Synthesis of N-vinyl compounds by reacting cylic NH-compounds with acetylene in presence of homogenous catalyst

Abstract

A process can be used to produce N-vinyl compounds by homogeneous catalysis. In the process, acetylene is reacted with a cyclic compound having at least one nitrogen as a ring member, hearing a substitutable hydrogen residue (cyclic compound C), in a liquid phase in the presence of a ruthenium complex containing at least one phosphine as a ligand (RuCat).

Claims

1. A process to produce N-vinyl compounds by homogeneous catalysis, the process comprising: reacting acetylene with a cyclic compound C having at least one nitrogen as a ring member, bearing a substitutable hydrogen residue, in a liquid phase in the presence of a ruthenium complex comprising at least one phosphine as a ligand (RuCat).

2. The process according claim 1, wherein the cyclic compound C is a cyclic amide, a cyclic urea or thiourea, or a cyclic carbamate or thiocarbamate.

3. The process according to claim 1, wherein the cyclic compound C is a cyclic amide.

4. The process according to claim 1, wherein the at least one phosphine is a mono-, di-, tri- or tetra dentate phosphine.

5. The process according to claim 1, wherein the at least one phosphine is a phosphine of formula (I) or (II), ##STR00054## wherein n is 0 or 1; R.sup.4 to R.sup.12 are, independently of one another, unsubstituted or at least monosubstituted C.sub.1-C.sub.10-alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10-heterocyclyl comprising at least one heteroatom selected from the group consisting of N, O, and S, C.sub.5-C.sub.14-aryl or C.sub.5-C.sub.10-heteroaryl comprising at least one heteroatom selected from the group consisting of N, O, and S, where substituents are selected from the group consisting of: F, Cl, Br, OH, CN, NH.sub.2 and C.sub.1-C.sub.10 alkyl; A is i) a bridging group selected from the group consisting of unsubstituted or at least monosubstituted N, O, P, C.sub.1-C.sub.6-alkane, C.sub.3-C.sub.10-cycloalkane, C.sub.3-C.sub.10-heterocycloalkane comprising at least one heteroatom selected from the group consisting of N, O, and S, C.sub.5-C.sub.14-aromatic, and C.sub.5-C.sub.10-heteroaromatic comprising at least one heteroatom selected from the group consisting of N, O and S, where substituents are selected from the group consisting of C.sub.1-C.sub.4-alkyl, phenyl, F, Cl, Br, OH, OR.sup.16, NH.sub.2, NHR.sup.16, and N(R.sup.16).sub.2, where R.sup.16 is selected from the group consisting of C.sub.1-C.sub.10-alkyl and C5-C.sub.10-aryl; or ii) a bridging group of the formula (VI) or (VII): ##STR00055## wherein m, q are, independently of one another, 0, 1, 2, 3 or 4; R.sup.13, R.sup.14 are, independently of one another, selected from the group consisting of C.sub.1-C.sub.10-alkyl, F, Cl, Br, OH, OR.sup.15, NH.sub.2, NHR.sup.15 and N(R.sup.15).sub.2, where R.sup.15 is selected from the group consisting of C.sub.1-C.sub.10-alkyl and C.sub.5-C.sub.10-aryl; X.sup.1, X.sup.2 are, independently of one another, NH, O or S; X.sup.3 is a bond, NH, NR.sup.16, O, S or CR.sup.17R.sup.18, R.sup.16 is unsubstituted or at least monosubstituted C.sub.1-C.sub.10-alkyl, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sub.10-heterocyclyl comprising at least one heteroatom selected from the group consisting of N, O and S, C.sub.5-C.sub.14-aryl or C.sub.5-C.sub.10-heteroaryl comprising at least one heteroatom selected from the group consisting of N, O and S, where substituents are selected from the group consisting of F, Cl, Br, OH, CN, NH.sub.2 and C.sub.1-C.sub.10-alkyl; R.sup.17, R.sup.18 are, independently of one another, unsubstituted or at least monosubstituted C.sub.1-C.sub.10-alkoxy, C.sub.1-C.sub.10-alkoxy, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sup.10 cycloalkoxy, C.sub.3-C.sub.10-heterocyclyl comprising at least one heteroatom selected from the group consisting of N, O and S, C.sub.5-C.sub.14-aryl, C.sub.5-C.sub.14-aryloxy or C.sub.5-C.sub.10-heteroaryl comprising at least one heteroatom selected from the group consisting of N, O, and S, where substituents are selected from the group consisting of F, Cl, Br, OH, CN, NH.sub.2, and C.sub.1-C.sub.10-alkyl; Y.sup.1, Y.sup.2, Y.sup.3 are, independently of one another, a bond, unsubstituted or at least monosubstituted methylene, ethylene, trimethylene, tetramethylene, pentamethylene or hexamethylene, where substituents are selected from the group consisting of F, Cl, Br, OH, OR.sup.15, CN, NH.sub.2, NHR.sup.15, N(R.sup.15).sub.2, and C.sub.1-C.sub.10-alkyl, where R.sup.15 is selected from the group consisting of C.sub.1-C.sub.10-alkyl and C5-C10-aryl.

