JP2728950B2 - Method for producing 3,5-dibenzylsalicylic acid derivative - Google Patents

Description

The present invention relates to an inexpensive 3,5-dibenzylsalicylic acid derivative useful as an intermediate of a color developer for pressure-sensitive copying paper or a developer for thermal paper. Production method.

[Conventional technology]

Conventionally, as a method for producing the 3,5-disubstituted salicylic acid, it has been known to produce the corresponding nuclear-substituted phenol and carbon dioxide by a Kolbe-Schmitt reaction.

For example, 3,5-di (α, α-dimethylbenzyl) salicylic acid disclosed in JP-B-49-10856 is obtained by using di (α, α-dimethylbenzyl) phenol obtained from phenol and α-methylstyrene as a raw material. Being manufactured.

On the other hand, some alkylation reactions of salicylic acid are known. For example, a method of reacting salicylic acid with isobutanol to obtain tert-butylsalicylic acid (Experimental Chemistry Lecture, Vol. 18, p. 30 (1950) Maruzen), reacting 2 mol of 1-phenylethanol with 1 mol of salicylic acid,
A method for obtaining a mixture with [α-methyl-4 ′-(α-methylbenzyl) -benzyl] salicylic acid and / or 3,5-di (α-methylbenzyl) salicylic acid
100493, 62-96449) and the like.

[Problems to be solved by the invention]

In general, a salicylic acid-based compound as a developer for pressure-sensitive paper and thermal paper is excellent in clarity of a color image, storage stability, and the like. On the other hand, pressure-sensitive paper has poor water resistance, such as a delay in the degree of coloring due to lack of compatibility with the capsule oil in which the colorless pigment is dissolved, and the color image disappears with water. Various attempts have been made to compensate. For example, a method of introducing an aromatic substituent or the like into a salicylic acid skeleton to make up for the above-mentioned disadvantage has been frequently used.

In the method of introducing such a substituent, a method using phenols as a starting material is typical as described above.

However, in this method, since the reaction of the portion into which the carboxyl group is introduced is carried out at a high temperature and a high pressure, there is a problem in the production, and there is a problem that it is generally expensive.

On the other hand, the method of condensing 1-phenylethanols with salicylic acid is produced as various mixtures, and is separated as a metal salt of a mixture of mono-substituted salicylic acid and / or di-substituted salicylic acid by a complicated operation. There is a problem that it is difficult to obtain reproducibility in quality such as coloring performance and storage stability of the color developing sheet.

[Means for solving the problem]

The present inventors have intensively studied to solve the above problems. As a result, they found that a 3,5-disubstituted salicylic acid useful as a color developer can be selectively produced by reacting salicylic acid with an aluminum chloride catalyst among Friedel Crafts catalysts using an inexpensive benzyl compound. The present invention has been completed.

That is, the present invention relates to 1) salicylic acid and a compound represented by the general formula (I) Or general formula (II) (Wherein, R ₁ and R ₂ represent a hydrogen atom, a halogen atom,
And up to 12 alkyl groups, aralkyl groups, aryl groups and cycloalkyl groups, wherein R ₃ is a hydrogen atom or a carbon atom
Wherein the benzyl compounds represented by the following formulas (1) to (4) are reacted in the presence of an aluminum chloride catalyst: 3,5-dibenzylsalicylic acid derivative.

The process of the present invention is selected by reacting 1 mole of salicylic acid with 2 to 3 moles of various benzyl alcohols or benzyl alkyl ethers or 1 to 1.5 moles of dibenzyl ethers in the presence of a catalytic amount of aluminum chloride. Various benzyl groups can be introduced at the 3- and 5-positions of salicylic acid, and surprisingly, side reactions other than those described above, such as the formation of mono-substituted dibenzylsalicylic acid and benzyl condensates due to dimerization of benzyl compounds, are suppressed. I understood.

On the other hand, when the reaction of the present invention was carried out using, for example, zinc chloride or p-toluenesulfonic acid as other Lewis acid catalyst, mineral acid catalyst and organic acid catalyst, the reaction became almost resinous in most cases. Isolation of the compound was difficult (see comparative examples).

Thus, the method of the present invention has been found in a situation which cannot be expected as a method for selectively producing a di-substituted salicylic acid compound.

