Description
Title of Invention: METHOD FOR PRODUCING ALCOHOL
AND/OR AMINE FROM AMIDE COMPOUND
Technical Field
[0001] The present invention relates to a method for producing an alcohol and/or an amine
from an amide compound under an atmosphere of hydrogen with the use of, as a
catalyst, a ruthenium carbonyl complex having a tridentate ligand containing two
phosphino groups and a -NH- group.
Background Art
[0002] Alcohols and amines are useful compounds widely used in industrial applications,
and therefore their production methods are important in industrial fields. An example
of known methods for producing an alcohol or an amine is described in Reference
Document 1 (Reductions by the Alumino-and Borohydrides in Organic Synthesis VCH
Publishers, INC. 1991), in which an amide compound is reduced using a metal
hydride. However, this method has problems such as the use of a dangerous metal
hydride reagent and the generation of waste from the reagent theoretically required in
an amount equal to or higher than that of the amide compound. For suchlike reason,
there is a demand for a chemical synthesis technique that is more environmentally
friendly and safer. An example of such a chemical synthesis method is the one in
which alcohols or amines are catalytically produced from an amide compound under
an atmosphere of hydrogen.
[0003] An example of a catalyst that catalyzes such a reaction is ruthenium complex. Along
with platinum, rhodium, and iridium, the ruthenium complex is one of metals often
used as a catalyst. However, the ruthenium complex is industrially advantageous in
that it is cheaper than the other metals. An example of such a ruthenium complex is the
one having a multidentate ligand. Patent Literature 1 discloses a dichloro complex as a
ruthenium complex having a tridentate ligand containing two phosphino groups and a -
NH- group, and Non-Patent Literature 1 discloses a dichloro complex or a hydride
complex having trimethylphosphine as a ligand. However, these complexes have no
carbonyl ligand. Further, Patent Literature 1 describes that the ruthenium dichloro
complex catalyzes the hydrogenation reduction of ketones in the presence of a base so
that an alcohol is obtained, but does not describe a method for obtaining an alcohol or
an amine from an amide under an atmosphere of hydrogen. Non-Patent Literature 1
describes that the ruthenium phosphine complex acts as a catalyst for dehydrogenation
of ammonia-borane, but does not describe a method for obtaining an alcohol or an
amine from an amide under an atmosphere of hydrogen. Non-Patent Literatures 2, 3,
and 4 disclose a ruthenium complex having a tridentate ligand containing two
phosphino groups and a pyridine ring, and a carbonyl ligand, but this tridentate ligand
does not contain a -NH- group. Further, it has been reported that the ruthenium
phosphine complex used as a catalyst is unstable. Non-Patent Literatures 2 and 3
describe that alcohols can be synthesized by hydrogenation reduction of an ester with
the pyridine ring-containing ruthenium complex as a catalyst, but do not describe a
method for obtaining alcohols or amines from an amide under an atmosphere of
hydrogen.
[0004] As methods for catalytically producing alcohols or amines from an amide under an
atmosphere of hydrogen, methods described in Patent Literatures 2 and 3 and Non-
Patent Literature 5 are known. However, the method described in Patent Literature 2
and the method described in Non-Patent Literature 5 are methods for obtaining an
amine, and the structures of the amine obtained by these methods are different from the
present invention. Even when an alcohol is produced, the alcohol is only obtained as a
by-product or in a low yield. Patent Literature 3 discloses a cyclopentadienyl complex
as a catalyst, but the cyclopentadienyl complex is different in structure from a catalyst
used in the present invention. Further, the reaction time of about 24 to 90 hours and 1
to 10 mol% of a catalyst with respect to a substrate are required to achieve a sufficient
conversion rate, except for cases where some substrates that achieve an exceptionallyhigh
reaction rate are used.
Citation List
Patent Literature
[0005] PTL 1: US Patent Application Publication No. 2005/0107638
PTL 2: US Patent Application Publication No. 20 1000 1026 1
PTL 3: Japanese Patent Application Publication No. 2010-168357
Non Patent Literature
[0006] NPL 1: Angew. Chem. Int. Ed. 2009,48, p.905-907
NPL 2: Angew. Chem. Int. Ed. 2006,45, p. 11 13-1 115
NPL 3: J. Am. Chem. Soc. 2005, 127, p. 10840-10841
NPL 4: Organometallics. 2004,23, p.4026-4033
NPL 5: Chem. Commun. 2007,3 154-3 156
Summary of Invention
Technical Problem
[0007] An object of the present invention is to provide a technique for producing an alcohol
and an amine from an amide compound under an atmosphere of hydrogen with a
ruthenium complex that is easily prepared, easy to handle, and relatively cheaply
obtained, as a catalyst.
Solution to Problem
[0008] In view of the above circumstances, the present inventors have extensively studied,
and as a result, have found that alcohols or amines can be efficiently produced from an
amide under relatively mild conditions and an atmosphere of hydrogen with the use of,
as a catalyst, a ruthenium complex having a tridentate ligand containing two phosphino
groups and a -NH- group and a carbonyl ligand. This finding has led to the completion
of the present invention.
[0009] The method according to the present invention can be used also to remove an acyl
group, which is a cheap and useful protective group for amines, for deprotection. As
described in, for example, Reference Document 2 (Protective Groups in Organic
Synthesis Second Edition, JOHN WILEY&SONS, INC. 199 I), removal of an acyl
group for deprotection requires heating under acidic conditions. However, the method
according to the present invention makes it possible to perform deprotection relatively
easily without exposure to acidic conditions. Further, the method according to the
present invention is advantageous in that a basic amine generated as a result of deprotection
can be purified without performing neutralization of a salt and subsequent
extraction.
[0010] More specifically, the present invention relates to the following (I) to (10).
(I) A method for producing an alcohol and/or an amine from an amide compound
represented by the following general formula (A) under an atmosphere of hydrogen in
the presence of a ruthenium carbonyl complex represented by the following general
formula (I):
[0011] [Chem. 1]
[0012] wherein R1 represents hydrogen, an alkyl group, a cycloalkyl group, an aryl group, an
aralkyl group, a heterocyclic group, an alkenyl group, an alkynyl group, or a cycloalkenyl
group, these alkyl group, cycloalkyl group, aryl group, aralkyl group, heterocyclic
group, alkenyl group, alkynyl group, and cycloalkenyl group may have one or
more than one substituent, Rn and Rnl may be the same or different from each other
and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl
group, an aralkyl group, a heterocyclic group, an alkenyl group, an alkynyl group, a
cycloalkenyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an
aralkyloxy group, a hydroxyl group, an alkoxycarbonyl group, a cycloalkyloxycarbonyl
group, an aryloxycarbonyl group, an aralkyloxycarbonyl group, an alkenyloxycarbonyl
group, an alkynyloxycarbonyl group, a cycloalkynyloxycarbonyl group,
or a sulfonyl group, these alkyl group, cycloalkyl group, aryl group, aralkyl group, heterocyclic
group, alkenyl group, alkynyl group, cycloalkenyl group, alkyloxy group, cycloalkyloxy
group, aryloxy group, aralkyloxy group, hydroxyl group, alkoxycarbonyl
group, cycloalkyloxycarbony1 group, aryloxycarbonyl group, aralkyloxycarbonyl
group, alkenyloxycarbonyl group, alkynyloxycarbonyl group, cycloalkynyloxycarbonyl
group, and sulfonyl group may have one or more than one substituent, and R1
and Rn and/or Rnl and Rn and Rnl may be linked together to form a ring; and
RuXY(CO)(L) (I)
wherein X and Y may be the same or different from each other and each represents an
anionic ligand and L represents a tridentate aminodiphosphine ligand represented by
the following general formula (2):
[OO 131 [Chem.2]
[0014] wherein R1, R2, R3, and R4 may be the same or different from one another and each
represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, an
aralkyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy
group, a heterocyclic group, or a substituted amino group, R1 and R2 or R3
and R4 may be linked together to form a ring with an adjacent phosphorus atom, these
alkyl group, cycloalkyl group, aryl group, aralkyl group, alkyloxy group, cycloalkyloxy
group, aryloxy group, aralkyloxy group, heterocyclic group, and substituted
amino group may have one or more than one substituent, Q1 and Q2 may be the
same or different from each other and each represents a divalent alkylene group that
may have one or more than one substituent, a divalent cycloalkylene group that may
have one or more than one substituent, or a divalent aralkylene group that may have
one or more than one substituent.
