JPS6222977B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing malonic acid diester, and more particularly, the present invention relates to a method for producing malonic acid diester using ketene, carbon monoxide, and nitrite as raw materials. Malonic acid diesters have important uses as raw materials for malonic acid, barbituric acids, and barbitals, as well as synthetic raw materials for pharmaceuticals, agricultural chemicals, and the like. Conventionally, malonic acid diester has been produced by reacting monochloroacetic acid and sodium cyanide in the presence of an alkali hydroxide to obtain sodium cyanoacetate, which is then hydrolyzed and further subjected to an esterification reaction. This method involves a complicated process and produces a large amount of waste liquid containing cyanide ions as a by-product, so it is not necessarily economically advantageous when considering its treatment. Various proposals have also been made regarding methods for producing malonic acid diesters by reacting halogenated acetic esters with carbon monoxide and alcohol. For example, JP-A-50-111015 discloses a method for carrying out this reaction in the presence of a metal carbonyl catalyst and a basic compound, and JP-A-51-146414 describes a method for conducting this reaction in the presence of a cobalt-containing compound catalyst and an alkali metal or alkaline earth metal alcoholate,
Alternatively, a method is carried out in the presence of alkali hydroxide in alcohol, and JP-A-52-100417 discloses
A method is disclosed in which this reaction is carried out in the presence of a basic compound, a rhodium catalyst, and optionally an iodine-containing compound. Furthermore, JP-A-53-7613 discloses a method of reacting methylene dihalide, carbon monoxide, and alcohol under a cobalt carbonyl catalyst.
has been done. However, all of these methods use expensive halogenated acetate as a raw material, require a large amount of alkali to scavenge the halogen produced in the reaction, and are difficult to effectively collect and reuse as a catalyst. It has many industrial disadvantages, such as the use of cobald carbonyl, which is difficult to use, and expensive rhodium and iodine compounds. Furthermore, JP-A-57-35896 discloses a method for producing malonic acid diester by bringing ketene, carbon monoxide, and nitrite into liquid phase contact in an organic solvent in the presence of palladium metal or its salts. Proposals have been made regarding this. This manufacturing method has many industrial advantages compared to the various methods described above. However, since this production method is a heterogeneous reaction that proceeds with the catalyst suspended in a solvent, various reactants are produced, making it difficult to separate and purify the malonic acid diester, the desired product. The catalyst, which exists in a suspended state in the reaction solution, tends to cause abrasion and clogging of the reactor, and the processing operations for recovering and reusing the catalyst become complicated. There is still room for improvement in the above. In view of this situation, the present inventors have developed various catalyst systems for the purpose of developing an industrially advantageous catalyst system in a method for producing malonic acid diester through a liquid phase reaction between ketene, carbon monoxide, and nitrite. I conducted research. As a result, when a platinum group metal complex having a specific composition, a tin halide, and a quaternary ammonium salt are used together as a catalyst, the reaction can be carried out in a homogeneous system, and the above-mentioned Japanese Patent Publication No. 57
- All the problems of the invention disclosed in Publication No. 35896 are improved, and the target product can be produced with a yield and selectivity superior to any of the above-mentioned prior art. This discovery led to the completion of the present invention. That is, the present invention provides ketene, carbon monoxide, and nitrite esters with the general formula: L ₂ MX ₂ (wherein L represents a ligand of an organic phosphorus compound, M represents a platinum group metal, and X represents An industrially excellent production method for malonic acid diester, which comprises carrying out a liquid phase reaction in an organic solvent in the coexistence of a platinum group metal complex having a halogen atom (representing a halogen atom), a tin halide, and a quaternary ammonium salt. It provides: Next, the present invention will be explained in detail. The method for producing malonic acid diester of the present invention is based on the reaction formula
(A)： CH ₂ CO＋CO＋2RONO→CH ₂ (COOR) ₂ ＋2NO
......(A) (wherein R represents an alkyl group or a cycloalkyl group), malonic acid diester is produced by reacting ketene, carbon monoxide and nitrite in a liquid phase. be. Nitrite esters that can be used are esters of nitrous acid and saturated monohydric aliphatic alcohols or alicyclic alcohols having 1 to 8 carbon atoms, and alcohol components include, for example, methanol and ethanol. , n-(and iso-)propanol, n-(and iso-, sec-, tert-)butanol, n-(and iso-)amyl alcohol, hexanol, aliphatic alcohols such as octanol, and cyclohexanol, methyl Examples include alicyclic alcohols such as cyclohexanol, and these alcohols may contain substituents such as alkoxy groups that do not inhibit the reaction. The nitrite ester used in this reaction does not necessarily have to be in the form of a nitrite ester, and a raw material that forms a nitrite ester within the reaction system may be used. That is, instead of nitrite, alcohol and nitrogen monoxide, nitrogen dioxide, dinitrogen trioxide,
It is also useful to use a nitrogen oxide selected from dinitrogen tetroxide or a hydrate thereof, by introducing a molecular oxygen-containing gas as necessary. Note that nitric acid, nitrous acid, and the like are effective as hydrates of nitrogen oxides. In these cases, the alcohol used is selected from the alcohol components that are constituents of the nitrite ester. The catalyst in the present invention is a three-component system of a platinum group metal complex, a tin halide, and a quaternary ammonium salt. First, a platinum group metal complex is represented by the general formula (): L ₂ MX ₂ (). In the general formula (), L represents a ligand of an organophosphorus compound, and examples of compounds that can be such a ligand include trialkylphosphine, triallylphosphine, trialkyl〓〓〓〓〓
Examples include phosphite and triallylphosphite. Examples of trialkylphosphines include those in which the alkyl group has 1 to 8 carbon atoms, such as trimethylphosphine, triethylphosphine, tri-n-(or iso)propylphosphine, tri-n-(or iso, tert-)butyl Examples include phosphine. Examples of triallylphosphine include triphenylphosphine in which the allyl group has 6 to 12 carbon atoms;
Alternatively, tri-substituted phenylphosphine (substituents include, for example, an alkyl group, an alkoxy group, and a halogen atom). Examples of the trialkyl phosphite include those in which the alkyl group has 1 to 8 carbon atoms, such as trimethyl phosphite, triethyl phosphite, tri-n-(or iso)propyl phosphite, and tri-n-
(or iso, tert-)butyl phosphite and the like. Examples of triallylphosphite include triphenylphosphite in which the allyl group has 6 to 12 carbon atoms, or tri-substituted phenylphosphite (substituents include, for example, an alkyl group, an alkoxy group, and a halogen atom). ) can be mentioned. In the general formula (), M represents a platinum group metal such as platinum or palladium, and X represents chlorine, bromine,
Represents a halogen atom such as iodine. The platinum group metal complex catalyst of the general formula () can be prepared, for example, according to the following reaction formula (B). MX ₂ +2L→L ₂ MX ₂ (B) In reaction formula (B), M, X and L have the same meanings as above. To give a specific example, by reacting palladium bromide [PdBr ₂ ] with triphenylphosphine [(C ₆ H ₅ ) ₃ P], bistriphenylphosphine dibromopalladium [[(C ₆ H ₅ ) ₃ P〕 ₂ PdBr ₂ 〕 can be obtained. Note that the reaction according to reaction formula (B) proceeds very quickly and forms a complex within an instant, so it is not necessarily necessary to introduce the complex form into the reaction system of the production method of the present invention, and the reaction according to reaction formula (B) By adding separately to the reaction system the amounts of each component based on the stoichiometry shown in
