The present invention relates to a process and an apparatus for producing
ketoisophorone derivatives by oxidizing β-isophorone derivatives.
Ketoisophorone derivatives [e.g., 2,6,6-trimethylcyclohex-2-ene-1,4-dione
(ketoisophorone, KIP)] are useful intermediates for medicines, pesticides, perfumes,
condiments, and polymer resins.
Japanese Patent Application Laid-Open No. 125316/1976 (JP-A-51-125316)
discloses a method for producing an ethylenically unsaturated dicarboxylic acid
(ketoisophorone) by oxidizing β-ethylenically unsaturated ketone (β-isophorone)
with molecular oxygen or a molecular oxygen-containing gas in the presence of an
inorganic or organic base and a cobalt or manganese chelate. In this literature,
as the solvent, there are enumerated aromatic hydrocarbons, chlorinated aliphatic
hydrocarbons, lower aliphatic alcohols, ketones, carboxyamides, nitriles, amines,
In Japanese Patent Application Laid-Open No. 53553/1998 (JP-A-10-53553)
discloses a method for producing ketoisophorone by oxidizing β-isophorone
with molecular oxygen in the presence of a manganese complex salt and an organic
base. In this literature, there are dIsclosed that the oxidation reaction is effected
in the presence of water and that an organic acid, such as acetic acid and butyric
acid, is added as an additive. Moreover, the use of a ketone (e.g., acetone, methyl
isobutyl ketone) or an ether as the solvent is also described.
In these methods, however, certain of bases may sometimes lower the
conversion of the substrate or selectivity considerably or cause β-isophorone
to isomerize to α-isophorone. Particularly, when the concentration of β-isophorone
in the reaction system is high (e.g.. 20% by weight or more), the yield of ketoisophorone
is significantly reduced. In these methods, If the reaction is repeated or performed
continuously with the solvent circulating, high conversions and high selectivities
are hardly kept.
β-isophorone can be prepared by isomerizing α-isophorone
in the presence of an isomerizing catalyst composed of an acid. For example, in
Japanese Patent Publication No. 8650/1979 (JP-B-54-8650) is disclosed a method
for producing β-isophorone by the isomerization of α-isophorone in the
presence of an isomerizing catalyst (an acid having a pK value of 2 to 5) followed
Here, there may be proposed a process of producing ketoisophorone
from α-isophorone by combining the isomerizing reaction and oxidizing reaction.
The use of β-ketoisophorone obtained by the isomerization of α-isophorone,
however, inhibits the oxidation reaction from efficiently proceeding, thus difficulty
in producing ketoisophorone continuously.
As a process of producing ketoisophorone from α-isophorone,
in Japanese Patent Publication No. 30696/1980 (JP-B-55-30696), Japanese Patent
Application Laid-Open No. 191645/1986 (JP-A-61-191645), and Japanese Patent Application
Laid-Open No. 93947/1975 (JP-A-50-93947) are disclosed methods of producing 4-oxoisophorone
by oxidizing α-isophorone with oxygen in the presence of a catalyst. Japanese
Patent Application Laid-Open No. 81347/1974 (JP-A-49-81347) discloses a method
for producing 4-oxoisophorone by oxidizing α-isophorone with an alkaline
metal chromic acid salt or a dichromate or a chromium trioxide. In the Chem. Lett.
(1983), (7), 1081, there is proposed a method of producing 4-oxoisophorone by
oxidizing α-isophorone with t-butylhydroperoxide in the presence of a palladium
catalyst. However, in these methods, since the selectivity to ketoisophorone is
low, separation of the by-product(s) formed or the metal catalyst and purification
of the object compound are made complicated. Moreover, these methods sometimes
involve the use of a heavy metal compound such as chromium which requires special
treatment, or a peroxide which needs to be handled with care, leading to a decrease
in working efficiency.
Thus, an object of the present invention is to provide a process
and an apparatus for producing ketoisophorone derivatives at high conversions and
Another object of the present invention is to provide a process and
an apparatus for continuously and efficiently producing ketoisophorone derivatives
even in the case where β-isophorone derivatives obtained from α-isophorone
derivatives are employed.
Still another object of the present invention is to provide a process
and an apparatus for producing ketoisophorone derivatives without causing a reduction
in conversion and selectivity even in the case of performing a reaction continuously
with a solvent circulating.
DISCLOSURE OF INVENTION
The inventors of the present invention made intensive and extensive
studies to achieve the aforementioned objects and found that, in an oxidation
reaction of a β-isophorone derivative, an acid component present in the solvent
in a very small amount adversely affects the catalyst, considerably deteriorating
activity of the catalyst. The present invention is based on the above findings.
Thus, the process for producing ketoisophorone derivatives of the
present invention comprises, in the presence of an oxidizing catalyst, oxidizing
a β-isophorone derivative represented by the following formula (1):
wherein the groups R1 are the same or different, each representing
an alkyl group, a cycloalkyl group, an aryl group, or a heterocyclic group
in a solvent which contains substantially no acid component to form a ketoisophorone
derivative represented by the following formula (2):
wherein the groups R1 have the same meaning as defined above.
The amount of the acid component in the solvent is about 0 to 4,000
ppm (weight basis), and the solvent may be one treated with an alkali. The acid
component is, for example, an organic carboxylic acid. A complex salt of a transition
metal and an N,N'-disalicylidenediamine may be employed as the oxidizing catalyst.
Optionally, a cyclic base may be used together as a co-catalyst. The solvent separated
from the reaction mixture may be recycled for reuse in oxidizing β-isophorone
derivatives after the acid component having been separated therefrom.
The present invention also includes an apparatus for producing ketoisophorone
derivatives which comprises a removing unit for removing the acid component in
the solvent, and a reactor for forming a ketoisophorone derivative of the formula
(2) by, in the presence of an oxidizing catalyst, oxidizing a β-isophorone
derivative of the formula (1) in the solvent supplied from the removing unit.
