JPS634818B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides a method for producing an N-substituted amino alcohol compound in which an epoxide compound and a primary amino compound or a secondary amino compound are reacted.
The present invention relates to a method for producing an N-substituted amino alcohol compound that uses a Lewis acid as a catalyst to significantly improve yield, time required for reaction, occurrence of side reactions, etc. As is well known, the reaction between an epoxide compound and a primary amino compound or a secondary amino compound is an addition reaction of an amine to an epoxy group, and the reaction is generally carried out in the presence or absence of a solvent. This reaction has a slow reaction rate, a low yield, and when an electron-withdrawing substituent that lowers the electron density is bonded to the nitrogen atom of the amino group, or when the nitrogen atom of the amino group is bonded to an electron-withdrawing substituent that reduces the electron density. If the substituent causes steric hindrance, there are problems such as significantly poor reactivity. For example, when glycidyl methacrylate and amine are reacted to produce addition polymerization monomers used in dental composite resins, adhesives, etc., conventionally, glycidyl methacrylate and amine are reacted in a solvent such as methanol or by using a solvent. However, as mentioned above, this reaction inherently has a low yield, the reaction rate is low, and the reaction takes a long time, so side reactions such as polymerization occur during the reaction, further reducing the yield. However, there were problems such as a tendency to reduce the The present inventors have studied various methods for producing N-substituted amino alcohol compounds in good yield by reacting epoxide compounds such as glycidyl methacrylate with primary amino compounds or secondary amino compounds. ZnCl ₂ , SnCl ₂ , SnCl ₄ , FeCl ₃ , TiCl ₃ , which function as electron pair acceptors;
TiCl ₄ , AlCl ₃ , CuCl, CuCl ₂ , SbCl ₅ , BF ₃・
When a Lewis acid such as CH ₃ OH, BF ₃ .(C ₂ H ₅ ) ₂ O, etc. is used as a reaction catalyst, the reaction between an epoxide compound and an amino compound is specifically promoted, resulting in the formation of an N-substituted amino alcohol compound. The present invention has been completed based on the finding that it can be produced with good yield and that the above problems can also be solved. That is, the present invention provides a method for producing an N-substituted amino alcohol compound in which an epoxy group of an epoxide compound shown by the following reaction formula A is reacted with a primary amino group or a secondary amino group of an amino compound.
A Lewis acid is used as a catalyst. The present invention will be explained in detail below. In the present invention, epoxide compounds include ethylene oxide, propylene oxide, 2.
Any of alkyl oxides and substituted alkyl oxides such as 3-epoxybutane, glycidyl derivatives such as glycidyl methacrylate and glycidyl acrylate, and other compounds having an epoxy group in the molecule can be used. Further, as the amino compound, a primary amino compound and a secondary amino compound are used. Primary amino compounds include monoalkylamines such as methylamine and ethylamine; aniline; halogen atoms, methoxy groups, ethoxy groups and other alkoxy groups, hydroxyl groups, carboxyl groups, carbonyl groups,
Any compound having a primary amino group in the molecule, such as an aromatic amino compound having a substituent such as an acyl group, can be used. Further, as secondary amino compounds, dialkylamines such as dimethylamine and diethylamine; diphenylamine;
N-alkylaniline such as N-methylaniline;
In addition, aromatic amino compounds having substituents such as a halogen atom, methoxy group, ethoxy group, other alkoxy group, hydroxyl group, carboxyl group, carbonyl group, or acyl group on the phenyl group have a secondary amino group in the molecule. Any compound can be used. In the present invention, the above-mentioned epoxide compound is reacted with a primary amino compound or a secondary amino compound, and the intended purpose can be achieved by using a Lewis acid as a catalyst at this time. It is something. As this Lewis acid, for example,
_ZnCl2 , _SnCl2 , _SnCl4 , _FeCl3 , _TiCl3 , _TiCl4 ,
AlCl ₃ , CuCl, CuCl ₂ , SbCl ₅ , BF ₃・CH ₃ OH,
Inorganic salts that function as electron pair acceptors such as BF ₃ .(C ₂ H ₅ ) ₂ O and derivatives thereof can be suitably used. Note that these Lewis acids may be used alone or in combination of two or more.
Further, the amount of Lewis acid added is preferably 0.01 to 0.1 mol per 1 mol of the epoxide compound. More preferably, it is 0.02 to 0.06 mol. The reaction can be carried out in a solvent or without the use of a solvent. As the solvent, a wide variety of commonly used solvents can be used, and esters such as ethyl acetate and alcohols such as methanol and ethanol are particularly suitable. Since the reaction of the present invention proceeds rapidly, there is no need to heat it to a particularly high temperature, and it is generally carried out at a relatively low temperature of -30 to 100°C, particularly -10 to 50°C, in order to avoid side reactions. preferable. The reaction is usually substantially complete within 3 to 8 hours;
Stirring accelerates the reaction. Accordingly, the present invention provides a method for producing an N-substituted amino alcohol compound in which an epoxide compound and a primary or secondary amino compound are reacted, and by using a Lewis acid as a catalyst, the reaction proceeds extremely smoothly. At the same time, the reaction conditions become milder and the yield becomes significantly higher. Moreover, the reaction time is also much shorter than before. Therefore, even if the conventional method yields almost zero due to steric hindrance, the method of the present invention allows the desired product to be obtained in high yield. Furthermore, even when producing compounds that tend to undergo side reactions such as polymerization during the reaction with conventional methods, resulting in a significant decrease in yield, the method of the present invention allows for short reaction times and mild reaction conditions. Since it is a compound, side reactions etc. can be effectively prevented and the target compound can be produced in high yield. Furthermore, many of the Lewis acids used as catalysts are inexpensive and post-treatment is simple, making this a very effective manufacturing method for industrial mass production. Hereinafter, the present invention will be explained in more detail with reference to Examples. Example 1 Glycidyl methacrylate 1.42g (10mmol)
and 1.23 g (10 mmol) of o-anisidine at 50°C in the presence of 0.06 g (0.4 mmol) of FeCl ₃ as a catalyst.
After stirring for 1 hour, 1.94 g of the target compound 3-
(2-methoxyphenylamino)-2-hydroxypropyl methacrylate was obtained. Yield 78% Comparative Example 1 A reaction was carried out under the same conditions as in Example 1 except that FeCl ₃ was not added, but the reaction did not proceed and the yield was 0%.
It was hot. Comparative Example 2 A reaction was carried out under the same conditions as Comparative Example 1, but with a reaction time of 10 hours. In this case the yield is 12%
It was hot. As is clear from the above results, according to the method of the present invention, the target substance could be obtained with a yield of 78%, whereas in the case of Comparative Example 1, in which no Lewis acid was used, almost no yield was obtained. The reaction does not proceed and the reaction time
Even when the reaction time was 10 hours, the yield was only 12% as shown in Comparative Example 2, thus confirming that the reaction yield and reaction time were significantly improved by using a Lewis acid as a catalyst. It was done. Examples 2 to 22 10 mmol of glycidyl methacrylate and 10 mmol of each amine shown in the table below were combined with the Lewis acid catalyst shown in the table below.
The reaction was carried out in the presence of 0.4 mmol at a reaction temperature of 50°C.
The results are shown in the table below. Further, for comparison, a case where no catalyst was used was shown in Comparative Example 3.

【table】

[Table] Comparative example 3
Example 23 2.20 g (50 mmol) of ethylene oxide and 4.66 g (50 mmol) of aniline were dissolved in 20 ml of methanol, and 0.27 g of zinc chloride was added as a Lewis acid catalyst.
After adding g (2 mmol), the mixture was reacted at 0° C. for 3 hours. Next, the resulting reaction mixture was filtered and the solvent was distilled off. N
-5.49 g of phenylethanolamine was obtained. yield
80% Example 24 2.90g (50mmol) of propylene oxide and N
- 5.36 g (50 mmol) of methylalinine was dissolved in 20 ml of methanol, and 0.3 g (2 mmol) of ferric chloride was added thereto as a Lewis acid catalyst, followed by reaction at room temperature for 3 hours. After the resulting reaction mixture was filtered, the solvent in the liquid was distilled off. By distilling the obtained residue and collecting the distillate at 262℃,
6.17 g of -phenylamino-2-butanol was obtained. Yield 75% Example 25 7.21 g (0.1 mol) of 2,3-epoxybutane and o
- 12.31 g (0.1 mol) of anisidine was placed in an eggplant-shaped colben, 0.5 g of zinc chloride was added, and the mixture was reacted at 50°C for 1 hour. The reaction mixture obtained then is SiO ₂
- adsorbed on the column, eluted with benzene, and from the second fraction O-methoxyphenylamino-2-
14.27 g (yield 73.1%) of butanol was obtained.

Claims (1)

[Scope of Claims] 1. A method for producing an N-substituted amino alcohol compound by reacting an epoxide compound with a primary amino compound or a secondary amino compound, characterized in that a Lewis acid is used as a reaction catalyst.
A method for producing a substituted amino alcohol compound. 2 Lewis acid is ZnCl ₂ , SnCl ₂ , SnCl ₄ , FeCl ₃ ,
_TiCl3 , _TiCl4 , _AlCl3 , CuCl, _CuCl2 , _SbCl5 ,
The manufacturing method according to claim 1, which is BF ₃ .CH ₃ OH or BF ₃ .(C ₂ H ₅ ) ₂ O.