JP4332084B2 - Process for producing N-alkyl-substituted aminophenols - Google Patents

Description

  The present invention relates to a method for producing N-alkyl-substituted aminophenols in which aminophenols and aldehydes are subjected to a reductive alkylation reaction.

  N-alkyl-substituted aminophenols are industrially extremely important compounds as intermediates for dyes for heat and pressure sensitive paper, xanthene dyes, fluorescent dyes and the like.

  A method for producing an N-alkyl-substituted aromatic amino compound by reductive alkylation reaction of an aromatic amino compound and aldehydes in the presence of an organic solvent, a reduction catalyst, and hydrogen is known. (See Patent Document 1)

  Conventionally, when reductive alkylation of aminophenols in the presence of an organic solvent, a reducing catalyst and hydrogen, an example of using an aliphatic alcohol as the organic solvent in terms of solubility of the aminophenols, reaction yield, etc. There are many. (Refer to Patent Documents 2 and 3) However, when reductive alkylation is performed using these aliphatic alcohol solvents, N-alkyl-substituted aminophenols, which are products or products in which aromatic rings are nuclear hydrogenated as by-products There has been a problem that a condensate obtained by reacting two molecules with one molecule of aldehyde or a tar component which has become heavier is easily generated. While these by-products cause a decrease in the yield of the target N-alkylaminophenols, for example, when N-alkylaminophenols are purified by distillation, condensates and heavy products are thermally decomposed. And the decomposed product is mixed into N-alkylaminophenols, causing a decrease in purity.

As a method for solving these problems, platinum or palladium catalyst supported on activated carbon is one or more metal elements selected from Group IB, Group IIB, Group IVB, Group VB and Group VIB of the periodic table. Or a catalyst for reduction obtained by supporting activated carbon with one or more metal elements selected from the metal group consisting of lead, tellurium and copper, or one or more selected from the above metal group There is a method of using a reduction catalyst in which the above metal element and palladium are supported on activated carbon. (See Patent Documents 4 and 5) However, it is difficult to completely suppress by-products in these methods.
JP 57-81444 A Japanese Patent Laid-Open No. 3-63249 JP-A-3-232846 JP-A-3-153649 Japanese Patent Laid-Open No. 3-153650

  The present invention relates to a method for producing N-alkyl-substituted aminophenols in which an aminophenol and an aldehyde are subjected to a reductive alkylation reaction, the suppression of the aromatic hydrogenation reaction, and the N-alkyl-substituted aminophenols and aldehydes. An object of the present invention is to provide a production method that suppresses the condensation and heavyization reaction.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have carried out a reductive alkylation reaction between aminophenols and aldehydes, and in the presence of an aprotic polar compound, a nuclear hydrogenation reaction of an aromatic ring. It has been found that the condensation reaction between N-alkyl-substituted aminophenols and aldehydes can also be suppressed, and the present invention has been completed.

That is, the present invention provides an aminophenol selected from o-aminophenol, m-aminophenol, and p-aminophenol and an aliphatic aldehyde in the presence of a reducing catalyst, hydrogen, and an aprotic polar compound. Is a process for producing N-alkyl-substituted aminophenols.

  According to the present invention, it is possible to suppress the nuclear hydrogenation reaction of aromatic rings and the condensation and heavyization reaction of N, N-alkylaminophenols and aldehydes, which are side reactions.

  Examples of aminophenols used in the present invention include o-aminophenol, m-aminophenol, and p-aminophenol.

  Examples of the aldehydes used in the present invention include aliphatic aldehydes such as formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isoamylaldehyde, cyclohexylaldehyde, heterocyclic aldehydes such as furfural, aromatics such as benzaldehyde and p-tolualdehyde. Family aldehydes and the like.

  As the reduction catalyst used in the present invention, any catalyst used for ordinary hydrogenation reaction such as Raney nickel, platinum oxide, copper-chromium oxide, nickel, platinum, palladium, etc. can be used. A supported catalyst, a platinum / alumina supported catalyst, a palladium / carbon supported catalyst, and a palladium / alumina supported catalyst are preferred.

  The amount of the reducing catalyst used in the reaction is not particularly limited, but is 0.006 to 0.6 wt%, preferably 0.03 to 0.3 wt% as a metal atom with respect to aminophenols. When the amount is 0.006 wt% or more, it is preferable from the viewpoint of suppressing the heavy reaction between aminophenols and aldehydes, or aminophenols and ketones, and when the amount is 0.6 wt% or less, nuclear water is added to the aromatic ring. This is preferable in that the addition reaction is suppressed.

  The hydrogen used in the present invention can be supplied to the reaction system at normal pressure, but can also be supplied under pressure.

  Hydrogen is usually supplied in the range of normal pressure to 0.98 MPa, preferably 0.19 to 0.98 MPa.

  It is preferable from the viewpoint of the yield of aminophenols that hydrogen is used in a molar amount of 2 times or more that is a theoretical amount with respect to aminophenols.

  Examples of the aprotic polar compound used in the present invention include N, N-dimethylformamide, N, N-dimethylacetamide, N, N-diethylformamide, N, N-diethylacetamide, dimethyl sulfoxide, 1,3-dimethyl- Examples include 2-imidazolidinone. These aprotic polar compounds also have a function as a reaction solvent.

  In the production method of the present invention, only the aprotic polar compound can be used as a reaction solvent. However, the aprotic polar compound and aliphatic alcohols, aromatic hydrocarbons, saturated hydrocarbons, Mixtures of halogenated hydrocarbons and compounds selected from esters can also be used as the reaction solvent.

  When using the above aprotic polar compounds and compounds such as aliphatic alcohols, aromatic hydrocarbons, saturated hydrocarbons, halogenated hydrocarbons, esters, etc. as the reaction solvent, the aprotic contained in the reaction solvent The concentration of the polar compound is 30% by weight or more, preferably 50% by weight or more.

  When the concentration of the aprotic polar compound contained in the reaction solvent is 30% by weight or more, a nuclear hydrogenation reaction of an aromatic ring as a side reaction, condensation of N, N-alkylaminophenols and aldehydes, and heavy It is preferable because the reaction can be suppressed.

  The reaction solvent is used in an amount of 2 to 12 times, preferably 4 to 10 times the weight of the starting aminophenol. When the amount of the reaction solvent used is 2 times or more, it is preferable in that the condensation reaction between the N-alkyl-substituted aminophenols and aldehydes can be suppressed, and when it is 12 times or less, the load of solvent recovery can be reduced. From the viewpoint of production efficiency.

  By reacting in the presence of the aprotic polar compound, the hydrogenation reaction to the aromatic ring and the condensation reaction with aldehydes can be suppressed.

  Examples of the N-alkyl-substituted aminophenols that are target products of the present invention include N-ethylaminophenol, N-ethylaminophenol, N-propylaminophenol, N-butylaminophenol, N-cyclohexylaminophenol, N-monoalkylaminophenols such as N-benzylaminophenol and N-isopropylaminophenol, N, N-dimethylaminophenol N, N-diethylaminophenol, N, N-dibutylaminophenol, N-ethyl-N-isobutyl N, N-dialkylaminophenols such as aminophenol and N-ethyl-N-isoamylaminophenol are exemplified.

  The reaction temperature is 0 to 100 ° C, more preferably 20 to 50 ° C. A temperature lower than 0 ° C. is not preferable because the reaction rate is remarkably reduced. A temperature higher than 100 ° C. is not preferable because the condensation reaction of N-alkyl-substituted aminophenols with aldehydes is remarkably accelerated, and self-condensation of aldehydes. Is not preferable from the viewpoint of the remarkable progress.

  The reaction pressure is usually in the range of normal pressure to 0.98 MPa, preferably 0.19 to 0.98 MPa.

  In the production of N-alkyl-substituted aminophenols by reacting aminophenols and aldehydes in the presence of a reducing catalyst, hydrogen, and an aprotic polar compound, the purpose is to coexist an organic acid in the reaction system. This is preferable because the production rate of the product can be increased.

  As the organic acid, those having an acid dissociation constant of pka of 3.0 to 5.0 are preferable. Monocarboxylic acids such as acetic acid, propionic acid, lactic acid, valeric acid, benzoic acid, succinic acid, isophthalic acid, terephthalic acid And dicarboxylic acids such as glycolic acid, lactic acid, malic acid and the like. Among organic acids, acetic acid, lactic acid, and benzoic acid are preferable. These organic acids can be used alone or in combination of two or more.

  The addition amount of the organic acid is usually used in a range of 0.01 to 10 mol% with respect to the charged amount of aminophenols, but is preferably used in a range of 1 to 6 mol%.

  The addition amount of the organic acid is 0.01 mol% or more from the viewpoint of reproducibility of the reaction rate, and it is preferably 10 mol% or less from the viewpoint of suppressing the formation of a heavy product.

  Although there is no restriction | limiting in particular in the addition method of an organic acid, The method of adding collectively to a reaction system, the method of adding continuously, the method of adding intermittently, etc. are mentioned.

  If the embodiment of the production method of the present invention is specifically exemplified, for example, aminophenols, an aprotic polar solvent and a reducing catalyst are charged in a reaction vessel, and aldehydes are continuously supplied under hydrogen pressure. Alternatively, a method in which the reaction is performed by supplying them all together, a method in which an aprotic polar compound and a reduction catalyst are charged, and then aminophenols and aldehydes are simultaneously supplied from separate inlets into the reaction system to react. .

  The target product can be recovered from the reaction mixture after completion of the reaction using a known means. For example, when the target product is a liquid at normal temperature, the reduction catalyst can be separated from the reaction mixture by means such as sedimentation or filtration, and then the target product can be recovered by distillation. When the target product is solid at room temperature, the reaction mixture separated from the reduction catalyst can be concentrated as necessary, and cooled to recover the target product crystals that precipitate.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in more detail, this invention is not limited to these Examples.

The liquid chromatography (hereinafter abbreviated as “HPLC”) analysis described in the examples was performed under the following conditions.
1) HPLC analysis conditions:
Column: YMC-PACK ODS-A A-312
Column temperature: 40 ° C
Mobile phase: acetonitrile / water = 2000: 1000 (pH = 5.5)
Detection wavelength: 260 nm

[Example 1]
In a SUS 500 ml autoclave with a stirrer, 32.7 g (0.3 mol) of m-aminophenol, 98.5 g of N, N-dimethylformamide (special grade of Wako Pure Chemical Industries), 0.7 g of benzoic acid, 2% by weight platinum-supported carbon An N, N-dimethylformamide solution 54 containing 50% by weight of isovaleraldehyde was charged with 3.2 g of catalyst (manufactured by NE Chemchem) (containing 50% water) at 30 ° C. and hydrogen pressure 0.8 Mpa. 0.2 g (0.315 mol of isovaleraldehyde) was continuously added over 1 hour. After completion of the addition of isovaleraldehyde, the mixture was kept at the same temperature for 30 minutes, and then 38.2 g of N, N-dimethylformamide solution containing 45% by weight of acetaldehyde (0.39 mol of acetaldehyde) was placed in the autoclave over 1 hour. Added continuously. After completion of the addition, the reaction solution was kept at the same temperature for 180 minutes and then cooled, and 234.4 g of a reaction solution obtained by filtration and separation of the catalyst was analyzed by liquid chromatography. As a result, N-ethyl-N-isoamyl-m-aminophenol was recovered. The production rate of the nuclear hydrogenated product [3- (isoamylamino) -2-hexen-1-one] as a by-product was 0.1%, and the production of condensate was 0.1 % Or less.

[Examples 2 to 5]
Other solvents were examined in place of N, N-dimethylformamide. The results are shown in Table-1.

[Example 6]
In a SUS 500 ml autoclave with a stirrer, 32.7 g (0.3 mol) of m-aminophenol, 98.5 g of N, N-dimethylformamide (special grade of Wako Pure Chemical Industries), 2.2 g of benzoic acid, 3 wt% palladium-supported alumina 2.7 g of a catalyst (manufactured by NE Chemchem) was charged, and 97.1 g of an N, N-dimethylformamide solution containing 50% by weight of n-butyraldehyde under the conditions of 30 ° C. and hydrogen pressure of 0.5 Mpa (n-butyl). Aldehyde 0.66 mol) was continuously added over 2 hours. After completion of the addition, the reaction mixture was kept at the same temperature for 180 minutes and then cooled, and the reaction solution obtained by filtering and separating the catalyst was analyzed by liquid chromatography. As a result, the yield of N, N-dibutyl-m-aminophenol was 92.0. %. The production of the nuclear hydrogenated product [3- (n-butylamino) -2-hexen-1-one] was 0.6%, and the production of the condensate was 0.1% or less.

[Example 7]
The reaction was carried out in the same manner as in Example 7 except that 2.7 g of the 3 wt% palladium-supported alumina catalyst (manufactured by NE. Chemcat) in Example 6 was replaced with 8.1 g of 1% palladium-supported alumina catalyst (manufactured by NE. Chemcat). Carried out. As a result of HPLC analysis, the yield of N, N-dibutyl-m-aminophenol was 95.0%. The production of the nuclear hydrogenated product [3- (n-butylamino) -2-hexen-1-one] was 0.5%, and the production of the condensate was 0.1% or less.

[Example 8]
Except that 2.7 g of the 3 wt% palladium-supported alumina catalyst (manufactured by NE. Chemcat) in Example 6 was replaced with 3.2 g of 2% platinum-supported carbon catalyst (manufactured by NE. Chemcat) (containing 50% water). The reaction was performed as in Example 7. As a result of HPLC analysis, the yield of N, N-dibutyl-m-aminophenol was 97.0%. The production of the nuclear hydrogenated product [3- (n-butylamino) -2-hexen-1-one] was 0.1% or less, and the production of the condensate was 0.5%.

[Comparative Example 1]
In a 500 ml autoclave made of SUS with a stirrer, 32.7 g (0.3 mol) of m-aminophenol, 98.5 g of methanol, and 3.3 g of a carbon catalyst supported on 2% by weight (manufactured by NE Chemchem) (containing 50% moisture) Then, 54.2 g of methanol solution containing 50% by weight of isovaleraldehyde (0.315 mol of isovaleraldehyde) was continuously added over 1 hour under the conditions of 30 ° C. and hydrogen pressure of 0.5 Mpa. After the addition of isovaleraldehyde, the mixture was kept at the same temperature for 30 minutes, and then 38.2 g of methanol solution containing 45% by weight of acetaldehyde and acetic acid (acetaldehyde 0.39 mol, acetic acid 0.01 mol) was continuously taken over 1 hour. Added. After completion of the addition, the reaction solution was kept at the same temperature for 180 minutes and then cooled, and 234.5 g of a reaction solution obtained by filtering and separating the catalyst was analyzed by liquid chromatography. As a result, N-ethyl-N-isoamyl-m-aminophenol was recovered. The rate was 94.0%. The production of the nuclear hydrogenated product [3- (isoamylamino) -2-hexen-1-one] was 1.5%, and the production of the condensate was 1.2%.

[Comparative Example 2]
Comparative Example 1 except that 3.3 g of a 2 wt% platinum-supported carbon catalyst (manufactured by NE. Chemcat) (product containing 50% moisture) was replaced with 2.7 g of a 5% palladium-supported alumina catalyst (manufactured by NE. Chemcat). The reaction was performed as in Example 1. As a result of HPLC analysis, the yield of N-ethyl-N-isoamyl-m-aminophenol was 27.6%. The production of the nuclear hydrogenated product [3- (isoamylamino) -2-hexen-1-one] was 4.0%, and the production of the condensate was 3.0%. Many other unknown peaks were detected.

[Comparative Example 3]
The reaction was carried out in the same manner as in Comparative Example 1 except that the methanol in Comparative Example 1 was replaced with toluene. As a result of HPLC analysis, the yield of N-ethyl-N-isoamyl-m-aminophenol was 23.1%. The production of [3- (isoamylamino) -2-hexen-1-one] was 3.3%, and the production of condensate was 32.2%. Many other unknown peaks were detected.

  The present invention is useful as a method for producing N-alkyl-substituted aminophenols. The N-alkyl-substituted aminophenols obtained by the present invention are useful compounds as intermediates for heat-sensitive / pressure-sensitive paper dyes, xanthene dyes, fluorescent dyes and the like.

Claims (2)

N-alkyl in which an aminophenol selected from o-aminophenol, m-aminophenol, and p-aminophenol is reacted with an aliphatic aldehyde in the presence of a reducing catalyst, hydrogen, and an aprotic polar compound. A method for producing substituted aminophenols. The process according to claim 1, wherein an organic acid selected from acetic acid, propionic acid, lactic acid, valeric acid, benzoic acid, succinic acid, isophthalic acid, terephthalic acid, glycolic acid, lactic acid, and malic acid is further coexisted.