BRIEF DESCRIPTION OF DRAWINGS
Figure 1 is a flow chart illustrating the process and apparatus of the present
Figure 2 is a flow chart illustrating another process and apparatus based on
the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described in further detail
with reference to the attached figures if necessary.
Figure 1 is a flow chart illustrating the process and apparatus of
the present invention. In this embodiment, a β-isophorone derivative is oxidized
in an oxidation reactor 1 to form a ketoisophorone derivative (oxidation step),
and the ketoisophorone derivative thus formed is, through a separation system,
continuously and successively separated and recovered from the reaction mixture
formed in the reactor 1 (separation step). The separation system is composed of
a distiller 2 for removing, among by-products, a high-boiling point component (HB)
from the reaction mixture formed in the oxidation reaction; a distiller 3 for
removing a low-boiling point component (LB) from the distillate came from the reactor
2; and a separation unit 4 for separating the resultant reaction mixture, which
is drained from the bottom of the distiller 3 and no longer contains the low-boiling
point impurities nor the high-boiling point impurities, into the ketoisophorone
derivative and the solvent. Through a recycle line 9, the solvent separated by
the separation unit 4 is supplied to an alkali-treatment unit 5a in which an alkaline
aqueous solution to wash with is added to eliminate an acid component from the
solvent. The mixture treated with the alkali is then fed to a liquid-separation
unit 5b for separating the mixture into the solvent phase and the aqueous phase.
On one hand part of the solvent from which the acid component has been removed(eliminated)
by the liquid-separation unit 5b is recycled to the oxidation reactor 1 through
a solvent-supply line 6 (recycling step) while on the other hand the rest of the
solvent is supplied to a mixing vessel 10 through a branch line to be mixed with
an oxidizing catalyst (oxidation catalyst). Thereafter, the catalyst-containing
mixture prepared in the mixing vessel 10 merges with the solvent-supply line 6
and is fed to the oxidation reactor 1. Moreover, in this embodiment, the distiller
3 constituted of a distilling column is further equipped with a dehydration system
composed of a cooling unit 7 and a liquid-separation unit 8 for eliminating the
low-boiling point component. In the liquid-separation unit 8, the low-boiling component
and water are separated from each other.
The β-isophorone derivative to be used in the present invention
can be obtained by, in the presence of an isomerizing catalyst (e.g., acid catalysts),
Isomerizing an α-isophorone derivative shown by the following formula (3):
wherein R1 has the same meaning as defined above [e.g., 3,5,5-triC1-4alkylcyclohex-2-ene-1-one
(e.g., 3,5,5-trimethylcyclohex-2-ene-1-one (α-isophorone, α-IP))]
and then distilling the β-isophorone derivative (2) thus formed under atmospheric
pressure or reduced pressure (about 13 to 800 hPa (about 10 to 600 Torr)). As the
catalyst for isomerization, organic carboxylic acids having boiling points higher
than those of the α-isophorone derivative and β-isophorone derivative,
such as C4-12dicarboxylic acids (e.g., glutaric acid, adipic acid,
suberic acid, sebacic acid), are available. The β-isophorone derivative formed
by the isomerization is separated and purified batchwise, semi-batchwise, or continuously
by distillation or other means, and then subjected to an oxidation step.
In the oxidation reactor 1, a ketoisophorone derivative of the formula
(2) is formed by, in the presence of an oxidizing catalyst (oxidation catalyst),
oxidizing a β-isophorone derivative of the formula (1) in a solvent containing
substantially no acid component.
In the formulae (1) and (2), exemplified as the alkyl group designated
by R1 are C1-10alkyl groups (e.g., C1-8alkyl groups
such as methyl, ethyl, butyl, isobutyl, t-butyl, pentyl, and hexyl). Examples of
the cycloalkyl group are C3-10cycloalkyl groups (e.g., cyclohexyl group).
Exemplified as the aryl group are C6-12aryl groups (e.g., phenyl group,
substituted phenyl groups such as p-methylphenyl group). As the heterocyclic group,
there are exemplified aromatic or non-aromatic 5- or 6-membered heterocyclic groups
having at least one hetero atom selected from nitrogen, oxygen, and sulfur (e.g.,
furyl, thienyl, nicotinyl, pyridyl). Included among the preferred groups designated
by R1 are C1-8alkyl groups, particularly C1-6alkyl
groups (e.g., C1-4alkyl groups such as methyl and ethyl).
As the β-isophorone derivative (1), there are exemplified 3,5,5-triC1-4alkylcyclohex-3-ene-1-one
(particularly, 3,5,5-trimethylcyclohex-3-ene-1-one (β-isophorone, β-IP)).
As the ketoisophorone derivative (2), there are exemplified 2,6,6-triC1-4alkylcyclohex-2-ene-1,4-dione
[particularly, 2,6,6-trimethylcyclohex-2-ene-1,4-dione (ketoisophorone, KIP)].
The species of the oxidizing catalyst is not particularly restricted,
and a complex salt (or a complex) of a transition metal and an N,N'-disalicylidenediamine
or the like can be used. Such complex salt is useful in forming the ketoisophorone
derivative (2) by oxidizing the β-isophorone derivative (1) with molecular
As to the transition metal, the species or valence is not particularly
restricted providing the transition metal can exercise its oxidation ability toward
the aforementioned oxidation reaction, and at least one transition metal selected
from the elements of the Groups 3 to 12 of the Periodic Table of Elements can be
used. The valence of the transition metal may be divalent to octavalent, and is
usually divalent, trivalent, or tetravalent. Examples of the preferred transition
metal are the Group 5 elements (e.g., vanadium V, niobium Nb), the Group 6 elements
(e.g., chromium Cr), the Group 7 elements (e.g., manganese Mn, rhenium Re), the
Group 8 elements (e.g., iron Fe, ruthenium Ru), the Group 9 elements (e.g., cobalt
Co. Rhodium Rh), the Group 10 elements (e.g., nickel Ni, palladium Pd), and the
Group 11 elements (e.g., copper Cu). The preferred transition metal is, for example,
V, Mn, Fe, Co, ,or Cu, with Mn particularly preferred. These transition metals
can be used either singly or in combination.
The transition metal, together with an N,N'-disalicylidenediamine,
can form a complex shown by the following formula (4a) or (4b):
wherein M stands for the transition metal; R2, R3, R4,
R5, R6, R7, R8, and R9 are
the same or different, each representing a hydrogen atom, a halogen atom, an alkyl
group, or a hydroxyl group, an alkoxyl group, a hydroxymethyl group; Y1,
Y2, and Y3 are the same or different, each representing an
alkylene group, a cycloalkylene group, or an arylene group; each ring Z stands
for an aromatic ring; and n is 0 or an integer of 1 or more.
As diamines corresponding to the above Y1, Y2,
and Y3, there may be exemplified aliphatic diamines such as straight-
or branched chain C2-10alkylenediamines and C2-10
containing an imino group (NH group); alicyclic diamines such as a diaminocyclohexane;
aromatic diamines such as diaminobenzene, diaminonaphthalene,
biphenyldiamine; and derivatives thereof.
Included among the preferred N,N'-disalicylidenediamines are N,N'-disalicylidene
C2-8alkylenediamines (preferably, N,N'-disalicylidene C2-5alkylenediamines)
such as N,N'-disalicylideneethylenediamine (H2 salene), N,N'-disalicylidenetrimethylenediamine,
and N,N'-disalicylidene-4-aza-1,7-heptanediamine; and N,N'-disalicylidene C6-12arylenediamines
such as N,N'-disalicylidene-o-phenylenediamine, and N,N'-disalicylidene-2,2'-biphenylenediamine.
Examples of the particularly preferred N,N'-disalicylidenediamine are N,N'-disalicylidene
C2-4alkylenediamines such as N,N'-disalicylideneethylenediamine (H2
salene) and N,N'-disalicylidenetrimethylenediamine.
As the aromatic rings Z, there may be exemplified hydrocarbon rings
(e.g., benzene, naphthalene) and heterocycles (e.g., nitrogen atom-containing heterocycles
such as pyridine, pyrazine, pyrimidine, and quinoline; sulfur atom-containing
heterocycles such as thiophene; and oxygen atom-containing heterocycles such as
As to the substituents R2 and R9 of the aromatic
rings Z, examples of the halogen atom are bromine, chlorine, and fluorine atoms,
and examples of the alkyl group are C1-6 alkyl groups such as methyl,
ethyl, propyl, butyl, and t-butyl groups. Examples of the alkoxy group are C1-6
groups such as methoxy, ethoxy, propoxy, and butoxy groups. Each of the substituents
R2 to R9 is usually a hydrogen atom, a C1-4 alkyl
group, or a hydroxymethyl group.
The complex may be amorphous, or crystalline like a compound represented
by the formula (4b). In the formula (4b), n is 0 or an integer of 1 or more (e.g.,
1 to 5, particularly 1 or 2).
In the above complex represented by the formula (4b), n+1 mol of
N,N'-disalicylidenediamine is coordinated with n mol of the transition metal, and
thus the complex is structurally different from a complex represented by the formula
(4a) in which 1 mol of N,N'-disalicylidenediamine is coordinated with 1 mol of
the transition metal. Moreover, in contrast to the complex (4a) which is amorphous,
the complex (4b) is crystalline and shows a clear melting point when subjected
to thermal analysis by TC/TDA. The melting point of the complex (4b) is usually
about 190 to 240°C and particularly about 200 to 220°C. The complex (4a) and (4b)
can be distinguished from each other by whether an absorption peak derived from
the hydroxyl group is observed in the infrared absorption spectrum or not.
Included among the preferred complexes are complexes of manganese
and N,N'-disalicylidene C2-4alkylenediamines such as N,N'-disalicylideneethylenediamine
(H2 salene) and N,N'-disalicylidenetrimethylenediamine, particularly
a complex of manganese and N,N'-disalicylideneethylenediamine (manganese-salene
The above complex can be obtained by coordinating an excess of N,N'-disalicylidenediamine
with a transition metal compound. As the transition metal compound, there may
be exemplified organic acid salts (e.g., acetic acid salts), halides (e.g., manganese
chloride), and inorganic acid salts. The ratio of the N,N'-disalicylidenediamine
to the transition metal compound is the former/the latter (molar ratio) = about
0.5 to 5, preferably about 0.9 to 3, and particularly about 1 to 2. The reaction
of the transition metal compound with the N,N'-disalicylidenediamine can be carried
out in an inert solvent (e.g., an organic solvent such as alcohol). The reaction
can be effected by stirring the reaction mixture in an atmosphere of an inert gas,
usually at a temperature of from 70°C to the reflux temperature of the solvent.
The complex salt may be employed in combination with a nitrogen-containing
compound as a co-catalyst to constitute a catalytic system. The nitrogen-containing
compound contains at least one component selected from cyclic bases and non-cyclic
bases. Preferred as the catalytic system Is one constituted of (1) a combination
of the complex salt or complex, and a cyclic base, (2) a combination of the complex
salt or complex, a cyclic base, and a non-cyclic base, or (3) a combination of
the complex and a non-cyclic base.
Exemplified as the cyclic base are alicyclic and aromatic bases having
at least one (preferably, two) nitrogen atom.
