Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~8564
This invention relates to a method for the hydrogena-
tion of prochiral olefines with induction of asymmetry by the
agency of complexes of transition metals immobilized in clay-
like minerals.
More exactly, the present invention relates to a
method for the asymmetric hydrogenation of a prochiral olefin
selected from the group consisting of alpha-acrylamide acrylic
acids, alpha-acetoamino-cinnamic acid, alpha-acetoamino-acrylic
acid, and 3-acetoxy-4-methoxy alpha-acetoaminocinnamic acid,
comprising contacting said olefin with a catalyst composed
of a cationic complex of rhodium with aminic derivatives
of phosphorus, the improvement comprising immobilizing said
catalyst on a silicate clay material selected from the group
consisting of smectites and kaolin.
The scrutiny~of the technical literature of these last
years shows a considerable interest in the use of the asymmetric
catalytic systems for the preparation of optica~lly active
compounds by reactions of hydrogenation, hydrosilylation and
hydroformylation.
In reactions of hydrogenation of alpha-acylamidoacrylic
acids, for example, catalyzed by chiral complexes of rhodium o-
anisylcyclohexylmethylphosphine, optical yields are reported as
high as 95%-96% which are virtually near those experienced in
enzymic processes.
However, the use of homogeneous catalysts involves a
great number of problems, including the difficulty of separating
the reaction product and the recovery of the catalyst; this
becomes especially cumbersome when traces of the catalyst are
retained in the reaction product. To overcome these difficulties,
the homogeneous catalysts have been insolubilized by covalent
bonds with substrates which are predominantly of an organic nature.
The polymers which are most frequently used are
~ '
-- 2 --
~1~8~i6'~
polystyrene which has been cross-linked with divinylbenzene
and functionalized with phosphine bonds to which transition
metal are co-ordinated. Also copolymers of the same fun-
ctionalized polystyrene are used.
We are proposing, that which is the subject matter of
the present invention, to use clay-like minerals, more
particularly of the class of smectites and kaolin~ as sub-
strates for homogeneous catalysts of asymmetric hydrogenation
reactions.
Smectites are fillosilicates the structural unit of
which is composed by a tetrahedral layer, an octahedral layer
and another tetrahedral layer with a layer charge of 0.25
0.60 per formula uni~due to isomorphic substitutions which
a~e distributed in the tetrahedral and the octahedral layers:
such a charge is balanced by easily exchangeable interlayer
cations. The exchange capacity is comparatively high and
varies from 80 and 150 milliequivalents per 100 grams.
In addition, particularly interesting are a few minerals
of the clay type in the group of serpentine kaolin such as
halloysite which is the most hydrous variety a~d has an
exchange capacity of about 40 milliequivalents per 100 grams.
The catalysts the subject of the present invention are
obtained by simple exchange reaction between the cationic
complex of the transition metal and the clay-like matexials.
Such catalytic systems have the considerable advantage
of the simplicity of preparation and cheapness, especially
when compared with the conventional heterogeneization
systems which employ modified organic polymeric matrices.
The cationic complex which is catalytically active in
the asymmetric hydroger:ation reaction can be selected among
th e having the formula P R'x (NR2R3)3_X,
detail in the Ca~adian Patent Application No. 275 . 775 of
6 .4. 1977
3-
85~4
Tlle catalysts in ~uestion can be used in the form
of a fine powder or granules or can have any shape which
is appropriate to the contact procedure to be used.
The process of asymmetric reduction is carried out at
a temperature comprised between -70C and +200C, preferably
between 0C and 50C at a hydrogen pressure up to 200 atnl,
preferably between 1 and 50 atm, and with a molar ratio of
the substrate to the catalyst variable between 10 and 10,000.
A few operative characteristics are described in the
ensuing examples, which are no limitation and are given
only to illustrate the invention.
E X A M P L E
One gram of Hectorite slurried in anhydrous methanol
has been exchanged with rhodium by placing them to reach
equilibrium overnight with 0.475 g of [Rh COD L]~ CL04 in
50 mls methanol.
COD - cyclooctadiene: L = N-N' bis (R(+) alpha-methyl-benzyl)
N-N' bis (diphenylphosphino) ethylenediamine.
- Hectorite takes an intense yellow color and is carefully
washed with anh.methanol and then dried. The Rhodium
contents is 1.6% by wt.
Such compound has been slurried in anh.ethanol and
hydrogenated in an autoclave at a pressure of 20 atm. of
hydrogen: there is obtained a product colored in dark red
which is characteristic of the hydride species of the Rhodium
complex, which has been used in the hydrogenation of the
alpha-acetaminocinnamic acid.
