DE4241747C2 - Improved procedure for performing a cross-coupling reaction - Google Patents

Description

The invention relates to an improved method for through conduct a cross-coupling reaction between arylboronic acids and aryl halides in a two-phase solvent system, in the presence of a transition metal catalyst and a base, wherein at least 3 mol base, based on 1 mol of boronic acid.

An overview of the use of the cross-coupling reaction you can see the articles by E. Poetsch in contacts (Darmstadt) 1988, Issue 2, pages 15 ff., And by G. W. Gray et al. a. in moles Cryst. Liq. Cryst. 1991, volume 206, pages 187 ff.

Usually, the classic cross-coupling craze tion arylboronic acid with bromoaromatics in the presence of carbo naten or hydrogen carbonates implemented. As a transition metal mostly palladium is used, which phosphine ligand, mostly has triphenylphosphine. T. Watanabe, M. Miyaura and A. Suzuki (Synlett. 1992, 207) examined the cross Coupling of aryl boronic acid with aryl halides in the presence by Tetrakis [triphenylphosphin] palladium (0) and various bases in a single-phase solvent system aqueous dimethylformamide or in two-phase solution system of benzene / water. They were watching at Verwen tion of 1.5 mol NaOH or Ba (OH) ₂ or adding one  stronger base than soda, based on 1 mol aryl halide, an acceleration of the cross-coupling reaction in comparison for using Na₂CO₃. Homocoupling products are called negligible under the coupling conditions with soda designated and are apparently considered negligible, with 1.5 mol NaOH or Ba (OH) ₂ as base additive.

It has now been found by the inventors of the present invention asked that in the cross-coupling reaction in the two-phase Solvent system with the stated amounts of base considerable amounts of by-products accrue through the homocoupling of the arylboronic acids are formed.

The object of the invention is an improved cross coupling Providing the process that has the disadvantages of the previous applied procedure does not have and risk free and is inexpensive to carry out on an industrial scale.

This object was achieved according to the invention by a improved method for performing a cross coupling reaction between aryl boronic acids and aryl halides in a two-phase solvent system, in the presence of a Transition metal catalyst and a base, with one at least 3 mol base, based on 1 mol boronic acid.

A preferred embodiment of the invention is Her position of bisaryl compounds of formula I,

wherein

each independently represents a naphthalene group or a 1- to 5-fold substituted phenyl group, in which one or two CH groups can also be replaced by N,
in which
an arylboronic acid derivative of the formula II,

wherein

has the meaning given, and
R⁴ is hydroxy or C _1-6 alkoxy,
with an aryl halide of the formula (III)

wherein

has the meaning given, and
Hal means Cl, Br or J
in the presence of a palladium catalyst and at least 3.5 mol of a base, based on 1 mol of arylboronic acid, in particular a process for the preparation of biphenyl derivatives of the formula Ia

wherein
MG ¹ and MG ² each independently of one another C _1-18 alkyl, C _1-18 alkoxy or a mesogenic residue, one of the residues MG ¹ and MG ² also -CN, -NCS, -F, -CF ₃ , -OCF ₃ , -OCF ₂ H or -OCH ₂ CF ₃ , and
m and n are each independently 0, 1 or 2
mean, wherein a phenylboronic acid derivative of the formula IIa

with a halobenzene derivative of the formula IIIa

implements.

The term mesogenic group is familiar to the person skilled in the art (e.g. H. Kelker, H. Hatz, Handbook of Liquid Crystals) and stands for a so-called "rod-like" rest consisting of ring glie other, if necessary bridge members and wing groups.  

