JPS60197650A - Preparation of aryl-substituted malonitrile - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for druts, etc. in high yield industrially advantageously in an extreme degree, by reacting an aryl halide with a malonitrile compound by the use of a specific catalyst in the presence of both a basic condensation agent and a solvent. CONSTITUTION:An aryl halide shown by the formula I (Ar is aryl or arylene; X is halogen; Y is -O-, -S-, etc.; m is 1 or 2; n is 0, or 1) is reacted with an malonitrile compound shown by the formula II (R<1> is H, alkyl, etc.) by the use of a divalent or zero valent palladium compound shown by the formula III [L is ligand shown by the formula IV (Z is P, etc.; R<2>, R<3>, and R<4> are alkyl, etc; R<2>, R<3>, and R<4> may be linked to R<2>, R<3>, and R<4> of another molecule to form at least one alkylene ether and to constitute L2); X* is halogen, etc.] in the presence of a basic condensation agent and a solvent such as THF, etc., to give the desired compound shown by the formula V or formula VI.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing aryl-substituted malonitriles.

It has been well known that alkylmalonitrile can be easily synthesized by reacting an alkyl halide with malonitrile in the presence of a basic condensing agent and a solvent. However, if an aryl halide is used instead of an alkyl halide.

Aryl halide and malonitrile could not be reacted at all.

As a result of various studies, the present inventors have succeeded in obtaining aryl-substituted malonitrile in high yield by reacting even aryl halide with malonitrile by using a specific catalyst.

That is, in the present invention, in the presence of a catalyst, a basic condensing agent, and a solvent.

General formula % Formula % (In the formula, Ar is an aryl group or an arylene group, X is a halogen atom, Y is 10-, -S'- or an alkylene group, 2m is an integer of 1 or 2, and n is 0 or When reacting a malonitrile compound represented by the general formula % (in which R represents a hydrogen atom, an alkyl group, or an aryl group) with an aryl halide represented by the formula % (in which R represents a hydrogen atom, an alkyl group, or an aryl group), a catalyst is The general formula % formula % () represents an elementary atom or an antimony atom, and R2, R3 or R4 are an alkyl group, an alkenyl group, an aralkyl group, an aryl group,
Indicates a group independently selected from a cycloalkyl group, an alkoxy group, or an aryloxy group.

12. R2, R3 or R4 is another molecule. R3 or R4
may be combined with each other to form at least one alkylene group or alkylene ether group to constitute R2)
In the ligand represented by

The reaction is carried out using a divalent or zero-valent palladium compound represented by the group -0OCR (where R represents a lower alkyl group) -0 or the group CH3C=CHCOCH3, respectively. This is a method for producing an aryl-substituted malonitrile represented by the general formula % (in which Ar, R, Y, , m and n have the same meanings as above).

The catalyst used in the method of the present invention has the above formula L2Pd
(II) A palladium compound represented by X: or R4Pd(0). Pd (■) is divalent palladium.

Pd(0) represents zero-valent palladium. L is one z (phosphorus atom, arsenic atom, or antimony atom) in one molecule
A ligand having two Zs in one molecule can also be expressed as R2.

Furthermore, if even a small amount of L2P d (II)X 2 is formed in the reaction system, R2 and Pd (1)
also has the same meaning as R2Pd (II)X2.

In the palladium compound represented by the general formula LzPd(II)
(CH2=CHCH2)3P.

(C3H7)3P, (C4He)aP・(C5H11
)3Pl (06H13)3P.

(C7HI5)3 PI (C8HI7)3Pl (C
aH2])aP・(CeHs)3P.

(CHaCeH4)aP, (CzC6H4)3P,
(CH30C6H4)3P.

(C6H5CH2)3P, (C4H9)2(C6H5)
P, (C4H9XC6H5)2P.

(CH30C6j(48c6Hs)kP, (C5Hs
)2PcH2CH2P(Caf(s)2゜P(C6H5
)21 (CH30)3P, (C2H50)3P, (C
3H70) 3P.

(C4H90)3Pl (C5H110)3P, (C5
H110) 3P.

(C6) (5CH20)3P, (C6f(50)3Pl
(C)13c6)I40)3P.

(C4CaH40)aP, (CH30C6H40)3P
l(CH30XC6H5)2P.

(C4H90)2(C6H5)PI (CH3C6H4
0XC6H5)2P.

Phosphorus compounds such as (C4H90XC6H50)2P
(CH3)aAs.

(C2H5)3 As , (CH2= CHCH2)
3 As , (C3H7) 3 As .