As the 3,5-dibenzylsalicylic acid derivative that can be produced by the method of the present invention, 3,5-dibenzylsalicylic acid, 3,5-
Di (p-methylbenzyl) salicylic acid, 3,5-di (o-
Methylbenzyl) salicylic acid, 3,5-di (m-methylbenzyl) salicylic acid, 3,5-di (p-ethylbenzyl)
Salicylic acid, 3,5-di (o-ethylbenzyl) salicylic acid, 3,5-di (p-isopropylbenzyl) salicylic acid, 3,5-di (p-tert-butylbenzyl) salicylic acid, 3,5-di (p -Cyclohexylbenzyl) salicylic acid, 3,5-di (o-phenylbenzyl) salicylic acid, 3,5
-Di (p-benzylbenzyl) salicylic acid, 3,5-di (o-chlorobenzyl) salicylic acid, 3,5-di (m-chlorobenzyl) salicylic acid, 3,5-di (p-chlorobenzyl) salicylic acid, 3 5,5-di (p-bromobenzyl) salicylic acid, 3,5-di (m-bromobenzyl) salicylic acid, 3,5-di (o-bromobenzyl) salicylic acid, 3,5-
Di (p-fluorobenzyl) salicylic acid, 3,5-di (2,3
-Dimethylbenzyl) salicylic acid, 3,5-di (2,4-dimethylbenzyl) salicylic acid, 3,5-di (2,5-dimethylbenzyl) salicylic acid, 3,5-di (3,4-dimethylbenzyl) salicylic acid 3,5-di (3,5-dimethylbenzyl) salicylic acid, 3,5-di (2,4-diethylbenzyl) salicylic acid, 3,5-di (3-methyl-4-ethylbenzyl) salicylic acid, Examples include, but are not limited to, 5-di (2,4-dichlorobenzyl) salicylic acid.

The method of the present invention will be described in detail. The benzyl nucleus of the starting benzyl alcohols, benzyl alkyl ethers and dibenzyl ethers has an unsubstituted or C1-C12 alkyl group, an aralkyl group, an aryl group. It has at least one group, cycloalkyl group or halogen atom such as chlorine, bromine or fluorine at the o, m and p positions. Further, in various benzyl alkyl ethers, the alkyl group of the alkyl ether has a fast reaction when the number of carbon atoms is 4 or less, and the esterification reaction does not occur,
The desired product is easily obtained. Further, when the number of carbon atoms is 4, that is, a butyl group, the tert-butyl group tends to have a slow reaction.

Therefore, benzyl alcohols used in the present invention,
Benzyl alkyl ethers or dibenzyl ethers include benzyl alcohols such as benzyl alcohol, o-methylbenzyl alcohol, m-methylbenzyl alcohol, p-methylbenzyl alcohol,
-Ethylbenzyl alcohol, m-ethylbenzyl alcohol, p-ethylbenzyl alcohol, o-isopropylbenzyl alcohol, pn-propylbenzyl alcohol, p-tert-butylbenzyl alcohol, p-
Nonylbenzyl alcohol, o-phenylbenzyl alcohol, p-cyclohexylbenzyl alcohol, p-
(Benzyl) benzyl alcohol, 2,3-dimethylbenzyl alcohol, 2,4-dimethylbenzyl alcohol,
2,5-dimethylbenzyl alcohol, 2,6-dimethylbenzyl alcohol, 3,4-dimethylbenzyl alcohol,
3,5-dimethylbenzyl alcohol, 2,4-diethylbenzyl alcohol, 3-methyl-4-ethylbenzyl alcohol, 2,5- (dimethylbenzyl) benzyl alcohol, p-chlorobenzyl alcohol, o-chlorobenzyl alcohol, p -Bromobenzyl alcohol, m-fluorobenzyl alcohol, and the like, but are not limited thereto.