A glass flask has been charged with 0.942 g of sub-
strate in 25 mls anh.ethanol and 0.450 g of previously
hydrogenated catalyst. The flask has been connected to a
hydrogenation apparatus working under atmospherical pressure.
The progress of the reaction has been monitored with the
conventional pressure-check-ng procedures. After 8 hours,
the reaction has been stopped: the catalyst has been
filtered off and the solution e~aporated to dryness. The
product, characterized through NMR analysis was R(+)N-
acetylphenylalanine with[~]2D = 21.5 (c = 1 anh.ethanol).
E X A M P L E S 2-6
With the same catalyst of the previous example there
have been performed hydrogenation cycles of the alpha-
acetaminocinnamic acid: the data which have been obtained
are collected in Table 1.
The catalyst is recovered after each cycle by filtration
of the reaction mixture, washed with anh.ethanol and reused
under the same conditions.
T A B L E 1
Cycles [c] Reaction [~]
substrate :time 1% Soln.
% hrs. anh.ethanol e.e.
1 4.4 2 + 0.170 37
2 4.4 2~: ~ 0.218 47
3 4.3 20 + 0.230 50
4 4.3 4 + 0.144 31
4.5 20 + 0.184 40
catalyst : Hectorite (RhCODL) g = 0.~10
substrate : alpha-acetaminocinnamic acid
pressure : 20 atm of H2
temperature : room temp. 23C
sol~ent : anhydrous ethanol
E X A M P T, E S 7-12
Hectorite, prior +o ba-ancing with the cationic complex
of Rhodium, has been treated with diluted acetic acid to
5~
remove the carbonatcs wllich were present and then thoroughly
washed until the washing waters were ne~tral~ The catalyst
has been prepared with the same procedure as described in
the previous example.
Table 2 reports the data as obtained in successive
cycles of reduction of the alpha-aceta~inoacrylic acid.
T A B L E 2
Cycles ~c] Reaction L ~ ~ %
substrate time c = 1,H20
% hrs. e.e.
I 1.9 1.1/2 - 0.355 53
2 2.0 1.1/4 - 0.425 64
3 2.0 1.0 _ -43 65
4 2.0 1.3/4 - 0.44 66
2.1 1.1/4 - 0.437 66
6 2.0 2.1/2 - 0.~12 6z
Hydrogenation of alpha-acetaminoacrylic acid
Catalyst : Hectorite (RhCODL) g 0.550
Room temperature : 23C
Pressure : 1 atm H2
Solvent : anhydrous ethanol
E X A M P L E 13
With the catalyst prepared as in example 7 there have
been reduced 0.725 g of 3-acetoxy, 4-methoxy, alpha-acetamino
cinnamic acid dissolved in 25 mls of anh.ethanol. The
reaction has been carried out in an autoclave (glass) with
a hydrogen pressure of 2 atm at room temperature. There
has been obtained 3-acetoxy, 4-methoxy, N-acetylphenylalanine
with an optical yield of 58%. ~d] 2D2 = + 12.8 (c = 1, acetonej
the[~ D (c = 1~ acetone) of enantiomerically pure 3-acetoxy,
6.
~8~i4
4-methoxy N-acetylphenyialanine is -- 22.
E X A M P L E S 14-18
In the following examples there are reported the data
obtained (Table 3) in tests of asy~netric hydrogenation
with a cata]yst obtained by immobilizing the cationic complex
of Rhodium on bentonite. The preparation of the catalyst
has been made as described in example 1. The reduction
cycles have been carried out as in example 2.
T A B L E 3
Cycles [c] Reaction r ~ 3 %
substrate time c = 1,H20
% hrs. e.e.
I 1.95 3 - 0.272 41
2 1.95 6 - 0.348 52
3 1.95 8 - 0.375 56
4 2.0 10 - 0.352 53
2.0 24 _ 0,416 62
Hydrogenation of alpha-acetaminoacrylic acid.
Catalyst s Benton~te (Rh COD L) g 0.450
Room temperature : 23C
Pressure : 1 atm H2
Solvent : anh.ethanol
E X A M P L E S 19-21
There are reported data obtained in reduction tests
with a catalyst obtained by immobilizing the cationic complex
of Rhodium on Halloysite. The preparation of the catalyst
has been effected as described in example 1. The reduction
cycles have been performed as described in example 2.
1 1~856'~
T ~ B L E 4
Cycles ~c] Reaction [ ~ ] %
substrate time c = l,H20 e.e.
% hrs.
1 1.8 3 - 0.495 74
2 2.0 3 - 0.515 77
3 2.0 24 - 0.500 75
Hydrogenation of alpha-acetaminoacrylic acid.
. Catalyst : Halloysite (P~C0~ L) g 0.500
Room temperature : 23C
Hydrogen pressure : 1 atm
Solvents : anh.ethanol.
