JPS5830339A - New selective oxidizing system and production of at least one kind of aromatic ortho-dihydroxylated or ortho- dialkoxylated derivative - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a new selective oxidation system and its application for the preparation of ortho-dihydrokimolated or ortho-dialkoxylated aromatic derivatives.

These latter orthohydroxylated or orthozoalkoxylated aromatic conductors clearly form compounds of great importance for the chemical and chemical-related industries, especially for the pharmaceutical industry. Unfortunately, the methods and techniques used to date for the synthesis of such compounds are complex, difficult to implement industrially, and even desirable - conductors are produced in insufficient yields. This often results in only being able to obtain

There is an increasing need for a simple and inexpensive method for obtaining ortho-dihydrokimolated or orthozoalkoxylated aromatic derivatives from readily available raw materials and in yields sufficient for use on an industrial scale. There is.

Therefore, the applicant undertook a thorough investigation into the selective oxidation of monohydroxylated aromatic derivatives with the aim of obtaining the desired derivatives.

The reagents used hitherto for the oxidation of monohydroxylated aromatic derivatives give rise to para-hydroxylated derivatives, with ortho-dihydroxylated derivatives being only possible secondary products. Furthermore, with these reagents, oxidation generally does not stop at the ortho-dihydroxylated derivative stage, but proceeds to the formation of ortho-quinone derivatives, which are unstable and cannot be easily isolated.

An essential object of the present invention is to obtain ortho-dihydroxylated (or orthozoalkoxylated) aromatic derivatives without forming para-dihydroxylated (or parazoalkoxylated) aromatic derivatives from monohydroxylated aromatic derivatives. The objective is to find a dredging system that can be selectively obtained.

This purpose is 1! This was achieved by a new selective oxidation system consisting essentially of L) metallic copper, b) cuprous salts, cupric salts or mixtures thereof and C) molecular oxygen.

Although the mechanism of action of this system is still not fully understood, it is currently believed that molecular oxygen is activated by cuprous salts present in the system or resulting from the reduction of cupric metal by metallic copper. It is thought that oxidation occurs in J:.

The cupric salt or cupric salt is preferably cupric chloride or cupric chloride.1. Moreover, the molecular oxygen may be atmospheric oxygen, pure oxygen, or a mixture thereof.

The oxidation system of the present invention can be used in the presence of a solvent that well dissolves copper salts in the form of complexes, especially cyanoaliphatic solvents,
Advantageously, the solvent is preferably used in the presence of acetonitrile, but the solvent is optionally a chlorinated organic solvent, preferably 1
- may be mixed with methylene chloride, dichloroethane and mixtures thereof.

The invention therefore relates to the application of the oxidation system as defined above, more precisely at least one aromatic ortho-dihydroxylated derivative (or pyrocatechol) or at least one aromatic ortho-dialkoxylated derivative. In the method for producing a derivative, each aromatic derivative containing at least one PII phenolic hydroxyl group and having at least one vacant position ortho to this group is subjected to the action of the oxidation system defined above, and then the obtained aromatic derivative is at least one aromatic ortho-dihydrokimolated conductor (or pyrocatechol) or at least one aromatic ortho-dialkokidyl, characterized in that the intermediate cupric pyrocatechol is hydrolyzed or alkylated; The present invention relates to a method for producing a chemical derivative.

The simplest starting hydroxylated aromatic derivative is of course phenol, but more particularly all mono- or polysubstituted phenolic or polyphenolic compounds, whether monocyclic or polycyclic, find use in the present invention. Within the scope of the starting compounds, the only condition is clearly that at least one of the positions ortho to the hydroxyl group is vacant.

As non-limiting examples, the following may be mentioned:

Namely, 2,4-sheet-tort-butylphenol, 6-hydroxyacetophenone, p-human gastric phenylacetic acid and its esters, p-hydroxyacetophenone, p-hydroxypropiophenone, p-hydroxybenzoic acid and its esters, m- Hydrobenzoic acid and its esters, p-hydroxybenzaldihyde, m-hydroxybenzaldehyde, vanillin, 6-hydroxy-5-methoxybenzoic acid and its esters,
p-hydroxyben, phenone, and estrone.

