JPS5939851A - Esterification - Google Patents

Abstract

PURPOSE:In reacting an alcohol with a carboxylic acid, to obtain an ester useful as a drug, etc. in high yield, by using a 1,3-dialkyl-2-halogeno-imidazolium halogenide as a condensation agent. CONSTITUTION:As shown by the reaction formula, an alcohol shown by the formula I (R3 is alcohol residue) is reacted with a carboxylic acid shown by the formula R4-COOH (R4 is carboxylic acid residue) using a 1,3-dialkyl-2-halogeno- imidazolium halogenide shown by the formula II (R1 and R2 are lower alkyl; X is halogen atom) as a condensation agent in the presence of a base such as pyridine, triethylamine, etc. at room temperature, to give an ester shown by the formula III. The condensation agent shown by the formula II can be easily synthesized by reacting a 1,3-dialkyl-2-imidazolidinone shown by the formula IVwith a halogenating agent such as oxalyl halogenide at room temperature - 70 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a novel canisterization method, more specifically, a canisterization method represented by the following general formula (1), (wherein R1 and R7 represent a lower alkyl group, and X represents a halogen atom) The present invention relates to an esterification method using a 1,3-dialkyl-2-halokenoimidazolinium halogenide as a condensing agent.

Conventionally, various methods have been known to produce esters from alcohols and carboxylic acids, one of which is a method using a condensing agent, and many condensing agents have been reported. ing.

On the other hand, since many of the organic compounds useful as pharmaceuticals are obtained by esterification reactions, the inventor of the present invention, while conducting intensive research on esterification reactions, discovered a compound represented by the above general formula +1). The present invention was completed by discovering that 1,3-dialkyl-2-710 genoimidazolinium norogenide (1,3-dialkyl-2-710 genoimidazolinium norogenide 1) This is an esterification method characterized by using k as a condensing agent to cause the reaction, and is shown by the following reaction formula.

(ml GV) (1+
M(VD (I) (wherein, R is an alcohol residue, R4 is a carboxylic acid residue, B is a base, and R2 and X have the meanings described above) Used as a condensing agent in the present invention The compound of formula (1) is
For example, the following general formula (
1,3-dialkyl 2-imidazolidinone represented by [1 (wherein R and R2 have the above-mentioned meanings)]
・Manufactured by reacting with a rogensing agent.

Examples of the norogenating agent used here include oxalyl halide, tri,S phosphorus halogenide, penta,\phosphorus halogenide, oxynorogenide phosphorus, phosgene, trichloromethyl chloroformate, and the like. Reaction: Either the 3-dialkyl-midazolidinone or the no-logogenating agent is dissolved in a suitable ies such as carbon tetrachloride, and the other is added little by little to this, followed by further reaction at room temperature to 70C for several hours to more than ten hours. It is done by letting

1,3-Dialkyl-2-halogeno-
Although imidazolinium/10genit 1 can be isolated, its reaction solution can also be used in the esterification reaction of the present invention without isolation.

To carry out the entire process of the present invention, 1 mol each of alcohols (I), carbo7HeAO, 1 + 3-dialkyl-2-halogeno-imidazolinium halogeni) (1) and pyridine, triethylamine, tributylamine are added. When z moles of a base (Vl) are admixed and reacted at room temperature, the reaction proceeds favorably to give the ester (VD) in high yield.

Next, reference examples and examples will be given and explained.

Reference example 1 1,3-dimethyl-2-imidazolidinone 26,9ff
50 ml of carbon tetrachloride was dissolved, 25 ff of oxalyl chloride was added dropwise thereto over 20 minutes, and the mixture was further heated at 60C for 5 hours to react. The reaction solution was cooled to room temperature, 14 precipitated crystals were collected, washed successively with carbon tetrachloride and n-hexane, and dried to give 1,3-dimethyl-2-chloro-imidazolinium chloride 231 (yield 69%).

1 1R (KBr) cm: 1630, 1540, 14
15,1340.

1300, 1230, 1140, 96ONMR (
δ, ppm, CDCes) ”3, 34 (S,
6H, -Cl(,X2)4,37(S,
4H, -CH2CH2-) Reference Example 2 1,3-dimethyl-2-imidazolidinone 20. 7 Dissolve 7 and add trichloromethylchloroforme)15. o76 was added dropwise, and the mixture was stirred as it was for 5 hours. One of the precipitated crystals was taken and treated in the same manner as in Reference Example 1 to obtain 1,3-dimethyl-2-chloro-imidazolinium chloride 2. 2? (Yield 9o.
6chi) was obtained.

Example 1 ε-guanidinocaproic acid methanesulfonate 30.
1i. Ethyl p-hydroxybenzoate 20.4 g
-, dichloromethane lO (l in a ml mixture, 1
．． 18.9%-i of 3-dimethyl-2-chloro-imidazolinium chloride was added, followed by 17.7f of pyridine.
It was added dropwise over 5 minutes. The whole was further stirred overnight, and the precipitated crystal wP was collected and washed with dichloromethane. The liquid 1 and the washing liquid were combined, the solvent was distilled off under reduced pressure, the mixture was diluted with water, and the mixture was added to 1.5 g of a saturated aqueous sodium bicarbonate solution with stirring. One portion of the precipitated crystals was washed with water and acetone and dried to obtain carbonate of ε-guanidinocaproic acid/p-ethoxycarbonylphenyl ester 32. s 5L (yield 75.8 cm) was obtained.

Example 2 In the same manner as in Example 1 except that ε-guanidinocaproic acid hydrochloride was used instead of ε-guanidinocaproic acid methanesulfonate, ε-guanidinocaproic acid p-ethoxycarbonylphenyl ester was prepared. The carbonate was obtained in a yield of 7 oz.

Example 3 Dichloromethane 50 mJKn-caproic acid 12.82,
Benzyl alcohol 9.91 and 1,3-dimethyl-2
-Chloro-imidazolinium chloride 18.6i'
(I@solve, add pyridine 17.4f!- dropwise to it,
The mixture was further stirred for 2 hours. Water was added to the reaction solution, and the dichloromethane layer was separated, washed with a saturated aqueous sodium bicarbonate solution, and then dried over anhydrous magnesium sulfate. Then, the solvent was distilled off, and the residue was distilled under reduced pressure to obtain 18.1 f (yield: 95.9) of benzyl caproic acid ester.

Example 4 Benzoic acid 14.657, ethanol 4.6f and 1,3-dimethyl-2-chloro-imidazolinium chloride 20281 were dissolved in 60ml of dichloromethane, and pyridine 19.6ml was dissolved therein. Of was added to react. The reaction solution was then treated in the same manner as in Example 3 to obtain ethyl benzoate 14.21i1- (yield: 947).

that's all

Claims (1)

[Claims] 1. Alcohols and carboxylic acids are represented by the following general formula (1
1. Reaction using 1,3-dialkyl-2-7-rogenoimidazolinium halide represented by (wherein R1 and R2 are lower alkyl groups and X is a halogen atom) as a condensing agent. An esterification method characterized by: 2. The esterification method according to claim 1, wherein the condensing agent is 1,3-dimethyl-2-chloro-imidazolinium chloride.