JPH05194301A - Optically active 2-chloropropionaldehyde and its production - Google Patents

Abstract

PURPOSE:To provide a new optically active 2-chloropropionaldehyde extremely useful from industrial viewpoint as an intermediate easily convertible to various optically active agricultural chemicals and pharmaceuticals. CONSTITUTION:Optically active 2-chloropropionaldehyde. The compound can be produced from an easily available industrial raw material in one step by a catalytic process by reacting vinyl chloride with carbon monoxide and hydrogen in the presence of (A) a rhodium compound, (B) an optically active phosphorus compound preferably the optically active compound of formula I and formula II (R<1> to R<4> are alkyl, aryl, biaryl, cycloalkyl, alkoxy, aryloxy, cycloalkoxy or OH; R<5> is structure obtained by cross-linking two P atoms with alkyl, aryl, biaryl, cycloalkyl, alkoxy, aryloxy, biaryloxy or cycloalkoxy), (C) a base and preferably (D) water.

Description

Detailed Description of the Invention

[0001]

The present invention relates to a novel substance such as optically active 2-chloropropionaldehyde and vinyl chloride,
The present invention relates to a method for producing optically active 2-chloropropionaldehyde using carbon monoxide and hydrogen as raw materials.

[0002]

2. Description of the Prior Art 2-Chloropropionaldehyde is 2
Although it is a compound having an asymmetric carbon at the position, its existence has not been known because there has been no synthetic example of its optically active substance.

However, racemic 2-chloropropionaldehyde is known and its production method is, for example,
French Patent No. 1397779 and HELVETICA CHIMICA AC
TA), Vol. 48, No. 5, pp. 1151 to 1157 and JP-A-61-226046, a catalytic 2-chloropropionaldehyde starting from vinyl chloride, carbon monoxide and hydrogen. There is a manufacturing method of.

[0004]

2-Chloropropionaldehyde is a compound that can be used as a very useful intermediate for various agricultural chemicals and pharmaceuticals, but all known hitherto are racemates. The existence of the optically active substance was not known.

An object of the present invention is to provide an optically active 2-chloropropionaldehyde which has hitherto been unknown and a method for producing the same.

[0006]

[Means for Solving the Problems] The inventors of the present invention have made diligent efforts to solve these problems and conducted detailed research. As a result, it was found that when vinyl chloride, carbon monoxide and hydrogen are reacted with a rhodium compound and an optically active phosphorus compound as a catalyst and a base as a cocatalyst, an optically active 2-chloropropionaldehyde is obtained. The present invention has been achieved through further detailed research.

That is, the present invention is characterized by reacting vinyl chloride, carbon monoxide and hydrogen in the presence of a novel substance, optically active 2-chloropropionaldehyde, a rhodium compound, an optically active phosphorus compound and a base. It is a method for producing active 2-chloropropionaldehyde.

The term “optically active substance or optically active substance” as used in the present invention means not only an optically pure compound but also one optical isomer is contained in a larger amount than the other optical isomer forming a pair. It is a general term for a mixture of optical isomers, and the optically active 2-chloropropionaldehyde of the present invention includes (R) -2-chloropropionaldehyde, (S) -2-chloropropionaldehyde, or a mixture of both. One of them contains more than the other.

The present invention will be described in detail below.

In the method of the present invention, the presence of the optically active phosphorus compound is essential. Among the optically active phosphorus compounds, the chemical structural formula (1) or the chemical structural formula (2) [Chemical formula 2]

[0011]

[Chemical 2] (In the formula, P is a phosphorus atom, and R ¹ , R ² , R ³ and R
⁴ represents an alkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an aryloxy group, a cycloalkoxy group or a hydroxyl group, respectively, and R ⁵ represents two phosphorus atoms by an alkyl group, an aryl group, a biaryl group, a cycloalkyl group, One or more optically active phosphorus compounds selected from the group consisting of compounds represented by a structure represented by crosslinking with an alkoxy group, an aryloxy group, a biaryloxy group or a cycloalkoxy group are preferably used.

