Alkyl, C ６ ~C １２ Aryl, C ３ ~C １０ Cycloalkyl, C ７ ~C １２ Alkaryl and C ７ ~C １２ aralkyl, each group being unsubstituted or C １ ~C ６ Alkyl, C １ ~C ６ substituted with alkoxy, dialkyl, or dialkylamino; Hal １ is a halogen; Hal ２ is a halogen; PG is hydrogen; X is -OR ３ Or -NR ３ R ４ where R ３ is C １ ~C １６ Alkyl, C ６ ~C １６ Aryl, C ３ ~C １６ Cycloalkyl, C ７ ~C １６ Aralkyl or C ７ ~C １６ and alkaryl, where each of these groups is unsubstituted or C １ ~C ６ substituted with alkyl; R ４ is hydrogen or R ３ 4. A process as defined in claim 3.

2. R 1 is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, hexyl, phenyl, benzyl, phenethyl, phenylpropyl, methylphenyl, ethylphenyl and propylphenyl; and / or The process of claim 1, wherein R 2 is C 1 -C 8 alkyl.

3. R １ But, C １ ~C １６ alkyl, cyclohexyl, cyclopentyl, or phenyl, where each group is unsubstituted or C １ ~C ６ Alkyl, C １ ~C ６ substituted with alkoxy or dialkylamino; R ２ But, C １ ~C ６ is alkyl; and / or Hal １ and Hal ２ 2. The process of claim 1 , wherein each is independently fluorine, chlorine, bromine, or iodine.

4. R 1 is methyl, ethyl, propyl, butyl, amyl or hexyl; and / or 4. The process of claim 3, wherein R2 is methyl, ethyl, propyl, butyl, amyl or hexyl.

5. R １ is methyl, R ２ is ethyl, PG is hydrogen, and Hal １ and Hal ２ 4. The process of claim 3, wherein each is independently chlorine.

6. 2. The process according to claim 1, characterized in that the compound of formula (II) is dichloromethylphosphine, dichloroethylphosphine, dichloropropylphosphine, dichlorobutylphosphine, dichlorocyclohexylphosphine, dichlorophenylphosphine, dichloro-4-methoxyphenylphosphine or dichloro-4-dimethylaminophenylphosphine.

7. 2. The process according to claim 1, characterized in that the alcohol of formula (III) is methanol, ethanol, n-propanol, isopropanol or n-butanol.

8. 8. Process according to any one of claims 1 to 7, characterized in that step a) is carried out by: mixing together a compound of formula (II), an alcohol of formula (III), a compound of formula (V) and a solvent; or by mixing a compound of formula (II) and an alcohol of formula (III) and then mixing the obtained product with a compound of formula (V); or by mixing a compound of formula (II) and a compound of formula (V) and then mixing the obtained product with an alcohol of formula (III).

9. The process according to any one of claims 1 to 7, characterized in that, when all the reactions of step a) are carried out in a microchannel reactor, the reaction of step a) is carried out at a reaction temperature in the range of -30°C to 50°C; or when the reaction of step a) is carried out in a reactor consisting of a microchannel reactor and a tubular reactor, or in a tank reactor, the reaction of step a) is carried out at a reaction temperature in the range of -30°C to 50°C.

10. The process described in claim 9, characterized in that when all the reactions in step a) are carried out in a microchannel reactor, the reactions in step a) are carried out at a reaction temperature in the range of -5°C to 30°C; or when the reactions in step a) are carried out in a reactor consisting of a microchannel reactor and a tubular reactor, or in a tank reactor, the reactions in step a) are carried out at a reaction temperature in the range of -15°C to 5°C.

11. The process according to any one of claims 1 to 7, characterized in that the molar ratio of the compound of formula (II) and the alcohol of formula (III) is 1:(0.1-1.1).

12. The process according to any one of claims 1 to 7, characterized in that the molar ratio of the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) is 1:(0.1-1.9):(0.1-2).

13. The process of claim 12, wherein the molar ratio of the compound of formula (II), the alcohol of formula (III) and the compound of formula (V) is 1:(0.9-1.1):(0.7-1).

