IE43229B1

IE43229B1 - Heterocyclic nitromethylene compounds

Info

Publication number: IE43229B1
Application number: IE634/78A
Authority: IE
Original assignee: Ile De France
Priority date: 1975-06-09
Filing date: 1976-06-01
Publication date: 1981-01-14
Also published as: IE43229L

Description

The present invention provides substituted heterocyclic M-alkanolamines of general formula: in which R^ is a C1-5 hydroxyalkyl group, R2 is a hydrogen atom or a straight or branched alkyl group with 1 to 3 carbon atoms, and m is 1, 2 or 3.

In accordance with the present invention, these amines are prepared by reacting a compound of formula: ----(CHjm '•N I R. ίη which m is 1, 2 or 3 and R^ is hydroxyalkyl or acyloxyilkyl, in the reaction scheme below with a alkyl sulphate, an alkali metal alcoholate and a primary titroalkane to give a heterocyclic 2-nitromethylene N.lkanolamine (III). The reaction scheme of course shows pacific reagents, to the use of which the invention is <'t limited: - 2 43229 1. (ch,)2so4 c=o '·ΝΖ . °ch3 2H5 OC„H_ CK -CKL-OKa J z (II) CH2-CH2-OH CB9-CH2-OH (III) Dimethyl sulphate, diethyl sulphate, dipropyl sulphate and diisopropyl sulphate may be mentioned as examples of 5 alkyl sulphates used to obtain the compound II.

The alkali metal alcoholate is formed in known manner by reacting an alcohol such as methanol, ethanol, propanol, isopropanol or butanol with an alkali metal such as sodium or potassium.

In the example shown above intermediate product (II) may be isolated and purified. It may also be used for the subsequent reaction without being isolated.

The compounds of the invention are intermediate compounds in the synthesis of substances possessing valuable therapeutic properties.

The following Examples are presented in order to illustrate the technical characteristics of the present invention.

Example 1 N-(2-hydroxyethyl)-2-nitromethylene-pyrrolidine 20 264 g. of N-(2-acetoxyethyl)-2-pyrrolidinone was placed in a 3-litre flask and 194 g of dimethyl sulphate 229 added drop by drop. Mie solution obtained was heated at 6O-63°C for 1¾ hours. The solution was cooled and a solution of sodium ethoxide (formed from 35.5 g of sodium) in absolute ethyl alcohol (1080 ml) was added at a temperature of 15°C.

The mixture was stirred for 1 hour and 141 g of nitromethane then added. The reaction mixture was then heated for 5 hours at the reflux temperature.

The sodium methyl sulphate was filtered off and the alcohol and ethyl acetate were then evaporated off.

The precipitate formed by adding chloroform was filtered off; after evaporation of the solvent an oil was obtained. This was dissolved in 450 ml of dioxane. The crystals obtained were filtered, washed and dried. 132.6 g of N-(2-hydroxyethyl)-2-nitromethylene-pyrrolidine was obtained (melting point 123-124°c).

Example 2 J-(3-hydroxypropyl)-2-nitromethylen e-pyrrolidine 289 g of N-(3-acetoxypropyl)-2-pyrrolidinone was jlaced in a 2-litre flask and 185.6 g of dimethyl sulphate idded drop by drop. The mixture was heated for 3¾ hours it 6O-65°C. After cooling, a solution of sodium propoxide I rmed from 35.7 g of sodium in propyl alcohol (850 ml) '· s added at a temperate re of 12°C and the mixture was i irred for 1 hour. After addition of 141.3 g of nitroethane and heating for 4 hours at 5O-55°C, the resulting recipitate of sodium methylsulphate was filtered off and he solvents (propyl alcohol and propyl acetate) were izaporated off. 1700 ml of chloroform was added and the mixture was _ Λ _ filtered. The oil obtained after evaporation of the chloroform was dissolved in 500 ml of methyl isobutyl ketone, After crystallisation, the precipitate was filtered, washed with methyl isobutyl ketone, and dried. 147 g of N-(3-hydroxypropyl)-2-nitromethylenepyrrolidine was obtained (m.p. 63°C).

The N-(3-acetoxypropyl)-2-pyrrolidinone, which serves as starting material, was prepared as follows: 208 g of N-(3-hydroxypropyl)-2-pyrrolidinone and 222 g of acetic anhydride were placed in a 1-litre flask. The temperature of the medium was raised to 30°C. 0.5 ml of 95% concentrated sulphuric acid was added and the mixture was carefullv heated on a water bath and then at 150°C for two hours. After cooling, 1.6 g of sodium acetate was added and 25'» .5 g of N-(3-acetoxypropyl)-2-pyrrolidinone obtained by distillation in vacuo. (Yield 96.4%, b.p. 12mm/Hg = 165-17O°C).

Claims

1. A compound of formulas in which R^ is a C^ 5 hydroxyalkyl group, R 2 is a hydrogen atom or a straight or branched alkyl group with 1 to 3 carbon atoms, and m is 1, 2 or 3.

2. N-(2-hydroxyethyl)-2-nitromethylene-pyrrolidine.

3. N-(3-hydroxypropyl)-2-nitromethylene-pyrrolidine.

4. A method of preparing a compound as claimed in Claim 1 that comprises reacting a compound of general formula: .n which m is 1, 2 or 3 and is hydroxyalkyl or acyloxyilkyl, with a C^ alkyl sulphate, an alkali metal alcoholate ind a primary C^_ a nitroalkane.

5. A method as claimed in Claim 4 that comprises eacting H-(2-acetoxy-ethyl)-2-oxo-pyrrolidine with dimethyl ulphate, sodium ethoxide and nitromethane to produce the ompound claimed in Claim 2.

6. A method as claimed in Claim 4 that comprises aacting N-(3-acetoxy-propyl)-2-oxo-pyrrolidine with dimethyl ilphate, sodium propoxide and nitromethane to produce the impound claimed in Claim 3. 43 2 29

7. A method as claimed in Claim 4, substantially as hereinbefore cescribed in Example 1 or 2.

8. A compound as claimed in Claim 1, when prepared by a method as claimed in any one of Claims 4 to 7.