The presence of metallic copper is essential. This is because the presence of this metallic copper allows the formation of cupric pyrocatechol, a stable compound that can be precipitated and isolated in monohydrate form. Therefore, metallic copper is required in at least a stoichiometric amount relative to the starting hydroxylated aromatic derivative (for 1 mole of starting derivative, there must be as many Durham atoms of copper as there are phenolic hydroxyl groups in which at least one ortho position is vacant). ), preferably in excess.

If the starting aromatic derivative contains substituents capable of reacting with one element or other elements of the oxidizing system, and this includes, for example, acid groups capable of reacting with metallic copper (in particular carboxyl or hydroxyl groups without vacant ortho positions), then ), this group may be blocked, if desired and within the scope of possibility, for example by forming an ester in the case of a carboxyl group. In the absence of such blocking, it may be advisable to operate in the presence of a larger amount of the reactable element than is normally required.

Depending on the position of the substituents on the starting hydroxylated aromatic derivative that is oxidized, and thus the number of vacant ortho positions (relative to the phenolic hydroxyl group), one or more different cupric pyrocatechols are formed. I know it will happen.

That is, if the starting aromatic derivative is a monohydroxylated aromatic derivative substituted, for example, in the meta position, two cupric pyrocatechols each corresponding to one of the two vacant ortho positions are present. is formed.

Furthermore, it is found that the use of catalytic amounts of cuprous or cupric salts is sufficient to obtain the desired oxidation, and of course even larger amounts of salt can be used with entirely satisfactory results.

The oxidation step is advantageously carried out at a pressure greater than or equal to atmospheric pressure, preferably using a dehydrating agent such as molecular sieves or an alkali metal sulfate or alkaline earth metal sulfate such as sodium sulfate, magnesium sulfate or calcium sulfate. Preferably, it is carried out in the presence of salt.

Furthermore, the temperature IW used during the reaction is 0°C and 50'0
It is preferable to vary between.

The hydrolysis reaction of the second step of the process according to the invention is carried out by reducing the acid, which is obtained using, for example, hydrochloric acid or sulfuric acid, sodium chloride hydrosulfite and sodium hydrosulfite-sodium bicarbonate or stannous chloride-hydrochloric acid mixtures, respectively. Alternatively, it may be carried out in an acid-reducing medium.

Acidic media are preferred as they are industrially the least expensive; however, reducing or acid-reducing media are used when the birocatecholate released by the hydrolysis button is highly oxidizing and therefore easily converted to ortho-quinone. That's T1.

Another alkylation reaction possible in the second step of the process of the invention is the formation of alkyl sulfates 1-, chloride, bromide, tosylate and mesylate, generally in the presence of a base such as sodium carbonate. This is accomplished by the alkylated derivative that can be chosen, the nature of the alkyl group depending of course on the final ortho-dialkoxylated aromatic derivative desired.

Finally, the process of the invention has the additional advantage that the blocked starting human tetraxylated aromatic derivative can be recovered in the form of copper carbonate, for example by simple hydrolysis of the copper carbonate with a methanol-water mixture under reflux. It can be seen that it gives

The following production examples are shown to specifically explain the present invention.

Example 1 6 from 2,4-di-tart-butylphenol
．． Preparation of 5-tert-butylpyrocatechol.

-No.''≦L size-Preparation of cupric 6,5-di-tert-butylpyrocatechol according to the following reaction scheme % () 5.51 2,4-
Tert-butylphenol (T), 5f (commercial) powdered steel, 0.61 g of anhydrous cupric chloride and 4z molecular sieves (6A) were stirred at 0°C for 6 hours and then placed in an oxygen atmosphere (large Stir at 20° C. for 18 hours in atmospheric pressure. Then, 10 ml of water are added and, after stirring for a further 15 minutes, the resulting precipitate is filtered and washed with 60 ml of acetonitrile containing 10% water. Pyrocatechol cupric(n) is then extracted from the precipitate by thorough washing with an aprotic organic solvent (e.g. ethyl ether, methylene chloride or chloroform), the filtrate is evaporated and then The desired cupric pyrocatechol (ID) is obtained with a yield of 92 fJ).

