JPH049349A - Production of 3-phenoxypropanal compound - Google Patents

Abstract

PURPOSE: To easily prepare the subject compound used as an intermediate of drugs, a plasticizer, a surface agent or the like in one process with high yield, by oxidizing ally phenyl ether in an alcohol solvent in the presence of a palladium complex compound and an oxidizing agent.

CONSTITUTION: Allyl phenyl ether optionally having a substituent on the benzene ring, is oxidized in an alcohol solvent such as methanol, ethanol, propanol or the like in the presence of a palladium complex compound such as PdCl₂, PbBr₂, PbSO₄ or the like, and an oxidizing agent such as CuCl₂; 2H₂O, CuCl₂, CuCl or the like, further preferably in the presence of an organic acid alkali metal salt such as sodium acetate, potassium acetate, sodium propionate, or the like and/or an acid such as glacial acetic acid, propionic acid, butyric acid or the like in the air of very low reaction temperature (25-50°C) without the addition of pressure and oxygen to form 3-phenoxypropanol derivative with high yield of about 76%.

COPYRIGHT: (C)1992,JPO

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing 3-phenoxypropanal compounds.

[Problems to be solved by conventional technology and invention] 3-
Phenoxypropanal compounds are synthetic intermediates for drugs,
It is used as a plasticizer, surfactant, etc., and has a wide range of applications.

For this reason, the industry is actively researching ways to synthesize this compound, but there is still no preferred method. All of the previously published synthetic methods in patents and literature have the following drawbacks: the reaction conditions are harsh, the yield is very low (the reaction chemicals used are expensive, the reaction steps are many, etc.) It will be done.

For example, the synthesis method described in U.S. Pat. No. 2,500,582 involves refluxing acrolein, phenol, pararesorcinol and pyridine together for 2.5 hours; The reaction formula is as follows: The reaction of the above method is violent and the yield is very low.

J. Crosby and J. M. Stirling et al. 19
1970 J, Chem, Soc.

(B), 4,671. (1970) describes a method for synthesizing 3-phenoxypropanal,
It is 3-phenoxypropanol, CbFlzN=
C=N-C,I(,1 and DMSO are reacted at 20°C for 16 hours to obtain 3-phenokidibrobanal, the yield is about 28%, and the reaction formula is as follows: Some of the above methods require expensive chemicals for the reaction and have low yields.

A, M, Yu Idashev et al. 5int, Re
akts, 5posobn, Org.

5oedin, 32 (1983); CA, 1
The synthesis method published in 01.72565q (1984) is to oxidize 2-phenoxyethanol and then use Grignard reaction to produce Ph0C)I2CH,CllM
Form eOH and oxidize it to obtain 3-phenoxypropanal. The reaction formula is as follows: The above method has many reaction steps, is not easy to synthesize, and has a low total acid rate.

An object of the present invention is to provide a novel method for synthesizing 3-phenoxypropanal compounds that does not have the above drawbacks.

Another object of the present invention is to achieve a very low reaction temperature (2550'C).
) in air, there is no need to add pressure or oxygen, and the reaction yield reaches about 76%.

[Means for Solving the Problems, Actions and Effects of the Invention] The present invention provides a method for producing a 3-phenoxypropanal compound represented by the following general formula (I): (wherein R+, Rz and R3 are independently hydrogen, C
) 13 or a halogen) That is, in the method of the present invention, an allyl phenyl ether compound represented by the following general formula (I[) is combined with a palladium salt complex compound, an oxidizing agent, optionally an organic acid alkali metal salt, and/or optionally The oxidation reaction is carried out in an alcoholic solvent in the presence of an acid:
) has the same meaning as defined in ) The present invention provides a method for synthesizing the 3-phenoxypropanal compound represented by general 2N) above. For this purpose, the allyl phenyl ether compound represented by the above general formula (II) is subjected to an oxidation reaction in an alcoholic solvent in the presence of a palladium salt complex compound, an oxidizing agent, optionally an organic acid alkali metal salt, and/or optionally an acid. let

Preferable allyl phenyl ether compounds represented by the above general formula (It) include allyl phenyl ether, 0
-methylallylphenyl ether, m-methylallylphenyl ether, p-methylallylphenyl ether,
2,6-dimethylallylphenyl ether, 2,4.6
-Dolimethylallylphenyl ether and parachloroallylphenyl ether. These allyl phenyl ether compounds are obtained by refluxing a phenol compound with allyl bromide and potassium carbonate in acetone for about 6 hours.

