Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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As originally filed
Process for the preparation of primary amines by homogeneously catalyzed
alcohol
amination
The present invention relates to a process for the preparation of primary
amines by
homogeneously catalyzed alcohol amination of alcohols and alkanolamines with
ammonia with the elimination of water in the presence of a complex catalyst
which
comprises at least one element selected from groups 8, 9 and 10 of the
Periodic Table
of the Elements and at least one nonpolar solvent.
Primary amines are compounds which have at least one primary amino group (-
NH2).
Primary diamines have two primary amino groups. Primary triamines have three
primary amino groups. Primary polyamines have more than three primary amino
groups.
Primary amines are valuable products with a large number of different uses,
for
example as solvents, stabilizers, for the synthesis of chelating agents, as
starting
materials for producing synthetic resins, inhibitors, interface-active
substances,
intermediates in the manufacture of fuel additives (US 3,275,554 A, DE 2125039
A
and DE 36 11 230 A), surfactants, drugs and crop protection agents, hardeners
for
epoxy resins, catalysts for polyurethanes, intermediates for producing
quaternary
ammonium compounds, plasticizers, corrosion inhibitors, synthetic resins, ion
exchangers, textile auxiliaries, dyes, vulcanization accelerators and/or
emulsifiers.
Primary diamines and triamines are valuable products with a large number of
different
uses, for example as solvents, stabilizers, for the synthesis of chelating
agents, as
starting materials for producing synthetic resins, drugs, inhibitors,
corrosion
protectants, polyurethanes, as hardeners for epoxy resins, and interface-
active
substances.
Primary diamines and triamines are currently prepared by heterogeneously
catalyzed
alcohol amination of primary diols and triols with ammonia. WO 2008/006752 Al
describes a process for the preparation of amines by reacting primary or
secondary
alcohols with ammonia in the presence of a heterogeneous catalyst which
comprises
zirconium dioxide and nickel. WO 03/051508 Al relates to a process for the
amination
of alcohols using specific heterogeneous Cu/Ni/Zr/Sn catalysts. EP 0 696 572
Al
discloses nickel-, copper-, zirconium- and molybdenum oxide-comprising
heterogeneous catalysts for the amination of alcohols with ammonia and
hydrogen.
According to the documents cited above, the reactions are carried out at
temperatures
in the range from 150 to 210 C and ammonia pressures in the range from 30 to
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200 bar. However, in the case of the heterogeneously catalyzed processes
described
in the above documents, the often undesired monoamination products and cyclic
amines such as piperazines, pyrrolidines and morpholines are formed as main
products. The desired primary diamines are obtained only in extremely low
yields, if at
all, in the processes described above. The documents cited above describe in
particular the reaction of diethylene glycol with ammonia.
0
NH3
o/
NH
0
0
In this process, monoaminodiethylene glycol and morpholine are obtained as
main
products. The desired diaminated diaminodiethylene glycol is obtained only in
extremely low yields, if at all, in the amination reactions of the documents
specified
above.
The highest yield of diaminodiethylene glycol, at 5%, is obtained according to
WO 03/051508 A1, with the formation of 22% morpholine and 36% monoamino-
diethylene glycol as by-products.
During the amination of diethanolamine with ammonia, piperazine is obtained as
the
main product. Here too, the desired linear diamination product
diethylenetriamine is
only produced in traces if high diethanolamine conversions are operated.
N NI-12
NH3
HN NH/
1-1(3.NOH
-H20
NH2
In the case of the reaction of polyetherols to give polyetheramines, with the
processes
described above, undesired secondary reactions to give the dimeric secondary
amine
or polymeric coupling product are observed to a high degree on account of the
harsh
reaction conditions prevailing during the heterogeneously catalyzed amination,
as is
illustrated below with reference to diethylene glycol. These by-products are
difficult to
separate off from the desired primary diamination product.
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H2N NH2
NI13
-1(20
A further problem which is observed during the amination of polyetherols,
especially in
the case of polyethylene and polypropylene glycol derivatives, is the
decomposition of
these ethers under the reaction conditions described above since, in
particular, the
high temperatures and a hydrogen support pressure are required. Under these
reaction
conditions, gaseous decomposition products are formed which make special
safety
precautions necessary.
Another disadvantage in the heterogeneous catalysis of the amination of
alcohols with
ammonia is the high pressures required therefor.
The homogeneously catalyzed amination of alcohols has been known since the
1970s
where, in most cases, ruthenium or iridium catalysts are described. Compared
with
heterogeneously catalyzed reactions, the homogeneously catalyzed amination
proceeds at significantly lower temperatures of from 100 to 150 C. The
reaction of
monoalcohols with primary and secondary amines is described, for example, in
the
following publications: US 3,708,539; Y. Watanabe, Y. Tsuji, Y. Ohsugi,
Tetrahedron
Lett. 1981, 22, 2667-2670; S. Bahn, S. Imm, K. Mevius, L. Neubert, A. Tillack,
J. M. J.
Williams, M. Beller, Chem. Eur. J. 2010, 001: 10.1002/chem.200903144; A.
Tillack, D.
Hollmann, D. Michalik, M. Beller, Tetrahedron Lett. 2006, 47, 8881-8885; D.
Hollmann,
S. Bahn, A. Tillack, M. Beller, Angew. Chem. Int. Ed. 2007, 46, 8291-8294; A.
Tillack,
D. Hollmann, K. Mevius, D. Michalik, S. Bahn, M. Beller, Eur. J. Org. Chem.
2008,
4745-4750; M. H. S. A. Hamid, C. L. Allen, G. W. Lamb, A. C. Maxwell, H. C.
Maytum,
A. J. A. Watson, J. M. J. Williams, J. Am. Chem. Soc. 2009, 131, 1766-1774; 0.
Saidi,
A. J. Blacker, M. M. Farah, S. P. Marsden, J. M. J. Williams, Chem. Commun.
2010,
46, 1541-1543; EP 239943; N. Andrushko, V. Andrushko, P. Roose, K. Moonen, A.
Borner, ChemCatChem, 2010, 2, 640-643; K. I. Fujita, R. Yamaguchi, Synlett,
2005, 4,
560-571; A. Tillack, D. Hollmann, D. Michalik, M. Beller, Tet. Lett. 2006, 47,
8881-8885;
A. Del Zlotto, W. Baratta, M. Sandri, G. Verardo, P. Rigo, Eur. J. Org. Chem.
2004,
524-529; A. Fujita, Z. Li, N. Ozeki, R. Yamaguchi, Tetrahedron Lett. 2003, 44,
2687-
2690; Y. Watanabe, Y. Morisaki, T. Kondo, T. Mitsudo J. Org. Chem. 1996, 61,
4214-
4218, B. Blank, M. Madalska, R. Kempe, Adv. Synth. Catal. 2008, 350, 749-750,
A.
Martinez-Asencio, D. J. Ramon, M. Yus, Tetrahedron Lett. 2010, 51, 325-327.
The
greatest disadvantage of the systems described above is that with these
processes
only the amination of alcohols with primary and secondary amines is possible.
The
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reaction of alcohols with ammonia to give primary amines, which is the
economically
most attractive amination reaction, is not described in these works. Neither
is any
reference made to an efficient recycling of the precious metal catalysts.
The homogeneously catalyzed amination of alcohols with ammonia is only
described in
a few works. S. Imm, S. Bahn, L. Neubert, H. Neumann, M. Beller, Angew. Chem.
2010, 122, 8303-8306 and D. Pingen, C. Muller, D. Vogt, Angew. Chem. 2010,
122,
8307-8310 disclose the amination of secondary alcohols such as cyclohexanol
with
ammonia homogeneously catalyzed with ruthenium catalysts. However, using the
systems disclosed therein, it is only possible to aminate secondary alcohols
with
ammonia. The amination of diols and triols is not described in these works.
WO 201 0/01 8570 and C. Gunanathan, D. Milstein, Angew. Chem. mt. Ed. 2008,
47,
8661-8664 discloses the amination of primary alcohols with ammonia to give
primary
monoamines with the help of ruthenium-phosphane complexes. For the amination,
specific, acridine-based pincer ligands are used. The reaction is carried out
at
temperatures of from 110 to 180 C and NH3 pressures of up to 7.5 bar. Under
these
conditions, when using primary alcohols, the by-products that are formed are
primarily
the corresponding imines and dialkylamines. The formation of dialkylamines is
especially disadvantageous during the amination of diols since, under these
conditions,
the cyclic amines are able to form, which likewise fall within the group of
secondary
amines. The amination of diols and triols with ammonia is not described.
R. Kawahara, K.I. Fujita, R. Yamaguchi, J. Am. Chem. Soc. DOI:
10.1021/ja107274w
describes the amination of primary monoalcohols and triols with ammonia using
an
iridium catalyst which has, as ligand, Cp* (1,2,3,4,5-
pentamethylcyclopentadienyl) and
ammonia. However, using the catalyst system described therein, when reacting
primary monoalcohols with ammonia, the undesired tertiary amines are
exclusively
obtained. The reaction of glycerol with ammonia leads exclusively to the
undesired
bicyclic quinolizidine.
EP 0 234 401 Al describes the reaction of diethylene glycol with ammonia in
the
presence of a ruthenium carbonyl compound. In the process described in
EP 0 234 401 Al, only the monoamination product (monoethanolamine), the
secondary
and tertiary amines (di- and triethanolamine) and cyclic products (N-
(hydroxyethyl)piperazine and N,N'-bis(hydroxyethyl)piperazine) are formed. The
desired 1,2-diaminoethane is not obtained in this process.
All of the processes described above for the reaction of alcohols with ammonia
have
the disadvantage that the desired primary amines are not formed as the main
products.
Moreover, no concepts for recycling the expensive precious metal catalysts are
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described, although this is required for an industrial transfer of these
processes for
reasons of cost.
It is an object of the present invention to provide a process for the
preparation of
5 primary
amines by alcohol amination of mono-, di-, tri- and polyols, and also of
alkanolamines with the favorable aminating agent ammonia, in which the
catalyst used
can be separated off and reused. The reaction should proceed under milder
conditions
and produce higher selectivities with regard to the formation of primary
amines than the
established, heterogeneously catalytic reactions. In particular, the
selectivity in the
preparation of linear primary amines, and also the selectivity in the
preparation of di-,
tri- and polyamines should be improved.
According to the invention, this object is achieved by the following process
for the
preparation of primary amines by alcohol amination of alcohols with ammonia
with the
elimination of water, comprising the steps
(a) homogeneously catalyzed reaction of a reaction mixture comprising at
least
one alcohol, ammonia, at least one nonpolar solvent and at least one
catalyst comprising at least one element selected from groups 8, 9 and 10
of the Periodic Table of the Elements in the liquid phase, giving a product
mixture (P),
(b) phase separation of the product mixture (P) obtained in step (a),
optionally
after lowering the temperature, lowering the pressure and/or adding at least
one polar solvent which has a miscibility gap with the nonpolar solvent, to
give at least one polar product phase (A) and at least one nonpolar phase
(B) comprising at least some of the catalyst used and separating off the
nonpolar phase (B),
(c) returning at least some of the nonpolar phase (B) to the reaction in
step (a)
and
(d) separating off the amination product from the polar product phase (A),
where the nonpolar solvent used in (a) and the catalyst used in step (a) are
selected such that the catalyst accumulates in the nonpolar phase (B).
Surprisingly, it has been found that with the complex catalysts used in the
process
according to the invention which comprise at least one element selected from
group 8,
9 and 10 of the Periodic Table of the Elements, it is possible to obtain
primary amines,
preferably di-, tri- and polyamines, and also alkanolamines by the
homogeneously
catalyzed amination of alcohols with ammonia with the elimination of water.
