JPH09239275A - Catalyst for synthesizing imine compound and production of imine compound using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an imine compd., especially, an α, β-unsaturated imine compd. in good yield. SOLUTION: One or more kinds of a carbonyl compd. and ammonia or a primary amine are reacted in the presence of a catalyst composed of a compd. of an element selected from the group III elements, such as samarium iodide. By using at least one kind of a carbonyl compd. wherein a carbon atom at an α-position has two hydrogen atoms as the carbonyl compd., and α, β-unsaturated imine compd. can be obtained in good yield. The α, β-unsaturated imine compd. can also be obtained by reacting an imine compd. wherein a carbon atom at an α-position has two hydrogen atoms with the carbonyl compd. in the presence of the catalyst.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a catalyst for synthesizing an imine compound useful as an intermediate raw material for a physiologically active substance, and a method for producing an imine compound, particularly an α, β-unsaturated imine compound.

[0002]

2. Description of the Related Art Imine compounds are very useful compounds as carbonyl compound equivalents in synthetic chemistry. In particular, it is used as a derivative in which a carbonyl group of a carbonyl compound is protected, and as a raw material for synthesizing a nitrogen-containing compound.

Generally, an imine compound is produced by a dehydration condensation reaction between a carbonyl compound and ammonia or a primary amine, which is a complete equilibrium reaction,
Since it decomposes easily with a small amount of water, it is very difficult to take it out stably and in high yield. In addition, imine compounds are known to have imine-enamine tautomerism,
This equilibrium is often favorable to the enamine side. Therefore, in order to stably exist as an imine, a substrate-specific environment such as (1) no active α-hydrogen in the carbonyl compound or (2) the amine is a specific primary amine was prepared. Only when.

In recent years, attempts have been made to consider imine compounds as useful carbonyl compound equivalents and further chemically modify them. Specifically, it is an attempt to extend the carbon chain of the imine compound skeleton by further subjecting the imine compound to an aldol reaction with a carbonyl compound. The α, β-unsaturated imine compound obtained by this reaction is itself a direct raw material for a nitrogen-containing pharmacologically active substance, etc., and also Diels-Alder with an unsaturated hydrocarbon compound.
Through a cyclization reaction, a nitrogen-containing heterocyclic compound which is advantageous in synthesis can be derived. This nitrogen-containing heterocyclic compound is usually capable of regioselective introduction of functional groups, and therefore, in introducing various functional groups into desired positions of the nitrogen-containing heterocyclic compound,
The α, β-unsaturated imine compound is extremely useful.

As described above, the α, β-unsaturated imine compound is industrially and academically useful, but no effective production method has been found at present. As a slightly exemplified method, for example, when an imine compound and a ketone are reacted at a reaction temperature of −70 ° C. or lower in the presence of an alkaline earth metal catalyst, β-is produced through a corresponding aldol reaction. It has been reported that a hydroxyimine compound is produced (Angew. Chem. Int. Ed. Engl., 2, 68).
3 (1963); Tetrahedron Lett., 11 (197).
6); J. Am. Chem. Soc., 99, 7365 (197).
7)). But with these methods, in each case,
The yield of the β-hydroxyimine compound is low, and it is extremely difficult to induce the desired α, β-unsaturated imine compound. Therefore, the above method cannot be said to be an effective method for producing an α, β-unsaturated imine compound.

On the other hand, the present inventor has proposed an equilibrium advantageous amidation reaction for an ester compound having a simple structure.
It was carried out in the presence of a samarium catalyst, and it was found that amide compounds proceed with higher performance than ordinary Lewis acid catalysts (Proceedings of the 69th Annual Meeting of the Chemical Society of Japan, II, 3H).
534, 3H535, p. 1178, p. 1179).
That is, paying attention to the metal characteristic that a rare earth metal compound such as samarium is a metal species having a large redox potential,
In anticipation that rare earth metal compounds can be utilized for activation of ester compounds and amide compounds having relatively low activity, the above amidation reaction was investigated. As a result, in the amidation reaction between the ester compound and the amine compound,
Divalent samalocene-type complex [(C ₅ Me ₅ ) having a pentamethylcyclopentadienyl ligand having a high electron donating property
₂ Sm; (PMSm)] was used as a catalyst, the amidation proceeded with a better result than the usual Lewis acid catalyst. For example, ethyl acetate and an equimolar amount of octylamine were stirred at room temperature for 3 hours in the presence of 0.1 mol% of PMSm to obtain N-octylacetamide in a yield of 91%. When the same reaction was carried out with an aluminum compound which is a typical Lewis acid catalyst, N-octylacetamide was obtained in a yield of 66%, but the reaction solution was colored yellow, and the presence of multiple by-products was confirmed. It was This remarkable difference in activity was also observed in the amidation reaction of carbonate compounds and other ester compounds, and it was found that PMSm is a highly active catalyst in the amidation reaction of ester compounds and the like.

However, the use of the rare earth metal compound as a catalyst has been limited to amidation reaction and esterification reaction.

[0008]

SUMMARY OF THE INVENTION It is, therefore, an object of the present invention to provide a catalyst for synthesizing an imine compound, which can produce an imine compound in good yield, and a method for producing the imine compound.

The present invention also provides a versatile catalyst for synthesizing an imine compound, which can obtain a wide range of imine compounds, and a method for producing the imine compound.

Further, the present invention is to provide a catalyst for synthesizing an imine compound which can easily obtain an α, β-unsaturated imine compound in a high yield, and a method for producing the imine compound.