Specific examples of these optically active phosphorus compounds are as follows. That is, as the optically active phosphorus compound represented by the chemical structural formula (1), 1,2-bis (diphenylphosphino) propane, 2,3-bis (diphenylphosphino) butane, 2,4-bis (diphenyl) Phosphino) pentane, 4,5-bis (diphenylphosphinomethyl) -2,2-dimethyl-1,3-dioxolane, 4,5-bis (dibenzophosphorylmethyl) -2,
2-dimethyl-1,3-dioxolane, 1,2-bis (diphenylphosphinomethyl) cyclohexane, 1-
tert-butoxycarbonyl-4-diphenylphosphino-2-diphenylphosphinomethylpyrrolidine, 1
-Tert-butoxycarbonyl-4-dicyclohexylphosphino-2-diphenylphosphinomethylpyrrolidine, 2,2'-bis (diphenylphosphino) -1,
An optically active form of a compound such as 1′-binaphthyl can be mentioned. Further, as the optically active phosphorus compound represented by the chemical structural formula (2), 1,2-bis (diphenylphosphinyl)
Propane, 2,3-bis (diphenylphosphinyl) butane, 2,4-bis (diphenylphosphinyl) pentane, 4,5-bis (diphenylphosphinylmethyl)-
2,2-dimethyl-1,3-dioxolane, 1,2-bis (diphenylphosphinylmethyl) cyclohexane,
1-tert-butoxycarbonyl-4-diphenylphosphinyl-2-diphenylphosphinylmethylpyrrolidine, 1-tert-butoxycarbonyl-4-dicyclohexylphosphinyl-2-diphenylphosphinylmethylpyrrolidine, 2,2 ′ Examples thereof include optically active compounds such as bis (diphenylphosphinyl) -1,1′-binaphthyl.

The rhodium compound used in the method of the present invention includes rhodium halides, oxides, and mineral salts.
Examples include organic acid salts or rhodium complex compounds. Examples of these are rhodium trichloride, rhodium oxide, rhodium nitrate, rhodium sulfate, rhodium acetate, trisacetylacetonato rhodium, dicarbonyl acetylacetonato rhodium, dodecacarbonyl tetrarhodium, hexadecacarbonyl hexalodium, dichlorobis (1, 5-
Examples thereof include cyclooctadiene) dirhodium and hydridocarbonyl tris (triphenylphosphine) rhodium.

As the above-mentioned optically active phosphorus compound and rhodium compound which are preferably used in the method of the present invention, those in which both form a complex compound are more preferably used. Examples of these include, for example, chemical structural formulas (3) [Chemical Formula 3], (4) [Chemical Formula 4] and (5) [Chemical Formula 5]

[0015]

[Chemical 3]

[0016]

[Chemical 4]

[0017]

[Chemical 5] The optically active complex compounds shown in 1) and the like can be mentioned.

In the method of the present invention, in addition to the rhodium compound and the optically active phosphorus compound as a catalyst, the presence of a base as a cocatalyst is essential. The base described here means a Lewis base containing a Group 15 element of the periodic table such as nitrogen, phosphorus or arsenic, or a carboxylate. In the absence of these bases, rhodium compounds show no catalysis for this reaction. Among these bases, nitrogen-containing compounds such as pyridine compounds, quinoline compounds, imidazole compounds and triazole compounds, and one or more bases selected from aromatic carboxylic acid salts are preferable.

Specific examples of these bases are as follows. That is, as the pyridine compound, the chemical structural formula (6)

[0020]

[Chemical 6] (In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each hydrogen, an alkyl group, an aryl group, a cycloalkyl group, a halogen, a hydroxyl group, an alkoxy group, an aryloxy group, a cycloalkoxy group, A compound represented by a carboxyl group or an acetyl group), and examples thereof include pyridine, picoline, ethylpyridine, lutidine, α-collidine, phenylpyridine, cyclohexylpyridine, benzylpyridine, chloropyridine, and 3-pyridinol. , Methoxypyridine, phenoxypyridine, nicotinic acid, picolinic acid, isonicotinic acid,
There is acetyl pyridine, and in addition to this, bipyridyl is also mentioned as an example of a pyridine compound.

As examples of quinoline compounds, in addition to quinoline, 2-methylquinoline, 4-methylquinoline, dimethylquinoline, 2-ethylquinoline, phenylquinoline, chloroquinoline, 8-quinolinol, methoxyquinoline, 2-quinoline. Examples include carboxylic acid and 4-quinolinecarboxylic acid.

On the other hand, as the imidazole compound, a chemical structural formula (7)

[0023]

[Chemical 7] (In the formula, R ¹ , R ² , R ³ and R ⁴ each represent hydrogen, an alkyl group, an aryl group or a cycloalkyl group, and R ³ and R ⁴ are imidazole ring 4,
A condensed ring imidazole which forms a ring containing a carbon at the 5-position may be formed), and examples of these include imidazole, N-methylimidazole, N
-Ethylimidazole, 2-methylimidazole, 2-
Ethyl-4-methylimidazole, 2-phenylimidazole, 2-undecylimidazole, N-benzyl-
2-Methylimidazole, 2,4,5-triphenylimidazole, benzimidazole, 2-methylbenzimidazole, 2-phenylbenzimidazole and the like can be mentioned.

Further, as an example of the triazole compound,
1H-1,2,3-triazole, 1H-1,2,4-
Examples thereof include triazole, benzotriazole, 5-methylbenzotriazole and the like.

Further, examples of aromatic carboxylic acid salts include sodium benzoate, potassium benzoate, sodium phthalate, potassium phthalate, disodium phthalate, dipotassium phthalate and the like.

Further, as the above base, one or more compounds selected from the optically active phosphorus compounds represented by the chemical structural formula (1) are also preferably used.

The method of the present invention can be carried out without using a solvent, but it is also carried out in the presence of a solvent. The solvent in this case is usually pentane, hexane, heptane,
Saturated hydrocarbons such as octane, decane and dodecane, aromatic hydrocarbons such as benzene, toluene and xylene, chlorobenzene, orthodichlorobenzene,
It is a halogenated hydrocarbon such as parachlorotoluene,
Methanol, ethanol, propanol, butanol,
Alcohols such as pentanol and octanol, esters such as butyl acetate and γ-butyrolactone, ethers such as tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and tetraglyme, and ketones such as acetone and methyl isobutyl ketone. , Aldehydes such as propionaldehyde and butyraldehyde, acid anhydrides such as acetic anhydride, nitriles such as acetonitrile and propionitrile, amides such as N-methylpyrrolidone, and dimethylimidazo Urea such as ridinone and tetramethylurea, and carbonic acid esters such as ethylene carbonate and propylene carbonate are used.

The process of the invention can also be carried out in the presence of water. The reaction proceeds with considerable results even in the absence of water, but the presence of water further improves this reaction result, and is a reaction that cannot be achieved simply by combining a rhodium compound, an optically active phosphorus compound and a base. Bring grades. The amount of water present during the reaction is not particularly limited, but if the amount is extremely small, the effect will be small. Usually, the amount of water may be 0.0001 or more in weight ratio with respect to vinyl chloride supplied to the reactor as a raw material. The upper limit of the amount of water used is also not particularly limited, but considering the productivity of the target product per volume of the reactor, the weight ratio to vinyl chloride supplied to the reactor as a raw material is 1,000 or less. Is suitable. In particular, the range of 0.001 to 100, where the effect is remarkable, is preferable. This water may be supplied in a liquid state, but in some cases, it may be supplied in the form of water vapor while coexisting with gases to be supplied to the reactor or dissolved in a solvent used for the reaction. ..

In the method of the present invention, the rhodium compound is from 10 −4 to 108 milligram atoms, preferably 0.
Used in an amount corresponding to the range of 1 to 50 milligram atoms. The optically active phosphorus compound used in the method of the present invention is used in an amount of 0.1 to 50 mol, preferably 0.5 to 20 mol, per 1 gram atom of rhodium.
The base used in the method of the present invention is used in an amount of 0.1 to 500 mol, preferably 0.5 to 100 mol, per 1 gram atom of rhodium.

The method of the present invention is usually carried out at a reaction temperature of -20 to 20.
It is performed at 100 ° C, preferably in the range of 0 to 50 ° C. 1
At a high temperature of 00 ° C or higher, the reaction product is optically active 2-
The racemization and decomposition of chloropropionaldehyde are significant and are not suitable for the reaction. Further, at a low temperature of −20 ° C. or lower, the catalytic activity becomes low, so that it is not appropriate in view of productivity. The reaction pressure is 10 to 200 kg / c.
m2 gauge, preferably in the range of 30 to 150 kg / cm2 gauge. The mixing molar ratio of carbon monoxide and hydrogen of the raw material is usually in the range of 0.05 to 20, preferably in the range of 0.1 to 10. Carbon monoxide and hydrogen may be any mixed gas containing both components in the above composition ratio, such as hydrogen gas, a gas inert to the reaction such as methane and nitrogen in the water gas, or carbon dioxide. What is contained is used. The other raw material, vinyl chloride, is used in the form of gas, liquid, or dissolved in the solvent used for the reaction.

The method of the present invention can be carried out by any of a batch method, a semi-batch method and a continuous method. For example, in the case of the batch method, vinyl chloride is added in the form of gas, liquid or solution to an autoclave charged with a catalyst, and optionally water and a solvent, and a gas containing carbon monoxide and hydrogen is added thereto in a predetermined manner. The reaction proceeds by introducing the pressure up to and heating to a predetermined temperature. In the case of the continuous method,
A liquid containing a catalyst, vinyl chloride, and optionally water and a solvent, and a gas containing carbon monoxide and hydrogen were continuously introduced from one pressure-resistant reactor, and the reaction product, the catalyst, and the The reaction is carried out by continuously extracting the reaction vinyl chloride, and optionally a liquid containing water and a solvent, and unreacted carbon monoxide and hydrogen. It is also possible to introduce vinyl chloride in a gaseous state into the reaction vessel together with a mixed gas containing carbon monoxide and hydrogen as raw materials. Further, as one variation of the continuous method, a catalyst and, if necessary, a solvent are charged in the reactor, and vinyl chloride, carbon monoxide, hydrogen, and water, which are raw materials, are continuously supplied from below the reactor. It is also possible to use a method in which unreacted vinyl chloride, carbon monoxide, hydrogen, reaction products and, if necessary, water are continuously withdrawn from above.

The optical purity of the optically active 2-chloropropionaldehyde of the present invention can be measured using a polarimeter.
Optically active 2-chloropropionaldehyde
Alternatively, it can be converted to anilide of chloropropionic acid and measured by liquid chromatography using an optically active column.

[0033]