(2) The production method according to the above (I), wherein the tridentate aminodiphosphine
ligand L is represented by the following general formula (3):
[OO 151 [Chem. 31
[0016] wherein R5, R6, R7, and R8 may be the same or different from one another and each
represents a hydrogen atom, an alkyl group that may have one or more than one substituent,
a cycloalkyl group that may have one or more than one substituent, an aryl
group that may have one or more than one substituent, or an aralkyl group that may
have one or more than one substituent, and n is an integer of 0 to 3.
(3) The production method according to the above (I) or (2), wherein the tridentate
aminodiphosphine ligand L is represented by the following general formula (4):
[OO 171 [Chem.4]
[0018] wherein Arl, Ar2, Ar3, and A14 may be the same or different from one another and
each represents an aryl group or an aromatic heterocyclic group, and these aryl group
and aromatic heterocyclic group may have one or more than one substituent.
(4) The production method according to the above (3), wherein Arl, Ar2, Ar3, and A14
in the general formula (4) are each a phenyl group that may have one or more than one
substituent.
(5) The production method according to the above (4), wherein the tridentate aminodiphosphine
ligand L is represented by the following general formula (5):
[OO 191 [Chem. 51
[0020] wherein Ph represents a phenyl group.
(6) The production method according to the above (I) or (2), wherein the tridentate
aminodiphosphine ligand L is an optically active tridentate aminodiphosphine ligand.
(7) The production method according to any one of the above (I) to (6), wherein the
anionic ligand represented by X in the general formula (I) is a hydride and the anionic
ligand represented by Y in the general formula (I) is C1.
(8) The production method according to any one of the above (I) to (6), wherein the
anionic ligand represented by X in the general formula (I) is a hydride and the anionic
ligand represented by Y in the general formula (I) is BH4-.
(9) The production method according to any one of the above (I) to (8), which is
performed in the presence of a base.
(10) The production method according to the above (9), wherein the base is sodium
methoxide.
Advantageous Effects of Invention
[0021] The ruthenium carbonyl complex of the present invention can be easily prepared
from a tridentate aminodiphosphine ligand and a ruthenium carbonyl complex as a
precursor. The tridentate aminodiphosphine ligand can be easily prepared by reacting a
bisalkylamine having elimination groups with a phosphine compound in the presence
of a base. Further, the ruthenium carbonyl complex as a precursor can be easily
prepared from an easily available inorganic ruthenium compound. Such a ruthenium
carbonyl complex of the present invention is not only easily prepared but also highly
stable and easy to handle, and is therefore suitable for use in industrial applications.
The ruthenium carbonyl complex of the present invention has high catalytic activity
even under relatively mild reaction conditions, which makes it possible to efficiently
produce an alcohol or an amine from an amide under an atmosphere of hydrogen and
relatively mild conditions.
Description of Embodiments
[0022] First, a ruthenium carbonyl complex of the present invention will be described. The
ruthenium carbonyl complex is represented by the following formula (I):
RuXY (CO) (L) ( 1)
wherein X and Y may be the same or different each other and each represents an
anionic ligand and L represents a tridentate aminodiphosphine ligand represented by
the following general formula (2):
[0023] [Chem.6]
[0024] wherein R1, R2, R3, and R4 may be the same or different from one another and each
represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, an
aralkyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy
group, a heterocyclic group, or a substituted amino group; R1 and R2 or R3
and R4 may be linked together to form a ring with an adjacent phosphorus atom; these
alkyl group, cycloalkyl group, aryl group, aralkyl group, alkyloxy group, cycloalkyloxy
group, aryloxy group, aralkyloxy group, and heterocyclic group may have
one or more than one substituent; and Q1 and Q2 may be the same or different from
each other and each represents a divalent alkylene group that may have one or more
than one substituent, a divalent cycloalkylene group that may have one or more than
one substituent, or a divalent aralkylene group that may have one or more than one
substituent.
[0025] The tridentate aminodiphosphine ligand used in the present invention will be
described. An example of the tridentate aminodiphosphine ligand represented by L in
the general formula (I) has containing two phosphino groups and a -NH- group. A
specific example of the tridentate aminodiphosphine ligand is the one represented by
the above general formula (2).
[0026] R1, R2, R3, and R4 in the general formula (2) will be described.
An example of the alkyl group is a linear or branched alkyl group having 1 to 50
carbon atoms, preferably 1 to 20 carbon atoms, more preferably 1 to 10 carbon atoms.
Specific examples thereof include a methyl group, an ethyl group, an n-propyl group,
an isopropyl group, an n-butyl group, an isobutyl group, an s-butyl group, a tert-butyl
group, an n-pentyl group, an n-hexyl group, an n-octyl group, and the like.
An example of the cycloalkyl group is a monocyclic, polycyclic, or fused-ring cycloalkyl
group having 3 to 30 carbon atoms, preferably 3 to 20 carbon atoms, more
preferably 3 to 10 carbon atoms. Specific examples thereof include a cyclopropyl
group, a cyclopentyl group, a cyclohexyl group, and the like.
An example of the aryl group is a monocyclic, polycyclic, or fused-ring aryl group
having 6 to 36 carbon atoms, preferably 6 to 18 carbon atoms, more preferably 6 to 14
carbon atoms. Specific examples thereof include a phenyl group, a naphthyl group, an
anthryl group, a phenanthryl group, a biphenyl group, and the like.
An example of the aralkyl group is a group obtained by substituting at least one
hydrogen atom of the above-mentioned alkyl group with the above-mentioned aryl
group. For example, the aralkyl group preferably has 7 to 15 carbon atoms. Specific
examples thereof include a benzyl group, a 1-phenylethyl group, a 2-phenylethyl
group, a 1-phenylpropyl group, a 3-naphthylpropyl group, and the like.
[0027] An example of the alkyloxy group is an alkyloxy group having a liner or branched
alkyl group having 1 to 20 carbon atoms, preferably 1 to 15 carbon atoms, more
preferably 1 to 10 carbon atoms. Specific examples thereof include a methoxy group,
an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an
isobutoxy group, an s-butoxy group, a tert-butoxy group, an n-pentyloxy group, and
the like.
An example of the cycloalkyloxy group is a cycloalkyloxy group having a polycyclic
or fused-ring cycloalkyl group having 3 to 20 carbon atoms, preferably 3 to 15 carbon
atoms, more preferably 3 to 10 carbon atoms. Specific examples thereof include a cyclopropyloxy
group, a cyclopentyloxy group, a cyclohexyloxy group, and the like.
An example of the aryloxy group is an aryloxy group having a monocyclic,
polycyclic, or fused-ring aryl group having 6 to 36 carbon atoms, preferably 6 to 18
carbon atoms, more preferably 6 to 14 carbon atoms. Specific examples thereof include
a phenoxy group, a tolyloxy group, a xylyloxy group, a naphtoxy group, and the like.
An example of the aralkyloxy group is a group obtained by substituting at least one
hydrogen atom of the alkyl group of the above-mentioned alkyloxy group or of the
above-mentioned cycloalkyl group with the above-mentioned aryl group. For example,
the aralkyloxy group preferably has 7 to 15 carbon atoms. Specific examples thereof
include a benzyloxy group, a 1-phenylethoxy group, a 2-phenylethoxy group, a
1-phenylpropoxy group, a 2-phenylpropoxy group, a 3-phenylpropoxy group, a
4-phenylbutoxy group, a 1-naphthylmethoxy group, a 2-naphthylmethoxy group, and
the like.