2nd step Production of 6,5-tart-pyrocatechol according to the following reaction scheme % () Pre-processing An ether solution of cupric pyrocatechol (II) obtained in the culm is colored red in the organic phase. The mixture is then decanted and the ether phase is removed until it is decolorized (6,5-tert-butylbenzoquinone-1 partially formed during hydrolysis). , 2 is reduced) with dilute hydrochloric acid solution and then washed with water.The ether phase is then evaporated and the residue is dried in vacuo in the presence of P, 0.0. Thus, 6.5-tert-butylpyrocatechol has the same physicochemical properties as a pure sample of 5-tert-butylpyrocatechol.
．． 1 Te (yield: 84 Te) of the compound is obtained.

2 Example 2 Production of 2.6-dihydroxyacetophenone and 6.4-dihydroxyacetophenone from 6-hydroxyacetophenone First step 6-acetylpyrocatechol cupric and 4-acetylpyrocatechol cupric according to the following reaction scheme Preparation of Copper 80 Ttl of dry acetonyl and 4 [41 of 6-hydroxyacetophenone (lV+, 6?) in 3 ml of methylene chloride.
(commercial) powdered steel and 0.11 cupric chloride are stirred at room temperature in an oxygen atmosphere (atmospheric pressure) for 70 hours. The solvent was then evaporated in vacuo and the residue
+nA' methanol (80%)-water (20%) mixture and then heated to reflux for 1 hour. The resulting precipitate is then filtered and washed with 40 ml of methanol. After evaporating the filtrate, 21% of unreacted 6-hydroxyacetophenone is recovered. The precipitate contains two types of cupric pyrocatechol (
V) and (VI) are formed from a mixture of metallic copper and copper oxide.

2nd step 2,6-dihydroxyacetophenone and 6.
The precipitate obtained in the pre-production process of 4-dihydroxyacetophenone was mixed with 61 sulfur sulfite (Na2S2).
40m containing O4) and 2z sodium bicarbonate
Stir vigorously in the aqueous solution of 1. The resulting mixture was then acidified with 10% sulfuric acid to a pH of about 4, extracted with ether, dried over the ether phase over magnesium sulfate, filtered, and the filtrate was evaporated to 2.5 P ( Yield 7
1%) of 2,6-dihydroxyacetophenone (VI)
and 6.4 - Sublimate this mixture. In this way, 60 units of 2,6-dihydroxyacetophenone (VT)
(melting point 98°C to 99°C) and 10qI) 5.
4-dihydroxyacetophenone (VI5 (melting point 115)
°C to 116 °C).

Example 6 Preparation of 2,6-dimethoxybenzaldehyde and 6,4-dimethoxybenzaldehyde from 6-hydroxybenzaldehyde 41 6-hydroxybenzaldehyde in 8 Qml dry acetonate) and 40 ml methylene chloride, 5y- powder steel and 0 A mixture of .1y of cupric chloride is stirred at room temperature under an atmosphere of oxygen (atmospheric pressure) for 72 hours. Then 19! il- sodium carbonate and 1
71 of methyl sulfate was added and the mixture was refluxed for 12
Heat for an hour. The mixture is filtered, the filtrate is evaporated, the residue is dissolved in ether, the resulting solution is washed with water, dried over magnesium sulfate, filtered and the solvent is evaporated.

25 2,6-dimethoxybenzaldehyde, 6 6,4-zome) =? The crude product (yield 8
0%) is obtained. By one or the other of the processes according to Example 1 and Example 2, for example also monophenol or 1,2-benzenediol, the methyl ester of -p-hydroxyphenylacetic acid to the methyl ester of 6,4-dihydroxyphenylacetic acid -p-hydroxy Acetophenone to 3.4-dihydroxyacetophenone, -methyl ester color of p-hydroxybenzoic acid 6.4
- methyl ester of dihydroxybenzoic acid, - methyl ester of m-hydroxybenzoic acid Kara 2.3
-di):) Methyl ester of oxybenzoic acid (main product) and methyl ester of 6,4-dihydroxybenzoic acid, -6,4-zolohydroxybenzaldehyde from p-hydroxybenzaldehyde, 2. 6-dihydroxybenzaldehyde (main product) and 6,4-dihydroxybenzaldehyde, -6.4- from vanillin
Dihydroxy-5-methoxybenzaldehyde, methyl ester of -6-hydroxy-5-methoxybenzoic acid to methyl ester of 2,3-dihydroxy-5-methoxybenzoic acid (main product) and 6,4-dihydroxy-5-methoxy Methyl ester of benzoic acid, p-hydroxybenzophenone or c]3,4-dihydroxybenzophenone, monoestrone to 2,6-dihydroxyester l-ryne (main product)
Oyohi 3,4-dihydroxyestrone, -4-methoxyphenol to 1,2-dihydroxy-4-methoxybenzene, -4-chlorophenol to 1,2-dihydroxy-4
-Chlorobenzene.