The alicyclic bases include bases in which at least one nitrogen
atom constitutes a hetero atom of the ring, for example, 5 to 10-membered monocyclic
(mono-,heterocyclic) compounds such as pyrrolidine or derivatives thereof [N-substituted
pyrrolidines (e.g., N-C1-4 alkylpyrrolidines such as N-methylpyrrolidine),
substituted pyrrolidines (e.g., 2-or 3-methylpyrrolidine, 2- or 3-aminopyrrolidine)],
piperidine or derivatives thereof [N-substituted piperidines (e.g., N-C1-4alkylpiperidines
such as N-methylpiperidine; piperylhydrazine), substituted piperidines (o-, m-,
or p-aminopiperidine)]; alkylene imines or derivatives thereof [hexamethylene
imine, N-substituted hexamethylene imines (e.g., N-methylhexamethylene imine)],
and piperazine or derivatives thereof [N-C1-4alkylpiperazines such as
N-methylpiperazine; N,N'-di-C1-4alkylpiperazines such as N,N'-dimethylpiperazine;
2-methylpiperazine]; and polyheterocyclic compounds such as azabicyclo C7-12alkanes
(e.g., quinuclidine, 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,5-diazabicyclo[3.2.1]octane,
1,5-diazabicyclo[3.3.0]octane, 1,4-diazabicyclo[4.2.0]octane, 1,5-diazabicyclo[3.3.1]nonane,
1,5-diazabicyclo[5.3.0]decane), azatricycloC8-16alkanes (e.g., 1,5-diazacyclo[3.3.0.02,6]octane,
hexamethylenetetramine); and derivatives thereof.
Among these alicyclic bases, those containing at least two (particularly,
2 to 6) nitrogen atoms (e.g., polycyclic compounds (poly-, heterocyclic compounds)
having a nitrogen atom at a bridgehead position) are preferable. Preferred as
the alicyclic base is, for example, a 6 to 8-membered mono-, heterocylcic compound
(e.g., piperazine, N-substituted piperazines. amino-substituted piperazines);
an azabicycloC7-10alkane (e.g., quinuclidine, DABCO, or derivatives
thereof); or hexamethylenetetramine.
Included among the aromatic bases are those having at least two nitrogen
atoms in which at least one nitrogen atom constitutes a hetero atom of the ring.
Examples of such aromatic base are aromatic heterocyclic compounds in which at
least one nitrogen atom constitutes a hetero atom of the ring (e.g., pyridine)
substituted with a substituent at least having a nitrogen atom (e.g., amino group,
an N-substituted amino group) [N,N-di-substituted aminopyridines such as 2-, 3-,
or 4-aminopyridine, 2-, 3-, or 4-mono- or di-alkylaminopyridines (e.g., di-C1-4alkylaminopyridines
such as dimethylaminopyridine), 2-, 3-, or 4-piperidinopyridine, and 4-pyrrolidinopyridine];
pyrazine or derivatives thereof (e.g., 2-methylpyrazine); phthalazine, quinazoline,
quinoxaline, or derivatives thereof; phenanthroline or its derivatives (e.g.,
1,10-phenanthroline); and 2,2-bipyridyl or its derivatives, with N,N-di-substituted
aminopyridines, pyrazine, phenanthroline, or derivatives thereof particularly
In the above cyclic base, a nitrogen atom(s) other than the one constituting
the ring is preferably a tertiary amine, and the nitrogen atom as a hetero atom
constituting the ring may be substituted with a substituent other than hydrogen
atom. The cyclic bases can be used either singly or in combination.
The proportion (molar ratio) of the cyclic base to the complex is
about 20/1 to 500/1, preferably about 30/1 to 300/1 (e.g., about 50/1 to 250/1).
As the co-catalyst, a non-cyclic base, such as a Schiff base, may
be employed in conjunction with or in lieu of the cyclic base. Exemplified as the
Schiff base are compounds having an imino bond or an anil bond. Schiff bases like
these include, for example, compounds shown by the following formulae (5a) to (5h)
and compounds having a similar structure.
wherein R10 and R11 are the same or different, each representing
a hydrogen atom, an alkyl group, an aryl group, or a cycloalkyl group; R12
represents a hydroxyl group, an amino group, an alkyl group, or an aryl group;
R13 represents a hydroxyl group, an amino group, an alkyl group, an
aryl group, or a pyridyl group; and Y4 represents an alkylene group
or a cyclohexylene group.
Exemplified as the groups designated by R10 to R12
Y4 are groups similar to those enumerated for R2 to R9
Y1 to Y3.
Included among the preferred non-cyclic bases are salicylaldoxime,
bisacetylacetone-ethylenediimine, dimethylglyoxime, diamine salicylaldimines as
constituents of the complexes listed above (e.g., N,N'-disalicylideneC2-5alkylenediamines
such as N,N'-disalicylideneethylenediamine, N,N'-disalicylidenetrimethylenediamine
and N,N'-disalicylidene-4-aza-1,7-heptanediamine), compounds having an imino
bond such as bisimine compounds, and compounds having an anil bond such as glyoxal
bishydroxyanil. N,N-disalicylidenediamines as constituents of the above complexes
include, for example, ligands for the complexes shown by the formula (1).
When the non-cyclic base is used, the ratio (molar ratio) of the
non-cyclic base to the complex is the former/the latter = about 0.1/1 to 20/1,
preferably about 0.5/1 to 15/1 (e.g., 0.5/1 to 10/1), and usually about 1/1 to
In the oxidation reaction, the amount of the oxidizing catalyst or
co-catalyst relative to 1 mol of the β-isophorone derivative is as follows.
Oxidizing catalyst: about 1 x 10-5 to 1 x 10-2 mol (preferably,
1 x 10-4
to 1 x 10-3 mol). Cyclic base: about 5 x 10-2
to 1 mol (preferably, 1 x 10-2 to 0.5 mol). Non-cyclic base: about
1 x 10-5 to 5 x 10-2 mol (preferably, 1 x 10-3
to 5 x 10-3
As the oxygen source for the oxidation reaction, compounds generating
oxygen are also employable providing they are capable of supplying molecular oxygen
as well as oxygen and oxygen-containing gases. As the oxygen source, although
high-purity oxygen gases can be used, it is preferred that an oxygen gas diluted
with an inert gas, e.g., nitrogen, helium, argon, or carbon dioxide is supplied
to the reaction system. In the present invention, the β-isophorone derivative
can be oxidized effectively even with air in lieu of oxygen as an oxygen source.
