JPH11228454A - Production of aryl bromide compounds substituted by alkynyl groups - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing an alkynyl-substituted aryl bromide compound, capable of selectively producing the alkynyl-substituted aryl bromide compound from a bromoaryl triflate and an alkynyl Grignard reagent. SOLUTION: This method for producing an alkynyl-substituted aryl bromide compound comprises reacting a bromoaryl triflate and an alkynyl Grignard reagent in the presence of a palladium catalyst having an aminoalkylphosphine ligand of the formula: R<2> R<3> N-CH(R<4> )CH2 -P(R<1> )2 (R<1> is phenyl which may have a substitutent; R<2> and R<3> are each independently a lower alkyl; R<4> is a lower alkyl group, a cycloalkyl group, an aralkyl group or phenyl group which may have a substituent).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing an alkynyl-substituted aryl bromide, and more particularly, to a reaction between a bromoaryl triflate and an alkynyl Grignard reagent in the presence of a palladium catalyst having a specific ligand. And a method for producing an alkynyl-substituted aryl bromide.

[0002]

BACKGROUND OF THE INVENTION Alkynyl-substituted aryls are compounds useful as intermediates such as liquid crystals and conductive polymers.
For example, a method of reacting an aryl bromide or aryl triflate with acetylene in the presence of a palladium-based catalyst having triphenylphosphine as a ligand and copper iodide is known (Tetrahedron Lett. 1975, 4).
467).

However, in order to produce more useful alkynyl-substituted aryl bromides,
When a reaction was performed using bromoaryl triflates having both bromide and triflate groups instead of aryl halide or aryl triflate, bromide reacted preferentially, and trifluoromethanesulfonyloxy (phenylethynyl) benzene Was produced in a large amount, and only a small amount of the desired product was obtained.

In addition, the inventors have reacted an aryl Grignard reagent with a bromoaryl triflate in the presence of a palladium catalyst having 1,3-bis (diphenylphosphino) propane (hereinafter abbreviated as dppp) as a ligand. A method for selectively producing aryl-substituted aryl bromides (Tetrahedron Lett. 1997.
38. 7087). However, after that, when this method was performed using an alkynyl Grignard reagent instead of the aryl Grignard reagent, it was found that the reaction did not proceed at all.

Under such circumstances, the present inventors have conducted intensive studies on palladium-based catalysts to produce alkynyl-substituted aryl bromides from bromoaryl triflates and alkynyl Grignard reagents. As a result, it was found that if a specific palladium-based catalyst having an aminoalkylphosphine-based ligand was used, the intended alkynyl-substituted aryl bromides could be produced selectively and in high yield. completed.

[0006]

That is, the present invention relates to a compound represented by the formula (I) R ² R ³ N-CH (R ⁴ ) CH ₂ -P (R ¹ ) ₂ (I) wherein R ¹ is a substituent A phenyl group which may have
R ² and R ³ each independently represent a lower alkyl group. R
⁴ represents a lower alkyl group, a cycloalkyl group, an aralkyl group or a phenyl group which may have a substituent. )
An alkynyl-substituted aryl bromide is industrially excellently produced by reacting a bromoaryl triflate with an alkynyl Grignard reagent in the presence of a palladium-based catalyst having an aminoalkylphosphine ligand represented by Is provided.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.
The present invention is characterized by using a palladium-based catalyst having an aminoalkylphosphine-based ligand represented by the above formula (I). In the formula (I), R ¹ represents a phenyl group which may have a substituent, and R ² and R ³ each independently represent a lower alkyl group. R ⁴ is a lower alkyl group,
Represents a cycloalkyl group, an aralkyl group or a phenyl group which may have a substituent.

Here, examples of the lower alkyl group include methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl, pentyl and the like.
Examples of the cycloalkyl group include cyclopentyl, cyclohexyl, cycloheptyl and the like. Examples of the aralkyl group include phenylmethyl, phenylethyl, phenylpropyl and the like. Examples of the phenyl group which may have a substituent include a phenyl group, a phenyl group substituted by a lower alkyl group as described above, a phenyl group substituted by a halogen atom such as a fluorine group and a chlorine group, a methoxy group, and an ethoxy group. , Propoxy group,
And a phenyl group substituted by a lower alkoxy group such as a butoxy group.