[0028] Examples of the heterocyclic group include an aliphatic heterocyclic group and an
aromatic heterocyclic group. An example of the aliphatic heterocyclic group is a 3- to
8-membered (preferably 4- to 6-membered) monocyclic, polycyclic, or fused-ring
aliphatic heterocyclic group having 2 to 14 carbon atoms and at least one heteroatom
(preferably 1 to 3 heteroatoms) such as a nitrogen atom, an oxygen atom, and/or a
sulfur atom. Specific examples of such an aliphatic heterocyclic group include an
azetidyl group, an azetidino group, a pyrrolidyl group, a pyrrolidino group, a
piperidinyl group, a piperidino group, a piperadinyl group, a piperadino group, a morpholinyl
group, a morpholino group, a tetrahydrofuryl group, a tetrahydropyranyl
group, a tetrahydrothiophenyl group, and the like.
An example of the aromatic heterocyclic group is a 5- or 6-membered monocyclic,
polycyclic, or fused-ring heteroaryl group having 4 to 15 carbon atoms and at last one
heteroatom (preferably 1 to 3 heteroatoms) such as a nitrogen atom, an oxygen atom,
and/or a sulfur atom. Specific examples thereof include a fury1 group, a thienyl group,
a pyridyl group, a pyrimidyl group, a pyrazyl group, a pyridazyl group, a pyrazolyl
group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a benzofuryl group, a
benzothienyl group, a quinolyl group, an isoquinolyl group, a quinoxalyl group, a phthalazyl
group, a quinazolyl group, a naphthyridyl group, a cinnolyl group, a benzoimidazolyl
group, a benzoxazolyl group, a benzothiazolyl group, an acridyl group, an
acridinyl group, and the like.
[0029] An example of the substituted amino group is an amino group obtained by substituting
two hydrogen atoms of an amino group with the above-mentioned alkyl, cycloalkyl,
aryl, aralkyl, and/or heterocyclic groups which are the same or different from
each other. Specific examples thereof include: a dialkylamino group such as an
N,N-diethylamino group or an N,N-diisopropylamino group; a dicycloalkylamino
group such as an N,N-dicyclohexylamino group; a diarylamino group such as an
N,N-diphenylamino group or an N-naphthyl-N-phenylamino group; a diaralkylamino
group such as an N,N-dibenzylamino group, and the like. The alkyl group, the cycloalkyl
group, the aryl group, the aralkyl group, and the heterocyclic group as substituents
of the substituted amino group may further have one or more than one substituent.
[0030] Examples of the substituents that may be possessed by the alkyl group, the cycloalkyl
group, the aryl group, the aralkyl group, the alkyloxy group, the cycloalkyloxy group,
the aryloxy group, the aralkyloxy group, the heterocyclic group, and the alkyl group,
the cycloalkyl group, the aryl group, the aralkyl group, and the heterocyclic group on
the substituted amino group include the above-mentioned alkyl group, cycloalkyl
group, aryl group, aralkyl group, alkyloxy group, cycloalkyloxy group, aryloxy group,
aralkyloxy group, heterocyclic group, substituted amino group, a halogen atom, a silyl
group, an optionally-protected hydroxyl group, and the like.
[003 11 Examples of the halogen atom as substituents of R1, R2, R3, and R4 include a fluorine
atom, a chlorine atom, a bromine atom, and an iodine atom.
[0032] Examples of the silyl group as substituents of R1, R2, R3, and R4 include one obtained
by replacing three hydrogen atoms of a silyl group with the above-mentioned alkyl, cycloalkyl,
aryl, and/or aralkyl groups, and the like. Specific examples thereof include a
trimethylsilyl group, a triethylsilyl group, a t-butyldimethylsilyl group, a tbutyldiphenylsilyl
group, a triphenylsilyl group, and the like.
[0033] Examples of the optionally-protected hydroxyl group as substituents of R1, R2, R3,
and R4 include a unprotected hydroxyl group and hydroxyl groups that may be
protected by common protective groups for a hydroxyl group for use in, for example,
peptide synthesis which are described in, for example, Reference Document 2
(Protective Groups in Organic Synthesis Second Edition, JOHN WILEY&SONS, INC.
1991). Examples of such protective groups include a silyl group such as a
trimethylsilyl group, a tert-butyldimethylsilyl group, and a tert-butyldiphenylsilyl
group, a benzyl group, a methoxymethyl group, and the like.
[0034] Q1 and Q2 in the general formula (2) will be described.
An example of the divalent alkylene group is a linear or branched divalent alkyl
chain having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1
to 6 carbon atoms. Specific examples thereof include a methylene group, an ethylene
group, a trimethylene group, a tetramethylene group, a pentamethylene group, and the
like.
An example of the divalent cycloalkylene group is a divalent group having a
monocyclic, polycyclic, or fused-ring cycloalkyl group having 3 to 15 carbon atoms,
preferably 3 to 10 carbon atoms, more preferably 3 to 6 carbon atoms. Specific
examples thereof include a cyclopropylene group, a cyclobutylene group, a cyclopenthylene
group, a cyclohexylene group, and the like.
An example of the divalent aralkylene group is a divalent group having 7 to 11
carbon atoms, which is obtained by removing one hydrogen atom from an aryl group
of an aralkyl group such as a benzyl group or a phenethyl group. Specific examples
thereof include a benzylene group (-Ph-CH2-), a 2-phenylethylene group (-Ph-CH2CH2-
), a 1-naphthylmethylene group (-Np-CH2-), a 2-naphthylmethylene group (-Np-CH2-),
and the like (in these formulas, -Ph- represents a phenylene group and - Np - represents
a naphthylene group).
[0035] Examples of the substituents that may be possessed by the divalent alkylene group,
the divalent cycloalkylene group, or the divalent aralkylene group include the alkyl
group, the cycloalkyl group, the aryl group, the aralkyl group, the alkyloxy group, the
cycloalkyloxy group, the aryloxy group, the aralkyloxy group, the heterocyclic group,
the halogen atom, the silyl group, the substituted amino group, the optionally-protected
hydroxyl group, and the like, which have been described above with reference to R1, R2
, R3, and R4 in the general formula (2).
[0036] Hereinbelow, a monovalent anionic ligand represented by X or Y in the general
formula (I) will be described.
Examples of the monovlalent anionic ligand include a hydride, an alkyloxy group, a
cycloalkyloxy group, an aryloxy group, an aralkyloxy group, a hydroxy group, an
acyloxy group, a sulfonyloxy group, a halogen ion, A1H4-,A 1H2(OCH2CH20CH2)B2-H,
4-,B H3CN-,B H(Et)3-,B H(S~C-BUa)n~d- ,t he like. Among them, BH4-,a hydride, and a
chlorine ion are preferred. It is to be noted that, in this specification, a hydride is also
sometimes simply referred to as "hydrogen" and a halogen ion is also sometimes
simply referred to as "halogen".
[0037] An example of the acyloxy group is the one represented by (RaC02). Examples of Ra
in the acyloxy group (RaC02) include a hydrogen atom, an alkyl group, a cycloalkyl
group, an aryl group, and an aralkyl group. Examples of the alkyl group, the cycloalkyl
group, the aryl group, and the aralkyl group include those described above with
reference to R1, R2, R3, and R4 in the general formula (2). These alkyl group, cycloalkyl
group, aryl group, and aralkyl group may further have one or more than one substituent,
and examples of such substituents include the alkyl group, the cycloalkyl
group, the aryl group, the aralkyl group, the alkyloxy group, the cycloalkyloxy group,
the aralkyloxy group, the aryloxy group, the heterocyclic group, the halogen atom, the
silyl group, and the optionally-protected hydroxyl group which have been described
above with reference to R1, R2, R3, and R4 in the general formula (2), an optionallyprotected
amino group, and the like.
