JPS61103861A - Preparation of aryl-substituted cyanoacetic acid ester - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a synthetic intermediate of pharmaceuticals, agricultural chemicals, dyes, functional polymers, organic electrically conductive materials, etc., in high yield, by reacting an aryl halide with a cyanoacetic acid ester in the presence of a small amount of a specific catalyst. CONSTITUTION:The objective compound of formula II or III can be prepared by reacting the aryl halide of formula Ar-Xm or formula I (Ar if aryl or arylene; X is halogen; Y is O, S or alkylene; m is 1 or 2; n is 0 or 1) with the cyanic acid ester of formula CNCH2COOR<1> (R<1> is alkyl, aralkyl or aryl) in nitrogen gas stream in the presence of a catalayst and basic condensation agent, in a solvent at 20-140 deg.C. The reaction is carried out in the presence of a catalyst consisting of a bivalent palladium complex of formula QaPd(II)X*b (Q is nitrile, pi-allyl, 1,5-diene, etc.; X*b is halogen; a and b are 1 or 2) and ligand compound of formura IV (Z is P, As, Sb, etc.; R<3>-R<5> are alkyl, alkenyl, aryl, etc.).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for producing aryl-substituted cyanacetic esters.

It has been well known that an alkyl-substituted cyanacetate can be easily synthesized by reacting an alkyl halide with a cyanacetate in the presence of a basic condensing agent and a solvent. However, when aryl halide was used instead of alkyl halide, it was not possible to cause the aryl halide and cyanacetic acid ester to react at all.

As a result of various studies, the present inventors have succeeded in obtaining aryl-substituted cyanacetate in high yield by reacting even aryl halide with cyanacetate 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 represents an aryl group or an arylene group, X represents a halogen atom, and Y represents a 10-, -S-, or alkylene group.
m is an integer of 1 or 2, and n is an integer of O or 1, respectively) to an aryl halide represented by the general formula % (in which R1 represents an alkyl group or an aralkyl group). For the reaction of ethyl, as a catalyst (a) general formula % formula %) [wherein Q is nitrile, innitrile, π-allyl,
1.5-Dienes. 1. Indicates 3-dienes, benzoquinone or olefins, provided that these compounds are Pd (
If) a divalent palladium complex represented by the general formula (wherein z is a phosphorus atom) and , arsenic atom or antimony atom,
R3, 4 or 5 is an alkyl group or an alkenyl group.

Ara/reki/shi group, ary/shi group. Represents a group independently selected from a cycloalkylalkoxy group or an aryloxy group, and R31ft' or R5 is R3 of another molecule.

The reaction is characterized in that the reaction is carried out using a ligand compound represented by R4 or R5 (which may be bonded to R4 or R5 to form at least one alkylene group or alkylene ether group in t).

This is a method for producing an aryl-substituted cyanoacetate ether represented by the general formula (wherein Ar+R"+Y+m and n have the same meanings as above).

In the divalent palladium complex represented by the general formula % (%) used in the method of the present invention, examples of Q include benzonitrile, benzisonitrile, π-allyl, cyclohexadiene, cyclooctanine. norformacien, butadiene.

Tetraphenylcyclogetadiene, penzoquinone tylene, π-cyclopentagenyl fx,
Due to the presence of the Fd(If) compound, these compounds are nidril rd (or) complex and isonitrile pa (
ff) complex, π-allyl pd(U) 8-body. l, 5-
Cyene Pd(b) complex, 1,3-diene Pa([1) complex, benzoquinone Pd([1) complex, olefin Pd(
b) Form a complex.

Examples of X* include chlorine atom, bromine atom, and iodine atom.

In addition, as a ligand compound represented by the general formula % formula % which is added to the above divalent palladium complex, 1, for example (CEi;
)J'.

CC2H3)3P, (CH2=CHCH2)3F
, (C3H7)3F , (C41=[9)3
1'.

(C5H1□)3F , (C6H13)3F , (
C7H1,)3F, (08H17)3F.

(C6H1□)3F, (06H6)3F,
(CH3C6H4)3F, (C4C,1i4)
3P.

(CH3006H4)3P, (C6H5CH2)3
F, (04H9)2(C6H5)P.

(C4H3) (06M5)2P , (OH3QC,H
4)(0,H5)2F.

(C6H5)2PCH2Ca20CH2C, H4F<C
,6H5)2. (OH30) 3F.

(C2H50)3P , (C3H70)3F , (C4
Toki0)3F, (0,J:11□0)3F.

(C8H,0)3P, (CH20 to C6)3F
, (C6H,0)3P.

(C1i3C6H40)3F , (C6C6H40)
3P, (CH30C6H40)3P.

(OH30XC6H3)2P, (04H0O)2(
C6H5)P , (C1i3C6H40) (C,H
5) 2P.

Phosphorus compounds such as (C4H90)(C6鴇0)2P, (
CH3)3As + (C2H6)3As I (CH
2=C)IcH2)3As l (03H7)3As
1(C4H3)3As T (L;, R1ρ3As
l (C8H07)3AS, (06H,
0H2)3As.

(C,H5)3As, (OH3C,H4)3As
, (OH3QC6H,)3As.

(C6C,H4)3Asl (0,H,)2AsCH
Arsenic compounds such as 20H2A5(06H,)2, (C
H3)3Sb, (C,H,)38b, (OH2
=CHCH2)3Sb.

(03H,)3Sb, (04H3)3Sb, (
CsHta)3Sb, (C6H3)38b.

CC106H4)38b, (CH3C6H4)3S
b , (CH3QC吃4)38b r(C6H,)2
Examples include antimony compounds such as SbCH2CM2Sb (0,H,;)2.

Examples of the aryl halide to be reacted with cyanacetate in the method of the present invention include compounds represented by the general formula.

In the above formula, X is a chlorine atom, a bromine atom, or an iodine atom, and R6 is a hydrogen atom, a halogen atom, or a nitrile group.

Acetyl group, 7-lukoxy group, alkyl group, aryl group,
independently selected from substituents such as aralkyl groups and aryloxy groups + R' represents a hydrogen atom or a lower alkyl group
m is an integer from 1 to 2, p is an integer from 1 to 5, and 19 is an integer from 1 to 4.
Indicate each integer.

Here, X is most preferably an iodine atom. Further, when there is a halogen substituent at +R' in the aryl halide, the reactivity toward cyanacetate increases in the order of iodine>>bromine>chlorine.

In the method of the present invention, the cyanacetic acid ester to be reacted with the aryl halide includes, for example, 1.

Methyl cyanogen acetate, ethyl cyanogen acetate, propyl cyanogen acetate, butyl cyanogen acetate, amyl cyanogen acetate, octyl cyanogen acetate, benzyl cyanogen acetate.

Examples include phenyl cyanacetate, and methyl cyanacetate, ethyl cyanacetate, and propyl cyanacetate are most commonly used.

The method of the present invention is generally carried out as follows.

That is, a basic condensing agent and a solvent are placed in a reaction vessel in a nitrogen stream, and cyanacetic acid ester dissolved in the solvent is gradually added to cause a reaction, and then a divalent palladium complex such as an aryl halide and a catalyst of a ligand compound are added. After adding and reacting for a certain period of time.

Take out the diluted product. Separation and purification of the product is performed using a recrystallization method, a chromatographic separation method, a sublimation method, etc.

Examples of basic condensing agents include sodium.

Alkali metals such as potassium, sodium methoxy, di-disodium, sodium isopropoxy, t-
Examples include alkali metal alcoholades such as butoxypotassium and t-amyloxysodium, alkali amides such as potassium amide, lithium amide, and sodium amide, sodium hydride, and triphenylmethyl sodium.

Examples of reaction solvents include tetrahydrofuran, ethylene glycol dimethyl ether/L/I, ethylene glycol dimethyl ether/L/I diethyl ether, diptyl ether, dihysane, Δxamethylene phosphorotriamide, dimethylformamide, and combinations of these and hydrocarbons. Examples include a mixed solvent of .

Reaction temperature is 20-150℃, preferably 50-80℃
The reaction time varies depending on the temperature.

For example, at 70°C for 5 hours or more. During the reaction, it is desirable to carry out the reaction under an inert gaff atmosphere.

In the method of the present invention, a divalent palladium complex and a ligand compound are added as catalysts.

The addition ratio of the divalent palladium complex and the ligand compound is
It may be arbitrary, but preferably 12 (molar ratio), and the amount of both added is 1/10 to 1/10,000 mono', preferably 1/100 to 1 mole of both raw materials of aryl halide and cyanacetic ester. It is ~1/soo mole.

Although the mechanism of action of the catalyst in the present invention is not clear, it is thought that the compound produced by replacing Q in the divalent palladium complex with a ligand compound acts as a catalyst.

According to the method of the present invention, aryl halide and cyanacetate are reacted using a very small amount of catalyst, and aryl-substituted cyanacetate can be obtained in high yield, so it is an extremely advantageous method industrially. .