-2-C4-hydroxyphenyl)-1,3-dioxolane to 2-(3,4-dihydroxyphenyl:]-
]1.3-Zoxolane-2-(4-hydroxy-6-medoxyphenyl)-1
, 6-dioxolane to 2-(4,5-dihydroxy-6-methoxyphenyl)-1,3-dioxolane, -(4-hydroxyphenyl]propanone to (3,4
-dihydroxyphenyl]propanone, 6,4-dihydroxyprobiophenone is obtained from p-hydroxypropiophenone.

Agent Akira Asamura @ Inventor Michiel Langlois France Book Plus César Franck 4 9 Procedural amendment (voluntary) July 22, 1980 To the Commissioner of the Japan Patent Office 1, Indication of the case 1988 Patent Application No. 75071 No. 3, Relationship with the case of the person making the amendment Patent applicant 4, Agent 5-t+l1il: Ordered Nikkan Showa Year Month Day 6, Number of inventions increased by amendment

Claims (1)

Claims: (1) A novel selective oxidation system comprising metallic copper; cuprous salt, cupric salt, or a mixture thereof; and molecular oxygen. (2) The oxidation system according to claim 1, wherein the cuprous salt or cupric salt is cuprous chloride or cupric chloride. (3) An oxidizing system according to claim 1 or 2, in which the molecular oxygen is formed by atmospheric oxygen, pure oxygen or a mixture thereof. (4) Claims further include a cyanaliphatic solvent optionally mixed with a chlorinated organic solvent, and claims wherein the chlorinated organic solvent is selected from among methylene chloride, dichloroethane, and mixtures thereof. Oxidizing systems according to range item 4. (6) A method for producing at least one aromatic ortho-dihydroxymolated or orthozoalkoxylated derivative, comprising at least one phenolic hydroxyl group,
Each aromatic derivative in which at least one of the positions ortho to this group is vacant is subjected to the action of an oxidation system according to one of the preceding claims, and then the cupric pyrocatechol intermediate obtained is A process for producing at least one aromatic ortho-dihydroxylated or orthozoalkoxylated derivative, characterized in that it is hydrolyzed or alkylated. (7) Metallic copper is used in at least a stoichiometric amount relative to the starting hydroxylated aromatic derivative, as claimed in claim 6.
How to follow section. (8) a cuprous or cupric salt is used in a catalytic amount;
A method according to claim 6 or 7. (9) A method according to claim 6, 7 or 8, wherein the oxidation step is carried out under an oxygen pressure of at least 1 atmosphere. (10) A method according to any one of claims 6 to 9, wherein the oxidation reaction is carried out in the presence of a dehydrating agent. (1υ) The dehydrating agent is selected from the group comprising molecular sieves, alkali metal sulfates or alkaline earth metal sulfates. Process according to claim 10. (1) The hydrolysis is carried out in an acid, reducing or acid-reducing medium. (13) The acid, reducing or acid-reducing medium is hydrochloric acid or sulfuric acid, sodium hydrosulfite and sodium hydrosulfite, respectively. Sodium carbonate or stannous chloride
Process according to claim 12, obtained by using a hydrochloric acid mixture. (+4) Any one of claims 6 to 71, wherein the alkylation is carried out in the presence of a base such as sodium carbonate with the aid of alkyl sulfates, chlorides, zolomides, tosylates and mesylates. How to follow section.