Examples of the optionally-protected amino group as substituents of Ra include: an
unprotected amino group; a mono- or dialkylamino group such as an N-methylamino
group, an N,N-dimethylamino group, an N,N-diethylamino group, an
N,N-diisopropylamino group, or an N-cyclohexylamino group; a mono- or diarylamino
group such as an N-phenylamino group, an N,N-diphenylamino group, an Nnaphthylamino
group, or an N-naphthyl-N-phenylamino group; a mono- or diaralkylamino
group such as an N-benzylamino group or an N,N-dibenzylamino group;
an acylamino group such as a formylamino group, an acetylamino group, a propionylamino
group, a pivaloylamino group, a pentanoylamino group, a hexanoylamino
group, or a benzoylamino group; an alkoxycarbonylamino group such as a methoxycarbonylamino
group, an ethoxycarbonylamino group, an n-propoxycarbonylamino
group, an n-butoxycarbonylamino group, a tert-butoxycarbonylamino group, a pentyloxycarbonylamino
group, or a hexyloxycarbonylamino group; an aryloxycarbonylamino
group such as a phenyloxycarbonylamino group; an aralkyloxycarbonylamino
group such as a benzyloxycarbonylamino group, and the like. Other
examples of the optionally-protected amino group include amino groups protected by
common protective groups for amino groups for use in, for example, peptide synthesis,
and the like which are described in, for example, the above-mentioned Reference
Document 1.
Specific examples of Ra include a methyl group, an ethyl group, a propyl group, a tertbutyl
group, a trifluoromethyl group, a phenyl group, a pentafluorophenyl group, and
the like.
[0038] An example of the sulfonyloxy group is the one represented by (&SO3). Examples of
Rs in the sulfonyloxy group RSSO3 are the same as the above-mentioned examples of Ra
in the acyloxy group.
Examples of the halogen ion include a fluorine ion, a chlorine ion, a bromine ion, and
an iodine ion. Among them, a chlorine ion and a bromine ion are preferred, and a
chlorine ion is more preferred.
[0039] A preferred example of the tridentate aminophosphine ligand is the one represented
by the following general formula (3).
[0040] [Chem.7]
1 R1R 2 P0 - 5 3 8
[0041] wherein R5, R6, R7, and R8 may be the same or different from one another and each
represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, or an
aralkyl group; R5 and R5, R5 and R6, R7, or R8, or R6 and R7 or R8 may be linked
together to form a ring together with an adjacent carbon atom(s); n is an integer of 0 to
3; and these alkyl group, cycloalkyl group, aryl group, and aralkyl group may have one
or more than one substituent.
[0042] Examples of the alkyl group, the cycloalkyl group, the aryl group, and the aralkyl
group represented by R5, R6, R7, and R8 in the general formula (3) include those
described above with reference to R1, R2, R3, and R4 in the general formula (2).
Examples of the substituents that may be possessed by these alkyl group, cycloalkyl
group, aryl group, and aralkyl group include the alkyl group, the cycloalkyl group, the
aryl group, the aralkyl group, the alkyloxy group, the cycloalkyloxy group, the aryloxy
group, the aralkyloxy group, the heterocyclic group, the halogen atom, the silyl group,
the substituted amino group, the optionally-protected hydroxyl group, and the like,
which have been described above with reference to R1, R2, R3, and R4 in the general
formula (2).
[0043] A more preferred example of the tridentate aminodiphosphine ligand is the one represented
by the following general formula (4).
[0044] [Chem. 81
[0045] wherein Arl, Ar2, Ar3, and A14 may be the same or different from one another and
each represents an aryl group or an aromatic heterocyclic group, and these aryl group
and aromatic heterocyclic group may have one or more than one substituent.
[0046] Examples of the aryl group and the aromatic heterocyclic group in the general
formula (4) include the aryl group, the aromatic heterocyclic group as an example of
the heterocyclic group, and the like, which have been described above with reference
to R1, R2, R3, and R4 in the general formula (2). Examples of the substituents that may
be possessed by these aryl group and aromatic heterocyclic group include the alkyl
group, the cycloaklyl group, the aryl group, the aralkyl group, the alkyloxy group, the
cycloalkyloxy group, the aryloxy group, the aralkyloxy group, the halogen atom, the
silyl group, the heterocyclic group, the substituted amino group, the optionallyprotected
hydroxyl group, and the like, which have been described above with
reference to R1, R2, R3, and R4 in the general formula (2).
[0047] An even more preferred example of the tridentate aminodiphosphine ligand is the one
represented by the following general formula (5).
[0048] [Chem.9]
[0049] The tridentate aminodiphosphine ligand represented by the general formula (2) or (3)
may be used as an optically active ligand of the ruthenium carbonyl complex represented
by the general formula (I) depending on the substituents on Q1 and Q2 or R1 to
R8.
[0050] A ruthenium compound as a starting material for producing a ruthenium carbonyl
complex used in the present invention is not particularly limited, and examples thereof
include inorganic ruthenium compounds such as a RuC1, hydrate, a RuBr, hydrate, and
a RuI, hydrate, RuC12(DMSO),, [Ru(cod)C12],, [Ru(nbd)C12],, (~od)Ru(2-methallyl)~,
[Ru(benzene)Cl2I2[,R u(benzene)Br212[, Ru(benzene)I2I2[, Ru(p-cyrnene)Cl2l2,
[Ru(p-cymene)Br22] , [Ru(p-cymene)122] , [Ru(mesitylene)Cl2I2[,R u(mesitylene)Br212,
[Ru(mesitylene)I2I2[, R~(hexamethylbenzene)Cl~[]R~u, (hexamethylbenzene)Br2I2,
[Ru(he~amethylbenzene)I~]R~u,C 12(PPh3),,R uBr2(PPh3),,R u12(PPh3),,R uH4(PPh3),,
RuClH(PPh,),, RuH(OAc)(PPh,),, RuH2(PPh3),, and the like. In the above examples,
DMSO represents dimethylsulfoxide, cod represents 1,5-cyclooctadiene, nbd
represents norbornadiene, and Ph represents a phenyl group.
[005 11 The ruthenium carbonyl complex represented by the general formula (I) can be
easily prepared from a tridentate aminodiphosphine ligand and a ruthenium carbonyl
complex as a precursor.
The tridentate aminodiphosphine ligand can be easily prepared by reacting a
bis(substituted alky1)amine having an elimination groups with a phosphide compound
of an alkali metal such as lithium, sodium, or potassium.
The ruthenium carbonyl complex as a precursor can be obtained by, for example, a
method described in Inorg. Synth, 1974, 15,45. The obtained ruthenium carbonyl
complex as a precursor is reacted with the tridentate aminodiphosphine ligand to
prepare a tridentate aminodiphosphine ligand-containing ruthenium carbonyl complex
used in the present invention.
[0052] For example, the ruthenium carbonyl complex represented by the general formula (I)
can be produced by reacting the tridentate aminodiphosphine ligand L represented by
the general formula (2) with RuXY(CO)(P(Ar5),), (wherein Ar5s may be the same or
different from one another and each represents an aryl group that may have one or
more than one substituent). Examples of the aryl group or the substituents thereof in Ar
include those mentioned above. Examples of the preferred Ar5 are a phenyl group that
may have one or more than one substituent, particularly a phenyl group.
The ruthenium carbonyl complex represented by the general formula (I) wherein X
is BH4- can be produced by reacting the ruthenium carbonyl complex wherein X is a
chlorine ion with NaBH4 according to, for example, a method described in J. Am.
Chem. Soc. 2005, 127,516.
[0053] The complex prepared in such a manner as described above may have stereoisomers
due to the coordination or conformation of the ligands. The complex used in the
reaction may be a mixture of these stereoisomers or a pure single isomer. These
complexes present relatively stably and are easy to handle.
