JPH09255601A - Production of 2,6-di-tert-alkylcyclohexanol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To safely produce 2,6-di-tert-alkylcyclohexanol useful as a synthetic intermediate for a coupler for color photography, and as a raw material for photograph such as a dispersion medium for photograph, a solvent, an intermediate for a dye and a synthetic intermediate for a drug and an agrochemical at a low cost on a large scale. SOLUTION: This 2,6-di-tert-alkylcyclohexanol is expressed by formula I [R and R' are each a tert-alkyl; X is a substituent; (n) is an integer of 0-3], and 2,6-di-tert-butyl-4-methylcyclohexanol as cited as an example. A compound of formula I is obtained by reducing 2,6-di-tert-alkylcyclohexanone of formula II with sodium borohydride in the presence of a metal salt (e.g. magnesium chloride) expressed by the formula MYm M is an alkali metal [when (m)=1], an alkaline earth metal [when (m)=2] or a typical metal [when (m)=3]; Y is a halogen} in a solvent such as diglyme.

Description

Detailed Description of the Invention

[0001]

The present invention is useful as a photographic material such as a synthetic intermediate for a color photographic coupler and a photographic dispersion medium, and as a solvent, a dye intermediate, a synthetic intermediate for a pharmaceutical or an agricultural chemical. The present invention relates to a method for producing 2,6-di-tert-alkylcyclohexanols.

[0002]

2. Description of the Related Art In recent years, couplers used in silver halide color photographic light-sensitive materials are required to have higher performance. For example, good coloring hue, high coupling activity, good stability of the resulting dye to the components of the fixer or bleach-fixer, and that the color density does not change even if the composition of these processing solutions changes. , Excellent color image fastness after processing (fastness in low density region and fastness in high density region) in a well-balanced manner.
The inventors of the present invention have diligently studied for the above problems,
In the pyrroloazole-based coupler, it was found that the above performance is excellent by the coupler having cycloalkoxycarbonyl groups having bulky substituents at both ortho positions introduced into the pyrroloazole ring. The pyrroloazole coupler having a bulky cycloalkoxycarbonyl group at both ortho positions is produced from the starting cyclic alcohols having bulky substituents at both ortho positions.

There are 2,6-di-tert-alkylcyclohexanols as cyclic alcohols having bulky substituents at both ortho positions.
Examples of the synthesis of rt-alkylcyclohexanols include Journal of American Chem.
Ial Society Volume 79 5019-502
3 (1957) describes a method of obtaining 2,6-di-tert-butylcyclohexanol by reducing 2,6-di-tert-butylcyclohexanone with lithium aluminum hydride. However, with this method, reduction with lithium aluminum hydride is essential, and it is unsuitable for mass supply in terms of price and safety. Further, catalytic hydrogenation of 2,6-di-tert-alkylphenols in the presence of a rhodium or ruthenium catalyst gives 2,6-di-ter.
Although t-butylcyclohexanols can be obtained, it is difficult to obtain a single stereochemically 2,6-di-tert-alkylcyclohexanols by this method, and therefore a pyrroloazole coupler using the same can be obtained. In the above synthesis, there arises a problem that the crystallization yield of the synthetic intermediate is extremely lowered. Therefore, there has been a strong demand for the development of a synthetic method capable of inexpensively and safely supplying a large amount of stereochemically single 2,6-di-tert-alkylcyclohexanols.

[0004]

The first object of the present invention is to prepare 2,6-di-tert-alkylcyclohexanols from corresponding 2,6-di-tert-alkylcyclohexanones inexpensively and safely. It is to provide a method that can be manufactured in large quantities. A second object is to provide a method for producing stereochemically single 2,6-di-tert-alkylcyclohexanols.

