JPH0341056A - Production of beta-hydroxyamino compound - Google Patents

Abstract

PURPOSE:To obtain a beta-hydroxyamino compound in good yield by reacting an epoxy compound with an amine in the presence of a specific amount of more of a hydrogen halide or ammonium salt thereof. CONSTITUTION:An epoxy compound expressed by formula I or II (R1 to R4 are H, halogen, alkyl, aryl, alkoxy or aryloxy; Z ir 3C or 4C alkylene) is reacted with an amine expressed by formula III (R5 is H, alkyl or aryl) at -50 to +150 deg.C to afford the objective compound expressed by formula IV or V. In the reaction, a hydrogen halide or ammonium salt thereof in a molar amount of >=1.1 times, preferably >=2 times based on the epoxy compound is used. The objective substance is useful as a raw material, etc., such as 1- aminopropanediol or 1-(methylamino)-propanediol, for roentgenographic contrast media.

Description

Detailed Description of the Invention [Industrial Field of Application] The β-hydroxyamino compound produced by the present invention is an industrially important compound, such as 1-aminopropanediol and 1-(methylamino) -Propadiol has been attracting attention as a raw material for X-ray contrast agents, whose demand has been increasing in recent years.

[Prior Art] Methods for producing β-hydroxyamino compounds are well known.

For example, as shown in the reaction formula below, there is a method for producing 1-aminopropanediol in which glycidol and ammonia are reacted (for example, ■L, Kno
rr et al., “Ber, deutsch, Chem, Ges.
,”,V.

1.32,750.1899, ■, Baum et al.”
J,Org,Chem,”,V.

1.27.2231, 1911i2, ■''Public Patent Publication °Sho 56-]61357, ■Domachi 56-161355,
■The same town 56-161356, etc.).

The reaction mechanism is thought to be a ring-opening addition reaction caused by ammonia's nucleophilic attack on the electron-deficient carbon atom of the epoxy ring of glycidol.

OOH / \ I Nu + H-C-C-C-H HHH H0HOH → H-N-C-C-C-H HHHH [Problem to be solved by the invention] However, in these conventional techniques, the reaction formula shown in the above In addition to the main reaction, there were many side reactions as shown in the reaction formula below, and therefore the yield of the target product was low and not sufficient.

OOH / \NH+2H-C-C-C-H HHH OHOHHH0HOH 1111 → H-C-C-C-N-C-C-HHHHH
HHH Also, as a technology related to the present invention, glycerin-α-
A method for producing 1-aminopropanediol from monochlorohydrin and aqueous ammonia is known (see Baum et al., "J, Org, Chell," Vol.
, 27.2231.1982).

This method is fundamentally different from the present invention in that it does not use an epoxy compound as a raw material and uses a halohydrin compound instead.

However, it is possible that an epoxy compound is used as an intermediate.

(l OH0H H-C-C-C-H HHH OOH / \ 1 → HCg + H-C-C-C-HI3 HHH The amount of by-produced hydrogen chloride is at most the It is only the equivalent molar amount to Dorin.

This amount does not improve the yield of 1-aminopropanediol.

Therefore, in this method, when producing a β-hydroxyamino compound from an epoxy compound and an amine, H
There is no suggestion that the presence of CfI increases yield.

This method also has the disadvantage that the reaction rate is lower than that of the present invention.

This is shown in (Reference Example 1) (Reference Example 2) (Reference Example 3) after Examples and Comparative Examples.

[Objective of the Invention] An object of the present invention is to develop a technique capable of producing a β-hydroxyamino compound with good yield from an epoxy compound and an amine.

In view of the above situation, the inventors of the present invention have made extensive studies and found that when an epoxy compound and an amine are reacted, if the reaction is carried out in the presence of a certain amount or more of hydrogen halide or its ammonium salt, β- The present invention was completed by discovering that the yield of hydroxyamino compounds is improved.