[0011]

The inventors of the present invention have made extensive studies in order to achieve the above object, and as a result, react the carbonyl compound with ammonia or a primary amine using a compound of the periodic table group 3 element as a catalyst. And (i) easily dehydration-condensation to produce a corresponding imine compound,
(Ii) When the imine compound has two hydrogen atoms at the α-position carbon atom, the α-position is activated by the catalyst despite its low chemical activity, The present inventors have completed the present invention by finding that the corresponding α, β-unsaturated imine compound can be obtained in good yield without the almine type reaction (dehydration condensation) progressing and the imine site being altered.

That is, the present invention is a catalyst for producing a corresponding imine compound by the reaction of a carbonyl compound with ammonia or a primary amine, which is an imine compound composed of a compound of Group 3 element of the periodic table. A catalyst for use is provided.

In the present invention, one or two carbonyl compounds are reacted with ammonia or a primary amine in the presence of a catalyst composed of an element compound of Group 3 of the periodic table,
Provided is a method for producing an imine compound to obtain a corresponding imine compound. In this method, as the carbonyl compound,
An α, β-unsaturated imine compound can be obtained by using at least one carbonyl compound having two hydrogen atoms at the α-position carbon atom. Further, in the above method, the carbonyl compound may be reacted with ammonia or a primary amine in the presence of an ester.

Further, the present invention is directed to reacting an imine compound having two hydrogen atoms at the α-position carbon atom with a carbonyl compound in the presence of a catalyst composed of a compound of Group 3 of the Periodic Table of Elements. A method for producing an imine compound for obtaining an α, β-unsaturated imine compound is provided.

[0015]

Embodiments of the present invention will be described below in detail. In the present specification, the “imine compound” is a corresponding “enamine compound” which is a tautomer.
Is used to mean that also includes.

The catalyst of the present invention is composed of a compound of Group 3 of the periodic table. Examples of the Group 3 elements in the periodic table include rare earth elements [eg, scandium, yttrium, lanthanoid series elements (lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium]. , Lutetium)], and actinide series elements (eg, actinium). Preferred Periodic Table Group 3 elements include
Rare earth elements such as scandium, yttrium, and lanthanoid series elements (samarium, gadolinium, ytterbium, etc.) are included. Especially samarium has a high catalytic activity.

In the periodic table group 3 element compound, periodic table 3
The valence of the group element is not particularly limited and is often divalent to tetravalent, particularly divalent or trivalent. The compound of Group 3 element of the periodic table is not particularly limited as long as it has catalytic activity, and it is a simple metal, an inorganic compound (halide, oxide, complex oxide, phosphorus compound, nitrogen compound, etc.) or an organic compound (organic acid, etc.). In many cases, it is a compound or complex with, and usually a hydroxide or oxyacid salt containing the above element, an organic acid salt, an inorganic acid salt, a halide, or a coordination compound (complex) containing the metal element. Often there is. The complex may be a π complex such as a metallocene compound. Further, the Group 3 element compound of the periodic table may be a composite metal compound with another metal. These catalysts may be used alone or in combination of two or more.

The catalyst component will be specifically described below by taking a samarium compound as an example, but other compounds of Group 3 element of the periodic table corresponding to the samarium compound can be effectively used. Hydroxides include, for example, samarium (II) hydroxide, samarium (III) hydroxide, and the like. Metal oxides include
For example, samarium oxide (II), samarium oxide (II
I) etc. are included. Examples of organic acid salts include organic carboxylic acids (monocarboxylic acids such as formic acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, propionic acid, butyric acid, valeric acid, naphthenic acid, stearic acid, oxalic acid, maleic acid, and the like. Carboxylic acid), oxycarboxylic acid (glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, etc.), thiocyanic acid, sulfonic acid (methanesulfonic acid, trichloromethanesulfonic acid, trifluromethanesulfonic acid, ethanesulfonic acid, etc.) Examples thereof include salts with organic acids such as sulfonic acid, benzenesulfonic acid, arylsulfonic acid such as p-toluenesulfonic acid, etc., and examples of inorganic acid salts include nitrates, sulfates, phosphates, carbonates, Perchlorate etc. are mentioned. Specific examples of the organic acid salt or the inorganic acid salt include, for example, samarium acetate (II), samarium acetate (III), and samarium trichloroacetate (I
I), Samarium (III) trichloroacetate, Samarium (II) trifluoroacetate, Samarium (III) trifluoroacetate, Samarium trifluoromethanesulfonate (I
I), samarium trifluoromethanesulfonate (II
I), samarium nitrate (II), samarium sulfate (II),
Examples include samarium (II) phosphate and samarium (II) carbonate. Halides include fluoride, chloride, bromide and iodide, and include, for example, samarium (II) iodide, samarium (III) iodide, samarium (II) bromide, samarium (III) bromide, chloride Examples include samarium (II) and samarium (III) chloride.

As the ligand forming the complex, an alkoxy group such as OH (hydroxo), methoxy, ethoxy, propoxy and butoxy groups, an acyl group such as acetyl and propionyl, an alkoxy group such as methoxycarbonyl (acetato) and ethoxycarbonyl. Carbonyl group, acetylacetonato, cyclopentadienyl, C _1-4 alkyl-substituted cyclopentadienyl (pentamethylcyclopentadienyl, etc.), chlorine, bromine and other halogen atoms, CO, C
N, oxygen atom, H ₂ O (aco), phosphine (for example,
Phosphorus compounds such as triarylphosphines such as triphenylphosphine), NH ₃ (ammine), NO, N
Examples thereof include nitrogen-containing compounds such as O ₂ (nitro), NO ₃ (nitrato), ethylenediamine, diethylenetriamine, pyridine, and phenanthroline. In the complex or complex salt, the same or different ligands may be coordinated by one kind or two or more kinds. The ligand in the preferred complex is
For example, OH, alkoxy group, acyl group, alkoxycarbonyl group, acetylacetonato, cyclopentadienyl, C _1-2 alkyl-substituted cyclopentadienyl, halogen atom, CO, CN, H ₂ O (aco), triphenyl Phosphine and other phosphorus compounds, NH ₃ , NO ₂ , NO ₃
In many cases, it is a nitrogen-containing compound including, for example, diacetylacetonatosamarium (II) and triacetylacetonatosamarium (II
I), dicyclopentadienyl samarium (II), tricyclopentadienyl samarium (III), dipentamethylcyclopentadienyl samarium (II), tripentamethylcyclopentadienyl samarium (III), etc. .