[0005]

Means for Solving the Problems From the above viewpoints, the present inventors have conducted various studies on the reduction reaction of 2,6-di-tert-alkylcyclohexanones, and have completed the present invention. That is, the object of the present invention was achieved by the manufacturing method described below. (1) 2,6-di-ter represented by the following general formula (I)
2,6 represented by the following general formula (III) characterized by reducing t-alkylcyclohexanones with sodium borohydride in the presence of a metal salt represented by the general formula (II).
-Method for producing di-tert-alkylcyclohexanols.

[0006]

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In the formula, R and R'are each tert-
Represents an alkyl group, X represents a substituent, and n represents an integer of 0 to 3. M represents an alkali metal (when m = 1), an alkaline earth metal (when m = 2), and a typical metal (when m = 3), and Y represents a halogen atom.

(2) The 2,6-di-tert-alkylcyclohexanols according to (1), wherein the metal salt represented by the general formula (II) is magnesium chloride or aluminum chloride. Production method. (3) In the reduction reaction described above, the reaction solvent is diglyme (diethylene glycol dimethyl ether), wherein the 2,6-di- is described in (1) or (2).
Process for producing tert-alkylcyclohexanols. (4) The 2,6-di-tert described in (1), (2) or (3), wherein the compound represented by the general formula (III) is obtained stereochemically in a single form. -Method for producing alkylcyclohexanols. The above "stereochemically single" means that the purity of the target compound is 90% or more as measured by gas chromatography.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. In the general formulas (I) and (III), X is, for example, an aliphatic group {for example, a linear or branched alkyl group having 1 to 36 carbon atoms, an aralkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkyl group, An alkenyl group, specifically, for example, methyl, ethyl, propyl, isopropyl, t-butyl, tridecyl, cyclohexyl,
4-pentadecyloxybenzyl, hexadecyloxycarbonylethyl, 2-ethoxytridecyl, trifluoromethyl, cyclopentyl, 3- (2,4-di-t-
Amylphenoxy) propyl}, aryl group {preferably having 6 to 36 carbon atoms, for example, phenyl, naphthyl, 4-t
-Butylphenyl, 2,4-di-t-amylphenyl,
4-tetradecanamidophenyl, 3- (2,4-di-
t-amylphenoxyacetamido) phenyl}, a heterocyclic group (preferably having 1 to 30 carbon atoms, for example, 3-pyridyl, 2-furyl, 2-pyridyl, 2-pyrimidyl), an alkoxy group (preferably having 1 to 30 carbon atoms). , For example, methoxy, ethoxy, 2-methoxyethoxy, 2-dodecyloxyethoxy), aryloxy group (preferably having 6 to 30 carbon atoms, for example, phenoxy, 2-methylphenoxy, 4-tert-butylphenoxy, 2,4 -Ge-t
ert-amylphenoxy, 2-chlorophenoxy, 4
-Cyanophenoxy, 3-methoxycarbamoylphenoxy), a heterocyclic oxy group (preferably having 1 to 30 carbon atoms,
For example, 2-benzimidazolyloxy, 1-phenyltetrazole-5-oxy, 2-tetrahydropyranylo

Xy), alkyl-aryl or heterocyclic acyloxy groups (preferably having 2 to 30 carbon atoms, eg acetoxy, hexadecanoyloxy), carbamoyloxy groups (preferably having 1 to 30 carbon atoms, eg N).
-Ethylcarbamoyloxy, N-phenylcarbamoyloxy), silyloxy group (preferably having 1 to 3 carbon atoms)
0, for example, trimethylsilyloxy, dibutylmethylsilyloxy), an acylamino group (preferably having 2 carbon atoms)
~ 30, for example, acetamide, benzamide, tetradecanamide, 2- (2,4-di-t-amylphenoxyacetamide, isopentadecaneamide, 2- (2,
4-di-t-amylphenoxy) butanamide, 4-
(3-t-butyl-4-hydroxyphenoxy) butanamide), alkylamino group (preferably having 1 to 3 carbon atoms)
0, for example, methylamino, butylamino, dodecylamino, dimethylamino, diethylamino, methylbutylamino, an arylamino group (preferably having 6 to 30 carbon atoms, for example, phenylamino, 2-chloroanilino,
2-chloro-5-tetradecanamido anilino, N-acetylanilino, 2-chloro-5-[(α-2-ter
t-butyl-4-hydroxyphenoxy) dodecylamide] anilino, 2-chloro-5-dodecyloxycarbonylanilino), a ureido group (preferably having 2 to 30 carbon atoms, for example, methyl).

Lureido, phenylureido, N, N-
Dibutylureido, dimethylureido), alkenyloxy group (preferably having 2 to 30 carbon atoms, for example, 2-propenyloxy), formyl group, alkyl aryl or heterocyclic acyl group (preferably having 1 to 30 carbon atoms, for example, acetyl). , Benzoyl, 2,4-di-tert-amylphenylacetyl, 3-phenylpropanoyl, 4
-Dodecyloxybenzoyl), alkyl aryl or heterocyclic oxycarbonyl group (preferably having 2 carbon atoms)
To 30, for example, methoxycarbonyl, butoxycarbonyl, dodecyloxycarbonyl, octadecyloxycarbonyl, phenyloxycarbonyl, 2-pentadecyloxycarbonyl), an alkyl aryl or a heterocyclic oxycarbonylamino group (preferably having 2 carbon atoms).
To 30, for example, methoxycarbonylamino, tetradecyloxycarbonylamino, phenoxycarbonylamino, 2,4-di-tert-butylphenoxycarbonylamino), a carbamoyl group (preferably having a carbon number of 1 to 1).
30, for example, N-ethylcarbamoyl, N, N-dibutylcarbamoyl, N- (2-dodecyloxyethyl)
Carbamoyl, N-methyl-N-dodecylcarbamoyl, N- [3- (2,4-di-tert-amylphenoxy) propyl] carbamoyl), phosphonyl group (preferably having 1 to 30 carbon atoms, for example, phenoxyphosphonyl, Octyloxyphosphonyl, phenylphosphonyl), imide group (preferably having 1 to 30 carbon atoms, for example,
N-succinimide, hydantoinyl, N-phthalimide, 3-octadecenylsuccinimide), azolyl group (for example, imidazolyl, pyrazolyl, 3-chloro-pyrazol-1-yl, triazolyl), halogen atom (for example, chlorine atom, bromine) Atom), hydroxy group, cyano group, carboxy group, nitro group, unsubstituted amino group and the like. The above-mentioned aliphatic group, aromatic group, and heterocyclic group (including these groups forming a part of the substituent) may further have the substituents listed above.

X preferably has 1 to 15 carbon atoms.
More preferably, a straight-chain or branched-chain alkyl group having 1 to 8 carbon atoms, an aralkyl group having 7 to 15 carbon atoms, more preferably an aralkyl group having 7 to 8 carbon atoms, or an alkyl group having 3 to 15 carbon atoms, and further preferably 5 ~ 8 cycloalkyl group, having 6 to 15 carbon atoms,
More preferably, it is an aryl group of 6 to 8, and particularly preferably as X, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t.
-Amyl group, t-octyl group, phenyl group or cyclohexyl group, most preferably methyl group. n
Is preferably 0 or 1, and when n is 1, X is an oxy group of general formula (I) or general formula (III)
It is preferred that it is in the para position of the hydroxyl group of. In the general formulas (I) and (III), R and R '
Are each a tert-alkyl group. R and R '
Can be shown in more detail by the general formula (IV). General formula (IV)

[0013]

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Here, R ₁ , R ₂ and R ₃ are all substituents. Examples of the substituent referred to herein include the substituents mentioned for X which are linked by a carbon atom.
R ₁ , R ₂ and R ₃ preferably have 1 to 15 carbon atoms,
More preferably, a linear or branched alkyl group having 1 to 8 carbon atoms, 7 to 15 carbon atoms, and further preferably 7 to 8 carbon atoms.
Is an aralkyl group having 3 to 15 carbon atoms, more preferably a cycloalkyl group having 5 to 8 carbon atoms, and an aryl group having 6 to 15 carbon atoms, further preferably 6 to 8 carbon atoms, and R ₁ , R ₂ and R
₃ is particularly preferably a linear or branched alkyl group having 1 to 4 carbon atoms, and most preferably a methyl group.
R ₁ , R ₂ and R ₃ may be the same or different and may be connected to each other to form a 5- or 6-membered saturated or unsaturated ring.

R and R'are preferably, for example, t
Examples thereof include an ert-butyl group, a tert-amyl group, a tert-octyl group and a 1-methylcyclohexyl group, and R and R ′ are most preferably a tert-butyl group. R and R ′ may be the same or different, but it is more preferable that they are the same. General formulas (I) and (III)
In, n represents an integer of 0 to 3. When n is 2 or 3, X may be the same or different and may be linked to each other to form a 5- or 6-membered saturated or unsaturated ring.

Preferred as the compounds represented by the general formulas (I) and (III) of the present invention are R and R'in the above-mentioned (IV), and R1, R2 and R3 each having 1 to 15 carbon atoms. An alkyl group, an aralkyl group having 7 to 15 carbon atoms, a cycloalkyl group having 3 to 15 carbon atoms, or an aryl group having 6 to 15 carbon atoms, and X represents an alkyl group having 1 to 15 carbon atoms and 7 to 15 carbon atoms. Aralkyl group with 3 carbon atoms
To a cycloalkyl group having 15 to 15 carbon atoms or an aryl group having 6 to 15 carbon atoms, n is 1, and X is at the para position of the oxy group of general formula (I) or the hydroxyl group of general formula (III). Compounds, among which R and R '
Are both tert-butyl group, tert-amyl group, t
is an ert-octyl group or a 1-methylcyclohexyl group, and X is a methyl group, an ethyl group, an n-propyl group, an iso-propyl group, an n-butyl group, a sec-butyl group, a tert-amyl group, a tert- Compounds that are octyl, phenyl or cyclohexyl are preferred. As X, a methyl group is particularly preferable. Specific examples of the compounds represented by formulas (I) and (III) of the present invention are shown below, but the present invention is not limited thereto.

[0017]

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[0018]

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[0019]

[Chemical 6]

[0020]

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[0021]

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In the general formula (II), M is an alkali metal (m = 1, for example, Li, Na, K), an alkaline earth metal (m = 2, for example, Mg, Ca, Ba), a typical metal (m =
3, for example B, Al). Y is a halogen atom (for example, chlorine, bromine or iodine atom), preferably a chlorine atom. Specific examples of the metal salt (II) are shown below, but the present invention is not limited thereto.

[0023]

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Of these, LiBr, LiCl, and
MgCl_Two, CaCl_Two, AlCl _ThreeAnd even better
More preferably LiCl, MgCl_Two, LiBr, AlCl_Three
It is. Particularly preferably MgCl_Two, AlCl_ThreeIn
You. In the present invention, 2,6 represented by the general formula (I)
-Di-tert-alkylcyclohexanones and general formula
The reaction molar ratio with the metal salt represented by (II) is the stoichiometric amount.
But preferably 1:10 to 1: 0.5, more preferably
Or 1: 3 to 1: 0.5, particularly preferably 1: 2 to 1:
0.5. The amount of sodium borohydride used is
0.25-10 mol per mol of the compound of general formula (I)
Necessary, preferably 0.5 to 5, more preferably 1
~ 3 molar equivalents.

Examples of the reaction solvent include esters such as ethyl acetate, ethers such as tetrahydrofuran, diethyl ether, dimethoxyethane, diglyme, triglyme and tetraglyme, hydrocarbons such as hexane, aromatic carbonization such as benzene and toluene. Hydrogen can be used. Of these, ethers and aromatic hydrocarbons are preferable, and ethers are particularly preferable.
Further, these may be mixed and used. The amount of the reaction solvent is appropriately 1 to 20 molar equivalents with respect to the compound of general formula (I), preferably 2 to 10, more preferably 2 to.
It is 5 molar equivalents. The reaction temperature depends on the solvent, but is preferably 30 to 180 ° C, more preferably 50 to 150 ° C.
And particularly preferably 80 to 120 ° C.

As a method of adding reagents, 2,6-di-
The tert-alkylcyclohexanones (I) were dissolved, followed by sodium borohydride and then the metal salt (I
I) is added, sodium borohydride is suspended in the solvent, followed by the metal salt (II) and then 2,6-di-te.
There is a method of adding rt-alkylcyclohexanones (I), but the former method is preferable.

[0027]

EXAMPLES The present invention will now be specifically described with reference to examples, but the present invention is not limited thereto. Example 1 (Synthesis of Exemplified Compound (III-1) Using Magnesium Chloride (II-5))

[0028]

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2,6-di-tert-butyl-4-methylcyclohexanone (I-1) (100 g, 0.45 m
ol) to diglyme (120.7 g, 0.90 mol)
, Sodium borohydride (20.4
g, 0.54 mol) was added. Then magnesium chloride (II-5) (51.4 g, 0.54 mol) was added at 25 ° C. The internal temperature was raised to 100 ° C. and the mixture was stirred for 3 hours. After completion of the reaction was confirmed by thin layer chromatography (TLC), 2
Cooled to 5 ° C. 160 ml of ethyl acetate was added, followed by a mixed solvent of acetone (165.7 ml, 2.25 mol) and ethyl acetate (70 ml). Next, 150m of water
l, concentrated hydrochloric acid (193 ml, 2.25 mol) was added to 50
The temperature was raised to ℃ and stirred for 30 minutes. After separating the organic layer, it was washed with water (100 ml) 5 times and saturated brine (100 ml) 1 times.
Washed times. The mixture was concentrated under reduced pressure to give 2,6-di-tert-butyl-4-methylcyclohexanol (III-1) at 9%.
7.4 g (0.43 mol, yield 96.5%) was obtained. It was 90:10 pure by stereochemistry by gas chromatography analysis. The structure is NMR
It was identified by spectrum.

Boiling point: 95 ° C./2 mmHg Density: 0.776 g / cm ³ (25 ° C.) Viscosity: 15.6 cp (25 ° C.) Refractive index: 1.4630 (25 ° C.) Dielectric constant: 3.89 (25 ° C.) NMR (CDCl3): 0.95 ppm, 18H
(S) 4.4 ppm, 1H (s)

Example 2 (aluminum chloride (II-11))
Synthesis of Exemplified Compound (III-1) Using

[0032]

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2,6-di-tert-butyl-4-methylcyclohexanone (I-1) (1.12 g, 5 mmo)
l) was dissolved in diglyme (2.5 ml, 17.5 mmol), followed by sodium borohydride (95 mg,
2.5 mmol) was added. Next, aluminum chloride (II
-11) (0.67 g, 5 mmol) was added at 25 ° C. The internal temperature was raised to 50 ° C. and the mixture was stirred for 1 hour. The end of the reaction is T
Confirm by LC and cool to 25 ° C. 1N hydrochloric acid water (10
ml) was carefully added and the mixture was extracted with ethyl acetate (10 ml). The organic layer was concentrated under reduced pressure to give 2,6-di-tert-.
1.0 g (4.7 mmol, yield 93.5%) of butyl-4-methylcyclohexanol (III-1) was obtained. By gas chromatographic analysis, it was 97: 3 pure in stereochemistry.

Comparative Example 5% rhodium-based on the same raw material (I-1, 100 g)
The same compound was obtained by catalytic hydrogenation of an alumina catalyst (5 g) in a 500 ml stainless steel autoclave.
(III-1) was obtained quantitatively. When this product was analyzed by gas chromatography, it was a mixture with a stereochemistry of purity 60:40. Using 2,6-di-tert-butyl-4-methylcyclohexanol (stereoisomeric ratio 90:10) synthesized according to Example 1, application of pyrroloazole coupler to intermediate synthesis was attempted. For comparison, 2,6-di-tert- synthesized in the above Comparative Example
The results of applying butyl-4-methylcyclohexanol (stereoisomer ratio 60:40) are also shown.

[0035]

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Application Example Ethyl malonate, 2,6-di-tert-butyl-4-
Synthesis of methylcyclohexyl ester (a) 2,6-di-tert-butyl-4-methylcyclohexanol (50.2 g, 0.2) synthesized according to Example 1.
2 mol) in ethyl acetate (200 ml) at 0 ° C. trifluoroacetic anhydride (41 ml, 0.29 mol)
Was added dropwise, and subsequently ethyl malonate monopotassium salt (41.6 g) was slowly added. After stirring at room temperature for 2 hours, 200 ml of water was added and 33 g of sodium hydrogencarbonate was slowly added to neutralize. After liquid separation, the organic layer was washed once with water and once with brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain crude ethyl malonate, 2,6-di-tert-butyl-4-.
76 g of methylcyclohexyl ester (a) was obtained. The obtained crude ethyl malonate and 2,6-di-tert-butyl-4-methylcyclohexyl ester (a) were directly used in the next step without purification.

Synthesis of hydrazide (b) The above ethyl malonate, 2,6-di-tert-butyl-
4-Methylcyclohexyl ester (a) (73 g) and hydrazine monohydrate (28.3 g, 0.57 mol)
An isopropanol (200 ml) solution of was stirred and refluxed for 6 hours. Water and ethyl acetate are added to the reaction solution at 500 m each
l was added for extraction. The organic layer was washed twice each with water and brine and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was recrystallized from hexane to give hydrazide (b) (58.5 g, 0.18 mo
1, 85% (based on 2,6-di-tert-butyl-4-methylcyclohexanol), melting point 105-106 ° C)
I got The structure was identified by 1H-NMR and mass spectrum.

Comparative Application Example 2,6-Di-tert-butyl-synthesized in the above Comparative Example
When hydrazide (b) was synthesized using 4-methylcyclohexanol by the same method as in the above application example, the yield was remarkably reduced. (22 g, 0.07 mol, 32
%, Based on 2,6-di-tert-butyl-4-methylcyclohexanol)

[0039]

According to the present invention, it is possible to inexpensively and safely supply a large amount of 2,6-di-tert-alkylcyclohexanols having a single stereochemistry.

Claims (4)

[Claims] 1. A 2,6-di-tert-alkylcyclohexanone represented by the following general formula (I) is represented by the general formula (I
Method for producing 2,6-di-tert-alkylcyclohexanols represented by the following general formula (III), characterized by reducing with sodium borohydride in the presence of a metal salt represented by I) . Embedded image In the formula, R and R ′ each represent a tert-alkyl group, X represents a substituent, and n represents an integer of 0 to 3.
M represents an alkali metal (when m = 1), an alkaline earth metal (when m = 2), and a typical metal (when m = 3), and Y represents a halogen atom. 2. The method for producing 2,6-di-tert-alkylcyclohexanols according to claim 1, wherein the metal salt represented by the general formula (II) is magnesium chloride or aluminum chloride. . 3. The method for producing 2,6-di-tert-alkylcyclohexanols according to claim 1, wherein the reaction solvent in the reduction reaction is diglyme. 4. The compound represented by the general formula (III) is stereochemically obtained as a single compound.
The method for producing 2,6-di-tert-alkylcyclohexanols according to 2 or 3.