DE803903C - Process for the preparation of pyrrolidine derivatives - Google Patents

Description

Process for the preparation of pyrrolidine derivatives It has been found that you get new, valuable pyrrolidine derivatives if you i, 4-dihalobutanes with diamines with at least one primary amine group or with primary oxyamines implements.

The implementation takes place z. B. according to the scheme where R = H, OH or another indifferent substituent, 1 = halogen and A is an amino or oxyalkyl or aryl group or aralkyl group.

Suitable starting materials are, on the one hand, the 1,4-dibromo-, -dichlor- or diiodobutane and its homologues, e.g. B. the 2, 5-dibromohexane or the r, 4-dichloropentane or hexane, also the so-called butadiene-bis-halohydrins, e.g. B. the Z, 4-dichloro-2, 3-dioxybutane, 2-methyl-r, 4-dibromo-2, 3-dioxybutane or their ethers and esters, on the other hand diamines, such as ethylene or propylene diamine, putrescine, cadaverine, hexa-, Octa- or decamethylene diamine, phenylene or toluene diamine, diaminodipropyl ether or oxyamines, such as ethanol, butanol or hexanolamine, the aminophenols, oxybenzylamines i.a.

The conversion often takes place sufficiently at ordinary temperature quickly; sometimes warming is required. One used to bind the split off Hydrogen halide expediently an excess of the diamine or oxyamine; one can but also a corresponding amount of alkali, alkaline earth oxide, a tertiary base or other agents that bind hydrogen halide. The use of Solventing is often beneficial. During the implementation arises at Use of excess amine initially a mixture of hydrohalic acids Salts of the pyrrolidine derivative formed and the excess diamine or oxyamine and the free bases, from which the desired pyrrolidine derivative can be obtained by adding from alkali and fractional distillation or recrystallization. In the case of the use of diprimary diamines, the by-product also arises Dipyrrolidino compound, e.g. B. from hexamethylenediamine and i, 4-dichlorobutane i, 6-dipyrrolidinohexane.

It is surprising that in the present case the implementation between two bifunctional compounds almost exclusively low molecular weight, monomeric Products of the pyrrolidine series is obtained, while generally in similar cases frequently polycondensation products with a chain-like structure and high molecular weight develop. One should therefore have expected that here, at least noticeably Amounts that would form open-chain high molecular weight polyimines. But in reality Here you mainly get ring-shaped, monomeric pyrrolidine derivatives.

The connections, some of which are new, easily accessible after the process are valuable intermediate products for dyes, plastics, textile auxiliaries and Pharmaceuticals.

Example i To 50o. Parts of i, 6-hexamethylenediamine are left at 100 ° 25o parts of 1,4-dichlorobutane slowly flow in while stirring that the temperature does not rise above 11o °. The mixture is heated to 110 ° for another hour and then 45 ° is added Add 50 per cent of potassium hydroxide solution. The whole is concentrated under reduced pressure, separating the precipitated potassium chloride from time to time. Finally rubbed it in one with methanol to remove the last amounts of potassium chloride, and distilled the filtrate at reduced pressure after a forerun, consisting of the excess applied hexamethylenediamine, the N- (6-aminohexyl) pyrrolidine formed in good yield distills from Kpr4 126 to i27 ° above. Smaller amounts of i, 6-dipyrrolidinohexane are obtained as tailings, Kp ,; 165 to 166 ° and almost no residue from higher polymer products.

Example 2 A mixture of 232 parts of i, 6-hexamethylenediamine and 45o parts of 5o ° / @ ger potassium hydroxide solution is heated to about 11o ° with stirring and reflux, gradually allowing 250 parts of i, 4-dichlorobutane to flow in. Some are moved Hours at 11o ° and added after cooling to about 70 ° for the separation of the Potassium chloride with 1 liter of common alcohol. After removal of the potassium chloride the filtrate is concentrated under reduced pressure, whereupon further amounts crystallized out Separates potassium chloride and then distilled under reduced pressure. The main product consists, as in example i, of N- (6-aminohexyl) pyrrolidine; next to it you get i, 6-Dipyrrolidinohexane, but no i, 4-butanediol and no significant amounts higher molecular weight products.

Example 3 To a solution of 324 parts of p-phenylenediamine in 1200 Parts of o-dichlorobenzene are allowed to flow in 125 parts of i, 4-dichlorobutane at 11o ° and stir the mixture for a few hours at this temperature. After it has cooled down the p-phenylenediamine dihydrochloride which has crystallized out is filtered off with suction and the filtrate directly subjected to distillation. After the dichlorobenzene has been distilled off an oily residue of about 100 parts remains, from which as the main fraction the N- (p-aminophenyl) pyrrolidine, bp "; 18o to 185 ', can be distilled off.

EXAMPLE 4 60o parts of 1,4-dichlorobirtane are allowed to flow in to a mixture, heated to 100%, of 268 parts of ethanolamine (91 °,% oig) and 90 ° parts of about 50% potassium hydroxide solution and stirring is continued for 20 hours at 100 °. Dinn is added at 70 ° to precipitate the potassium chloride 1 liter of ordinary alcohol and cool by placing it in ice. The precipitated potassium chloride is filtered off with suction and the filtrate is distilled under reduced pressure. The N-oxethylpyrrolidine formed in good yield passes over between 86 and 88 ' at a pressure of 23 mm.

EXAMPLE A solution of 116 parts of hexamethylenediamine in 464 parts of water is added dropwise with cooling to a solution of 124 parts of i, 4-dibromo-2,3-dioxybutane in 496 parts of water. The mixture is left to stand at room temperature until the titer no longer changes, 40 parts of caustic soda are then added and the mixture is concentrated under reduced pressure until the resulting sodium bromide crystallizes, which is removed by trituration with ethanol and filtration. The filtrate is evaporated down and finally distilled. The N- (6-aminohexyl) -3, 4-dioxypyrrolidine of the formula passes under 1.3 mm pressure at 189 'and shows the F. 84 °.

In an analogous manner, a good yield is obtained when using 6o parts of ethylenediamine the N- (ß-aminoethyl) -3, 4-dioxypyrrolidine from the boiling point 177 to 179 ° under 1.9 mm pressure.

Claims (1)

Claim: Process for the preparation of pyrrolidine derivatives, characterized in that i, 4-dihalobutanes are reacted with diamines having at least one primary amino group or with primary oxyamines.