The catalyst composed of the compound of Group 3 of the periodic table may be a homogeneous system or a heterogeneous system.
Further, the catalyst may be a solid catalyst in which a carrier carries a catalyst component composed of a compound of Group 3 of the periodic table. As the carrier, a porous carrier such as activated carbon, zeolite, silica, silica-alumina and bentonite is often used. The supported amount of the catalyst component in the solid catalyst is 100
0.1 to 50 parts by weight of Group 3 compound of the periodic table, preferably 0.5 to 30 parts by weight, more preferably 1 to 30 parts by weight.
It is about 20 parts by weight.

The catalyst of the present invention is useful as a catalyst for an imination reaction of a carbonyl compound and an aldol-type dehydration condensation reaction between an imine compound produced by the reaction and a carbonyl compound.

In the present invention, the carbonyl compound may be an aldehyde such as an aliphatic saturated aldehyde, an aliphatic unsaturated aldehyde, a non-aromatic carbocyclic aldehyde, an aromatic aldehyde or a heterocyclic aldehyde; an aliphatic saturated ketone, A wide variety of organic carbonyl compounds can be used, such as aliphatic unsaturated ketones, alicyclic ketones, aromatic ketones, and heterocyclic ketones. The carbonyl compound may have a plurality of carbonyl groups in the molecule.

The carbonyl compound may be a carbonyl compound having two hydrogen atoms at the α-position carbon atom, such as the general formula (I) R ¹ CH ₂ COR ² (I) [in the formula, R ¹ and R ² Are the same or different and represent a non-reactive atom or an organic group, and R ¹ and R ² may combine with each other to form a ring].

The non-reactive atom or organic group represented by R ¹ is a hydrogen atom, a halogen atom, an alkyl group,
Examples thereof include an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, a heterocyclic group, an alkoxy group and a carboxyl group.

The halogen atom includes fluorine, chlorine, bromine and iodine atoms. As the alkyl group, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tetradecyl,
1 to 18 carbon atoms such as octadecyl (preferably 1 to 1)
Alkyl groups of about 0, especially about 1 to 6) are included. As alkenyl groups, vinyl, allyl, 1-butenyl, 2
Examples thereof include alkenyl groups having about 2 to 18 carbon atoms (preferably 2 to 10, particularly 2 to 6) such as -hexenyl and 3-decyl. Examples of the alkynyl group include alkynyl groups having about 2 to 18 carbon atoms (preferably 2 to 10, particularly 2 to 6) such as ethynyl, 1-propynyl and 1-heptynyl groups.

The cycloalkyl group includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
3 to 8 carbon atoms such as cyclooctyl group (preferably 3 to 8 carbon atoms)
6, especially about 5-6) cycloalkyl groups and the like are included. Examples of the aryl group include aryl groups having about 6 to 14 carbon atoms such as phenyl and naphthyl groups.

The heterocyclic ring corresponding to the above-mentioned heterocyclic group is, for example, a heterocyclic ring containing an oxygen atom as a hetero atom (for example,
5-membered ring such as furan, oxazole, isoxazole, and tetrahydrofuran, 6-membered ring such as pyran, benzofuran, isobenzofuran, dibenzofuran, xanthone, xanthene, condensed ring such as chroman, isochroman, and chromene), and sulfur atom as a hetero atom Heterocycles (eg thiophene, thiazole, isothiazole,
Thiadiazole, benzothiophene, etc.), heterocycles containing a nitrogen atom as a hetero atom (eg, 5-membered ring such as pyrrole, pyrazole, imidazole, triazole, pyrrolidine, etc., 6-membered ring such as pyridine, pyridazine, pyrimidine, pyrazine, piperidine, morpholine, etc. , Indole, indolene, isoindole, indazole, indoline, isoindoline, quinoline, isoquinoline, quinoline quinoline, quinoxaline, quinazoline, phthalazine, purine, carbazole, acridine, naphthoquinoline, phenanthrazine, phenanthroline, naphthyridine, benzoquinoline, phenoxazine, Condensed rings such as phthalocyanine and anthracyanine).

Examples of the alkoxy group include alkoxy groups having about 1 to 10 (preferably 1 to 6) carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy and hexyloxy groups.

These non-reactive atoms or organic groups may have various substituents as long as the reaction is not impaired. For example, the substituent that the alkyl group, alkenyl group, and alkynyl group may have include a halogen atom, a hydroxyl group, a cyano group, and a cycloalkyl group (for example, a cyclohexyl group or other cycloalkyl group having about 3 to 8 carbon atoms). Alkyl group), an aryl group (for example, an aryl group having about 6 to 14 carbon atoms such as phenyl and naphthyl groups),
A heterocyclic group (for example, 2-furyl, 2-thienyl, 3-pyridyl, piperidino group, or the like, which has about 1 to 3 heteroatoms of at least one kind selected from oxygen atom, sulfur atom and nitrogen atom) 5 A 6-membered heterocyclic group or a condensed heterocycle in which a benzene ring or the like is condensed), an alkoxy group (for example, an alkoxy group having about 1 to 10 carbon atoms such as methoxy or ethoxy group), an aryloxy group (for example, Phenyloxy, naphthyloxy groups and other C6-14 aryl groups, etc.), amino groups, substituted amino groups (for example, di-C _1-6 alkyl-substituted amino groups such as dimethylamino groups), carboxyl groups, Alkoxycarbonyl groups (eg, alkoxycarbonyl groups having about 2 to 7 carbon atoms such as methoxycarbonyl and ethoxycarbonyl groups), sulfinyl groups, sulfur Examples include a sulfonyl group and the like. Further, as the substituent that the cycloalkyl group, aryl group, or heterocyclic group may have, in addition to the substituent that the alkyl group or the like may have, a nitro group, or a carbon number of about 1 to 6 And an alkenyl group having about 2 to 6 carbon atoms, an alkynyl group having about 2 to 6 carbon atoms, a halogenated alkyl group (for example, a trifluoromethyl group, etc.) and the like.

The non-reactive atom or organic group represented by R ² is a hydrogen atom, an alkyl group, an alkenyl group,
Examples thereof include an alkynyl group, a cycloalkyl group, an aryl group and a heterocyclic group. Examples of the alkyl group, alkenyl group, alkynyl group, cycloalkyl group, aryl group and heterocyclic group are the same as those for R ¹ .

Examples of compounds in which R ¹ and R ² are bonded to each other to form a ring include cyclobutanone, cyclopentanone, cyclohexanone, cyclododecanone, and other alicyclic ketones having about 3 to 15 carbon atoms. .

Examples of the carbonyl compound having two hydrogen atoms at the α-position carbon atom include compounds represented by the general formula (I), and compounds having a plurality of carbonyl groups in the molecule. Such compounds include the compounds of formula (I) in which R ¹ is an acyl group. The acyl group includes formyl, acetyl,
Propionyl, butyryl, isobutyryl, valeryl, acryloyl, cyclohexanecarbonyl, benzoyl and other aliphatic, alicyclic or aromatic acyl groups having about 1 to 10 carbon atoms; nicotinoyl and other oxygen, sulfur and nitrogen atoms A 5- or 6-membered heterocyclic group having 1 to 3 selected at least one kind of hetero atom or a heterocyclic acyl group having a condensed hetero ring in which a benzene ring or the like is condensed is included.

As the carbonyl compound having two hydrogen atoms at the α-position carbon atom, preferred aldehydes are acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, pentanal, 3
-Methyl butanal, hexanal, heptanal, octanal, decanal, undecanal, dodecanal, tetradecanal, octadecanal and the like saturated aliphatic aldehydes having 2 to 20 carbon atoms (preferably 2 to 10, particularly 2 to 8) A carbon number of 4 to 20, such as 3-butenal or 3-octenal (preferably 4 to 10, particularly 4)
~ 8) aliphatic unsaturated aldehyde; phenylacetaldehyde, 3-phenylpropanal, etc. having 8 carbon atoms
~ 15 (preferably 8-11) aromatic aldehyde; 2-furylacetaldehyde, 2-thienylacetaldehyde, 2-pyridylacetaldehyde, 3-pyridylacetaldehyde, 4-pyridylacetaldehyde, 3- (2-quinolyl) propanal, etc. Of at least one selected from oxygen atom, sulfur atom and nitrogen atom
Examples thereof include heterocyclic aldehydes having a 5- or 6-membered heterocycle having about 1 to 3 heteroatoms or a condensed heterocycle in which a benzene ring or the like is condensed.

As the above-mentioned carbonyl compound, preferable ketones are acetone, methyl ethyl ketone, methyl propyl ketone, methyl isopropyl ketone, methyl butyl ketone, methyl isobutyl ketone, methyl pentyl ketone, methyl isopentyl ketone and the like having 3 to 15 carbon atoms.
(Preferably 3 to 10, particularly 3 to 8) aliphatic saturated ketone; methyl vinyl ketone, mesityl oxide, methyl heptenone and other aliphatic unsaturated ketones having about 4 to 15 carbon atoms; cyclobutanone, cyclopentanone, cyclohexanone A cycloaliphatic ketone having about 3 to 15 carbon atoms (preferably 4 to 12, particularly 5 to 6) such as cyclododecanone; carbon such as acetophenone, propiophenone, butyrophenone, valerophenone, dibenzyl ketone, and 2-acetonaphthone. Aromatic ketone having a number of about 8 to 18 (preferably 8 to 15, particularly 8 to 12); acetothienone, 2
-At least one heteroatom selected from oxygen atom, sulfur atom and nitrogen atom, such as acetofuron, 2-acetylpyridine, 3-acetylpyridine, 3-propionylpyridine, 4-acetylpyridine and 3-acetylquinoline. Examples of the heterocyclic ketone include a 5- to 6-membered heterocycle having about 3 to 3 or a condensed heterocycle in which a benzene ring or the like is condensed.

Particularly preferable carbonyl compounds as the carbonyl compound include aliphatic saturated aldehydes having about 2 to 10 carbon atoms such as propionaldehyde and butyraldehyde; and 8 to 8 carbon atoms such as phenylacetaldehyde.
About 11 aromatic aldehydes; saturated aliphatic ketones having about 3 to 10 carbon atoms such as acetone and methyl ethyl ketone;
Cyclopentanone, cyclohexanone, cyclododecanone, and other alicyclic ketones having about 4 to 12 carbon atoms; acetophenone, propiophenone, and other aromatic ketones having about 8 to 15 carbon atoms, and the like are included.

