Process for preparing amines

Abstract

The present invention refers to a process for preparing amines comprising reacting a compound of the formula R.sup.1COR.sup.2 comprising a carbonyl moiety with a amine compound of the formula HNR.sup.3R.sup.4 and carbon monoxide in the presence of a catalyst.

Claims

1. A process for preparing an amine of formula I comprising reductive amination of a carbonyl compound of the formula II with an amine compound of the formula III and carbon monoxide as reductant in the presence of a catalyst and without introducing hydrogen (H.sub.2) from an external hydrogen source to yield said amine of formula I: ##STR00009## wherein: R.sup.1 and R.sup.2 are each independently hydrogen or a substituent selected from the group consisting of C.sub.1-C.sub.20 alkyl, C.sub.2-C.sub.20 alkenyl, C.sub.2-C.sub.20 alkynyl, aryl, C.sub.1-C.sub.20 carboxylate, C.sub.1-C.sub.20 alkoxy, C.sub.2-C.sub.20 alkenyloxy, C.sub.2-C.sub.20 alkynyloxy, aryloxy, C.sub.2-C.sub.20 alkoxycarbonyl, C.sub.1-C.sub.20 alkylthiol, arylthiol, C.sub.1-C.sub.20 alkylsulfonyl, and C.sub.1-C.sub.20 alkylsulfinyl, each of which is optionally substituted with one or more moieties selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.1-C.sub.10 alkoxy, aryl, and one or more functional groups selected from the group consisting of hydroxyl, thiol, thioether, ketone, aldehyde, ester, ether, amine, imine, amide, nitro, carboxylic acid, disulfide, carbonate, isocyanate, carbodiimide, carboalkoxy, carbamate, and halogen, wherein at least one of R.sup.1 and R.sup.2 is not hydrogen; and R.sup.3 and R.sup.4 are each independently hydrogen or a substituent selected from the group consisting of C.sub.1-C.sub.20 alkyl, C.sub.2-C.sub.20 alkenyl, C.sub.2-C.sub.20 alkynyl, aryl, C.sub.1-C.sub.20 carboxylate, C.sub.1-C.sub.20 alkoxy, C.sub.2-C.sub.20 alkenyloxy, C.sub.2-C.sub.20 alkynyloxy, aryloxy, C.sub.2-C.sub.20 alkoxycarbonyl, C.sub.1-C.sub.20 alkylthiol, arylthiol, C.sub.1-C.sub.20 alkylsulfonyl, and C.sub.1-C.sub.20 alkylsulfinyl, each of which is optionally substituted with one or more moieties selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.1-C.sub.10 alkoxy, aryl, and one or more functional groups selected from the group consisting of hydroxyl, thiol, thioether, ketone, aldehyde, ester, ether, amine, imine, amide, nitro, carboxylic acid, disulfide, carbonate, isocyanate, carbodiimide, carboalkoxy, carbamate, and halogen, wherein at least one of R.sup.3 and R.sup.4 is not hydrogen.

2. The process according to claim 1, wherein the reaction is carried out in a solvent, selected from aliphatic, cycloaliphatic or aromatic solvents, esters, ethers or mixtures thereof.

3. The process according to claim 1, wherein the reaction is carried out at a reaction pressure of 1 to 200 bar.

4. The process according to claim 1, wherein the reaction is carried out at an elevated temperature between 50 to 350 C.

5. The process according to claim 1, wherein the amine of formula I is obtained in a yield of at least 93%.

Description

EXAMPLE 1

(1) ##STR00002##

(2) 0.2 mg of Rh.sub.2(OAc).sub.4 was put. Then 27.6 mg of p-anisidine were added. The reaction vial was evacuated and carbon monoxide was added. 0.1 mL of THF (3.7 ppm of water) was added. 20 L of 2-butanone was added. Autoclave was degassed after which carbon monoxide was added. A CO-pressure of 20 bar was established. The autoclave was heated up to 120 C. After 4 h, the reaction mixture was cooled down to room temperature and the pressure was released. The product was isolated in quantitative yield.

(3) 1H NMR (500 MHz, CDCl.sub.3) ppm 6.79 (d, J=8.9 Hz, 2H), 6.57 (d, J=8.9 Hz, 2H), 3.75 (s, 3H), 3.38-3.28 (m, 1H), 3.18 (br s, 1H), 1.55-1.67 (m, 1H), 1.40-1.51 (m, 1H), 1.16 (d, J=6.3 Hz, 3H), 0.96 (t, J=7.4 Hz, 3H)

(4) 13C NMR (125 MHz, CDCl.sub.3) ppm 10.3, 20.1, 29.5, 50.7, 55.7, 114.6, 114.8, 141.9, 151.7

EXAMPLE 2

(5) ##STR00003##

(6) 8.8 mg (0.2 mol %) of Rh.sub.2(OAc).sub.4 were put into a 36 ml autoclave. Then 1.21 g of p-anisidine was added. The autoclave was degassed and carbon monoxide was added. 2 mL of THF were added. 1 mL of benzaldehyde was added. The pressure of CO was 20 bar. The autoclave was heated to 120 C. After 6 h, the reaction mixture was cooled down to room temperature and the pressure was released. The product was isolated in 97% yield.

