JP2003183204A - Method for producing adamantanols - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To realize a method for producing an adamantanol from adamantanes in a high yield and high selectivity by an industrially advantageous method. <P>SOLUTION: This method for producing adamantanols comprises reacting adamantanes such as adamantine in a reaction solution comprising a concentrated sulfuric acid, a carbocation-producing compound such as tertiary butyl alcohol and an organic nitrile compound such as acetonitrile and mixing the resultant reaction solution with water at 20-90°C, preferably in such water amount used that sulfuric acid concentration after mixing with the reaction solution becomes 30-60 wt.%. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing adamantanols by reacting adamantanes with concentrated sulfuric acid, a carbocation-forming compound, and an organic nitrile compound.

[0002]

2. Description of the Related Art Adamantanols having a hydroxyl group bonded to an adamantane skeleton such as 1-adamantanol are
Pharmaceutical intermediates, raw materials for photoresist monomers, raw materials for photochromic compounds, paints, adhesives, adhesives, films,
It is widely used as a raw material for materials such as adsorbents, and is an industrially important compound.

A method for producing adamantanols from adamantanes, carbocation-forming compounds, and organic nitrile compounds is known, and is disclosed in JP-A-1-283236.
The publication discloses that adamantanes are reacted with concentrated sulfuric acid, a carbocation-forming compound, and an organic nitrile compound, and the resulting reaction solution is poured into ice water to produce adamantanols.

[0004]

However, although this method can obtain adamantanols in a fairly good yield and selectivity, it is not sufficient yet, and it is desired to further improve these values. It was

Furthermore, in the examples of this publication, the amount of ice water used for emptying the reaction solution was such that the sulfuric acid concentration was 24 at the dilution ratio.
The amount of the reaction solution that can be added to the reactor used in such an operation is small, and the amount of the target product per batch is small. The yield was low. For example, when the method described in JP-A-1-283236 is carried out in a reactor of 1 cubic meter, the yield of adamantanols is as low as 5.5 kg, which is not economical on an industrial scale. It was

Therefore, in the above-mentioned method for producing adamantanol, the reaction can be carried out with a high yield and a high selectivity, and the yield per batch is also high, so that an industrially advantageous method can be developed. It was a big challenge.

[0007]

In view of such circumstances, the inventors of the present invention have made earnest studies. As a result, adamantanes are reacted in a reaction solution consisting of concentrated sulfuric acid, a carbocation-forming compound, and an organic nitrile compound, and the resulting reaction solution is mixed with water at a specific temperature to solve the above problems. The inventors have found what can be done and have completed the present invention.

That is, the present invention provides adamantanes
A method for producing adamantanols, which comprises reacting in a reaction solution composed of concentrated sulfuric acid, a carbocation-forming compound, and an organic nitrile compound, and mixing the obtained reaction solution with water at 20 to 90 ° C. .

Another aspect of the present invention is the above method, wherein adamantane is used as adamantane.
-A method for producing 2-adamantanone, characterized in that 2-adamantanone is obtained by oxidizing adamantanol in concentrated sulfuric acid.

Still another invention is 2-adamantanone obtained by the above method, and (1) an alkyl lithium, (2) a Grignard reagent, and (3) an alkyl halide compound and at least one selected from lithium metal. The method for producing an alkyl adamantyl ester compound is characterized in that the alkyl adamantyl alkoxide compound is reacted with the alkylating reagent to obtain an alkyl adamantyl alkoxide compound, and then the alkyl adamantyl alkoxide compound is reacted with an acid halide or an acid anhydride.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, adamantanes include adamantane and four 3 groups on an adamantane skeleton.
It refers to a compound in which at least one of the carbon atoms at the primary carbon, ie, the 1-, 3-, 5- and 7-positions is unsubstituted. Usually, one represented by the following formula (I) is used.

[0012]

[Chemical 1]

(Wherein R¹Is an alkyl group, aryl
Group, aralkyl group, amino group, hydroxyl group, cyano group, cal
Is a voxyl group or a halogen atom, and n is 0 to 4
Is an integer of the 1st, 3rd, 5th and 7th carbon atoms
At least one is R above¹Is not replaced. ) In the above formula (I), R¹The alkyl group of is not particularly limited
But not limited to methyl group, ethyl group, propyl
Having 1 to 6 carbon atoms such as groups, isopropyl groups, and butyl groups
Is preferred. The aryl group has 6 carbon atoms such as a phenyl group.
Those of 10 are preferable. Aralkyl group is benzyl group
And others having 7 to 12 carbon atoms are preferable. The amino group is
C1-4 carbon atoms such as methylamino and ethylamino
Is preferred. Halogen atom is chlorine atom, bromine atom,
A fluorine atom and the like are preferable. These R ¹Even though
Alkyl group, amino group, hydroxyl group, cyano group, carboxyl
A group or a halogen atom is particularly preferable.

When a plurality of R ^1's are substituted on the adamantane skeleton, these may be the same or different.

Specific examples of the adamantanes represented by the above formula (I) include adamantane: 1-methyl adamantane, 1-ethyl adamantane, 2-methyl adamantane, 2-ethyl adamantane, 1,3-dimethyl adamantane, 1 , 3-diethyl adamantane, 1,2-dimethyl adamantane, 1,2-diethyl adamantane and the like alkyl adamantanes; 1-adamantanamine,
Aminoadamantanes such as 1,3-diaminoadamantane and 1-adamantanemethylamine; Hydroxyadamantanes such as 1-adamantanol, 2-adamantanol and 1,3-dihydroxyadamantane; 1-cyanoadamantane and 2-cyanoadamantane And the like cyanoadamantanes; 1-adamantanecarboxylic acid, 1,3-
Carboxyadamantanes such as adamantane dicarboxylic acid; 1-fluoroadamantane, 2-fluoroadamantane, 1-chloroadamantane, 2-chloroadamantane, 1-bromoadamantane, 2-bromoadamantane, 1-iodoadamantane, 2-iodoadamantane, 1 , 3-difluoroadamantane, 1,3-dichloroadamantane, 1,3-dibromoadamantane, 1,
Examples thereof include halogenated adamantane such as 3-diiodo adamantane, but not limited thereto.

Among the adamantane compounds represented by the above formula (I), adamantane, 1-methyladamantane, 1-chloroadamantane, 1-bromoadamantane, 1,3 are used because of their reactivity and availability. -Dichloroadamantane and the like are particularly preferable.

In the present invention, first, the adamantanes are reacted in a reaction solution containing concentrated sulfuric acid, a carbocation-forming compound, and an organic nitrile compound. As a result of this reaction, in the general formula (I), among the tertiary carbon atoms at the 1-position, 3-position, 5-position and 7-position, a position not substituted by the group represented by R ¹ is

[0018]

[Chemical 2]

A compound having a group represented by
It is presumed that an intermediate product) is produced. When a plurality of tertiary carbon atoms are present, the intermediate compound is mainly a compound into which one of the above groups is introduced, and a compound in which two or more of the above groups are introduced is usually small even if produced. Absent.

In the above reaction, concentrated sulfuric acid is used as an oxidizing agent, and reagents or available industrial raw materials can be used without any limitation. In the present invention, concentrated sulfuric acid means
It has a sulfuric acid concentration of 90 to 100% by mass. In order to sufficiently increase the reaction rate, the sulfuric acid concentration is preferably 95 to 98% by mass. When the sulfuric acid concentration is 90% by mass or less, the reaction rate is lowered, which is not preferable.

In the present invention, the sulfuric acid concentration means the proportion of the mass of H ₂ SO ₄ in the total mass of H ₂ SO ₄ and water present in the reaction solution.

The amount of concentrated sulfuric acid to be used is not particularly limited, but it is not economical to use it in a too large amount, and even if it is too small, the oxidizing power to adamantane is weakened.
Usually, H ₂ SO ₄ is 3 to 20 for adamantane.
It is used in an amount of 0 times, preferably 5 to 100 times.

The carbocation-forming compound in the present invention is one which easily forms a carbocation in concentrated sulfuric acid to cationize the tertiary carbon atom on the adamantane skeleton, and known compounds having such an action are limited. Can be used without. Tertiary alcohols, tertiary halides, secondary alcohols, and the like, and the tertiary hydrogenated carbon group of the former two compounds has a carbon number of 4 to 6 such as t-butyl group. Tertiary alkyl group; a tertiary aralkyl group having 9 to 25 carbon atoms such as a trityl group and the like. Examples of the secondary hydrocarbon group contained in the secondary alcohol include secondary alkyl groups having 4 to 6 carbon atoms such as isopropyl group, s-butyl group and isopentyl group.

Specific examples of these carbocation-forming compounds include tertiary alcohols such as t-butyl alcohol and triphenylmethyl alcohol; t-butyl chloride, t-butyl bromide, triphenylmethyl chloride and triphenylmethyl. Examples thereof include tertiary halides such as bromide; secondary alcohols such as isopropyl alcohol, s-butyl alcohol, and isopentyl alcohol. Of these, t-butyl alcohol, t-butyl chloride, t-butyl bromide, triphenylmethyl alcohol, triphenylmethyl chloride, triphenylmethyl bromide, etc., which are particularly reactive and readily available, are preferably used.

The amount of the carbocation-forming compound used is not particularly limited, but if the amount is too small relative to the adamantane, the reaction rate may be slow and the reaction may not be completed. As a result, the content of 0.1 to 1 mol of adamantane is usually increased.
It may be 10 mol, preferably 1 to 5 mol.

In the present invention, the organic nitrile compound is a substrate that forms the skeleton of the N- (adamantyl) amide compound together with the adamantane, and the compound represented by the following formula (II) is usually used.

[0027]

[Chemical 3]

[In the formula, R ² is an alkyl group, an aryl group, an aralkyl group, or an XR ³ group (X is a halogen atom, R ³
Is an alkyl group having 1 to 6 carbon atoms). } Here, the alkyl group has a carbon number of 1 to 6 such as a methyl group, an ethyl group and a propyl group, the aryl group has a carbon number of 6 to 10 such as a phenyl group, and the aralkyl group has a carbon number such as a benzyl group. Those of 7 to 12 can be preferably used. Examples of the XR ³ group include chloromethyl, chloroethyl, chloropropyl and the like.

Specific examples of these organic nitrile compounds include acetonitrile, propionitrile, benzonitrile, benzyl nitrile, vinylacetonitrile,
Chloroacetonitrile, 2-chloropropionitrile,
3-chloropropionitrile, 2-bromophenylacetonitrile, 3-bromophenylacetonitrile, 4-
Examples thereof include bromophenylacetonitrile, and among them, acetonitrile, propionitrile, benzonitrile, benzylnitrile, vinylacetonitrile, chloroacetonitrile, and 2-bromophenylacetonitrile are particularly preferable.

In the present invention, since the reaction between the adamantane and the organic nitrile compound is a stoichiometric reaction, the amount of the organic nitrile compound used is not particularly limited as long as it is used in an amount of 1 mol or more per 1 mol. When the amount is large, the amount of by-products may increase. Therefore, it is usually preferable to use 1 to 10 mol, preferably 1 to 5 mol per 1 mol of adamantane.

In the present invention, the reaction between the adamantane and the organic nitrile compound can be carried out without using an organic solvent, but from the viewpoint of dissolving the atamantane and accelerating the reaction rate, an organic solvent is used. It is preferably carried out and used. The organic solvent is incompatible with water, does not inhibit the reaction, and can dissolve adamantane compounds can be used without any limitation, and it is preferable to proceed the reaction in a suspension state of these organic solvent and concentrated sulfuric acid. .

Specific examples of these organic solvents include halogenated aliphatic hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride; aliphatic hydrocarbons such as hexane and heptane; halogenated chlorobenzene and the like. Aromatic hydrocarbons; aromatic hydrocarbons such as benzene, xylene, toluene; ethers such as diisopropyl ether, 1,4-dioxane; esters such as ethyl acetate, propyl acetate, butyl acetate; carbonates such as dimethyl carbonate You can list the kind. Among these, halogenated aliphatic hydrocarbons, aliphatic hydrocarbons, halogenated aromatic hydrocarbons, aromatic hydrocarbons and the like are preferably used because high yield can be expected.

The amount of these organic solvents to be used is not particularly limited, but if it is too large, the yield per batch will be small, so it is not economical. Even if the amount is too small, the adamantane can be dissolved. It is usually preferable to use an organic solvent so that the amount of adamantane compounds in the whole reaction solution is 0.1 to 60% by mass, preferably 1 to 50% by mass, because the reaction rate is lowered. .

The reaction temperature of the reaction between the adamantane and the organic nitrile compound is not particularly limited, but if the temperature is too high, a side reaction is promoted, and if the temperature is too low, the reaction rate becomes small. , -70 ° C to 70 ° C, preferably -30 ° C to 60 ° C.

The reaction time is not particularly limited and cannot be unconditionally determined because it varies depending on the sulfuric acid concentration used or the carbocation-forming compound, but usually 0.5 to 100 hours is sufficient.

Further, the above reaction can be carried out under any conditions of normal pressure, reduced pressure and increased pressure. Also, the reaction is preferably carried out with stirring.

Next, in the present invention, the reaction solution obtained by the above reaction is mixed with water at 20 to 90 ° C, preferably 30 to 80 ° C. As a result, the intermediate product which is presumed to be generated in the reaction solution is

[0038]

[Chemical 4]

The group represented by is hydrolyzed in two steps, and the intermediate product is converted to adamantanols after passing through N- (adamantyl) amides. In the present invention, the greatest feature is that the temperature of the water mixed with the reaction solution is raised to the above value.

