JP3440141B2 - Method for producing 2-diphenylphosphinopyridine - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improved method for producing 2-diphenylphosphinopyridine. The object of the present invention, 2-diphenylphosphinopyridine, is useful as a catalyst component for the carbonylation of alkynes and alkenes and for the synthesis of other organic compounds such as amides. [0003] The following is known as a method for producing diphenylphosphinopyridine. A method of obtaining diphenylphosphinopyridine (yield: 20%) by a Grignard reaction between pyridylmagnesium bromide and diphenylphosphine chloride, Journal of Organic Chemistry, Vol. 13, page 502 (1948). [0005] Journal of Organic Chemistry, Vol. 43, p. 947 (1948) A method of reacting lithium diphenylphosphide with 2-bromopyridine in tetrahydrofuran to obtain diphenylphosphinopyridine (yield 55%). [0006] Zeit Schliff Fuer
Natzer Forcing Tail Bee Unorganized Chemie Organic Chemie Biochemie Biophysical Biology (Zeitschr
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Vol. 5 (B), p. 1329 (1980) A method of obtaining 2-phenylphosphinepyridine (20-44% yield) by reacting phenylphosphine chloride and 2-pyridyllithium represented by the following reaction formula. [0007] (Wherein, n represents an integer of 1 to 3.) Journal of the American
Chemical Society, Vol. 106, p. 1323 (1984) Diphenylphosphine chloride is reacted with lithium in tetrahydrofuran. After stirring it for 12 hours-
Cool to 5 ° C. and react with 2-bromopyridine. After distilling off tetrahydrofuran and extracting with ether, the ether is distilled off and dried. Then, tetrahydrofuran is distilled off, and after ether extraction, ether is distilled off and dried. Then, recrystallization with hot methanol to obtain 2-diphenylphosphinopyridine (yield 84%). JP-A-5-92984 (a) Triarylphosphine is reacted with about 2 equivalents of an alkali metal in a substantially aprotic solvent to form an alkali diaryl phosphide and an alkali aryl, (B) selectively removing the formed alkali aryl, (c) reacting the alkali diaryl phosphide with about 1 equivalent of an appropriately substituted pyridyl halide per halogen group, and (d) forming the resulting diaryl phosphino A method for producing a diarylphosphinopyridine, comprising separating pyridine. [0010] In the above-method [0006], the yield of diphenyl phosphinic Nopirijin 20-60
% And low. In addition, the above method has a high yield (84
%), The reaction of diphenylphosphine chloride with lithium requires 12 hours, and the subsequent reaction with 2-bromopyridine requires a low temperature of -5 ° C. In addition, it is difficult to say that this method is technically and economically advantageous, such as using expensive lithium. The above-mentioned method is not preferable as an industrial production method, for example, the reaction operation is complicated, and expensive lithium is used to complete the reaction in a short time. Therefore, there is a demand for the development of an industrial process for producing 2-diphenylphosphinopyridine, which can make the reaction operation simpler, use less expensive raw materials and obtain the desired product in high yield. The present invention provides a 2-
It is an object to provide a method for producing diphenylphosphine Bruno pyridine. Means for Solving the Problems The present inventors have made various studies to achieve the above object. As a result, as shown in the following reaction formula, diphenylphosphine halide (2) was used as a starting material, and was reacted with molten alkali metal (M) in the presence of an inert organic solvent to form diphenylphosphine alkali. By forming the metal salt (3) and subsequently reacting with the 2-halopyridine (4), a high yield (9
4.5%) 2-diphenylphosphinopyridine (1)
Can be manufactured, and the present invention has been completed. Reaction formula ## STR6 ## Process 1 Embedded image Process 2 (In the formula, M represents sodium or potassium, X ₁ represents a halogen atom, X ₂ represents chlorine, bromine, or iodine.) Next, a specific method for carrying out the present invention will be described. I do. (1) Implementation of Process 1 The following method is used to produce the diphenylphosphine alkali metal salt of the formula (3) from the diphenylphosphine halide of the formula (2) as a raw material. First, an organic solvent is put into a reaction vessel equipped with a reflux condenser, a stirrer, a thermometer, and a dropping funnel, and an alkali metal (M) is put therein and melted while heating and stirring. In this case, it is preferable to replace the inside of the reaction vessel with nitrogen in advance before adding the alkali metal, since the reaction can proceed smoothly. A diphenylphosphine halide solution of the formula (2) dissolved in an organic solvent is added dropwise thereto. At this time, a small amount of the diphenylphosphine halide solution of the formula (2) is added first, and after a while, the reaction solution turns yellow and the reaction starts. After confirming this, the remaining diphenylphosphine halide solution of the formula (2) is gradually added dropwise. Thereafter, the reaction is completed under heating and refluxing for about 2 hours. The next process can proceed as it is. As the alkali metal (M) used in the process 1, metal sodium and metal potassium are used. The amount of the alkali metal (M) to be used is at least 2 moles per 1 mole of diphenylphosphine halide (2) as a raw material. If less than this,
There is a tendency for by-products such as diphenylpyridylphosphine oxide to increase. On the other hand, the upper limit of the amount of the alkali metal (M) to be used is not particularly problematic even if it is excessive in the reaction. It is enough. Therefore, the amount of the alkali metal (M) used is 2 to 3 mol, preferably 2.2 to 2 mol per 1 mol of diphenylphosphine halide.
2.8 mol. The halogen atom of the diphenylphosphine halide used may be any of chlorine, bromine and iodine, but the use of diphenylphosphine chloride, which is easily available chlorine, is preferred. The organic solvent used in the reaction has a boiling point higher than the melting point of the alkali metal (M). Considering the ease of post-treatment at the end of the reaction, those which are immiscible with water are preferred. Such organic solvents may be either polar or non-polar. As such examples, di-n-butyl ether, benzene, toluene, tetrahydrofuran, 1,4-dioxane and the like are useful, and among them, use of 1,4-dioxane is particularly preferable. (2) Process 2 implementation method (Process 1)
The following method is used to obtain the desired 2-diphenylphosphinopyridine from the diphenylphosphine alkali metal salt obtained in Process 1. First, in a reaction solution containing the alkali metal salt of diphenylphosphine (3) obtained in the above process,
The reaction may be carried out by dropping 2-halopyridine (4).
Diphenylphosphine alkali metal salt in this case (3)
The reaction molar ratio of the 2-halopyridine to the former is 1 mol, and the latter is 0.7 to 1.2 mol, preferably 0.9 mol.
What is necessary is just to make it react in the ratio of 1.0 mol. The halogen of the 2-halopyridine used herein is chlorine, bromine or iodine, and any of them can be effectively used, but chlorine or bromine is particularly preferable. When the reaction temperature of the diphenylphosphine alkali metal salt (3) and 2-halopyridine (4) is low, the reaction rate is slow, and when it is high, the generation of impurities increases. From these facts, the reaction temperature is suitably in the range of 0 to 100 ° C, preferably 20 to 50 ° C. When the diphenylphosphine alkali metal salt (3) and 2-halopyridine (4) are continuously stirred under such temperature conditions, the reaction is completed in 1 to 2 hours. After completion of the reaction, the desired product can be obtained and purified as follows. First, while keeping the reaction solution at 50 ° C. or lower,
Water is slowly added thereto to dissolve unreacted alkali metal (M) and by-product salts (MX ₁ , MX ₂ ). The amount of water is preferably an amount that can sufficiently dissolve these alkali metals (M) and by-produced salts. Usually, the used alkali metal 1
Approximately 800 ml per mole is good. Then, an organic solvent such as benzene, toluene and di-n-butyl ether is added thereto, the organic layer is separated, washed with water and dried, and the organic solvent is distilled off. Diphenylphosphinopyridine (1) is obtained. The crude product can be purified by, for example, recrystallization with a mixed solvent of methanol and hexane (ratio of 1: 2 to 2: 1). Hereinafter, the method of the present invention will be described in more detail by way of representative examples, but the present invention is not limited to the examples. The diphenylphosphine chloride used in Example 1 was replaced with diphenylphosphine bromide and diphenylphosphine iodide.
When 2-bromopyridine and 2-iodopyridine were used in place of 2-chloropyridine and the reaction was carried out in the same manner as in Example 1, 2-diphenylphosphinopyridine was obtained in high yield as in Example 1. Can be obtained. Among them, as the diphenylphosphine halide of the formula (2),
In particular, diphenylphosphine chloride or diphenylphosphine bromide is 2-halopyridine,
Particularly, use of 2-chloropyridine or 2-bromopyridine is preferred. EXAMPLES Example 1 Method for producing 2-diphenylphosphinopyridine (1) Process 1 A 2 L-sized four- liter container equipped with a Dimroth condenser, a thermometer, a dropping funnel and a stirrer was purged with nitrogen. Tsu
Put the mouth round bottom flask 1,4-dioxane 400ml and metallic sodium 22.3 g (0.968 mol), was heated with stirring and refluxed. After melting of the metallic sodium, 88.3 g (0.4%) of diphenylphosphine chloride dissolved in 90 ml of 1,4-dioxane.
3) while maintaining reflux with the heat of reaction.
Add. After about 20 minutes, the reaction solution turns yellow, which is used as the start of the reaction. The remaining diphenylphosphine chloride solution is not dropped until the reaction has started. Thereafter, the remaining diphenylphosphine chloride solution was added to about 1.5
Drop slowly over time. After completion of the dropwise addition, the mixture was heated with stirring and reacted under reflux for 2 hours. Thus diphenylphosphine
Obtain the sodium salt. (2) Process 2 Next, the reaction solution was cooled to about 30 ° C., and 45.4 g (0.40 mol) of 2-chloropyridine was added thereto at a reaction temperature of 30 ° C.
The solution was added dropwise in about 40 minutes while maintaining the temperature at ４０40 ° C. After completion of the dropwise addition, the mixture was reacted at the same temperature for 2 hours while stirring. The conversion to 2-diphenylphosphine Bruno pyridine after 2 hours 2-chloropyridine was 100% (analytical value by gas chromatography). After the completion of the reaction, 800 ml of water was slowly added dropwise while maintaining the temperature at 50 ° C. or lower to dissolve unreacted metallic sodium and by-produced salts. Further benzene 60
After adding 0 ml and stirring for 20 minutes, the mixture was allowed to stand, separated, and the organic layer was separated. The remaining aqueous layer was extracted again with 200 ml of benzene. And the combined organic layers are 200m water
l. After the solvent of the organic layer was distilled off,
C., the pressure was reduced to 1 to 2 mmHg, and the mixture was distilled to obtain 116.2 g (0.38 g) of crude 2-diphenylphosphinopyridine.
Mol). Purity was 85.6% by gas chromatography internal standard analysis, and the yield was 94.5%. When recrystallized using 180 ml of a mixed solvent of methanol / hexane (2: 1), 92.0 g of 100% pure 2-diphenylphosphinopyridine (yield: 87.4%, melting point: 83.5 to 84). .5 ° C.) as a white powder. According to the present invention, the following advantages are obtained as compared with similar conventional methods (for example, the above-described method). That is, the reaction time may be about 1/3 or less. Further, the desired 2-diphenylphosphinopyridine can be obtained with high purity and high yield by a simple operation without using expensive lithium. Therefore, it is useful for implementation on an industrial scale.

Continuation of front page (56) References Am. Chem. Soc. , 1984, Vol. 106, no. 5, P1323-1332 Inorg. Chem. , 1982, Vol. 21, No. 11, P3961-3967 (58) Field surveyed (Int. Cl. ⁷ , DB name) C07F 9/58 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claim 1] In the presence of an inert organic solvent, a compound represented by the general formula (2)
Diphenyl phosphine halide (Wherein X ₁ represents a halogen atom) and a molten alkali metal (M) are reacted to form a compound represented by the general formula (3): (Wherein M represents sodium or potassium) to obtain a diphenylphosphine alkali metal salt represented by the following general formula (4): (Wherein X ₂ represents chlorine, bromine or iodine), characterized by reacting with 2-halopyridine represented by A method for producing 2-diphenylphosphinopyridine represented by the formula: