HU193045B - Process for producing sulfuric acid derivatives - Google Patents

Abstract

Esters of sulphuric-acid of formula (I) are prepd. by reacting cpds. of formula (III) (sic) in the presence of solvent with sulphur-trioxide or an agent used to introduce sulphur-trioxide. In the formula R1 and R2 are each straight or branched satd. 1-6C alkyl or unsatd. 2-4C alkyl with -NR1R2 may mean a 5-7 membered ring contg. opt. apart from the nitrogen a further hetero atom like oxygen, sulphur or another nitrogen.

Description

The present invention relates to a process for the preparation of new sulfuric acid esters of the formula I in the following formula

R 'and R ² are the same and are C 1-4 alkyl.

Compounds of formula (I) are useful intermediates in the preparation of a number of furan derivatives formed by the interaction of compounds of formula (I) with nucleophilic reaction partners. For example, the compound of formula (I) wherein R ¹ and R ² are both methyl, known excellent gastric and duodenal l- antiulcer activity, (II) {2- [5- (dimethylamino) -2 - A useful intermediate in the preparation of (furylmethylthio) ethyl] - (amino-1-methylamino) -2-nitroethylene (internationally known as ranitidine).

All of the products of formula (I) obtained by the process of the present invention are new compounds and, according to the present state of the art, represent a class of compounds which have not been previously known.

According to the present invention, compounds of formula I are prepared by reacting a compound of formula III wherein R 1 and R ² are the same as in formula I, in the presence of a solvent, with sulfur trioxide or with a sulfur trioxide. -trioxide.

Suitable sulfur trioxide include, for example, a complex compound of sulfur trioxide with dimethylformamide or pyridine or dioxane; it is preferred to use the dimethylformamide complex with sulfur trioXide. Preferred solvents are, for example, acetonitrile or dimethylformamide.

All starting materials of formula (ΙΙΪ) [J. Chem. Soc., 69, 464 (1947)], and the above-mentioned complexes for the introduction of sulfur trioxide are known compounds. (See, e.g., J. Am. Chem. Soc. 81, 1764 (1959); Chem. And Ind. 1966, 900.] The present invention is preferably carried out by reacting a compound of formula (III) with a dimethylformamide sulfur trioxide complex in acetonitrile at a molar ratio of about 1: 1. As the reaction proceeds, the corresponding compound of formula (I) precipitates in solid form and is readily isolated upon completion of the reaction. The following examples illustrate the process of the invention.

Example 1 [5- (Dimethylaminomethyl) -2-furylmethyl] bisulfate (Compound of Formula I, R '= R ² = CH ₃ )

The step:

Preparation of dimethylformamide sulfur trioxide (DMF.SO ₃ ) complex 2

To the dimethylformamide (152 g, 2.0 moles) was added 40-50 g (0.50-0.62 moles) of liquid sulfur trioxide with stirring and cooling so that the temperature of the reaction mixture did not rise above 20 ° C. The mixture is then cooled to 5 ° C, whereupon a portion of the complex precipitates in crystalline form. The sulfur trioxide content of the complex was determined to be 5.80-6.40 mmol / g after nucleation.

B 'step:

Preparation of [5- (Dimethylaminomethyl) -2-furylmethyl] hydrogen sulfate: Cooling and stirring to a solution of 22.70 g (143.2 mmol) of the wet aqueous DMF.SO ₃ complex in 258 mL of acetonitrile while 22.23 g (143.2 mmol) of (5-dimethylaminomethyl) -furfuryl alcohol is added at a rate such that the internal temperature is maintained between 15 and 20 ° C. Thereafter, 258 ml of acetonitrile were added and the mixture was cooled to 4 ° C the next day. The precipitated crystalline precipitate was filtered off with suction, washed with acetonitrile and dried to give 17.30 g (51.3%) of product.

Example 1 for the title product, m.p. 179-181 ° C.

Example 2 [5- (Dimethyl-1-aminomethyl) -2-furylmethyl] hydrogen sulfate

Under stirring and cooling, 9.93 g (124.02 mol) of sulfur trioxide are introduced into 190 ml of anhydrous dimethylformamide at such a rate that the internal temperature of the reaction mixture does not rise above 20 ° C. Then, while maintaining the reaction temperature below 20 ° C with stirring, 19.25 g / 124.02 moles /

5-Dimethylaminomethyl-furfuryl-a-1-ol is added. After addition, the reaction mixture was stirred for an additional 30 minutes at the above temperature and then held overnight at 0 to 4 ° C. The precipitate was filtered off, washed with anhydrous dimethylformamide and then with ether, and dried in vacuo at room temperature. Product weight: 27.10 g. Yield: 92.8%. 179-181 ° C.

Claims (4)

PATENT CLAIMS A process for the preparation of a novel sulfuric acid ester of formula (I): wherein: R ¹ and R ² are the same and are characterized by a C 1-4 alkyl group that is a compound of formula III wherein R ¹ and R ² are the same as in formula I in the presence of a solvent, sulfur trioxide or with an agent suitable for introducing sulfur trioxide. 2. A process according to claim 1 wherein the sulfur trioxide is used as a complexing agent with a complex of sulfur trioxide with dimethylformamide 2193045, pyridine or dioxane. The process according to claim 1 or 2, wherein the solvent is acetonitrile or dimethylformamide. 4. A process according to any one of claims 1-3 wherein the starting compound is a compound of formula III wherein R ¹ and R ² are both methyl.