The concentration of oxygen in the oxygen source is, e.g., 5 to 100%
by volume, preferably about 5 to 50% by volume, and particularly about 7 to 30%
by volume. Even if the concentration of oxygen is as low as 8 to 25% by volume,
the oxidation reaction proceeds effectively.
As to the way molecular oxygen is supplied to a reaction vessel or
container, the reaction may be effected in a closed system previously supplied
with sufficient molecular oxygen, or may be conducted with molecular oxygen continuously
flowing. When allowing molecular oxygen to flow continuously, the flow rate is,
for example, about 0.1 to 10L/min and preferably about 0.5 to 5L/min per unit
In the present invention, since a solvent which is substantially
free from acid component (e.g., protonic acids having a pKa value of 5 or less,
particularly organic carboxylic acids (e.g., C1-10aliphatic carboxylic
acids)) is employed, the ketoisophorone derivative (2) is produced at a high conversion
and a high selectivity with maintaining a high activity of the oxidizing catalyst.
The source of the acid component cannot be determined exactly, but
it may be ascribed to something decomposed in the oxidation reaction procedure.
For example, the acid component may be ascribed to the solvent (e.g., diisobutyl
ketone) decomposed in the oxidation reaction (e.g., decomposed into a C1-10carboxylic
acid, such as formic acid, acetic acid, isobutyric acid, isovaleric acid), or
to a by-product (e.g., valeric acid, butyric acid) produced in the step of forming
the starting material β-isophorone derivative (isomerization step of α-isophorone).
The amount of the acid component in the solvent is, e.g., about 0
to 4,000 ppm (weight basis), preferably about 0 to 2,000 ppm (weight basis), and
more preferably about 0 to 900 ppm (weight basis).
There are no special restrictions on the choice of the solvent, provided
that the solvent does riot adversely affect or inhibit the reaction. A solvent
phase-separable from water (or a solvent separable from water) such as a water-insoluble
or hydrophobic solvent, particularly a non-water-miscible solvent, is usually employed,
as the acid component in the solvent will later be removed by being washed with
an alkali (e.g., an alkaline aqueous solution). As the solvent, there are exemplified
aliphatic hydrocarbons such as hexane, heptane, and octane; aromatic hydrocarbons
such as benzene, toluene, and xylene: alicyclic hydrocarbons such as cyclohexane;
ketones (particularly, dialkyl ketones) such as methyl ethyl ketone and dibutyl
ketones (e.g., dibutyl ketone, diisobutyl ketone, dit-butyl ketone); ethers such
as diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane,
ethylene glycol monomethyl ether, ethylene glycol dimethyl ether, diethylene glycol
monomethyl ether, and diethylene glycol dimethyl ether; halogenated hydrocarbons
such as monochloroethane, dichloroethane, chloroform, carbon tetrachloride, and
1,2-dichloroethane; and esters such as methyl acetate, ethyl acetate, and butyl
acetate. These solvents can be used either independently or in mixture. Preferred
solvents include C2-5alkyl-C2-5alkyl ketones (particularly,
A commercially available solvent also may be employed as the solvent
to be used in the present invention. Also, the solvent once used for the oxidation
reaction and recovered through the recycle line 9 may be sent back through the
solvent supply line 6 to be reused. Usually, it is economical and advantageous
to reuse the solvent recovered.
The concentration of the substrate in the reaction system is not
particularly limited, but usually selected within the range of about 5 to 70% by
weight, preferably about 15 to 60% by weight (e.g., 20 to 55% by weight).
The water content of the reaction system at the initial stage of
the reaction can be selected freely unless the activity or other characteristics
of the oxidizing catalyst are adversely affected, and is 1% by weight or less
(about 0.001 to 1% by weight), preferably 0.5% by weight or less (0.001 to 0.5%
by weight). A water content exceeding 1% by weight accelerates the reaction at
its initial stage, but may cause the reaction to stop proceeding further or lower
the selectivity to the ketoisophorone derivative. The reaction system contains
not only the water present at the initial stage of the reaction but water produced
by the reaction, and a finite amount of water Is usually present in the present
reaction system. Accordingly, the water present in the oxidizing reaction system
(particularly, the water produced in the reaction) is separable and removable
from the reaction system in the separation step which will later be described.
The amount of water to be removed from the reaction system is at least 30% by
weight, preferably at least 50% by weight, and more preferably at least about 80%
by weight, relative to the total of the water generated.
The reaction temperature can be selected according to the reaction
rate, selectivity, and a solvent to be used. To eliminate the risk of explosions,
it is desirable that the reaction is conducted at a temperature lower than the
flash point of the reaction solvent. For example, in the case of diisobutyl ketone
(flash point: about 49°C) employed as the solvent, the reaction can be effected
at a temperature of about 35 to 45°C. Moreover, the reaction is usually carried
out at atmospheric pressure, though possible to conduct at either atmospheric pressure
or applied pressure (up to about 150 atm).
The reaction time (residence time in a flow reaction) is not particularly
restricted, and usually about 0.5 to 30 hours (e.g.. 1 to 10 hours).
In the oxidation step, there can be used a gas-liquid agitation-type
oxidation reactor, and the amount of oxygen supplied and the conditions for stirring
may sometimes affect the reaction selectivity. The preferred reactor is a reactor
of high stirring efficiency, and such reactor may be equipped with a plurality
of tiers (e.g., two tiers) of disc turbine rotor blades (e.g., 4 to 8 blades),
and/or one or plural of buffle plates (e.g., 2 to 6 buffle plates). Further, oxygen
may be supplied to the reaction system by being squirted in bubbles by a sparger.
The stirring energy of the reactor per unit volume can be selected within the range
of about 0.5 to 5 kw/m3 (preferably. 0.7 to 2.5 kw/m3).
