JPS6227058B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for purifying tertiary amines. More specifically, formaldehyde and/or formaldehyde derivatives remaining in a tertiary amine obtained by reductively methylating a primary or secondary amine with formaldehyde and formic acid or formaldehyde and hydrogen are heated to 80 to 150°C under acidic conditions. The present invention relates to a method for purifying a tertiary amine, which is characterized by:

Methods for producing tertiary amines under relatively mild conditions include a method using formaldehyde and formic acid (Org Synth.Coll.Vol P723), and a method using formaldehyde and hydrogen (Org Reactions.
Vol4P174) and the like are well known, but when implementing these methods, it is common to use a large excess of formaldehyde for the purpose of suppressing by-products and speeding up the reaction rate. However, there is no suitable means for separating the excess formaldehyde from the product, which usually results in a heavy purification burden and a low final yield. Unlike ordinary drugs, it is particularly difficult to separate formaldehyde because (a) Formaldehyde has an equilibrium relationship with paraformaldehyde, which has completely different physical properties, and (b) It exhibits a complex gas-liquid equilibrium with water, methanol, etc. , (c) urea, amide, amine,
It is possible that methylol adducts or Schiff bases are formed in equilibrium with active hydrogen such as active methylene, but this remains a matter of speculation.

On the other hand, formaldehyde has problems such as mucous membrane irritation, and its remaining in products is socially unacceptable.

The present inventors have conducted intensive studies on a method for separating reaction products from unreacted or excess formaldehyde or formaldehyde derivatives (hereinafter referred to as "formaldehydes") when producing tertiary amines using formaldehyde as a methylation source. As a result, we have arrived at the present invention.

Known 3 using formaldehyde as a methylation source
In the production method for primary amines, when separating tertiary amines,
For the purpose of neutralizing acids used as reagents or catalysts, or for separating tertiary amines, use a large excess of alkali metal hydroxides such as sodium hydroxide or potassium hydroxide, or alkali metals such as sodium carbonate or potassium carbonate. It is common to treat with carbon salts. Although these treatments can sufficiently achieve the above-mentioned neutralization and/or separation functions, they are not intended to remove formaldehyde, so the removal effect is not sufficient. Therefore, the present inventors conducted intensive studies on methods for removing formaldehyde from tertiary amines, and found that formaldehydes remaining in tertiary amines can be effectively removed by heating to 80 to 150°C under acidic conditions. I discovered that.

That is, if the reaction solution after the reaction is acidic, the reaction solution is left as is or an acid is added to it, or if the reaction solution is neutral or basic, an acid is added to make the reaction solution acidic and then heat treatment is performed.

Examples of acids used in the present invention include organic acids such as formic acid, acetic acid, and propionic acid, and inorganic acids such as sulfuric acid and hydrochloric acid. Preferably, formic acid, acetic acid, hydrochloric acid, etc. are used, and formic acid is most preferably used.

The amount of acid to be used depends on the amount of amine present in the reaction solution, but it is necessary that at least the system is acidic, and it is preferable to adjust the pH to 6.5 or less.

The heating time and heating temperature vary depending on the type of tertiary amine and the amount of formaldehyde, but in general, it is heated until the liquid temperature reaches 120 to 150 °C by concentration under normal pressure.
Preferably, the reaction is carried out. However, if the tertiary amine is a compound that is susceptible to hydrolysis or if there is a small amount of formaldehyde present, the
In some cases, this objective can be achieved by concentrating at 110°C under normal or reduced pressure.

Although the heating time cannot be specified because it varies depending on the heating temperature, the operation may be stopped when the reaction is substantially completed.

Formaldehydes that can be removed in the present invention include derivatives that can reversibly generate formaldehyde, such as formaldehyde, paraformaldehyde, methylol form of urea, and methylol form of amide. In the case of derivatives, for example, formaldehyde is decomposed and removed from the methylol form of urea or the methylol form of amide.
When the target tertiary amine has this functional group, it has the effect of improving the yield of the target tertiary amine.

Among the methylol forms of tertiary amines having such functional groups, the methylol form of tertiary amines having a cyclic amide group in particular can be demethylolated as shown in the following formula, and the desired tertiary amine can be obtained in good yield. , the method of the present invention can be applied more effectively.

In the present invention, the formaldehyde and/or formaldehyde derivatives remaining in the tertiary amine used in the heat treatment under acidic conditions are mainly those obtained by the reaction obtained by a normal tertiary amine manufacturing method using formaldehyde as a methylation source. Refers to what is contained in the liquid.

