JP2589564B2 - Preparation of styrene derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing styrene derivatives, and more specifically, to a method of formula (II) (Wherein R may be the same or different, and a halogen atom,
A cyano group or a nitro group; a lower alkyl group which may be substituted by a halogen atom or a lower alkoxy group which may be substituted by a halogen atom; n represents an integer of 0 to 5; X represents a halogen atom; Represents a phenyl group. Wherein the phosphonium salt represented by the formula is reacted with formaldehyde in the presence of water, an organic solvent insoluble in water and a base. (Wherein, R and n are the same as described above).

Styrene derivatives are important compounds as synthetic intermediates in the pharmaceutical, agricultural, and other chemical industries, and many methods are known for their production. However, these conventional methods are not optimal for industrially producing high-yield and high-purity styrene derivatives.

For example, JP-A-61-212526 discloses N-acyl-β
Disclosed is a method for treating phenethylamines with a base and removing styrene formed during the reaction to produce styrenes. However, the process does not utilize the starting N
There is a problem that many steps are required to produce -acyl-β-phenethylamines. Org.Synth., Coll.
Vol. 3, 204 (1955) discloses a method of reacting a substituted benzaldehyde with a Grignard reagent and dehydrating the resulting α-hydroxyethylbenzene with an acid to produce a styrene derivative. However, this method requires precision in setting reaction conditions in the Grignard reaction and dehydration reaction, and is not sufficiently satisfactory in the yield of the product, and it is often difficult to obtain benzaldehydes as a raw material. There is. Org.Synt
h., Coll. Vol. 4,731 (1963) discloses a method for producing a styrene by condensing an aldehyde with malonic acid and decarboxylating the resulting cinnamic acid. However, the production of styrenes by the production method has a low yield, and the development of a novel production method for producing styrenes at a high yield industrially is desired.

Next, Synthetic Communication, 6 (1) 53-57 (19
No. 76) discloses a method for preparing a phosnium salt from benzyl chloride and triphenylphosphine, and reacting the phosphonium salt with formaldehyde in the presence of a base in an aqueous solvent to produce styrenes. However, in this method, a large amount of triphenylphosphine oxide is produced as a by-product during the reaction, and the disposal of the triphenylphosphine oxide is problematic.
Also, formaldehyde as a reactant is a substance specified as a specific chemical substance, and since formaldehyde is used in a large excess in the reaction, treatment of waste liquid containing these is a serious problem in terms of environment and occupational safety and health. In addition, since the reaction products, starting compounds, and by-products are present in a heterogeneous state (for example, a suspension state, a crystallization state, and the like) in the reaction system, the stirring efficiency greatly affects the reaction yield. The production of certain styrenes shows a significant reduction in yield.

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have completed the present invention.

The present invention provides a styrene derivative represented by the general formula (I) by reacting a phosphonium salt represented by the general formula (II) with formaldehyde in an aqueous solvent in the presence of a water-insoluble organic solvent and a base. It can be produced, and the feature of the present invention is a two-phase reaction which is easy to stir, and it is only necessary to use equimolar amount or a slight excess of formaldehyde and base. The by-product triphenylphosphine oxide can be easily separated from the reaction solution by a simple operation, for example, a method such as filtration, so that the objective styrene derivatives with high yield and high purity can be produced. The industrial significance is great.

The invention can be illustrated, for example, schematically as follows:

(Wherein R, n, X and Ph are the same as described above). That is, the phosphonium salt represented by the general formula (II) is reacted with formaldehyde in the presence of water, a water-insoluble organic solvent and a base. Thus, a styrene derivative represented by the general formula (I) can be produced.

This reaction uses water and an organic solvent that is insoluble in water, and water is used in an amount of 500 to 1000 ml as a total amount of the reaction system per 1 mol of the phosphonium salt represented by the general formula (II). When formaldehyde as a reactant is used as an aqueous solution, and when a base is used as an aqueous solution, the amount of these waters is also considered, and preferably 700
Can be selected from the range of ~ 900ml.

Examples of the water-insoluble organic solvent that can be used in this reaction include ethers, aliphatic hydrocarbons or aromatic hydrocarbons which may be halogenated, and ethers such as dimethyl ether, diethyl ether, and diisopropyl ether. , N-pentane, n-hexane and the like; chlorinated aliphatic hydrocarbons such as carbon tetrachloride; and aromatic hydrocarbons such as benzene. The amount of the organic solvent insoluble in water is 100 to 5 mol per mol of the phosphonium salt represented by the general formula (II).
It can be used in the range of 00 ml, and preferably can be selected from the range of 100 to 200 ml. When an organic solvent insoluble in water such as ethers such as dimethyl ether and diisopropyl ether, chlorinated aliphatic hydrocarbons such as carbon tetrachloride, and aromatic hydrocarbons such as benzene, the reaction is terminated. Thereafter, the solution may be transferred to an aliphatic hydrocarbon such as n-pentane or n-hexane for isolation.