Examples of the palladium salt complex compound oxidizing agent used in the method of the present invention include PdCf 2+ PbBrzP
dSOa, Pd(NO:+)2, CuBr2, Li
Examples include zPdC14, NazPdCfi, and zPdCf4, with PdCffi□ being particularly preferred.

The amount used is approximately 0.01-200 moles of alkenyls.
%, especially about 10%.

The oxidizing agents used in the method of the present invention include monovalent and divalent copper salt complex compounds, such as CuCl□.2F1. O.

CuC1z+ CuCCCu(NOz)2, CuBr2
, CuBr2, CuBr2, CuBr, CuSO4
Rosebenzoquinone + HPA (HQPMO6 604o
), FIzOz and tert-butyl peroxide,
Particularly preferred is CuCl2.2H20. The amount used is preferably about 0.01 to 1000%, particularly about 300%, based on the number of moles of the alkenyl.

The alcohol solvents used in the above method of the present invention include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, tert-butanol, 1,2-ethylene glycol, 1,3-ethylene glycol and There is a mixture of the above alcohol and water. When the above method of the present invention is carried out using different alcohols and the above organic acid alkali metal salt is used in the reaction system, the higher the series of the alcohol, the slower the reaction, but the resulting products acetal and ketal are It is easy to hydrolyze and has excellent selectivity for aldehydes in the product. For example, if the reaction is carried out with methanol (-grade), 2-propanol (secondary), and tertiary-butanol (tertiary), it will take only 40 minutes with methanol, but 2 hours with 2-propanol and tertiary-butanol; When carried out, the products obtained are mainly ketals and acetals, but 2-
With propanol and tert-butanol, the products obtained are mainly ketal and acetal hydrolyzed aldehydes and ketones, among which the selectivity of acecool obtained with tert-butanol is the best. Adding water to methanol solvent can promote ketal and acetal hydrolysis and increase the yield of aldehydes and ketones. The amount of the alcohol or mixture with water used is 0.0 based on the number of moles of alkenyl.
01-10000 d1 mol, especially 2678-4464
d 1 mol is preferred.

Examples of alkali metal salts of organic acids used as optional ingredients in the method of the present invention include sodium acetate, potassium acetate, sodium propionate, potassium propionate, sodium butyrate, potassium butyrate, sodium benzoate, potassium benzoate, etc. Among them, sodium acetate is particularly preferred. The amount used is approximately the number of moles of alkenyl O,
(11-1000%, particularly 40-500% is preferred.

Furthermore, the acids used in the method of the present invention which are used as optional ingredients include organic acids and inorganic acids, including glacial acetic acid, propionic acid, butyric acid, benzoic acid, hydrochloric acid, phosphoric acid, sulfuric acid and nitric acid, with acetic acid being particularly preferred. preferable. The amount of the acid used is preferably 0.001-10000 d1 mol, particularly 800-1000 d1 mol, based on the number of moles of the alkenyl.

In the above method of the present invention, if an organic acid alkali metal salt and an acid are not added, the reaction rate is very slow; if an organic acid alkali metal salt or an organic acid alkali metal salt/acid is added, the reaction rate is accelerated. In the preliminary test of the present invention, the number of moles 1=
30 PdC1,z /CuC1z ・2) 120 and allyl phenyl ether were dissolved in methanol and heated at 25°
The conversion rate when reacting for 24 hours at
It is 1%. However, when glacial acetic acid and sodium acetate were added to the above system, the conversion rate after 4.5 hours of reaction at 25°C was 98%, and if only sodium acetate was added, the conversion rate was 98%.
The conversion rate after 40 minutes of reaction at C was 100%. or,
By changing the reaction temperature and the amount of sodium acetate used in the method of the present invention, when the temperature is low, the reaction rate is slow but the selectivity is good, and when the amount of sodium acetate is large, the reaction is fast but the selectivity is low. bad. Therefore, by changing the appropriate reaction temperature and the amount of sodium acetate used, reaction conditions with excellent conversion and selectivity can be obtained.

The suitable reaction temperature range for the above method of the present invention is about 5-100
C, especially 25-30 C. The reaction pressure is not limited, generally 1-10 atm, and normal pressure is preferred.

Examples will be described below, but the scope of the present invention is not limited thereto.

〔Example〕

Example 1 The purpose of this example is to synthesize an allyl phenyl ether compound used in the method of the present invention.