The reaction solution is, for example, one in which a primary or secondary amine, formic acid, and formaldehyde are reacted in water and/or alcohol at a temperature of 60°C to reflux for 3 to 12 hours, or the amine or a salt of the amine is reacted in the presence of formaldehyde. Below, there is a reaction solution that is reduced with hydrogen in the presence of a catalyst such as palladium.

These reaction solutions can be subjected to heat treatment under acidic conditions in the method of the present invention after a portion of the solvent and/or formaldehyde has been removed by concentration under normal pressure or reduced pressure.

Furthermore, it is of course possible to subject formaldehyde and/or formaldehyde derivatives contained in the crude product of tertiary amine separated from the above reaction solution to heat treatment under acidic conditions in the method of the present invention.

Examples of primary or secondary amines that can be used as raw materials for producing tertiary amines in the present invention include alkylamines such as ethylamine, hexylamine, and lauramine, alkyldiamines such as ethylenediamine, hexamethylenediamine, and undecadiamine, and cyclohexyl amines, side chain aminos such as 1,611-triaminoundecane, aralkylamines such as benzylamine and phenethylamine,
Alicyclic amines such as piperidine and pyrrolidine, α
- Any amine that can be reductively methylated with formaldehyde and formic acid or formaldehyde and hydrogen to produce a tertiary amine, such as polyfunctional amines that have an amide group at the same time as a primary amine such as amino-ε-caprolactam. It may be similar.

After the reaction is completed, a conventional method can be used to separate the tertiary amine from the reaction mixture. For example, after neutralizing the reaction mixture with an alkaline aqueous solution such as sodium hydroxide or ammonia, the separated tertiary amine is separated by liquid separation, or extracted from the alkaline aqueous solution with a water-insoluble organic solvent such as chloroform or trichlene. Examples include methods.

The present invention will be explained in more detail below using Examples.

Example 1 128.2 g of α-amino-ε-caprolactam, 257.1 g of a 35% aqueous formalin solution, 90% aqueous formalin in a 2 three-necked flask equipped with a reflux tube, a thermometer, and a stirrer.
A mixture of 255.5 g of formic acid aqueous solution and 200 g of water was charged, and after reacting at 80°C for 8 hours, the mixture was concentrated under normal pressure until the liquid temperature reached 135°C.

The residue was dissolved in 300 ml of 20% aqueous sodium hydroxide solution and extracted three times with 500 ml of chloroform.

After the chloroform layer was dehydrated, chloroform was distilled off under reduced pressure. The residue was distilled under reduced pressure to obtain 123.6 g of α-dimethylamino-ε-caprolactam as a fraction with a bp of 126 to 130°C/3 mmHg. The yield was 79.1%.

The amount of formaldehyde contained in the obtained α-dimethylamino-ε-caprolactam was determined using the Schiff reagent method (“Formaldehyde” edited by Minoru Imoto et al. (1965).
It was quantified at 25ppm (2013) p409).

Example 2 α-Amino-ε-
128.2 g of caprolactam, 156.8 g of 88% formic acid and 500 ml of water were charged and stirred at 100°C. 172 g of an aqueous suspension containing 60 g of paraformaldehyde was added dropwise at a rate of gentle reflux. After the completion of the dropwise addition, the mixture was heated and stirred for 3 hours, and then concentrated under normal pressure until the liquid temperature reached 125°C.

The residue was treated in the same manner as in Example 1 to obtain 144.2 g of α-dimethylamino-ε-caprolactam.
The yield was 92.3%. Further, the formaldehyde content was 5 ppm.

Example 3 10 g of α-dimethylamino-N-methylol-ε-caprolactam, 10 g of 90% formic acid and 100 ml of water were added to a 300 ml two-necked flask equipped with a distillation device and a thermometer and heated.

After distilling under normal pressure until the liquid temperature rose to 125°C, the mixture was returned to room temperature and made basic by adding 10 ml of a 10% aqueous sodium hydroxide solution.

After extraction twice with 50 ml of chloroform, the chloroform layer was dehydrated, chloroform was removed under reduced pressure, and then distilled under reduced pressure to obtain 7.9 g of α-dimethylamino-ε-caprolactam as a fraction with a bp of 128-130°C/3 mmHg. The yield was 94.2%.

Further, the formaldehyde content was 5 ppm or less.

