JPH10120678A - N-(1,3-dialkyl-2-imidazolidinyldene)-4-pyridineamine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound which is useful as a catalyst that can force the condensation reaction typified by esterification in high yield. SOLUTION: The objective compound is represented by formula I (R<1> and R<2> are each an alkyl), typically N-(1,3-dimethyl-2-imidazolizinylidene)-4- pyridineamine. This compound is prepared by allowing a 1,3-dialkyl-2- imidazolizinone to react with a halogenating agent, followed by reaction of the product which is 1,3-dialkyl-2-halogeno-imidazolium halogenide of formula III with 4-pyridineamide of formula IV in the presence of a base in a solvent such as acetonitrile at about room temperature.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to N- (1,3-dialkyl-2-imidazolidinylidene) -4-pyridineamine useful as a basic catalyst in an esterification reaction or the like.

[0002]

2. Description of the Related Art Many industrially useful organic compounds such as pharmaceuticals and agricultural chemicals include compounds having an ester bond.
As a method for producing a compound having an ester bond, a method in which an alcohol and a carboxylic acid are used as starting materials and an ester is formed by condensing the two compounds is generally used. Therefore, the condensation reaction is known as one of the most important reactions in the synthesis of organic compounds.

As a method for condensing a carboxylic acid and an alcohol, a method in which a carboxylic acid is converted into an active derivative such as an acid halide or a carboxylic anhydride and then reacted with an alcohol or a condensing agent such as dicyclohexylcarbodiimide is used. Many methods have been reported, for example, a dehydration reaction using an acid catalyst or heat. Among them, the method using dicyclohexylcarbodiimide as a condensing agent is widely used because the reagent is inexpensive, the carboxylic acid can be used as it is, and the reaction conditions are mild. The carboxylic anhydride method is also widely used when the anhydride is available because the reaction operation is easy.

[0004]

However, in the method using dicyclohexylcarbodiimide as a condensing agent, for example, in the condensation reaction of benzoic acid and phenol, the yield is about 10% [Tetrahedron Letters, 4475-4478 (1971).
8)] may not be applicable to some compounds. Further, it is known that when a compound having a large steric hindrance is esterified, there are problems such as a low yield and a by-product of a rearranged compound. The method using a carboxylic anhydride also has a low yield when esterifying a compound having a large steric hindrance.For example, in the presence of triethylamine, the reaction of acetic anhydride with 1-methylcyclohexanol gives no target product. Not known [Tetrahedron, 34 , 2069-2076 (1978)].

Therefore, there has been a demand for a production method in which the type of the compound to be esterified is not limited, for example, an ester compound can be obtained with a high yield even from a compound having a large steric hindrance. Accordingly, an object of the present invention is to provide a reagent capable of causing a condensation reaction represented by an esterification reaction to proceed with high yield.

[0006]

Means for Solving the Problems In view of such circumstances, the present inventors have conducted intensive studies. As a result, if a novel compound represented by the following general formula (1) is used as a catalyst, the esterification reaction can be carried out smoothly. The present invention was advanced, and it was found that an ester compound could be produced in high yield, and the present invention was completed.

That is, the present invention provides the following general formula (1)

[0008]

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Wherein R ¹ and R ² are the same or different and each represents an alkyl group. N- (1,3-dialkyl-2-imidazolidinylidene) -4-pyridineamine represented by the formula: is there.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The N- (1,3-dialkyl-2-imidazolidinylidene) -4-pyridineamine of the present invention is represented by the above general formula (1),
^The alkyl group represented by ¹ and R ² has 1 to 2 carbon atoms.
And 4 straight-chain or branched-chain alkyl groups. Specifically, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, t-butyl group,
n-pentyl group, n-hexyl group, n-heptyl group, n
-Octyl group, n-nonyl group, n-decyl group, n-undecyl group, n-dodecyl group and the like. this house,
Those having 1 to 6 carbon atoms are preferred, and those having 1 to 4 carbon atoms are particularly preferred. R ¹ and R ² may be the same or different.

The compound (1) of the present invention can be prepared, for example, by reacting a 1,3-dialkyl-2-imidazolidinone (2) with a halogenating agent according to the following reaction formula. -Halogenoimidazolinium halogenide (3) can be produced by reacting 4-pyridineamine (4).

[0012]

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Wherein R ¹ and R ² are the same as above, X is a halogen atom, and B is a base.

Hereinafter, the above reaction will be described step by step.

(1) Step 1 Halloyminium salt (3) can be prepared, for example, by adding oxalyl halide, phosphorus trihalide to 1,3-dialkyl-2-imidazolidinone (2), which is known as a readily available solvent. Or a known halogenating agent such as phosphorus pentahalide, phosphorus oxyhalide, phosgene, or trichloromethyl chloroformate. In this reaction, one of the compound (2) and the halogenating agent is dissolved in an appropriate solvent such as carbon tetrachloride, and the other is added little by little, and furthermore, at room temperature to 70 ° C. for several hours to more than It is performed by reacting for a time. The haloiminium salt (3) thus obtained can be isolated,
The reaction solution can be used for the next reaction without isolation.

(2) Step 2 The reaction between the haloiminium salt (3) and 4-pyridineamine (4) is carried out by acetonitrile, dichloromethane, toluene,
The reaction is carried out by stirring in a solvent such as tetrahydrofuran in the presence of a base at around room temperature. As the base, an organic base such as trimethylamine, triethylamine, tri-n-butylamine, dimethylaniline, and pyridine, and an inorganic base such as potassium carbonate and potassium hydrogen carbonate can be used.

The compound (1) of the present invention can be used as a catalyst in various esterification reactions. In order to carry out the esterification reaction using the compound (1) of the present invention, a catalytic amount of the compound (1) may be added to a mixture of a condensing agent such as carboxylic acid, alcohol and dicyclohexylcarbodiimide, and the mixture may be stirred at around room temperature. When a carboxylic acid anhydride is used, a catalytic amount of compound (1) may be added in the presence of a carboxylic acid anhydride, an alcohol, and a base such as triethylamine.

Compound (1) used in the esterification reaction
Is 0.1 to carboxylic acid or carboxylic anhydride.
It is sufficient to add 100 mol%, and it is particularly preferable to add 5 to 25 mol%.

Thus, when the compound (1) of the present invention is used as a catalyst, an esterification reaction with a low yield using only a condensing agent such as dicyclohexylcarbodiimide or an alcohol which does not react only with a carboxylic anhydride and a base alone can be used. The ester is obtained in yield. The compound (1) of the present invention is also useful as a basic catalyst in reactions other than the esterification reaction.

[0020]

EFFECTS OF THE INVENTION When the compound of the present invention is used as a catalyst, esters can be produced under mild reaction conditions and in high yield.

[0021]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 N- (1,3-dimethyl-2-
Preparation of imidazolidinylidene) -4-pyridineamine:
5.0 g of 4-pyridineamine in 100 ml of methylene chloride
(53 mmol) and 10.7 g of triethylamine (106
mmol), and a solution of 9.0 g (53 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride in 40 ml of methylene chloride was added dropwise thereto.
Stirring was continued for hours. Next, an aqueous sodium hydroxide solution was added to the reaction solution, and the mixture was extracted with methylene chloride. The extract was dried over anhydrous potassium carbonate, and the solvent was distilled off under reduced pressure to obtain 8.1 g of a residue as a red oil. Silica gel chromatography of this residue (solvent: chloroform / methanol)
Then, 3.8 g (yield: 38%) of the title compound was obtained.

[0023] The oil ^{_{UVλ max MeOH nm: 289.2 (ε19300}} ), 206.0 (ε14300) IRν max neat: 1615, 1570, 1280, 1030, 980, 965, 8
30 ¹ H-NMR (CDCl ₃ ) δ: 2.70 (6H, s), 3.38 (4H,
s), 6.70 (2H, d, J = 4.7 Hz), 8.25 (2H, d, J = 4.7 Hz) ¹³ C-NMR (CDCl ₃ ) δ: 35.13, 48.31, 117.49,
149.74, 157.36,157.50

Reference Example 1 Production of benzoic acid phenyl ester: 1.00 g of benzoic acid (8.
19 mmol), 0.85 g (9.01 mmol) of phenol,
1.86 g of dicyclohexylcarbodiimide (9.01
mmol) and 0.16 g of N- (1,3-dimethyl-2-imidazolidinylidene) -4-pyridineamine (0.82
mmol) and stirred at room temperature for 18 hours. The precipitated dicyclohexylurea was separated by filtration and washed with methylene chloride. The filtrate was washed sequentially with water, a 5% acetic acid aqueous solution and water, and dried over anhydrous magnesium sulfate. Next, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (solvent: n-hexane / chloroform) to obtain 1.54 g (yield: 95%) of the title compound.

IRν _max ^KBr : 1720

As described above, without using the compound of the present invention,
When this reaction was performed, the yield of phenyl benzoate was about 10% (Tetrahedron Letters, 4475).
~ 4478)), it can be seen that the esterification reaction is extremely accelerated by the compound of the present invention.

Reference Example 2 Preparation of ethyl diphenylacetate: Diphenylacetic acid was dissolved in 40 ml of acetonitrile.
00g (9.42 mmol), ethanol 0.48 g (1
0.40 mmol), dicyclohexylcarbodiimide.
15 g (10.40 mmol) and 0.18 g (0.94 mmol) of N- (1,3-dimethyl-2-imidazolidinylidene) -4-pyridineamine were added, and the mixture was stirred at room temperature for 21 hours. Thereafter, the same operation as in Reference Example 1 was performed to obtain 1.97 g (yield: 87%) of the title compound.

IRν _max ^neat : 1730

Reference Example 3 Production of 1-methylcyclohexyl acetic acid: 1.50 g (13.16 mmol) of 1-methylcyclohexanol, 2.68 g (26.27 mmol) of acetic anhydride, and 2.65 g of triethylamine (26 ml in 15 ml of acetonitrile) .24 mmol) and 0.25 g (1.32 mmol) of N- (1,3-dimethyl-2-imidazolidinylidene) -4-pyridineamine were added, and the mixture was stirred at room temperature for 24 hours. Thereafter, the same operation as in Reference Example 1 was performed to obtain 0.88 g (yield 43%) of the title compound.

IRν _max ^neat : 1725

As described above, without using the compound of the present invention,
When this reaction was carried out, acetic acid 1-methylcyclohexyl ester was not obtained (Tetrahedron, 34 , 2069-2).
076 (1978)), it can be seen that the esterification reaction is extremely accelerated by the compound of the present invention, and that the compound of the present invention enables the esterification reaction using a raw material having a large steric hindrance.

Claims (1)

[Claims] 1. The following general formula (1): [Wherein R ¹ and R ² are the same or different and each represents an alkyl group] N- (1,3-dialkyl-2-imidazolidinylidene) -4-pyridineamine.