US 12,252,501 B2Granted

Methods of preparing glufosinate

AssigneesYongnong Biosciences Co., Ltd., Ningxia Yongnong Biosciences Co., Ltd.

InventorsWenjie Tang, Chengjun Wu, Nan Li, Jianjie Xu, Xianzhong Tang, Chunhui Mao

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Abstract

Disclosed is a method of preparing glufosinate, and specifically a method of preparing glufosinate represented by formula (I) or its salt or enantiomer, or a mixture of its enantiomers in any ratio, comprising a step of hydrolyzing a compound of formula (III) to generate a compound of formula (I). Due to a distinctive reaction mechanism adopted in the method of the present disclosure, a halogenated hydrocarbon by-product in the Michaelis-Arbuzov reaction can be avoided and thus the destructive impact of the halogenated hydrocarbon by-product on ozone in the aerosphere can be prevented. Accordingly, the equipment and engineering investments required for the separation, purification, and collection of the foregoing by-product are eliminated, and the potential environmental and safety hazards brought by the foregoing by-product are also avoided.

Claims33

Dependent claims

A method of preparing glufosinate represented by formula (I) or its salt or enantiomer, or a mixture of its enantiomers in any ratio, comprising:

hydrolyzing a compound of formula (III) to generate a compound of formula (I);
wherein:
X1 is halogen;
Y is —OR3 or —N(R4)(R5);
R1 and R2 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R1 and R2 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R3, R4, and R5 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R4 and R5 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
and
* denotes a chiral carbon atom.

5 more elements

A compound of formula (III) or its salt or enantiomer, or a mixture of its enantiomers in any ratio;

wherein:
X1 is halogen;
Y is —OR3 or —N(R4)(R5);
R1 and R2 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R1 and R2 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R3, R4, and R5 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R4 and R5 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
and
* denotes a chiral carbon atom.

4 more elements

A method of preparing a compound of formula (III) or its salt or enantiomer, or a mixture of its enantiomers in any ratio, comprising:

subjecting a compound of formula (II)
to a reaction with any one of the following compounds or mixtures:
a compound of formula (IV);
a compound of formula (V);
a compound of formula (IV) and a compound of formula (V);
a compound of formula (IV) and a compound of formula (VII);
a compound of formula (V) and a compound of formula (VII);
or a compound of formula (IV), a compound of formula (V), and a compound of formula (VII);
wherein:
X1 is halogen;
X2 is halogen;
Y is —OR3 or —N(R4)(R5);
R1 and R2 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R1 and R2 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R3, R4, and R5 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R4 and R5 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R9 and R10 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R9 and R10 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
and
* denotes a chiral carbon atom.

14 more elements

A method of preparing a compound of formula (III) or its salt or enantiomer, or a mixture of its enantiomers in any ratio, comprising:

preparing the compound of formula (III) from a reaction with the compound of formula (VI);
wherein:
X1 is halogen;
Y is —OR3 or —N(R4)(R5);
R1 and R2 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R1 and R2 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R3, R4, and R5 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R4 and R5 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
and
* denotes a chiral carbon atom.

5 more elements

A compound of formula (VI) or its salt or enantiomer, or a mixture of its enantiomers in any ratio;

wherein:
X1 is halogen;
Y is —OR3 or —N(R4)(R5);
R1 and R2 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R1 and R2 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R3, R4, and R5 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R4 and R5 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
and
* denotes a chiral carbon atom.

4 more elements

A method of preparing a compound of formula (VI) or its salt or enantiomer, or a mixture of its enantiomers in any ratio, comprising:

subjecting a compound of formula (II)
to a reaction with any one of the following compounds or mixtures:
a compound of formula (IV);
a compound of formula (V);
a compound of formula (IV) and a compound of formula (V);
a compound of formula (IV) and a compound of formula (VII);
a compound of formula (V) and a compound of formula (VII);
or a compound of formula (IV), a compound of formula (V), and a compound of formula (VII);
wherein:
X1 is halogen;
X2 is halogen;
Y is —OR3 or —N(R4)(R5);
R1 and R2 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R1 and R2 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R3, R4, and R5 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R4 and R5 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R9 and R10 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R9 and R10 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
and
* denotes a chiral carbon atom.

14 more elements

A method of preparing a compound of formula (VI) or its salt or enantiomer, or a mixture of its enantiomers in any ratio, comprising:

subjecting a compound of formula (II);
to a reaction with a compound of formula (VII) and a compound of formula (VIII);
wherein:
X1 is halogen;
X2 is halogen;
Y is —OR3 or —N(R4)(R5);
R1 and R2 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R1 and R2 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
R3, R4, and R5 are each independently selected from hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a three-membered to six-membered heterocycloalkyl group, a C6-C10 aryl group, or a five-membered to ten-membered heteroaryl group, or R4 and R5 form a three-membered to six-membered heterocycloalkyl group together with the N atom to which they are attached, wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the three-membered to six-membered heterocycloalkyl group, the C6-C10 aryl group, or the five-membered to ten-membered heteroaryl group is optionally substituted by halogen, a carboxyl group, a hydroxyl group, a cyano group, an amino group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C3-C6 cycloalkyl group, or a C6-C10 aryl group;
and
* denotes a chiral carbon atom.

7 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/307,911Filed 27 Apr 2023
Priority: CN 202211440553.X17 Nov 2022
Published: US 2024/0116960 A111 Apr 2024
Granted: 18 Mar 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification4 codes

C07F 9/301
Phosphinic acids [R2P]; Thiophosphinic acids ; [R2P ]: acyclic saturated acids which can have further substituents on alkyl
C07F 9/28
Phosphorus compounds: with one or more P—C bonds
C07F 9/65844
Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring: the phosphorus atom being part of a five-membered…
C07F
Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen