Note: Descriptions are shown in the official language in which they were submitted.
CA 02828166 2013-08-23
PF0000071686/MKr As originally filed
1
Process for the preparation of primary amines by homogeneously catalyzed
alcohol
am ination
The present invention relates to a process for the preparation of primary
amines by
alcohol amination of primary alcohols with ammonia, with the elimination of
water, in
the presence of a complex catalyst which comprises at least one element
selected from
groups 8 and 9 of the Periodic Table of the Elements and also at least one
phosphorus
donor ligand of the general formula (I).
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 amines are currently prepared by the heterogeneously catalyzed alcohol
amination of alcohols with ammonia. WO 2008/006752 Al describes a process for
the
preparation of amines by reacting primary 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 oxide-,
copper
oxide-, zirconium oxide- and molybdenum oxide-comprising heterogeneous
catalysts
for the amination of alcohols with ammonia and hydrogen. In 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 200 bar.
The homogeneously catalyzed amination of monoalcohols with primary and
secondary
amines has been known since the 1970s where, in most cases, ruthenium or
iridium
catalysts are described. Compared to heterogeneously catalyzed reactions, the
homogeneously catalyzed amination proceeds at significantly lower temperatures
of
from 100 to 150 C. The reaction of alcohols with primary and secondary amines
is
described, for example, in the following publications: US 3708539; 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, DOI:
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.
mt. Ed. 2007, 46, 8291-8294; A. Tillack, D. Hollmann, K. Mevius, D. Michalik,
S. Bahn,
EK10-1686PC
PF0000071686/MKr CA 02828166 2013-08-23
2
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; A.
Tillack,
D. Hol!mann, 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, with the formation of
secondary and tertiary amines, is possible. The reaction of alcohols with
ammonia,
which is the economically most attractive amination reaction, is not described
in these
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
describe
the amination of secondary alcohols such as cyclohexanol with ammonia
homogeneously catalyzed with ruthenium catalysts. EP 0 320 269 A2 discloses
the
palladium-catalyzed amination of primary allyl alcohols with ammonia to give
primary
alkylamines. WO 2010/018570 and C. Gunanathan, D. Milstein, Angew. Chem. mt.
Ed.
2008, 47, 8661-8664 describe the amination of primary alcohols with ammonia to
give
primary amines with the help of a specific ruthenium catalyst with acridine-
based pincer
ligands.
R. Kawahara, K.I. Fujita, R. Yamaguchi, J. Am. Chem. Soc. DOI:
10.1021/ja107274w
describes the amination of primary alcohols with ammonia using an iridium
catalyst
which has, as ligands, Cp* (1,2,3,4,5-pentamethylcyclopentadienyl) and
ammonia.
However, using the catalyst system described therein, when reacting primary
alcohols
with ammonia, the undesired tertiary amines are exclusively obtained.
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, the monoamination product (monoethanolamine) is formed.
However, it is disadvantageous that the secondary and tertiary amines (di- and
triethanolamine) and cyclic products (N-(hydroxyethyl)piperazine and N,N'-
bis(hydroxyethyl)piperazine) are formed as by-products.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
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Although the prior art describes processes for the homogeneously catalyzed
reaction of
primary alcohols to give primary amines, there is still a great need for
alternative,
improved preparation processes with simpler and readily accessible phosphane
ligands.
It is an object of the present invention to provide a process for the
preparation of
primary amines by homogeneously catalyzed alcohol amination of primary
alcohols
with ammonia, with the elimination of water, in which no acridine-based
complex
catalyst is used and in which the formation of undesired by-products, such as
secondary and tertiary amines and also cyclic amines, is largely avoided.
The object is achieved by a process for the preparation of primary amines
which have
at least one functional group of the formula (-CH2-NH2) by alcohol amination
of starting
materials which have at least one functional group of the formula (¨CH2-0H),
with
ammonia, with the elimination of water, where the alcohol amination is carried
out
under homogeneous catalysis in the presence of at least one complex catalyst
which
comprises at least one element selected from groups 8 and 9 of the Periodic
Table of
the Elements, and also at least one phosphorus donor ligand of the general
formula (I),
1
R
p_y1y2-p/R3
R2R
Y3
FR,
R6
(I)
where
n is 0 or 1;
R1, R2, R3, R4, R5,
11 are,
independently of one another, unsubstituted or at
least monosubstituted C1-04-
alkyldiphenylphosphine (-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,
EK10-1686PC "as originally filed"
,
PF0000071686/MKr CA 02828166 2013-08-23
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4
where the substituents are selected from the group consisting of:
F, Cl, Br, OH, ON, NH2 and Cr-Curalkyl;
A is
i) a bridging group selected from the group unsubstituted or at least
monosubstituted N, 0, P, C1-C6-alkane, 03-C10-cycloalkane, C3-C10-
heterocycloalkane comprising at least one heteroatom selected from N, 0
and S, C6-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:
CI-Ca-alkyl, phenyl, F, Cl, Br, OH, OR7, NH2, NHR7 or N(R7)2,
where R7 is selected from CI-Cur-alkyl and C6-C10-aryl;
or
ii) a bridging group of the formula (II) or (III):
1 1 1 1
;(i x2
(II) (III)
m, q are, independently of one another, 0, 1, 2, 3 or 4;
R9, R9 are, independently of one another, selected
from the group
C1-C10-alkyl, F, Cl, Br, OH, OR7, NH2, NHR7 and N(R7)2,
where R7 is selected from C1-C10-alkyl and C6-C10-aryl;
X1, X2 are, independently of one another, NH, 0 or
S;
X3 is a bond, NH, NR19, 0, S or 0R11 iR 2;
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
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,
5 0 and S,
where the substituents are selected from the group consisting
of: F, Cl, Br, OH, CN, NH2 and C1-C10-alkyl;
R11, R12 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, ON, NH2 and C1-C10-alkyl;
y1, y2, Y3are, 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, OR7, ON, NH2, NHR7, N(R7)2 and CI-Gm-alkyl,
where R7 is selected from C1-C10-alkyl and C5-C10-aryl.
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
groups 8
and 9 of the Periodic Table of the Elements and also at least one phosphorus
donor
ligand of the general formula (I), primary amines are obtained in considerably
improved
yields 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 largely avoided.
Starting materials
In the process according to the invention, alcohols which have at least one
functional
group of the formula (¨CH2-0H) are used as starting materials.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
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Suitable starting materials are practically all alcohols which satisfy the
prerequisites
specified above. The alcohols may be straight-chain, branched or cyclic.
Moreover, the
alcohols can carry substituents which exhibit inert behavior under the
reaction
conditions of the alcohol amination, for example alkoxy, alkenyloxy,
alkenyloxy,
alkylamino, dialkylamino and halogens (F, Cl, Br, l). According to the
invention, besides
monoalcohols, also diols, triols, polyols and alkanolamines which have at
least one
functional group of the formula (¨CH2-0H) can be used as starting materials.
Monoalcohols to be used according to the invention are alcohols which have
only one
functional group of the formula (¨CH2-0H). Diols, triols and polyols to be
used
according to the invention are alcohols which have at least one functional
group of the
formula (¨CH2-0H) and one, two or more further hydroxyl groups. Alkanolamines
to be
used according to the invention are compounds which have at least one
functional
group of the formula (¨CH2-0H) and at least one further primary, secondary or
tertiary
amino group.
Suitable alcohols are, for example, those of the general formula (IV):
Ra-CH2-0H
(IV),
where
Ra is selected from the group hydrogen, unsubstituted or at least
monosubstituted
C1-C30-alkyl, C3-C10-cycloalkyl, C3-C10-heterocycly1 comprising at least one
heteroatom selected from N, 0 and S, C5-C14-aryl and C5-C14-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,
OR7, ON, NH2, NHR7 or N(R7)2, C1-C10-alkyl, C3-C10-cycloalkyl, C3-Cio-
heterocycly1 comprising at least one heteroatom selected from N, 0 and S,
C5-C14-aryl and C5-C14-heteroaryl comprising at least one heteroatom selected
from N, 0 and S,
where R7 is selected from C1-C10-alkyl and C5-C10-aryl.
Preferably, for example, the following alcohols are aminated: methanol,
ethanol, n-
propanol, n-butanol, isobutanol, n-pentanol, n-hexanol, n-heptanol, n-octanol,
n-
nonanol, 2-ethylhexanol, tridecanol, stearyl alcohol, palmityl alcohol, benzyl
alcohol, 2-
EK10-1686PC "as originally filed"
.
PF0000071686/MKr CA 02828166 2013-08-23
,
7
phenylethanol, 2-(p-methoxyphenyl)ethanol, 2-(3,4-dimethoxyphenyl)ethanol,
allyl
alcohol, propargyl alcohol, 2-hydroxymethyl-furan, lactic acid and serine.
Starting materials which can be used are all known diols which have at least
one
functional group of the formula (¨CH2-0H). 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-propanediol (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,
1,10-
decanediol, 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,
polyethylene
glycols, polypropylene glycols, such as 1,2-polypropylene glycol and 1,3-
polypropylene
glycol, polytetrahydrofuran, diethanolamine, 1,4-bis(2-
hydroxyethyl)piperazine, diiso-
propanolamine, N-butyldiethanolamine, 2,5-(dimethanol)-
furan, 1,4-
bis(hydroxymethyl)cyclohexane and N-methyldiethanolamine. 2,5-(dimethanol)-
furan is
also called 2,5-bis(hydroxymethyl)-furan.
Preference is given to diols which have two functional groups of the formula (-
CH2-0H).
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.
Starting materials which can be used are all known triols which have at least
one
functional group of the formula (¨CH2-0H). Examples of triols which can be
used as
starting materials in the process according to the invention are glycerol,
trimethylolpropane and triethanolamine.
Preference is given to triols which have at least two functional groups of the
formula
(-CH2-0H).
Particularly preferred triols are glycerol and triethanolamine.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
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Starting materials which can be used are all known polyols which have at least
one
functional group of the formula (¨CH2-0H). Examples of polyols which can be
used as
starting materials in the process according to the invention are 2,2-
bis(hydroxymethyl)-
1,3-propanediol (pentaerythritol), sorbitol, inositol, sugars and polymers
with primary
hydroxyl groups (¨CH2-0H) 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).
Particularly preferred polyols are cellulose, polyvinyl alcohol and glucose.
Starting materials which can be used are all known alkanolamines which have at
least
one primary hydroxyl group (¨CH2-0H). Examples of alkanolamines 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, N-(2-aminoethyl)ethanolamine, 1-(2-
hydroxyethyl)piperazine, 2-(2-aminoethoxy)ethanol, N-
butylethanolamine, N-
ethylethanolamine, N-methylethanolamine, N,N-
dimethylethanolamine, N-(2-
hydroxyethyl)-1,3-propanediamine, 3-(2-
hydroxyethyl)amino-1-propanol, 3-
dimethylamino-1-propanol, N,N-dibutylethanolamine, N,N-dimethylisopropylamine
and
N,N-diethylethanolamine.
Preference is given to alkanolamines which have at least one primary hydroxyl
group
(¨CH2-0H) and at least primary amino group of the formula (-CH2-NF12).
A particularly preferred alkanolamine is monoaminoethanol.
Complex catalyst
The process according to the invention uses at least one complex catalyst
which
comprises at least one element selected from groups 8 and 9 of the Periodic
Table of
the Elements (nomenclature in accordance with IUPAC), and also at least one
phosphorus donor ligand of the general formula (I),
EK10-1686PC "as originally filed"
,
PF0000071686/MKr CA 02828166 2013-08-23
,
9
R1 \,
/R3
p¨yl¨A_y2¨p/
I \ R
4
R2 I
I
Y3
1
/P\
R5 R6
1 1 n
(I)
where
n is 0 or 1;
R1, R2, R3, R4, R5, R6 are, independently of one another, unsubstituted or at
least monosubstituted C1-C10-alkyl, C1-C4-alkyldiphenylphosphine (-01-C4-
alkyl-P(phenYI)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, ON, 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-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, Cl, Br, OH, OR7, NH2, NHR7 or N(R7)2,
where R7 is selected from C1-C10-alkyl and C5-C10-aryl;
or
ii) a bridging group of the formula (II) or (III):
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
(R8)m (RN
(II) (Ill)
5 m, q are, independently of one another, 0, 1, 2, 3 or 4;
R9, R9 are, independently of one another, selected from the
group
C1-C10-alkyl, F, Cl, Br, OH, OR7, NH2, NHR7 and N(R7)2,
10 where R7 is selected from Cr-Cm-alkyl and C5-C10-aryl;
X1, X2 are, independently of one another, NH, 0 or S;
X3 is a bond, NH, NR19, 0, S or CR11w2;
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;
R11, R12 are, independently of one another, unsubstituted or at least
monosubstituted C1-C10-alkyl, CrCio-alkoxy, C3-C10-cycloalkyl,
C3-C10-cycloalkoxy, 03-Cl0-heterocycly1 cornprising 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, ON, NH2 and 01-010-alkyl;
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
11
)11, y2, r = ,3
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, OR7, ON, NH2, NHR7, N(R7)2 and C1-C10-alkyl,
where R7 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
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.
The elements of groups 8 and 9 of the Periodic Table of the Elements comprise
iron,
cobalt, ruthenium, rhodium, osmium and iridium. 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 groups 8 and 9 of the Periodic Table of the Elements, and also
at least
one phosphorus donor ligand of the general formula (I), where
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
12
n is 0 or 1;
R1, R2, R3, R4, R5, R6 are, independently of one another, unsubstituted
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;
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 (II) or (Ill):
(R8)m
(R9) (R8)
(R9)q
X2
(III)
m, q are, independently of one another, 0, 1, 2, 3 or 4;
Fe, R9 are, independently of one another, selected from the
group C1-C10-alkyl, F, Cl, Br, OH, OR7, NH2, NHR7 and
N(R7)2,
where R7 is selected from C1-C10-alkyl and C5-C10-aryl;
X1, X2 are, independently of one another, NH, 0 or S;
X3 is a bond, NH, NW , 0, S or CR11w2;
EK10-1686PC "as originally filed"
s
PF0000071686/MKr CA 02828166 2013-08-23
,
13
R10
is unsubstituted C1-C10-alkyl, C3-C10-cycloalkyl, Cy-C10-
heterocycly1 comprising at least one heteroatom selected
from N, 0 and S, C5-014-aryl or C5-C10-heteroaryl
comprising at least one heteroatom selected from N, 0
and S;
R11, R12
are, independently of one another, unsubstituted Cl-Cio-
alkyl, C1-C10-alkoxy, C3-C10-cycloalkyl, C3-C10-cycloalkoxy,
C3-010-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;
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 and 9 of the Periodic Table of the Elements, and also
at least
one phosphorus donor ligand of the general formula (V),
R1
\
p_ yl¨ A- y2¨p/\R3
/ R4
R2
(V)
where
R1, R2, R3, R4 are, independently of one
another, unsubstituted or at least
monosubstituted C1-010-alkyl, C1-C4-alkyldiphenylphosphine (-C1-a4-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, ON, NH2 and CI-Cm-alkyl;
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
14
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-C-
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, OR7, NH2, NHR7 or
where R7 is selected from C1-C10-alkyl and C5-C10-aryl;
or
ii) a bridging group of the formula II or III:
(R8),õ
RN (1:0),X3A.
(R9)q
...\----,
1 1 1 1
)(1 X2
(II) (III)
m, q are, independently of one another, 0, 1, 2, 3 or 4;
R8, R9 are, independently of one another, selected from the
group
C1-C10-alkyl, F, Cl, Br, OH, OR7, NH2, NHR7 and N(R7)2,
where R7 is selected from C1-C10-alkyl and C5-C10-aryl;
X1, X2 are, independently of one another, NH, 0 or S;
X3 is a bond, NH, NR19, 0, S or CR"R12;
R10 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-
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
heteroaryl comprising at least one heteroatom selected from N,
0 and S,
where the substituents are selected from the group consisting
5 of: F, Cl, Br, OH, CN, NH2 and CrCuralkyl;
R11, R12 are, independently of one another, unsubstituted or at
least
monosubstituted C1-C10-alkyl, C1-C10-alkoxy, C3-C10-cycloalkyl,
C3-C10-cycloalkoxy, 03-Ci0-heterocycly1 cornprising at least one
10 heteroatom selected from N, 0 and S, C5-C14-aryl, C5-Ci4
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
15 of: F, Cl, Br, OH, CN, NH2 and Cl-Curalkyl;
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,
Cl, Br, OH, OR7, CN, NH2, NHR7, N(R7)2 and C1-C10-alkyl,
where R7 is selected from C1-C10-alkyl and C5-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
selected from groups 8 and 9 of the Periodic Table of the Elements, and also
at least
one phosphorus donor ligand of the general formula (VI),
RI\ /R3
P¨Y1¨ A¨ Y2¨P
R2/
\ R4
V3
/P\
R5
R6
(VI)
where
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
16
R1, R2, R3, R4, R5, R6 are, independently of one another, unsubstituted or at
least monosubstituted C1-C10-alkyl, C1-C4-alkyldiphenylphosphine, C3-C10-
cycloalkyl, C3-C10-heterocycly1 corn prising at least one heteroatom selected
from N, 0 and S, C6-C14-aryl or C6-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 a bridging group selected from the group unsubstituted or at
least
monosubstituted N, P, C1-C6-alkane, C3-C10-cycloalkane, C3-C10-
heterocycloalkane comprising at least one heteroatom selected from N, 0
and S, C5-C14-aromatic and C6-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, OR7, NH2, NHR7 or N(R7)2,
where R7 is selected from C1-C10-alkyl and C6-C10-aryl;
yl, 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, OR7, CN, NH2, NHR7, N(R7)2 and C1-C10-alkyl,
where R7 is selected from C1-C10-alkyl and C6-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
selected from groups 8 and 9 of the Periodic Table of the Elements, and at
least one
phosphorus donor ligand of the general formula (V), where
R1, R2, R3, R4 are,
independently of one another, methyl, ethyl, isopropyl, tert-
butyl, cyclopentyl, cyclohexyl, phenyl or mesityl;
A is
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
17
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 (VII) or (VIII):
401 x' 401 140 x3
x2
(VII)
X1, X2 are, independently of one another, NH, 0 or S;
X3 is a bond, NH, 0, S or CR11R12;
R11, R12 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 and 9 of the Periodic Table of the Elements,
and also
at least one phosphorus donor ligand of the general formula (IX) or (X),
(R9)m (R9)q (R9), (R9)
q
X1
R1 R2 R R43 R
R1 R2 R4
(IX) (X)
where for m, q, R1, R2, R3, R4, R9, R9, X1, X2 and X3, the definitions and
preferences
listed above are applicable.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
18
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 ,2-bis(dicylohexylphosphino)ethane, 1 ,3-
bis(diphenylphosphino)propane
(dPPP), 1 ,4-bis(diphenylphosphino)butane
(dppb), 2,3-bis(d icyclohexyl-
phosphino)ethane (dcpe), 4,5-
bis(diphenylphosphino)-9,9-dimethylxanthene
(xantphos), 1 , 1
'42,7-bis(1 , 1 -dimethylethyl)-9,9-dimethy1-9H-xanthene-4,5-diyl]bis[1 , 1 -
diphenyl]phosphin (t-bu-xantphos), bis(2-
diphenylphosphinoethyl)phenylphosphine and
1 ,1 ,1-tris(diphenylphosphinomethyl)ethane (triphos). Further preferred is
the
phosphorous donor ligand t-bu-xanthphos.
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 also
at least one phosphorus donor ligand selected from the group 4,5-bis(diphenyl-
phosphino)-9,9-dimethylxanthene (xantphos), bis(2-
diphenylphosphinoethyl)phenyl-
phosphine 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, Cy-Cm-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,
C6-C10-
aryloxy, C5-C10-alkylaryloxy, C5-C10-heteroaryloxy comprising at least one
heteroatom
selected from N, 0, S, oxo, C3-C10-cycloalkyl, phenyl, C6-C10-heteroaryl
comprising at
least one heteroatom selected from N, 0, S, C6-C10-heterocycly1 comprising at
least
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
,
19
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,
5 sulfonylamino, sulfinyl, sulfinylamino, thiol, C1-C10-alkylthiol, C5-C10-
arylthiol or Cl-Clo-
alkylsulfonyl.
The above definition for C1-C10-alkyl applies accordingly to C1-C30-alkyl and
to C1-C6-
alkane.
10 In the present case, C3-C10-cycloalkyl is understood 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 relation to the group C1-C10-alkyl.
The definition of C3-C10-cycloalkyl specified above applies accordingly to C3-
C10-
cycloalkane.
Within the context of the present invention, C5-C14-aryl is understood as
meaning an
20 aromatic ring system having 5 to 14 carbon atoms. The aromatic ring
system can be
monocyclic or bicyclic. Examples of aryl groups are phenyl, naphthyl, such as
1-
naphthyl and 2-naphthyl. The aryl group can be unsubstituted or substituted
with one or
more substituents as defined above under C1-C10-alkyl.
25 The definition of C5-C14-aryl given above applies accordingly to C5-C14-
aromatic.
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
30 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, furyl, benzofuryl, pyrrolyl, imidazolyl,
pyrazolyl, pyridyl,
pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, indazolyl, purinyl,
isoquinolinyl,
quinolinyl, acridinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl,
piperidinyl,
35 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.
The definition for C5-C10-heteroaryl given above applies accordingly to C5-C6-
40 heteroaromatic.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
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
5 of suitable heterocyclic ring systems are piperidinyl, pyrrolidinyl,
pyrrolinyl, pyrazolinyl,
pyrazolidinyl, morpholinyl, thiomorpholinyl, pyranyl, thiopyranyl,
piperazinyl, indolinyl,
dihydrofuranyl, tetrahydrofuranyl, dihydrothiophenyl,
tetrahydrothiophenyl,
dihydropyranyl and tetrahydropyranyl.
10 The definition of C3-C10-heterocycly1 given above applies accordingly to
C3-Clo-
heterocycloalkane.
Alcohol amination
15 The homogeneous catalysts can either 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],
20 [Ru(PPh3)3(C0)(H)C11, [Ru(PPh3)3(CO)C12], (Ru(PPh3)3(C0)(H)21,
[Ru(PPh3)3C12],
[Ru(cyclopentadienyl)(PPh3)2C1],
[Ru(cyclopentadienyl)(C0)2C1], [Ru(cyclopenta-
dienyl)(C0)2F1], [Ru(cyclopentadienyl)(C0)212,
[Ru(pentamethylcyclo-
pentadienyl)(C0)2C1], [Ru(pentamethylcylcopentedienyl)(C0)21-1],
[Ru(pentamethyl-
cyclopentadienyl)(CO)2]2, [Ru(indenyl)(C0)2C1], (Ru(indenyl)(C0)2H1,
[Ru(indenyI)-
(C0)212, ruthenocene, [Ru(binap)Cl2], [Ru(bipyridine)2C12*2H20],
[Ru(COD)C12]2,
[Ru(pentamethylcyclopentadienyl)(COD)CI], [Ru3(C0)12], [Ru(tetraphenylhydroxy-
cyclopentadienyl)(C0)2F1], [Ru(PMe3)4(H)2], [Ru(PEt3)4(H)2]. [Ru(PnPr3)4(H)2],
[Ru(PnBu3)4(H)2], [Ru(Rnocty13)4(H)2], [11-C13*F-1201, KIrCI4, K3IrC16,
Ur(COD)C1]2,
r(cyclooctene)2C1h, r(ethene)2C1h,
r(cyclopentadienyl)C12]2, r(pentamethyl-
cyclopentadienyl)C12]2, [Ir(cyclopentadienyl)(C0)2], p
r(pentamethylcyclopentadienyl)-
(C0)2], Dr(PPh3)2(C0)(1-1)], Pr(PPh3)2(C0)(C1)1, Pr(PPh3)3(C1)].
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
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.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
21
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
medium.
The reaction 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 can generally be carried out at a total pressure of from 0.1 to
20 MPa
absolute, which can either be the intrinsic pressure of the solvent at the
reaction
temperature, or else 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 in
the range from 0.5 to 15 MPa absolute, particularly preferably at a total
pressure in the
range from 1 to 10 MPa absolute.
The average reaction time is generally 15 minutes to 100 hours.
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 1.5- to 250-fold, preferably
in a 2- to
100-fold, in particular 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 process according to the invention can be carried out either in a solvent
or else
without solvents. Suitable solvents are polar and nonpolar solvents which can
be used
in pure form or in mixtures. For example, only one nonpolar or one polar
solvent can be
used in the process according to the invention. It is also possible to use
mixtures of two
or more polar solvents or mixtures of two or more nonpolar solvents or
mixtures of one
or more polar solvents with one or more nonpolar solvents. The product can
also be
used as solvent in pure form or in mixtures with polar or nonpolar solvents.
Suitable nonpolar solvents are, for example, saturated and unsaturated
hydrocarbons
such as hexane, heptane, octane, cyclohexane, benzene, toluene, xylene and
mesitylene, and linear and cyclic ethers such as THF, diethyl ether, 1,4-
dioxane, MTBE
(tert-butyl methyl ether), diglyme and 1,2-dimethoxyethane. Preference is
given to
using toluene, xylenes or mesitylene. Depending on the polarity of the
product, the
product can also be used as nonpolar solvent for the reaction.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
22
Suitable polar solvents are, for example, water, dimethylformamide, formamide,
tert-
amylalcohol and acetonitrile. Preference is given to using water. The water
can either
be added before the reaction, be formed during the reaction as water of
reaction, or
else be added after the reaction in addition to the water of reaction.
Depending on the
polarity of the product, the product can also be used as polar solvent for the
reaction. A
further preferred solvent is tert-amylalcohol.
For the reaction in the liquid phase, ammonia, the starting material having at
least one
functional group of the formula (¨CH2-0H), optionally together with one or
more
solvents, are introduced into a reactor together with the complex catalyst.
The introduction of ammonia, starting material, optionally solvent and complex
catalyst
can take place here simultaneously or separately from one another. The
reaction can
be carried out continuously, in semibatch procedure, in batch procedure, back-
mixed in
product as solvent or not back-mixed in a straight run.
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 reactors or bubble column reactors.
During the amination reaction, at least one primary hydroxyl group (¨CH2-0H)
of the
starting material is reacted with ammonia to give a primary amino group (-CH2-
NEI2),
where, in each case, one mol of water of reaction is formed per mole of
reacted
hydroxyl group.
Thus, during the reaction of alkanolamines which have only one primary
hydroxyl group
(¨CH2-0H), the corresponding diamines are formed. The reaction of monoamino-
ethanol thus leads to the corresponding 1,2-diaminoethane.
During the reaction of starting materials which, besides the functional group
of the
formula (¨CH2-0H), have a further hydroxyl group (diols), preferably only the
primary
alcohol group (¨CH2-0H) is aminated. The reaction of 1,2-ethylene glycol thus
leads to
the corresponding monoethanolamine. It is also possible to aminate both
hydroxyl
groups to give 1,2-diaminoethane.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
23
In the case of the reaction of starting materials which, besides the
functional group of
the formula (¨CH2-0H), have two further hydroxyl groups (triols), preferably
only one
primary alcohol group (¨CH2-0H) is aminated. It is also possible to react two
or three
hydroxyl groups with ammonia to give the corresponding primary diamines or
triamines. The formation of primary monoamines, diamines or triamines can be
controlled here via the amount of ammonia used and via the reaction
conditions.
In the case of the reaction of starting materials which, besides the
functional group of
the formula (¨CH2-0H), have more than three further hydroxyl groups (polyols),
preferably only one primary alcohol group (¨CH2-0H) is aminated. It is also
possible to
react two, three or more hydroxyl groups with ammonia to give the
corresponding
primary monoamines, diamines, triamines or polyamines. The formation of the
primary
monoamines, diamines, triamines and polyamines can be controlled here via the
amount of ammonia used and via the reaction conditions.
The reaction product which is formed during the reaction generally comprises
the
corresponding amination products, optionally the one or more solvents, the
complex
catalyst, any unreacted starting materials and ammonia, and also the water of
reaction
that is formed.
Any excess ammonia present, the optionally present solvents, the complex
catalyst
and the water of reaction are removed from the reaction product. The amination
product obtained can be worked-up further. The excess ammonia, the complex
catalyst, optionally the solvent or solvents and any unreacted starting
materials can be
returned to the amination reaction.
If the amination reaction is carried out without solvents, then the
homogeneous
complex catalyst is dissolved in the product after the reaction. This can
remain in the
product or be separated off from it by means of a suitable method.
Possibilities for
separating off the catalyst are, for example, washing with a product-
immiscible solvent
in which the catalyst dissolves better through appropriate choice of the
ligands than in
the product. Optionally, the concentration of the catalyst is reduced by means
of
multistage extraction from the product. The extractant used is preferably a
solvent also
suitable for the target reaction, such as toluene, benzene, xylenes, alkanes,
such as
hexanes, heptanes and octanes, and acyclic or cyclic ethers, such as diethyl
ether and
tetrahydrofuran, which, following concentration by evaporation, can be used
again for
the reaction together with the extracted catalyst. It is also possible to
remove the
catalyst with a suitable absorber material. Removal can also take place by
adding
water to the product phase if the reaction is carried out in a water-
immiscible solvent. If
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
,
24
the catalyst here dissolves preferentially in the solvent, it can be separated
off with the
solvent from the aqueous product phase and optionally be re-used. This can be
brought about by choosing suitable ligands. The resulting aqueous mono-, di-,
tri- or
polyamines can be used directly as technical-grade amine solutions. It is also
possible
5 to separate the amination product from the catalyst by distillation.
If the reaction is carried out in a solvent, then this may be miscible with
the amination
product and can be separated off by distillation after the reaction. It is
also possible to
use solvents which have a miscibility gap with the amination products or the
starting
10 materials. Suitable solvents for this purpose which may be mentioned
are, for example,
toluene, benzene, xylenes, alkanes, such as hexanes, heptanes and octanes, and
acyclic or cyclic ethers, such as diethyl ether, tetrahydrofuran and dioxane.
Through
appropriate choice of the phosphine ligands, the catalyst preferentially
dissolves in the
solvent phase, i.e. in the non-product-comprising phase. The phosphine ligands
can
15 also be selected such that the catalyst dissolves in the amination
product. In this case,
the amination product can be separated from the catalyst by distillation.
The solvent can also be miscible with the starting materials and the product
under the
reaction conditions and only form a second liquid phase which comprises the
majority
20 of the catalyst after cooling. Solvents which exhibit this property
which may be
mentioned are, for example, toluene, benzene, xylenes, alkanes, such as
hexanes,
heptanes and octanes. The catalyst can then be separated off together with the
solvent
and be re-used. The product phase can also be admixed with water in this
variant. The
fraction of the catalyst comprised in the product can then be separated off by
means of
25 suitable absorber materials such as, for example, polyacrylic acid and
salts thereof,
sulfonated polystyrenes and salts thereof, active carbons, montmorillonites,
bentonites
and also zeolites, or else be left in the product.
The amination reaction can also be carried out in two phases. For the
embodiment of
30 the two-phase reaction procedure, suitable nonpolar solvents are in
particular toluene,
benzene, xylenes, alkanes, such as hexanes, heptanes and octanes, in
combination
with lipophilic phosphine ligands on the transition metal catalyst, as a
result of which
the transition metal catalyst accumulates in the nonpolar phase. In this
embodiment, in
which the product and also the water of reaction and optionally unreacted
starting
35 materials form a second phase enriched with these compounds, the
majority of the
catalyst can be separated off from the product phase by simple phase
separation and
be re-used.
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
If volatile by-products or unreacted starting materials or else the water
formed during
the reaction or added after the reaction to improve extraction are undesired,
these can
be separated off from the product without problems by distillation.
5 It can 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.
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, of which 0.01 to 100 molar
equivalents, based on the metal catalyst used, can be used.
The present invention further provides for the use of a complex catalyst which
comprises at least one element selected from groups 8 and 9 of the Periodic
Table of
the Elements, and also at least one phosphorus donor ligand of the general
formula (I),
111\ /R3
p_yl-A--y2--p
___________________________________________ \R4
R2
Y3
/P\
R5
R6
(I)
where
n is 0 or 1;
R1, R2, R3, R4, R5, R6 are, independently of one another, unsubstituted or at
least monosubstituted C1-C10-alkyl, C1-C4-alkyldiphenylphosphine (-01-04-
alkyl-P(pheny1)2), C3-C10-cycloalkyl, 03-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,
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
26
where the substituents are selected from the group consisting of:
F, CI, Br, OH, ON, NH2 and 01-010-alkyl;
A is
i) a bridging group selected from the group unsubstituted or at least
monosubstituted N, 0, P, 01-06-alkane, 03-010-cycloalkane, 03-C10-
heterocycloalkane comprising at least one heteroatom selected from N, 0
and S, 05-C14-aromatic or 05-06-heteroaromatic comprising at least one
heteroatom selected from N, 0 and S,
where the substituents are selected from the group consisting of:
01-C4-alkyl, phenyl, F, Cl, Br, OH, OR7, NH2, NHR7 or N(R7)2,
where R7 is selected from 01-010-alkyl and 05-010-aryl;
Or
ii) a bridging group of the formula (II) or (III):
(R9)õ (Fe)m (R9)
(R8)m
)(1 =X2
(I1) (iii)
m, q are, independently of one another, 0, 1, 2, 3 or 4;
R8, R9 are, independently of one another, selected from the
group
01-010-alkyl, F, Cl, Br, OH, OR7, NH2, NHR7 and N(R7)2,
where R7 is selected from 01-010-alkyl and 05-C10-aryl;
X1, X2 are, independently of one another, NH, 0 or S;
X3 is a bond, NH, NR19, 0, S or CR11w2;
EK10-1686PC "as originally filed"
PF0000071686/MKr CA 02828166 2013-08-23
27
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;
R11, R12 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, ON, NH2 and C1-C10-alkyl;
, 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, OR7, ON, NH2, NHR7, N(R7)2 and CI-Cm-alkyl,
where R7 is selected from C1-C10-alkyl and C5-C10-aryl,
for the homogeneously catalyzed preparation of primary amines which have at
least
one functional group of the formula (-CH2-NH2), by alcohol amination of
starting
materials which have at least one functional group of the formula (¨CH2-0H)
with
ammonia.
For the use of the complex catalyst for the homogeneously catalyzed
preparation of
primary amines which have at least one functional group of the formula (-CH2-
NH2) by
alcohol amination of starting materials which have at least one functional
group of the
formula (¨CH2-0H) with ammonia, the definitions and preferences described for
the
process according to the invention are applicable.
EK10-1686PC "as originally filed"
,
PF0000071686/MKr CA 02828166 2013-08-23
28
The invention is illustrated by the examples below without limiting it
thereto.
Examples
General procedure for the catalytic amination according to the invention of
alcohols
with ammonia:
Ligand L, metal salt M, solvent and the stated alcohol were introduced as
initial charge
under an Ar atmosphere in a 160 ml Parr autoclave (hte, (stainless steel V4A))
with
magnetically coupled slanted-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 stated time with stirring (500 revolutions/minute). After
cooling to
room temperature, decompressing the autoclave and outgassing the ammonia at
atmospheric pressure, the reaction mixture was analyzed by means of GC (30 m
RTX5
amine 0.32 mm 1.5 pm). Purification of the particular product can be carried
out, for
example, by distillation. The results for the amination of octanol (Table 1 a
and 1 b), 1,4-
butanediol (Table 2), diethylene glycol (Table 3), 1,9-nonanediol, 1,6-
hexanediol, 1,10-
decandiol (Table 4) and 1,2-dimethanolfuran (Table 5) are given below:
Ligand name (L) CAS IUPAC
Triphos 22031-12-5 1,1,1-
Tris(diphenylphosphinomethyl)ethane
Xantphos 161265-03-8 4,5-Bis(diphenylphosphino)-
9,9-dimethylxanthene
S-Phos 657408-07-6 2-Dicyclohexylphosphino-
2',6'-dimethoxybiphenyl
Rhodaphos n.a. 1,1,1-
Tris(diethylphosphinomethyl)ethane
DPPEPP 23582-02-7 Bis(2-
diphenylphosphinoethyl)phenylphosphine
Tetraphos 23582-03-8 Tris[2-
(diphenylphosphino)ethyl]phosphine
tBu-Xantphos 221462-97-1 1,1'-[2,7-bis(1,1-
dimethylethyl)-9,9-dimethy1-9H-
xanthene-4,5-diyl]bis[1,1-diphenyl]phosphine
tBuPPyP 338800-13-8 2,6-Bis[(di-tert-
butylphosphino)methyllpyridine
DPEPhos 166330-10-5 Bis[2-
(diphenylphosphanyl)phenyllether
Depe 6411-21-8 1,2-
Bis(diethylphosphino)ethane
EK10-1686PC "as originally filed"
PF0000071686/MKr As originally filed
29
Table la
NH3
SH H2
-H20
0
Reaction Met.