14. Hal ２ is chlorine; PG is H; and X is -OR ３ where R ３ is C １ ~C ８ Alkyl or C ７ ~C １０ 2. The process of claim 1, wherein the compound is an aralkyl.

15. The process of claim 14, wherein R 3 is C 1 -C 6 alkyl or C 7 -C 9 aralkyl.

16. The process of claim 15, wherein R 3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl or benzyl.

17. 8. The process according to any one of claims 1 to 7, characterized in that the hydrolysis is an acid hydrolysis or a base hydrolysis, wherein the acid hydrolysis is carried out with an inorganic or organic acid and the base hydrolysis is carried out with an inorganic or organic base.

18. The process of claim 17, wherein the inorganic acid is hydrochloric acid or sulfuric acid.

19. 8. The process according to any one of claims 1 to 7, characterized in that step a) is carried out in the absence of a solvent or in the presence of an inert solvent, which is any one or more of a benzene solvent, an amide solvent, a hydrocarbon solvent, a halohydrocarbon solvent, a sulfone or sulfoxide solvent, an ether solvent or an ester solvent.

20. The process of claim 19, wherein the inert solvent is selected from any one or more of chlorobenzene, trimethylbenzene, 1,4-dioxane, 1,2-dichloroethane, dimethylsulfoxide, N-methylpyrrolidone, N,N-dimethylformamide, petroleum ether, n-heptane, tetrahydrofuran, methyltetrahydrofuran, benzene, toluene, ethyl acetate, and butyl acetate.

21. The process according to any one of claims 1 to 7, characterized in that a base is added at the start of, during and / or after the reaction of step a).

22. The process of claim 21, wherein a base is added after the reaction of step a).

23. The process of claim 21, wherein the base is an organic base or ammonia.

24. 24. The process according to claim 23, characterized in that the organic base is an organic amine selected from triethylamine, pyridine or a pyridine derivative having 1 to 3 substituents attached to one or more carbon atoms in the heterocycle, or piperidine or a piperidine derivative having 1 to 3 substituents attached to one or more carbon atoms in the heterocycle.

25. Step a) is: (i) simultaneously charging a compound of formula (II), an alcohol of formula (III) and a compound of formula (V) in a first reactor and reacting them with each other in the presence of a solvent, then charging the resulting product and a base together in a second reactor; or (ii) simultaneously charging a compound of formula (II) and an alcohol of formula (III) in a first reactor and reacting them with each other in the presence of a solvent or in the absence of another solvent, then charging the resulting product and a compound of formula (V) in a second reactor, and finally charging the resulting product and a base together in a third reactor and reacting them with each other; or (iii) simultaneously charging a compound of formula (II) and a compound of formula (V) in a first reactor and reacting them with each other in the presence of a solvent or in the absence of another solvent, then charging the resulting product and a compound of formula (V) in a second reactor, and finally charging the resulting product and a base together in a third reactor and reacting them with each other; 8. The process according to any one of claims 1 to 7, characterized in that it is carried out by: (i) simultaneously charging the compound of formula (II) and the alcohol of formula (III) in a first reactor and reacting with each other in the presence of a solvent or in the absence of other solvents, then charging the obtained product and the alcohol of formula (III) in a second reactor and finally charging the obtained product and the base together in a third reactor and reacting with each other; or (iv) simultaneously charging the compound of formula (II) and the alcohol of formula (III) in a first reactor and reacting with each other in the presence of a solvent or in the absence of other solvents, then charging the obtained product, the compound of formula (V) and the base together in a second reactor and reacting with each other.

26. 26. The process of claim 25, wherein the first reactor, the second reactor and / or the third reactor are each independently selected from a microchannel reactor, a tubular reactor, a tubular packed reactor, a stirred tank reactor or any combination thereof.

27. The process of claim 26, wherein the first reactor, the second reactor and / or the third reactor each independently comprise one or more microchannel continuous flow reactors; or each independently comprise one or more microchannel continuous flow reactors and one or more tubular reactors.