[0054] A preferred example of the complex is the one represented by the following general
formula (8):
RuHCl(CO)(L) (8)
wherein (L) represents a tridentate aminodiphosphine represented by the above
general formula (5). This complex is easily prepared by appropriately mixing the
tridentate aminodiphosphine ligand L represented by the general formula (5) and
RuC~H(CO)(PPi~n ~a )s~ol vent.
[0055] Another preferred example of the complex is the one represented by the following
general formula (9):
RuH(BH,)(CO)(L) (9)
wherein L represents a tridentate aminodiphoshine represented by the above general
formula (5). The complex is easily prepared by appropriately mixing the ruthenium
carbonyl complex represented by the general formula (8) and NaBH4 in a solvent.
The use of such a ruthenium carbonyl complex as a catalyst makes it possible to
produce, from an amide, a corresponding alcohol or amine under an atmosphere of
hydrogen in a good yield with high catalyst efficiency.
[0056] Hereinbelow, an amide compound, an alcohol, and an amine in the present invention
will be described. An amide compound used as a substrate of a raw material in the
present invention may be substituted with any substituent that does not have adverse
effects on a catalytic synthesis method according to the present invention. A method
for producing an alcohol and/or an amine from an amide compound according to the
present invention is a method for producing, from an amide compound, a corresponding
alcohol (B) and/or a corresponding amine (C) by performing a reaction represented
by the following chemical equation (D) under an atmosphere of hydrogen
with the use of a ruthenium carbonyl complex represented by the general formula (I):
[0057] [Chem. 101
[0058] wherein R1 represents hydrogen, an alkyl group, a cycloalkyl group, an aryl group, an
aralkyl group, a heterocyclic group, an alkenyl group, an alkynyl group, or a cycloalkenyl
group; these alkyl group, cycloalkyl group, aryl group, aralkyl group, heterocyclic
group, alkenyl group, alkynyl group, and cycloalkenyl group may have one or
more than one substituent; Rn and Rnl may be the same or different from each other
and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl
group, an aralkyl group, a heterocyclic group, an alkenyl group, an alkynyl group, a
cycloalkenyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an
aralkyloxy group, a hydroxyl group, an alkoxycarbonyl group, a cycloalkyloxycarbonyl
group, an aryloxycarbonyl group, an aralkyloxycarbonyl group, an alkenyloxycarbonyl
group, an alkynyloxycarbonyl group, a cycloalkynyloxycarbonyl group,
or a sulfonyl group; these alkyl group, cycloalkyl group, aryl group, aralkyl group, heterocyclic
group, alkenyl group, alkynyl group, cycloalkenyl group, alkyloxy group, cycloalkyloxy
group, aryloxy group, aralkyloxy group, hydroxyl group, alkoxycarbonl
group, cycloalkyloxycarbony1 group, aryloxycarbonyl group, aralkyloxycarbonyl
group, alkenyloxycarbonyl group, alkynyloxycarbonyl group, cycloalkynyloxycarbonyl
group, and sulfonyl group may have one or more than one substituent; and R1
and Rn and/or Rnl, and Rn and Rnl may be linked together to form a ring.
[0059] The generated alcohol (B) is represented by the following general formula (B):
R1 - CH2 - OH (B)
wherein R1 is the same as that described above.
The generated amine (C) is represented by the following general formula (C):
HN(Rn) - R"' (C)
wherein Rn and Rnl are the same as those described above.
The method according to the present invention is a method for producing, from an
amide compound, a corresponding alcohol (B) and a corresponding amine (C) at the
same time. However, when attention is focused on only one of the products (i.e., on
only one of the alcohol (B) and the amine (C)), the method according to the present
invention can be regarded as a method for producing only one of the compounds (i.e.,
only one of the alcohol (B) and the amine (C)).
As will be described below, when the amide compound forms a ring, that is, when
the amide compound is a lactam, R1 of the alcohol (B) and Rn and/or Rnl of the amine
(C) are linked together so that an amino alcohol is obtained as a product.
[0060] R1, Rn, and Rnl in the general formula (A) will be described. Examples of the alkyl
group, the cycloalkyl group, the aryl group, the aralkyl group, and the heterocyclic
group represented by R1 include those described above with reference to R1, R2, R3, and
R4 in the general formula (2). An example of the alkenyl group represented by R1 is a
linear or branched alkenyl group having 2 to 20 carbon atoms, preferably 2 to 15
carbon atoms, more preferably 2 to 10 carbon atoms. Specific examples thereof include
an ethenyl group, a propenyl group, a 1-butenyl group, a pentenyl group, a hexenyl
group, a heptenyl group, an octenyl group, a nonenyl group, a decenyl group, and the
like. An example of the alkynyl group represented by R1 is a linear or branched alkynyl
group having 2 to 20 carbon atoms, preferably 2 to 15 carbon atoms, more preferably 2
to 10 carbon atoms. Specific examples thereof include an ethynyl group, a 1-propynyl
group, a 2-propynyl group, a 1-butynyl group, a 3-butynyl group, a pentynyl group, a
hexynyl group, and the like. An example of the cycloalkenyl group represented by R1 is
a 4- to 10-membered mono- to tricyclic aliphatic hydrocarbon group having one or two
double bonds in the ring. Specific examples thereof include a cyclobutenyl group, a cyclopentenyl
group, a cyclohexenyl group, a cycloheptenyl group, and a cyclooctenyl
group.
Examples of the substituents that may be possessed by these alkyl group, cycloalkyl
group, aryl group, aralkyl group, the heterocyclic group, alkenyl group, alkynyl group,
and cycloalkenyl group include the alkyl group, the cycloalkyl group, the aryl group,
the aralkyl group, the alkyloxy group, the cycloalkyloxy group, the aryloxy group, the
aralkyloxy group, the halogen atom, the silyl group, the heterocyclic group, the optionally-
protected amino group, the optionally-protected hydroxyl group, and the like,
which have been described above with reference to R1, R2, R3, and R4 in the general
formula (2) and the alkenyl group, the alkynyl group, the cycloalkenyl group, the
alkoxycarbonyl group, the cycloalkyloxycarbony1 group, the aryloxycarbonyl group,
the aralkyloxycarbonyl group, the alkenyloxy group, the alkynyloxy group, and the cycloalkynyloxy
group which have been described above with reference to R1 in the
general formula (A). It is to be noted that when the protective group for the optionallyprotected
hydroxyl or amino group is an acyl group, there is a case where a resulting
product does not have the protective group. Further, when the alkoxycarbonyl group,
the cycloalkyloxycarbony1 group, the aryloxycarbonyl group, the aralkyloxycarbonyl
group, the alkenyloxycarbonyl group, the alkynyloxycarbonyl group, or the cycloalkynyloxycarbony1
group is present as the substituents, there is a case where a
product reduced by hydrogenation is formed.
[006 11 Examples of the alkoxycarbonyl group, the cycloalkyloxycarbony1 group, the aryloxycarbonyl
group, the aralkyloxycarbonyl group, the alkenyloxycarbonyl group, the
alkynyloxycarbonyl group, and the cycloalkynyloxycarbonyl group as the substituents
include those represented by the following general formula (13):
[0062] [Chem. 1 1]
[0063] Wherein R13 represents an alkyl group, a cycloalkyl group, an aryl group, an aralkyl
group, a heterocyclic group, an alkenyl group, an alkynyl group, or a cycloalkenyl
group, and these alkyl group, cycloalkyl group, aryl group, aralkyl group, heterocyclic
group, alkenyl group, alkynyl group, and cycloalkenyl group may have one or more
than one substituent.
[0064] R13 in the general formula (13) will be described. Examples of the alkyl group, the
cycloalkyl group, the aryl group, the aralkyl group, and the heterocyclic group include
those described above with reference to R1, R2, R3, and R4 in the general formula (2).