The starting materials can be added to the reaction system in any
order, and there is no particular restriction on the order of addition. However,
for preventing the isomerization to an α-isophorone derivative, at an early
stage of the reaction, it Is preferred that the β-isophorone derivative is
supplied to the reactor last, that is, after components (e.g., an oxidizing catalyst)
other than the β-isophorone derivative has been fed to the reactor. Further,
for inhibiting the generation of heat, the β-isophorone derivative may be
continuously or intermittently supplied to the reaction system in drops, or in
[Separation step and recycling step]
In the separation step, using at least one purifying means (e.g.,
a distiller, a separator), the ketoisophorone derivative, the solvent, low-boiling
point impurities, and high-boiling point impurities (e.g., oxidizing catalyst)
are individually separated from the reaction mixture formed in the oxidation reaction.
In the recycling step, using the alkali-treatment unit 5a and the liquid-separation
unit 5b, the acid component is removed from the solvent separated in the separation
step. The solvent is then circulated back to the oxidation step through the solvent-supply
[Separation of high-boiling point impurities (HB)]
The reaction mixture from the bottom of the oxidation reactor 1 is
subjected to a first separation step for separating high-boiling point impurities,
such as the oxidizing catalyst. This separation step may be carried out in a conventional
manner, for example, using the distilling column 2 (particularly, a flash distiller).
As the flash distiller, conventional ones, such as WFE (Wiped Film Evaporator)
and FFE (Falling Film Evaporation), are available. Conditions under which a flash
distillation is conducted depend on the species of the catalytic component, and
the temperature is, for example, 80 to 150°C (preferably 90 to 120°C) and the pressure
is about 13 to 133 hPa (10 to 100 mmHg) (preferably, 17 to 107 hPa (20 to 80 mmHg)).
This distilling operation permits the recovery of the oxidizing catalyst from
the bottom and the distillate mainly composed of the ketoisophorone derivative,
solvent, and low-boiling point impurities from the overhead.
The oxidizing catalyst recovered from the bottom of the distilling
column 2 is directly, or after being regenerated(reactivated) if necessary, sent
back to the oxidation step for reuse.
[Removal of low-boiling point component (HB)]
The distillate collected from the overhead of the distilling column
2 is then subjected to a second separation step for removing low-boiling point
impurities (e.g., reaction by-products). The low-boiling point component (impurities)
includes products by-produced in the production step of the starting material β-isophorone
derivative (isomerization step of α-isophorone) (particularly, decomposed
products of the isomerizing catalyst), such as cyclic ketones, hydroxyl group-containing
compounds (alcohols such as cyclic alcohols), and carboxyl group-containing compounds
(carboxylic acids such as cyclic carboxylic acids). The boiling point of the low-boiling
point component (impurities) is usually 100 to 180°C (e.g., 100 to 160°C), particularly
120 to 140°C.
The low-boiling point component(s) (impurities) can be removed by
a conventional separating means, and condensation, distillation, extraction, or
a combination means thereof may for example be adopted. Usually, the removal is
carried out using a distilling column (or a rectifying column). The distilling
column may be either a packed column or a plate column.
The low-boiling point component (impurities) may be removed in a
single separation step or plural separation steps, or through a series of separation
steps. In Figure 1, when eliminating the low-boiling point component in a single
separation step using a distilling column 3, the number of plates of the distilling
column is not particularly restricted, and may for example be about 5 to 50 plates,
preferably about 5 to 30 plates. The distilling operation can be performed at an
overhead temperature of about 30 to 80°C (preferably, about 30 to 70°C), a bottom
temperature of about 80 to 150°C (preferably, about 100 to 130°C) and at a pressure
of about 17 to 267 hPa (20 to 200 mmHg) (preferably, 53 to 200 hPa (40 to 150
mmHg)). The distilling operation can be conducted in a conventional manner, for
example, by refluxing the solvent at a suitable reflux ratio (e.g., about 0.5 to
5, preferably about 1 to 3).
A combination of several separating steps is advantageous in separating
water or the solvent from the low-boiling point component as well as the low-boiling
point component from the reaction mixture. For example, the low-boiling point
component and water can be removed simply through distillation (distilling column
3), but it is nevertheless more effective to remove the low-boiling point component
and water by, if necessary, combining a cooling operation (using a cooling unit
7) of the low-boiling component distilled off and a separating operation of the
liquid (using a liquid-separation unit 8) for eliminating the water contained in
the low-boiling point component.
[Recovery of the ketoisophorone derivative]
From the bottom of the distilling column 3 is drained a bottom product
containing the solvent and the ketoisophorone derivative but free from the high-boiling
point component (HB) and low-boiling point component (LB). The bottom product
(bottoms) containing the solvent is then subjected to a recovering step comprised
of separation of the ketoisophorone derivative from the solvent and recovery of
the ketoisophorone derivative, followed by a recycling step of recycling the solvent.
The separation of the ketoisophorone from the solvent and the recovery of the
ketoisophorone may be effected using a conventional purification means, such as
a distilling column 4 (recovering column).
The number of plates of the distilling column (recovering column)
may be about 10 to 80, and preferably about 20 to 50. The distilling operation
may be performed at an overhead temperature of about 30 to 100°C (preferably,
50 to 80°C), a bottom temperature of about 120 to 200°C (preferably. 150 to 180°C),
and at a pressure of about 7 to 133 hPa (5 to 100 mmHg) (preferably 13 to 67 hPa
(10 to 50 mmHg)). The distillation may be performed in a conventional manner,
for example, under reflux at a suitable reflux ratio (e.g., about 1 to 5, preferably
about 1 to 3).
According to the boiling points of the ketoisophorone derivative
and the solvent, although the keotoisophorone derivative may be distilled off from
the overhead of the distilling column, the solvent, which boils at a temperature
lower than the boiling point of the ketoisophorone derivative, is usually distilled
off from the overhead. It is preferred that the ketoisophorone derivative is recovered
by side-cut (e.g., at a plate at a height of 40 to 80% of the total number of the
plates counted from the bottom).
From the bottom of the distilling column are discharged the remnants
of the high-boiling point impurities (oxidizing catalyst) which the distilling
column 2 was unable to remove. If necessary, the product from the bottom may be
recycled to the distilling column 2 to be further separated into the high-boiling
point impurities and the ketoisophorone derivative.