EXAMPLES The method of the present invention will be described in more detail below with reference to examples. Example 1 After the inside of a stainless steel autoclave with an internal volume of 70 ml equipped with a stirrer was replaced with nitrogen gas, ((R)-
2,2'-bis (diphenylphosphino) -1,1'-
Binaphthyl) (1,5-cyclooctadiene) rhodium perchlorate 187 mg (rhodium 0.2 mg atom) and disodium phthalate 105 mg (0.5
10m aqueous solution of disodium phthalate containing
l was added, and 2.0 g (32 mmol) of vinyl chloride was added.
10 ml of a vinyl chloride solution containing vinyl chloride was added. In this autoclave, the molar ratio of carbon monoxide and hydrogen is 1 :.
After injecting the mixed gas of No. 2 at room temperature until the pressure reached 50 kg / cm ² gauge, the temperature was raised to 40 ° C. and the reaction was performed for 150 minutes. After collecting the unreacted raw material mixed gas in the gas sampling bag after cooling the autoclave to room temperature,
The autoclave was opened, and the reaction mixture containing the catalyst, solvent, water and reaction product was taken out. As a result of analyzing the gas and the liquid by gas chromatography, the amount of 2-chloropropionaldehyde produced was 1.0 mmol. The produced 2-chloropropionaldehyde was converted into 2-chloropropionic acid anilide and analyzed by liquid chromatography using an optically active column (CHIRALCEL-OB manufactured by Daicel Chemical Industries, Ltd.). As a result, the optical property of 2-chloropropionaldehyde was obtained. Purity is 12% (12%
e. e. ), The (S) -form was in excess. Example 2 After replacing the inside of a stainless steel autoclave with an internal volume of 70 ml equipped with a stirrer with nitrogen gas, chlorocarbonyl ((4R, 5R) -4,5-bis (diphenylphosphinomethyl) -2,2- Dimethyl-1,3-dioxolane) rhodium 133 mg (rhodium 0.2 mg atom), (4R, 5R) -4,5-bis (diphenylphosphinomethyl) -2,2-dimethyl-1,3-dioxolane 100 mg ( 0.2 mmol) and 10 ml of an aqueous solution of disodium phthalate containing 105 mg (0.5 mmol) of disodium phthalate were added, and 10 ml of a toluene solution of vinyl chloride containing 2.0 g (32 mmol) of vinyl chloride was added thereto. added. In this autoclave,
After injecting a mixed gas of carbon monoxide and hydrogen in a molar ratio of 1: 7 at room temperature to a pressure of 80 kg / cm ² gauge,
The reaction was carried out at 10 ° C for 300 minutes. After the same post-treatment as in Example 1, the analysis showed that the amount of 2-chloropropionaldehyde produced was 0.5 mmol and the optical purity was 29%.
(29% ee), and the (S) -form was in excess. Example 3 After replacing the inside of a stainless autoclave with an internal volume of 70 ml equipped with a stirrer with nitrogen gas, chlorocarbonyl ((4S, 5S) -4,5-bis (dibenzophosphorylmethyl) -2,2-dimethyl was obtained. 66 mg (0.1 mg of rhodium), (4S, 5S) -4,5-bis (dibenzophosphorylmethyl) -2,2-dimethyl-1,3-dioxolane 49 mg (0.-1,3-dioxolane) rhodium. 1 ml) and 10 ml of an aqueous solution of disodium phthalate containing 105 mg (0.5 mmol) of disodium phthalate were added, and 10 ml of a toluene solution of vinyl chloride containing 1.0 g (16 mmol) of vinyl chloride was added thereto. .. A gas mixture of carbon monoxide and hydrogen having a molar ratio of 1: 7 was introduced into the autoclave at room temperature until the pressure reached 80 kg / cm ² gauge, and then 30 ° C.
And reacted for 240 minutes.

After the same post-treatment as in Example 1, analysis was conducted. As a result, the amount of 2-chloropropionaldehyde produced was 1.1 mmol, and the optical purity was 40% (40% ee).
Thus, the (S) -form was in excess [Fig. 1].

[0035]

Industrial Applicability According to the method of the present invention, catalytically optically active 2-chloropropionaldehyde can be produced in one step from vinyl chloride, carbon monoxide and hydrogen which are industrially available. INDUSTRIAL APPLICABILITY The present invention provides an optically active 2-chloropropionaldehyde and a method for producing the same, which can be easily converted into various optically active agricultural pharmaceuticals and which is very useful in industry.

[Brief description of drawings]

FIG. 1 shows the result of optical purity analysis of the 2-chloropropionaldehyde produced in Example 3 by liquid chromatography using an optically active column.

FIG. 1 is an optical purity analysis diagram by liquid chromatography using an optically active column.

[Explanation of symbols]

 B (R) -body b (S) -body

Claims (4)

[Claims] 1. An optically active 2-chloropropionaldehyde. 2. A process for producing optically active 2-chloropropionaldehyde, which comprises reacting vinyl chloride, carbon monoxide and hydrogen in the presence of a rhodium compound, an optically active phosphorus compound and a base. 3. The optically active phosphorus compound is a chemical structural formula (1) or a chemical structural formula (2) [Chemical Formula 1] (In the formula, P is a phosphorus atom, and R ¹ , R ² , R ³ and R
⁴ represents an alkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an aryloxy group, a cycloalkoxy group or a hydroxyl group, respectively, and R ⁵ represents two phosphorus atoms by an alkyl group, an aryl group, a biaryl group, a cycloalkyl group, The method according to claim 2, which is an optically active phosphorus compound represented by a structure which is crosslinked with an alkoxy group, an aryloxy group, a biaryloxy group or a cycloalkoxy group. 4. The method according to claim 2 or 3, which is carried out in the presence of water.