In the production method of the present invention, two kinds of carbonyl compounds may be used. When two kinds of carbonyl compounds are used, the first carbonyl compound which reacts with ammonia or a primary amine and the second carbonyl compound which reacts with an imine compound produced by dehydration condensation are different due to the difference in reactivity. Therefore, by combining two kinds of carbonyl compounds, α, β-unsaturated imine compounds having various skeletons can be obtained.

When two kinds of carbonyl compounds are used, for example, the carbonyl compound represented by the general formula (I) and the general formula (IV) R ⁴ COR ⁵ (IV) [wherein R ⁴ and R ⁵ are the same. Or differently, it represents a non-reactive atom or an organic group, and R ⁴ and R ⁵ may combine with each other to form a ring].

As R ⁴ and R ⁵ , the atoms or organic groups exemplified for R ² can be used, as long as they are different from the carbonyl compound represented by the formula (I).

The compound represented by the general formula (IV) includes, in addition to the carbonyl compound represented by the general formula (I), a carbonyl compound having no hydrogen atom at the α-position carbon atom or having one hydrogen atom. Compounds. Among such carbonyl compounds, aldehydes include, for example, 2-methylpropanal, 2-methylbutanal and the like having 2 to 20 carbon atoms (preferably 2 to 10, particularly 2 to 2) having a branched chain at the α-position. About 8) Aliphatic saturated aldehyde; α, β-unsaturated aldehyde having about 3 to 20 (preferably 3 to 10) carbon atoms such as acryl aldehyde and cinnamaldehyde; aryl formyl group such as benzaldehyde and tolualdehyde An aromatic aldehyde having a carbon number of about 8 to 15 (preferably 8 to 11) directly bonded to; an oxygen atom, a sulfur atom and an oxygen atom such as 2-furancarbaldehyde, 2-thiophenecarbaldehyde, and 3-pyridinecarbaldehyde. A 5- or 6-membered heterocycle having about 1 to 3 at least one heteroatom selected from nitrogen atoms, or a benzene ring Fused heterocyclic ring down ring and fused are mentioned heterocyclic aldehydes such as directly bonded to a formyl group.

Among the carbonyl compounds having no hydrogen atom at the carbon atom at the α-position or having one hydrogen atom, the ketone is branched to the α-position and α'-position of the carbonyl group such as diisopropyl ketone. 3 to 3 carbon atoms with a chain
Aliphatic saturated ketone of about 15 (preferably 3 to 10, especially 3 to 8); α, β- and α ', β'-uncontaining about 5 to 15 (preferably 5 to 10) carbon atoms such as divinyl ketone. Saturated ketone; carbon number 7 to 15 in which two cycloalkyl groups are bonded to a carbonyl group, such as dicyclohexyl ketone
Alicyclic ketone of about 7 to 12 (preferably 7 to 12); aromatic ketone having 13 to 18 carbon atoms in which two aryl groups are bonded to a carbonyl group such as diphenyl ketone; di (3
At least one heteroatom selected from oxygen atom, sulfur atom and nitrogen atom, such as -pyridyl) ketone.
Examples include a 5- or 6-membered heterocyclic ring having about 3 to 3 or a heterocyclic ketone in which two condensed heterocyclic rings in which a benzene ring or the like is condensed are bonded to a carbonyl group.

In the present invention, examples of the primary amine include saturated aliphatic amine, unsaturated aliphatic amine, alicyclic amine, aromatic amine, heterocyclic amine, hydroxylamine or its derivative, hydrazine or its derivative. A wide variety of primary amines such as can be used. The primary amine may have a plurality of primary amino groups in the molecule.

The ammonia or the primary amine used in the present invention is a compound represented by the general formula (II) R ³ NH 2 (II) [wherein R ³ represents a non-reactive atom or an organic group]. Is included.

The non-reactive atom or organic group represented by R ³ is a hydrogen atom, an alkyl group, an alkenyl group,
Examples thereof include an alkynyl group, a cycloalkyl group, an aryl group, a heterocyclic group, an alkoxy group, a hydroxyl group and a substituted amino group. Examples of these groups include the groups exemplified in the above description of R ¹ . Also, these groups
It may have various substituents as long as the reaction is not impaired. As such a substituent, for example, those mentioned above can be used.

Preferred amines as the primary amine include methylamine, ethylmine, propylamine, isopropylamine, butylamine, isobutylamine,
s-butylamine, t-butylamine, pentylamine, isopentylamine, neopentylamine, t-pentylamine, hexylamine, isohexylamine,
Heptylamine, octylamine, 2-ethylhexylamine, nonylamine, decylamine, monoethanolamine, and other aliphatic saturated amines having about 1 to 15 (preferably 1 to 10) carbon atoms; allylamine, 3-butenylamine, and other carbon atoms having 2 to 2 carbon atoms 15 (preferably 2 to 10) aliphatic unsaturated amines; alicyclic amines having about 3 to 8 (preferably 3 to 6) carbon atoms such as cyclopropylamine, cyclobutylamine, cyclopentylamine, cyclohexylamine; Arylamines having about 6 to 14 carbon atoms such as aniline, toluidine, xylidine, anisidine, α-naphthylamine, β-naphthylamine, benzylamine, 2-methylbenzylamine, 4-chlorobenzylamine, 3-methoxybenzylamine, 2- Phenylethylamine, 3-phen Aromatic amines such as aralkylamines having about 7 to 15 carbon atoms such as nylpropylamine and 4-phenylbutylamine; from oxygen atoms, sulfur atoms and nitrogen atoms such as 2-aminofuran, 2-aminothiophene and 3-aminopyridine. Heterocyclic amine having a 5- or 6-membered heterocyclic ring having 1 to 3 selected at least one kind of hetero atom or a condensed heterocyclic ring in which a benzene ring or the like is condensed; hydroxylamine; N-methylhydrazine, etc. Substituted hydrazines; alkoxyamines having about 1 to 10 carbon atoms such as methoxyamine and ethoxyamine.