A complex can also be formed within the reaction system and used as a catalyst. The amount of platinum group metal complex catalyst present in the reaction system of the production method of the present invention is preferably in the range of 0.1 to 100 mmol, preferably 1 to 20 mmol, per 1 reaction solvent. Examples of the tin halide used in the present invention include stannous chloride, stannous bromide, stannous fluoride, and stannous iodide. By having these tin halides present in the reaction system, the stability of the platinum group metal complex is significantly improved, and there is no occurrence of phenomena such as the catalyst becoming insoluble and precipitating during the reaction. The yield and selectivity of malonic acid diester are significantly improved. The amount used is usually 0.5 to 10 mol, preferably 1 to 5 mol, per 1 mol of the platinum group metal complex. Furthermore, the quaternary ammonium salt used in the present invention has the general formula (): (R) ₄ NY can be expressed as (). In the general formula (),
R can be a lower alkyl group such as methyl, ethyl, n(or iso)-propyl, n(or iso)-butyl, n(or iso)-pentyl, etc., a phenyl group, a tolyl group or a benzyl group. Further, Y represents a halogen atom such as chlorine, bromine, or ioic acid. The presence of these quaternary ammonium salts in the reaction system significantly improves the yield and selectivity of malonic acid diester, which is the target product of the reaction. Its usage is usually
The amount is 0.5 to 10 mol, preferably 1 to 5 mol, per mol of platinum group metal complex. In addition, these tin halides or quaternary ammonium salts, like the platinum group metal complex (L ₂ MX ₂ ) or its constituent components (MX ₂ , L), may be used in combination with the raw material nitrite ester or organic solvent in some cases. It is also possible to dissolve it in water and replenish it sequentially during the reaction. The manufacturing method of the present invention is based on a liquid-phase homogeneous reaction as described above. Therefore, each raw material and each catalyst of the present invention must be present in a state dissolved in an organic solvent in the reaction system. That is, the organic solvent used in the present invention includes each raw material in the present invention and
and organic solvents that can dissolve each catalyst. Examples of such organic solvents include, for example, N-methylpyrrolidone; dimethylaniline; halogenated aliphatic hydrocarbons such as chloroform, trichloroethane, tetrachloroethane; toluene, xylene, decalin, tetralin, chlorobenzene, dichloromethane; Examples include aromatic hydrocarbons such as benzene and halogenated aromatic hydrocarbons; esters such as oxalate ester, acetate ester, and carbonate ester; ethers such as dioxane and diethylene glycol dimethyl ether; It is also possible to use solvents in combination. In carrying out the present invention, a platinum group metal complex, a tin halide, a quaternary ammonium salt, and a nitrite ester are usually added to a reaction solution in which ketene and monomer are dissolved in an organic solvent. This is done by supplying carbon oxide. The feed rate of ketene to the reaction solution is 1 to 200ml/
It is desirable that the amount of nitrite be within the range of (reaction solution).minutes, and it is desirable that the nitrite ester is supplied to the reaction solution in an amount of at least twice the molar amount of ketene. The reaction is preferably carried out at a temperature of room temperature to 200°C and a partial pressure of carbon monoxide of 0.5 atm or more. The malonic acid diester, which is the target product of the present invention, can be isolated and obtained from the reaction system by, for example, appropriately employing operations such as distillation, filtration, and separation. Next, examples of the present invention will be shown. Note that the yield of the product in each example is based on ketene. Example 1 In a 300 ml four-necked flask, 0.791 g (1 mmol) of bistriphenylphosphine dibromopalladium, 0.380 g (2 mmol) of stannous chloride, 0.555 g (2 mmol) of tetra-n-butylammonium chloride and 85 ml (569.6 mmol) of n-amyl nitrate was charged together with 200 ml of monochlorobenzene. The reaction mixture was heated and held at 90 °C with stirring, and nitrogen gas containing 24.0% ketene by volume was added.
