A process for preparing an n-substitued-2-oxazolidinone

Abstract

The invention is directed to a process for preparing an N-substitued-2-oxazolidinone comprising reacting a cyclic carbonate or a di-alkyl carbonate with an amine-alcohol compound in the presence of a base catalyst, wherein the base catalyst has a basicity pKaH+ of above 25 as measured in acetonitrile. Especially wherein 4-methyl- 1,3-dioxolan-2-one (PC) is reacted with 2-(methylamino)ethanol (NMEA) to prepare 3-methyloxazolidin-2-one (MeOx) and propane-1, 2-diol (PG) as a byproduct or wherein 1,3-dioxolan-2-one (EC) is reacted with 2-(methylamino)ethanol (NMEA) to prepare 3-methyloxazolidin-2-one (MeOx) and ethane-1, 2-diol (ethylene glycol) as a byproduct.

Description

[0001] A PROCESS FOR PREPARING AN N-SUBSTITUED-2-OXAZOLIDINONE

[0002] The invention is directed to a process for preparing an N-substitued-2- oxazolidinone comprising reacting a cyclic carbonate or a di-alkyl carbonate with an amine-alcohol compound in the presence of a base catalyst

[0003] Such a process is described in WO2024 / 147895. In this process propylene carbonate is reacted with 2-(methylamino) ethanol to form an intermediate carbonate which cyclizes to the N-substitued-2-oxazolidinone in the presence of potassium carbonate. The potassium carbonate is referred to as the base catalyst. After adding the starting compounds, the reaction mixture was kept at reaction conditions for 3 hours. The resultant yield was 93 %.

[0004] JP2010013399 describes the preparation of 3-methyl-2-oxazolidinone by reacting N-methyl ethanolamine with ethylene carbonate in the presence of a base catalyst. The examples showed that when the base catalyst was sodium hydroxide less impurities are formed than when the base catalyst was 1 ,5-diazabicyclo[4.3.0]-5- nonene (DBN). The publication describes heterogeneous and homogeneous base catalysts for this reaction.

[0005] A problem with the process of WO2024 / 147895 is that the yield can still be improved.

[0006] This object is achieved with the following process. A process for preparing an N- substitued-2-oxazolidinone comprising reacting a cyclic carbonate or a di-alkyl carbonate with an amine-alcohol compound in the presence of a base catalyst, wherein the base catalyst has a basicity pKaH+ of above 25 as measured in acetonitrile.

[0007] Applicant found that when this specific base catalyst is used the yield improves. Further it is found that the reaction can be performed at a higher rate when compared to when the state-of-the-art base catalyst is used. In the process a cyclic carbonate is reacted with an amine-alcohol compound or a di-alkyl carbonate is reacted with an amine-alcohol compound. The cyclic carbonate may be 1 ,3-dioxolan-2-one (also referred to as ethylene carbonate); 4- methyl-1 ,3-dioxolan-2-one (also referred to as propylene carbonate); 4- hydroxymethyl-1 ,3-dioxolan-2-one; 4,5-dimethyl-1 ,3-dioxolan-2-one; 4-ethyl-1 ,3- dioxolan-2-one; 4,4-dimethyl-1 ,3-dioxolan-2-one (previous three also referred to as butylene carbonates); 4-methyl-5-ethyl-1 ,3-dioxolan-2-one; 4,5-diethyl-1 ,3-dioxolan- 2-one; 4,4-diethyl-1 ,3-dioxolan-2-one; 1 ,3-dioxan-2-one; 4,4-dimethyl-1 ,3-dioxan-2- one; 5,5-dimethyl-1 ,3-dioxan-2-one; 5,5-dihydroxymethyl-1 ,3-dioxan-2-one; 5-methyl- 1 ,3-dioxan-2-one; 4-methyl-1 ,3-dioxan-2-one; 5-hydroxy-1 ,3-dioxan-2-one; 5- hydroxymethyl-5-methyl-1 ,3-dioxan-2-one; 5 ,5-diethy 1-1 ,3-dioxan-2-one; 5-methyl-5- propyl-1 ,3-dioxan-2-one; 4,6-dimethyl-1 ,3-dioxan-2-one; and 4,4,6-trimethyl-1 ,3- dioxan-2-one.

[0008] The di-alkyl carbonate may be a carbonate having the same or different allyl or alkyl groups having between 1 and 10 carbon atoms. In the reaction the alkyl moiety ends up as the corresponding alcohol as a byproduct of the reaction. In order to avoid the formation of a mixture of different alcohols the alkyl groups of the di-alkyl carbonate are preferably the same. Examples of suitable alkyl groups are methyl, ethyl, propyl, butyl, tert-butyl, 2-ethylhexyl, and cyclohexyl.