The
process according to the invention has the advantage that it produces primary
mono-,
di-, tri- and polyamines and also alkanolamines in considerably improved
yields
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compared with the processes described in the prior art. Moreover, the
formation of
undesired by-products such as secondary and tertiary amines and also cyclic
amines is
reduced compared with the prior art. Through appropriate choice of the
catalyst and the
solvent used, after the reaction, a liquid two-phase system is obtained in
which the
catalyst accumulates preferentially in the nonpolar phase and the amination
product
accumulates preferentially in the polar phase, meaning that the catalyst can
be easily
separated off from the product phase with the nonpolar phase and be
reutilized.
Starting materials
In the process according to the invention, alcohols which have at least one OH
group,
preferably in the form of the functional group of the formula (¨CH2-OH)
(primary alcohol
group) or (>CH-OH) (secondary alcohol group), are used as starting materials.
Preferably, the alcohols have at least one further functional group (-X),
where (-X) is
selected from hydroxyl groups (-OH) and primary amino groups (-NH2). In this
connection, in the process according to the invention, particular preference
is given to
using starting materials in which (-X) is selected from the group of
functional groups of
the formulae (¨CH2-0H) and (>CH-OH) and (-CI-12-NH2) and (>CH-NH2). The
starting
materials then have at least one functional unit of the formula (¨OH),
preferably of the
formula (¨CH2-0H) and (>CH2-0H) and/or at least one further functional group
selected from the group of functional groups of the formula (¨CH2-0H) and
(>CH2-0H)
and (-CH2-NH2) and (>CH2-NH2). According to the invention, very particular
preference
is given to using the starting materials described above which, when reacted
with NH3,
produce linear primary amines, and very particular preference is given to
using linear
diols which have at least 2 OH groups, i.e. have two primary and/or secondary
alcohol
groups, and also linear alkanolamines which have at least one primary or
secondary
alcohol group in the form of (¨CH2-0H) or (>CH-OH).
Suitable starting materials are practically all alcohols which satisfy the
prerequisites
specified above. The alcohols may be linear, branched or cyclic, preferably
linear.
Moreover, the alcohols can carry substituents which exhibit inert behavior
under the
reaction conditions of the alcohol amination, for example alkoxy, alkenyloxy,
alkylamino, dialkylamino and halogen (F, CI, Br, l).
Suitable starting materials which can be used in the process according to the
invention
are, for example, monoalcohols, diols, triols, polyols and alkanolamines which
have at
least one OH group, preferably in the form of the functional groups of the
formula
(-CH2-0H) or (>CH-OH) and at least one further functional group (-X), where (-
X) is
selected from hydroxyl groups and primary amino groups.
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Moreover, diols, triols, polyols and alkanolamines which have at least one OH
group
and at least one further functional primary or secondary OH unit or NH2 unit
are
suitable.
5 Starting materials which can be used are all known diols which have at
least one
primary or secondary OH group. Examples of diols which can be used as starting
materials in the process according to the invention are 1,2-ethanediol
(ethylene glycol),
1,2-propanediol (1,2-propylene glycol), 1,3-propandiol (1,3-propylene glycol),
1,4-
butanediol (1,4-butylene glycol), 1,2-butanediol (1,2-butylene glycol), 2,3-
butanediol, 2-
methyl-1,3-propanediol, 2,2-dimethy1-1,3-propanediol (neopentyl glycol), 1,5-
pentanediol, 1,2-pentanediol, 1,6-hexanediol, 1,2-hexanediol, 1,7-heptanediol,
1,2-
heptanediol, 1,8-octanediol, 1,2-octanediol, 1,9-nonanediol, 1,2-nonanediol,
2,4-
dimethy1-2,5-hexanediol, hydroxypivalic acid neopentyl glycol ester,
diethylene glycol,
triethylene glycol, 2-butene-1,4-diol, 2-butyne-1,4-diol, poylethylene
glycols,
15 polypropylene glycols, such as 1,2-polypropylene glycol and 1,3
polypropylene glycol,
polytetrahydrofu ran, diethanolamine,
1,4-bis-(2-hydroxyethyl)piperazine,
diisopropanolamine, N-butyldiethanolamine, 1 ,10-decanediol, 1,12-
dodecanediol, 2,5-
(dimethanol)-furan, 1,4-bis(hydroxymethyl)cyclohexane, C36-diol (mixture of
isomers of
alcohols of the empirical formula (Cs6H7402)) and N-methyldiethanolamine,
isosorbide
(1,4:3,6¨dianhydroglucitol), isomannitol (1,4:3,6-dianhydromannitol,
diisopropanol-p-
toluidine, N,N-di(2-hydroxyethyl)anilines, diisopropanolamine.
Preference is given to diols which have two functional groups of the formula (-
CH2-0H).
25 Particularly preferred diols are 1,2-ethanediol (ethylene glycol), 1,2-
propanediol (1,2-
propylene glycol), 1,3-propanediol (1,3-propylene glycol), 1,4-butanediol (1,4-
butylene
glycol), 2-methyl-1,3-propanediol, 2,2-dimethy1-1,3-propanediol (neopentyl
glycol), 1,5-
pentanediol, 1 ,6-hexanediol, 1 ,7-heptanediol,
1 ,8-octanediol, 1 ,9-nonanediol,
diethylene glycol, triethylene glycol, polyethylene glycols, polypropylene
glycols, such
as 1,2-polypropylene glycol and 1,3 polypropylene glycol, polytetrahydrofuran,
diethanolamine, diisopropanolamine, N-butyldiethanolamine, 2,5-(dimethanol)-
furan
and N-methyldiethanolamine.
All known triols can be used as starting materials, preference being given to
triols
35 which have at least one functional group of the formula (¨CH2-0H) or
(>CH-OH), and
particular preference being given to triols with at least two functional
groups of the
formula (¨CH2-0H) or (>CH-OH). Examples of triols which can be used as
starting
materials in the process according to the invention are glycerol,
trimethylolpropane,
triisopropanolamine and triethanolamine.
Particularly preferred triols are glycerol, trimethylolpropane and
triethanolamine.
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All known polyols can be used as starting materials; these preferably comprise
at least
one functional group of the formula (¨CH2-0H) or (>CH-OH). Examples of polyols
which can be used as starting materials in the process according to the
invention are
polyvinylalcohol, 2,2-bis(hydroxymethyl)-1,3-propanediol (pentaerythritol),
sorbitol,
inositol, sugars and polymers such as, for example, glucose, mannose,
fructose,
ribose, deoxyribose, galactose, N-acetylglucosamine, fucose, rhamnose,
sucrose,
lactose, cellobiose, maltose and amylose, cellulose, starch and xanthan.
Preference is given to polyols which have at least two functional groups of
the formula
(-CH2-0H) or (>CH-OH).
Particularly preferred polyols are glucose and cellulose.
Starting materials which can be used are also all known alkanolamines which
have at
least one OH group, preferably a primary or secondary hydroxyl group and at
least one
primary amino group (-NH2). Within the context of the invention, the
alkanolamines are
included among the alcohols to be used as starting materials. Examples of
alkanol-
amines which can be used as starting materials in the process according to the
invention are monoaminoethanol, 3-aminopropan-1-ol, 2-aminopropan-1-ol, 4-
aminobutan-1-ol, 2-aminobutan-1-ol, 3-aminobutan-1-ol, 5-aminopentan-1-ol, 2-
aminopentan-1-ol, 6-aminohexan-1-ol, 2-aminohexan-1-ol, 7-aminoheptan-1-ol, 2-
aminoheptan-1-ol, 8-aminooctan-1-ol, 2-aminooctan-1-ol, N-(2-
hydroxyethyl)aniline, 2-
(2-aminoethoxy)ethanol, N-(2-hydroxyethyl)-1,3-propanediamine and
aminodiethylene
glycol (2-(2-aminoethoxy)ethanol).
Preference is given to alkanolamines which have at least one primary hydroxyl
group
(-CH2-0H) and at least one primary amino group of the formula (-CH2-NF12).
Particularly preferred alkanolamines are monoaminoethanol, 3-aminopropan-1-ol,
2-
aminopropan-1-01, 4-aminobutan-1-ol and 2-(2-aminoethoxy)ethanol.
Complex catalyst
The process according to the invention uses at least one complex catalyst
which
comprises at least one element selected from groups 8, 9 and 10 of the
Periodic Table
of the Elements (nomenclature in accordance with IUPAC). The elements of group
8, 9
and 10 of the Periodic Table of the Elements comprise iron, cobalt, nickel,
ruthenium,
rhodium, palladium, osmium, iridium and platinum. Preference is given to
complex
catalysts which comprise at least one element selected from ruthenium and
iridium.
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The complex catalyst comprises preferably at least one donor ligand, in
particular one
phosphorus donor ligand. The complex catalyst particularly preferably
comprises at
least one element selected from ruthenium and iridium and at least one
phosphorus
donor ligand.
In one embodiment, the process according to the invention is carried out in
the
presence of at least one complex catalyst of the general formula (I):
xi
i
\R
R2
1/H
L1--------%ii---------=-_12
L3 Y
(I)
in which
L1 and L2 independently of one another, are phosphine
(PRaRb), amine
(NRaRb), sulfide, SH, sulfoxide (S(=0)R), C5-C10-heteroaryl
comprising at least one heteroatom selected from nitrogen (N),
oxygen (0) and sulfur (S), arsine (AsRaRb), stibane (SbRaRb) or N-
heterocyclic carbenes of the formula (II) or (III):
1
R4
N¨ R3 ¨N( R4
R5 N¨R5
= =
(II) (III) .
,
L3 is a monodentate two-electron donor selected
from the group
carbon monoxide (CO), PRaRbRc, NO, AsRaRbRc, SbRaRbRe,
SRaRb, nitrite (RCN), isonitrile (RNC), nitrogen (N2), phosphorus
trifluoride (PF3), carbon monosulfide (CS), pyridine, thiophene,
tetrahydrothiophene and N-heterocyclic carbenes of the formula
(II) or (III);
R1 and R2 are both hydrogen or, together with the carbon atoms to which
they are bonded, are a phenyl ring which, together with the
quinolinyl unit of the formula (I), forms an acridinyl unit;
R, Ra, Rb, Rc, R3, V< ¨4,
and R5, independently of one another, are unsubstituted or
at least monosubstituted C1-C10-alkyl, C3-C10-cycloalkyl, C3-Ci0-
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heterocyclyl comprising at least one heteroatom selected from N,
0 and S, C5-C10-aryl or C5-C10-heteroaryl comprising at least one
heteroatom selected from N, 0 and S,
5 where the substituents are selected from the group
consisting of:
F, Cl, Br, OH, CN, NH2 and C1-C10-alkyl;
Y is monoanionic ligand selected from the group H,
F, Cl, Br, I,
OCOR, OCOCF3, OSO2R, OSO2CF3, CN, OH, OR and N(R)2 or
10 neutral molecule selected from the group NH3, N(R)3 and
R2NSO2R;
X1 is one, two, three, four, five, six or seven
substituents on one or
more atoms of the acridinyl unit or one, two, three, four or five
substituents on one or more atoms of the quinolinyl unit,
where X1, independently of the others, is selected from the group
consisting of hydrogen, F, Cl, Br, I, OH, NH2, NO2, -NC(0)R,
C(0)NR2, -0C(0)R, -C(0)0R, CN and borane derivatives which
are obtainable from the catalyst of the formula (I) by reaction with
NaBH4, and unsubstituted or at least monosubstituted C1-C10-
alkoxy, Cl-C10-alkyl, C3-C10-cycloalkyl, C3-C10-heterocycly1
comprising at least one heteroatom selected from N, 0 and S,
C5-C10-aryl and C5-C10-heteroaryl comprising at least one
heteroatom selected from N, 0 and S,
where the substituents are selected from the group consisting of:
F, CI, Br, OH, CN, NH2 and C1-C10-alkyl;
and
M is iron, cobalt, nickel, ruthenium, rhodium,
palladium, osmium,
iridium or platinum.