Aminoalkylphosphine ligand (I)
Representative examples of, for example, 1-diphenylphosphino-2
-N, N-Dimethylaminopropane (hereinafter abbreviated as alaphos), 1-diphenylphosphino-2-N, N-dimethylamino
3-methylbutane (hereinafter abbreviated as valphos), 1-diphenylphosphino-2-N, N-dimethylamino-3-phenylpropane (hereinafter abbreviated as phephos) and the like. Aminophosphine ligands (I) are described, for example, in J. Org. Chem., 48
2195 (1983). The palladium-based catalyst used in the present invention is prepared from the above-mentioned aminoalkylphosphine-based ligand (I) and a palladium compound, for example, “Experimental Chemistry Course” edited by The Chemical Society of Japan, 18 393 (19
91), and can be produced according to the method described in 91). Examples of the palladium compound include palladium chloride bisacetonitrile, tris (dibenzylideneacetone) palladium, allyl palladium dichloride, palladium acetate and the like. The palladium-based catalyst may be prepared in advance or may be prepared in a reaction system.

According to the present invention, a bromoaryl triflate is reacted with an alkynyl Grignard reagent in the presence of such a palladium-based catalyst.

[0011] (In the formula, TfO represents a trifluoromethanesulfonyloxy group, R ⁵ represents a hydrogen atom, a fluorine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyl group. R ⁶ and R ⁷ each independently represent a hydrogen atom , Fluorine atom,
It represents an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyl group, or represents a naphthyl group which may have a substituent together with R ⁶ and R ⁷ together with a benzene ring. )).

Here, the alkyl group in the triflate represented by the formula (II) includes, for example, methyl, ethyl, n-propyl, I-propyl, n-butyl, I-propyl,
chain alkyl groups such as sec-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, palmityl, stearyl, cyclic alkyl groups such as cyclopentyl and cyclohexyl, trifluoromethyl, 2 And halogenated alkyl groups such as -chloroethyl and 2-bromoethyl.
Examples of the alkoxy group include an alkoxy group in which the alkyl moiety is the above-described alkyl group or the like. As the aralkyl group, for example, in addition to benzyl, phenylethyl, naphthylmethyl, these phenyl, naphthyl moieties include a fluorine atom, a chlorine atom, a bromine atom,
Examples include those substituted with the above-mentioned alkyl groups and the above-mentioned alkoxy groups. Examples of the aralkyloxy group include an aralkyloxy group in which the aralkyl aralkyl moiety is the aralkyl group as described above.

As the aryl group, for example, in addition to phenyl and naphthyl, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group as described above, an alkoxy group as described above, an aralkyl group as described above, etc. Phenyl and naphthyl and the like. Further, as a naphthyl group which may have a substituent together with a benzene ring while R ⁶ and R ⁷ are bonded, in addition to naphthyl, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group as described above, Examples include the above-mentioned alkoxy group and naphthyl substituted with the above-mentioned aralkyl group and the like. Representative examples of bromoaryl triflates (II) include, for example, 1-bromophenyl triflate, 2-bromophenyl triflate, 3-bromophenyl triflate, 2-bromo-6-trifluoromethanesulfonyloxynaphthalene, 1-bromo-2- Trifluoromethanesulfonyloxynaphthalene and the like.

Examples of the alkynyl Grignard reagent include, for example, R ⁸ -C≡C-Mg-X (III) wherein R ⁸ is an alkyl group, an aryl group or a substituted silyl group, and X is a chlorine atom. Or a bromine atom.).

The alkyl group in the Grignard reagent represented by the formula (III) includes, for example, methyl, ethyl, n-propyl, I-propyl, n-butyl, I-propyl, sec-butyl, t-butyl, Chain alkyl groups such as pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, palmityl and stearyl, cyclic alkyl groups such as cyclopentyl and cyclohexyl, trifluoromethyl, 2-chloroethyl and 2-bromoethyl; And a halogenated alkyl group.