Particularly preferred primary amines are aliphatic saturated amines having about 1 to 10 carbon atoms such as propylamine and butylamine; aliphatic unsaturated amines having about 2 to 10 carbon atoms such as allylamine; carbons such as aniline. Number 6-10
Approximate arylamines; aralkylamines having about 7 to 11 carbon atoms such as 2-phenylethylamine are included.

In the present invention, as the imine compound having two hydrogen atoms at the α-position carbon atom, the carbonyl compound having two hydrogen atoms at the α-position carbon atom, and the ammonia or primary amine The corresponding imine compound formed by dehydration condensation of

Such imine compounds have the general formula (V
I) R ¹ CH ₂ C (R ² ) ═NR ³ (VI) [wherein R ¹ , R ² and R ³ are the same or different and represent a non-reactive atom or an organic group, and R ¹ and R ² may combine with each other to form a ring]. Examples of R ¹ , R ² and R ³ include the groups described above. Preferred imine compounds include imines formed from the preferred carbonyl compounds (aldehydes and ketones) and the preferred amines.

In the method of the present invention, an imine compound is obtained by reacting a carbonyl compound with ammonia or a primary amine in the presence of a catalyst composed of the group 3 element compound of the periodic table. In particular, when a carbonyl compound having two hydrogen atoms at the carbon atom at the α-position of the carbonyl group is used as the carbonyl compound, an α, β-unsaturated imine compound is produced. This is because the corresponding imine compound is produced by dehydration condensation of the carbonyl group of the carbonyl compound and the amino group of ammonia or the primary amine, and the carbonyl compound has two hydrogen atoms at the α-position carbon atom. In this case, aldol-type dehydration condensation with another molecule of the carbonyl compound occurs at the α-position of the imine compound thus produced, and the corresponding α,
It is considered that a β-unsaturated imine compound is produced.

For example, when the carbonyl compound represented by the general formula (I) is reacted with the ammonia or the primary amine represented by the general formula (II), the reaction is considered to proceed as follows. In the formula, R ^{1 to} R ³ have the same meanings as described above.

[0050] In addition, two kinds of carbonyl compounds, for example, the general formula (I)
When the carbonyl compound represented by and the carbonyl compound represented by the general formula (IV) are reacted with ammonia or a primary amine represented by the general formula (II), for example,
The following reaction produces the corresponding α, β-unsaturated imine compound. In the formula, R ^{1 to} R ⁵ have the same meanings as described above.

[0051] In this case, the carbonyl compound represented by the general formula (IV) does not have a hydrogen atom at the α-position carbon atom, or 1
A carbonyl compound having a number of hydrogen atoms, particularly a carbonyl compound having no hydrogen atom at the carbon atom at the α-position of the carbonyl group, or a carbonyl compound represented by the general formula (I) When the carbonyl compound having low reactivity is used, the α, β-unsaturated imine compound represented by the general formula (V) can be obtained in high yield.

In the method of the present invention, the reaction of the carbonyl compound with ammonia or the primary amine can be carried out without a solvent, but it is usually carried out in an organic solvent. The organic solvent is not particularly limited as long as it does not impair the reaction.

As the solvent, for example, aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene; carbon tetrachloride, chloroform, dichloromethane, 1,
Halogenated hydrocarbons such as 2-dichloroethane; Aliphatic hydrocarbons such as pentane, hexane, heptane, octane; Alicyclic hydrocarbons such as cyclohexane and methylcyclohexane; Diethyl ether, dibutyl ether, ethylene glycol dimethyl ether, dioxane , Ethers such as tetrahydrofuran; esters such as ethyl acetate; aprotic polar solvents such as acetonitrile, N, N-dimethylformamide, dimethylsulfoxide, and the like. Among these, cyclic ethers such as dioxane and tetrahydrofuran;
Polar solvents such as aprotic polar solvents such as N, N-dimethylformamide and dimethylsulfoxide are preferred.

The amount of the carbonyl compound used is not particularly limited, but is, for example, 0.8 mol or more (about 0.8 to 5 mol), preferably 1 mol or more (for example, 1 mol or more relative to 1 mol of ammonia or the primary amine. 1 to 2.5 mol), and more preferably 1 to 2.5 mol. When a carbonyl compound having two hydrogen atoms at the α-position carbon atom is used as the carbonyl compound and an α, β-unsaturated imine compound is the target, the amount of the carbonyl compound used is ammonia or 1.5 mol or more (for example, about 1.5 to 5 mol) per 1 mol of the primary amine,
Preferably 1.8 to 3 mol (for example, about 2 to 3 mol),
More preferably, it is about 2 to 2.5 mol.

The amount of the group 3 element compound used in the periodic table is, for example, 0.1 to 100 relative to ammonia or the primary amine.
Mol%, preferably 0.5 to 50 mol%, more preferably 1 to 25 mol%.

The reaction temperature is, for example, -10 to 120 ° C, preferably 0 to 100 ° C, more preferably 10 to 50 ° C.
It is a degree. The reaction can be carried out under any conditions of normal pressure, reduced pressure and increased pressure.

In the above reaction, when a carbonyl compound having two hydrogen atoms at the α-position carbon atom is used as the carbonyl compound, an ester may be present in the reaction system. When the reaction is carried out in the presence of the ester, the effect of the ester temporarily trapping ammonia or a primary amine or the like may give an equilibrium to the product side, or
The yield of the α, β-unsaturated imine compound is significantly improved.

Examples of such esters include methyl formate, ethyl formate, propyl formate, isopropyl formate, butyl formate, isobutyl formate, s-butyl formate, pentyl formate, isopentyl formate, neopentyl formate, hexyl formate, isohexyl formate, Formic acid esters such as heptyl formate, octyl formate, 2-ethylhexyl formate, nonyl formate, decyl formate, cyclohexyl formate and the like; and acetic acid, propionic acid, butyric acid, isobutyric acid, which correspond to the formate ester. Examples thereof include valeric acid, isovaleric acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, and dodecanoic acid. These esters may contain a general substituent such as a cyano group, an acyl group, a carboxyl group and a halogen atom. Examples of the acyl group include those mentioned above.

Preferred esters include formic acid esters, especially formic acid C _1-12 alkyl esters (eg formic acid C _1-8).
Alkyl ester), or formic acid C _3-6 cycloalkyl ester and the like.

The amount of the ester used is, for example, 0.2 to 3 moles, preferably 0.5 to 2 moles, and more preferably 0.1 to 1 mole of ammonia or a primary amine.
It is about 8 to 1.5 mol.

In the reaction system, acids that are usually used as catalysts for the dehydration condensation reaction (for example, mineral acids such as sulfuric acid, sulfonic acids such as p-toluenesulfonic acid, acetic acid, etc.) within a range that does not inhibit the reaction. Organic acid, etc.) may be added. Further, in order to favor the equilibrium on the product side, the reaction may be carried out while distilling off water by-produced by azeotropic distillation or the like. In this case, it is preferable to use a high boiling point solvent or an azeotropic solvent as the solvent. Further, in order to trap water produced as a by-product, a dehydrating agent such as molecular sieve may be added to the reaction system.

In the method of the present invention, when an imine compound having two hydrogen atoms at the α-position carbon atom is reacted with a carbonyl compound in the presence of a catalyst composed of the group 3 element compound of the periodic table, the imine compound is reacted. At the α position of the compound,
Aldol-type dehydration condensation occurs with carbonyl compounds,
The corresponding α, β-unsaturated imine compound is formed.

For example, when an imine compound represented by the general formula (VI) is reacted with a carbonyl compound represented by the general formula (IV), the reaction is considered to proceed as follows. In the formula, R ^{1 to} R ⁵ have the same meanings as described above.

[0064] The imine compound used as a raw material can be obtained by a conventional method, for example, a dehydration condensation reaction between a corresponding carbonyl compound and ammonia or a primary amine. Further, this imine compound can also be produced using the catalyst of the present invention, as described above.

The reaction of the imine compound with the carbonyl compound can be carried out under the same conditions as the reaction of the carbonyl compound with ammonia or a primary amine. The amount of the carbonyl compound used is not particularly limited, but is, for example, 0.8 mol or more (about 0.8 to 5 mol), preferably 0.9 to 2 mol, relative to 1 mol of the imine compound.
More preferably, it is about 1 to 1.5 mol. Also in this system, by adding the ester,
The yield can be significantly improved.

The imine compound thus obtained can be isolated by a conventional separation and purification means such as extraction, distillation, crystallization, recrystallization, column chromatography and the like.

[0067]

INDUSTRIAL APPLICABILITY According to the catalyst for imine synthesis and the method for producing an imine compound of the present invention, the imine compound can be produced in a good yield under mild conditions. Moreover, a wide range of imine compounds can be obtained, and the versatility is excellent.

Furthermore, an industrially important α, β-unsaturated imine compound can be obtained easily and in good yield.

[0069]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited thereto.

Example 1 A mixture of 1.46 g (20 mmol) of n-butylamine, 0.81 g (2 mmol) of samarium (II) iodide and 2.92 g (40 mmol) of n-butyraldehyde was added together with 5 ml of tetrahydrofuran (THF) at 25 ° C. In 3
Stirred for hours. When the reaction liquid was analyzed by gas chromatography, N- (2-ethyl-2-hexenylidene) butylamine was obtained in a yield of 87% (based on n-butylamine).

Example 2 1.46 g (20 mmol) of n-butylamine, 0.81 g (2 mmol) of samarium (II) iodide, 1.46 g (20 mmol) of n-butyraldehyde, 1.76 g (20 mmol) of n-propyl formate. A mixture of THF5
Stirred with ml at 25 ° C. for 3 hours. When the reaction liquid was analyzed by gas chromatography, the yield of N- (2-ethyl-2-hexenylidene) butylamine was 97%.
(N-butylamine standard).

Example 3 1.46 g (20 mmol) of n-butylamine, 1.02 g (2 mmo) of ytterbium triflate (III)
l), n-butyraldehyde 2.92 g (40 mmo
The mixture of l) was stirred with 5 ml of THF at 25 ° C. for 3 hours. When the reaction solution was analyzed by gas chromatography, N- (2-ethyl-2-hexenylidene) butylamine was obtained with a yield of 84% (n-butylamine standard).

Example 4 1.46 g (20 mmol) of n-butylamine, 0.98 g (2 mmol) of samarium triflate (III),
A mixture of 2.92 g (40 mmol) of n-butyraldehyde was stirred with 5 ml of THF at 25 ° C. for 3 hours.
When the reaction solution was analyzed by gas chromatography, N- (2-ethyl-2-hexenylidene) butylamine was obtained with a yield of 83% (based on n-butylamine).

Example 5 1.46 g (20 mmol) of n-butylamine, 0.77 g (2 mmo) of scandium triflate (III)
l), n-butyraldehyde 2.92 g (40 mmo
The mixture of l) was stirred with 5 ml of THF at 25 ° C. for 3 hours. When the reaction liquid was analyzed by gas chromatography, N- (2-ethyl-2-hexenylidene) butylamine was obtained in a yield of 75% (based on n-butylamine).