[0009] The amine alcohol compound is suitably a N-substituted ethanolamine having the below general formula:

[0010] HO-(C2H4)-NHR1

[0011] Where R1is a hydrocarbyl group having from 1 to 10 carbon atoms, a cycloalkyl group, an aralkyl group or a hydroxyalkyl group. R1may be a cycloalkyl group, such as a cyclohexyl group or a methyl cyclohexyl group. R1may also be a an aralkyl group, such as a benzyl group. R1may also be a hydroxyalkyl group, such as a hydroxymethyl group, a hydroxyethyl group or a hydroxypropyl group. Preferably R1is a hydrocarbyl group having from 1 to 6 carbon atoms, such as an alkyl group such as methyl group, an ethyl group, a propyl group, an isopropyl group or a butyl group. Examples of suitable N-substituted ethanolamine compounds are 2- (methylamino)ethanol, 2-(ethylamino)ethanol, 2-(butylamino)ethanol, 2- (benzylamino)ethanol and 2-(cyclohexylamino)ethanol.

[0012] A preferred reaction between a di-alkyl carbonate with an amine-alcohol compound may be represented as below: wherein R2 and RS are the different or preferably the same alkyl groups having 1 to 6 carbon atoms.

[0013] A preferred reaction between a cyclic carbonate with an amine-alcohol compound may be represented as below: wherein R^ is hydrogen, methyl, ethyl, propyl or hydroxymethyl.

[0014] A preferred reaction is wherein 4-methyl-1 ,3-dioxolan-2-one (PC) is reacted with 2-(methylamino)ethanol (NMEA) to prepare 3-methyloxazolidin-2-one (MeOx) and propane-1 ,2-diol (PG) as a byproduct.

[0015] Another preferred reaction is wherein 1 ,3-dioxolan-2-one (EC) is reacted with 2- (methylamino)ethanol (NMEA) to prepare 3-methyloxazolidin-2-one (MeOx) and ethane-1 ,2-diol (ethylene glycol) as a byproduct.

[0016] The base catalyst has a basicity pKaH+ of above 25 as measured in acetonitrile. The pKaH as measured in acetonitrile of various base compounds are well documented and described in https: / / doi.Org / 10.1002 / esoc 201900958. Examples of possible base catalysts suitable for use in the process of this invention are: inorganic bases, such as potassium tert-butoxide (CAS# 865-47-4), sodium tert- butoxide (CAS# 865-48-5), lithium tert-butoxide (CAS# 1907-33-1 ), potassium bis(trimethylsilyl)amide (CAS# 40949-94-8), potassium hydroxide (CAS# 1310-58-3) linear phosphazenes, such as N,N,N',N',N",N''-Hexamethylphosphorimidic triamide, Phosphazene base P1-H (CAS# 49778-01-0), tert-Butylimino- tris(dimethylamino)phosphorane, N'-tert-Butyl-N,N,N',N',N",N"- hexamethylphosphorimidic triamide (CAS# 81675-81-2), tert-Octylimino- tris(dimethylamino)phosphorane (CAS# 161118-69-0), 1 -Ethyl-2,2,4,4,4- pentakis(dimethylamino)-2A5,4A5-catenadi(phosphazene), Tetramethyl(tris(dimethylamino)phosphoranylidene)phosphorictriamid-Et-imin (CAS# 165535-45-5), 1 -tert-Butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)- phosphoranylidenamino]-2A5,4A5-catenadi(phosphazene) (CAS# 111324-04-0), N- tert-butyl-1 ,1 , 1 -tri(pyrrolidin-1 -yl)-l5-phosphanimine (CAS# 161118-67-8), 1 , 1 ,1 , 3,3,3- Hexakis(dimethylamino)diphosphazenium tetrafluoroborate (CAS# 137334-98-6) cyclic phoshpazenes, such as Hexafluorocyclotriphosphazene (CAS# 15599- 91-4), Ethoxy(pentafluoro)cyclotriphosphazene (CAS# 33027-66-6), Pentafluoro(phenoxy)cyclotriphosphazene (CAS# 33027-68-8), Hexamethoxyphosphazene (CAS# 957-13-1 ), Hexakis(3-fluoropropoxy)phosphazene (CAS# 1346521-36-5), Hexakis(1 H,1 H-perfluorononyloxy)phosphazene (CAS# 1365808-72-5)

[0017] 1-8-disubstituted naphthalenes, such as N,N,N',N'-Tetramethyl-1 ,8- naphthalenediamine (CAS# 20734-58-1), N",N"'"-1 ,8-Naphthalenediylbis(N,N,N',N'- tetramethyl-guanidine) (CAS# 442873-72-5)

[0018] Another group of base catalysts having such a high pKaH as measured in acetonitrile are bicyclic guanidine compounds. The bicyclic guanidine compound may have the formula: where R8, R7, R8, R9, R10, R11, R12, R^8, and R14are independently chosen from hydrogen, a linear or branched alkyl comprising 1 to 10 carbon atoms, an aromatic group comprising 6 to 12 carbon atoms, or one or more of the R7-R14may be eliminated and replaced with a double bond between successive carbon atoms; and t and u are independently 1-5. Preferably R7, R8, R9, R10, R11, R^2, R^8, and R14are hydrogen, t and u are 1 or 2 and R8is hydrogen or methyl.