As the aryl group, for example, in addition to phenyl and naphthyl, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group as described above, an alkoxy group as described above, an aralkyl group as described above, etc. Phenyl and naphthyl and the like. Examples of the substituted silyl group include trimethylsilyl, triethylsilyl, triisopropylsilyl, triphenylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl and the like. Representative examples of the Grignard reagent include, for example, phenylethynylmagnesium bromide, heptynylmagnesium bromide, t-butylethynylmagnesium bromide, triethylsilylethynylmagnesium bromide, triphenylsilylethynylmagnesium bromide and the like.

In reacting a bromoaryl triflate with a Grignard reagent, the palladium-based catalyst is usually used in an amount of 0.1 to 20 with respect to the bromoaryl triflate.
Mol%, preferably 0.5 to 10 mol%, and the Grignard reagent is usually used at 1 to 5 mol times, preferably 1 to 3 mol times. In this reaction, ethers such as diethyl ether, aromatics such as benzene and toluene are usually used, and the reaction is carried out in a mixture of triflates, a palladium-based catalyst and a solvent at -40 to 100 ° C., preferably −40 ° C. 20-80
It is usually carried out by adding a mixture of a Grignard reagent and a solvent at 0 ° C.

In the present invention, by performing the reaction in the coexistence of inorganic salts, the reaction can proceed efficiently and the yield of the desired product can be improved. In this case, the inorganic salts are preferably added in advance together with the palladium catalyst or the like. Examples of such inorganic salts include lithium bromide, lithium iodide, magnesium bromide, magnesium iodide, potassium bromide, potassium iodide, cesium fluoride, cesium chloride, cesium bromide, cesium iodide, magnesium chloride, and odor. Examples thereof include alkali metal halides such as magnesium iodide, magnesium iodide, calcium bromide, and calcium iodide, and alkaline earth metal halides. When using an inorganic salt, it is usually 0.1 to 10 equivalents, preferably 1 to 10 equivalents to the bromoaryl triflates.
~ 3 equivalent times.

The resulting alkynyl-substituted aryl bromides are acidified by adding, for example, an aqueous solution of a mineral acid such as dilute hydrochloric acid to the reaction mass, and then extracted with an organic solvent if necessary.
After washing and drying, the solvent can be removed from the reaction mass by distilling off the solvent. The obtained alkynyl-substituted aryl bromides can be further purified by applying means such as distillation, recrystallization, and various kinds of chromatography, if necessary.

[0020]

As described above, the alkynyl-substituted aryl bromides, which are the object of the present invention, can be obtained. According to the present invention, a palladium-based catalyst having a specific ligand called an aminoalkylphosphine-based ligand is used. By doing
The desired alkynyl-substituted aryl bromides can be produced selectively and in high yield from Grignard reagents and bromoaryl triflates.

[0021]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

Reference Example 1 (Preparation Example of Catalyst) Under a nitrogen atmosphere, 5.64 mmol (1 g) of palladium chloride was added with 5 ml of acetonitrile, stirred at room temperature for 14 hours, and 2 ml of the solvent was distilled off and filtered. By drying the obtained solid,
1.39 g of palladium chloride bisacetonitrile complex was obtained (95% yield). Under a nitrogen atmosphere, the resulting complex 0.385 mmol
(100 mmg) was suspended in 3 ml of benzene, and alaphos 0.4 mmol (1
By adding 5 ml of a benzene solution of PdCl ₂ (al
aphos) 157 mg were obtained. Yield 91%.

Example 1 Lithium bromide 1 dried in 4 ml of ether under a nitrogen atmosphere
mmol (86 mg), PdCl ₂ (alaphos) 0.05 mmol (22.4 mg), 4-
1 mmol (305 mg) of bromophenyl triflate was added and suspended. Then, 2 ml of phenylethynylmagnesium bromide (ether: toluene = 1: 1 mixed solvent, 1M, 2 ml) was added to this suspension under ice-cooling and stirring, and the temperature was raised to 30 ° C., followed by stirring at the same temperature for 3 hours. . Analysis of a small amount of the sample by gas chromatography revealed that bromophenyl triflate had completely disappeared. After decomposing excess Grignard reagent with 1N hydrochloric acid, ether extraction, washing the organic layer with saturated saline, drying over anhydrous sodium sulfate, distilling off the solvent, and treating the obtained crude product by silica gel chromatography. As a result, 247 mg of 4-phenylethynylbromobenzene was obtained. 96% yield. 4-trifluoromethanesulfonyloxy (phenylethynyl) benzene is
It was below the detection limit.