As benzyl alkyl ethers, benzyl methyl ether, benzyl ethyl ether, benzyl isopropyl ether, benzyl-n-butyl ether, o-methyl benzyl methyl ether, o-methyl benzyl ethyl ether, o-methyl benzyl isobutyl ether,
m-methylbenzyl methyl ether, m-methylbenzylethyl ether, m-methylbenzylisopropyl ether, o-ethylbenzylmethylether, o-ethylbenzylethylether, o-ethylbenzylisopropylether, p-ethylbenzylmethylether,
p-ethylbenzyl methyl ether, p-ethylbenzyl isopropyl ether, p-ethylbenzyl-n-butyl ether, o-isopropylbenzyl ethyl ether, p-isopropylbenzyl ethyl ether, pn
-Propylbenzylethyl ether, p-tert-butylbenzylethylether, p-tert-butylbenzylisopropylether, p-tert-octylbenzylethylether, p-nonylbenzylmethylether, p-
Dodecyl benzyl methyl ether, p-phenylbenzyl methyl ether, o-phenylbenzyl isopropyl ether, p-cyclohexyl benzyl ethyl ether, 2,3-dimethylbenzyl methyl ether, 2,4-dimethylbenzyl methyl ether, 2,5-dimethylbenzyl Methyl ether, 2,6-dimethylbenzyl methyl ether, 3,4-dimethylbenzyl methyl ether, 3,5-dimethylbenzyl methyl ether, 2,4-diethylbenzyl methyl ether, 3,4-dimethylbenzyl ethyl ether, 3, 5-dimethylbenzyl ethyl ether, 2,3-dimethylbenzyl isopropyl ether, 2,4-dimethylbenzyl-n-propyl ether, 3,4-dimethylbenzyl-n-butyl ether, 2,4-dimethylbenzyl-sec
-Butyl ether, 3,5-dimethylbenzyl-n-amyl ether, 2,4-diethylbenzylethyl ether,
3,5-diethylbenzyl isopropyl ether, 2,3-diethylbenzyl-n-butyl ether, 2,4-diisopropylbenzyl methyl ether, 3,5-diisopropylbenzyl ethyl ether, 3-methyl-4-ethylbenzyl methyl ether, -Methyl-5-tert-butylbenzyl methyl ether, p-methylbenzylmethyl ether, p-methylbenzylethyl ether, p-methylbenzyl-n-propyl ether, p-methylbenzylisopropyl ether, p-methylbenzyl-n- Butyl ether, p-methylbenzyl-sec-butyl ether, p-methylbenzyl isobutyl ether, p-chlorobenzyl methyl ether, p-fluorobenzyl isopropyl ether, o-bromobenzyl methyl ether, m-bromobenzyl methyl Examples include ethers, but are not limited thereto.

As dibenzyl ethers, dibenzyl ether,
Di (o-methylbenzyl) ether, di (m-methylbenzyl) ether, di (p-methylbenzyl) ether, di (o-ethylbenzyl) ether, di (m-ethylbenzyl) ether, di (p-ethyl) Benzyl) ether, di (o-isopropylbenzyl) ether, di (pn-propylbenzyl) ether, di (p-tert
-Butylbenzyl) ether, di (p-nonylbenzyl) ether, di (o-phenylbenzyl) ether,
Di (p-cyclohexylbenzyl) ether, di [p-
(Benzyl) benzyl] ether, di (2,3-dimethylbenzyl) ether, di (2,4-dimethylbenzyl) ether, di (2,5-dimethylbenzyl) ether, di (2,6-dimethylbenzyl) ether , Di (3,4-dimethylbenzyl) ether, di (3,5-dimethylbenzyl)
Ether, di (2,4-diethylbenzyl) ether, di (3-methyl-4-ethylbenzyl) ether, di [2,
5- (dimethylbenzyl) benzyl] ether, di (p
-Chlorobenzyl) ether, di (o-chlorobenzyl) ether and the like, but are not limited thereto.

The amount of each benzyl compound used is 2 to 3 moles of benzyl alcohols or benzyl alkyl ethers and 1 to 1.5 moles of dibenzyl ethers per mole of salicylic acid.

Aluminum chloride used as a catalyst may be anhydrous or one having water of crystallization, and the amount used is 0.02 to 50 mol% based on salicylic acid. Preferably 0.1 to 1 in consideration of economy
It is in the range of 0 mol%. The reaction temperature is in the range of 50 to 180C, preferably 70 to 160C. The reaction time is between 1 and 20 hours.

In the method of the present invention, a solvent may be used if necessary. As the solvent, those inert to the reaction, for example, aromatic hydrocarbons such as benzene, toluene, xylene, 1,2-dichloroethane, 1,1,2-trichloroethane,
Halogenated hydrocarbons such as monochlorobenzene, acetic acid,
Organic acids such as propionic acid can be used. When these solvents are used, the content is preferably 30 volumes / weight or less in consideration of the economy of the raw materials.

As a general method of practicing the present invention, a predetermined amount of salicylic acid, a benzyl compound and a catalyst are simultaneously added, and the temperature is raised and the reaction is performed at a predetermined temperature, or the reaction is performed while the benzyl compound is added dropwise during the reaction. Is also good. Water or alcohol generated as the reaction proceeds is trapped outside the system. If necessary, a trace amount of water or alcohol remaining in the system is removed from the system with nitrogen. After the completion of the reaction, if crystals are precipitated, they can be isolated as crystals. When it is in a dissolved state, the solvent can be distilled off, and the crystals can be taken out with a suitable recrystallization solvent.
Means for knowing the progress of the reaction and the purity of the isolated product can be determined by analysis by high performance liquid chromatography.

[Action and effect]

The present invention uses a general-purpose raw material and can easily produce useful 3,5-dibenzylsalicylic acid by using an aluminum chloride catalyst. It can be supplied to the field at low cost. This greatly contributes to the development of industry.

〔Example〕

 Hereinafter, the present invention will be described in detail with reference to examples.

Example 1 6.9 g (0.05 mol) of salicylic acid, benzyl alcohol 1
1.9 g (0.11 mol) and aluminum chloride 6 as catalyst
0.32 g of hydrate was charged into a glass reactor, and the reaction temperature was 110 ~
The mixture was condensed at 135 ° C. for 5 hours. On the way, generated water was removed from the system by passing a nitrogen gas through. Crystals were precipitated during the reaction, and at the end of the reaction, most of the crystals were in a precipitated state as crystals. After the completion of the reaction, 50 ml of acetic acid was added, and the mixture was dissolved by heating and slowly cooled to precipitate crystals. This was filtered to obtain crude crystals, which were further recrystallized with acetic acid to obtain 8.2 g of white needle-like crystals. This was confirmed to be 3,5-dibenzylsalicylic acid from the following analysis results. 51.5% yield
The results of melting point, elemental analysis and NMR analysis were as follows.

Mp 160 to 162 ° C. Elemental analysis _{(C 12 H 18 O) C} H Calculated (%) 79.22 5.17 Analytical values (%) 79.12 5.84 NMR measurement solvent acetone D ₆ Measurement temperature room temperature Example 2 Salicylic acid 6.9 g (0.05 mol), p-methylbenzyl methyl ether 17.7 g (0.13 mol), chlorobenzene 20 ml
Then, 0.45 g of anhydrous aluminum chloride as a catalyst was charged into a glass reactor and reacted for 8 hours under reflux of chlorobenzene. After the reaction, when cooled, white crystals precipitated, which were filtered and dried to obtain 12.3 g of 3,5-di (p-methylbenzyl) salicylic acid (yield: 71.0%). This was repeated twice with acetic acid to obtain a pure white needle-like product having a melting point of 185 to 187 ° C.

Elemental analysis _{(C 23 H 22 O 3)} C H Calculated (%) 79.74 79.26 analysis (%) 6.40 6.56 Example 3 Salicylic acid 6.9 g (0.05 mol), dibenzyl ether 1
Using 0.3 g (0.052 mol) and 0.065 g of anhydrous aluminum chloride as a catalyst, the same procedure as in Example 1 was carried out to give crude 3,5
-11.0 g (69.2% yield) of dibenzylsalicylic acid was obtained.

Examples 4 to 7 To 6.9 g (0.05 mol) of salicylic acid and 0.32 g of aluminum chloride hexahydrate as a catalyst, 0.11 mol of various benzyl compounds were used as shown in Table 1, and the same procedure as in Example 1 was carried out. −
A dibenzylsalicylic acid derivative was synthesized.

Comparative Example 1 The same reaction was carried out in the same manner as in Example 1 except that anhydrous zinc chloride was used instead of aluminum chloride. As a result, no reaction product was obtained as crystals. When the reaction composition was analyzed by high performance liquid chromatography, it was a mixture composed of 7 to 8 components containing 28.5% of 3,5-dibenzylsalicylic acid as a target substance.

Comparative Example 2 In the reaction of Example 2, p-
When 1.2 g of toluenesulfonic acid was used in the same manner as in Comparative Example 1, the reaction product was a mixture of 5 to 8 components.

Claims (1)

(57) [Claims] (1) salicylic acid and a compound of the formula (I) Or general formula (II) (Wherein, R ₁ and R ₂ represent a hydrogen atom, a halogen atom,
And up to 12 alkyl groups, aralkyl groups, aryl groups and cycloalkyl groups, wherein R ₃ is a hydrogen atom or a carbon atom
Wherein the benzyl compounds represented by the following formulas (1) to (4) are reacted in the presence of an aluminum chloride catalyst: (3) a process for producing a 3,5-dibenzylsalicylic acid derivative.