The thus obtained allinyl-substituted cyanacetic esters can be used, for example, in pharmaceuticals, agricultural chemicals, veterinary drugs, various physiologically active substances, dyes, functional polymers, liquid crystals, organic conductive materials (electrolytic capacitors,
It is used as an intermediate for storage batteries, solar cells, electronics-related materials such as organic semiconductors), etc.
.

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

Example 1 In a three-piece flask equipped with a reflux condenser, a stirrer, an addition funnel, and a thermometer, 2.47 ml of potassium t-butoxide was added in a nitrogen stream. (22 mmol) and ethylene glycol dimethyl ether) V40 ml, and ethylene glycol dimethyl ether II solution (if) r of ethyl cyanacetate lv1.451 (13 mmol)
rLl) was added gradually. Then iodobenzene 2
．． 04? (lQmmol) and Ncrooctadienepalladium dichloride 57cm (0.2mmol) as a catalyst
mol) Tripheni/Lephosphine 105η(04
mmol) was added thereto, and the mixture was reacted at 70° C. for 8 hours while stirring. After distilling off the solvent, distillation is performed to reduce the boiling point to 154
1.459 phenylcyanoethyl acetate was obtained at ~156°C/11 mmHz. The yield was 76.5%.

Examples 2 to 12 Into the same reaction vessel as in Example 1, put the basic condensing agent and solvent shown in Table 1 below, and add 1.45 F (1
3 mmol) solution (10 mL) was gradually added.

Next, iodobenze: / 2.04 S' (lQmmo
1) and the catalyst shown in Table 1 below were added and reacted for 9 times. Thereafter, the same reactions and operations as in Example 1 were carried out, and the boiling point was 15.
Ethyl phenylcyanoacetate (reaction product) having a temperature of 4 to 156°C/llmmHg was obtained.

The results are shown in Table 1.

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

Ph: phenyl group, Et: ethyl group + Bu nibutyl group.

M, e: methyl group, Am nearyl group, CHD
Nidichlorohexadiene, COD Nidichlorooctadiene, NBD: norbornadiene.

Examples 13 to 28 The above Table 2-1 and Table 2 were placed in the same reaction container as in Example 1.
-22 mmol of basic condensing agent and 40 rnl of solvent from Table 2
and add cyanic acid NTE) v 13 m mol
solution (10d) was added gradually. Then aryl halide 10mmo! and cyclooctadieneparasyram cyclolide 57 my (0.2 mmol) totriphenylhonuphine 105 my (0.4 mmol) as a catalyst.
l) was added and reacted. Thereafter, the same reactions and operations as in Example 1 were carried out to obtain aryl-substituted cyanoacetate (reaction product).

Note that reactive halogen atoms (e.g. bromine atoms,
Aryl halide with two iodine atoms) 10 mmo
When using l, in the above basic condensing agent 50mm
ol, cyanacetic acid x Nute/L/40 rr!
mol.

It was carried out using solvent 50-.

The above results are shown in Table 2-1 and Table 2-2.

(Note) The symbols in Tables 2-1 and 2-2 represent the following.

Me: methyl group, Et: ethyl group + 'Pr' isopropyl group + Bu nibbutyl group.

Claims (1)

[Claims] In the presence of a catalyst, a basic condensing agent, and a solvent, there is a general formula Ar-Xm or ▲mathematical formula, chemical formula, table, etc.▼ (where Ar is an aryl group or an arylene group, and atom, Y is -O-, -S- or alkylene group,
m is an integer of 1 or 2, and n is an integer of 0 or 1, respectively) with the general formula CNCH_2COOR^1 (wherein R^1 is an alkyl group, an aralkyl group, or an aryl group). In reacting the cyanacetic acid ester represented by the formula (a) as a catalyst, the general formula Q_aPd(II)X^*_b [wherein Q is nitriles, isonitriles, π-allyl,
Indicates 1,5-dienes, 1,3-dienes, benzoquinone or olefins, provided that these compounds are Pd(
II) A divalent palladium complex represented by (b) General formula ▲ Numerical formula, chemical formula, table etc.▼ (In the formula, Z is a phosphorus atom, arsenic atom or antimony atom,
R^3, R^4 or R^5 represents a group independently selected from an alkyl group, an alkenyl group, an aralkyl group, an aryl group, a cycloalkyl group, an alkoxy group or an aryloxy group, and R^3, R ^4 or R^5 is R^3 of another molecule
, R^4 or R^5, and may form at least one alkylene group or alkylene ether group). Represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, Ar, R^1, Y, m, and n have the same meanings as above) A method for producing an aryl-substituted cyanacetic ester.