The term mesogenic group accordingly preferably includes one Rest of formula IV

-Z ¹ [-A ¹ -Z ² ] -mA ² -R ⁵ IV

wherein
R ^{5 is} an unsubstituted or at least one halogen-substituted alkyl, alkoxy or alkylene radical having 1 to 15 carbon atoms, one or more CH ₂ groups in these radicals each being independently of one another by -O-, -S-,

-CO-, -CO-O-, -O-CO- or -O-CO-O- can be replaced so that O atoms are not directly linked to each other, or also -CN, -NCS, -Cl, - F, -CF ₃ , -OCF ₃ , -OCF ₂ H or -OC ₂ F ₅ can be
A ¹ and A ² each independently

• (a) trans-1,4-cyclohexylene radical, in which one or more non-adjacent CH ₂ groups can also be replaced by -O- and / or -S-,
• (b) 1,4-phenylene radical, where also one or two CH groups can be replaced by N,
• (c) radical from the group 1,4-cyclohexenylene, 1,4- Bicyclo (2,2,2) octoylene, piperidine-1,4-diyl, Naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4-tetrahydronaphthalene-2,6-diyl,  where the radicals (a) and (b) have a substituent, which has the meaning of R¹ and R², substituted could be,

Z¹ and Z² each independently of one another -CO-O-, -O-CO-, -CH₂O-, -OCH₂-, -CH₂CH₂-, -CH = CH-, -C≡C- or a single bond and
m means 0, 1 or 2.

Further preferred embodiments are:

• a) Process, wherein in formula III or IIIa
  Hal means Cl.
• b) method, wherein the base is an alkali or alkaline earth is metal hydroxide.
• c) Process wherein the transition metal is palladium.
• d) method, wherein the reaction at temperatures between 15 and 130 ° C, especially where one the reaction at the boiling point of the reaction performs mixture.
• e) process, wherein the transition metal catalyst in 0.5 to 5 mol%, based on one of the Ver to be coupled bindings, deploys.

The reaction temperature is usually in the range of 20 ° C to 130 ° C. It is preferably set to a range of 70 ° C to 90 ° C set.

Suitable two-phase solvents are mixtures of coals Hydrogen, such as toluene and aqueous media.

Preferred coupling components are

• a) Arylboronic acids, in particular of the formulas II or IIa and
• b) aryl halides.

Of the halogen aromatics, bromine and chloroaryl, in particular especially the chlorophenyl compounds are particularly preferred.

Preferred bases are alkali or alkaline earth metal hydroxides, especially sodium hydroxide or barium hydroxide.

As a rule, at least 3 mol of base, preferably NaOH, based on 1 mol of arylboronic acid. Preferably 3.5 to 8.0 mol, in particular 3.8 to 5.0 mol, are used Base on 1 mol arylboronic acid.

The type of transition metal catalyst is not critical. Preferred transition metal catalysts are:

Palladium / C, complex bound palladium, in particular Bis [triaryl- or trialkylphosphine] palladium (II) or Tetrakis [triaryl- or trialkylphenyl] palladium (0).  

The method has the advantage that all Synthesis steps in a temperature range that is technical can be mastered without difficulty can.

Furthermore, the inventive method, which Yield-reducing side reaction of homocoupling almost completely suppressed.

The following examples are intended to illustrate the invention without limit them.

Typical experimental procedure

A two-phase solvent system is made from 75 ml of toluene, 40 ml of water and the amount specified in each case at base. To this system, 0.03 mol of the to coupling boronic acid, 0.03 mol of the halogenaro to be coupled mat and 0.06 mmol of the palladium catalyst to be used added.

The mixture is stirred at the boiling temperature for 2 hours.

After the usual work-up, the product obtained is chro matographically isolated.

The results of different approaches with different aryl Kaliden and phosphine ligands are in Tables I and II listed:

Table 1

Influence of the phosphine ligand on the cross-coupling reaction between PCH-5B (OH ₂ ) and 1,2-difluoro-4-bromobenzene

The results clearly show that when using a Excess of base the cross-coupling reaction smooth, d. H. without significant homocoupling (approaches 1 and 2), whereas the use of smaller amounts of base (approaches 3 and 4) or from weak bases (approaches 5 and 6) to high Leads to homocoupling.

Table 2

The results clearly show that with the help of a Excess base the homocoupling in cross coupling reactions can be almost completely suppressed.

Claims (1)

Process for carrying out a cross-coupling reaction between arylboronic acids and aryl halides in a two-phase solvent system, in the presence of a transition metal catalyst and a base, characterized in that at least 3 mol of base, based on 1 mol of boronic acid, are used.