6. The process according to claim 5, wherein the at least one phosphine is a phosphine of formula (I).

7. The process according to claim 6, wherein the at least one phosphine is a trialkyl phosphine.

8. The process according to claim 1, wherein the ruthenium complex is prepared separately or in situ during the reaction of the cyclic compound C with acetylene.

9. The process according to claim 8, wherein 1 to 10 mol of phosphine per mol of ruthenium are used in the preparation of the ruthenium complex.

10. The process according to claim 1, wherein the ruthenium complex is used in an amount of 0.01 to 5 mot % based on an amount of the cyclic compound C.

11. The process according to claim 1, wherein the reaction of the cyclic compound C and the acetylene is performed in presence of a N-base.

12. The process according to claim 1, wherein the liquid phase comprises a solvent.

13. The process according to claim 1, wherein the acetylene is fed to the reaction with a pressure of 1 to 2 bar at 20° C.

14. The process, according to claim 1, wherein the reaction is performed at a temperature of 50 to 200° C.

15. The process according to claim 1, wherein a pressure during the reaction is at maximum 10 bar.

Description

EXAMPLES

[0144] A) General procedure for examples 1, 9, 10, 11, 12, 14, 18, 21, 22, 23, 25, 27, 29, 30, 31, 32, 33, 38, 40, 42: An approximately 40 mL autoclave (Premex, Hastelloy) was charged with CodRu(met)2 (0,001-0.06 mmol), cyclic compound C (1 mmol), toluene (5.0-10.0 mL) or dichloromethane (10 ml, entry 9) or dimethylformamide (5 ml, entries 20, 36, 37, 40, 41), and tri-n-butylphosphine (0,005-0.18 mmol) or trioctylphosphine (0.1 mmol, entry 12) or tricyclohexylphosphine (0.1 mmol, entry 13) under argon atmosphere in the Glove-box. After closing the reaction vessel, the system was purged with acetylene (3 times). Finally, the autoclave was pressurized with acetylene (at 1,5 bar for 15 min at room temperature) and heated at 100-140° C. The mixture was then stirred at the specified temperature for 14-18 h. Note: At this temperature the internal pressure rises to 3-4 bar. Then, the reaction was cooled down on a water bath and depressurized carefully. The crude mixture was collected in a round bottom flask and concentrated under vacuum. Subsequently, it was dissolved in 1 mL of CH2Cl2 and coated on silica. The product was isolated by column chromatography (petroleum ether/ethyl: acetate 8/2—for different products the system ratio was slightly varied). When the reaction was performed in DMF, the product was either extracted with dichloromethane from aqueous solution of the reaction mixture, organic layer was washed with water minimum 5 times (entries 40, 41) or collected in a round bot-tom flask and concentrated under vacuum followed by column chromatography isolation (petroleum ether/ethyl: acetate, entries 20, 36, 37).

[0145] B) General procedure for examples 13, 15, 16, 17, 19, 20, 26, 28, 34, 35, 36, 37, 39, 41: An approximately 40 mL autoclave (Premex, Hastelloy) was charged with CodRu(met)2 (0.02 0.06 mmol), cyclic compound C (1 mmol), toluene (5.0 mL, entries 15, 17, 18, 19, 21, 22, 33, 35, 43, 47, 49) or dimethylphormamide (5-8 mL, entries 42, 44, 45), DMAP (0.04-0.12 mmol) and trin-butylphosphine (0.06-0.18 mmol) under argon atmosphere in the Glovebox. After closing the reaction vessel, the system was purged with acetylene (3 times). Finally, the autoclave was pressurized with acetylene (at 1,5 bar for 15 min at room temperature) and heated at 100-150° C. The mixture was then stirred at the specified temperature for 14-18 h. Note: At this temperature the internal pressure rises to 4-6 bar. Then, the reaction was cooled down on a water bath and depressurized carefully. The crude mixture was collected in a round bottom flask and concentrated under vacuum. Subsequently, it was dissolved in 1 mL of CH2Cl2 and coated on silica. The product was isolated by column chromatography (petroleum ether/ethyl: acetate 8/2—for different products the system ratio was slightly varied).

[0146] C) General procedure for the comparative examples 2 and 3: An approximately 40 mL auto clave (Premex, Hastelloy) was charged with Ruthenium 5% on activated charcoal (100 mg), 2-pyrrolidinone (13.1 mmol, 1.116 g), and diglyme (for entry 13) or toluene (for entry 14) (8.0 mL) under argon atmosphere in the Glovebox. After closing the reaction vessel, the system was purged with acetylene (3 times). Finally, the autoclave was pressurized with acetylene (at 1,5 bar for 15 min at room temperature) and heated at 170° C. The mixture was then stirred at the specified temperature for 14 h. Note: At this temperature the internal pressure rises to 5 (diglyme)/7 (toluene) bar. Then, the reaction was cooled down on a water bath and depressurized carefully. The crude mixture was collected in a round bottom flask and concentrated under vacuum. The crude mixture was analyzed by GC and/or NMR. Product was not isolated. The comparative examples 2 and 3 show, that by using a heterogeneous Ru-catalyst only gives the de sired product in minor amounts.

[0147] D) General procedure for comparative example 4: An approximately 40 mL autoclave (Premex, Hastelloy) was charged with Ruthenium 5% on activated charcoal (10 mg), 2-pyrrolidinone (1 mmol, 0,085 g), and toluene (10.0 mL) under argon atmosphere in the Glovebox. After closing the reaction vessel, the system was purged with acetylene (3 times). Finally, the autoclave was pressurized with acetylene (at 1,5 bar for 15 min at room temperature) and heated at 170° C. The mixture was then stirred at the specified temperature for 14 h. Note: At this temperature the internal pressure rises to 7 bar. Then, the reaction was cooled down on a water bath and depressurized carefully. The crude mixture was collected in a round bottom flask and concentrated under vacuum. The crude mixture was analyzed by GC and/or NMR. Product was not isolated. The comparative example 4 shows, that by using a heterogeneous Ru-catalyst only gives the desired product in minor amounts.

[0148] E) General procedure for the comparative examples 5, 6, 7 and 8: An approximately 40 mL autoclave (Premex, Hastelloy) was charged with 2 mol % Ruthenium catalyst (RuCl3.3H2O entry 5; Ru(AcAc)3-entry 6; Ru3(CO)12-entry 7; codRumet2-entry 8), 2-pyrrolidinone (1 mmol, 0,085 g), and toluene (5.0 mL) under argon atmosphere in the Glovebox. After closing the reaction vessel, the system was purged with acetylene (3 times). Finally, the autoclave was pressurized with acetylene (at 1,5 bar for 15 min at room temperature) and heated at 100° C. The mixture was then stirred at the specified temperature for 16-19 h. Note: At this temperature the internal pressure rises to 3-4 bar. Then, the reaction was cooled down on a water bath and depressurized carefully. The crude mixture was collected in a round bottom flask and concentrated under vacuum. The crude mixture was analyzed by GC. Product was not isolated. The comparative examples 5, 6, 7 and 8 show, that by using only a Ruthenium complex without a phosphine ligand, under the same conditions only trace amounts of the desired product are formed.

[0149] F) General procedure for the comparative example 43: An approximately 40 mL autoclave (Premex) was charged with 20 mol % of tri-n-butylphosphine (0.2 mmol, 0,042 g), 2-pyrrolidinone (1 mmol, 0,085 g), and toluene (10.0 mL) under argon atmosphere in the Glovebox. After closing the reaction vessel, the system was purged with acetylene (3 times). Finally, the autoclave was pressurized with acetylene (at 1,5 bar for 15 min at room temperature) and heated at 100° C. The mixture was then stirred at the specified temperature for 16 h. Note: At this temperature the internal pressure rises to 3-4 bar. Then, the re-action was cooled down on a water bath and depressurized carefully. The crude mixture was collected in a round bottom flask and concentrated under vacuum. The crude mixture was analyzed by GC. Product was not formed. The comparative examples 43 shows, that by using only the phosphine ligand without a Ruthenium complex gives no product under these conditions.

[0150] G) General procedure for the example 24: An approximately 40 mL autoclave (Premex, Hastelloy) was charged with anhydrous ruthenium (Ill) chloride (0.03 mmol, entry 26) or ruthenium (Ill) chloride hydrate (0.03-0.09 mmol, entries 27, 29, 30, 31), 5-methyl-1,3-oxazolidin-2-one (1 mmol, 0,101 g), toluene (5.0 mL), and tri-n-butylphosphine (0,06-0.12 mmol, entries 26, 27, 29, 30) or triphenylphosphine (0.1 mmol, entry 31) under argon atmosphere in the Glovebox. After closing the reaction vessel, the system was purged with acetylene (3 times). Finally, the autoclave was pressurized with acetylene (at 1,5 bar for 15 min at room temperature) and heated at 100° C. The mixture was then stirred at the specified temperature for 14-16 h. Note: At this temperature the internal pressure rises to 3-4 bar. Then, the reaction was cooled down on a water bath and depressurized carefully. The crude mixture was collected in a round bottom flask and concentrated under vacuum. The crude mixture was analyzed by GC and/or NMR. Product was not isolated.