NH3Lig. [L]
Selec- 0
No.a) Solvent T [ C]
[Eg.]n pressure Metal salt [M] [M] Ligand [L]
Conversionb)
"
(M01%)
tiVityC) CO
N
[bar] (mol%)
CO
H
1 p-Xylene 155 6 42 [RuHCI(C0)(PPh3)3] 0.10
6.1 1.4 (5)
(5)
2 p-Xylene 155 6 41 [RuHCI(C0)(PPh3)3] 0.10 Triphos 0.10
58.6 83.6 I.)
0
H
3 Toluene 180 6 40 [RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20
99.1 91.8 u.)
1
0
p-Xylene 155 6 43 [Ru(COD)methylally12] 0.10 Tetraphos
0.10 13.1 21.4 co
1
I.)
6 p-Xylene 155 6 43 [RuHCI(C0)(PPh3)3] 0.10
Xantphos 0.10 ' 29.8 77.1 u.)
7 p-Xylene 155 6 42 [RuHCI(C0)(PPh3)3] 0.10
Triphenylphosphine 0.30 6.4 0.4
8 p-Xylene 155 6 41 [Ru(COD)methylally12] 0.10
Sphos 0.10 3.5 21.7
9 Toluene 155 6 42 [RuHCI(C0)(PPh3)3] 0.10 DPPEPP 0.10
46.9 74.4
Toluene 155 6 44 [RuHCI(C0)(PPh3)3] 0.10 Rhodaphos 0.10 24.0
44.8
11 di p-Xylene 160 6 n.d. [Ru(COD)methylally12] 0.20
DPEPhos 0.20 14.7 20.0
12 d' e) p-Xylene 160 6 n.d. (Ru(COD)C12]
0.20 depe 0.20 16.6 29.5
1361 p-Xylene 160 6 n.d. [Ru(COD)methylally12] 0.20
tBuPPyP 0.20 19.5 25.2
Toluene 155 6 38 [Ir(COD)C1]2 0.10 Triphos 0.20 2.4
1.3
EK10-1686PC
PF0000071686/MKr
16 Toluene 155 6 42 pr(COD)C11 2 0.10 Xantphos 0.20
11.6 48.8
a) 50 ml of solvent; batch size: 50 mmol of octanol, reaction time: 12 h; b)
evaluation by means of GC (area %); c) product selectivity to n-
octylamine determined by means of GC (area %); d) 10 ml of solvent; batch
size: 25 mmol of substrate; e) addition of 0.4 mol% of KOtBu
(based on octanol); f) molar equivalents of NH3 per OH function on the
substrate.
0
1.)
co
1.)
co
1.)
0
0
CO
EK10-1686PC "as originally filed"
,
,
PF0000071686/MKr As originally filed
31
Table lb
NH3 Reaction Met. [1111] Lig. [L] Conver- Selectivity
Noa) Solvent T [ C] NH3
salt [M] Ligand [L]
[Eq.] ) pressure [bar] (mol%)
(mor/o) sionb) b)
1 Toluol 180 6 41,8 [RuHCI(C0)(PPh3)3l 0,10 DPPEPP 0.10
91.5 81.8
t-Bu-
2 6 [Ru(COD)C12]
Toluol 155 43,2 0,10 Xantphos 0.10
18.7 67.3
3e1 Toluol 155 6 39,2 [RuHCI(C0)(PPh3)3] 0,2
Triphos 0.2 , 47.0 83.8
0
4" Toluol 155 6 42,2 [RuHCI(C0)(PPh3)3] 0,2 Triphos 0.2
70.4 84.5
0
591 Toluol 155 6 43,0 [RuHCI(C0)(PPh3)3] 0,2 Triphos 0.2
50.7 85.6 I.)
co
I.)
6i" Toluol 155 6 42,1 [RuHCI(C0)(PPh3)3] 0,2 Triphos 0.2
67.2 85.9 CO
H
0)
7 THF 155 6 39,9 [RuHCI(C0)(PPh3)3] 0,2 dppb 0.2
35.2 75.2 c7,
I.)
a) 50 ml solvent; batch size: 50 mmol octanol, reaction time: 12 h; b)
evaluation by GC (% by area); c) product selectivity to n-octylamine
determined by 0
H
GC (% by area); d) molar equivalents NH3 per OH function on the substrate; e)
addition of 50 mmol H20; f) addition of 50 mmol hexylamine; g) addition of
u.)
1
0
25 mmol H2O; h) addition of 25 mmol hexylamine
co
1
1.3
u.)
EK10-1686PC
,
PF0000071686/MKr As originally filed
32
Table 2
HO....õ...--_,..,...--, NH3 Ho
OH ________________ > NH2 + I-12N NH2 + L J
N N
H
a b c
No.a) T NH3 Reaction Metal salt [M] Met. [M] Ligand [L] Lig. [L]
Conversion b) Selectivity `)
rC) [Eg.]e) pressure (mol%) (mol%)f)
a : b : c
[bar]
n
1 155 6 49 [RuHCI(C0)(PPh3)3] 0.1
Triphos 0.1 74.7 59.1 0.7 6.7 0
I.)
2 155 6 66" [RuHCI(C0)(PPh3)3] 0.1
Triphos 0.1 61.8 78.0 0.6 5.4 co
I.)
co
3 180 6 49 [RuHCI(C0)(PPh3)3] 0.2
Triphos 0.2 99.9 1.7 4.7 37.7 H
1:71
0,
4 155 6 45 [RuHCI(C0)(PPh3)3] 0.1
Xantphos 0.1 35.0 81.8 0.0 6.4 I.)