28. Step a) is: (i) simultaneously feeding a compound of formula (II) and an alcohol of formula (III) and a compound of formula (V) into a first microchannel reactor to react with each other in the presence of a solvent, and then feeding the resulting product and a base together into a second microchannel reactor; or (ii) simultaneously feeding a compound of formula (II) and an alcohol of formula (III) into a first microchannel reactor to react with each other in the presence of a solvent or in the absence of a solvent, then feeding the resulting product and a compound of formula (V) into a second microchannel reactor, and finally feeding the resulting product and a base together into a third microchannel reactor to react with each other; or (iii) simultaneously feeding a compound of formula (II) and 26. The process according to claim 25, characterized in that it is carried out by simultaneously feeding the compound of formula (II) and the alcohol of formula (III) into a first microchannel reactor and reacting them with each other in the presence or absence of a solvent, then feeding the resulting product and the alcohol of formula (III) into a second microchannel reactor, and finally feeding the resulting product and the base together into a third microchannel reactor and reacting them with each other; or (iv) feeding the compound of formula (II) and the alcohol of formula (III) into a first microchannel reactor and reacting them with each other in the presence or absence of a solvent, then feeding the resulting product, the compound of formula (V) and the base together into a tubular reactor and reacting them with each other.

29. The process of claim 28, wherein the base is ammonia gas.

30. In embodiment (i), the temperature of the first microchannel reactor and / or the second microchannel reactor is each independently in the range of −30° C. to 50° C., and said temperatures are the same or different; In embodiment (ii), the temperature of the first microchannel reactor, the second microchannel reactor, and / or the third microchannel reactor is each independently in the range of −30° C. to 50° C., and the temperatures are the same or different; In embodiment (iii), the temperature of the first microchannel reactor, the second microchannel reactor, and / or the third microchannel reactor is each independently in the range of −30° C. to 50° C., and the temperatures are the same or different; The process according to claim 28, characterized in that in embodiment (iv), the temperature of the first microchannel reactor is in the range of -30°C to 50°C; and / or the temperature of the tubular reactor is in the range of -30°C to 50°C.

31. In embodiment (i), the temperature of the first microchannel reactor and / or the second microchannel reactor is each independently in the range of −5° C. to 30° C., and the temperatures are the same or different; In embodiment (ii), the temperature of the first microchannel reactor, the second microchannel reactor, and / or the third microchannel reactor is each, independently, in the range of −5° C. to 30° C., and the temperatures are the same or different; In embodiment (iii), the temperature of the first microchannel reactor, the second microchannel reactor, and / or the third microchannel reactor is each, independently, in the range of −5° C. to 30° C., and the temperatures are the same or different; The process according to claim 30, characterized in that in embodiment (iv), the temperature of the first microchannel reactor is in the range of -25°C to 5°C; and / or the temperature of the tubular reactor is in the range of -20°C to 5°C.

32. 26. The process according to claim 25, characterized in that in step a), if the reactors consist of only microchannel reactors, the total residence time in all the reactors is in the range of 0.1 s to 300 s; or if the reactors consist of microchannel reactors and tubular reactors, the total residence time in all the reactors is in the range of 1 min to 20 min.

33. The process of claim 32, wherein in step a), if the reactors consist of only microchannel reactors, the total residence time in all the reactors is in the range of 10 seconds to 40 seconds; or if the reactors consist of microchannel reactors and tubular reactors, the total residence time in all the reactors is in the range of 9 minutes to 14 minutes.

34. 8. The process according to any one of claims 1 to 7, characterized in that step b) is carried out by: increasing the temperature of the reaction product obtained from step a) to be in the range of 30°C to 130°C for a period of 1 to 24 hours; followed by hydrolysis of the product with acid at a temperature in the range of 50°C to 120°C.

35. The method of claim 35, wherein step b) comprises: increasing the temperature of the reaction product resulting from step a) to be in the range of 90°C to 100°C; Maintain temperature for 5-8 hours; Hydrolyzing the product with acid at a temperature in the range of 100°C to 110°C; and / or The acid is hydrochloric acid.

35. The process according to claim 34, characterized in that it is carried out by

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