[Structure of the Invention] That is, the present invention provides an epoxy compound represented by the following general formula A-1 or general formula A-2 / \R-C-C-R (formula A-1) 4 1 R2R3 / \R -C-C-R (formula A-2) 4 \ / [However, in the above general formula A-1 and general formula A-2, R1
, R, R, R are hydrogen atoms, halogen atoms 2 3
4 represents a substituent selected from alkyl groups, aryl groups, alkoxy groups, and aryloxy groups that can be the same or different combinations, and Z represents an alkylene group having 3 or 4 carbon atoms in the main chain] and the following general formula B
The following general formula C -1 or a hydroxyamino compound represented by the general formula C-2 ROM 1 R-N-C-C-R (formula C-1) 4 HR2R3 R,OH 1 ( R-N-C-C-R (formula C-2) A β-hydroxyamino compound characterized in that the method for producing 4\/z is characterized in that the reaction is carried out in the presence of an excess amount of hydrogen halide or ammonium salt thereof on a molar basis with respect to the epoxy compound. ``Production method''.

The method for producing the β-hydroxyamino compound of the present invention will be explained in detail below.

(Epoxy compound) The raw material epoxy compound used in the present invention is an epoxy compound represented by the following general formula A-1 or general formula A-2. 3 / \ R-C-C-R (formula A-2) 4 \ / [However, in the above general formula A-1 and general formula A-2, R,
RSR3 and R4 represent substituents that can be the same or different combinations selected from hydrogen atoms, 2 halogen atoms, alkyl groups, aryl groups, alkoxy groups, and aryloxy groups, and 2 represents the number of carbon atoms in the main chain. 3 or 4 alkylene group].

Examples of specific epoxy compounds include glycidol, ethylene oxide, propylene oxide, epoxidized soybean oil, epoxidized linseed oil, allyl glycidyl ether,
Examples include butyl glycidyl ether, phenyl glycidyl ether, 2-ethylhexyl glycidyl ether, trimethylolpropane polyglycidyl ether, glycerol polyglycidyl ether, ethylene glycol polyglycidyl ether, cyclohexene monoepoxide, vinylcyclohexene monoepoxide, etc. The compound may further have a substituent within a range that does not interfere with the reaction.

(Amine) The amine used in the present invention is an amine 5-N-H represented by the following general formula B (Formula B) [However, in the general formula B, R5 is selected from a hydrogen atom, an alkyl group, or an aryl group. ].

Specific examples of amines include ammonia, methylamine, ethylamine, ethanolamine, benzylamine, cyclohexylamine, etc. These amines may have further substituents within the range that does not interfere with the reaction. It's okay.

In the reaction system, some or most of these are thought to exist as salts (ammonium salts) with the raw material amine and/or the product β-hydroxyamino compound, and such ammonium Even the salt form is effective in improving the yield of the β-hydroxyamino compound.

Therefore, the form to be added to the reaction system is not only in the form of the hydrogen halide mentioned above, but also in the form of an ammonium salt with the raw material amine or an ammonium salt with other amines (including ammonia). It's okay.

Hydrogen fluoride, hydrogen chloride, hydrogen bromide used in the present invention,
Hydrogen iodide and the like may be used alone or in combination of several kinds.

In view of cost, hydrochloric acid, hydrobromic acid, and hydriodic acid are preferred, with hydrochloric acid being particularly preferred.

All of these can be used in the form of anhydrous or aqueous solutions.

(Concentration Ratio) The concentration ratio of the above-mentioned epoxy compound, amine, hydrogen halide, or ammonium salt thereof must be in the following order in terms of molar ratio.

Epoxy compounds, hydrogen halides, or their ammonium salts (If the concentration of the amine/epoxy compound is equal to or greater than the concentration of the hydrogen halides or its ammonium salts, there is little yield improvement effect as shown in the reference example. do not have.

Therefore, the required amount of hydrogen halide or its ammonium salt is 1.1 times or more, preferably 2 times or more, the amount of the epoxy compound (both are molar ratios).

Also, it is easy to see from the reaction formula that the amine is required in an amount equivalent to or more than the equivalent mole of the epoxy compound, but if it is not excessive even if it appears due to the hydrogen halide or its ammonium salt present in the system, 1) the reaction will not proceed. It does not progress completely, and 2
) There are disadvantages such as an increase in side reactions due to the system being biased toward acidity.

Therefore, the amine should be used in excess over the hydrogen halide or its ammonium salt.

Although the specific concentration ratio of each component cannot be absolutely limited, the molar ratio of hydrogen halide or its ammonium salt/epoxy compound is 1.1 times or more, preferably 2 times or more by mole.

It is not preferable to use 100 moles or more because purification costs increase (neutralization and amine recovery). The amine/epoxy compound molar ratio is 2 times or more, preferably 5 times or more.
That's more than double that.