(7) 1H NMR (500 MHz, CDCl.sub.3) ppm 7.35-7.45 (m, 4H), 7.31 (t, J=7.0 Hz, 1H), 6.82 (d, J=8.9 Hz, 2H), 6.64 (d, J=8.9 Hz, 2H), 4.32 (s, 2H), 3.78 (s, 3H), 3.70 (br s, 1H). 13C NMR (125 MHz, CDCl.sub.3) ppm 49.1, 55.7, 114.0, 114.8, 127.1, 127.5, 128.5, 139.6, 142.4, 152.1

EXAMPLE 3

(8) ##STR00004##

(9) 0.31 mg (0.21 mol %) of Rh.sub.2(OAc).sub.4 was put. Then 28 L (100 mol %) of pyrrolidine were added. 0.2 mL of THF (18.1 ppm of water) was added. 35 L of benzaldehyde were added. The pressure of CO was 20 bar. The autoclave was heated to 120 C. After 4 h, the reaction mixture was cooled down to room temperature and the pressure was released. 85% yield.

(10) 1H NMR (500 MHz, CDCl.sub.3) ppm 7.20-7.45 (m, 5H), 3.66 (s, 2H), 2.50-2.60 (m, 4H), 1.75-1.87 (m, 4H).

(11) 13C NMR (125 MHz, CDCl.sub.3) ppm 23.4, 54.1, 60.7, 126.8, 128.1, 128.8, 139.3

EXAMPLE 4

(12) ##STR00005##

(13) 0.44 mg of Rh.sub.2(OAc).sub.4 was put. Then 56.9 mg (100 mol %) of p-anisidine were added. 0.1 mL of THF (19.7 ppm of water) was added. 50 L of pivaldehyde were added. The pressure of CO was 20 bar. The autoclave was heated to 120 C. After 4 h, the reaction mixture was cooled down to room temperature and the pressure was released. Quantitative yield.

(14) 1H NMR (500 MHz, CDCl.sub.3) ppm 6.82 (d, J=8.9 Hz, 2H), 6.63 (d, J=8.9 Hz, 2H), 3.77 (s, 3H), 3.40 (br s, 1H), 2.88 (s, 2H), 1.03 (s, 9H)

(15) 13C NMR (125 MHz, CDCl.sub.3) ppm 27.6, 31.7, 55.7, 59.9, 113.8, 114.8, 143.4, 151.7

EXAMPLE 5

(16) ##STR00006##

(17) 0.40 mg of Rh.sub.2(OAc).sub.4 was put. Then 21 L of N-methyl-N-benzylamine were added. 0.1 mL of THF (5.7 ppm of water) was added. 18 L of benzaldehyde were added. The pressure of CO was 20 bar. The autoclave was heated to 140 C. After 12 h, the reaction mixture was cooled down to room temperature and the pressure was released. 93% yield.

(18) 1H NMR (500 MHz, CDCl.sub.3) ppm 7.10-7.33 (m, 10H), 3.44 (s, 4H), 2.10 (s, 3H).

(19) 13C NMR (125 MHz, CDCl.sub.3) ppm 42.2, 61.8, 126.9, 128.2, 128.9, 139.2

EXAMPLE 6

(20) ##STR00007##

(21) 23 mg of 10% Rh/C was put. Then 40 L of aniline were added. 0.1 mL of THF (21.3 ppm of water) was added. 44 L of benzaldehyde were added. The pressure of CO was 100 bar. The autoclave was heated to 140 C. After 42 h, the reaction mixture was cooled down to room temperature and the pressure was released. 50% yield.

(22) 1H NMR (500 MHz, CDCl.sub.3) ppm 7.26-7.44 (m, 5H), 7.17-7.22 (m, 2H), 6.72-6.78 (m, 1H), 6.63-6.79 (m, 2H), 4.35 (s, 2H).

(23) 13C NMR (125 MHz, CDCl.sub.3) ppm 48.2, 112.8, 117.5, 127.1, 127.4, 128.5, 129.2, 139.4, 148.1

EXAMPLE 7

(24) ##STR00008##

(25) 1.28 mg of Ru.sub.3(CO).sub.12 were put into a 36 ml autoclave. Then 27.1 mg of p-anisidine was added. The autoclave was degassed and carbon monoxide was added. 0.15 mL of THF (11.0 ppm of water) were added. 20 L of benzaldehyde was added. The pressure of CO was 95 bar. The autoclave was heated to 100 C. After 6 h, the reaction mixture was cooled down to room temperature and the pressure was released. The product was isolated in 2% yield.

(26) 1H NMR (500 MHz, CDCl.sub.3) ppm 7.35-7.45 (m, 4H), 7.31 (t, J=7.0 Hz, 1H), 6.82 (d, J=8.9 Hz, 2H), 6.64 (d, J=8.9 Hz, 2H), 4.32 (s, 2H), 3.78 (s, 3H), 3.70 (br s, 1H). 13C NMR (125 MHz, CDCl.sub.3) ppm 49.1, 55.7, 114.0, 114.8, 127.1, 127.5, 128.5, 139.6, 142.4, 152.1

(27) As shown above, the present invention provides a simple and efficient process for preparing amines in a direct way by making use of carbon monoxide as reductant. This novel inventive process has safety advantages and shows to be economically viable. Thus, the inventors found an efficient, robust, and general catalytic reductive amination that does not require an external hydrogen source but rather utilizes the existing hydrogen atoms of the substrates and carbon monoxide (CO) as the terminal reductant.

(28) In addition to carbon monoxide being a very useful C-1 building block and known to act as a reductant, mostly proceeding via the water gas shift reaction, the present inventors have shown that carbon monoxide can be also used as a reductant in reductive amination without any external hydrogen source which process being entirely unknown.