Here, it is to be noted that the complex catalyst of the formula (I) for cases
where Y is a
neutral molecule from the group NH3, NR3, R2NSO2R, carries a positive charge.
In a preferred embodiment, the process according to the invention is carried
out in the
presence of at least one homogeneously dissolved complex catalyst of the
formula (I),
where the substituents have the following meaning:
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L1 and L2, independently of one another, are PRaRb, NRaRb, sulfide, SH,
S(=0)R,
C5-C10-heteroaryl comprising at least one heteroatom selected from N, 0
and S;
L3 is a monodentate two-electron donor selected from the group CO,
PRaRbRc, NO, RCN, RNC, N2, FF3, CS, pyridine, thiophene and
tetrahydrothiophene;
R1 and R2 are both hydrogen or, together with the carbon atoms to which
they are
bonded, are a phenyl ring which, together with the quinolinyl unit of the
formula (I), forms an acridinyl unit;
R, Ra, Rb, Rb, R3, R4, and R5, independently of one another, are unsubstituted
C1-C10-
alkyl, C3-C10-cycloalkyl, C3-C10-heterocycly1 comprising at least one
heteroatom selected from N, 0 and S, C5-C10-aryl or C5-C10-heteroaryl
comprising at least one heteroatom selected from N, 0 and S;
is monoanionic ligand selected from the group H, F, Cl, Br, OCOR,
OCOCF3, OSO2R, OSO2CF3, CN, OH, OR or N(R)2;
X1 is one, two, three, four, five, six or seven substituents on
one or more
atoms of the acridinyl unit or one, two, three, four or five substituents on
one or more atoms of the quinolinyl unit,
where X1, independently of the others, is selected from the group
consisting of hydrogen, F, Cl, Br, I, OH, NH2, NO2, -NC(0)R, C(0)NR2,
-0C(0)R, -C(0)0R, CN and borane derivatives which are obtainable
from the catalyst of the formula (I) by reaction with NaBH4, and
unsubstituted Cl-Cio-alkoxy, C3-C10-
cycloalkyl, C3-C10-
heterocyclyI comprising at least one heteroatom selected from N, 0 and
S, C5-C1o-aryl and C5-C10-heteroaryl comprising at least one heteroatom
selected from N, 0 and S;
and
is ruthenium or iridium.
In a further preferred embodiment, the process according to the invention is
carried out
in the presence of at least one homogeneously dissolved complex catalyst,
where R1
and R2 are both hydrogen and the complex catalyst is a catalyst of the formula
(IV):
EK10-1687PC
,
PF0000071687/MKr CA 02828330 2013-08-27
12
xi
N"--L.-
1/H
LI--------7--------L2
L3 1
Y
(iv)
and X1, Ll, L2, L3 and Y have the meanings given above.
In a further preferred embodiment, the process according to the invention is
carried out
in the presence of at least one homogeneously dissolved complex catalyst,
where R1
and R2, together with the carbon atoms to which they are bonded, form a phenyl
ring
which, together with the quinolinyl unit of the formula (I), forms an
acridinyl unit and the
complex catalyst is a catalyst of the formula (V):
xi
\
N
1/1
Li--------/-rr-s-'-L2
L3 Y
(v)
and X1, Ll, L2, L3 and Y have the meanings given above.
By way of example, a number of complex catalysts (formulae (VI), (VII),
(VIII), (IX), (X),
(XI), (XII) and (XIII)) which can be used in the process according to the
invention are
listed below:
EK10-1687PC
,
PF0000071687/MKr CA 02828330 2013-08-27
13
xi xi
* *
N
N
R
/ oc
Rb Y Rb Y
Rb Rb
(VI) (VII)
Ix 110
x'
40 N
IN /H
R
,,,
......''W
Rb Y
Rb
Rb Y
Rb
(VIII) (IX)
x' x'
10 N \
N
I /H
IR I /H
-..._ , R
Rp r N R
,
, 0. \ / oc \
Rb Y Rb Y
Rb Rb
(X) (XI)
x\ l xl
10 \N
N
I /H R I /H
R -........ N7"------_________ N../
Re--......N__________-----11------______:1_,N _..."-
/ OC I \ / \
y
Rb Y Rb
OC
Rb Rb
(Xii) (Xiii)
In a further preferred embodiment, the process according to the invention is
carried out
in the presence of at least one complex catalyst from the group of catalysts
of the
5 formula (VI), (VII), (VIII),
(IX), (X), (XI), (XII) and (XIII), where
Ra and Rb independently of one another, are unsubstituted or at
least mono-
substituted Cl-C10-alkyl, C3-C10-cycloalkyl, C3-C10-heterocycly1 comprising at
least one heteroatom selected from N, 0 and S, C5-C10-aryl or C5-C10-
heteroaryl
10 comprising at least
one heteroatom selected from N, 0 and S,
EK10-1687PC
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CA 02828330 2013-08-27
14
where the substituents are selected from the group consisting of: F, Cl, Br,
OH,
ON, NH2 and C1-C10-alkyl;
= is a monoanionic ligand selected from the group H, F, Cl, Br, OCOR,
000CF3,
OSO2R, OSO2CF3, ON, OH, OR, N(R)2;
= is unsubstituted or at least monosubstituted C1-C10-alkyl, 03-C10-
cycloalkyl, C3-
010-heterocycly1 comprising at least one heteroatom selected from N, 0 and S,
05-C10-aryl, C5-C10-heteroaryl comprising at least one heteroatom selected
from
N, 0 and S,
where the substituents are selected from the group consisting of: F, Cl, Br,
OH,
ON, NH2 and 01-C10-alkyl;
X1 is one, two or three substituents on one or more atoms of the acridinyl
unit or
one or two substituents on one or more atoms of the quinolinyl unit,
where X1, independently of the others, is selected from the group consisting
of
hydrogen, F, CI, Br, I, OH, NH2, NO2, -NC(0)R, C(0)NR2, -OC(0)R, -C(0)OR,
ON and borane derivatives which are obtainable from the catalyst of the
formula (I) by reaction with NaBH4, and unsubstituted 01-010-alkoxy, 01-010--
alkyl, C3-C10-cycloalkyl, C3-C10-heterocycly1 comprising at least one
heteroatom
selected from N, 0 and S, 05-010-aryl and 05-C10-heteroaryl comprising at
least
one heteroatom selected from N, 0 and S;
and
= is ruthenium or iridium.
In a further preferred embodiment, the process according to the invention is
carried out
in the presence of at least one complex catalyst from the group of catalysts
of the
formula (VI), (VII), (VIII), (IX), (X), (XI), (XII) and (XIII), where
Ra and Rb independently of one another, are methyl, ethyl, isopropyl, tert-
butyl,
cyclohexyl, cyclopentyl, phenyl or mesityl;
is a monoanionic ligand selected from the group H, F, CI, Br, 000CH3,
OCOCF3, OSO2CF3, CN and OH;
X1 is a substituent on an atom of the acridinyl unit or a substituent
on an atom of
the quinolinyl unit,
EK10-1687PC
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CA 02828330 2013-08-27
where X' is selected from the group consisting of hydrogen, F, CI, Br, OH,
NH2,
NO2, -NC(0)R, C(0)NR2, -0C(0)R, -C(0)0R, ON and borane derivatives which
are obtainable from the catalyst of the formula (I) by reaction with NaBH4,
and
unsubstituted C1-C10-alkoxy, C1-010-alkyl, C3-C10-cycloalkyl, C3-C10-
heterocycly1
5 comprising at least one heteroatom selected from N, 0 and S, C5-C10-aryl
and
C5-C10-heteroaryl comprising at least one heteroatom selected from N, 0 and S;
is ruthenium or iridium.
10 In a further preferred embodiment, the process according to the
invention is carried out
in the presence of at least one complex catalyst from the group of catalysts
of the
formula (VI), (VII), (VIII), (IX), (X), (XI), (XII) and (XIII), where
Ra and Rb, independently of one another, are methyl, ethyl, isopropyl, tert-
butyl,
15 cyclohexyl, cyclopentyl, phenyl or mesityl;
is monoanionic ligand from the group F, Cl, Br, I, 0000H3, OCOCF3, OSO2CF3,
ON and OH;
X' is hydrogen;
and
is ruthenium or iridium.
In a particularly preferred embodiment, L3 is carbon monoxide (CO).
In a particularly preferred embodiment, the process according to the invention
is carried
out in the presence of a complex catalyst of the formula (XlVa):
1101
NO
1/H
.==
==< OC I
CI
(XlVa)
In a veryl particularly preferred embodiment, the process according to the
invention is
carried out in the presence of a complex catalyst of the formula (XIVb):
EK10-1687PC
PF0000071687/MKr
CA 02828330 2013-08-27
16
./ 1101
/H
/ I
(pc
ci
(X1Vb)
In a further particularly preferred embodiment, the process according to the
invention is
carried out in the presence of at least one homogeneously dissolved complex
catalyst
of the formula (XV) in which R1, R2, R3, Ll, L2 and L3 have the meanings
described
above.
H
L1 U2
p
B.
Ff
L3
(XV)
Complex catalysts of the formula (XV) are obtainable by reacting catalysts of
the
formula (I) with sodium borohydride (NaBH4). The reaction follows the general
reaction
equation:
H
40\
Na131-14
R2 R2
N
2
L3 L/
In a further particularly preferred embodiment, the process according to the
invention is
carried out in the presence of a complex catalyst of the formula (XVIa):
EK10-1687PC
. PF0000071687/MKr
CA 02828330 2013-08-27
17
11, H
S.,
11101
1
, I: I, . .. p
N--.) ,
B
1 Fli
X OC I
H
(XVIa)
In a further particularly preferred embodiment, the process according to the
invention is
carried out in the presence of a complex catalyst of the formula (XVIb):
hi, H
µ
1
,...õ1-14 ti õ.......õ,
N---_.. --
I FB
(15 0 C I
H
(XVIb)
The borane derivative of the formula (XVIa) is accessible according to the
following
reaction equation:
H H
#4,,
IPNaB H 4 (1 equivalent)
N r > )4 r
1 H 2 li loom tempet atm e 110
N----.)13-
,......,pt1
I -----------P
/K Cl
OC I
H
1 0
The borane derivative of the formula (XVIb) is accessible according to the
following
reaction equation:
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18
H 1:1
4111 ASP
NaBH 4 (1 =cpu, akin) sin 41---/Er.
H 2 11 room t,=mpclature
CLp
OC/
00,
Within the context of the present invention, C1-C10-alkyl are understood as
meaning
branched, unbranched, saturated and unsaturated groups. Preference is given to
alkyl
groups having 1 to 6 carbon atoms (C1-C6-alkyl). More preference is given to
alkyl
groups having 1 to 4 carbon atoms (C1-C4-alkyl).
Examples of saturated alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-
butyl,
isobutyl, sec-butyl, tert-butyl, amyl and hexyl.
Examples of unsaturated alkyl groups (alkenyl, alkynyl) are vinyl, allyl,
butenyl, ethynyl
and propynyl.