Comparative Example 1 In a nitrogen atmosphere, PdCl ₂ (PPh ₃ ) ₂ 0.10 mmol (60.
4 mg), 1 mmol of 4-bromophenyltriflate (305 mg),
0.10 mmol (19 mg) of copper iodide and 1 ml of triethylamine were added and suspended. Then, 2 mmol (204 mg) of phenylacetylene was added to the suspension. After raising the temperature to 40 ° C,
Stirred for 24 hours. Then, ether extraction, the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off.
By treating the obtained crude product with silica gel chromatography, 4-phenylethynylbromobenzene
26 mg (8% yield) and 187 mg (73% yield) of 4-trifluoromethanesulfonyloxy (phenylethynyl) benzene were obtained.

Comparative Example 2 In Example 1, PdCl ₂ (alaphos) was replaced with PdCl _2
The procedure was performed in the same manner as in Example 1 except that 0.10 mmol (60.4 mg) of ₂ (PPh ₃ ) ₂ was used and the reaction temperature was stirred at 40 ° C. for 24 hours. 4-phenylethynyl bromobenzene 20mg (6% yield), 4-trifluoromethanesulfonyloxy (phenylethynyl)
54 mg of benzene (21% yield) were obtained.

Comparative Example 3 In Example 1, PdCl ₂ (alaphos) was replaced with PdCl _2
The procedure was performed in the same manner as in Example 1 except that 0.10 mmol (58.9 mg) of ₂ (dppp) was used and the reaction temperature was stirred at 40 ° C. for 24 hours. The reaction did not proceed, and the raw material 4-bromophenyl triflate was recovered. 96% recovery rate

Comparative Example 4 In Example 1, PdCl ₂ (alaphos) was replaced with PdCl _{2
Using 2} (meo-mop) ₂ 0.10 mmol (111.4 mg), the reaction temperature was 40 ° C,
Stirred for 24 hours. The reaction did not proceed, and the raw material 4-bromophenyl triflate was recovered. Meo-mop means 2- (diphenylphosphino) -2′-methoxy-1,1′-binaphthyl.

Example 2 The procedure of Example 1 was repeated, except that triethylsilylethynylmagnesium bromide was used instead of phenylethynylmagnesium bromide, to obtain 4-triethylsilylethynylbromobenzene. The results are shown in Table 1. 4-trifluoromethanesulfonyloxy (triethylsilylethynyl) benzene was below the detection limit.

Example 3 The procedure of Example 1 was repeated, except that heptynylmagnesium bromide was used instead of phenylethynylmagnesium bromide, to give 4-heptynylbromobenzene. The results are shown in Table 1. 4-trifluoromethanesulfonyloxy (heptynyl) benzene was below the detection limit.

Example 4 The procedure of Example 1 was repeated, except that tert-butylethynylmagnesium bromide was used instead of phenylethynylmagnesium bromide, to obtain 4-t-butylethynylbromobenzene. The results are shown in Table 1. Four-
Trifluoromethanesulfonyloxy (t-butylethynyl) benzene was below the detection limit.

Example 5 The procedure of Example 1 was repeated, except that 2-bromophenyl triflate was used instead of 4-bromophenyl triflate, to give 2-phenylethynyl bromobenzene. The results are shown in Table 2. 2-trifluoromethanesulfonyloxy (phenylethynyl) benzene is
It was below the detection limit.

Example 6 The procedure of Example 1 was repeated except that 2-bromophenyltriflate was used instead of 4-bromophenyltriflate and triethylsilylethynylmagnesium bromide was used instead of phenylethynylmagnesium bromide. 2-Triethylsilylethynyl bromobenzene was obtained. The results are shown in Table 1. 2-trifluoromethanesulfonyloxy (triethylsilylethynyl) benzene was below the detection limit.

Example 7 The procedure of Example 1 was repeated, except that 3-bromophenyl triflate was used instead of 4-bromophenyl triflate, to give 3-phenylethynylbromobenzene. The results are shown in Table 1. 3-trifluoromethanesulfonyloxy (phenylethynyl) benzene is
It was below the detection limit.