The reaction was carried out for 3 hours while blowing carbon monoxide into the reaction solution at a rate of 131.6 ml/min and 300 ml/min. After cooling the reaction solution to room temperature, the solvent was distilled off, and the reaction product contained in the residue was collected at 200°C using gas chromatography (Apiezon Grease 3m column).
Quantitative analysis was performed at a temperature of The results are shown in Table 1. Example 2 Instead of tetra-n-butylammonium chloride,
An experiment was conducted in the same manner as in Example 1, except that 0.331 g (2 mmol) of tetraethylammonium chloride was used. The results are shown in Table 1. Examples 3 and 4 Bistriphenylphosphine dibromopalladium was replaced by 0.702 g (1 mmol) of bistriphenylphosphine dichloropalladium in Example 3 and 0.671 g (1 mmol) of bistriphenylphosphine dibromopalladium in Example 4. An experiment was conducted in the same manner as in Example 1, except that 1 mmol) was used in each case. The results are shown in Table 1.

[Table] 〓〓〓〓〓

[Table] Example 5 Bistriphenylphosphine Instead of dibromopalladium, 0.266 g (1 mmol) of palladium bromide and 0.525 g (2 mmol) of triphenylphosphine were used.
The experiment was conducted in the same manner as in Example 1, except that 1 mmol) was used. The results were as follows. Amount of di-n-amyl malonate produced: 175.7 mmol (yield: 69.2%) Amount of by-product n-amyl acetate: 44.6 mmol (yield:
17.6%) Example 6 The experiment was carried out in the same manner as in Example 1, except that the amount of n-amyl nitrite charged was changed to 50 ml (341.5 mmol) and the ketene content in the nitrogen gas was changed to 12.8% by volume. I went to The results were as follows. Amount of di-n-amyl malonate produced: 105.9 mmol (yield: 78.3%) Amount of by-product n-amyl acetate: 12.1 mmol (yield:
9.0%) Comparative Example 1 An experiment was conducted in the same manner as in Example 6, except that tetra-n-butylammonium chloride was not used. The results were as follows. Amount of di-n-amyl malonate produced: 83.7 mmol (yield: 61.9%) Amount of by-product n-amyl acetate: 12.8 mmol (yield:
20.7%) Example 7 Instead of n-amyl nitrite, 45 ml of ethyl nitrite
The experiment was conducted in the same manner as in Example 1, except that (570.0 mmol) was used. The results were as follows. Amount of diethyl malonate produced: 203.5 mmol (yield: 80.1%) Amount of ethyl acetate by-product: 24.1 mmol (yield: 9.5
%) Example 8 In a 300 ml four-necked flask, 0.396 g (0.5 mmol) of bistriphenylphosphine dibromopalladium, 0.190 g (1 mmol) of stannous chloride, and 0.278 g (1 mmol) of tetra-n-butylammonium chloride. and 25 ml (171.0 mmol) of n-amyl nitrite were charged together with 200 ml of monochlorobenzene. The reaction mixture was heated and held at 90 °C with stirring, and nitrogen gas containing 24.2% ketene by volume was added.