0
155 6 47 [Ru(COD)methylally12] 0.1
Tetraphos 0.1 6.0 8.5 0.0 1.6 H
CA
1
6 155 6 39 [RuHCI(C0)(PPh3)31 0.2
Rhodaphos 0.2 39.8 17.5 0.0 4.6 0
co
1
7 155 6 38 [RuHCI(C0)(PPh3)3] 0.2
DPPEPP 0.2 66.6 68.1 0.1 11.0 I.)
u.)
a) 50 ml of toluene; batch size: 25 mmol of 1,4-butanediol, reaction time: 12
h; b) evaluation as per GC (area %); c) product selectivity determined by
means of
GC (area %); d) injected cold: 5 bar of H2, 8 bar of NH3; e) molar equivalents
of NH3 per OH function on the substrate; f) nnol% based on the number of OH
functions on the substrate.
EK10-1686PC
PF0000071686/MKr
33
Table 3
NH3
/ \
HO.,.....-----....o..----...õ...OH ----)-- 1-10-....õ--------0------,,,,N1-12
4. H2N.õ..----,..0,---....____AH2 + 0 NH
a b
c
No.a) T rC] NH3 Reaction Metal salt [M] Met. [M] Ligand
[L] Lig. [L] Conversionbl Selectivity `)
[Eq.] e) pressure (mol /0)÷ (mol%)f)
a : b : c
[bar]
1 155 6 41 [RuHCI(C0)(PPh3)3] 0.1 Triphos 0.1
51.0 66.2 0.9 5.9 n
2 155 6 59a) [RuHCI(C0)(PPh3)3] 0.1 Triphos 0.1
16.2 87.3 0.1 2.3 0
I.)
3 180 6 41 [RuHCI(C0)(PPh3)3] 0.2 Triphos 0.2 97.6
26.4 13.4 54.0 0
I.)
0
4 180 6 43 [RuHCI(C0)(PPh3)3] 0.2 Xantphos 0.1
27.7 67.1 0.2 5.3 H
c7,
c7,
155 6 44 [Ru(COD)methylally12] 0.1 Tetraphos 0.1
3.9 0.0 0.0 1.1 I.)
6 155 6 40 [RuHCI(C0)(PPh3)3] 0.2 Rhodaphos
0.2 21.8 4.8 0.0 1.3 0
F-,
la
I
7 155 6 38 [RuHCI(C0)(PPh3)3] 0.2 OPPEPP 0.2
21.5 46.0 0.0 1.8 0
0
a) 50 ml of toluene; batch size: 25 mmol of diethylene glycol, reaction time:
12 h; b) evaluation as per GC (area %); c) product selectivity determined by
means of GC i
iv
(area %); d) injected cold: 5 bar of H2, 8 bar of NH3; e) molar equivalents of
NH3 per OH function on the substrate; f) mol% based on the number of OH
functions on the u.)
substrate.
EK10-1686PC "as originally filed"
,
,
PF0000071686/MKr As originally filed
34
Table 4:
HO.,ey--.0riõ _ NH3__,.. HO(c->rNH + H2N....t.r NH2
n n 2 n
a b
0
0
Time Reaction SolventI.)
No T NH3 Met. [M]
Lig. [L] Conver- Selectivity c co
a) Substrate [t] [Eg.]e) pressure (waterfree) Metall salt [M]
(mol%)0 Ligand [L] (mol%)
si-on 14
I.)
co
[ C]
o a : b H
[bar]
c7,
c7,
_
.
1 1,6-hexanediol 155 12 6 42 Toluol
[RuHCI(C0)(PPh3)3] -0.10 Triphos 0.10 83.0 61.3 25.7 I.)
0
H
2 1,6-hexanediol 155 12 6 36 ' Toluol
[RuHCI(C0)(PPh3)3] 0.10 Xantphos 0.10 .33.4 84.9 4.6
u.)
1
3 1,6-hexanediol 155 12 6 40 - Toluol
[RuHCI(C0)(PPh3)3] 0.10 DPPEPP 0.10 70.7 66.5 16.0 0
co
1
4 1,6-hexanediol 155 12 -6 44 Toluol
[RuHCI(C0)(PPh3)3] 0.10 Rhodaphos 0.10 -35.1 53.0 2.0 I.)
u.)
5 1,10-decandiol 155 24 -6 39 Toluol
[RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20 -85.7 -43.0 44.4
_
6 1,10-decandiol 180 24 6 43 Toluol
[RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20 93.3 2.0 90.1
7d) 1,9-nonanediol 155 24 12 14
Mesitylen [RuHCI(C0)(PPh3)3] 0.20 Triphos 0.20 79.3 54.0 31.1
a) 50 ml solvent; batch size: 25 mmol diol; b) evaluation by GC (% by area);
c) product selectivity determined by means of GC (% by area); d) batch size:
50 mmol substrate;
e) molar equivalent NH3 per OH function on the substrate; f) mol% based on the
number of OH functions on the substrate
EK10-1686PC
PF0000071686/MKr As originally filed
Table 5:
HO OH H2NOH H2N N H2
a b
Time conc. Reaction Solvent
Selectivity n
No T NH3
Met. [M] Ligand Lig. [L] Conver- 0
a)
Substrate [t] [mo1/1] pressure (water- Metall salt
[M]
[ C] [Eq.]
(mol%) e) [L] (mol%) e) sion b) o
Iv
[bar] free) a : b co
_
_______________________________________________________________________________
___________________________________ I.)
1 2,5-dimethanolfuran 140 24 1 6 15 THF
[RuHCI(C0)(PPh3)3] 0,20 Triphos 0.20 46.8 63.1 10.2 CO
H
al
al
IV
a) 40 ml solvent; batch size: 40 mmol diol; b) evaluation by GC (% by area);
c) product selectivity determined by means of GC ( /0 by area); d) molar
equivalents NH3 per OH 0
H
u.)
function on the substrate; e) mol% based on the number of OH functions on the
substrate I
0
5
co
1
I.)
u.)
EK10-1686PC