[Recycle of the solvent]
Since the solvent separated from the ketoisophorone derivative (the
solvent recovered) usually contains an acid component (e.g., organic carboxylic
acids), the solvent is advantageously reused in the oxidation step when made substantially
free of the acid component through removal.
A variety of physical and chemical techniques are available as ways
of removing such acid component, and examples of which are adsorption and distillation.
For removing the acid component efficiently, treatment of the solvent with an
alkali is favorable. As the alkali-treatment, there are exemplified: a process
of removing the acid component by bringing a solid alkaline component into contact
with the solvent (by running the solvent through), and a process comprised of mixing
an alkaline aqueous solution (or slurry) with the solvent and then separating
the liquid (alkaline washing).
Figure 2 shows another way of alkaline washing. In Figure 2, an apparatus
for producing ketoisophorone comprises: an oxidation reactor 1 for oxidizing a
β-isophorone derivative to form a ketoisophorone derivative, a distiller
2 for removing high-boiling point impurities from the reaction mixture resulted
from the oxidation, a distiller 3 for separating low-boiling point impurities
from the distillate from the distiller 2, and a separation unit 4 for separating
the ketoisophorone and the solvent from the reaction mixture from which the high-boiling
point impurities and low-boiling point impurities have been removed. The solvent
separated from the ketoisophorone in the separation unit 4 is fed to a removing
unit 5 to be washed with an alkali. In the removing unit 5, the solvent is mixed
with an alkaline aqueous solution (or slurry), and the mixture is then separated
into phases to remove the acid component from the solvent.
Exemplified as the alkali for the alkali- treatment are hydroxides
or salts of alkaline metals (e.g., lithium, sodium, potassium) or alkaline earth
metals (e.g., magnesium, calcium), such as alkaline metal hydroxides (e.g., lithium
hydroxide, sodium hydroxide, potassium hydroxide); alkaline metal hydrogencarbonates
(e.g., lithium hydrogencarbonate, sodium hydrogencarbonate, potassium hydrogencarbonate);
alkaline metal carbonates (e.g., lithium carbonate, sodium carbonate, potassium
carbonate); alkaline earth metal hydroxides (e.g., magnesium hydroxide, calcium
hydroxide); and alkaline earth metal carbonates (e.g., magnesium carbonate, calcium
carbonate). Ammonium or an organic base (e.g., amines) may be used, if necessary.
Preferred as the alkali is an alkaline metal hydroxide (e.g., lithium hydroxide,
sodium hydroxide, potassium hydroxide).
As the alkaline aqueous solution (or slurry) with which to wash,
an aqueous solution with a pH of 8 or higher is usually usable (preferably, a pH
of 10 or higher).
Although the concentration of the alkaline aqueous solution (or slurry)
can be selected within a wide range, it is usually selected within a range suitable
in view of operability. For example, the concentration is about 10 to 90% by weight,
preferably about 15 to 60% by weight.
If necessary, the concentration of the alkaline aqueous solution
is adjusted to about 20 to 50% by weight, particularly to about 30 to 45% by weight.
Useful components contained in the recovered solvent, such as the cyclic base
(DABCO) and the non-cyclic base, are inhibited from being dissolved and removed
with the alkaline aqueous solution by adjusting the concentration to such values.
The solvent from which the acid component has thus been removed is
recycled to the oxidation reactor 1 through a solvent-supply line 6. If needed,
the solvent thus recovered from which the acid component has been removed may
be mixed together with an oxidizing catalyst in a mixer 10, and the resulting mixture
is recycled to the oxidation reactor 1 through the solvent-supply line 6.
In the present invention, the oxidation reaction need only be effected
in a solvent which is substantially free from acid components, and may be effected
in a semi-batch system or batch system, as well as in a continuous system. For
example, the apparatus illustrated in Figure 2 may be used when producing ketoisophorone
derivatives batchwise or semi-batchwise, while the apparatus shown in Figure 1
is usually used when producing ketoisophorone derivatives in a continuous system.
The reaction solvent is not necessarily recycled.
The number of distilling columns to be employed in the distillation
of the high-boiling point component, low-boiling point component, ketoisophorone
derivative, or the solvent Is not limited to one, and a plurality of distilling
columns may be used if necessary. Although the distillation may be performed in
batches, continuous distillation is industrially advantageous.
Moreover, as to the separation of the high-boiling point component
(impurities) and low-boiling point component (impurities), inverse to the order
of the steps and units described above, the oxidizing catalyst may be recovered
after the removal of the low-boiling point component (impurities) followed by the
high-boiling point component (oxidizing catalyst).
As was described above, in the present invention, since the oxidation
reaction is effected using a solvent which substantially contains no acid component,
ketoisophorone derivatives can be produced at high conversions and high selectivities.
Particularly, the present invention realizes stable and continuous production
of ketoisophorone derivatives from β-isophorone derivatives with efficiency.
In addition, removal of an acid component by treatment with an alkali makes it
possible to produce ketoisophorone derivatives without a deterioration in conversion
and selectivity even if the reaction is continuously effected with the solvent
Hereinafter, the present invention will be described in further detail
and should by no means be construed as defining the scope of the present invention.
Using the apparatus shown in Figure 1, a ketoisophorone derivative
was produced through an isomerizing reaction and an oxidizing reaction in the
(1) Oxidation step
0.92 g of manganese salene complex (Mn-salen) and 68 g of diazabicyclooctane
(DABCO) were fed to a glass atmospheric oxidation reactor (volume: 10L), and 1036.5
g of β-IP and 3420.6 g of diisobutylketone (DIBK) were added thereto. The
mixture was stirred with a disk turbine blade (100 mm⊘) rotating at speed
of 300 rpm for reaction while air is allowed to flow at 40°C. After being reacted
for 5 hours, the reaction mixture was analyzed by gas chromatography, and it was
found that 996 g of a ketoisophorone derivative (KIP) was formed at a conversion
of 93% and a selectivity of 94%.
