JPS60222437A - Production of 1-phenyl-2-alkanone - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate raw material of agricultural chemicals and pharmaceuticals, in a few reaction steps, economically in an industrial scale, by reducing 1-hydroxy-1-phenyl-2-alkanone. CONSTITUTION:The objective compound of formula II can be prepared by reducing a 1-hydroxy-1-phenyl-2-alkanone of formula I (R is 1-4C alkyl; X and Y are H, OH, halogen, amino, 1-4C alkyl, alkoxy, or together with a part of the benzene ring form a 5-7-membered heterocyclic group containing 1-2 O atoms), e.g. 1-hydroxy-1-(4-hydroxyphenyl)-2-propanone, etc. The reduction can be carried out e.g. by reacting a metallic powder such as zinc powder, iron powder, etc. with a mineral acid such as sulfuric acid, or reacting the compound with hydrogen in the presence of a catalyst such as palladium, platinum, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing l-phenyl-2-alkanones. l-phenyl-2-alkanones are
It is useful as an intermediate raw material for agricultural chemicals and medicines.9 For example, 1-
(4-hydroxy-3-methoxyphenyl)-2-propanone and 1-(3,4-dimethoxyphenyl)-2
-Propanoneha.

It is an important compound as a raw material for the production of L-α-methyldopa, which is useful as a hypotensive agent.

Conventionally, several proposals have been made regarding methods for producing these compounds.

For example, British Patent No. 1119612 i1:
1-(3+4-dimethoxyphenyl)propylene is reacted with a peroxide such as peracetic acid, and the resulting diol-type product is treated with an acidic substance such as zinc chloride to form 1-(3,4-dimethoxyphenyl). A method for obtaining phenyl)-2-propanone is disclosed. However, this method has problems in that the yield of the treatment step with acidic substances is low, and the peroxide used is explosive, so special care must be taken when handling it. This is not a desirable method.

Also, co-educational magazine, 74,975 (195'4) Id,
A method has been disclosed in which l -(3,4-methylenedioxyphenyl)propylene is treated with formic acid and hydrogen peroxide, and the resulting diol ester product is treated with sulfuric acid. The yield of the process is low,
Since the peroxide used is explosive, it is prone to problems such as the need to be especially careful when handling it.
This cannot be said to be an industrially preferable method.

In addition, 1%, in Kaisho 49-100044, ]-(3,
A method is disclosed in which 4-dimethoxynoenyl)propylene is reacted with peracetic acid or performic acid and the obtained 1-('3,4-dimethoxy)-1-oxo-2-propanol is treated with sulfuric acid. However, the method is also described in the aforementioned Pharmaceutical Journal, 7
It has the same drawbacks as 4.975 (lc+54) and cannot be said to be an industrially preferred method.

Also, in the Journal on American Chemical Society (JAC8), 77, 700 (1955),
-(3,4-dimethoxyphenyl)-2- A method for producing propanone is disclosed. However, in order to prevent the hydrolysis of sodium ethoxide, this method requires that the process using it be carried out in a system from which water has been strictly removed.

The low yield of the hydrolysis process is that the raw material is still 3゜4-
Considering the steps necessary to produce dimethoxyphenylacetonitrile itself from readily available chemical raw materials, there are problems such as an increase in the total number of steps, and this method cannot be said to be industrially preferable.

In view of these circumstances, the present inventors have determined that l-phenyl-2
- Conducted nine types of intensive research with the aim of developing industrially advantageous production methods for alkanones. As a result, we have arrived at the present invention.

According to the invention.

formula %formula% (11 (In the formula, R represents an alkyl group having 1 to 4 carbon atoms.

X and Y each represent a hydrogen atom, a hydroxyl group, a halogen atom, an amine group, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group; may form a 5- to 7-membered heterocyclic ring. ) wherein X, Y and R1'i have the same meanings as above. ) A method for producing l-phenyl-2-alkanones represented by

Next, nine aspects of the present invention will be described in detail.

l-hydroxy-1-phenyl-2 used in the present invention
- Specific examples of alkanones include 1-hydroxy-1
-(4-hydroxyphenyl)-2-propanone, 1-
Hydroxy-1-(3-methoxy-4-hydroxyphenyl)-2-propanone, 1-hydroxy-1-(3,
4-dihydroxyphenyl)-2-propanone, 1-hydroxy-1-(2-hydroxyphenyl)-2-propanone, 1-hydroxy-ni(C-methoxyphenyl)-2-7'lovanone, l-hydroxy-1 -(3,4
-dimethoxyphenyl) to 2-propanone.