(04H9)3AS, (C6I(13)3AS, (C8
H1? )3AS.

(C6H5CH2)3AS, (C6H6)3ASl (
CH3C6H4)3AS.

(CH30C6H4)3AS, (CtC6H4)3AS
.

Arsenic compounds such as (C6H5)2ASCH2CH2AS(C6H5)2.

(CH3)3Sb, (CzHs)asb, (CH2=C
HCH2)3Sb.

(C3f(7)3Sb, (C4)IQ)3Sb, (Ca
Hla)asb, (CeHs)3sb.

(CzC6H4)3Sb, (CH3C6H4)3Sb,
('CH30C6H4)3Sb.

Examples include antimony compounds such as (C6H5)2SbCH2CH2Sb(C6H5)2.

Also, X* means chlorine atom, bromine atom, iodine atom, group -00CCH3, group -00CC2H5, group -00CC3
Examples include H7, group -0-0OCC4H9, group CH3C=CHCOCH3, and the like.

Examples of the aryl halide to be reacted with the malonitrile compound in the method of the present invention include compounds represented by 2.

In the above formula, X is a chlorine atom, a bromine atom, or an iodine atom, and R is a hydrogen atom, a halogen atom, or an alkyl group.

are independently selected from substituents such as aryl groups, alkoxy groups, nitrile groups, acetyl groups, etc., R is a hydrogen atom or a lower alkyl group, and 1m is an integer of 1 to 2.

P represents an integer of 1 to 5, and 9 represents an integer of 1 to 4.

Here, X is most preferably an iodine atom. In the aryl halide, when R has a halogen substituent, the reactivity toward malonitrile compounds increases in the order of iodine>>bromine>chlorine.

In the method of the present invention, the malonitrile compound to be reacted with the ester halide is, for example, 2.

Malonitrile, methylmalonnitrile, ethylmalonnitrile, flobylmalonnitrile, butylmalonnitrile, amylmalonnitrile, octylmalonnitrile, phenylmalonnitrile.

Examples include dorylmaronnitrile, and maronnitrile is the most commonly used.

The process of the invention is carried out in a conventional manner.

That is, a basic condensing agent and a solvent were placed in a reaction vessel in a nitrogen stream, and a malonium compound dissolved in the solvent was gradually added to react.After that, an aryl halide and a palladium compound catalyst were added, and the reaction was allowed to continue for a certain period of time. After doing 1
Take out the reaction product.

The product is separated and purified by recrystallization method and chromatographic separation method.

This is done using a method such as sublimation.

Moreover, a ligand compound and Pd(n)X'' can be separately introduced as a catalyst; in this case, the ligand compound.

It is desirable to add the basic condensing agent, the malonitrile compound, the aryl...ride, and pct(n)x* in this order.

Examples of basic condensing agents include alkali metals such as sodium and potassium, and sodium methoxy.

Sodium ethoxy, sodium impropoxy.

Examples include alkali metal alcoholades such as [-butoxypotassium and [-amyloxysodium], alkali amides such as potassium amide, lithium amide, and sodium amide, sodium hydride, and triphenylmethyl sodium.

Examples of the reaction solvent include 1, for example, tetrahydrofuran.

Examples include ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, diethyl ether, dibutyl ether, dioxane, hexamethylphosphortriamide, dimethylformamide, and mixed solvents of these with hydrocarbons.

The reaction temperature is 20 to 150°C, preferably 50 to 80°C, and the reaction time varies depending on the temperature, but for example, 70°C.
It takes more than 3 hours. During the reaction, it is desirable to carry out the reaction under an inert gas atmosphere.

In the method of the present invention, the amount of palladium compound catalyst added is 1/2 for both raw materials of aryl halide and malonitrile compound.
The amount is 1/10 to 1/10,000 mol, preferably 1/100 to 11,500 mol.

According to the method of the present invention, aryl halide and maronni)
Reacting the IJ compound using a very small amount of catalyst,
This method is industrially extremely advantageous since it is possible to obtain aryl-substituted malonitrile in high yield.

The aryl-substituted malonitrile thus obtained is:

For example, pharmaceuticals, agricultural chemicals, veterinary drugs, and various physiologically active substances.

It is used as an intermediate for dye bifunctional polymers, liquid crystals, organic conductive materials (electronics-related materials such as electrolytic capacitors, storage batteries, Yayo batteries, and organic semiconductors).

Next, the present invention will be explained with reference to Examples.

Example 1 (Method A) Into a Mitsuro flask equipped with a reflux condenser, a stirrer, 1 dropping funnel, and a thermometer, 530 ml of sodium hydride was added in a nitrogen stream.
(22 m mot) and 40 m of tetrahydrofuran, and add 740 m of malonitrile (11 m mot) to this.
A solution of m04) in tetrahydrofuran (10 td) was gradually added. After hydrogen evolution had subsided, 2.04 t (10 m mot ) of iodobenzene and 100 t (10 m mot ) of dichlorobis(triphenylphosphine)haladium catalyst were added.
(0.14 m mot) was added, and the mixture was reacted for 5 hours under refluxing tetrahydrofuran while stirring. After cooling to room temperature, the reaction mixture was treated with dilute hydrochloric acid and extracted with ether. After concentrating the ether solution, the product was separated by silica gel column chromatography. Hexane-methylene chloride (1:
1) Elute during mixed welding.

Phenylmarononi with a melting point of 68-69℃) IJ Ruwo 1
．． I got 212. The yield was 85%.

Example 2 (Method B) Triphenylphosphine 105 trQ (0.4 m mat ), sodium hydride 530 W (22 mmol), and tetrahydrofuran y 40 fnt were placed in the same reaction vessel as in Example 1, and malonitrile was added thereto. A solution of 740 mg (11 m mot) in tetrahydrofuran (10 mg) was added slowly.

After hydrogen generation subsides, iodobenzene 2.04f
(10mmOA) and palladium diacetate 45~(
0.2 m mot) was added thereto, and the mixture was reacted for 5 hours under refluxing tetrahydrofuran while stirring. Thereafter, the same operations as in Example 1 were performed to obtain nophenylmalonitrile with a melting point of 68 to 69° C. (1.17 f C yield: 83%).

Examples 3 to 18 - + in Example 1 (Method A) or Example 2 (Method B)
aJv # /7-I Qμ h If τeko ΔW
a 1” dantTz 4&yama m 4 1yu 81 dou 1-
L 1. S.J.

Using the same raw materials, basic condensing agent and solvent as in Example 1 or Example 2, the reaction and operation were carried out in the same manner to obtain 2 reaction product (phenylmalone nitrile).

The results are shown in Table 1.

Table 1 (f) The symbols in Table 1 represent the following.

Ph: phenyl group, Bu nibutyl group, Me: methyl group, Oct + octyl group, acac niacetylacetonato group.

Examples 19 to 26 A basic condensing agent and a solvent (
Table 2 below) and Maronitrile 740 W (1
A solution (10 m) of 1 m mot) was slowly added.

Next, iodobenzea 2.04 f (10m mot
) (!: Schiff o.

Bis(triphenylphosphine)palladium or hachitrakis(triphenylphosphine)palladium 0.2 m
mot was added and two reactions were carried out. Thereafter, the same reactions and operations as in Example 1 were carried out, and phenylmalonitrile (
product) was obtained.

The results are shown in Table 2.

Examples 27-37 In a reaction vessel similar to Example 1, 530 ml of sodium hydride was added.
■ (22m mot) and tetrahydrofuran 401 are added, and malonitrile 740■ (11m moz
) tetrahydrofuran solution (10 m/) was gradually added.

(After the generation of elements had subsided, 10 mm 0 t of arycehalide shown in Table 3 below and 0.14 m moz of dichlorobis(triphenylphosphine) palladium catalyst were added and one reaction was carried out. Thereafter, the same procedures as in Example 1 were carried out to obtain an aryl-substituted malon nidriole (product).

Note that reactive halogen atoms (e.g. bromine atoms,
Aryl halide IQ m having two iodine atoms)
When using mot, in the above, 1.44 t (60 m mot) of arsenium hydrogen, =,
The test was carried out using Tolire 2.64 r (40 m mot) and tetrahydrofuran 70 -.

The above results are shown in Table 3.

Claims (1)

[Claims] In the presence of a catalyst, a basic condensing agent and a solvent. General formula Ar-1 or x ÷ y KD-containing x (In the formula, Ar represents an aryl group or an arylene group,
m is an integer of 1 or 2, and n is an integer of 0 or 1, respectively). In reacting the malonitrile compound represented by the formula %(0) as a catalyst, R, R or R is an alkyl group, an alkenyl group, an aralkyl group, an aryl group, a cycloalkyl group, Indicates a group independently selected from an alkoxy group or an aryloxy group. R, R or R is mutually bonded to R, R or R of another molecule,
X* is a halogen atom. Group -00CR5 (where R5 represents a lower alkyl group)
Patent RI R1 (where Ar, R1, Y, m and n has the same meaning as above).