[0019] Examples of suitable bicyclic guanidine compounds are 1 ,5,7-triazabicyclo (4.4.0)dec- 5-ene (TBD), 7-methyl-1 ,5,7- triazabicyclo(4.4.0)dec-5-ene (MTBD), 1- butyl-2,3-dimethyl-1 ,5,6,7-tetrahydroimidazo[1 ,2-a]pyrimidine (IP), 1 -butyl-2, 3,6,6- tetramethyl-1 ,5,6,7-tetrahydroimidazo[1 ,2-a]pyrimidine (Me2-IP).

[0020] The base catalyst can be a liquid and present as part of a homogeneous reaction mixture or be immobilised on a suitable carrier. The carrier may be a metal oxide, such as for example silica, alumina, titanium dioxide, a cross-linked polymer such as cross-linked poly(vinylpyridine) beads, polystyrene or a styrene and chloromethyl styrene copolymer, silicon carbide, or magnesium chloride. The base catalyst may also be a solid itself.

[0021] The reaction is exothermic and preferably cooling is performed to keep the temperature between 50 and 130 °C.

[0022] The reaction is performed in the liquid phase. The amount of base catalyst can vary and will also depend on if a homogeneous catalyst is used, or a heterogeneous catalyst is used. The process may be performed in two steps wherein in a first step the cyclic carbonate and the amine-alcohol compound are contacted in the absence of the base catalyst to obtain an intermediate adduct. In a subsequent step the formed mixture is contacted with the base catalyst wherein the intermediate addict cyclises to the desired N-substitued-2-oxazolidinone.

[0023] The molar ratio of the cyclic carbonate and the amine-alcohol compound or the molar ratio of the di-alkyl carbonate and the amine-alcohol compound is between 0.99:1 and 1 :0.99. The invention shall be illustrated by the following non-limiting examples.

[0024] Example 1

[0025] A 4 mL vial was charged with 0.88 g of 2-(methylamino)ethanol (NMEA), 1.20 g of 4- methyl-1 ,3-dixolan-2-one (propylene carbonate, PC), 13.09 mg of potassium tert- butoxide (KOtBu) and a stirring bar. The vial was closed and stirred at 100 °C at 900 rpm for 0.25 hours. After this time, a sample was analyzed by GC chromatography. Based on GC-analysis it was concluded 99.2% of PC was converted according to the reaction scheme of Figure 1. The main products are the intermediate adduct (0.05%) and MeOx (99.95%).

[0026] Example 2

[0027] Example 1 was repeated except that instead of potassium tert-butoxide (KOtBu) 16.23 mg of are 1 ,5,7-triazabicyclo (4.4.0)dec-5-ene (TBD) having a pKaH as measured in acetonitrile of 26.02 was used. The vial was closed and stirred at 100 °C at 900 rpm for 0.25 hours. After this time, a sample was analyzed by GC chromatography. Based on GC-analysis it was concluded 98.5% of PC was converted. The main products are the intermediate adduct (3.2%) and MeOx (96.8%).

[0028] Example 3

[0029] Example 1 was repeated except that instead of potassium tert-butoxide (KOtBu) 17.87 mg of 7-methyl-1 ,5,7- triazabicyclo(4.4.0)dec-5-ene (MTBD) having a pKaH as measured in acetonitrile of 25.47 was used. The vial was closed and stirred at 100 °C at 900 rpm for 1 hours. Based on GC-analysis it was concluded 98.8 % of PC was converted. The main products are the intermediate adduct (4.9%) and MeOx (95.1 %).

[0030] Comparative Experiment A

[0031] Example 1 was repeated except that instead of potassium tert-butoxide (KOtBu) 17.75 mg of 1 ,8-Diazabicyclo(5.4.0)undec-7-ene (DBU) having a pKaH as measured in acetonitrile of 24.31 was used. The vial was closed and stirred at 100 °C at 900 rpm for 0.25 hours. Based on GC-analysis it was concluded 97.0 % of PC was converted. The main products are the intermediate adduct (75.9%) and MeOx (24.1 %). Comparative Experiment B

[0032] Example 1 was repeated except that instead of potassium tert-butoxide (KOtBu) 14.48 mg of 1 ,5-Diazabicyclo(4.3.0)non-5-ene (DBN) having a pKaH as measured in acetonitrile of 23.89 was used. The vial was closed and stirred at 100 °C at 900 rpm for 1 hours. Based on GC-analysis it was concluded 98.2 % of PC was converted. The main products are the intermediate adduct (70.3%) and MeOx (29.7%).

[0033] Comparative experiment C

[0034] Example 1 was repeated except that no potassium tert-butoxide (KOtBu) was added and the temperature was 25 °C. The vial was closed and stirred at room temperature at 900 rpm for 19 hours. After this time, a sample was analyzed by GC chromatography. Based on GC-area analysis it was concluded 96.8% of PC was converted. The main products are the intermediate adduct (96.4%) and MeOx (3.6%).

[0035] Comparative experiment D

[0036] Comparative experiment B was repeated at 100 °C at 900 rpm for 19 hours. After this time, a sample was analyzed by GC chromatography. Based on GC-analysis it was concluded 98.7% of PC was converted. The main products are the intermediate adduct (84.6%) and MeOx (15.4%).

[0037] The results of the above examples and experiments are summarized in the below table.

[0038] Table 1 .

[0039] The yield to MeOx in time for Examples 1 , 2 and comparative experiment A in time are shown in Figure 2.

Claims

CLAIMS1 . A process for preparing an N-substitued-2-oxazolidinone comprising reacting a cyclic carbonate or a di-alkyl carbonate with an amine-alcohol compound in the presence of a base catalyst, wherein the base catalyst has a basicity pKaH+ of above 25 as measured in acetonitrile.

2. The process according to claim 1 , wherein the base catalyst is a bicyclic guanidine compound.

3. The process according to claims 1-2, wherein the base catalyst is a bicyclic guanidine compound of the formula:where R8, R7, R8, R9, R10, R11, R12, R13, and R14are independently chosen from hydrogen, a linear or branched alkyl comprising 1 to 10 carbon atoms, an aromatic group comprising 6 to 12 carbon atoms, or one or more of the R7-R^4may be eliminated and replaced with a double bond between successive carbon atoms; and t and u are independently 1 -5.

4. The process according to claim 3, wherein R7, R8, R9,and R^4are hydrogen, t and u are 1 or 2 and R8is hydrogen or methyl.

5. The process according to claim 4, wherein the base catalyst is 1 ,5,7- triazabicyclo(4.4.0)dec-5-ene (TBD) or 7-methyl-1 ,5,7- triazabicyclo(4.4.0)dec-5-ene (MTBD).

6. The process according to claim 1 , wherein the base catalyst is an alkaline tert, butoxide compound.

7. The process according to claim 6, wherein the alkaline tert, butoxide compound is potassium tert, butoxide.

8. The process according to any one of claims 1-7, wherein the amine alcohol compound is a N-substituted ethanolamine having the below general formula:HO-(C2H4)-NHR1 is a hydrocarbyl group having from 1 to 10 carbon atoms, a cycloalkyl group, an aralkyl group or a hydroxyalkyl group.

9. The process according to claim 8, wherein R1 is an alkyl group having 1 to 6 carbon atoms.

10. The process according to any one of claims 1-9, wherein a di-alkyl carbonate is reacted with an amine-alcohol compound as is presented belowwherein R2 and R^ are the different or preferably the same alkyl groups having 1 to 6 carbon atoms.

11. The process according to any one of claims 1-9, wherein a cyclic carbonate is reacted with an amine-alcohol compound as is represented below:wherein R^ is hydrogen, methyl, ethyl, propyl or methylhydroxy.

12. The process according to claim 11 , wherein 4-methyl-1 ,3-dioxolan-2-one(PC) is reacted with 2-(methylamino)ethanol (NMEA) to prepare 3- methyloxazolidin-2-one (MeOx) and propane-1 ,2-diol (PG) as a byproduct or wherein 1 ,3-dioxolan-2-one (EC) is reacted with 2-(methylamino)ethanol (NMEA) to prepare 3-methyloxazolidin-2-one (MeOx) and ethane-1 ,2-diol (ethylene glycol) as a byproduct.

13. The process according to any one of claims 1-12, wherein the temperature is between 50 and 130 °C.

14. The process according to any one of claims 1-13, wherein the molar ratio of the cyclic carbonate and the amine-alcohol compound or the molar ratio of the di-alkyl carbonate and the amine-alcohol compound is between 0.99:1 and 1 :0.99.

15. A process for preparing an N-substitued-2-oxazolidinone comprising reacting a cyclic carbonate or a di-alkyl carbonate with an amine-alcohol compound in the presence of a base catalyst, wherein the base catalyst is an alkaline tert, butoxide compound.

16. The process according to claim 15, wherein the alkaline tert, butoxide compound is potassium tert, butoxide.

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