Examples of the alkenyl group, the alkynyl group, and the cycloalkenyl group include
those described above with reference to R1 and Rn in the general formula (A).
[0065] Examples of the substituents that may be possessed by R13 in the general formula
(13) include the alkyl group, the cycloalkyl group, the aryl group, the aralkyl group,
and the heterocyclic group which have been described above with reference to R1, R2,
R3, and R4 in the general formula (2) and the alkenyl group, the alkynyl group, and the
cycloalkenyl group which have been described above with reference to R1 in the
general formula (A).
[0066] Examples of the alkyl group, the cycloalkyl group, the aryl group, the aralkyl group,
the heterocyclic group, the alkenyl group, the alkynyl group, and the cycloalkenyl
group represented by Rn and Rnl include those described above with reference to R1.
Examples of the alkyloxy group, the cycloalkyloxy group, the aryloxy group, and the
aralkyloxy group represented by Rn and Rnl include those described above with
reference to R1, R2, R3, and R4 in the general formula (2). Examples of the substituents
that may be possessed by these alkyl group, cycloalkyl group, aryl group, aralkyl
group, heterocyclic group, alkenyl group, alkynyl group, cycloalkenyl group, alkyloxy
group, cycloalkyloxy group, aryloxy group, and aralkyloxy group include the alkyl
group, the cycloalkyl group, the aryl group, the aralkyl group, the alkyloxy group, the
cycloalkyloxy group, the aryloxy group, the aralkyloxy group, the halogen atom, the
silyl group, the heterocyclic group, the optionally-protected amino group, the optionally-
protected hydroxyl group, and the like, which have been described above with
reference to R1, R2, R3, and R4 in the general formula (2) and the alkenyl group, the
alkynyl group, the cycloalkenyl group, the alkoxycarbonyl group, the cycloalkyloxycarbonyl
group, the aryloxycarbonyl group, the aralkyloxycarbonyl group, the
alkenyloxy group, the alkynyloxy group, and the cycloalkynyloxy group which have
been described above with reference to R1 in the general formula (A). It is to be noted
that when the protective group for the optionally-protected hydroxyl or amino group is
an acyl group, there is a case where a resulting product does not have the protective
group.
[0067] Examples of the alkoxycarbonyl group, the cycloalkyloxycarbony1 group, the aryloxycarbonyl
group, the aralkyloxycarbonyl group, the alkenyloxycarbonyl group, the
alkynyloxycarobnyl group, and the cycloalkynyloxycarbonyl group represented by Rn
and Rnl include those described above as the substituents that may be possessed by the
alkyl group, the cycloalkyl group, the aryl group, the aralkyl group, the heterocyclic
group, the alkenyl group, the alkynyl group, and the cycloalkenyl group represented by
R'.
[0068] It is to be noted that when the alkoxycarbonyl group, the cycloalkyloxycarbony1
group, the aryloxycarbonyl group, the aralkyloxycarbonyl group, the alkenyloxycarbonyl
group, the alkynyloxycarobnyl group, or the cycloalkynyloxycarbonyl group
is present as the substituents, there is a case where a product reduced by hydrogenation
is formed.
[0069] In the reaction according to the present invention, when R1 and Rn and/or Rnl form a
ring, preferably when R1 and Rn or Rnl form a ring (i.e., when R1 and Rn form a ring or
when R1 and Rnl form a ring), the compound represented by the general formula (A) is
a lactam. When a ring is formed by R1 and Rn and/or Rnl, R1 and Rn and/or Rnl need to
be linked together. When R1 and Rn and Rnl are linked together, R1 releases two
hydrogen atoms, and is chemically linked to a position on Rn from which one
hydrogen atom has been removed and to a position on Rnl from which one hydrogen
atom has been removed so that a ring is formed. When R1 and Rn or Rnl are linked
together, R1 releases one hydrogen atom, and is chemically linked to a position on Rn
or Rnl from which one hydrogen atom has been removed so that a ring is formed.
As described above, when R1 and Rn and/or Rnl form a ring, the compound represented
by the general formula (A) is a lactam. In this case, an amino alcohol is
obtained as a reduction product, in which R1 in the alcohol (B) and Rn and/or Rnl in the
amine (C) are linked together.
[0070] An example of the sulfonyl group represented by Rn and Rnl is one represented by (R
S1S02)E. xamples of RS1i n the sulfonyl group RS1S02a re the same as the abovementioned
examples of RS in the sulfonyloxy group. Further, RS1 may be linked to R1,
Rn, or Rnl to form a ring.
[007 11 The method for producing an alcohol and/or an amine according to the present
invention can be properly performed without any solvent or in a solvent, but is
preferably performed in a solvent. The solvent to be used is preferably capable of
dissolving the substrate and the catalyst, and may be a single solvent or a mixed
solvent. Specific examples of such a solvent include: aromatic hydrocarbons such as
toluene and xylene; aliphatic hydrocarbons such as hexane and heptane; halogenated
hydrocarbons such as methylene chloride and chlorobenzene; ethers such as diethyl
ether, tetrahydrofuran, methyl tert-butyl ether, and cyclopentyl methyl ether; alcohols
such as methanol, ethanol, isopropyl alcohol, n-butyl alcohol, 2-butanol, and tert-butyl
alcohol; and polyhydric alcohols such as ethylene glycol, propylene glycol,
1,2-propanediol, and glycerin. Among them, ethers and alcohols are preferred, and
tetrahydrofuran, methanol, and isopropanol are particularly preferred. The amount of
the solvent to be used can be appropriately selected depending on, for example,
reaction conditions. If necessary, the reaction is performed with stirring.
[0072] The amount of the catalyst to be used depends on, for example, the type of catalyst
used, the type of amide used as a substrate, reaction conditions, or the like, but a molar
ratio of a ruthenium metal to the amide as a substrate is usually 0.0001 mol% to 10
mol%, preferably 0.005 mol% to 5 mol%. According to the method of the present
invention, the reaction temperature during hydrogenation reduction is 0 to 180 degrees
C, preferably 0 to 120 degrees C. If the reaction temperature is too low, there is a case
where a large amount of the unreacted raw material remains. On the other hand, if the
reaction temperature is too high, there is a case where decomposition of, for example,
the raw material, the catalyst, and the like undesirably occurs.
According to the method of the present invention, the pressure of hydrogen during
hydrogen reduction is 0.1 to 10 MPa, preferably 3 to 6 MPa. Further, the reaction time
is 30 minutes to 72 hours, preferably 2 to 48 hours, which makes it possible to achieve
a sufficiently high raw material conversion rate.
[0073] After the completion of the reaction, a target alcohol is obtained by using, singly or
in combination, purification techniques usually used such as extraction, filtration, crystallization,
distillation, and various chromatography techniques.
[0074] According to the present invention, the reaction may be performed by adding an appropriate
additive.
An example of the additive is a basic compound. Specific examples of the basic
compound include amines such as triethylamine, diisopropylethylamine,
N,N-dimethylaniline, piperidine, pyridine, 4-dimethylaminopyridine,
1,5-diazabicyclo[4.3.O]nona-5-ene,1 ,8-diazabicyclo[5.4.O]undeca-7-ene,tr in-
butylamine, and N-methylmorpholine; alkali metal carbonates such as potassium
carbonate, sodium carbonate, lithium carbonate, and cesium carbonate; alkaline-earth
metal carbonates such as magnesium carbonate and calcium carbonate; alkali metal
hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen
carbonate; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide,
and lithium hydroxide; alkaline-earth metal hydroxides such as magnesium hydroxide
and calcium hydroxide; alkali metal alkoxides such as sodium methoxide, sodium
ethoxide, sodium isopropoxide, sodium tert-butoxide, potassium methoxide, potassium
ethoxide, potassium isopropoxide, potassium tert-butoxide, lithium methoxide, lithium
isopropoxide, and lithium tert-butoxide; alkaline-earth metal alkoxides such as
magnesium methoxide and magnesium ethoxide; and metal hydrides such as sodium
hydride and potassium hydride. Among these bases, sodium methoxide and potassium
tert-butoxide are particularly preferred.
