Process for the preparation of substituted N-(benzyl)cyclopropanamines by imine hydrogenation
View Patent ↗The present invention relates to a process for the preparation of substituted N-(benzyl)cyclopropanamines of the general formula (II) starting from N-[(aryl)methylene]cyclopropanamine derivatives. The present invention further provides the N-[(aryl)methylene]cyclopropanamine derivatives used as starting compounds in this process according to the invention, and their use for the preparation of substituted N (benzyl)cyclopropanamines.
1. A process for the preparation of N-(benzyl)cyclopropanamines of the general formula (II)
wherein
Z is hydrogen, C 1 -C 8 -alkyl, C 1 -C 4 -haloalkyl or C 3 -C 7 -cycloalkyl,
X 1 is halogen or C 1 -C 8 -haloalkyl having up to 9 identical or different halogen atoms,
X is C 1 -C 8 -alkyl or C 1 -C 8 -haloalkyl having up to 9 identical or different halogen atoms,
n is 1, 2, 3, or 4,
wherein N-[(aryl)methylene]cyclopropanamine compounds of the general formula (I)
in which Z, X, X 1 and n have the meanings given above,
are catalytically hydrogenated.
2. The process according to claim 1 , wherein a hydrogenation catalyst that is used is selected from the group consisting of a precious metal catalyst and a Wilkinson catalyst.
3. The process according to claim 1 , wherein a hydrogenation catalyst that is used is selected from the group consisting of a ruthenium catalyst, a palladium catalyst, a platinum catalyst, a rhodium catalyst, a Raney nickel catalyst, a Raney cobalt catalyst, a Lindlar catalyst, and a Wilkinson catalyst.
4. The process according to claim 2 , wherein the catalyst is used in supported form applied to carbon, activated carbon, aluminium oxide, silicon dioxide, zirconium dioxide, calcium carbonate or titanium dioxide.
5. The process according to claim 3 , wherein the catalyst is used in supported form applied to carbon, activated carbon, aluminium oxide, silicon dioxide, zirconium dioxide, calcium carbonate or titanium dioxide.
6. The process according to claim 1 , wherein the catalyst is used in a concentration of about 0.01% to about 30% by weight.
7. The process according to claim 2 , wherein the catalyst is used in a concentration of about 0.01% to about 30% by weight.
8. The process according to claim 3 , wherein the catalyst is used in a concentration of about 0.01% to about 30% by weight.
9. The process according to claim 4 , wherein the catalyst is used in a concentration of about 0.01% to about 30% by weight.
10. The process according to claim 5 , wherein the catalyst is used in a concentration of about 0.01% to about 30% by weight.
11. A process for the preparation of N-(benzyl)cyclopropanamines of the general formula (II)
wherein
Z is hydrogen, C 1 -C 8 -alkyl, C 1 -C 4 -haloalkyl or C 3 -C 7 -cycloalkyl,
X 1 is halogen or C 1 -C 8 -haloalkyl having up to 9 identical or different halogen atoms,
X is C 1 -C 8 -alkyl or C 1 -C 8 -haloalkyl having up to 9 identical or different halogen atoms,
n is 1, 2, 3, or 4,
wherein, in a first step [process (B)], cyclopropylamine is condensed with carbonyl compounds of the general formula (III)
wherein Z, X, X 1 and n have the meanings given above, and the resulting N-[(aryl)methylene]cyclopropanamine compounds of the general formula (I)
wherein Z, X, X 1 and n have the meanings given above, are catalytically hydrogenated in a second step [process (A)].
12. N-[(Aryl)methylene]cyclopropanamine compounds of the general formula (I)
wherein
Z is hydrogen, C 1 -C 8 -alkyl, C 1 -C 4 -haloalkyl or C 3 -C 7 -cycloalkyl,
X 1 is halogen or C 1 -C 8 -haloalkyl having up to 9 identical or different halogen atoms,
X is C 1 -C 8 -alkyl or C 1 -C 8 -haloalkyl having up to 9 identical or different halogen atoms,
n is 1, 2, 3, or 4.