Example 8 The procedure of Example 1 was repeated, except that 3-bromophenyl triflate was used instead of 4-bromophenyl triflate and triethylsilylethynyl magnesium bromide was used instead of phenylethynyl magnesium bromide. 3-Triethylsilylethynyl bromobenzene was obtained. The results are shown in Table 1. 3-trifluoromethanesulfonyloxy (triethylsilylethynyl) benzene was below the detection limit.

Example 9 The procedure of Example 1 was repeated, except that 2-bromo-6-trifluoromethanesulfonyloxynaphthalene was used instead of 4-bromophenyltriflate.
2-Bromo-6-phenylethynylnaphthalene was obtained. The results are shown in Table 1. 2-Phenylethynyl-6-trifluoromethanephonyloxynaphthalene was below the detection limit.

Example 10 Example 1 was repeated except that 2-bromo-6-trifluoromethanesulfonyloxynaphthalene was used in place of 4-bromophenyltriflate and triethylsilylethynylmagnesium bromide was used instead of phenylethynylmagnesium bromide. To obtain 2-bromo-6-triethylsilylethynylnaphthalene. The results are shown in Table 1. 2-Triethylsilylethynyl-6-trifluoromethanesulfonyloxynaphthalene was below the detection limit.

Example 11 The procedure of Example 1 was repeated, except that 1-bromo-2-trifluoromethanesulfonyloxynaphthalene was used instead of 4-bromophenyltriflate.
Bromo-2-phenylethynylnaphthalene was obtained. The results are shown in Table 1. 2-trifluoromethanesulfonyloxy (phenylethynyl) naphthalene was below the detection limit.

Example 12 The procedure of Example 1 was repeated, except that 1-bromo-2-trifluoromethanesulfonyloxynaphthalene was used instead of 4-bromophenyltriflate and triethylsilylethynylmagnesium bromide was used instead of phenylethynylmagnesium bromide. The procedure was performed in the same manner as in Example 1 to obtain 1-bromo-2-triethylsilylethynylnaphthalene.
The results are shown in Table 1. 2-trifluoromethanesulfonyloxy (triethylsilylethynyl) naphthalene was below the detection limit.

[0039]

Table 1 Reaction time Reaction temperature Yield Example 2 1h 20 ° C 99% Example 3 12 30 92 Example 4 20 30 90 Example 5 4 20 92 Example 6 4 30 91 Example 7 1 20 99 Example 8 1 20 93 Example 9 12 20 95 Example 10 4 20 92 Example 11 4 40 94 Example 12 6 40 90

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI // C07B 61/00 300 C07B 61/00 300

Claims (6)

[Claims] (1) a compound represented by the formula (I): R ² R ³ N-CH (R ⁴ ) CH ₂ -P (R ¹ ) ₂ (I) wherein R ¹ is a phenyl group which may have a substituent;
R ² and R ³ each independently represent a lower alkyl group. R
⁴ represents a lower alkyl group, a cycloalkyl group, an aralkyl group or a phenyl group which may have a substituent. )
A method for producing alkynyl-substituted aryl bromides, which comprises reacting a bromoaryl triflate with an alkynyl Grignard reagent in the presence of a palladium-based catalyst having an aminoalkylphosphine-based ligand represented by the formula: 2. A bromoaryl triflate of the formula (II) (In the formula, TfO represents a trifluoromethanesulfonyloxy group, R ⁵ represents a hydrogen atom, a fluorine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyl group. R ⁶ and R ⁷ each independently represent a hydrogen atom , Fluorine atom,
It represents an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyl group, or represents a naphthyl group which may have a substituent together with R ⁶ and R ⁷ together with a benzene ring. The method according to claim 1, wherein the compound is represented by the formula: 3. An alkynyl Grignard reagent of the formula (II)
I) R ⁸ —C ＲC—Mg—X (III) (wherein R ⁸ represents an alkyl group, an aryl group or a substituted silyl group, and X represents a chlorine atom or a bromine atom). The method according to claim 1, wherein: 4. The method according to claim 1, wherein the reaction is carried out in the presence of an inorganic salt. 5. The method according to claim 4, wherein the inorganic salt is at least one selected from an alkali metal halide and an alkaline earth halide. 6. The method according to claim 4, wherein the amount of the inorganic salt used is 0.1 to 10 equivalents relative to the bromoaryl triflate.