The C1-C10-alkyl group can be unsubstituted or substituted with one or more
substituents selected from the group F, Cl, Br, hydroxy (OH), C1-C10-alkoxy,
05-010-
aryloxy, C6-C10-alkylaryloxy, C6-C10-heteroaryloxy comprising at least one
heteroatom
selected from N, 0, S, oxo, C3-Cl0-cycloalkyl, phenyl, C5-C10-heteroaryl
comprising at
least one heteroatom selected from N, 0, S, C5-C10-heterocycly1 comprising at
least
one heteroatom selected from N, 0, S, naphthyl, amino, C1-C10-alkylamino, C5-
C10-
arylamino, C5-C10-heteroarylamino comprising at least one heteroatom selected
from
N, 0, S, C1-C10-dialkylamino, C10-C12-diarylamino, C10-C20-alkylarylamino, C1-
C10-acyl,
C1-C10-acyloxy, NO2, C1-C10-carboxy, carbamoyl, carboxamide, cyano, sulfonyl,
sulfonylamino, sulfinyl, sulfinylamino, thiol, C1-C10-alkylthiol, C5-C10-
arylthiol or 0l-C10-
alkylsulfonyl.
In the present case, 03-C10-cycloalkyl is understood as meaning saturated,
unsaturated
monocyclic and polycyclic groups. Examples of 03-C10-cycloalkyl are
cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. The cycloalkyl groups can
be
unsubstituted or substituted with one or more substituents, as has been
defined above
in relation to the group C1-C10-alkyl.
Within the context of the present invention, 06-010-aryl is understood as
meaning an
aromatic ring system having 5 to 10 carbon atoms. The aromatic ring system can
be
monocyclic or bicyclic. Examples of aryl groups are phenyl, naphthyl such as
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,
19
1-naphthyl or 2-naphthyl. The aryl group can be unsubstituted or substituted
with one
or more substituents as defined above under C1-C10-alkyl.
Within the context of the present invention, C5-C10-heteroaryl is understood
as meaning
a heteroaromatic system which comprises at least one heteroatom selected from
the
group N, 0 and S. The heteroaryl groups can be monocyclic or bicyclic. For the
case
that nitrogen is a ring atom, the present invention also comprises N-oxides of
the
nitrogen-comprising heteroaryls. Examples of heteroaryls are thienyl,
benzothienyl, 1-
naphthothienyl, thianthrenyl, fury!, benzofuryl, pyrrolyl, imidazolyl,
pyrazolyl, pyridyl,
pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, indazolyl, purinyl,
isoquinolinyl,
quinolinyl, acridinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl,
piperidinyl,
carbolinyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl. The heteroaryl
groups can be
unsubstituted or substituted with one or more substituents which have been
defined
above under C1-C10-alkyl.
Within the context of the present invention, C3-C10-heterocycly1 is understood
as
meaning five- to ten-membered ring systems which comprise at least one
heteroatom
from the group N, 0 and S. The ring systems can be monocyclic or bicyclic.
Examples
of suitable heterocyclic ring systems are piperidinyl, pyrrolidinyl,
pyrrolinyl, pyrazolinyl,
pyrazolidinyl, morpholinyl, thiomorpholinyl, pyranyl, thiopyranyl,
piperazinyl, indolinyl,
dihydrofuranyl, tetrahydrofuranyl,
dihydrothiophenyl, tetrahydrothiophenyl,
dihydropyranyl and tetrahydropyranyl.
In a further embodiment, the process according to the invention uses at least
one
complex catalyst which comprises at least one element selected from the groups
8, 9
and 10 of the Periodic Table of the Elements (nomenclature according to
IUPAC), and
also at least one phosphorus donor ligand of the general formula (XXI),
R21
\
p/R23
/
R22 1 I I\ R24
Y3
I
P,
/\
R25 R26
i in
(XXI)
where
EK10-1687PC
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CA 02828330 2013-08-27
n is 0 or 1;
R21, R22, R23, R24, R25, R26 are, independently of one another,
unsubstituted or
at least monosubstituted C1-C10-alkyl, C1-C4-alkyldiphenylphosphine
5 (-C1-C4-alkyl-P(pheny1)2), C3-C10-cycloalkyl, C3-C10-heterocycly1
comprising
at least one heteroatom selected from N, 0 and S, C5-C14-aryl or C5-C10-
heteroaryl comprising at least one heteroatom selected from N, 0 and S,
where the substituents are selected from the group consisting of: F, Cl, Br,
10 OH, CN, NH2 and C1-C10-alkyl;
A is
i) a bridging group selected from the group unsubstituted or at least
monosubstituted N, 0, P, C1-C6-alkane, C3-C10-cycloalkane, C3-C10-
15 heterocycloalkane comprising at least one heteroatom selected from N,
0
and S, C5-C14-aromatic and C5-C6-heteroaromatic comprising at least one
heteroatom selected from N, 0 and S,
where the substituents are selected from the group consisting of:
20 C1-C4-alkyl, phenyl, F, Cl, Br, OH, OR27, NH2, NHR27 or N(R27)2,
where R27 is selected from C1-C10-alkyl and C5-C10-aryl;
Or
ii) a bridging group of the formula (XXII) or (XXIII):
(R28)m (R29)q (R28)õ,
X13 (R29) q
X 1 1 x12
(XXII) (XXIII)
m, q are, independently of one another, 0, 1, 2, 3 or 4;
R28, R29 are, independently of one another, selected from the
group
C1-C10-alkyl, F, CI, Br, OH, OR27, NH2, NHR27 and N(R27)2,
where R27 is selected from C1-C10-alkyl and C5-C10-aryl;
x11, x12 are, independently of one another, NH, 0 or S;
EK10-1687PC
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21
X13 is a bond, NH, NR30, 0, S or CR31R32;
R3 is
unsubstituted or at least monosubstituted C1-C10-alkyl,
C3-C10-cycloalkyl, C3-C10-heterocycly1 comprising at least one
heteroatom selected from N, 0 and S, C5-C14-aryl or C5-C10-
heteroaryl comprising at least one heteroatom selected from N,
0 and S,
where the substituents are selected from the group consisting
of: F, Cl, Br, OH, CN, NH2 and C1-C10-alkyl;
R31, R32 are,
independently of one another, unsubstituted or at least
monosubstituted C1-C10-alkyl, C1-C10-alkoxy, C3-C10-cycloalkyl,
C3-C10-cycloalkoxy,C3-C10-heterocycly1 comprising at least one
heteroatom selected from N, 0 and S, C5-C14-aryl, C5-C14-
aryloxy or C5-C10-heteroaryl comprising at least one heteroatom
selected from N, 0 and S,
where the substituents are selected from the group consisting
of: F, Cl, Br, OH, CN, NH2 and C1-C10-alkyl;
yl, y2, s
T are,
independently of one another, a bond, unsubstituted or at least
monosubstituted methylene, ethylene, trimethylene, tetramethylene,
pentamethylene or hexamethylene,
where the substituents are selected from the group consisting of: F,
Cl, Br, OH, OR27, CN, NH2, NHR27, N(R27)2 and C1-C10-alkyl,
where R27 is selected from C1-C10-alkyl and C5-C10-aryl.
According to the invention, A is a bridging group. For the case that A is
selected from
the group unsubstituted or at least monosubstituted C1-C6-alkane, C3-C10-
cycloalkane,
C3-C10-heterocycloalkane, C5-C14-aromatic and C5-C6-heteroaromatic and
bridging
groups of the formula (II) or (III), for the case (n = 0), two hydrogen atoms
of the
bridging group are replaced by bonds to the adjacent substituents Y1 and Y2.
For the
case (n = 1), three hydrogen atoms of the bridging group are replaced by three
bonds
to the adjacent substituents Y1, Y2 and Y3.
For the case that A is P (phosphorus), the phosphorus forms for the case (n =
0) two
bonds to the adjacent substituents Y1 and Y2 and one bond to a substituent
selected
EK10-1687PC
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22
from the group consisting of CI-al-alkyl and phenyl. For the case (n = 1), the
phosphorus forms three bonds to the adjacent substituents Y1, Y2 and Y3.
For the case that A is N (nitrogen), the nitrogen for the case (n = 0) forms
two bonds to
the adjacent substituents Y1 and Y2 and one bond to a substituent selected
from the
group consisting of C1-C4-alkyl and phenyl. For the case (n = 1), the nitrogen
forms
three bonds to the adjacent substituents Y1, Y2 and Y3.
For the case that A is 0 (oxygen), n = 0. The oxygen forms two bonds to the
adjacent
substituents Y1 and Y2.
Preference is given to complex catalysts which comprise at least one element
selected
from ruthenium and iridium.
In a preferred embodiment, the process according to the invention is carried
out in the
presence of at least one complex catalyst which comprises at least one element
selected from the groups 8, 9 and 10 of the Periodic Table of the Elements and
also at
least one phosphorus donor ligand of the general formula (XXI), where
n is 0 or 1 ;
R21, R22, R23, R24, R25, R26 are, independently of one another,
unsubstituted
C1-C10-alkyl, C3-C10-cycloalkyl, C3-Cl0-heterocycly1 comprising at least one
heteroatom selected from N, 0 and S, C5-C14-aryl or C5-C10-heteroaryl
comprising at least one heteroatom selected from N, 0 and S;
A is
i) a bridging group selected from the group unsubstituted C1-C6-alkane,
C3-C10-cycloalkane, C3-C10-heterocycloalkane comprising at least one
heteroatom selected from N, 0 and S, C5-C14-aromatic and C5-C6-
heteroaromatic comprising at least one heteroatom selected from N, 0 and
S;
Or
ii) a bridging group of the formula (XXII) or (XXIII):
EK10-1687PC
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23
(R28)m
(R29) (R286
X13 (R29)q
)(11 x12
(XXII) (XXIII)
m, q are, independently of one another, 0, 1, 2, 3 or 4;
R28, R29 are, independently of one another, selected from the group
C1-C10-alkyl, F, Cl, Br, OH, OR27, NH2, NHR27 and N(R27)2,
where R27 is selected from C1-C10-alkyl and C5-C10-aryl;
x11, x12 are, independently of one another, NH, 0 or S;
X13 is a bond, NH, NR30, 0, S or CR31R32;
R3 is unsubstituted C1-C10-alkyl, C3-C10-cycloalkyl, C3-00-
heterocyclyl comprising at least one heteroatom selected from
N, 0 and S, C5-C14-aryl or C5-C10-heteroaryl comprising at least
one heteroatom selected from N, 0 and S;
R31, R32 are, independently of one another, unsubstituted C1-C10-
alkyl,
C1-C10-alkoxy, C3-C10-cycloalkyl, C3-C10-cycloalkoxy, C3-Clo-
heterocyclyl comprising at least one heteroatom selected from
N, 0 and S, C5-C14-aryl, C5-C14-aryloxy or C5-C10-heteroaryl
comprising at least one heteroatom selected from N, 0 and S;
yl, y2, r s,3
are, independently of one another, a bond, unsubstituted methylene,
ethylene, trimethylene, tetramethylene, pentamethylene or
hexamethylene.
In a further preferred embodiment, the process according to the invention is
carried out
in the presence of at least one complex catalyst which comprises at least one
element
selected from groups 8, 9 and 10 of the Periodic Table of the Elements and
also at
least one phosphorus donor ligand of the general formula (XXV),
EK10-1687PC
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CA 02828330 2013-08-27
24
R21 R23
\
p_yl_A- y2- p/
/ \
R22 R24
(XXV)
where
R21 , R22, R23, R24 are, independently of one another, unsubstituted or at
least
monosubstituted Cl-C10-alkyl, Craralkyldiphenylphosphine (-C1-C4-alkyl-
P(pheny1)2), C3-C10-cycloalkyl, C3-C10-heterocycly1 comprising at least one
heteroatom selected from N, 0 and S, C5-C14-aryl or C5-C10-heteroaryl
comprising at least one heteroatom selected from N, 0 and S,
where the substituents are selected from the group consisting of: F, Cl, Br,
OH, CN, NH2 and C1-C10-alkyl;
A is
i) a bridging group selected from the group unsubstituted or at least
monosubstituted N, 0, P, C1-C6-alkane, C3-C10-cycloalkane, 03-010-
heterocycloalkane comprising at least one heteroatom selected from N, 0
and S, C5-C14-aromatic and C5-C6-heteroaromatic comprising at least one
heteroatom selected from N, 0 and S,
where the substituents are selected from the group consisting of:
C1-C4-alkyl, phenyl, F, Cl, Br, OH, OR27, NH2, NHR27 or N(R27)2,
where R27 is selected from C1-C10-alkyl and C5-C10-aryl;
Or
ii) a bridging group of the formula (XXII) or (XXIII):
(R28)m (R29)_ (R286 29
x13 (R)9
\.,
1 1 1
)(11 x12
(XXII) (XXIII)
EK10-1687PC
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CA 02828330 2013-08-27
m, q are, independently of one another, 0, 1, 2, 3 or 4;
R28, R29 are, independently of one another, selected from the
group
01-C10-alkyl, F, Cl, Br, OH, OR27, NH2, NHR27 and N(R27)2,
5
where R27 is selected from 01-010-alkyl and 05-C10-aryl;
X11,
x12 are, independently of one another, NH, 0 or S,
10 X13 is a bond, NH, NR30, 0, S or CR31 R32;
R3 is unsubstituted or at least monosubstituted 01-010-
alkyl,
03-010-cycloalkyl, 03-C10-heterocycly1 comprising at least one
heteroatom selected from N, 0 and S, 05-C14-aryl or C5-C10-
15 heteroaryl comprising at least one heteroatom selected
from N,
0 and S,
where the substituents are selected from the group consisting
of: F, Cl, Br, OH, ON, NH2 and 01-010-alkyl;
R31, R32 are, independently of one another, unsubstituted or at
least
monosubstituted 01-C10-alkyl, 01-010-alkoxy, 03-010-cycloalkyl,
03-010-cycloalkoxy, C3-010-heterocycly1 comprising at least one
heteroatom selected from N, 0 and S, 05-C14-aryl, C5-014-
aryloxy or 05-C10-heteroaryl comprising at least one heteroatom
selected from N, 0 and S,
where the substituents are selected from the group consisting
of: F, Cl, Br, OH, ON, NH2 and 01-010-alkyl;
Y1,
y2 are, independently of one another, a bond, unsubstituted or at least
monosubstituted methylene, ethylene, trimethylene, tetramethylene,
pentamethylene or hexamethylene,
where the substituents are selected from the group consisting of: F,
CI, Br, OH, OR27, ON, NH2, NHR27, N(R27)2 and 01-C10-alkyl,
where R27 is selected from 01-010-alkyl and 05-C10-aryl.
In a further preferred embodiment, the process according to the invention is
carried out
in the presence of at least one complex catalyst which comprises at least one
element
EK10-1687PC
PF0000071687/MKr CA 02828330 2013-08-27
26
selected from groups 8, 9 and 10 of the Periodic Table of the Elements and
also at
least one phosphorus donor ligand of the general formula (XXVI),
R21 \R
/23
p_yi_A___. y2- p/
I \
R22 R24
Y3
I
P
/ \
R25 R26
(XXVI)
where
R21, R22, R23, R24, R25, R26 are,
independently of one another, unsubstituted or
at least monosubstituted C1-C10-alkyl, C1-C4-alkyldiphenylphosphine,
C3-C10-cycloalkyl, C3-C10-heterocycly1 comprising at least one heteroatom
selected from N, 0 and S, C5-C14-aryl or C5-C10-heteroaryl comprising at
least one heteroatom selected from N, 0 and S,
where the substituents are selected from the group consisting of: F, Cl, Br,
OH, ON, NH2 and C1-C10-alkyl;
A is a bridging group selected from the group unsubstituted or at
least mono-
substituted N, P, C1-C6-alkane, C3-C10-cycloalkane, C3-Clo-
heterocycloalkane comprising at least one heteroatom selected from N, 0
and S, C5-C14-aromatic and C5-C6-heteroaromatic comprising at least one
heteroatom selected from N, 0 and S,
where the substituents are selected from the group consisting of:
C1-C4-alkyl, phenyl, F, CI, Br, OH, OR27, NH2, NHR27 or N(R27)2,
where R27 is selected from C1-C10-alkyl and C5-C10-aryl;
Y1,
y2, y3 are,
independently of one another, a bond, unsubstituted or at least
monosubstituted methylene, ethylene, trimethylene, tetramethylene,
pentamethylene or hexamethylene,
where the substituents are selected from the group consisting of: F, Cl, Br,
OH, OR27, ON, NH2, NHR27, N(R27)2 and C1-C10-alkyl,
where R27 is selected from C1-C10-alkyl and C5-C10-aryl.
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In a further preferred embodiment, the process according to the invention is
carried out
in the presence of at least one complex catalyst which comprises at least one
element
selected from groups 8, 9 and 10 of the Periodic Table of the Elements and
also at
least one phosphorus donor ligand of the general formula (XXV), where
R21, R22, R23, R24 are, independently of one another, methyl, ethyl,
isopropyl, tert-
butyl, cyclopentyl, cyclohexyl, phenyl, or mesityl;
A is
i) a bridging group selected from the group methane, ethane, propane,
butane, cyclohexane, benzene, napthalene and anthracene;
Or
ii) a bridging group of the formula (XXVII) or (XXVIII):
xi, x13
x12
(XXVII) (XXVIII)
Xi', x12 are, independently of one another, NH, 0 or S;
X13 is a bond, NH, 0, S or CR31R32;
R31, R32 are, independently of one another, unsubstituted C1-C10-alkyl;
y1, y2 are, independently of one another, a bond, methylene or
ethylene.
In a particularly preferred embodiment, the process according to the invention
is carried
out in the presence of at least one complex catalyst which comprises at least
one
element selected from groups 8, 9 and 10 of the Periodic Table of the Elements
and
also at least one phosphorus donor ligand of the general formula (XXIX) or
(XXX),
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(R28)m (R29)q R28 29
(R29)q
xõ )(12
R21 R22 R23 R24 R21 R22 R23 R24
(XXIX) (XXX)
where for m, q, R21, R22, R23, R24, R28, R29, x19, x12 and X13,
the definitions and
preferences listed above are applicable.
In a further particularly preferred embodiment, the process according to the
invention is
carried out in the presence of at least one complex catalyst which comprises
at least
one element selected from the group ruthenium and iridium and also at least
one
phosphorus donor ligand selected from the group 1,2-
bis(diphenylphosphino)ethane
(dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,4-
bis(diphenylphosphino)butane
(dppb), 2,3-bis(dicyclohexylphosphino)ethane (dcpe), 4,5-
bis(diphenylphosphino)-9,9-
dimethylxanthene (xantphos), bis(2-diphenylphosphinoethyl)phenylphosphine and
1,1,1-tris(diphenylphosphinomethyl)ethane (triphos).
In a further particularly preferred embodiment, the process according to the
invention is
carried out in the presence of a complex catalyst which comprises ruthenium
and at
least one phosphorus donor ligand selected from the group 4,5-
bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), bis(2-
diphenylphosphino-
ethyl)phenylphosphine and 1,1,1-tris(diphenylphosphinomethyl)ethane (triphos).
In a further particularly preferred embodiment, the process according to the
invention is
carried out in the presence of a complex catalyst which comprises iridium and
also at
least one phosphorus donor ligand selected from the group 4,5-
bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), bis(2-
diphenylphosphino-
ethyl)phenylphosphine and 1,1,1-tris(diphenylphosphinomethyl)ethane (triphos).
Within the context of the present invention, C1-C10-alkyl is understood as
meaning
branched, unbranched, saturated and unsaturated groups. Preference is given to
alkyl
groups having 1 to 6 carbon atoms (C1-C6-alkyl). More preference is given to
alkyl
groups having 1 to 4 carbon atoms (C1-C4-alkyl).
Examples of saturated alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-
butyl,
isobutyl, sec-butyl, tert-butyl, amyl and hexyl.
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Examples of unsaturated alkyl groups (alkenyl, alkynyl) are vinyl, allyl,
butenyl, ethynyl
and propynyl.
The C1-C10-alkyl group can be unsubstituted or substituted with one or more
substituents selected from the group F, Cl, Br, hydroxy (OH), C1-C10-alkoxy,
C5-C10-
aryloxy, C5-C10-alkylaryloxy, C5-C10-heteroaryloxy comprising at least one
heteroatom
selected from N, 0, S, oxo, C3-C10-cycloalkyl, phenyl, C5-C10-heteroaryl
comprising at
least one heteroatom selected from N, 0, S, C5-C10-heterocycly1 comprising at
least
one heteroatom selected from N, 0, S, naphthyl, amino, C1-C10-alkylamino, C5-
C10-
arylamino, C5-C10-heteroarylamino comprising at least one heteroatom selected
from
N, 0, S, C1-C10-dialkylamino, C10-C12-diarylamino, C10-C20-alkylarylamino, C1-
C10-acyl,
C1-C10-acyloxy, NO2, C1-C10-carboxy, carbamoyl, carboxamide, cyano, sulfonyl,
sulfonylamino, sulfinyl, sulfinylamino, thiol, C1-C10-alkylthiol, C5-C10-
arylthiol or C1-C10-
alkylsulfonyl.
The above definition for C1-C10-alkyl applies correspondingly to C1-C30-alkyl
and to
C1-C6-alkane.
C3-C10-cycloalkyl is understood in the present case as meaning saturated,
unsaturated
monocyclic and polycyclic groups. Examples of C3-C10-cycloalkyl are
cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. The cycloalkyl groups can
be
unsubstituted or substituted with one or more substituents as has been defined
above
in connection with the group C1-C10-alkyl.
The definition of C3-C10-cycloalkyl specified above applies accordingly to C3-
C10-
cycloalkane.
The homogeneous catalysts can be generated directly in their active form or
else are
only generated under the reaction conditions starting from customary
precursors with
the addition of the corresponding ligands. Customary precursors are, for
example,
[Ru(p-cymene)C12]2, [Ru(benzene)C12], [Ru(C0)2C12],, [Ru(C0)3C12]2
[Ru(COD)(allyI)],
[RuCI3*H20], [Ru(acetylacetonate)3],
[Ru(DMS0)4C12], [Ru(PPh3)3(C0)(H)CI],
[Ru(PPh3)3(CO)C12], [Ru(PPh3)3(C0)(H)2],
[Ru(PPh3)3Cl2], [Ru(cyclopenta-
dienyl)(PRh3)2C1], [Ru(cyclopentadienyl)(C0)2CIL
[Ru(cyclopentadienyl)(C0)2H],
[Ru(cyclopentadienyl)(C0)2]2, [Ru(pentamethylcyclopentadienyl)(C0)2C1],
[Ru(penta-
methylcylcopentadienyl)(C0)2H],
[Ru(pentamethylcyclopentadienyl)(C0)212,
[Ru(indenyl)(C0)2C1], [Ru(indenyl)(C0)21-1], [Ru(indenyl)(C0)2]2, Ruthenocene,
[Ru(binap)C12], [Ru(bipyridine)2C12*2H20], [Ru(COD)C12]2, [Ru(pentamethylcyclo-
pentadienyl)(COD)C1], [Ru3(C0)12],
[Ru(tetraphenylhydroxycyclopentadienyl)(C0)2H],
[Ru(PMe3)4(1--1)2], [Ru(PEt3)4(H)2], [Ru(PnPr3)4(H)2],
[Ru(PnBu3)4(H)2],
[Ru(PnOcty13)4(H)2], [IrCI3*H20], KIrCI4, K3IrC16, [Ir(COD)C1]2,
Dr(cyclooctene)2C92,
[I r(ethene)2C1]2, [I r(cyclopentadienyl)C12]2, [I
r(pentamethylcyclopentadienyl)C12]2,
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[Ir(cylopentadienyl)(C0)2], [Ir(pentamethylcyclopentadienyl)(C0)2],
[Ir(PPh3)2(C0)(H)l,
[Ir(PPh3)2(C0)(C1)], [I r(PPh3)3(C1)].
Alcohol amination (step (a))
5
The alcohol amination in step (a) takes place by homogeneously catalyzed
reaction of
one or more hydroxyl-group-comprising starting materials with ammonia in the
presence of at least one of the complex catalysts described above.
10 During the amination reaction, according to the invention, at least one
hydroxyl group
(-OH) of the starting material is reacted with ammonia to give a primary amino
group
(-N H2), with the formation of in each case 1 mol of water of reaction per
mole of reacted
hydroxyl group.
15 Thus, in the case of the reaction of alkanolamines which have only one
hydroxyl group,
the corresponding diamines are formed. The reaction of monoaminoethanol thus
leads
to the corresponding 1,2-diaminoethane.
In the case of the reaction of starting materials which have a further
hydroxyl group
20 (diols), reaction with ammonia leads to the corresponding primary
diamines or alkanol-
amines depending on the reaction conditions. The reaction of 1,2-ethylene
glycol thus
leads to the corresponding 1,2-diaminoethane or monoaminoethanol.
In the case of the reaction of starting materials which have two further
hydroxyl groups
25 as well as one hydroxyl group (triols), two or three hydroxyl groups are
reacted with
ammonia to give the corresponding primary diamines or triamines. The formation
of
diamines or triamines can be controlled here via the amount of ammonia used
and via
the reaction conditions. The reaction of glycerol thus leads to the
corresponding 1,3-
diaminopropanol (1,3-diaminopropan-2-ol) or to 1,2,3-triaminopropane.
In the case of the reaction of starting material which, as well as the one
hydroxyl group,
have more than three further hydroxyl groups (polyols), two, three or more
hydroxyl
groups are reacted with ammonia to give the corresponding primary diamines,
triamines or polyamines. The formation of the corresponding primary diamines,
triamines or polyamines can be controlled here via the amount of ammonia used
and
via the reaction conditions.
Within the context of the present invention, homogeneously catalyzed is
understood as
meaning that the catalytically active part of the complex catalyst is present
in at least
partially dissolved form in the liquid reaction medium. In a preferred
embodiment, at
least 90% of the complex catalyst used in the process is present in dissolved
form in
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the liquid reaction medium, more preferably at least 95%, especially
preferably more
than 99%, most preferably the complex catalyst is present in completely
dissolved form
in the liquid reaction medium (100%), in each case based on the total amount
in the
liquid reaction medium.
The amount of metal component in the catalyst, preferably ruthenium or
iridium, is
generally 0.1 to 5000 ppm by weight, in each case based on the total liquid
reaction
mixture in the reaction space.
The reaction in step (a) takes place in the liquid phase generally at a
temperature of
from 20 to 250 C. Preferably, the process according to the invention is
carried out at
temperatures in the range from 100 C to 200 C, particularly preferably in the
range
from 110 to 160 C.
The reaction is generally carried out at a total pressure of from 0.1 to 20
MPa absolute,
which can either be the intrinsic pressure of the solvent and of the ammonia
at the
reaction temperature, and also the pressure of a gas such as nitrogen, argon
or
hydrogen. Preferably, the process according to the invention is carried out at
a total
pressure up to 15 MPa absolute, particularly preferably at a total pressure of
up to
10 MPa absolute.
The aminating agent (ammonia) can be used in stoichiometric, substoichiometric
or
superstoichiometric amounts with regard to the hydroxyl groups to be aminated.
In a
preferred embodiment, ammonia is used in a 1.0- to 250-fold, preferably in a
1.5- to
100-fold, especially in a 2- to 10-fold, molar excess per mole of hydroxyl
groups to be
reacted in the starting material. Even higher excesses of ammonia are
possible. The
ammonia can be added in gaseous form, in liquid form or dissolved in one of
the
solvents.
According to the invention, the reaction takes place in the presence of at
least one
nonpolar solvent. In this connection, one nonpolar solvent or mixtures of two
or more
nonpolar solvents can be used.
The nonpolar solvent is generally selected from saturated hydrocarbons such as
hexane, heptane, octane and cyclohexane; linear and cyclic ethers such as
diethyl
ether, 1,4-dioxane, tert-butyl methyl ether, tert-amylalcohol, tert-butanol,
diglyme and
1,2-dimethoxyethane and aromatic hydrocarbons such as benzene, toluene, o-, m-
, p-
xylene and mesitylene and mixtures thereof. Preference is given to using
aromatic
solvents, particularly preferably toluene, o-, m-, p-xylene, mesitylene and
mixtures
thereof.
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In this connection, nonpolar solvent and homogeneous catalyst are selected
such that
the catalyst accumulates in the nonpolar phase (B) obtained following the
phase
separation in step (b). According to the invention, accumulated is understood
as
meaning that the quantitative partition coefficient Pmc = [amount of dissolved
catalyst in
the nonpolar phase (B)]/[amount of dissolved catalyst in the polar product
phase (A)] is
greater than 1. Preferably, Pm, is at least 1.5, particularly preferably at
least 5.
In a preferred embodiment, nonpolar solvent and homogeneous catalyst are
selected
such that the catalyst dissolves better in the nonpolar phase (B) obtained
following the
phase separation in step (b) than in the polar phase (A). The catalyst
concentration is
then higher in the nonpolar phase (B) than in the polar phase (A), i.e. the
partition
coefficient Pc, = [concentration of the dissolved catalyst in the nonpolar
phase
(B)]/[concentration of the dissolved catalyst in the polar product phase (A)]
is greater
than 1. Preferably, Pc is at least 1.5, particularly preferably at least 5.
The choice of the homogeneous catalyst and of the nonpolar solvent is usually
made
by means of a simple experiment in which the partition coefficient P of the
chosen
catalyst is determined experimentally under the planned process conditions
together
with the substrate and product and also the polar solvent. In particular, the
lipophilicity
of the catalyst and thus its solubility in nonpolar and/or polar phases can be
influenced
in a targeted manner by the choice of ligands.
As a rule, the nonpolar solvent is selected such that the homogeneous catalyst
preferentially dissolves therein compared to the polar solvent. According to
the
invention, this means that the partition coefficient Pc2 = [concentration of
the catalyst in
the nonpolar solvent]/[concentration of the catalyst in the polar solvent] is
greater than
1, preferably at least 2 and particularly preferably at least 5. Further
preferred Pc2 is at
least 1.5.
For the reaction in the liquid phase, ammonia, the at least one alcohol, the
at least one
nonpolar solvent are usually fed into a reaction space together with the
complex
catalyst. The reaction can be carried out in customary devices or reactors
known to the
person skilled in the art for liquid-gas reactions in which the catalyst is
present in
homogeneously dissolved form in the liquid phase. For the process according to
the
invention, all reactors can in principle be used which are fundamentally
suitable for
gas/liquid reactions under the stated temperature and the stated pressure.
Suitable
standard reactors for gas-liquid and for liquid-liquid reaction systems are
discussed for
example in K.D. Henkel, "Reactor Types and Their Industrial Applications", in
Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH Verlag GmbH &
Co.
KGaA, DOI: 10.1002/14356007.b04_087, Chapter 3.3 "Reactors for gas-liquid
reactions". Examples which may be mentioned are stirred-tank reactors, tubular
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reactors or bubble column reactors. The introduction of ammonia, starting
material,
nonpolar solvent and complex catalyst can take place here simultaneously or
separately from one another. The reaction can be carried out here
discontinuously in a
batch procedure or continuously, semicontinuously with or without recycling.
The
average residence time in the reaction space is generally 15 minutes to 100
hours.
The product mixture (P) obtained in step (a) comprises the homogeneous
catalyst, the
amination product, nonpolar solvent, unreacted starting materials and any by-
products
formed, and also water formed during the amination. It may also be
advantageous to
continuously remove the water formed during the reaction from the reaction
mixture.
The water of reaction can be separated off directly by distillation from the
reaction
mixture or as azeotrope with the addition of a suitable solvent (entrainer)
and using a
water separator, or can be removed by adding water-removing auxiliaries.
In step (b) of the process according to the invention, a phase separation of
the product
mixture (P) obtained in step (a) takes place, optionally after lowering the
temperature
and/or adding at least one polar solvent which has a miscibility gap with the
nonpolar
solvent used in step (a), to give at least one polar product phase (A) and at
least one
nonpolar phase (B) comprising at least some of the catalyst used, and
separating off
the nonpolar phase (B).
Both phases (A) and (B) are liquid phases, the catalyst being present in
accumulated
form in the nonpolar phase (B), and the amination product being present in
accumulated form in the polar phase. With regard to the amination product,
"accumulated" in the present case means that the quantitative partition
coefficient of
the amination product PA = [amount of amination product in the polar phase
(A)]/[amount of amination product in the nonpolar phase (B)] is greater than
1,
preferably at least 1.5, particularly preferably at least 5.
In a preferred embodiment, the polar solvent is selected such that the
amination
product dissolves better in the polar phase (A) obtained following phase
separation in
step (b) than in the nonpolar phase (B). The amination product concentration
is then
higher in the polar phase (A) than in the nonpolar phase (B), i.e. the
partition coefficient
of the amination product PAi = [concentration of the amination product in the
polar
phase (A)]/[concentration of the amination product in the nonpolar phase (B)]
is greater
than 1, preferably at least 1.5, particularly preferably at least 5.
Depending on the choice of components, it is possible that the product
mixtures (P) is
present in single-phase liquid form after step (a). In this case, a phase
separation can
be achieved by cooling and/or adding one or more polar solvents.
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Suitable polar solvents are, for example, water, dimethylformamide, formamide,
acetonitrile, the alcohol(s)/alkanolamine(s) used as starting materials in
step (a), and
mixtures thereof. In addition, the product can also be used as solvent.
Preference is
given to using water. The polar solvent can be added either already to the
reaction
mixture before or in step (a), or after the reaction in step (b) in addition
to the water of
reaction that is formed during the reaction.
According to the invention, the polar solvent should be matched to the
nonpolar solvent
and the amination product that is formed in such a way that the amination
product is
present in accumulated form in the polar phase (A). The selection of nonpolar
and
polar solvent generally takes place by simple experimentation, in which the
solubility of
the desired product is determined experimentally in the two phases (A) and (B)
under
the planned process conditions.
As a rule, the polar solvent is selected such that the amination product
preferentially
dissolves therein compared to the nonpolar solvent used. According to the
invention,
this means that the partition coefficient PA2 = [concentration of amination
product in
polar solvent]/[concentration of amination product in nonpolar solvent] is
greater than 1,
preferably at least 2 and particularly preferably at least 5. Further
preferred PA2 is at
least 1.5.
Within the context of the present invention, in each case it is possible to
use one
solvent or mixtures of 2 or more solvents. This applies to the nonpolar
solvents and
also the polar solvents.
The dielectric constant DC can be used as a measure for assigning a solvent to
the
group polar/nonpolar. Solvents with DC greater than about 15 are usually
regarded as
polar (e.g. acetonitrile has a DC of about 37), solvents with a lower DC are
usually
regarded as nonpolar, for example the DC of benzene is 2.28.
Even if the product mixture obtained in step (a) is already present in two
phases, the
addition of polar solvent may be advantageous if, as a result, a more
favorable partition
of the catalyst and of the amination product in the two phases (A) and (B) is
achieved.
The same applies to the lowering of the temperature.
The phase separation of the two phases (A) and (B) in step (b) generally takes
place
by gravimetric phase separation. The reaction space in which the reaction
according to
step (a) has taken place, for example a reactor, can serve as phase separation
vessel.
The separation of two liquid phases is per se a standard procedure which is
known to
the person skilled in the art. Standard methods and processes are described,
for
example, in E. Muller et al., "Liquid-Liquid Extraction" in Ullmann's
Encyclopedia of
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Industrial Chemistry, 2005, Wiky-VCH-Verlag, 10.1002/14356007.603-06, Chapter
3,
"Apparatus".
In step (c) of the process according to the invention, at least some of the
phase (B)
5 separated off in step (b), is returned again to the reaction in step (a),
optionally after
one or more steps for the purposes of purification, such as distillation. In
this
connection, the entire separated-off nonpolar phase (B) can be returned,
although it
may also be sensible, for the purposes of removing undesired by-products and
impurities, to remove some of the nonpolar phase from the process in order to
avoid an
10 accumulation of undesired components in the process.
As a rule, the polar phase will also comprise at least small amounts of the
catalyst. If it
is necessary to further reduce the catalyst fraction in the polar phase (A),
then it can be
extracted with a nonpolar solvent. The extraction of the catalyst can be
carried out in
15 any suitable device known to the person skilled in the art, preferably
in countercurrent
extraction columns, mixer settler cascades or combinations of mixer settler
apparatuses with extraction columns. The nonpolar extract comprising the
catalyst can
then, optionally after removing excess nonpolar solvent by evaporation, be
returned
again to the amination reaction in step (a). Preferably, the extractant used
is the
20 nonpolar solvent used in step (a). The extraction of the catalyst from
the polar product
phase (B) can be carried out before or after separating off the amination
product in step
(d). According to a preferred embodiment, the extracted catalyst is returned
at least in
part to the reaction.
25 In step (d) of the process according to the invention, the amination
product is separated
off from the polar product phase (A). Thus, in step (d), the polar solvent can
be
separated off from the amination product by distillation and either be
returned to the
process or be discarded. Unreacted starting material (alcohol), any excess
ammonia
present or by-products can likewise be removed from the amination product by
30 distillation. Thermal removal of the polar solvent takes place by prior
art methods
known to the person skilled in the art, preferably in an evaporator or in a
distillation unit,
comprising evaporator and column(s), which usually has a plurality of trays,
arranged
packing or dumped packing.
35 The addition of bases can have a positive effect on the product
formation. Suitable
bases which may be mentioned here are alkali metal hydroxides, alkaline earth
metal
hydroxides, alkali metal alcoholates, alkaline earth metal alcoholates, alkali
metal
carbonates and alkaline earth metal carbonates, which can be used in an amount
of
from 0.01 to 100 molar equivalents based on the metal catalyst used.
The invention is illustrated by the examples below without limiting it
thereto.
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36
Examples:
General procedure for the catalytic amination according to the invention of
alcohols
5 with ammonia
Ligand L, metal salt M or catalyst complex XlVb (for preparation see below,
weighing in
under inert atmosphere), solvent (sufficient for the total solvent volume to
be 50 ml)
and the alcohol to be reacted were introduced as initial charge under an Ar
atmosphere
in a 160 ml Parr autoclave (stainless steel V4A) with magnetically coupled
slanted-
10 blade stirrer (stirring speed: 200-500 revolutions/minute). The stated
amount of
ammonia was either precondensed at room temperature or directly metered in
from the
NH3 pressurized-gas bottle. If hydrogen was used, this was carried out by
means of
iterative differential pressure metering. The steel autoclave was heated
electrically up
to the stated temperature and heated (internal temperature measurement) for
the
15 stated time with stirring (500 revolutions/minute). After cooling to
room temperature,
decompressing the autoclave and outgassing the ammonia at atmospheric
pressure, 5
or 50 ml of water were added, whereupon two liquid phases were obtained, which
were
separated by means of phase separation. The reaction mixture was analyzed by
means of GC (30 m RTX5 amine 0.32 mm 1.5 pm). The ruthenium content of the
20 respective liquid phase was ascertained by means of atomic absorption
spectroscopy.
The results for the amination of 1,4-butanediol (Table 1), diethylene glycol
(Table 2)
and monoethylene glycol (Table 3) are given below:
Synthesis of the catalyst complex XlVb
PCy2
,Br
410
/ "N / \ N 1111(¨
HPCy2 [RuH0I(C0)(PPh3)3]
N 31...
Me0H Toluene
= 410 ( 3`- -
7`4
Fi --)"
Br ''', CO
\
PCy2
XlVb
a) Synthesis of 4,5-bis(dicyclohexylphosphinomethyl)acridine
A solution of 4,5-bis(bromomethypacridine1 (5.2
g, 14.2 mmol) and
30 dicyclohexylphosphine (8.18 g, 36.8 mmol) in 65 ml of anhydrous,
degassed methanol
was heated at 50 C under an inert argon atmosphere for 66 h. After cooling to
room
temperature, triethylamine (5.72 g, 56.7 mmol) was added and the mixture was
stirred
for 1 h. Evaporation of the solvent produced a yellow-white solid in red oil.
Extraction
by means of 3 x 40 ml of MTBE and concentration of the filtrate produced a red-
brown
35 oil (1H NMR: mixture of product & HPCy2). Taking up in a small amount of
warm MTBE
EK10-1687PC
=
PF0000071687/MKr CA 02828330 2013-08-27
37
followed by addition of ice-cooled methanol resulted in precipitation of a
yellow,
microcrystalline solid. Isolation and drying in vacuo gave air-sensitive 4,5-
bis(dicyclo-
hexylphosphinomethyl)acridine (2.74 g, 33%) as yellow powder. 1H NMR (360.63
MHz,
toluene-d8): 6 [ppm] = 8.07 (s, 1H, H9), 7.91 (d, J = 8.3 Hz, 2H, Ar-H), 7.42
(d, J =
8.3 Hz, 2H, Ar-H), 7.21 (dd, J = 8.3 Hz, J = 7.2 Hz, 2H, Ar-H), 3.89 (bs, 4H, -
CH2-P),
1.96-1.85 (m, 8H, Cy-H), 1.77-1.54 (m, 20H, Cy-H), 1.26-1.07 (m, 16H, Cy-H).
31P{1H}
NMR (145.98 MHz, toluene-d8): 6 [ppm] = 2.49 (s, -CH2-P(CY)2).
b) Synthesis of the catalyst complex XlVb
4,5-Bis(dicyclohexylphosphinomethyl)acridine (1855 mg, 3.1 mmol)
and
[RuHCI(C0)(PPh3)3]2 (2678 mg, 2.81 mmol) were heated at 70 C in 80 ml of
degassed
toluene for 2 h. The resulting dark-brown solution was evaporated to dryness,
the
residue was slurried in 3 x 20 ml of hexane and isolated by filtration. Drying
in vacuo
gave Ru-PNP pincer complex XlVb (1603 mg, 75%) as an orange-brown powder.
1H NMR (360.63 MHz, toluene-d8): 6 [ppm] = 8.06 (s, 1H, H9), 7.43 (d, J= 7.6
Hz, 2H,
Ar-H), 7.33 (d, J= 6.5 Hz, 2H, Ar-H), 7.06-7.02 (m, 2H, Ar-H), 5.02 (d, J=
11.9 Hz, 2H,
-CHH-PCy2), 3.54 (d, J = 12.2 Hz, 2H, -CHH-PCy2), 2.87 (bs, 2H, -
P(CaH(CH2)5)2), 2.54
(bs, 2H, -P(CbH(CH2)5)2), 2.18 (bs, 2H, Cy-H), 1.88-1.85 (m, 8H, Cy-H), 1.65
(bs, 6H,
Cy-H), 1.42-1.35 (m, 14H, Cy-H), 1.17-0.82 (m, 12H, Cy-H), -16.29 (t, J= 19.1
Hz, 1H,
Ru-H). 31P{1H} NMR (145.98 MHz, toluene-d8): 6 [ppm] = 60.89 (s, -CH2-P(CY)2).
1 J. Chiron, J.P. Galy, Synlett, 2003, 15, 2349-2350.
2 Literature procedure: Inorganic Syntheses 1974, 15, 48. See also: T. Joseph,
S. S.
Deshpande, S. B. Halligudi, A. Vinu, S. Ernst, M. Hartmann, J. Mol. Cat. (A)
2003, 206,
13-21.
EK10-1687PC
PF0000071687/MKr
38
Table 1: Reaction of 1,4-butanediol
L J J
NH 3 H(:)
NH2 + H2NN H2 4. N N
H
a b c
No!) T Time NH3 Reac- Metal salt Metal Ligand [L] Ligand Pmc
Pc Con- Selectivityc)
( C) (h) [eq.] e} tion [M] (mol%) [L] (Ru)q)
(Ru)q) ver- a : b : c
n
pres- (mol%)4 (mol /0)
sion b)
0
I\)
sure r)
ico
I.)
[bar]
CO
UJ
UJ
1d) 155 12 6 49 [RuHCI(C0)(PPh3)3] 0.1 Triphos 0.1
1.8 74.7 59.1 0.7 6.7 0
I.)
2d) 155 12 6 66h) [RuHCI(CO)(PPh3)3] 0.1 Triphos
0.1 3.2 61.8 78.0 0.6 5.4 0
F-,
UJ
I
3d) 155 12 6 45 [RuHCI(C0)(PPh3)3] 0.1 Xantphosg) 0.1 1.4
35.0 81.8 0.0 6.4 0
0
1
4d) 155 60 6 61 h) [RuHCI(C0)(PPh3)3] 0.2 Triphos
0.2 11.5 1.7 99.5 23.6 8.2 62.3 I.)
-1
5d) 155 60 6 61h) [RuHCI(C0)(PPh3)3] 0.1 Triphos
0.1 14.0 2.0 98.5 34.2 11.4 49.6
6d) 155 12 6 81') [RuHCI(C0)(PPh3)3] 0.1 Triphos
0.1 10.0 1.4 10.5 97.3 0 0.9
7d) 180 12 6 89 [RuHCI(C0)(PPh3)3] 0.1 Triphos
0.1 12.0 1.7 9.2 97.5 0 0.8
8k) 155 12 6 90') Catalyst complex XlVb 0.1 -
3.5 3.6 74,8 44.7 2.1 41.0
9c 155 12 6 41 [RuHCI(C0)(PPh3)3] 0.1 Triphos 0.1
2.1 66.3 62.1 0.5 5.8
10d) 155 12 6 41 [RuHCI(C0)(PPh3)3] 0.1 Xanthphosg) 0.1
1.6 34.3 79.6 0 4.9
11d) 155 12 6 41 _ Catalyst complex XlVb 0.1 1.1
63.0 71.8 9.3 17.3
EK10-1687PC
,
,
PF0000071687/MKr
39
12d) 155 12 6 61 h) [RuHCI(C0)(PPh3)3] 0.1
Xanthphosg) 0.1 1.4 29.3 79.8 0 3.3
13d) 155 12 6 61 h) [Ru(COD)methylally12] 0.1
(Tetraphos)l) 0.1 1.3 10.9 33.2 0 0.6
14d) 155 12 6 5511) Catalyst complex XlVb 0.1 1.5
' 25 81 4.8 13.6
15d) 180 12 6 39h) [RuHCI(C0)(PPh3)3] 0.2 Triphosf) 0.2 5.7
99.9 1.7 4.7 37.7
16d) 155 12 ' 6 35 [RuHCI(C0)(PPh3)3] 0.2 Triphosf)
0.2 1.8 75.5 60.4 0.7 20.5
17d) 155 12 6 40 Catalyst complex XlVa 0.1 1.2
56.1 79.7 3 16.3
18d) 180 2 6 53 Catalyst complex XlVb 0.2 1.1
91.5 36.4 25.8 35.4
19d) 180 12 6 70h) Catalyst complex XlVb 0.1 1.2
94.2 30.1 37.2 31.6 n
20d) 155 12 1.5 11 Catalyst complex XlVb 0.1 1.1
81.6 35.4 9 51 0
I.)
