SU727145A3 - Method of preparing n-substituted oxazolidines - Google Patents

Abstract

PRODUCTION OF N-SUBSTITUTED OXAZOLIDINES N-substituted oxazolidines having the formula in which: a) R is C1-C10 haloalkyl, C1-C10 alkyl or lower alkylthio; R1 and R2 are independently hydrogen, C1-C12 alkyl, lower alkoxyalkyl or lower alkylol; and R3, R4, R5 and R6 are independently hydrogen, lower alkyl, lower alkoxyalkyl or lower alkylol, or in which: b) R is haloalkyl or chloroalkenyl, R1 is hydrogen, lower alkyl, phenyl, naphthyl, or substituted phenyl wherein the substituents are mono- or dichloro, nitro, methyl, methoxy or hydroxyl; R2 is hydrogen or lower alkyl; R3 is hydrogen, lower akyl, hydroxymethyl, N-methyl carbamoyloxymethyl or dichloroacetoxymethyl; R4 is hydrogen or lower alkyl; R5 is hydrogen, lower alkyl or phenyl and R6 is hydrogen; provided that at least one of R1 or R5 is phenyl, substituted phenyl or naphthyl, are prepared by reacting an oxazolidine with an acid chloride or analogous compound in the presence of a hydrogen chloride acceptor and water. The process is characterized by minimization of by-product formation.

Description

one

This invention relates to a process for the preparation of N-substituted oxaeolidines of formula I

where R and R j are as defined above, from the resulting oxazolidine formula

This goal is achieved by alkanolamine of formula (II) reacting with a carbonyl compound of formula (III) and the resulting oxazolidine of formula (IV) is directly acylated by treatment with an acid chloride of formula (Y) in the presence of water formed in the preparation of oxazolidine during cooling to organic solvent in the presence of an acceptor of hydrogen chloride.

The N-acylation of oxazolidine formula (IY) is carried out in the presence of reaction water formed during the preparation stage.

This allows minimization (by-product formation).

Sodium hydroxide is used as a hydrogen chloride acceptor. The acceptor of hydrogen chloride is usually taken in quantities in hephedela from about 5 to 50%.

Before the addition of the acid chloride, an alkali solution containing 5-50% sodium hydroxide is introduced into the system.

Since the reaction of oxazolidine and acid chloride is carried out in an aqueous solution, it is not necessary to use relatively expensive hydrogen chloride acceptors, such as triethylamine. However, they can also be used because they facilitate the passage of this reaction. As an acceptor of hydrogen chloride, less expensive substances can be used, for example, a weak alkaline solution or a hydroxide of another alkali metal, such as potassium hydroxide (BORN solution). Most conventional hydrogen chloride acceptors are displaced with water or dissolved in water under the reaction conditions, however, it is possible to use water-immiscible acceptors of hydrogen chloride, such as dimethylaniline.

Preferably, the process is carried out at a temperature ranging from 5 to. The reaction can be carried out at a higher temperature, for example, up to 25 ° C. However, at these temperatures, the product yield may be somewhat lower.

Example 1-3. Preparation of 2,2-, cimethyl-3-dichloroacetyloxazolidine

Example 1. (known method).

5.1 g of 2,2-dimethyloxazolidine dissolved in 50 ml of benzene, 5.5 g of triethylamine are added to the mixture, and 7.4 g of dichloroacetic anhydride chloride is added dropwise to the mixture while stirring and cooling in an ice bath. The mixture was poured into water, a solution of benzene was separated, which was dried over anhydrous magnesium sulphate, and then the solvent was distilled off under vacuum. Product is

is a waxy solid with so pl. 113-11 during recrystallization from diethyl ether.

Example 2. In a two-liter reactor, 122 ml (122 g) of eta5 nolamine, 150 ml of acetone and 600 ml of benzene were introduced. The mixture was heated to reflux, the water was distilled off, and then the reaction mixture was allowed to cool. To the reaction mixture are added 200 ml of 37% sodium hydroxide and 175 ml of water. The mixture is maintained at approximately 100 ml of dichloroacetic anhydride while adding. The mixture is kept for 1 hour, then another 93 ml of dichloroacetic anhydride chloride is added, the pH of the mixture becomes below 13, and 25 ml of 20% sodium hydroxide are added. As a result, the pH reaches 13.8.

0 The reaction product is neutralized with concentrated hydrochloric acid, the benzene is distilled off and the resulting product is filtered and dried. This gives -282 g (66.7% of theoretical) solid,

5 having so pl. 11 7, 5-11 9, 5 S.

Example 3. 122 ml (122 g) of ethanolamine, 150 ml (116 g) of acetone and 600 ml of benzene were introduced into a two-liter reactor. The reaction is carried out at

Q temperature is about 33-34 ° C. The reaction mixture is stirred for 1 h, then 200 ml of 33% sodium hydroxide is added, the temperature of the mixture is reduced to about 5 ° C with

 acetone ice bath and stir the mixture for 3 hours. 110 ml (168.5 g) of dichloroacetic anhydride chloride is added over 1 hour, and then 25 ml of 33% sodium hydroxide, and then slowly added

0 second portion of 100 ml of dichloroacetic acid anhydride. The reaction product is neutralized with concentrated hydrochloric acid. 190 ml of water are added to dissolve the sodium chloride formed, the benzene is distilled off, the product is filtered and dried. Receive 347 g (82% yield from theory) of the product, t. P.P. 117.5-119 C.

Q Examples 4-6. Getting

2,2,5 trimethyl-3-dichloroacetyloxazolidine.

PRI me R 4 (known method). 18 ml of solution is added to 25 ml of benzene and 4.5 g of triethylamine.

 in benzene, 4.6 g of 2,2,5-three methyloxazolidine. While cooling in an ice bath and stirring, 5.9 g of dichloroacetic anhydride chloride is added dropwise to the mixture. After

When the reaction is complete, the mixture is poured into water and the benzene layer is separated. The latter is dried over anhydrous magnesium sulphate, after which the benzene is removed in vacuo. 7.7 g oily oil are obtained.

5 product, n || 1,4950.

Example 5. 150 ml (116 g; acetone and 600 ml of benzene are mixed with 150 g (162 ml) of isopropanolamine with a density of 0.961. Water is distilled off, the reaction mixture is cooled, and 200 ml of 20% sodium hydroxide and 175 ml are mixed with it water. Then, 2.2 ml (310 g) of 96% purity of dichloroacetic anhydride chloride is added. The temperature is maintained. The reaction product is neutralized with concentrated hydrochloric acid, introduced into a separating funnel and washed once with distilled water. Benzene is distilled off. To obtain 343 g 2, 2, 5-trimethyl-3-dichloroacetyloxazolidine (76% of theory ) with mp. 77-84c.

Claims (2)

Example 6. 150 g (16.2 ml) of isopropanolamine, 150 ml (116 g) of acetone and 600 ml of benzene were introduced into a two-liter reactor. With stirring, the mixture is kept at. 200 ml of 33% sodium hydroxide are added and the resulting mixture is stirred for an additional 2 hours. The mixture is cooled with an ice-cold acetone bath to 5 seconds and 110 ml of a mordant dichloroacetic anhydride is slowly added over 1 hour. The mixture was kept for 1.5 hours, and then another 110 ml of dichloroacetic anhydride chloride was added along with 10 ml of 33% sodium hydroxide over 1 hour. The pH of the reaction product is 11.1. The reaction products are neutralized with hydrochloric acid until pH 3. Add 185 ml of water to dissolve the resulting sodium chloride. The benzene is distilled off in vacuo. The product is filtered, distilled and dried without subsequent crystallization. 346.2 g of product were isolated (77% of theory) with a mp. 87-88 with. Invention Formula 1, Method for preparing N-substituted oxazolidines of formula ABOUT R "/ N d - I (I) lh o to cd where R is C-C-haloalkyl; R and R is C-Cd-alkyl and Nd is a hydrogen atom or C-Cd-alkyl, by reacting an alkanolamine of the general formula (YU (lHj-tH-tin where is as defined above, with a carbonyl compound of the formula ABOUT  , (W) 15 where R and R are as defined above, with the formation of an oxazolidine of the formula 20 Н1 (W) ABOUT H K Kz where Rg, Rg and R are as defined above, and water followed by acylation of oxazolidine of formula (IV) with an acid chloride of the formula ABOUT -C-C1 (NJ KI where R has the above values, when cooled in the medium of an organic solvent in the presence of an acceptor of hydrogen chloride, about t and h with the fact that, in order to increase the purity of the target product, the acylation is carried out in the presence of water formed oxazolidine formula (IY). 2. The method according to Claim 1 is also distinguished by the fact that the acylation carried out at a temperature of from -5 to 0 C.  Sources of information taken into account in the examination 1, Published for the Federal Republic of Germany No. 2350547, cl. x2 p, 3, pub. 1974.