Example 6 2.54 g (20 mmo) of N-butylidene butylamine
l), 0.81 g of samarium (II) iodide (2 mmo
l), n-butyraldehyde 1.46 g (20 mmo
The mixture of l) was stirred with 10 ml of THF at 25 ° C. for 3 hours. When the reaction liquid was analyzed by gas chromatography, N- (2-ethyl-2-hexenylidene) was obtained.
Butylamine was obtained with a yield of 42%.

Example 7 Example 6 was repeated except that 0.98 g (2 mmol) of neodymium triflate was used instead of samarium (II) iodide.
The same operation as described above was performed. When the reaction solution was analyzed by gas chromatography, N- (2-ethyl-2-hexenylidene) butylamine was obtained in a yield of 28%.

Example 8 N-butylidenebutylamine 2.54 g (20 mmo)
l), 0.81 g of samarium (II) iodide (2 mmo
l), n-butyraldehyde 1.46 g (20 mmo
A mixture of 1) and n-hexyl formate (2.6 g, 20 mmol) was stirred with 10 ml of THF at 25 ° C. for 3 hours. When the reaction liquid was analyzed by gas chromatography, N- (2-ethyl-2-hexenylidene) butylamine was obtained with a yield of 90%.

Example 9 The same operation as in Example 6 was carried out except that 1.06 g (2 mmol) of samarium (III) iodide was used instead of samarium (II) iodide. When the reaction liquid was analyzed by gas chromatography, N- (2-ethyl-2-
Hexenylidene) butylamine was obtained with a yield of 99%.

Claims (11)

[Claims] 1. A catalyst for producing a corresponding imine compound by the reaction of a carbonyl compound and ammonia or a primary amine, which is a catalyst for synthesizing an imine compound composed of a compound of Group 3 element of the periodic table. 2. The catalyst for synthesizing an imine compound according to claim 1, wherein the compound of Group 3 element of the periodic table is a rare earth element compound. 3. The catalyst for synthesizing an imine compound according to claim 2, wherein the rare earth element compound is a compound containing at least one element selected from the group consisting of scandium, ytteribium, gadolinium and samarium. 4. The catalyst for synthesizing an imine compound according to claim 2, wherein the rare earth element compound is a divalent or trivalent samarium compound. 5. An imine compound which is obtained by reacting one or two carbonyl compounds with ammonia or a primary amine in the presence of a catalyst composed of a compound of Group 3 element of the periodic table to obtain a corresponding imine compound. Manufacturing method. 6. A carbonyl compound having at least one carbonyl compound having two hydrogen atoms at the α-position carbon atom is reacted with ammonia or a primary amine to give an α, β-unsaturated imine compound. The method for producing the imine compound according to claim 5, which is obtained. 7. A compound represented by the general formula (I) R ¹ CH ₂ COR ² (I), wherein R ¹ and R ² are the same or different and each represents a non-reactive atom or an organic group, and R ¹ and R 2 ² may combine with each other to form a ring], and a carbonyl compound represented by the general formula (II) R ³ NH ₂ (II) [wherein R ³ is a non-reactive atom or an organic compound]. A group represented by the formula] is reacted with ammonia or a primary amine to give a compound represented by the general formula (III) R ¹ CH ₂ C (R ² ) ═C (R ¹ ) —C (R ² ) ═NR ³ (III The method for producing an imine compound according to claim 6, wherein an α, β-unsaturated imine compound represented by the formula: wherein R ¹ , R ² and R ³ are the same as above. 8. A carbonyl compound as general formula (I) R ¹ CH ₂ COR ² (I) [wherein R ¹ and R ² are the same or different and each represents a non-reactive atom or an organic group, R ¹ and R ² may combine with each other to form a ring] and a carbonyl compound represented by the general formula (IV) R ⁴ COR ⁵ (IV) [wherein R ⁴ and R ⁵ are The same or different and each represents a non-reactive atom or an organic group, and R ⁴ and R ⁵ may combine with each other to form a ring], and a carbonyl compound represented by the general formula (II) R ³ NH ₂ (II) [wherein R ³ represents a non-reactive atom or an organic group] and is reacted with ammonia or a primary amine,
Formula ^{(V) R 4 C (R} 5) = C (R 1) -C (R 2) = NR 3 (V) [ ^{wherein, R 1, R 2, R} 3, R 4, R 5 are the Same as]
The method for producing an imine compound according to claim 6, wherein the α, β-unsaturated imine compound represented by: is obtained. 9. The method according to claim 6, wherein the reaction is carried out in the presence of an ester.
A method for producing the described imine compound. 10. An imine compound having two hydrogen atoms at the α-position carbon atom is reacted with a carbonyl compound in the presence of a catalyst composed of a compound of Group 3 element of the periodic table,
A method for producing an imine compound to obtain a corresponding α, β-unsaturated imine compound. 11. A compound represented by the general formula (VI) R ¹ CH ₂ C (R ² ) ═NR ³ (VI), wherein R ¹ , R ² and R ³ are the same or different and are non-reactive atoms or And an imine compound represented by the formula, wherein R ¹ and R ² may be bonded to each other to form a ring] and a general formula (IV) R ⁴ COR ⁵ (IV) [in the formula, R ⁴ , R ⁵ are the same or different and each represents a non-reactive atom or organic group, and R ⁴ and R ⁵ may be bonded to each other to form a ring]. General formula (V) R ⁴ C (R ⁵ ) = C (R ¹ ) −C (R ² ) = NR ³ (V) [wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ Is the same as above]
The method for producing an imine compound according to claim 10, wherein an α, β-unsaturated imine compound represented by: is obtained.