After heating 0.1 mol of phenolic compound, 0.1 mol of potassium carbonate, 0.1 mol of allyl bromide and 100 d of acetone in a 200 d round bottom flask under reflux for 6 hours, the reaction mixture was cooled to room temperature. Pour into 200ml of water, extract with ether, wash twice with saturated sodium bicarbonate water,
After washing 5 times with water, drying over magnesium sulphate and filtration, the solvent is evaporated.

The yield of the obtained product is shown in Table 1.

Table 1 Yield of allyl phenyl ether → compound 25 Z two trivial compounds Yield
83m-methylallylphenyle→P-cresyl 85P-methylallylphenyle→
2.6-dimethylphenol 34 2.6
-dimethylallylphenyl ether 2.4.6-drimethylphenol 20 2.4.6-)limethylallylphenyl ether → chlorophenol 77
p-chloroallylphenyl ether Example 2 This example uses PdCf z/CuCf with a molar number of 1:30.
Oxidation of allyl phenyl ether with 2.2 HzO and different amounts of glacial acetic acid and sodium acetate in methanol at 25°C and 50°C.

0.1 g (0.56 mmol) of PdCIlt,
2.87 g (16.8 mmol) of CuC1z 2H1O and sodium acetate were placed in a 100 d round bottom flask, and glacial acetic acid, methanol and 5.6 mmol of allyl phenyl ether were added, and the mixture was heated at 25°C or 50°C. Stir and react for a certain period of time. The products of the reaction were extracted with ether and the results are listed in Table 2.

Table 2 PdCl z/CuCl z with a mole number of 1:30
- Allyl phenyl ether was oxidized with 2FlzO and different amounts of glacial acetic acid and sodium acetate in methanol at 25°C and 50''C.

16.8 16.8 16.8 16.8 O/20 0/20 5/15 0/20 0/20 5/15 0 (24t'!”D 25 98 (4,5 open plane 5 acetal ketal ketone 95 (6 hours) 25 Acetal ketal ketone 51 (1° open) Acetal ketal ketone 100 (pubic bone) 50 Acetal ketal ketone 10100 (4507 Cetal ketal ketone From the data in Table 2 above, the reaction of C in methanol The products are mainly ketals and acetals, of which a small amount of ketal is decomposed into ketone and acetal is not decomposed at all (l/).Also, if sodium acetate or sodium acetate/acetic acid is not added to the reaction mixture, The selectivity of the acetal obtained is good), and the selectivity of the acetal obtained is 68% at 50 °C, and when sodium acetate is added, the selectivity of the acetal obtained is poor, and the selectivity of the acetal obtained is poor when sodium acetate is added. Or with the addition of sodium acetate/acetic acid, the selectivity of acecool at 50°C is lower than at 25°C.

Example 3 This example differs from the above examples in that this example uses a methanol/water mixture as the solvent.

0.1 g (0.56 mmol) of Pd1Z, Cu
Cj! z 2.87 g (16.8 mmol) of 2H20 and 1.38 g (16.8 mmol) of sodium acetate were placed in a 100 d round bottom flask, and 5 d of glacial acetic acid,
Then, different amounts of methanol and water, and 5.6 mmol of allyl phenyl ether were added and reacted with stirring. The products of the reaction were extracted with ether and the results are listed in Table 3.

Table 3 PdC1z /CuCj! Allyl phenyl ether was oxidized with methanol aqueous solutions in different proportions of z·2HzO and glacial acetic acid and sodium acetate.

50 100 (40 minutes) Acetal ketal ketone 50 99 (2.5 hours) Acetal ketone 19 50 99 (3.5 hours) Ketone phenol 10 90 97 (20 minutes) 15 90 93 (30 minutes) Ketone ketone 39 Phenol 39 3- Phenoxy 20 Propanal (1) The definitions of acetal, ketal and ketone are the same as in Table 2 above.

From the data in Table 3 above, adding water to methanol decreases the reaction rate, but promotes the hydrolysis of ketals and acetals, and the main products obtained are ketones or aldehydes.However, when the amount of water is large, ether Bonds are easily cleaved to produce phenol; the higher the temperature, the easier the bonds are to cleave.

Example 4 This example used different alcohol solvents to oxidize allyl phenyl ether at 50°C.

0.1 g (0.56 mmol) of PdCfz, Cu
2.87g (16.8 mmol) of Cl2.2H20
and sodium acetate L3Bg (16.8 mmol) were placed in a 100 d littermate flask, 20 d of alcohol solvent and 5.6 mmol of allyl phenyl ether were added, and the mixture was stirred and reacted at 50°C. The products of the reaction were extracted with ether and the results are listed in Table 4.