TABLE-US-00001 Conver- sion to product (% in reaction mixture de- Pro- termined Ex- ce- Cyclic com- T, Yield, % by ample dure pound C Cat, mol % L1, mol % L2, mol % Solvent ° C. t, h product (isolated) GC) 1 A [00009] codRumet.sub.2/2 P(nBu).sub.3/ 10 — Tol 100 15 [00010] 89 100 2 C Ru/C/5 — — Diglyme 170 14 — 6 3 C Ru/C/5 — — Tol 170 16 — 10 4 D Ru/C/5 — — Tol 170 16 — <1 5 E RuCl.sub.3—3H.sub.2O/2 — — Tol 100 19 — 5 6 E Ru(AcAc).sub.3/2 — — Tol 100 19 — 0 7 E Ru.sub.3(CO).sub.12/2 — — Tol 100 19 — 8 8 E codRumet.sub.2/2 — — Tol 100 16 — 0, 9 9 A codRumet.sub.2/1 P(nBu).sub.3/ 10 — Tol 100 17 78 10 A codRumet.sub.2/0, 1 PnBu.sub.3/ 0, 5 — Tol 100 17 26 11 A codRumet.sub.2/2 P(OCt).sub.3/ 10 — Tol 100 17 79 12 A codRumet.sub.2/2 PCy.sub.3 — Tol 100 17 35 13 B [00011] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 100 6 [00012] 85 100 14 A [00013] codRumet.sub.2/2 P(nBu).sub.3/ 10 — Tol 100 17, 5 [00014] 33 33 15 B codRumet.sub.2/2 P(nBu).sub.3/ 10 (6) DMAP/4 Tol 100 16 80 100 16 B [00015] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 100 14, 5 [00016] 60 74 17 B [00017] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 150 15 [00018] 75 100 18 A [00019] codRumet.sub.2/4 P(nBu).sub.3/ 6 — DMF 140 17 [00020] 13 Nd 19 B [00021] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 140 16 [00022] 58 nd 20 B [00023] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 100 16 [00024] 9 100 21 A codRumet.sub.2/2 P(nBu).sub.3/ 6 — Tol 100 16 29 100 22 A [00025] codRumet.sub.2/2 P(nBu).sub.3/ 10 — Tol 100 16 [00026] 84 100 23 A codRumet.sub.2/2 PPh.sub.3/ 10 — Tol 100 16 17 20 24 G RuCl.sub.3—H.sub.2O/9 P(nBu).sub.3/ 12 — Tol 100 14.5 nd 100 25 A [00027] codRumet.sub.2/2 P(nBu).sub.3/ 6 — Tol 100 16 [00028] 82.2 100 26 B [00029] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 100 16 [00030] 10 nd 27 A codRumet.sub.2/2 P(nBu).sub.3/ 10 — Tol 100 15 25 nd 28 B [00031] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 120 16 [00032] 15 nd 29 A [00033] codRumet.sub.2/2 P(nBu).sub.3/ 6 — DMF 140 16 [00034] 25 57 30 A [00035] codRumet.sub.2/6 P(nBu).sub.3/ 18 — DMF 140 16 [00036] 27 nd 31 A [00037] codRumet.sub.2/2 P(nBu).sub.3/ 6 — Tol 130 16 [00038] 37 nd 32 A [00039] codRumet.sub.2/2 P(nBu).sub.3/ 10 — DMF 100 16 [00040] 56 nd 33 A [00041] codRumet.sub.2/2 P(nBu).sub.3/ 10 — DMF 100 18 [00042] 38 nd 34 B codRumet.sub.2/6 P(nBu).sub.3/ 18 DMAP/1 2 DMF 130 18 30 nd 35 B [00043] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 150 14 [00044] 14 nd 36 A [00045] codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 DMF 150 16 [00046] 20 nd 37 B codRumet.sub.2/6 P(nBu).sub.3/ 18 DMAP/1 2 DMF 150 16 [00047] 11 nd 38 A [00048] codRumet.sub.2/2 P(nBu).sub.3/ 6 — Tol 100 15 [00049] 22 64 39 B codRumet.sub.2/2 P(nBu).sub.3/ 6 DMAP/4 Tol 100 15 nd 82 40 A codRumet.sub.2/2 P(nBu).sub.3/ 10 — Tol 100 15 nd 51 41 B codRumet.sub.2/3 P(nBu).sub.3/ 6 DMAP/4 Tol 100 15 49 97 42 A [00050] codRumet.sub.2/2 P(nBu).sub.3/ 10 — Tol 100 16 [00051] 57 82 43 F [00052] — P(nBu).sub.3/ 20 — Tol 100 16 [00053] 0 0