JPS61291549A - Production of aromatic secondary amino compound - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for medicines, etc., industrially and advantageously in high yield, by reacting an aniline with an alcohol in the presence of a catalyst consisting of a specific metal oxide. CONSTITUTION:An aniline expressed by formula I (X is H, halogen, lower alkyl or lower alkoxy; n is an integer 1-3) is reacted with an alcohol expressed by the formula ROH (R is alkyl or phenyl) in the presence of a catalyst consisting of two kinds of metal oxides selected from Mg, Ca, Al, Zn, Cd and Fe to afford the aimed compound expressed by formula II. The composition of the two kinds of catalysts in the above-mentioned catalyst varies with the kinds of the metals, but the molar ratio is within 0.01-1:1 range. MgO-ZnO, MgO-Al2O3, etc., may be cited as the preferred combination in the catalyst. The catalyst is readily handled, and the aimed compound is obtained in good yield at a relatively low temperature without forming by-products, e.g. high polymer tarry materials and ethers.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing aromatic secondary amino compounds.

That is, the present invention provides anilines represented by the general formula (I): (wherein X represents a hydrogen atom, a /S rogen atom, a lower alkyl group, or a lower alkoxy group, and n is an integer of 1 to 3); General formula (■): OH(II
) (wherein R represents an alkyl group or a phenyl group) and an alcohol represented by magnesium (Mg )
, calcium (Ca), aluminum (A/), zinc (
General 2〇〇): (in the formula, X%n and R represents the same meaning as above).

It is generally well known that anilines and alcohols are reacted in the presence of various catalysts to perform N-alkylation and N-arylation. For example, the sulfuric acid catalytic method (
Unit Process Inorganic Chemistry, page 850.

(1958), concentrated phosphoric acid catalyst method (U.S. Pat. No. 299,131)
1), the alumina catalyst method (Hemisches Teentralplatt, p. 2579, 1955), and the like. However, all of these methods not only result in a decrease in the yield of the target product due to the production of polymeric tar-like substances as by-products, but also, in particular, in the sulfuric acid and concentrated phosphoric acid catalyst methods, handling of the catalyst, separation of the product, and Purification is difficult and production on an industrial scale is a very complicated process that requires expensive equipment.Also, in the alumina catalyst method, ethers in particular are produced as by-products, resulting in the need for equipment in the alcohol recovery and separation process. costs become even more expensive. Another method is the magnesia catalyst method (US Pat. No. 3,558,706), but in this case, the reaction temperature is high and the upper conversion rate is low, which is industrially disadvantageous.

The present inventors have demonstrated the ability to selectively N-monoalkylate anilines and N-
As a result of examining the method of monoarylation, Mg%Ca
, A/, Zn, Cd.

It was discovered that a method using two metal oxides selected from Fe as catalysts has excellent catalytic activity, is easy to prepare and handle, and is economical and industrially advantageous. The method of the present invention has been completed.

The metal oxide catalyst used in the method of the present invention is Mg, Ca
, A4 Zn, and Cd%re. In this case, the composition ratio of the two oxides in the catalyst varies depending on the type of metal, but the molar ratio is α0
selected from the range of 1 to 1:1.

Examples of preferred combinations of these catalysts include MgO-Z
nO1Mg0-Zn0l@, MgO-Cd0. C
aO-Fe2O3.

Zn0-F ego@, Cd0-F e203%
CdOA/101 is mentioned.

Although there are various methods for preparing these catalysts, typical examples include alkoxide hydrolysis method and alkali coprecipitation method.

For example, in the alkoxide hydrolysis method, the alkoxide of the component element (for example, magnesium methoxide in the Mg 0-Alx Os system, dehydration in aluminum isoglobo
etc.) dissolved in t-ethyl alcohol.

After adding water and refluxing to complete hydrolysis, water and alcohol are distilled off and calcined in air at 300-800°C for 2-5 hours.

In addition, in the coprecipitation method, soluble salts of required component elements (e.g., nitrate, calcium nitrate, zinc nitrate, aluminum nitrate, etc.)
Mix the aqueous solutions of and add alkali to obtain a precipitate. The obtained precipitate was thoroughly washed with water, dried, and heated to 500 to 8
Bake at 00°C for 2-5 hours.

The fired product obtained by firing in this way is not crushed,
Prepare the catalyst by tabletting. Further, in this case, the catalyst may or may not be supported on the carrier.

Although the desired reaction method can be achieved using either a pressure contact method or a gas phase contact method, the gas phase contact method is more preferred since the reaction can be carried out continuously.

Further, the molar ratio of the alcohol to the aniline may be at least 1 times α by mole, but is preferably 15 to 10 times by mole.

Further, the reaction temperature is preferably in the range of 150 to 450°C, and the reaction is carried out in the presence or absence of hydrogen gas, carbon dioxide gas, argon gas, helium gas, or nitrogen gas.

Catalysts whose activity has decreased due to reaction can be regenerated by supplying heated air.

After the completion of the reaction, the aqueous layer produced as a by-product is separated and the oil layer is fractionated to obtain the desired product, but if necessary, it is also possible to further purify it by methods such as recrystallization and column chromatography.

The aromatic secondary amino compound obtained in this way is
It is useful as an intermediate in the general chemical industry, especially in pharmaceuticals, agricultural chemicals, etc.

Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1: To an aqueous solution consisting of 5 parts by weight of magnesium nitrate and 6 parts by weight of zinc nitrate, 1 to 1 times the theoretical amount of aqueous ammonia was dropped under stirring to obtain a precipitate. This precipitate was thoroughly washed with water and dried.
After baking at 6℃ for 5 hours, crush and sieve to obtain particles with a particle size of 60 to 80.
Obtained Metsuyu Catalyst. A part of a glass reaction tube for gas phase contact with a diameter of 5 wg and a length of 5 G scratches was filled with 5 g of this catalyst α and heated to 350°C.Next, nitrogen gas was introduced into the reaction tube for 20 d/day.
10μ of a mixture of 1 part by weight of aniline and 5 parts by weight of methyl alcohol is poured into the evaporator at a speed of 10 minutes. Injected. The generated mixed vapor comes into contact with the catalyst in the reaction tube, reacts, and is distilled out. The distilled reactants were collected with dioxane and the products were analyzed using gas chromatography.
Only N-methylaniline was detected, and the conversion rate was 24.5-9 based on aniline.

Example 2: A catalyst was prepared in the same manner as in Example 1 from an aqueous solution consisting of 95 parts by weight of magnesium nitrate and 5 parts by weight of aluminum nitrate, and the reaction was carried out under the same conditions. Reactions were also carried out using other catalysts in the same manner. The results are also shown in Table 1.

Example 3: A catalyst was prepared in the same manner as in Example 1 from an aqueous solution consisting of 4 parts by weight of cadmium nitrate and 1 part by weight of aluminum nitrate, and anilines and alcohols were added to Table 2 under the same conditions as in Example 1. The reaction was performed by changing it to the one shown. The results are shown in Table 2.

Example 4: Example 1 except that phenol is used as the alcohol
When the reaction was carried out in the same manner as above, N-7 enylaniline was obtained in high yield.

Patent applicant: Nihon Nohyaku Co., Ltd. (1 other person)

Claims (1)

[Claims] General formula (I): ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, X represents a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group, and n is 1 to An integer of 3) and an alcohol represented by general formula (II): ROH (II) (wherein R represents an alkyl group or a phenyl group) are combined with magnesium (Mg),
Calcium (Ca), aluminum (Al), zinc (Z
General formula (III) characterized in that the reaction is carried out in the presence of a catalyst consisting of two metal oxides selected from n), cadmium (Cd), and iron (Fe): ▲Mathematical formula, chemical formula, table, etc. ▼(III) A method for producing an aromatic secondary amino compound represented by the formula (wherein X, n and R have the same meanings as above).