JPH0346461B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing a novel amide derivative. The present invention relates to a method for producing a novel amide derivative in which only primary amino groups are selectively amidated.

[Conventional technology and its problems]

Conventionally, general methods for producing amide derivatives from aminoalcohol derivatives include producing acyl derivatives using acid anhydrides, acid halides, fatty acid esters, fatty acids, etc. without catalyst or in the presence of a base catalyst such as sodium methylate or triethylamine. Methods are known and in practice.

However, when this method is applied to a compound in which a primary alcoholic hydroxyl group and a secondary amine are in the same molecule, the primary alcoholic hydroxyl group and the secondary amine are simultaneously acylated, making it impossible to obtain the desired compound. There was a drawback that there was no. Therefore,
For example, as shown in the formula below, there is a method in which only the ester is selectively hydrolyzed under basic conditions such as potassium hydroxide, potassium carbonate, or sodium methylate from the acyl compound obtained by the reaction. The yield was not very good.

(In the formula, R and R' represent hydrocarbon groups.) There is also a method for producing selective amide derivatives by a general production method, which involves direct acylation using the above-mentioned acid anhydride, acid halide, or fatty acid. However, this method not only requires a longer reaction process, but also
Because large amounts of fatty acids or fatty acid salts are produced as by-products,
There is a disadvantage that post-treatment of the reaction becomes complicated. Furthermore, when a fatty acid is used, there is a drawback that the selectivity is lowered, various by-products are produced, and the yield is poor, and this drawback is particularly noticeable when secondary amines are acylated.

[Means to solve the problem]

Under these circumstances, the present inventors have conducted intensive research to perform selective amidation of amino alcohols having a primary alcoholic hydroxyl group and a secondary amino group. It has been found that selective amidation occurs when a fatty acid lower alkyl ester is allowed to act on an amino alcohol while distilling off the lower alcohol.

That is, the present invention is characterized by reacting a fatty acid lower alkyl ester with a secondary amine compound having a primary alcoholic hydroxyl group in the molecule in the presence of a base catalyst while distilling off the lower alcohol produced. This is a method for producing grade amide derivatives.

The secondary amine compound having a primary alcoholic hydroxyl group in the molecule of the present invention (hereinafter simply referred to as "secondary amine")
), for example, the following formula () [In the formula, R ¹ is a linear or branched saturated or unsaturated hydrocarbon group, X is an oxygen atom or a methylene group, and Y is a group -(CH ₂ -) _o OH (where n
represents a number from 2 to 6), a group -(CH ₂ CH ₂ O-) ₂ H or a group -CH ₂ CH (OH) CH ₂ -OH].

This amino alcohol derivative () can be prepared by a known method (for example, Pol. J. Chem. 52 1283 (1978), etc.).
For example, in the formula (), X=O,
Compound (Ia) represented by Y=-CH ₂ CH ₂ OH can be produced from glycidyl ether and ethanolamine according to the reaction formula shown below.

(In the formula, R ¹ has the above-mentioned meaning and preferably has 10 to 26 carbon atoms.) Also, fatty acid lower alkyl ester used in the present invention (hereinafter abbreviated as "fatty acid ester")
Preferred examples include the following formula () R ² COOR ³ () (wherein R ² represents a linear or branched, saturated or unsaturated hydrocarbon group, and R ³ represents a lower hydrocarbon group. Examples include those represented by the following formulas, particularly those in which R ² has 9 to 25 carbon atoms and R ³ has 1 to 5 carbon atoms. More specifically, saturated straight chain fatty acid esters such as methyl caprate, methyl laurate, methyl myristate, methyl palmitate, ethyl palmitate, isopropyl palmitate, methyl stearate, methyl behenate; methyl branched methyl isostearate. , methyl 2-heptylundecenoate, isopropyl methyl branched isostearate, and other saturated branched fatty acid esters; unsaturated fatty acid esters such as methyl oleate, methyl linoleate, and methyl linolenate, but are not limited to these. It's not something you can do. The amount of fatty acid ester to be used is preferably 0.95 to 1.05 mol per 1 mol of secondary amine.

Furthermore, specific examples of the basic catalyst used in the present invention include sodium hydroxide, potassium hydroxide,
Examples include, but are not limited to, potassium carbonate, sodium methylate, sodium ethylate, and potassium t-butoxide. The amount of the basic catalyst used is preferably 0.01 to 0.2 mol per 1 mol of secondary amine.

Furthermore, in the method of the present invention, more favorable results can be obtained by using polyether compounds, and specifically, polyethylene glycol (with an average molecular weight of
200-50000), polyethylene glycol methyl ether (average molecular weight 350-5000), triethylene glycol dimethyl ether, tris(dioxa-
Chain polyether compounds such as 3,6-heptyl)amine; 18-crown-6, dibenzo-18-crown-6, 4,13-diaza-18-crown-6
Cyclic polyether compounds such as, but not limited to, are used. The amount of these polyether compounds used is preferably 0.1 to 100 parts by weight per 100 parts by weight of the secondary amine.

In the reaction of the present invention, it is necessary to efficiently distill the lower alcohol produced by the reaction out of the system, and for this purpose, the reaction is carried out under normal pressure to reduced pressure, preferably under a pressure of about 100 to 0.01 mmHg. ~200℃,
Preferably, it is heated to 80 to 100°C.

In the method of the present invention, it is sufficient to add the fatty acid ester dropwise for about 1 to 3 hours, and the reaction time after completion of the dropwise addition is preferably within 1 to 2 hours.

〔Effect of the invention〕

According to the method of the present invention, the production of an ester is suppressed, and the amino alcohol of (a) is used as the desired secondary amide derivative, for example, a secondary amine.
When the above compound () is employed as the fatty acid ester, the following formula () A secondary amide compound represented by can be obtained with high selectivity.

〔Example〕

EXAMPLES The present invention will be described in detail below with reference to Examples, but the present invention is not limited thereto.

Example 1 N-(2-Hydroxy-3-tetradesyloxypropyl)-N-2-hydroxyethyl octadecanamide: N- in a 100 ml four-necked flask equipped with a stirrer, addition funnel, thermometer, and distillation device. (2-hydroxy-
Add 6.63 g (20 mmol) of 3-tetradesyloxypropyl)-N-2-hydroxyethylamine, 0.056 g (1 mmol) of potassium hydroxide, and 0.33 g of polyethylene glycol 4000, and heat and stir at 80°C/20 mmHg. Methyl stearate 5.98
g (20 mmol) was added dropwise over about 1 hour. After the addition was completed, the mixture was further heated and stirred for 1 hour under the same conditions, and then recrystallized once from hexane and once from methanol to obtain 11.33 g of the target compound as a colorless powder.
I got it. Yield 94.7%.

mp.: 78~80℃ IR (KBr, cm ^-1 ): 3298 (br), 2920, 2854, 1617, 1467, 1110,
1062 NMR ( _CDCl3 , δ): 0.86 (6H, t), 1.1-1.7 (54H, m), 2.2-2.5
(2H, m), 3.1-4.1 (13H, m) Elemental analysis: Calculated value (%) C74.31 H12.64 N2.34 Actual value (%) C74.42 H12.58 N2.35 Example 2 N- (2-hydroxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamide: N-(2-hydroxy-3-hexadecyloxypropyl)-N-2-hydroxyethylamine
7.19g (20mmol), methyl palmitate 5.42g
(20mmol), potassium hydroxide 0.056g (1mmol)
11.20 g of the target compound as a colorless powder was obtained in the same manner as in Example 1 using 3.60 g of polyethylene glycol 4000. Yield 93.6%.

Melting point: 74.9-75.3℃ IRν _KBr (cm ^-1 ): 3320br, 2924, 2852, 1616, 1468, 1442,
1378, 1112, 1062, 722 ¹ H-NMR δ _CDCl3 : 0.86 (6H, t), 1.0 to 1.6 (54H, m), 2.2 to 2.5
(2H, m), 3.1-4.1 (13H, m) Elemental analysis Calculated value (%) C74.31 H12.64 N2.34 Actual value (%) C74.12 H12.70 N2.23 Example 3 Example 1 In the same reaction as above, 0.35 g of triethylene glycol dimethyl ether was used instead of 0.33 g of polyethylene glycol 4000 to produce 11.51 g of the target compound as a colorless powder.
I got it. Yield 96.2%.

Example 4 In the same reaction as in Example 1, 0.32 g of tris(dioxa-3,6-heptyl)amine was used instead of 0.33 g of polyethylene glycol 4000 to produce the target compound as a colorless powder.
11.45g was obtained. Yield 95.7%.

Example 5 In the same reaction as in Example 1, 18-crown-6 was used instead of 0.33 g of polyethylene glycol 4000.
By carrying out the reaction using 0.25 g, 11.55 g of the target compound as a colorless powder was obtained. Yield 96.5%.

Example 6 In the same reaction as in Example 1, without adding polyethylene glycol 4000, 100°C/20
When the reaction was carried out at mmHg, 10.76 g of the target compound was obtained as a colorless powder. Yield 89.9
%.

Example 7 In the same reaction as in Example 6, 0.193 g of sodium methylate (28% methanol solution) was used instead of potassium hydroxide to obtain 10.70 g of the target compound as a colorless powder. yield
89.4%.

Claims (1)

[Claims] 1. Having a primary alcoholic hydroxyl group in the molecule. 2.
A method for producing a secondary amide derivative, which comprises reacting a fatty acid lower alkyl ester with a secondary amine compound in the presence of a base catalyst while distilling off the lower alcohol produced. 2. The method for producing a secondary amide derivative according to claim 1, wherein the secondary amine compound has two or more hydroxyl groups. 3 The secondary amine compound has the following general formula () [In the formula, R ¹ is a linear or branched saturated or unsaturated hydrocarbon group, X is an oxygen atom or a methylene group, and Y is a group -(CH ₂ -) _o OH (where n
represents a number from 2 to 6), a group -(CH ₂ CH ₂ O-) ₂ H or a group -CH ₂ CH (OH) CH ₂ -OH] A method for producing a secondary amide derivative according to item 1.