Production method of biarylphosphine

Patent metadata

Field	Value
Publication number	US-11453687-B2
Application number	US-202017600251-A
Country	US
Kind code	B2
Filing date	Mar 30, 2020
Priority date	Apr 5, 2019
Publication date	Sep 27, 2022
Grant date	Sep 27, 2022

Abstract

A production method by which a biarylphosphine useful as a Buchwald phosphine ligand can be obtained in high purity is provided through an industrially advantageous process. The production method of a biarylphosphine comprises a step A of reacting a lithiated product obtained through lithiation of a halogenated benzene derivative with a benzene derivative to obtain a biphenyl derivative, and a step B of the reacting the biphenyl derivative with a halogenated phosphine. In the step A, the charge molar ratio of the halogenated benzene derivative to the benzene derivative is preferably 1.0 to 5.0.

First claim

The invention claimed is:

1. A production method of a biarylphosphine comprising:
a step A of preparing
a liquid a comprising a lithiated product obtained by adding a lithiating agent to a liquid containing a halogenated benzene derivative represented by the following general formula (1):

wherein R 1 to R 3 represent an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, a heteroaralkyl group, an alkoxy group or an amino group, and the alkyl group, the cycloalkyl group, the aryl group, the heteroaryl group, the aralkyl group, the heteroaralkyl group, the alkoxy group and the amino group may be substituted with an alkyl group, a cycloalkyl group, a halogen group or an alkoxy group; R 1 to R 3 may be a same group or a different group; and X 1 represents a halogen atom;

for lithiation so that a molar ratio of the lithiating agent to the halogenated benzene derivative represented by the general formula (1) is 2.0 to 7.0, and
a liquid b comprising a benzene derivative represented by the following general formula (2):

wherein R 4 to R 5 represent an alkyl group, an alkoxy group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, a heteroaralkyl group or an amino group; and the alkyl group, the cycloalkyl group, the aryl group, the heteroaryl group, the aralkyl groups, the heteroaralkyl group, the alkoxy groups and the amino group may be substituted with an alkyl group, a cycloalkyl group, a halogen groups or an alkoxy groups; R 4 to R 5 may be a same group or a different group; and X 2 represents a halogen atom; and
mixing the liquid a and the liquid b for reaction so that a charge molar ratio of the halogenated benzene derivative represented by the general formula (1) to the benzene derivative represented by the general formula (2) is 1.2 to 3.0
to obtain a biphenyl derivative represented by the following general formula (3):

wherein R 1 to R 5 are the same as described above;
and a subsequent step B of reacting the biphenyl derivative with a halogenated phosphine represented by the following general formula (4):
(R 6 )(R 7 )PX 3   (4)

wherein R 6 to R 7 represent an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group or a heteroaralkyl group; and R 6 to R 7 may be a same group or a different group; the alkyl group, the cycloalkyl group, the aryl group, the heteroaryl group, the aralkyl group, and the heteroaralkyl group may be substituted with an alkyl group, a cycloalkyl group, a halogen group or an alkoxy group; and X 3 represents a halogen atom;
the biarylphosphine being represented by the following general formula (5):

wherein R 1 to R 7 are the same as described above.

2. A production method of a biarylphosphine comprising:
a step A of preparing
a liquid a comprising a lithiated product obtained by adding a lithiating agent to a liquid containing a halogenated benzene derivative represented by the following general formula (1):

wherein R 1 to R 3 represent an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, a heteroaralkyl group, an alkoxy group or an amino group, and the alkyl group, the cycloalkyl group, the aryl group, the heteroaryl group, the aralkyl group, the heteroaralkyl group, the alkoxy group and the amino group may be substituted with an alkyl group, a cycloalkyl group, a halogen group or an alkoxy group; R 1 to R 3 may be a same group or a different group; and X 1 represents a halogen atom;

for lithiation so that a molar ratio of the lithiating agent to the halogenated benzene derivative represented by the general formula (1) is 2.0 to 7.0, and
a liquid b comprising a benzene derivative represented by the following general formula (2):

wherein R 4 to R 5 represent an alkyl group, an alkoxy group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, a heteroaralkyl group or an amino group; and the alkyl group, the cycloalkyl group, the aryl group, the heteroaryl group, the aralkyl groups, the heteroaralkyl group, the alkoxy group and the amino group may be substituted with an alkyl group, a cycloalkyl group, a halogen groups or an alkoxy groups; R 4 to R 5 may be a same group or a different group; and X 2 represents a halogen atom; and
mixing the liquid a and the liquid b for reaction so that a charge molar ratio of the halogenated benzene derivative represented by the general formula (1) to the benzene derivative represented by the general formula (2) is 1.2 to 3.0
to obtain a biphenyl derivative represented by the following general formula (3):

wherein R 1 to R 5 are the same as described above;
a subsequent step C of reacting the biphenyl derivative with a brominating agent or an iodinating agent to obtain a halogenated biphenyl derivative represented by the following general formula (6):

wherein R 1 to R 5 are the same as described above, and A represents a bromine atom or an iodine atom;
and a subsequent step D of reacting a lithiated product obtained through lithiation of the halogenated biphenyl derivative with a halogenated phosphine represented by the following general formula (4):
(R 6 )(R 7 )PX 3   (4)

wherein R 6 to R 7 represent an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group or a heteroaralkyl group; and R 6 to R 7 may be a same group or a different group; the alkyl group, the cycloalkyl group, the aryl group, the heteroaryl group, the aralkyl group, and the heteroaralkyl group may be substituted with an alkyl group, a cycloalkyl group, a halogen group or an alkoxy group; and X 3 represents a halogen atom;
the biarylphosphine being represented by the following general formula (5):

wherein R 1 to R 7 are the same as described above.

3. The production method of a biarylphosphine according to claim 1 , wherein the step B is performed by a reaction in succession with the step A.

4. The production method of a biarylphosphine according to claim 1 , wherein R 1 to R 3 in the formulas are the same group, and R 4 to R 5 are the same group.

5. The production method of a biarylphosphine according to claim 4 , wherein R 1 to R 3 in the formulas are an iso-propyl group.

6. The production method of a biarylphosphine according to claim 4 , wherein R 4 to R 5 in the formulas are a methoxy group or a methyl group.

7. The production method of a biarylphosphine according to claim 4 , wherein R 6 to R 7 in the formulas are the same group.

8. The production method of a biarylphosphine according to claim 7 , wherein R 6 to R 7 in the formula are an adamantyl group, a tert-butyl group or a cyclohe

Assignees

• Nippon Chemical Ind

Inventors

• Tamura Ken
• SAWATSUGAWA Yuki
• Sano Natsuhiro

Classifications

• C07F9/5072 Primary

  from starting materials having the structure P-H (C07F9/5059 takes precedence) · CPC title

• C07C41/22

  by introduction of halogens; by substitution of halogen atoms by other halogen atoms · CPC title

• C07F9/5068

  from starting materials having the structure >P-Hal · CPC title

• C07F9/50 Primary

  Organo-phosphines · CPC title