0
21d) 155 12 6 70n) [RuHCI(C0)(PPh3)3] 0.1 Triphosf) 0.1
3.4 19.8 95.4 0 1.5 K)
0
u.)
22d) 155 12 6 38 [RuHCI(C0)(PPh3)3] 0.2 DPPEPP 0.2 1.0
66.6 68.1 0.1 11 u.)
0
23d) ) 155 12 6 41 [RuHCI(C0)(PPh3)31 0.2 DPPEPP 0.2 4.3
39.4 56.2 0 4.3 "
0
H
2e) 180 12 6 82n) Catalyst complex XlVb 0.1 2.3
89.9 36.2 35.4 27.7 u.)
1
0
a) 50 ml of toluene; batch size: 25 mmol of 1,4-butanediol,
co
1
1.3
b) Evaluation by means of GC (area `)/0);
C) Product selectivity determined by means of GC;
d) Ru partition coefficient was determined by reference to the measured Ru
contents in 50 ml of organic solvent and 5 ml of water (addition after the end
of the
reaction);
e) Molar equivalents of NH3 per OH function on the substrate;
f) Triphos = 1,1,1-tris(diphenylphosphinomethyl)ethane, CAS 22031-12-5;
. g) Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, CAS 161265-03-
8;
' h) 5 bar H2 injected cold;
i) 20 bar H2 injected cold;
j) 30 bar H2 injected cold;
k) Ru partition coefficient was determined by reference to the measured Ru
contents in 50 ml of organic solvent and 50 ml of water (addition after the
end of the
EK10-1687PC
PF0000071687/MKr
reaction),
I) Tetraphos = tris[2-(diphenylphosphino)ethyllphosphine, CAS 23582-03-8,
m) 5 mol% water per OH function on the substrate,
n) 10 bar H2 injected cold,
o) 0.2 mol% potassium tert-butanolate,
p) Bis(2-diphenylphosphinoethyl)phenylphosphine, CAS: 23582-02-7
q) Pmc = mRu (upper phase)/mRu (lower phase); Pc = cRu (upper phase)/cRu
(lower phase);
r) mol% based on number of OH functions on the substrate
0
co
co
0
0
0
CO
EK10-1687PC
PF0000071687/MKr
41
Table 2: Reaction of diethylene glycol
NH3 /----- \
HO,..õ.-----, -----,_,....OH -1.- HO,.....õ----. ts11-4, 4. H2N,õ....---...
----....õ.NH2 +
0 NH
0 0 0 \ /
a b c
No. T ( C) Time (h) Reaction Metal salt Metal Ligand N Ligand Pc (m) PC
(c) Conver- Selectivity
pressure [M] (mol%) (Ru)
(RU) sion a : b : c r)
[bar] (mol%)
0
I.)
0
1d) 155 12 59k) [RuHCI(C0)(PPh3)31 0.1 Triphosf)
0.1 2.5 16.2 87.3 0.1 2.3 I.)
co
u.)
u.)
0
2d) 135 12 37 Catalyst complex XlVb 0.1 3.3
42.1 87.1 3.3 6.5 I.)
0
3d) 155 12 43 Catalyst complex XlVb 0.1 1.7
82.4 55.3 20.1 10.9 H
LO
I
0
CO
4d) 180 12 87" [RuHCI(C0)(PPh3)3] 0.2 Triphos" 0.2 15.6 2.3 24.1 93.0
1.2 5.3 1
I.)
-.1
59) 155 12 67" Catalyst complex XlVb 0.1 1.9
2.0 12.2 94.1 2.1 ' 2.0
69) 155 12 82" Catalyst complex XlVb 0.1 5.9
6.1 4.2 93.3 0 2.1
79) 155 12 94n) Catalyst complex XlVb 0.1 5.4
5.7 2.2 91.9 0 0
89) 155 12 43 Catalyst complex XlVb 0.1 1.9
2.0 79.6 57.6 22.4 12.8
9d/ 155 12 42.6 [RuHCI(C0)(PPh3)3] 0.10
Xanthphost) 0.10 1.1 27.7 67.1 0.2 5.26
EK10-1687PC
PF0000071687/MKr
42
10d) 155 15 46.4 Catalyst complex XlVb 0.10 1.1
77.5 49.1 23.7 13.08
0)
11d) 155 12 41.8 [RuHCI(C0)(PPh3)3] 0.10 Triphos" 0.10 1.0
52.4 66.2 0.9 6.60
12d) 155 12 61.2k) [RuHCI(C0)(PPh3)3] 0.10
Xanthphos" 0.10 1.2 19.0 75.0 0.1 5.85
13d) 155 12 57.1k) Catalyst complex XlVb 0.10 1.3
29.4 87.0 6.7 3.58
140) 180 12 64.7 [RuHCI(C0)(PPh3)3] 0.20 Triphos" 0.20 2.0
97.6 26.4 13.4 53.98
n
15" 155 12 7.5 Catalyst complex XlVb 0.10 1.4
85.9 18.4 7.5 41.55
0
op
I.)
160) 155 12 58.8 [RuHCI(C0)(PPh3)3] 0.40 Triphos" 0.40 1.1
64.7 65.2 1.3 17.97 op
u.)
u.)
0
170) 180 12 61.1k) [RuHCI(C0)(PPh3)3] 0.20 Triphos" 0.20 1.7
93.0 43.7 11.6 38.76 I.)
0
H
LO
I
180) 180 12 60.6 k) [RuHCI(C0)(PPh3)3] 0.40
Triphos" 0.40 2.4 95.3 38.0 9.8 48.00 0
op
1
190) 155 60 60.1 k) [RuHCI(C0)(PPh3)3] 0.20
Triphos" 0.20 6.0 86.1 52.4 6.9 35.35 I.)
-A
200) 155 60 58.8 k) [RuHCI(C0)(PPh3)3] 0.10
Triphos" 0.10 3.4 85.1 52.8 8.3 31.65
210) 155 12 42.2 [RuHCI(C0)(PPh3)3] 0.20 OPPEPP1) 0.20 2.0
23.1 46.9 0.0 5.51
p)
22" 180 12 75.6" Catalyst complex XlVb 0.10 2.3
86.1 35.7 47.2 13.77
23d) 180 12 95.9" Catalyst complex XlVb 0.10 3.4
29.1 71.8 18.2 5.32
240) 180 12 79.7" [RuHCI(C0)(PPh3)3] 0.20 Triphos" 0.20 6.39
54.1 83.5 3.3 11.96
EK10-1687PC
PF0000071687/MKr
43
a) 50 ml of toluene; batch size: 25 mmol of diethylene glycol, 6 molar
equivalents of NH3 per OH function on the substrate (unless stated otherwise)
b) Evaluation by means of GC (area %);
c) Product selectivity determined by means of GC;
d) Ru partition coefficient was determined by reference to the measured Ru
contents in 50 ml of organic solvent and 5 ml of water (addition after the end
of the
reaction);
e) Pmc = mRu (upper phase)/mRu (lower phase); Pc = cRu (upper phase)/cRu
(lower phase);
f) Triphos = 1,1,1-tris(diphenylphosphinomethyl)ethane, CAS 22031-12-5;
g) Ru partition coefficient was determined by reference to the measured Ru
contents in 50 ml of organic solvent and 50 ml of water (addition after the
end of the
reaction),
h) mol% based on number of OH functions on the substrate,
i) Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, CAS 161265-03-
8; 0
j) Bis(2-diphenylphosphinoethyl)phenylphosphine, CAS: 23582-02-7
co
k) 5 bar H2 injected cold;
co
1)10 bar H2 injected cold;
0
m) 20 bar H2 injected cold;
0
n) 30 bar H2 injected cold;
o) 5 mol% water per OH function on the substrate,
0
co
p) 0.2 mol% potassium tert-butanolate,
q) Only 1 molar equivalent of NH3 per OH function on the substrate
EK10-1687PC
PF0000071687/MKr
44
Table 3: Reaction of MEG
HO NH3 HO '
..--...õ,OH ,õ. NH2 + H2N...".õõ14H2 + HOH
"-'
a b c
NO. a) T ( C) Time Reaction Further Metal salt Metal
Ligand Ligand Pc (m) Pc (c) Conver- Selectivity c
(h) pressure conditions [NA] [Li h) (M01%)g)
(Re' e) (Ru)" sionb a : b : c
[bar] (mol%)
n
1 180 12 36 [RuHCI(C0)(PPh3)3] 0.20
Triphos 0.20 20.4 2.6 45.2 8.8 1.5 59.9
0
2 155 12 42 [RuHCI(C0)(PPh3)3] 0.20
Triphos 0.20 13.3 1.7 20.8 23.2 3.6 40.4 "
co
I.)
3 155 12 57 [RuHCI(C0)(PPh3)3] 0.20
Triphos 0.20 21.0 2.7 19.9 25.1 3.4 34.4 co
u.)
u.)
4 155 12 57 [RuHCI(C0)(PPh3)3] 0.40
Triphos 0.40 14.4 1.8 34.3 19.9 2.8 15.3 0
I.)
0
180 12 48 1mol% KOtBu
[RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20 19.4 2.5 43.8 34.0
13.0 20.6 H
La
I
0
CO
6 155 12 42 1morY0 KOtBu
[RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20 9.3 1.2 20.0 50.5
11.1 6.9 1
I.)
--3
7 180 12 47 Inject 5 bar H2
[RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20 8.0 1.0 41.2 10.3
2.8 57.0
cold
8 155 12 42 Inject 5 bar H2
[RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20 19.9 2.6 21.6 22.2
3.5 33.9
cold
9 180 12 51 5mol% H20 [RuHCI(C0)(PPh3)3] 0.20
Triphos 0.20 11.9 1.5 39.3 11.1 3.01 54.6
155 12 40 5mol% H20 [RuHCI(C0)(Plph3)3] 0.20
Triphos 0.20 17.7 2.3 19.6 21.7 3.1 33.5
11 155 60 57 Inject 5 bar H2
[RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20 63.9 8.2 57.6 14.0
5.4 62.1
cold
EK10-1687PC
PF0000071687/MKr
12 155 60 57 Inject 5 bar H2 [RuHCI(C0)(PPh3)3] 0.10 Triphos
0.10 24.9 3.2 35.0 15.7 7.1 63.6
cold
a) 50 ml of toluene; batch size: 25 mmol of ethylene glycol, 6 molar
equivalents of NH3 per OH function on the substrate;
b) evaluation by means of GC (area %);
c) product selectivity determined by means of GC;
d) Ru partition coefficient was determined by reference to the measured Ru
contents in 50 ml of organic solvent and 5 ml of water;
e) Pc (m) = mRu (upper phase)/mRu (lower phase);
f) Pc (c) = cRu (upper phase)/cRu (lower phase); =
g) mol% based on number of OH functions on the substrate;
h) Triphos = 1,1,1-tris(diphenylphosphinomethyl)ethane, CAS 22031-12-5
co
co
0
I\)
0
0
CO
I\)
EK10-1687PC