The reaction was carried out for 3 hours while blowing carbon monoxide into the reaction solution at a rate of 132.0 ml/min and 300 ml/min. In addition, after starting the reaction, triphenylphosphine
0.066 g (0.25 mmol) of n-amyl nitrite 50
ml (342.0 mmol) was added to the reaction system over a period of 2.5 hours. As a result, the reaction progressed steadily, and no catalyst deactivation phenomenon was observed during the reaction. The amount of the product was as follows. Amount of di-n-amyl malonate produced: 165.6 mmol (yield: 64.5%) Amount of by-product n-amyl acetate: 32.9 mmol (yield:
12.8%) Example 9 In a 300 ml four-necked flask, 0.198 g (0.25 mmol) of bistriphenylphosphine dibromopalladium, 0.095 g (0.5 mmol) of stannous chloride,
Tetra n-butylammonium chloride 0.139g (0.5
〓〓〓〓〓
mmol) and n-amyl nitrite 60 ml (406.6
mmol) was added together with 200 ml of monochlorobenzene. Heat the reaction mixture to 90°C with stirring;
The reaction was carried out for 5 hours while blowing nitrogen gas containing 9.4% by volume of ketene into the reaction solution at a rate of 110.4 ml/min and carbon monoxide at a rate of 300 ml/min. After starting the reaction, triphenylphosphine
0.066 g (0.25 mmol) and stannous chloride
10 ml of a solution of 0.048 g (0.25 mmol) dissolved in N-methylpyrrolidone was added to the reaction system in 2.5 ml portions every hour. As a result, the reaction progressed steadily, and no catalyst deactivation phenomenon was observed during the reaction. The amount of the product was as follows. Amount of di-n-amyl malonate produced: 116.2 mmol (yield: 83.8%) Amount of by-product n-amyl acetate: 20.5 mmol (yield:
14.7%) Example 10 In a 300 ml four-necked flask, 0.791 g (1 mmol) of bistriphenylphosphine dibromopalladium, 0.558 g (2 mmol) of stannous bromide, and 0.420 g (2 mmol) of tetraethylammonium bromide. and 50 ml (356.0 mmol) of n-amyl nitrite were charged together with 200 ml of monochlorobenzene. The reaction mixture was heated and held at 90 °C with stirring, and nitrogen gas containing 10.0% by volume of ketene was added.
The reaction was carried out for 3 hours while blowing carbon monoxide into the reaction solution at a rate of 116.1 ml/min and 200 ml/min.
The results were as follows. Amount of di-n-amine malonate produced: 63.0 mmol (yield: 49.4%) Amount of n-amyl acetate by-product: 28.3 mmol (yield:
36.5%) Example 11 In a 300 ml four-neck flask, 0.885 g (1 mmol) of bistriphenylphosphine diiodide, 0.285 g (1.5 mmol) of stannous chloride, and 0.416 g (1.5 mmol) of tetra-n-butylammonium chloride were added. 45 ml (327.6 mmol) of n-amyl nitrite were charged together with 200 ml of monochlorobenzene. The reaction mixture was heated and held at 90 °C with stirring, and nitrogen gas containing 13.6% ketene by volume was added.
The reaction was carried out for 3 hours while blowing carbon monoxide into the reaction solution at a rate of 115.8 ml/min and 200 ml/min. The results were as follows. Amount of di-n-amyl malonate produced: 89.8 mmol (yield: 70.8%) Amount of by-product n-amyl acetate: 19.5 mmol (yield:
12.1%) Example 12 In a 300 ml four-necked flask, 0.702 g (1 mmol) of bistriphenylphosphine dichloropalladium, 0.190 g (1 mmol) of stannous chloride, 0.166 g (1 mmol) of tetraethylammonium chloride and 50 ml (350.5 mmol) of n-amyl nitrate was charged together with 200 ml of monochlorobenzene. The reaction mixture was heated and maintained at 100 °C with stirring, and nitrogen gas containing 16.4% by volume of ketene was added.
The reaction was carried out for 3 hours while blowing carbon monoxide into the reaction solution at a rate of 119.6 ml/min and 200 ml/min. The results were as follows. Amount of di-n-amyl malonate produced: 115.3 mmol (yield: 73.2%) Amount of by-product n-amyl acetate: 24.1 mmol (yield:
15.3%) 〓〓〓〓〓

Claims (1)

[Claims] 1 Ketene, carbon monoxide and nitrite ester are represented by the general formula: L ₂ MX ₂ (wherein L represents a ligand of an organic phosphorus compound, M represents a platinum group metal, and X represents a halogen atom.) A method for producing a malonic acid diester, which comprises carrying out a liquid phase reaction in an organic solvent in the coexistence of a platinum group metal complex having a halogenated metal complex, a tin halide, and a quaternary ammonium salt.