1-human 0#cy 1-(3,4-methylenedioxyphenyl)-2-propanone, l-hydroxy-1-(
2-methoxyphenyl)-2-propanone.

l-hydroxy-1-(3-methyl-4-hydroxyphenyl)-2-propanone, 1-hydroxy-1-(3
-chloro-4-hydroxyphenyl)-2-propanone, 1-hydroxy-1-(3-amino-4-hydroxyphenyl)-2-propanone, 1-hydroxy-1-(
Mention may be made of 4-hydroxyphenyl)-2-butanone and 1-hydroxy-1-(4-hydroxyphenyl)-2-pentanone.

As a method for reducing 1-hydroxy-1-phenyl-2-alkanones, any known reduction method can be appropriately employed.

Examples include a method in which mineral acids such as sulfuric acid and hydrochloric acid are applied to metal powders such as zinc, iron, cobalt, and tin, a method using phosphorus, and a catalytic reduction method in which hydrogen is applied in the presence of a catalyst such as palladium or platinum. Examples include, but are not particularly limited to.

In the method of combining metal powder and mineral acid.

For example, 1 to 3 grams of metal powder is added to 1 mole of 1-hydroxy-1-phenyl-2-alkanone as a raw material, and an aqueous solution of 3 to 6 N mineral acid equivalent to 2 to 10 ordinary leaves is added. React at 50-100°C for 10-30 hours, and after cooling, benzene, toluene, xylene, ethyl ether,
The target 1-phenyl-2-alkanones can be obtained by extracting MTBK with an organic solvent and distilling the extracted solvent layer.

In the case of the catalytic reduction method, the amount corresponds to 491 moles of 1-hydroxy-1-phenyl-2-alkanone as a raw material.

Using a catalyst of 0.001~Ol gram atom, the solvent O1~
5 after adding a small amount of mineral acid if necessary.

Hydrogen pressure o5-8Ky/caa', 0 at 60-100℃
．． The reaction may be carried out for 5-3 hours. Examples of the solvent in this case include water, lower alcohols such as methanol and ethanol, and organic acids such as acetic acid.

Examples of catalysts used include platinum and palladium. Among these, palladium is preferred and usually used.

1 to 15 wt% was supported on activated carbon. It is convenient to use so-called palladium carbon (=pcb/a).After one reaction is completed, the catalyst is separated, and when water is used as a solvent, organic compounds such as benzene, toluene, xylene, ethyl ether, MIBK, etc. The target cophenylated 2-alkanone can be obtained by extracting with a solvent and distilling the extracted bath agent layer, or by directly distilling the liquid Ii when alcohol or organic acid is used as the solvent. .

Next, examples of the present invention will be shown.

In addition, the yield of the product on each side, 1-phenyl-2-alkanone, is a value calculated according to the following formula.

In all of the examples shown below, gas chromatography after one reaction revealed that the raw material was 99% of the charged amount.
It was confirmed that those in charge and above responded.

To Example 1・13 1-Hydroxy-1-phenyl-2-alkanones as raw materials 0. ], 0 mol and 120 m of 5N-HCU
7! was charged into all the reactors, and 252 (0,
2 grams atom) and heated at 80° C. for 24 hours.

After cooling, the reaction solution 9 was filtered, the i:J solution was extracted with ethyl ether, and the product 1-phenyl-2-alkanones contained in the ethyl ether layer was quantified by gas chromatography. The results are shown in Table 1.

Examples 14-21 1-hydroxy-1-phenyl-2-alkanones as raw materials 0. 'l O mol and 5 wt% pa/c 2. O
g and 200m7 of ethanol! into the reactor.

Add sulfuric acid 'TM O, 1trdt, hydrogen pressure 1.5 K
The reaction was carried out at y/crla, e o °C for 2 hours with stirring. After cooling the reaction solution, the pa/a of the catalyst was separated by 1,
The target 1-phenyl-2-alkanones produced in P acid were quantified by gas chromatography. The results are shown in Table 2.

Table 1 Continuation of Table 1 Table 2 Continuation of Table 2

Claims (1)

[Claims] Formula (wherein R represents an alkyl group having 1 to 4 carbon atoms; X and Y each represent a hydrogen atom, a hydroxyl group, a halogen atom, an amine group, an alkyl group having 1 to 4 carbon atoms, or represents an alkoxy group, and X and Y may form a 5- to 7-membered heterocycle having 1 to 2 oxygen atoms together with a part of the benzene ring. A formula characterized by reducing -1-phenyl-2-alkanones (wherein X, Y and R have the same meanings as above)
A method for producing 1-phenyl-2-alkanones represented by