Table 4 PdCj! ! /CuCl! - Allyl phenyl ether was oxidized with 2LO and sodium acetate at 50°C in different alcohol solvents.

Methanol 100 (40 minutes) Acetal Ketal Ketone 2-Propanol 100 (2 hours) Ketone 3-propanal Tert-butanol 100 (2 hours) Ketone 3-propanal (i) Definitions of acetal, ketal and ketone are as in Table 2 above. It's the same.

From the data in Table 4 above, the higher the alcohol series, the lower the reaction rate, but the higher the aldehyde selectivity of the obtained product.

Example 5 In this example, the amount of sodium acetate used and the reaction temperature were varied and the effects on the reaction were observed.

0.1 g of PdCj2 Z (0.56 mmF-/
L/), Cu (2.87g of J z '2H20 (
16.8 mmol) and sodium acetate in a 100 d littermate flask, 20 m tert-butanol, and 5.
Add 6 mmol of allyl phenyl ether and stir to react. The products of the reaction were extracted with ether and the results are listed in Table 5.

Table 5 PdCl z/CuCI! X ・2RzO
When allyl phenyl ether was oxidized with sodium acetate and tert-butanol, the effect of changes in the amount of sodium acetate and reaction temperature on the reaction. Reactions with excellent rate and selectivity can be obtained.

Example 6 The purpose of this example is to show that the method of the present invention can also be applied to allyl phenyl ethers having substituents on the benzene ring.

0.0 g of PdCl. 1 g (0.56 mmol), 2.87 g (16.8 mmol) of CuClz.2H20 and 1.0 g (16.8 mmol) of sodium acetate. 1 g (13.
4 mmol) in a 100 d littermate flask, 20 d
of tert-butanol and 5.6 mmol of various allyl phenyl ethers having substituents on the benzene ring,
Stir and react at ℃.

The products of the reaction were extracted with ether and the results are listed in Table 6.

ketones (i) The definition of ketone is the same as in Table 2 above.

Based on the data in Table 5 above, the method of the present invention is based on acetic acid. 2, 4.61
Limethylallylphenyl ether p-chloroallylphenyl ether raw nail stand 1 translation
3-(2,6-dimethylphenoxy)propanal 712,6-dimethylphenoxyacetone 2
72,4.6-Dolimethylphenoxyacetone 433
-(o-chlorophenoxy)propanal 850
-chlorophenoxyacetone methylphenoxy)propanal p-methylphenoxyacetone

Claims (1)

[Claims] 1. Allyl phenyl ether or allyl phenyl ether having a substituent on the benzene ring is subjected to an oxidation reaction in an alcohol solvent in the presence of a palladium salt complex compound and an oxidizing agent to produce 3-phenoxypropanal-based Methods of manufacturing compounds. 2. Allyl phenyl ether or allyl phenyl ether having a substituent on the benzene ring is treated with a palladium salt complex compound, an oxidizing agent, an organic acid alkali metal salt, and/or
Or perform an oxidation reaction in an alcohol solvent in the presence of an acid,
A method for producing a 3-phenoxypropanal compound. 3. Palladium salt complex compound is PdCl_2, PdB
r_2PdSO_4, Pd(NO_3)_2, Li_2
PdCl_4, Na_2PdCl_4 and K_2PdC
3. A method according to claim 1 or 2, characterized in that the method is selected from the group consisting of l_4. 4. Oxidizing agent is CuCl_2・2H_2O, CuCl_2
, CuCl, Cu(NO_3)_2, CuBr_2, C
uBr, CuSO_4, parabenzoquinone, HPA(H
3. The method according to claim 1 or 2, characterized in that it is selected from the group consisting of H_2O_2 and tert-butyl peroxide. 5. Claim 2, wherein the organic acid alkali metal salt is selected from the group consisting of sodium acetate, potassium acetate, sodium propionate, potassium propionate, sodium butyrate, potassium butyrate, sodium benzoate, and potassium benzoate. Method described. 6. The method of claim 2, wherein said acid is selected from the group consisting of glacial acetic acid, propionic acid, butyric acid, benzoic acid, hydrochloric acid, phosphoric acid, sulfuric acid and nitric acid. 7. Alcohol solvent is methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-
3. A process according to claim 1 or 2, characterized in that the alcohol is selected from the group consisting of butanol, tert-butanol, 1,2-ethylene glycol, 1,3-ethylene glycol and mixtures of the alcohols and water.