Examples
[0075] The present invention will be described in detail with reference to the following
Examples, but the present invention is not limited to these Examples.
It is to be noted that the reaction was evaluated by determining an isolated yield or a
gas chromatography (GC) area percentage (%). Apparatuses used are as follows.
[0076] GC system GC-2010 manufactured by Shimadzu Corporation
[0077] GC; capillary Neutra Bond- 1
Injection temperature: 220 degrees C, Detection temperature: 250 degrees C
40 degrees C (0 min)-5 degrees Clmin-100 degrees C-10 degrees Clmin-250 degrees
C (8 min)
[0078] lH-NMR spectrum and 31P-NMR spectrum were measured using MERCURY plus
300 manufactured by Varian.
[0079] Example 1
A ruthenium carbonyl complex 1 was produced according to the following equation.
[0080] [Chem. 121
1 15% NaOHaq.
[008 11 Under the stream of nitrogen, 4.18mmol of amine hydrochloride shown in the above
equation was placed in a 100 mL-flask and suspended in 33 mL of toluene, and 14 mL
of 15% aqueous NaOH solution was added thereto and the resulting mixture was
stirred at room temperature until no solid remained. The resulting solution was
separated into an organic phase and an aqueous phase, and the organic phase was
washed with 14 mL of distilled water (2 times) and the aqueous phase was subjected to
extraction with 14 mL of toluene (2 times). The thus obtained organic phases were
mixed and dried with sodium sulfate, and then the solvent was distilled away to obtain
a free amine.
4.18 mmol of the ruthenium carbonyl complex shown in the above equation was
placed in a 200 mL-flask, and the flask was purged with nitrogen. Then, the free amine
dissolved in 33 mL of toluene was added to the flask, and the resulting mixture was
heated under reflux for 60 minutes. 82 mL of Hexane was added, and then a crystal
was separated by filtration under an atmosphere of nitrogen. The thus obtained crystal
was washed with 10 mL of hexane and 40 mL of ethanol, and dried under a reduced
pressure to obtain 1.4 g (2.3 mmol) of a ruthenium carbonyl complex 1 shown in the
above equation.
[0082] [Math. 1]
'H-NMR (3 00MH z CD2C l ,) : 6 =
-1 5.23 (t, J = 29.3Hz, 1 H) , 2.40-2.65 (m, 4H), 2. 90-3.05 (m, 2H), 3.30-3.55 (m, 2H),
3. 92 (bs, 1H) , 7. 08-7. 34 (m, 4H), 7. 38-7. 46 (m, 8H), 7.40-7. 88 (m, 8H)
3 1 ~ - N M R ( 1 2 1 . 5MHz CD2C l ,) : 6=52.8(d, J = 14Hz)
[0083] Example 2
1-octanol was produced from N,N-dimethyloctanamide according to the following
equation.
[0084] [Chem. 131
I MeOH(Substrate concentration 1.25M),
100~C1, 6hours
[0085] 0.01 mmol of the complex 1 produced in Example 1 was placed in a 50 mLautoclave
equipped with a stirrer, and the autoclave was purged with nitrogen. 300 microliters
of methanol, l mmol of N,N-dimethyloctanamide, and 500 microliters of
methanol solution of 2.0 M sodium methoxide were added to the autoclave, and the
autoclave was purged with hydrogen. The resulting mixture was stirred under
hydrogen atmosphere (5 MPa) and 100 degrees C for 16 hours to obtain a reaction
solution. The reaction solution was analyzed by gas chromatography, and as a result, it
was confirmed that the GC area percentage of the amide as a raw material was 2% and
the GC area percentage of 1-octanol was 92%.
[0086] Examples 3 to 8
An alcohol was produced in the same manner as in Example 2 except that the type of
raw material used and the amount of the catalyst were changed. The results of
Examples 2 to 8 are shown in Table 1.
WO 20121039098
[0087] [Table I]
[0088] Example 9
1-octanol and aniline were produced from N-phenyloctanamide according to the
following equation.
[0089] [Chem. 141
Sample No.
2
3
4
5
6
8
ph , NaOMe, H2 (5MPa)
* -OH +
H MeOH(Substrate concentration 1.25M), H2N
[0090] 0.01 mmol of the complex 1 produced in Example 1 and 1 mmol of NSubstrate
H3C(H2C)68 ,I -
0
H3c(H2ckKNa
KN/ H3C(H2C)6 ,,
.l H3C(H2C)6 NH2
dN- I
dD
dNf H
phenyloctanamide were placed in a 50 mL-autoclave equipped with a stirrer, and the
Catalyst
(mol%)
1
1
1
1
0 . 1
1
1
Material
(GC area %)
2
6 8
6 7
0
0
9
4 5
Alcohol
(GC area %)
9 2
2 5
3 3
9 6
1 0 0
8 9
5 5
autoclave was purged with nitrogen. 300 microliters of Methanol and 500 microliters
of methanol solution of 2.0 M sodium methoxide (500 microliters) were added to the
autoclave, and the autoclave was purged with hydrogen. The resulting mixture was
stirred under hydrogen atmosphere (5 MPa) and 100 degrees C for 16 hours to obtain a
reaction solution. The reaction solution was analyzed by gas chromatography, and as a
result, it was confirmed that the amide as a raw material disappeared and the total GC
area percentage of 1 -0ctano1 and aniline was 93 %.
[0091] Examples 10 to 15
An alcohol and an amine were produced in the same manner as in Example 9 except
that the type of raw material used and the amount of the catalyst were changed. The
results of Examples 10 to 15 are shown in Table 2.
[0092] [Table 21
[0093] Example 16
Octanol and N,N-diphenylamine were produced from N,N-diphenyloctanamide
according to the following equation, and were isolated by silica-gel column chromatography.
[0094] [Chem. 151
MeOH(Substrate concentration 1.25M),
10o°C, 16hours
[0095] 0.01 mmol of the complex 1 produced in Example 1 and 5 mmol of
N,N-diphenyloctanamide were placed in a 50 mL-autoclave equipped with a stirrer,
and the autoclave was purged with nitrogen. 1.5 mL of methanol and 2.5 mL of
methanol solution of 2.0 M sodium methoxide were added to the autoclave, and the
autoclave was purged with hydrogen. The resulting mixture was stirred under
hydrogen atmosphere (5 MPa) and 100 degrees C for 16 hours to obtain a reaction
solution. After the completion of reaction, the reaction solution was cooled, diluted
with 40 mL of dichloromethane, and subjected to silica gel filtration (eluting solvent:
dichloromethane/methanol=10/1). The thus obtained solution was concentrated, and
then the resulting residue was purified by silica gel column chromatography (silica gel:
40 g, hexanelethyl acetate=8/1 to 411). As a result, 1-octanol (500 mg, 77%) and
N,N-diphenylamine (800 mg, 95%) were obtained.
[0096] NMR of 1-octanol
[Math.2]
'H-NMR ( 3 0 0 M H z CDC I , ) : 6=
3. 63 (t, J 8.8Hz, 2H), 2.00-1.46 (m, 2H) , 1.40-1. 30 (m, 10H) , 0. 90 (t, J=8. 8Hz, 3H)
[0097] NMR of N,N-diphenylamine
[Math.3]
'H-NMR ( 3 0 0 M H z CDC l : 6=
7.38-7. 21 (m, 4H), 27.05-7. 15 (m, 4H), 7.00-6.90 (m, 2H)
[0098] Example 17
Benzyl alcohol and N-methyl-N-phenylamine were synthesized from Nmethyl-
N-phenylbenzamide according to the following equation, and were isolated by
silica gel column chromatography.
[0099]
WO 20121039098
[Chem. 161
Ph , NaOMe, Hi! (5MPa)
t
I H N
MeOH(Substrate concentration 1.25M), I
10o°C, 16hours
[0100] 0.01 mmol of the complex 1 produced in Example 1 and 5 mmol of Nmethyl-
N-phenylbenzamide were placed in a 50 mL-autoclave equipped with a stirrer,
and the autoclave was purged with niti-ogen. 1.5 inL of Methanol and 2.5 inL of
methanol solution of 2.0 M sodium methoxide were added to the autoclave, and the
autoclave was purged with hydrogen. The resulting mixture was stirred under
hydrogen atmosphere (5 MPa) and 100 degrees C for 16 hours to obtain a reaction
solution. After the completion of reaction, the reaction solution was cooled, diluted
with 40 mL of dichloromethane, and subjected to silica gel filtration (eluting solvent:
dichloromethane/methanol=10/1). The thus obtained solution was concentrated, and
then the resulting residue was purified by silica gel column chromatography (silica gel:
40 g, hexanelethyl acetate=8/1 to 411). As a result, benzyl alcohol (425 mg, 90%) and
N-methyl-N-phenylamine (440 mg, 82%) were obtained.
[0101] NMR of benzyl alcohol
[Math.4]
'H-NMR ( 3 0 0 M H z CDC I,) : 6=
7.40-7. 30 (m, 5H), 4.69 (s, 2H), 1. 72 (brs, 1H)
[0102] NMR of N-methyl-N-phenylamine
[Math.5]
'H-NMR ( 3 0 0 M H z CDC 1 , ) : 6=
7.20 (dd, J 11. 6, 9. 6Hz, 2H), 6. 74 (d, J = 9.6HZ, 1 H) , 6. 65 (d, J = 11. 6Hz, 2H),
3. 22 (brs, 1H) , 2.85 (s, 3H)
[0103] Comparative Example 1
A reaction was performed using a catalyst described in Patent Literature 2 and Non-
Patent Literature 5.
[O 1041 0.005 mmol of Ru(a~aca)n~d 0.0 1 mmol of Triphos
( 1 , 1 , 1 -tris(diphenylphosphinomethyl)ethane) were placed in a 50 mL-autoclave
equipped with a stirrer, and the autoclave was purged with nitrogen. 1.5 mL of
Methanol, 5 mmol of N,N-dimethylbenzamide, and 2.5 mL of methanol solution of 2.0
M sodium methoxide were added to the autoclave, and the autoclave was purged with
hydrogen. The resulting mixture was stirred under hydrogen atmoshpere(5 MPa) and
100 degrees C for 16 hours to obtain a reaction solution. The reaction solution was
analyzed by gas chromatography. As a result, it was confirmed that the GC area
percentage of benzyl alcohol was I%, the GC area percentage of methyl benzoate was
12%, and the GC area percentage of N,N-dimethylbenzamide as a raw material was
86%.
Claims
[Claim I] A method for producing an alcohol and/or an amine from an amide
compound represented by the following general formula (A) under an
atmosphere of hydrogen in the presence of a ruthenium carbonyl
complex represented by the following general formula (1):
[Chem. 171
wherein R1 represents hydrogen, an alkyl group, a cycloalkyl group, an
aryl group, an aralkyl group, a heterocyclic group, an alkenyl group, an
alkynyl group, or a cycloalkenyl group, these alkyl group, cycloalkyl
group, aryl group, aralkyl group, heterocyclic group, alkenyl group,
alkynyl group, and cycloalkenyl group may have one or more than one
substituent, Rn and Rnl may be the same or different from each other
and each represents a hydrogen atom, an alkyl group, a cycloalkyl
group, an aryl group, an aralkyl group, a heterocyclic group, an alkenyl
group, an alkynyl group, a cycloalkenyl group, an alkyloxy group, a cycloalkyloxy
group, an aryloxy group, an aralkyloxy group, a hydroxyl
group, an alkoxycarbonyl group, a cycloalkyloxycarbony1 group, an
aryloxycarbonyl group, an aralkyloxycarbonyl group, an alkenyloxycarbonyl
group, an alkynyloxycarbonyl group, a cycloalkynyloxycarbonyl
group, or a sulfonyl group, these alkyl group, cycloalkyl
group, aryl group, aralkyl group, heterocyclic group, alkenyl group,
alkynyl group, cycloalkenyl group, alkyloxy group, cycloalkyloxy
group, aryloxy group, aralkyloxy group, hydroxyl group, alkoxycarbonyl
group, cycloalkyloxycarbony1 group, aryloxycarbonyl group,
aralkyloxycarbonyl group, alkenyloxycarbonyl group, alkynyloxycarbonyl
group, cycloalkynyloxycarbonyl group, and sulfonyl group
may have one or more than one substituent, and R1 and Rn and/or Rnl
and Rn and Rnl may be linked together to form a ring; and
RuXY(CO)(L) (I)
wherein X and Y may be the same or different from each other and
each represents an anionic ligand and L represents a tridentate aminodiphosphine
ligand represented by the following general formula (2):
[Claim 21
[Claim 31
[Chem. 181
wherein R1, R2, R3, and R4 may be the same or different from one
another and each represents a hydrogen atom, an alkyl group, a cycloalkyl
group, an aryl group, an aralkyl group, an alkyloxy group, a
cycloalkyloxy group, an aryloxy group, an aralkyloxy group, a heterocyclic
group, or a substituted amino group, R1 and R2 or R3 and R4
may be linked together to form a ring with an adjacent phosphorus
atom, these alkyl group, cycloalkyl group, aryl group, aralkyl group,
alkyloxy group, cycloalkyloxy group, aryloxy group, aralkyloxy group,
heterocyclic group, and substituted amino group may have one or more
than one substituent, Q1 and Q2 may be the same or different from each
other and each represents a divalent alkylene group that may have one
or more than one substituent, a divalent cycloalkylene group that may
have one or more than one substituent, or a divalent aralkylene group
that may have one or more than one substituent.
The production method according to claim 1, wherein the tridentate
aminodiphosphine ligand L is represented by the following general
formula (3):
[Chem. 191
wherein R5, R6, R7, and R8 may be the same or different from one
another and each represents a hydrogen atom, an alkyl group that may
have one or more than one substituent, a cycloalkyl group that may
have one or more than one substituent, an aryl group that may have one
or more than one substituent, or an aralkyl group that may have one or
more than one substituent, and n is an integer of 0 to 3.
The production method according to claim 1 or 2, wherein the
tridentate aminodiphosphine ligand L is represented by the following
general formula (4):
[Claim 41
[Claim 51
[Claim 61
[Claim 71
[Claim 81
[Claim 91
[Claim 101
wherein Arl, Ar2, Ar3, and A1-4 may be the same or different from one
another and each represents an aryl group or an aromatic heterocyclic
group, and these aryl group and aromatic heterocyclic group may have
one or more than one substituent.
The production method according to claim 3, wherein Arl, Ar2, Ar3, and
A1-4 in the general formula (4) are each a phenyl group that may have
one or more than one substituent.
The production method according to claim 4, wherein the tridentate
aminodiphosphine ligand L is represented by the following general
formula (5):
[Chem.2 11
wherein Ph represents a phenyl group.
The production method according to claim 1 or 2, wherein the
tridentate aminodiphosphine ligand L is an optically active tridentate
aminodiphosphine ligand.
The production method according to any one of claims 1 to 6, wherein
the anionic ligand represented by X in the general formula (I) is a
hydride and the anionic ligand represented by Y in the general formula
(I) is C1.
The production method according to any one of claims 1 to 6, wherein
the anionic ligand represented by X in the general formula (I) is a
hydride and the anionic ligand represented by Y in the general formula
(I) is BH4-.
The production method according to any one of claims 1 to 8, which is
performed in the presence of a base.
The production method according to claim 9, wherein the base is
sodium methoxide.