(2) Recovering step of the catalyst from the high-boiling point component
Using a stainless steel flash-distiller (WFE, Wiped film evaporator,
100 mm⊘ x height 200 mm), the reaction mixture was flash-distilled at a pressure
of 53 hPa (40 mmHg) and a distilling rate of 600 g/hr to remove the manganese
salene complex as the catalyst and high-boiling point component (HB) by-produced
in the reaction, and a distillated composed of the reaction product KIP, the solvent
DIBK, low-boiling point component (impurities), a co-catalyst DABCO, and an acid
component (acetic acid) were distilled off as a distillate. The temperature of
the distillate was 98°C.
(3) Removing step of the low-boiling point component
The distillate from the overhead of the distilling column 2 was supplied
to a bottom of an oldershow distilling column (10 plates, 40 mm⊘) equipped
with a vacuum jacket at a supplying rate of 600 g/hr, and distilling off the low-boiling
point component (LB) and water generated in the reaction while only the upper layer
of the distillate was refluxed within the column at a pressure of 53 hPa (40 mmHg).
The temperature of the bottom was 115°C, and the temperature of the distillate
(4) Recovery step of KIP
The product (KIP, DIBK, co-catalyst DABCO, acid component) from the
bottom of the oldershow distilling column mentioned above was supplied to the thirteenth
plate from the top of an oldershow distilling column equipped with a vacuum jacket
(30 plates, 40 mm⊘) at a supplying rate of 600 h/hr, and distilled at a pressure
of 40 hPa (30 mmHg) and a reflux ratio of 2.0 for separation-purifying KIP and
DIBK. 956 g of KIP as a side-cut solution was collected at the 23th plate from
the top. 1657 g of the distillate (DIBK, DABCO, acid component) from the overhead
was supplied to a liquid-separation unit equipped with a stirrer, and the bottom
product was fed to a flash-distiller. The temperature of the bottom was 162°C,
the temperature of the side-cut plate was 131°C, and the temperature of the distillate
was 74°C. Analysis of the separated solvent by gas chromatography showed that the
concentration of the acid component (acetic acid) to be 1,000 ppm (weight basis).
(5) Washing step of the solvent
The recovered solvent (DIBK) containing the acid component and DABCO
distilled out from the overhead of the distiller, and 65 g of sodium hydroxide
aqueous solution (40% by weight) were fed to the liquid-separation unit, and the
mixture was violently stirred at room temperature (25°C). After completion of the
stirring, the lower layer (alkali layer) was separated to give DIBK substantially
free of the acid component (acid component concentration: 0 ppm). The distribution
ratio of the DABCO contained in the organic phase to that in the aqueous phase
Concentration in the organic phase (weight%): Concentration in the aqueous
phase (weight%) = 1 : 0.08
Repeating the series of operations four times gave little or no influences
over the activity the oxidizing catalyst showed In the oxidation reactions (conversion:
91%, selectivity: 95%). That is, its activity was kept high.
Comparative Example 1
Except that a solvent containing 5,000 ppm of an acid component (acetic
acid) was used in the oxidation step, the same procedure was followed. Analysis
of the reaction mixture by gas chromatography showed that a conversion to be 29%
and a selectivity to be 81%.
Reference Example 1
97 g of the solvent In Example 1, recovered but not yet free of the
acid component, and 3 g of sodium hydroxide aqueous solution were mixed and stirred.
The distribution ratio of the contents of DABCO in the organic phase and the aqueous
phase were determined. The results are shown in Table 1.
As was obvious from Table 1, the higher the concentration of the
sodium hydroxide is, the lower the concentration of DABCO in the aqueous phase.
In contrast to the aqueous phase, the concentration of DABCO in the solvent becomes
A process for producing a ketoisophorone derivative, which comprises, in the
presence of an oxidizing catalyst, oxidizing a β-isophorone derivative represented
by the following formula (1):
wherein the groups R1 are the same or different, each representing
an alkyl group, a cycloalkyl group, an aryl group, or a heterocyclic group
in a solvent substantially free from acid component to form a ketoisophorone
derivative represented by the following formula (2):
wherein the groups R1 have the same meaning as defined above.
A process according to claim 1, wherein the amount of the acid component in
the solvent is 0 to 4,000 ppm (weight basis).
A process according to claim 1, wherein a solvent treated with an alkali is
used as the solvent.
A process according to claim 1, wherein the acid component is an organic carboxylic
A process according to claim 4, wherein the organic carboxylic acid is a C1-10aliphatic
A process according to claim 1, wherein the oxidizing catalyst is a complex
salt of a transition metal and an N,N'-disalicylidenediamne.
A process according to claim 6, wherein the transition metal is an element
of the Group 5 of the Periodic Table of Elements.
A process according to claim 1, which further employs a cyclic base as a co-catalyst.
A process according to claim 8, wherein the co-catalyst is a polycyclic compound
having a nitrogen atom at a bridgehead position.
A process according to claim 1, wherein the solvent is a ketone which is non-miscible
A process according to claim 1, wherein the reaction is conducted, in the presence
of an oxygen source, at a temperature lower than the flash point of the solvent.
A process according to claim 1, wherein an α-isophorone derivative shown
by the following formula (3):
wherein each R1 has the same meaning as defined above
is isomerized in the presence of an acid catalyst to form the β-isophorone
A process according to claim 1, which comprises removing the acid component
from the solvent separated from the reaction mixture, and recycling the resultant
solvent to the oxidation reaction of β-isophorone derivatives.
An apparatus for producing a ketoisophorone derivative, which comprises
a removing unit for removing an acid component in a solvent and
a reactor in which a β-isophorone represented by the following formula
wherein each R1 has the same meaning as defined above
is, in the presence of an oxidizing catalyst, oxidized in the solvent supplied
from the removing unit to form a ketoisophorone derivative represented by the
following formula (2):
wherein each R1 has the same meaning as defined above.