Although the yield of the β-hydroxyamino compound tends to be higher when the amount is larger, the use of 100 moles or more is also disadvantageous because the purification cost (recovery of the amine) increases.

(Solvent) The method for producing a β-hydroxyamino compound of the present invention includes:
A solvent may or may not be used.

When a solvent is used, it is of course necessary that it be inert to the reaction.

Examples of preferred solvents include water, alcohols, ethers, hydrocarbons, and the like.

(Reaction temperature) There is no particular range of reaction temperature when carrying out the method for producing a β-hydroxyamino compound of the present invention, but
The temperature is usually -50 to 150°C, preferably 0 to 100°C.

(Pressure> There is no particular limit to the reaction pressure when carrying out the method for producing a β-hydroxyamino compound of the present invention, but
Usually 50mmHg ~ 200a tml preferably,
It is carried out in the range of normal pressure to 5 Qa tm.

(Reaction format) The reaction in the production method of the present invention is carried out in a liquid phase reaction, but the format is not particularly limited. Any reaction format such as continuous flow type, batch type, or semi-batch type may be used. .

The following can be considered as specific embodiments for carrying out the method for producing a β-hydroxyamino compound of the present invention.

(a) The amount of hydrogen halide or its ammonium salt is 1.1 with respect to the epoxy compound that is one of the raw materials.
The method according to the claims, wherein the molar amount is more than double.

(b) The method according to claim 1, wherein the amount of hydrogen halide or its ammonium salt is 2 times or more by mole relative to the epoxy compound as one of the raw materials.

The method according to claim 1, wherein the amine (C) is ammonia or methylamine.

(d) The method according to claim 1, wherein the epoxy compound is glycidol.

The effects of the present invention will be explained below using Examples and Comparative Examples, but the present invention is not limited thereto.

[Example 1] Volume 150m equipped with stirrer, condenser, and thermometer
26.4 g of ammonium chloride [NH4Cρ] (493 mmol, 5 times mole relative to glycidol) was added to a jacketed glass reactor of J7, and then ammonia (28%) water, which is a specific example of the compound of formula B, was added. 90.
0 g (of which, 1480 mmol as NHs) was charged.

While stirring the reaction solution, the temperature of the hot water circulating through the jacket was adjusted to raise the temperature of the reaction solution to 28°C.

Glycidol 7, which is a specific example of the compound of formula A-1, is then
．． 3 g (98.6 mmol) were charged to the reactor.

The temperature of the reaction solution rose at the same time as glycidol was charged, and the reaction solution temperature was then kept at 33°C and the reaction continued for 3 hours (ammonia was used at 15.0 times the mole of glycidol).
.

After the reaction was completed, ammonia was distilled off from the reaction solution under reduced pressure.

The residual liquid after ammonia distillation was neutralized with an aqueous NaOH solution.

Analysis of the neutralized solution by gas chromatography revealed that the desired product, 1-aminopropanediol, had been produced in a yield of 82.0 mol%.

This example is compared with Comparative Example 1 and shows the effect of improving the yield of 1-aminopropanediol by adding ammonium chloride.

[Example 2] Ammonium bromide [NH
The experiment of Example 1 was repeated, except that 48.3 g of 4Br (493 mmol, 5 mole times relative to glycidol) was added to the reactor.

As a result, 1-aminopropanediol was produced with a yield of 81.8 mol%.

This example is compared with Comparative Example 1, and shows the effect of improving the yield of 1-aminopropanediol by adding ammonium bromide.

[Example 3] Instead of 26.4 g of ammonium chloride [NH4 (l), 38.5 g of a 35% by weight aqueous hydrogen chloride solution (of which, as HCg, 13.5 g, 370 mmol, 5 times the mole relative to glycidol) was reacted. Stick to the container, glycidol 5.4
The experiment of Example 1 was repeated, except that 8 g (74.0 mmol) was charged to the reactor.

As a result of analysis by gas chromatography, 1-aminopropanediol was produced at a yield of 82.7 mol%.

This example is compared with Comparative Example 2, and shows the effect of improving the yield of 1-aminopropanediol by adding hydrochloric acid.

