Method for producing bispyrrolidine compounds

Abstract

The present application relates to a method for preparing compounds of the formula I in which, in a first step, γ-butyrolactone is reacted with diamines of the formula II to form bisamides of the formula Ill, with the amide function of the bisamides of the formula Ill then undergoing partial or complete catalytic hydrogenation in step II) to form bispyrrolidine compounds of the formula I.

Claims

1. A method for preparing bispyrrolidine compounds of the formula (I) ##STR00010## where Z is oxygen, n is a whole natural number selected from 1, m and o are independently a natural number selected from 1 to 12, comprising reacting, in a step I) γ-butyrolactone with diamines of formula II ##STR00011## where Z, n, m, and o are as defined above, to form bisamides of the formula III and, ##STR00012## catalytically hydrogenating, in a step II), the bisamides of the formula III to form the bispyrrolidine compounds of formula I.

2. The method as claimed in claim 1, wherein step I) is carried out at temperatures in the range from 100 to 300° C. with simultaneous or subsequent removal of the excess water by distillation.

3. The method as claimed in claim 1, wherein step II) is carried out in the presence of a hydrogenation catalyst in which the hydrogenation catalyst comprises at least one metal selected from the group consisting of Cu, Cr, Ni, Co, Fe, Pt, Pd, Re, Ru, and Rh.

4. The method as claimed in claim 1, wherein step II) is carried out using a heterogeneous catalyst.

5. The method as claimed in claim 1, wherein step II) is carried out in the presence of a Raney cobalt, Raney nickel or doped or undoped catalyst of the Cu—Cr type.

6. The method as claimed in claim 1, wherein the hydrogenation in step II) is carried out in the presence of a Raney cobalt catalyst or of a doped catalyst of the Cu—Cr type at temperatures in the range from 100 to 300° C. and at a hydrogen pressure in the range from 100 to 350 bar.

7. The method as claimed in claim 1, wherein, in the bispyrrolidine compounds of the formula I, Z=oxygen, n=1, and m=o=1.

Description

EXAMPLES

Example 1: Method for Preparing 1,1′-(oxybis(ethane-2,1-diyl))dipyrrolidine

Step I: Preparation of 1,1′-(oxybis(ethane-2,1-diyl))bis(pyrrolidin-2-one)

(1) A flask is filled with 100 g of 2,2′-oxybis(ethan-1-amine) and heated to 100° C. 165 g of γ-butyrolactone (GBL) is added dropwise and the solution is then stirred for 2 h. At the end of the addition, the mixture is stirred at 100° C. for a further 2 h. The mixture is then heated to 220° C. for 10 h and thereafter heated to 240° C. for a further 14 h with simultaneous removal of water by distillation. After cooling, the mixture was analyzed by gas chromatography. The mixture comprises 94.1% (area-%) of 1,1′-(oxybis(ethane-2,1-diyl))bis(pyrrolidin-2-one).

Step II: Preparation of a Mixture of 1,1′-(oxybis(ethane-2,1-diyl))dipyrrolidine and 1-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)pyrrolidin-2-one

(2) 10 g of Grace Raney cobalt 2724 (50% slurry in H.sub.2O) as catalyst is washed anhydrous with tetrahydrofuran (THF) and transferred to a 300 ml autoclave. The autoclave is filled with 50 g of 1,1′-(oxybis(ethane-2,1-diyl))bis(pyrrolidin-2-one) from step I and then closed. The autoclave is pressurized with 180 bar of H.sub.2 and the mixture is heated to 170° C. for 48 h. After cooling and depressurizing, the resulting mixture is analyzed by gas chromatography. The mixture comprises 36.7% (area-%) of 1,1′-(oxybis(ethane-2,1-diyl))dipyrrolidine and 47.2% (area-%) of 1-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)pyrrolidin-2-one.

Step III: Preparation of 1,1′-(oxybis(ethane-2,1-diyl))dipyrrolidine

(3) 5 g of Grace Raney cobalt 2724 (50% slurry in H.sub.2O) as catalyst is washed anhydrous with THE and transferred to a 300 ml autoclave. The autoclave is filled with 50 g of 1-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)pyrrolidin-2-one from step II and then closed. The autoclave is pressurized with 180 bar of H.sub.2 and the mixture is heated to 170° C. for 48 h. After cooling and venting, the resulting mixture is analyzed by gas chromatography. The mixture comprises 81.7% (area-%) of 1,1′-(oxybis(ethane-2,1-diyl))dipyrrolidine.

General Procedures for the Results of Tables 3-5 for the Hydrogenation

Hydrogenation of the Bisamide (1,1′-(oxybis(ethane-2,1-diyl))bis(pyrrolidin-2-one) with Raney-Co (Ra—Co)

(4) Bisamide (100 g), Ra—Co (5 g), and optionally the percent amount of solvent and/or additive shown in tables 3-5, in which the percent value indicates the proportion of solvent and/or additive in the total amount, are transferred to an autoclave (internal volume 300 mL). The filled reactor is carefully filled with hydrogen to the pressure indicated in tables 3-5. The reaction is stirred at 500 rpm at the temperature indicated in tables 3-5. On reaching the reaction temperature indicated in tables 3-5, stirring under the reaction conditions is continued for the period of time indicated in tables 3-5. At the end of the time interval indicated in tables 3-5, the reactor is cooled to room temperature, depressurized, and opened. A dark solution containing the solid catalyst is obtained. For analysis purposes, a sample is investigated by gas chromatography.

