Method for the methylation of nitrogen-containing organic compounds

Abstract

A method for the methylation of amines, amides and imines comprises the step of reacting these compounds with CO.sub.2 and H.sub.2 in the presence of a Ruthenium-phosphine complex.

Claims

1. A method for the N-methylation of nitrogen-containing compounds comprising the step of: a) reacting the nitrogen-containing organic compound with CO.sub.2 and H.sub.2 in the presence of a Ruthenium-Phosphine-complex.

2. The method according to claim 1, wherein step a) is performed under acidic conditions.

3. The method according to claim 1, wherein the Phosphine in the Ruthenium-Phosphine-Complex is a Trisaryl, Trisheteroaryl, Bisarylalkyl and/or Bisheteroarylalkyl Phosphine.

4. The method according to one of claims 1, wherein the Ruthenium-Phosphine-Complex comprises a bisphosphororganic component, trisphosphororganic or higher phosphororganic component.

5. The method according to claim 1, wherein step a) is performed under acidic conditions whereby the acid is selected out of the group comprising sulfonic acids, especially methanesulfonic acid, trifluormethansulfonic acid, p-toluolsulfonic acid, p-bromobenzosulfonic acid, p-nitrobenzosulfonic acid, sulfuric acid, hydrochloric acid, hydrofluoric acid, trifluoracetic acid, perchloric acid, bis(trifluoromethane)sulfonimide or mixtures thereof.

6. The method according to claim 1, wherein step a) is carried out at an initial hydrogen pressure of 1 bar.

7. The method according claim 1, wherein step a) is carried out at an initial CO.sub.2 pressure of 1 bar.

8. The method according to claim 1, wherein the initial pressure ratio of H.sub.2: CO.sub.2 is 0.5:1 to 5:1.

9. The method according to claim 1, wherein step a) is carried out in a dipolar protic or aprotic solvent or in CO.sub.2.

Description

EXAMPLES

(1) Synthesis of [Ru(Triphos)(TMM)]

(2) ##STR00002##

(3) A 35 mL schlenk tube was charged with 159.5 mg (0.5 mmol) [Ru(cod)(methylallyl).sub.2] and 312.0 mg 1,1,1-tris(diphenylphosphinomethyl)ethane (Triphos) in 25 mL toluene. After heating for 2 h at 110 C., the resulting solution was concentrated in vacuo and treated with 10 mL of pentane. The precipitating complex was isolated and washed three times with 10 mL pentane. After drying, [Ru(Triphos)(TMM)] was obtained as a bright yellow powder in 75% yield.

(4) General procedures for direct methylation of amines with CO.sub.2/H.sub.2.

(5) All high pressure batch experiments were conducted in stainless steel 10 mL autoclaves equipped with a glass inlet and a magnetic stir bar. Prior to use, the autoclave was dried under vacuum for 3 hours and repeatedly filled with argon. Under an argon atmosphere, catalyst [Ru(Triphos)(TMM)] (0.019 g, 0.025 mmol) and HNTf.sub.2 (0.014 g, 0.05 mmol) were weighed in a Schlenk tube. After dissolving in THF (1.0 mL), the mixture was transferred viaqa cannula to the autoclave followed by the addition of the aniline substrate (1.0 mmol) in THF (1.0 mL). The autoclave was then pressurized with CO.sub.2 to 20 bar and then H.sub.2 was added up to a total pressure of 80 bar. The reaction mixture was stirred and heated to 150 C. in an oil bath. After 10 h, the autoclave was cooled in an ice bath and then carefully vented. The reaction solution was analyzed by .sup.1H-NMR with internal standard mesitylene and the results confirmed by gas chromatography using dodecane as internal standard.

Example I

Methylation of N-methylaniline to N,N-Dimethylaniline

(6) The reaction was carried out as described above, except where indicated. The results are shown in the following Table I:

(7) TABLE-US-00001 TABLE I Temp Time Yield Entry Acid [mol %] [ C.] [h] [%] 1 140 10 2 2 HNTf.sub.2 (0.5) 140 22 11 3 HNTf.sub.2 (2.5) 140 22 84 4 HNTf.sub.2 (5), 140 22 0 no catalyst added 5 HNTf.sub.2 (5), 1% 140 10 50 catalyst used 6 HNTf.sub.2 (5) 140 22 97 7 HNTf.sub.2 (5), 140 22 25 CO.sub.2/H.sub.2: (10/30 bar) 8 HNTf.sub.2 (5) 120 22 81 9 HNTf.sub.2 (5) 100 22 58 10 HNTf.sub.2 (5) 150 0.5 9 11 HNTf.sub.2 (5) 150 1 20 12 HNTf.sub.2 (5) 150 1.5 29 13 HNTf.sub.2 (5) 150 2 34 14 HNTf.sub.2 (5) 150 3 49 15 HNTf.sub.2 (5) 150 4 69 16 HNTf.sub.2 (5) 150 8 97 17 HNTf.sub.2 (5) 150 10 99 18 MSA (5) 150 10 95 19 p-TsOH (5) 150 10 97

Example II

Methylation of Various Secondary Amines

(8) The following amides were reacted as described above, using the following conditions: Substituted aromatic amine (1.0 mmol), [Ru(Triphos)(TMM)] (2.5 mol %), HNTf.sub.2 (5 mol %), THF (2 mL), CO.sub.2/H.sub.2 (20/60 bar), 150 C. Results are shown in the following Table II:

(9) TABLE-US-00002 TABLE II Entry Amine Product Time [h] Yield [%] 1 22 90 2 10 90 3 10 35 4 0 20 73 5 20 70 6 15 64 7 48 27

Example III

Methylation of Various Primary amines and Amides

(10) Several primary amines and Acetanilide were reacted using the following conditions: Substituted primary aniline or amide (1.0 mmol), [Ru(Triphos)(TMM)] (2.5 mol %), HNTf.sub.2 (5 mol %), THF (2 mL), CO.sub.2/H.sub.2 (20/60 bar), 150 C. The results are shown in the following Table III

(11) TABLE-US-00003 TABLE III En- Time Yield try amine/amide Product [h] [%] 1 15 94 2 0 10 93 3 24 93 4 20 94 5 15 84 6 24 69

Example IV

Reductive Methylation of Various Imines

(12) Several imines were reacted using the following conditions: Substituted imine (1.0 mmol), [Ru(Triphos)(TMM)] (2.5 mol %), HNTf.sub.2 (5 mol %), THF (2 mL), CO.sub.2/H.sub.2 (20/60 bar), 100 C. The results are shown in the following Table IV

(13) TABLE-US-00004 TABLE IV Time Yield Entry Imine Product [h] [%] 1 0 24 90 2 24 80 3 24 96

(14) Although the present invention has been disclosed in the form of preferred embodiments and variations thereon, it will be understood that numerous additional modifications and variations could be made thereto without departing from the scope of the invention.

(15) For the sake of clarity, it is to be understood that the use of a or an throughout this application does not exclude a plurality, and comprising does not exclude other steps or elements. The mention of a unit or a module does not preclude the use of more than one unit or module.