Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
1997-09-10
2004-11-23
Kumar, Shailendra (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S212000, C564S248000, C564S271000, C564S398000, C564S415000, C549S068000
Reexamination Certificate
active
06822118
ABSTRACT:
The present invention relates to a process for the hydrogenation of imines with hydrogen under elevated pressure in the presence of iridium catalysts and a halide, wherein the reaction mixture contains an inorganic or organic acid.
U.S. Pat. No. 4,994,615 describes a process for the asymmetric hydrogenation of prochiral N-arylketimines wherein iridium catalysts having chiral diphosphine ligands are used. U.S. Pat. No. 5,011,995 describes a process for the asymmetric hydrogenation of prochiral N-alkylketimines using the same catalysts. U.S. Pat. No. 5,112,999 discloses polynuclear iridium compounds and a complex salt of iridium, which contain diphosphine ligands, as catalysts for the hydrogenation of imines.
Those homogeneous catalysis processes have proved valuable, although it is evident, especially in the case of relatively large batches or on an industrial scale, that the catalysts frequently tend to become deactivated to a greater or lesser extent depending on the catalyst precursor, the substrate and the diphosphine ligands that are used. In many cases, especially at elevated temperatures—for example at temperatures >25° C., which are necessary for a short reaction time—it is not possible to achieve complete conversion. For industrial applications of the hydrogenation process, therefore, the catalyst productivity is too low from the point of view of economic viability.
It has now been found, surprisingly, that the catalyst activity can be increased by a factor of 10 or more if the reaction mixture essentially contains a halide and also contains an acid. It has also unexpectedly been found that at the same time the deactivation of the catalysts can be considerably reduced or completely eliminated. It has also been found, surprisingly, that the enantioselectivity under the chosen conditions is high, and high optical yields of, for example, up to 80% can be achieved, even at reaction temperatures of more than 50° C.
The invention relates to a process for the hydrogenation of imines with hydrogen under elevated pressure in the presence of iridium catalysts and with or without an inert solvent, wherein the reaction mixture contains an ammonium chloride, bromide or iodide, or a metal chloride, bromide or iodide that is soluble in the reaction mixture, the metal preferably being an alkali metal, and additionally contains an acid.
Suitable imines are especially those that contain at least one
group. If the groups are substituted asymmetrically and are thus compounds having a prochiral ketimine group, it is possible in the process according to the invention for mixtures of optical isomers or pure optical isomers to be formed if enantioselective or diastereoselective iridium catalysts are used. The imines may contain further chiral carbon atoms. The free bonds in the above formulae may be saturated with hydrogen or organic radicals having from 1 to 22 carbon atoms or organic hetero radicals having from 1 to 20 carbon atoms and at least one hetero atom from the group O, S, N and P. The nitrogen atom of the group
may also be saturated with NH
2
or a primary amino group having from 1 to 22 carbon atoms or a secondary amino group having from 2 to 40 carbon atoms. The organic radicals may be substituted, for example, by F, Cl, Br, C
1
-C
4
haloalkyl wherein halogen is preferably F or Cl, —CN, —NO
2
, —CO
2
H, —CONH
2
, —SO
3
H, —PO
3
H
2
, or C
1
-C
12
alkyl esters or amides, or by phenyl esters or benzyl esters of the groups —CO
2
H, —SO
3
H and —PO
3
H
2
. Aldimine and ketimine groups are especially reactive, with the result that using the process according to the invention it is possible selectively to hydrogenate
groups in addition to the
and/or
groups. Aldimine and ketimine groups are also to be understood to include
hydrazone groups.
The process according to the invention is suitable especially for the hydrogenation of aldimines, ketimines and hydrazones with the formation of corresponding amines and hydrazines, respectively. The ketimines are preferably N-substituted. It is preferable to use chiral iridium catalysts and to hydrogenate enantiomerically pure, chiral or prochiral ketimines to prepare optical isomers, the optical yields (
e
nantiomeric
e
xcess, ee) being, for example, higher than 30%, preferably higher than 50%, and yields of more than 90% being achievable. The optical yield indicates the ratio of the two stereoisomers ford, which ratio may be, for example, greater than 2:1 and preferably greater than 4:1.
The imines are preferably imines of formula I
which are hydrogenated to form amines of formula II
wherein
R
3
is preferably a substituent and wherein
R
3
is linear or branched C
1
-C
12
alkyl, cycloalkyl having from 3 to 8 ring carbon atoms; heterocycloalkyl bonded via a carbon atom and having from 3 to 8 ring atoms and 1 or 2 hetero atoms from the group O, S and NR
6
; a C
7
-C
16
aralkyl bonded via an alkyl carbon atom or C
1
-C
12
alkyl substituted by the mentioned cycloalkyl or heterocycloalkyl or heteroaryl;
or wherein
R
3
is C
6
-C
12
aryl, or C
4
-C
11
heteroaryl bonded via a ring carbon atom and having 1 or 2 hetero atoms in the ring, R
3
being unsubstituted or substituted by —CN, —NO
2
, F, Cl, C
1
-C
12
alkyl, C
1
-C
12
alkoxy, C
1
-C
12
alkylthio, C
1
-C
6
haloalkyl, —OH, C
6
-C
12
-aryl or -aryloxy or -arylthio, C
7
-C
16
-aralkyl or -aralkoxy or -aralkylthio, secondary amino having from 2 to 24 carbon atoms, —CONR
4
R
5
or by —COOR
4
, and the aryl radicals and the aryl groups in the aralkyl, aralkoxy and aralkylthio in turn being unsubstituted or substituted by —CN, —NO
2
, F, Cl, C
1
-C
4
-alkyl, -alkoxy or -alkylthio, —OH, —CONR
4
R
5
or by —COOR
4
;
R
4
and R
5
are each independently of the other hydrogen, C
1
-C
12
alkyl, phenyl or benzyl, or R
4
and R
5
together are tetra- or penta-methylene or 3-oxapentylene;
R
6
has independently the same meaning as given for R
4
;
R
1
and R
2
are each independently of the other a hydrogen atom, C
1
-C
12
alkyl or cycloalkyl having from 3 to 8 ring carbon atoms, each of which is unsubstituted or substituted by —OH, C
1
-C
12
alkoxy, phenoxy, benzyloxy, secondary amino having from 2 to 24 carbon atoms, —CONR
4
R
5
or by —COOR
4
; C
6
-C
12
aryl or C
7
-C
16
aralkyl that is unsubstituted or substituted as R
3
, or —CONR
4
R
5
or —COOR
4
, wherein R
4
and R
5
are as defined hereinbefore; or
R
3
is as defined hereinbefore and R
1
and R
2
together are alkylene having from 2 to 5 carbon atoms that is optionally interrupted by 1 or 2 —O—, —S— or —NR
6
— radicals, and/or unsubstituted or substituted by ═O or as R
1
and R
2
above in the meaning of alkyl, and/or condensed with benzene, pyridine, pyrimidine, furan, thiophene or pyrrole; or
R
2
is as defined hereinbefore and R
1
and R
3
together are alkylene having from 2 to 5 carbon atoms that is optionally interrupted by 1 or 2 —O—, —S— or —NR
6
— radicals, and/or unsubstituted or substituted by ═O or as R
1
and R
2
above in the meaning of alkyl, and/or condensed with benzene, pyridine, pyrimidine, furan, thiophene or pyrrole.
The radicals R
1
, R
2
and R
3
may contain one or more chirality centres.
R
1
, R
2
and R
3
can be substituted in any desired positions by identical or different radicals, for example by from 1 to 5, preferably from 1 to 3, substituents.
Suitable substituents for R
1
and R
2
and R
3
are: C
1
-C
12
-, preferably C
1
-C
6
-, and especially C
1
-C
4
-alkyl, -alkoxy or -alkylthio, e.g. methyl, ethyl, propyl, n-, iso- and tert-butyl, the isomers of pentyl, hexyl, octyl, nonyl, decyl, undecyl and dodccyl, and corresponding alkoxy and alkylthio radicals;
C
1
-C
6
-, preferably C
1
-C
4
-haloalkyl having preferably F and Cl as halogen, e.g. trifluoro- or trichloro-methyl difluorochloromethyl, fluorodichloromethyl, 1,1-difluoroeth-1-yl, 1,1-dichloroeth-1-yl, 1,1,1-trichloro- or 1,1,1-trifluoroeth-2-yl, pentachloroethyl, pentafluoroethyl, 1,1,1-trifluoro-2,2-dichloroethyl, n-perfluoropropyl, iso-perfluoropropyl, n-perfluorobutyl, fluoro- or chloro-methyl, difluoro- or dichloro-methyl, 1-fluoro- or 1-c
Blaser Hans-Ulrich
Hanreich Reinhard Georg
Jalett Hans-Peter
Spindler Felix
Allen Rose M.
Kumar Shailendra
Syngenta Crop Protection Inc.
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