Hydrogenation of the Bisamide (1,1′-(oxybis(ethane-2,1-diyl))bis(pyrrolidin-2-one) with the Catalysts in Tables 3 and 4 that are not Raney Co

(5) Bisamide (50 g), catalyst (5 g), and the percent amount of solvent shown in tables 3-5, in which the percent value indicates the proportion of solvent in the total mixture, are transferred to an autoclave (internal volume 300 mL). The filled reactor is carefully filled with hydrogen to the pressure indicated in tables 3-5. The reaction is heated to the reaction temperature indicated in tables 3-5 and stirred at 500 rpm. On reaching the desired reaction temperature, stirring under the reaction conditions is continued for the period of time indicated in tables 3-5. At the end of this reaction time as indicated in tables 3-5, the reactor is cooled to room temperature, depressurized, and opened. A dark solution containing the solid catalyst is obtained. For analysis purposes, a sample is investigated by gas chromatography.

Continuous Hydrogenation of the Bisamide (1,1′-(oxybis(ethane-2,1-diyl))bis(pyrrolidin-2-one) with Ra—Co in Accordance with Table 5

(6) A 70 mL tubular reactor is filled with hydrogenation catalyst and the catalyst is optionally activated in a stream of hydrogen with application of heat. After activation, the reactor is continuously fed, at the temperature and pressure indicated in table 5, with a mixture of hydrogen, 1,1′-(oxybis(ethane-2,1-diyl))bis(pyrrolidin-2-one), and optionally solvent as specified in table 5 and the reaction output is analyzed by gas chromatography.

(7) Table 1 shows the composition of the copper chromite type catalysts used. Table 2 comprises the temperature, pressure, solvents, and additives used with the preferred hydrogenation catalyst systems of the method of the invention.

(8) TABLE-US-00001 TABLE 1 BASF % by % by % by designation Metal 1 weight Metal 2 weight Dopant weight Cu 0202 P CuO 83 Cr.sub.2O.sub.3 17 — — Cu 0396 P CuO 48 Cr.sub.2O.sub.3 48 MnO.sub.2 4 (E-396) Cu 1800P CuO 52 Cr.sub.2O.sub.3 48 — — Cu 1885 P CuO 53 Cr.sub.2O.sub.3 47 — — Cu 1950 P CuO 47 Cr.sub.2O.sub.3 46 MnO.sub.2 5.5 E 108 P CuO 44 Cr.sub.2O.sub.3 45 BaO 11

(9) TABLE-US-00002 TABLE 2 Temperature Pressure Solvent/ Catalyst system range (° C.) range (bar) Additive Raney Co 170-240 150-200 Dibutylamine Cu 0202 P 170-270 100-300 Hexane E-396 170-270 100-300 Hexane Cu 1950 P 170-270 100-300 Hexane E 108 P 170-270 100-300 Hexane Cu 1885 P 170-270 100-300 Hexane

(10) Tables 3-5 show the different yields in the hydrogenation of 1,1′-(oxybis(ethane-2,1-diyl))bis(pyrrolidin-2-one) in the presence of different catalyst systems for different further parameters

(11) TABLE-US-00003 TABLE 3 Pressure Temperature Reaction Conversion Yield Test (bar) (° C.) Catalyst Solvent/Additive time (h) (%) (% by GC) 1 80 170 Ra—Co Monoglyme 90% 12 100 51.3 2 260 170 Ra—Co — 36 98.9 70.3 3 260 170 Ra—Co Monoglyme 90% 24 100 71.5 4 180 170 Ra—Co — 60 100 60.9 5 180 200 Ra—Co — 15 87.6 26.5 6 180 200 Ra—Co Dibutylamine 10% 15 95.3 28.0 7 180 200 Cu—Cr/Ba — 15 61.8 10.5 E 108 P 8 180 240 Cu—Cr/Ba — 15 77.2 19.3 E 108 P 9 180 240 Cu—Cr/Ba Hexane 50% 15 100 66.3 E 108 P 10 180 240 Cu—Cr/Ba Hexane 25% 12 100 59 E 108 P

(12) TABLE-US-00004 TABLE 4 Pressure Temperature Reaction Conversion Yield Test (bar) (° C.) Catalyst Solvent/Additive time (h) (%) (% by GC) 13 180 200 Cu—Cr/Mn — 15 12.0 0.3 (Cu 1950 P) 14 180 200 Cu—Cr — 15 16.9 0.7 (Cu 1885 P)

(13) TABLE-US-00005 TABLE 5 Pressure Temperature Loading Conversion Yield Test (bar) (° C.) Catalyst Solvent/Additive (kg/L*h) (%) (% by GC) 15 200 170 Ra—Co — 0.21 87.8 25.4 16 200 190 Ra—Co — 0.21 99.0 51.8 17 200 190 Ra—Co THF (25%) 0.21 99.3 55.2 18 200 190 Ra—Co THF (50%) 0.14 99.9 48.1