That is, in the method disclosed in the above-mentioned JP-A-1-283236, the water mixed with this reaction solution is ice water and is cold. Therefore, in this method, after the N- (adamantyl) amides are formed, It is presumed that the hydrolysis reaction is likely to be stopped, and that a large amount of compounds in which the decomposition does not proceed further occur.

On the other hand, according to the present invention, the temperature of this water is set to 20 to 90 ° C. as described above, so that the above-mentioned two steps of hydrolysis are smoothly progressed and the desired adamantanols are obtained. It is possible to manufacture with high yield and high selectivity. When the temperature of the water mixed with the reaction solution is higher than 90 ° C., it becomes close to the boiling point of water, which makes it difficult to stably perform the hydrolysis reaction.

In addition, in mixing the reaction solution with water,
The amount of water used is such that the sulfuric acid concentration after mixing with the reaction solution is 30 to 60.
It is preferable that the amount is, by mass, more preferably 35% by mass to 55% by mass. That is, the above-mentioned JP-A-1-283
In the method disclosed in Japanese Patent No. 236, the amount of ice water used is such a large amount that the sulfuric acid concentration of the reaction solution decreases to 24% by mass on the dilution ratio, and further, N- (adamantyl) amides to adamantanols are used. In the hydrolysis reaction in which is generated, ammonia is also produced as a by-product, so that the sulfuric acid concentration is further reduced by several percent, specifically about 2 to 3% due to neutralization. Therefore, when the sulfuric acid concentration of the resulting mixture is low when the reaction solution is mixed with water in this way, the progress of the second-stage hydrolysis reaction is one step closer to the end of the mixing performed by means such as dropping. Will not be enough.

On the other hand, in the present invention, in addition to the requirement that the temperature of the water mixed with the reaction solution is 20 to 90 ° C.,
If the sulfuric acid concentration of the mixed solution is adjusted to the above value, the progress of the second-step hydrolysis reaction will become more active at the end of the mixing, and the target adamantanols will be extremely high in yield and high in selectivity. You can get at a rate.

Here, when the sulfuric acid concentration after mixing the reaction solution and water becomes higher than 60% by mass, the reactivity of hydrolysis is lowered and the production amount of adamantanols is reduced.

In the present invention, the sulfuric acid concentration after mixing the reaction liquid and water is a value measured by neutralization titration with an alkaline compound such as 1N sodium hydroxide. Further, the sulfuric acid concentration refers to a measured value in a state where the sulfuric acid concentration of the liquid is stabilized after the reaction liquid is completely mixed with water.

In the present invention, the procedure for mixing the reaction solution with water and adjusting the sulfuric acid concentration to the above value is not particularly limited, and the reaction solution may be diluted with water by an appropriate method until the sulfuric acid concentration reaches the above value. . Specifically, it is preferable to carry out the method by dropping the reaction solution into water at the reaction temperature. When an organic solvent is used for the reaction, the organic solvent may be distilled off prior to this operation.

The above-mentioned two-step hydrolysis reaction for producing adamantanol is one in which the reaction is actively progressed and rapidly terminated in a short time when the reaction solution is mixed with water. To fully complete, the mixture should be
After the sulfuric acid concentration reaches the above value, it is preferable to hold the sulfuric acid for about 1 to 5 hours. The holding is preferably performed while stirring the liquid.

The method for isolating and purifying the adamantanols thus obtained is not particularly limited, and a known method can be adopted. For example, the precipitated crystals can be filtered or centrifuged. Preferably, to the mixed solution after the hydrolysis reaction, if necessary, an organic solvent is added for extraction, and the reaction system is completely neutralized by adding an aqueous solution of sodium hydrogencarbonate, etc., and the obtained organic solvent is dried to remove the solvent. After distilling off the solvent under reduced pressure, the residue is preferably purified by a technique such as silica gel column chromatography or recrystallization.

In the present invention, the adamantanols thus obtained may be, for example, pharmaceutical intermediates, raw materials for photoresist monomers, raw materials for photochromic compounds, paints, adhesives, adhesives, films, adsorbents, etc. It can be usefully used as various industrial materials such as raw materials. When 1-adamantanol is produced as the adamantanol using adamantanol as the adamantane, it is preferably used as a raw material when producing the alkyladamantyl ester compound via 2-adamantanone. It is known that the alkyl adamantyl ester compound has high dry etching resistance in a semiconductor manufacturing process, for example, in a resist manufactured using the same as a raw material (for example, JP-A-5-2652).
12), the potential as a semiconductor resist material is drawing attention. Since 1-adamantanol obtained in the present invention has high purity, when used as a raw material for producing the above alkyladamantyl ester compound, the compound is advantageous in high yield and is highly purified, which is advantageous.

The reaction for obtaining an alkyladamantyl ester compound from 1-adamantanol will be described below.

In the above manufacturing method, first, 2-adamantanone is manufactured from 1-adamantanol. This reaction is, for example, tetrahydrone 1968 24, 5361.
It can be carried out by oxidizing 1-adamantanol with concentrated sulfuric acid as described on pages -5368.

Concentrated sulfuric acid can be used without limitation as long as it is defined above, but 95 to 98% by mass is preferably used. Further, if the concentration is high, it is also possible to adjust by adding fuming sulfuric acid or the like to the sulfuric acid having a low concentration. The amount of concentrated sulfuric acid used is 3 to 5 relative to 1-adamantanol.
The amount is 00 times, preferably 5 to 300 times.

The reaction temperature of the above reaction is not particularly limited and may be appropriately determined depending on the concentration of concentrated sulfuric acid used. Usually, 10 ° C to 80 ° C, preferably 20 ° C to 70 ° C.
It is performed in the range of ° C. Although the reaction time depends on the sulfuric acid concentration used and the reaction temperature, it is generally 0.5 hour to 1 hour.
00 hours is enough.

Although the above reaction can be carried out without using an organic solvent, it is preferable to carry out using an organic solvent from the viewpoint of dissolving 1-adamantanol and accelerating the reaction rate. As the organic solvent, those which are incompatible with water, do not inhibit the reaction, and dissolve 1-adamantanol can be used without any limitation, and it is preferable to proceed the reaction in a suspension state of these organic solvent and concentrated sulfuric acid. Is.

As specific examples of these organic solvents, those exemplified in the above-mentioned production of adamantanols can be similarly used. Among these, halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons, and the like are preferably adopted because high yield can be expected.

The amount of these organic solvents to be used is not particularly limited, but if the amount is too large, the yield per batch will be small, which is not economical. Even if the amount is too small, 1-adamantanol can be dissolved. Since the reaction rate cannot be controlled and the reaction rate decreases, an organic solvent is usually used so that the amount of 1-adamantanol in the whole reaction solution is 0.1 to 60% by mass, preferably 1 to 50% by mass. Preferably.

Synthesis of an alkyl adamantyl ester compound using 2-adamantanone thus obtained is carried out by synthesizing the 2-adamantanone, (1) alkyllithium, (2) Grignard reagent, and (3) halogen. Alkyl adamantyl alkoxide compound is obtained by reacting at least one alkylating reagent selected from halogenated alkyl compounds and metallic lithium, and then reacting the alkyl adamantyl alkoxide compound with an acid halide or acid anhydride. Is preferred.

The alkylating reagent used in this reaction is at least one selected from (1) alkyl lithium, (2) Grignard reagent, and (3) halogenated alkyl compound and metallic lithium (that is, a combination of both). The compound is not particularly limited as long as it is used, and various compounds depending on the kind of the alkyl group to be introduced are appropriately used.
Specific examples of compounds that can be suitably used as the alkylating reagent include methyllithium, ethyllithium and butyllithium as the alkyllithium; methylmagnesium bromide, ethylmagnesium chloride and the like as the Grignard reagent; halogen. Examples of the alkyl iodide include methyl iodide and ethyl bromide.

The method for obtaining the alkyladamantyl alkoxide compound by reacting these alkylating reagents with 2-adamantanone is not particularly limited. For example, an approximately equimolar or small excess of alkylating reagent relative to 2-adamantanone is used. It can be suitably carried out by reacting in an organic solvent. As the solvent at this time, a known organic solvent can be used without limitation as long as it does not react with the alkylating agent. Examples of organic solvents that can be suitably used include ether solvents such as diethyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, and hydrocarbon solvents such as hexane and toluene.

The reaction conditions for the above reaction are not particularly limited, but the amount of the alkylating reagent used is 0.9 to 1.5 mol, particularly 1.0 to 1.0 mol per 1 mol of 2-adamantanone.
It is preferably 1.3 mol. However, when the combination of the halogenated alkyl compound of the above (3) and metallic lithium is used as the alkylating reagent, the suitable amount of each of these reagents is 2 mol of 2-adamantanone, respectively. 0.8-2.0 mol and 1.5-2.5 gram atom, especially 1.0-1.2 mol and 1.8-2.0 gram atom.

The reaction temperature is not particularly limited and may be appropriately determined depending on the type of the alkylating agent used. When the alkylating reagent of the above (1) or (2) is used, it is usually 20 ° C to 80 ° C. Done. Further, in the case of using the alkylating agent of the above (3), when iodide is used as the alkyl halide, it is preferable to react at −80 ° C. to 20 ° C., and when using bromide or chloride. It is preferable to react at 0 ° C to 100 ° C. Furthermore, the reaction time is usually 0.5 to 24 hours, though it depends on the kind of the alkylating agent used.

The alkyladamantyl alkoxide compound thus obtained is generally used for the reaction with an acid halide or an acid anhydride without isolation. As the acid halide or acid anhydride used at this time,
An acid halide or acid anhydride having a corresponding structure may be used depending on the kind of the target alkyl adamantyl ester compound.

Examples of acid halides that can be preferably used include acetyl chloride, methacrylic acid chloride and benzoyl chloride. On the other hand, examples of acid anhydrides that can be preferably used include acrylic acid anhydride and methacrylic acid anhydride.

The reaction method of the alkyladamantyl alkoxide compound and the acid halide or acid anhydride is not particularly limited, and a known method can be used. For example, it can be suitably carried out by mixing both in the presence of a solvent. At this time, the amount of the acid halide used is 0.9 with respect to 1 mol of the alkyladamantyl alkoxide compound.
It is preferable to use ˜2.0 mol, especially 1.0 to 1.3 mol.

When the acid halide is used in an excessive amount, it is possible to add 1 mol or more of the tertiary amine compound to 1 mol of the excess acid halide, which is particularly desirable. When the alkyladamantyl ester compound is unstable to acid, it is more preferable to add such an amount of the tertiary amine compound. At this time, the tertiary amine compound is not particularly limited, but triethylamine, pyridine, dimethylaminopyridine, diazabicyclo [2.2.2. ] Octane etc. can be used.

The amount of the acid anhydride used is 0.8 to 1 mol with respect to 1 mol of the alkyladamantyl alkoxide compound.
It is preferable to use 2.0 mol, particularly 0.9 to 1.3 mol.

The reaction temperature and reaction time depend on the type of acid halide or acid anhydride, but when an acid halide is used, it is generally 0.5 to 20 ° C. to 100 ° C.
The reaction may be performed for about 24 hours. On the other hand, when an acid anhydride is used, the reaction temperature is 0 ° C to
It is preferable to react at 40 ° C. for 0.5 hours to 6 hours.

The alkyl adamantyl ester compound thus obtained is subjected to usual post-treatments such as washing with water, drying, distilling off the solvent and the like, and subjected to usual purification methods such as silica gel column chromatography, distillation and recrystallization. It can be isolated by using the method.

[0069]

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

Example 1 In a 2 L four-necked flask, 136 g (1 mol) of adamantane dissolved in 300 ml of dichloromethane and 1840 g of 96% concentrated sulfuric acid were added and kept at 25 ° C.
2.1 g (2 mol), t-butyl alcohol 111.
A mixed solution of 2 g (1.5 mol) was added dropwise, the temperature was returned to room temperature, and the reaction was performed for 12 hours.

After confirming that adamantane in the reaction system had disappeared by gas chromatography, dichloromethane was distilled off, and the reaction solution was added dropwise to 2620 g of water at 60 ° C. which was placed in a 4 L four-necked flask. After the dropwise addition, the sulfuric acid concentration was measured by neutralization titration with a 1N aqueous sodium hydroxide solution and found to be 37.9% by mass. Also,
The mixture was stirred for 30 minutes.

After cooling to room temperature, the precipitated crystals were filtered and dried to give 147 g of white crystals of 1-adamantanol (yield 97%, gas chromatography (hereinafter referred to as GC) purity 99.5%). Got

Example 2 In Example 1, 34 g of adamantane (0.25 mo)
l) 96% concentrated sulfuric acid 460 g, acetonitrile 20.5 g
(0.5 mol), 27.8 g of t-butyl alcohol
(0.375 mol), and the same operation as in Example 1 was performed except that the sulfuric acid concentration of the mixed solution after the reaction solution was added dropwise to water was 49.1% by mass (437.5 g of water).

As a result, 34.6 g of white crystalline 1-adamantanol (yield 91%, GC purity 99.5%) was obtained.

Example 3 The same operation as in Example 2 was carried out except that the sulfuric acid concentration of the mixed solution after dropping the reaction solution into water was changed to 24.2% by mass (1200 g of water).

As a result, 35.72 g of white crystals of 1-adamantanol (yield 94%, GC purity 90%) was obtained.

Example 4 In Example 1, 34 g (0.25 mo) of adamantane was used.
l) 96% sulfuric acid 460 g, acetonitrile 20.5 g
(0.5 mol), 27.8 g of t-butyl alcohol
(0.375 mol), the amount of water to which the reaction solution is dropped 655
g (The sulfuric acid concentration of the mixed solution after the reaction solution was dropped into water was 3
It was 7.8% by mass), and the same operation as in Example 1 was performed except that the temperature of the water to which the reaction liquid was dropped was set to 80 ° C.

As a result, 35.7 g (yield 94%, GC purity 99.1%) of white crystalline 1-adamantanol was obtained. Example 5 In Example 4, the temperature of the water to which the reaction solution was dropped was 40 ° C.
The same operation as in Example 4 was carried out except that

As a result, 34.2 g (yield 90%, GC purity 96.4%) of 1-adamantanol as white crystals was obtained.

Examples 6 to 8 The same operation as in Example 1 was carried out except that the compounds shown in Table 1 were used instead of acetonitrile.
The results are shown in Table 1.

[0081]

[Table 1]

Examples 9 to 12 In Example 1, Table 2 was used instead of t-butyl alcohol.
The same operation as in Example 1 was performed except that the compound shown in 1 was used. The results are shown in Table 2.

[0083]

[Table 2]

Examples 13 to 15 The same operations as in Example 1 were carried out except that in Example 1, the compounds shown in Table 3 were used instead of adamantane. The results are shown in Table 2.

[0085]

[Table 3]

Comparative Example 1 The same operation as in Example 2 was carried out except that the temperature of the water to which the reaction solution of the mixed solution after dropping the reaction solution was dropped was 15 ° C.

As a result, 140 g of a mixture of 82.6% 1-adamantanol and 7.2% N- (1-adamantyl) acetamide was obtained by GC. This mixture was recrystallized from a heptane / dichloromethane solution to give 69.4 g of 1-adamantanol (yield 45.6%, GC purity 95.7%).
Got

Example 16 76 g of 1-adamantanol obtained in Example 1 (0.
5 mol) to which 820 g of 96% concentrated sulfuric acid was added,
Stir for 5 hours. After that, the mixture was stirred at 60 ° C. for 5 hours, and it was confirmed that the GC area ratio of 1-adamantanol was 3% or less. The reaction solution was poured into 1300 g of ice, extracted with 700 ml of dichloromethane, and 10% aqueous sodium hydrogen carbonate solution was added. ,
It was washed successively with 10% saline.

Then, by distilling off dichloromethane, 56.3 g (0.375 mo) of 2-adamantanone was obtained.
1, 75%) was obtained.

Example 17 7.5 g of 2-adamantanone obtained in Example 16 (5
0 mmol) was dissolved in 25 mL of tetrahydrofuran, and 50 mL of a previously prepared solution of methylmagnesium bromide in tetrahydrofuran (1 mol / L) was added to 40 mL.
It was added dropwise at a temperature of not higher than 0 ° C.

After confirming the progress of the reaction by GC, 1.25 g (12.5 mmol) of triethylamine and 7.5 g (75 mmol) of methacrylic acid chloride were added to the reaction solution to give 50
The mixture was stirred at ℃ for 3 hours. Confirm the progress of the reaction by GC, water 5m
The reaction was stopped by adding L. After that, tetrahydrofuran was distilled off under reduced pressure and 50 mL of heptane was added,
It was washed successively with an ammonium chloride aqueous solution, a 10% sodium hydroxide aqueous solution, and ion-exchanged water.

Then, heptane was distilled off under reduced pressure to obtain a crude product. 0.75 g of diethylene glycol was added to the crude product, followed by vacuum distillation (92 ° C./0.4 mm
Hg), 6.12 g (52 mmol, 52%) of 2-methyl-2-adamantyl methacrylate was obtained.

Example 18 7.5 g of 2-adamantanone obtained in Example 16 (5
0 mmol) was dissolved in 25 mL of tetrahydrofuran, and 6 g (55 mmol) of ethyl bromide was added. While vigorously stirring the solution, 0.1 g of metallic lithium was added to the solution so that the temperature of the solution did not exceed 30 ° C., and the total amount was 0.75 g.
(85 mmol) was added.

After confirming the progress of the reaction by GC and visually confirming that the metallic lithium had disappeared, 5 g (50 mmol) of methacrylic acid chloride was added to the reaction solution. After confirming that the reaction had proceeded sufficiently by GC, 1.5 mL of methanol and 1.5 mL of 5% sodium hydroxide aqueous solution were added to the reaction solution.
Was added and stirred at room temperature for 1 hour to stop the reaction. Then, the organic solvent was distilled off under reduced pressure, 100 mL of hexane was added, and the resulting solution was added with a 10% sodium hydroxide aqueous solution and 2%.
It was washed successively with 0% saline.

Then, hexane was distilled off under reduced pressure to obtain a crude product, which was recrystallized from isopropanol to give 2-ethyl-2.
-Adamantyl methacrylate 3.97 g (16 mmo
1, 32%).

Example 19 7.5 g of 2-adamantanone obtained in Example 16 (5
0 mmol) was dissolved in 25 mL of tetrahydrofuran, and 50 mL of a previously prepared solution of methylmagnesium bromide in tetrahydrofuran (1 mol / L) was added to 40 mL.
It was added dropwise at a temperature of not higher than 0 ° C.

After confirming the progress of the reaction by GC, 5.34 g (51 mmol) of acrylic acid anhydride was added to the reaction solution, and the mixture was stirred at room temperature for 4 hours. After confirming the progress of the reaction by GC, 1.5 mL of methanol and 1.5 m of 5% sodium hydroxide aqueous solution
L was added at 10 ° C. or lower and stirred for 1 hour, and the organic layer was separated. The organic layer was further washed with 10% aqueous sodium hydroxide solution, and then the solvent was distilled off to obtain a crude product.

The crude product was distilled under reduced pressure (85 ° C./0.3 m).
mHg), 6.77 g (27.5 mmol, 55%) of 2-methyl-2-adamantyl acrylate was obtained.

Example 20 7.5 g of 2-adamantanone obtained in Example 16 (5
0 mmol) was dissolved in 25 mL of tetrahydrofuran, and 6 g (55 mmol) of ethyl bromide was added. While vigorously stirring the solution, 0.1 g of metallic lithium was added to the solution so that the temperature of the solution did not exceed 30 ° C., and the total amount was 0.75 g.
(85 mmol) was added.

After confirming the progress of the reaction by GC and visually confirming that the metallic lithium disappeared, 5.34 g (51 mmol) of acrylic acid anhydride was added to the reaction solution. After confirming that the reaction had proceeded sufficiently by GC, 1.5 mL of methanol and 1.5 m of 5% sodium hydroxide aqueous solution were added to the reaction solution.
L was added and stirred at room temperature for 1 hour to stop the reaction.

Then, the organic layer was separated, the organic layer was further washed with a 10% sodium hydroxide aqueous solution, the organic solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure to give 2-ethyl-2-adamantyl acrylate 4. 64 g (20 mmol, 4
0%).

[0102]

According to the present invention, by reacting an adamantane with an organic nitrile compound, an adamantanol can be produced with an extremely high yield and a high selectivity.

In particular, when the sulfuric acid concentration after mixing the reaction solution and water is set to 30 to 60% by mass, the yield and selectivity of the above-mentioned object are further improved. Moreover, when the concentration of sulfuric acid when the reaction liquid and water are mixed is increased in this way, the amount of the reaction liquid that can be charged into the reactor can be significantly increased. The yield can be increased. For example, it is possible to obtain adamantanols in a yield of 30 kg or more when carried out in a 1 cubic meter reactor.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) C07C 67/14 C07C 67/14 69/54 69/54 B

Claims (5)

[Claims] 1. An adamantane compound is reacted in a reaction solution comprising concentrated sulfuric acid, a carbocation-forming compound, and an organic nitrile compound, and the resulting reaction solution is mixed with water at 20 to 90 ° C. A method for producing adamantanols. 2. The method for producing an adamantanol according to claim 1, wherein the amount of water used is such that the concentration of sulfuric acid after mixing with the reaction liquid becomes 30 to 60% by mass. 3. The adamantane is adamantane,
The method for producing an adamantanol according to claim 1, wherein the adamantanol to be produced is 1-adamantanol. 4. A product obtained by the manufacturing method according to claim 3.
-A method for producing 2-adamantanone, which comprises oxidizing adamantanol in concentrated sulfuric acid. 5. 2-adamantanone obtained by the production method according to claim 3, and (1) alkyllithium,
(2) Grignard reagent, and (3) alkyl halide compound and at least one alkylating reagent selected from metallic lithium are reacted to obtain an alkyladamantyl alkoxide compound, and then the alkyladamantyl alkoxide compound and an acid halide or A method for producing an alkyladamantyl ester compound, which comprises reacting with an acid anhydride.