[Example 4] The reactor was replaced with one with a volume of 300 r+dl, and 35% by weight
Hydrogen chloride aqueous solution 38.5g (of which, as HCg, 13
．． 5 g, 370 mmol, 5 molar times relative to glycidol) was added to the reactor, and an aqueous solution of methylamine (40%), another specific example of the compound of formula B, was added to the reactor, followed by 5.48 g of glycidol (74,0 The experiment of Example 1 was repeated, except that the reactor was charged with 1 mmol).

As a result of analysis by gas chromatography after neutralization,
1-(methylamino)-propanediol was produced at a yield of 84.1 mol%.

This example is compared with Comparative Example 3, and shows the effect of improving the yield of 1-(methylamino)-propanediol by adding hydrochloric acid.

[Comparative Example 1] The same experiment as in Example 1 was repeated except that ammonium chloride was used and the residual solution after ammonia distillation was neutralized with an aqueous NaOH solution.

The residual liquid was analyzed by gas chromatography.

As a result, 6.7 g (74.0 mmol) of 1-aminopropanediol was produced.

That is, the yield based on the raw material glycidol is 7560
It was mol%.

[Comparative Example 2] The same experiment as Comparative Example 1 was repeated except that the amount of glycidol charged was reduced to 5.48 g (74°0 mmol) (ammonia was used in an amount of 20.0 times the amount of glycidol by mole).

As a result, 1-aminopropanediol was produced with a yield of 79.0 mol%.

[Comparative Example 3] The reactor was replaced with one with a capacity of 300 nl, and instead of ammonia water, 184 g of a 25% by weight methylamine aqueous solution (including 73.6 g as CH3NH2) was used.

The experiment of Comparative Example 2 was repeated except that 1,480 mmol) was added (methylamine was used in an amount 20.0 times the amount of glycidol).

As a result, 1-(methylamino)-propanediol was produced at a yield of 81.0 mol%.

(Reference Example 1) In ■, BauIi et al., “J, Org, Chem,” vo
The following experiment was conducted according to the method of J. I., 27.2231.1962.

Comparative Example 1 except that instead of glycidol, 10.9 g of glycerin-α-monochlorohydrin (98.6 mmol, 15 times the mole of NH3) was added, neutralized, and then analyzed by gas chromatography. The experiment was repeated.

As a result, 1-aminopropanediol was produced with a yield of 66.7%.

This reference example is compared with Comparative Example 1, and the raw material is glycerin-
In the case of α-monochlorohydrin, the same reaction time (3 hours) shows a lower yield.

(Reference Example 2) The experiment of Reference Example 1 was repeated except that the reaction time was changed to 24 hours.

As a result, 1-aminopropanediol was produced with a yield of 75.5%.

This reference example is compared with Comparative Example 1 and Reference Example 1, and the fact that glycerin-α-monochlorohydrin has a lower reaction rate than glycidol and that the yield of 1-aminopropanediol is low even when reacted for a long time. indicates that it is comparable to that of glycidol. Further, the amount of hydrogen chloride produced as a by-product in this reference example was at most an equivalent molar amount to the charged glycerin-α-monochlorohydrin.

(Reference Example 3) Before adding aqueous ammonia, 10.3 g of a 35% by weight hydrogen chloride aqueous solution (of which, as HCρ, 3°60 g, 98.0 g)
The experiment of Comparative Example 1 was repeated, except that 6 mmol (1 mole times glycidol) was added to the reactor, neutralized, and analyzed by gas chromatography.

As a result, 1-aminopropanediol was produced with a yield of 75.1 mol%.

This reference example is compared with Comparative Example 1, and shows that merely adding hydrogen chloride in an equivalent molar amount to glycidol has almost no effect on improving the yield of 1-aminopropanediol.

Claims (1)

[Claims] An epoxy compound represented by the following general formula A-1 or A-2 ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (Formula A-1) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (Formula A-2) [However, in the above general formula A-1 and general formula A-2, R_
1, R_2, R_3, and R_4 represent substituents that can be the same or different combinations selected from hydrogen atoms, halogen atoms, alkyl groups, aryl groups, alkoxy groups, and aryloxy groups, and Z is a main chain [Indicates an alkylene group having 3 or 4 carbon atoms] and amines shown by the following general formula B ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (Formula B) [However, in general formula B, R_5 is a hydrogen atom, an alkyl or a substituent selected from an aryl group], a hydroxyamino compound represented by the following general formula C-1 or general formula C-2 ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (Formula C -1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (Formula C-2) In the method for producing A method for producing a β-hydroxyamino compound.