The formaldehyde used in this reaction is commercially available in the form of a 30 to 40% aqueous solution, but it is generally preferable to use a 35% aqueous formaldehyde, but it is not particularly limited thereto.

As the base that can be used in this reaction, an inorganic base can be used.For example, hydroxides or carbonates of alkali metals such as sodium and potassium can be used, and these bases are used in the form of an aqueous solution. Preferably, the base may be used as an aqueous solution having a concentration in the range of 1 to 10N, and more preferably, an aqueous solution having a concentration in the range of 5 to 10N.

The amount of the reactant used in this reaction is 1 mole to 1 mole of the phosphonium salt represented by the general formula (II), and the amount of formaldehyde used is equimolar to a slight excess, and the amount of the base used is equimolar to a slight excess. It may be used in an amount, but it is preferable to use equimolar amounts of formaldehyde and a base.

The reaction temperature can be selected from the range of 0 ° C. to 60 ° C., and a temperature of about 30 ° C. is suitable.

The reaction time is not fixed depending on the reaction amount, the reaction temperature and the like, but may be selected from the range of several minutes to 24 hours.

After completion of the reaction, the water-insoluble organic solvent layer containing the target substance is separated, washed with water, dried, and then the solvent is distilled off under reduced pressure to produce the target styrene derivative in high yield and high purity. It can be purified by an appropriate purification method if necessary.

The phosphonium salt represented by the general formula (II) is synthetic
Commnication, 6 (1) 53-57 (1976).

Hereinafter, typical examples of the present invention will be illustrated, but the present invention is not limited thereto.

Example 1. Production of o-chlorostyrene.

472 g (1.10 mol) of o-chlorobenzyltriphenylphosphonium chloride, a 35% aqueous solution of formalin (1.17 mol) and 700 ml of water were placed in a reaction vessel, and 200 ml of n-hexane was further added. An aqueous solution (110 ml, 1.10 mol) was gradually added dropwise over 30 minutes.

After completion of the dropwise addition, the reaction solution was stirred for 2 hours at the same temperature to carry out the reaction. After the completion of the reaction, the reaction solution was cooled, and the insoluble material was separated by filtration.
An organic layer was separated from the obtained filtrate. After the obtained organic layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 151 g of the desired o-chlorostyrene as a colorless oil.

As a result of analyzing the obtained oil by gas chromatography, the purity of o-chlorostyrene was 98.9%.

The yield was 98.9%. Since the compound was a known compound, it was identified by gas chromatography using a sample.

NMR (CDCl ₃ / TMS, 60 MHz) δ 5.35 (dd, J = 1.8 Hz, J = 11.2 Hz, 1H) 5.71 (dd, J = 1.
(8 Hz, J = 17.9 Hz, 1H) 6.85 to 7.70 (m, 6H) Example 2 The procedure of Example 1 was repeated, except that the organic solvent shown in Table 1 was used instead of n-hexane of Example 1. The results are shown in Table 1.

When diethyl ether and carbon tetrachloride were used, they were transferred to n-hexane after completion of the reaction, and insolubles were removed by filtration.

Example 3 It carried out similarly to Example 1 using the phosphonium salt and organic solvent shown in Table 2. The results are shown in Table 2.

Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI Technical indication location C07C 41/18 C07C 41/18 43/215 43/215 43/225 43/225 201/12 201/12 205 / 06 205/06 253/30 253/30 255/50 255/50

Claims (4)

(57) [Claims] 1. A compound of the general formula (II) (Wherein R may be the same or different, and a halogen atom,
A cyano group, a nitro group, a lower alkyl group which may be substituted by a halogen atom or a lower alkoxy group which may be substituted by a halogen atom, n represents an integer of 0 to 5, X represents a halogen atom, Ph represents a phenyl group. Wherein the phosphonium salt represented by the formula is reacted with formaldehyde in the presence of water, an organic solvent insoluble in water and a base. (Wherein, R and n are the same as described above). 2. The process for producing styrene derivatives according to claim 1, wherein an equimolar amount or a slight excess of formaldehyde is used relative to the phosphonium salt represented by the general formula (II). 3. The process for producing a styrene derivative according to claim 2, wherein the water-insoluble organic solvent is an ether, an aliphatic hydrocarbon which may be halogenated or an aromatic hydrocarbon. 4. An organic solvent insoluble in water is n-pentane or n-pentane.
The method for producing a styrene derivative according to claim 3, which is -hexane.