Example 4 Paraformaldehyde was added to the same apparatus as in Example 2.
Prepare 60g, 156.8g of 88% formic acid and 300ml of water.
Stirred at 100°C. 200 g of an aqueous solution containing 58.1 g of hexamethylene diamine at a rate of gentle reflux.
was dripped. After the dropwise addition was completed, the mixture was heated and stirred for 3 hours, and then concentrated under normal pressure until the liquid temperature reached 125°C. residue
500ml after dissolving in 122g of 28% ammonia aqueous solution
Extracted with trichlene three times.

After the trichlene layer was dehydrated, the trichlene was distilled off under reduced pressure. The residue was distilled under reduced pressure,
N・N・N′・ as a fraction of bp113℃/18mmHg
N'-tetramethylhexamethylenediamine 78.3g
I got it. The yield was 91.1%. Further, the formaldehyde content was 5 ppm or less.

Example 5 A reaction was carried out in the same manner as in Example 4 using 93.2 g of undecamethylene diamine instead of hexamethylene diamine, followed by distillation under reduced pressure.
N・N・N′・ as a fraction of bp126℃/1mmHg
N′-Tetramethylundecamethylenediamine
114.0g was obtained. The yield was 93.1%.

Further, the formaldehyde content was 5 ppm or less.

Example 6 Paraformaldehyde was added to the same apparatus as in Example 2.
Prepare 90g, 88% formic acid 235.2g and water 200ml,
Stirred at 100°C.

In the same manner as in Example 2, 250 g of an aqueous suspension containing 101 g of 1,6,11-triaminoundecane was added dropwise, reacted for 3 hours, and then concentrated under normal pressure until the temperature of the solution reached 125°C. 28% ammonia water to the residue
After adding 360 g, it was extracted three times with 500 ml of trichloride. After dehydrating the trichlene layer and removing the trichlene under reduced pressure, it was distilled under reduced pressure to bp144℃/1mm.
132.1 g of 1,6,11-tris(dimethylamino)undecane was obtained as a Hg fraction. Yield is 92.5
It was %.

Further, the formaldehyde content was 5 ppm or less.

Example 7 After reacting for 8 hours in the same manner as in Example 1, concentrated hydrochloric acid
After adding 180 g, the mixture was concentrated under reduced pressure. The residual crystals were washed with 100 ml of methanol and then dried.
The crystals were dissolved in 300 g of a 20% aqueous sodium hydroxide solution, and then extracted three times with 500 ml of trichlene. It was treated in the same manner as in Example 1 to obtain 119.5 g of α-dimethylamino-ε-caprolactam. yield
It was 76.5%.

Further, the formaldehyde content was 15 ppm or less.

Example 8 Paraformaldehyde was added to the same apparatus as in Example 2.
Prepare 60g, 88% formic acid 104.5g and water 300ml
Stirred at 100°C. hexamethylene diamine
A mixed aqueous solution of 58.1 g of acetic acid, 65 g of acetic acid, and 100 ml of water was added dropwise at a rate of gentle reflux. After the dropwise addition was completed, the mixture was heated and stirred for 3 hours, and then concentrated under normal pressure until the liquid temperature reached 120°C. The residue was treated in the same manner as in Example 4 to obtain 76.5 g of N.N.N'.N'-tetramethylhexamethylenediamine. The yield was 89.0%. Further, the formaldehyde content was 10 ppm or less.

Comparative Example 1 24 equipped with cooling pipe, thermometer and stirrer
α-Amino-ε-caprolactam in a neck flask
A mixture of 128.2g, 35% formalin aqueous solution 257.1g, 90% formic acid aqueous solution 255.5g (molar ratio: 1.0/3.0/5.0) and water 200g was added, and the mixture was heated at 80°C for 8 hours to complete the reaction. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in 360 g of 44.4% aqueous sodium hydroxide solution and extracted three times with 500 ml of chloroform.

After dehydrating the chloroform, the chloroform was distilled off under reduced pressure. The residue was distilled under reduced pressure to 126-130
C/3 mmHg fractions were collected to obtain 123.1 g of α-dimethylamino-ε-caprolactam.

The yield from α-amino-ε-caprolactam is
It was 78.8%.

Further, the formaldehyde content was 1.22%.

Claims (1)

[Claims] 1. Heating the formaldehyde and/or formaldehyde derivatives remaining in the tertiary amine obtained by reductively methylating a primary or secondary amine with formaldehyde and formic acid or formaldehyde and hydrogen to 80 to 150°C under acidic conditions. A method for purifying a tertiary amine, characterized by: