JP5968301B2 - Process for producing esters derived from bulky hydroxyl-containing compounds - Google Patents

Description

  The present invention relates to a method for producing an ester derived from a bulky hydroxyl group-containing compound.

  A bulky hydroxyl group-containing compound, for example, an ester derived from a bulky tertiary alcohol is a useful compound for the synthesis of a functional material such as an electronic material. More specifically, adamantyl esters are useful as resist agents for various electronic substrates (Patent Document 1).

  Such bulky tertiary alcohol-derived esters are extremely difficult to synthesize, so that no production method suitable for mass synthesis has yet been found.

  Examples of methods for synthesizing esters derived from tertiary alcohols known to date include, for example, a method using di-2-pyridylthionocarbanate as a condensing agent by Mukaiyama et al. A method combining an oxidizing agent (Non-Patent Document 2), a method using lanthanum isopropoxide by Ishihara et al. As a catalyst (Non-Patent Document 3), and the like are known. However, the raw material alcohols used in these methods are all alcohols with relatively few steric hindrances, have poor versatility, and cannot be said to be an industrial production method.

  In addition, a method for producing an ester derived from a bulky tertiary alcohol has been studied by the method shown in the following reaction formula-1.

  However, in the method shown in the above reaction scheme-1, the target bulky tertiary alcohol-derived ester is only obtained in a low yield.

  The inventors of the present invention have intensively studied to develop a method capable of producing a bulky tertiary alcohol-derived ester with high yield. As a result, it was found that an ester derived from a bulky tertiary alcohol can be produced with high yield by the method shown in the following reaction formula-2 (Non-patent Document 4).

  In the method shown in Reaction Formula-2, ester (A) used as a starting material is dialkylated, and then strontium alkoxide (C) to be produced is reacted with 2 equivalents or more of benzoyl chloride (E) in several steps. Is the method. According to this method, a bulky tertiary alcohol-derived ester (F) can be produced in a yield of about 82%.

  However, the method shown in Reaction Formula-2 has various drawbacks, and it is difficult to say that it is an industrially advantageous production method for bulky tertiary alcohol-derived esters. That is, the method shown in Reaction Formula-2 has the following various disadvantages.

  (1) In addition to strontium alkoxide (C), strontium alkoxide (D) is by-produced in the same equivalent amount as (C) by the reaction. Therefore, it is industrially disadvantageous from the viewpoint of the procurement cost of the reaction material and the post-treatment of the unreacted material.

  (2) The bulky tertiary alcohol-derived ester (F) produced by the method shown in Reaction Formula-2 and the by-produced ester (G) are contained in substantially the same amount, and (F) and (G ) Is the same ester, so the physical properties are very similar. For this reason, it is extremely difficult to isolate both by recrystallization and chromatographic techniques. The ester (F) cannot be produced with high purity.

  (3) The method shown in Reaction Formula-2 is a method for producing a bulky tertiary alcohol-derived ester by utilizing dialkylation of ester (A), and is thus limited to the alcohol moiety of product (F). There is a lack of versatility.

  Moreover, the method shown in patent document 2 is proposed as a manufacturing method of ester derived from tertiary alcohol. This method is represented by the general formula (H)

[Wherein Z represents a non-aromatic or aromatic monocyclic or polycyclic ring. R ^A and R ^B are the same or different and represent a hydrocarbon group. R ^A and R ^B may be bonded to each other to form an alicyclic ring together with adjacent carbon atoms. ]
And a tertiary alcohol represented by the general formula (I) using a Grignard reagent or an organolithium reagent.

[Wherein, R ^C represents a hydrocarbon group or a heterocyclic group. Z, R ^A and R ^B are the same as above. ]
It is a method of manufacturing.

However, the inventors have clarified that the above method cannot produce a bulky tertiary alcohol-derived ester. According to Patent Document 2, in Examples 1 to 6, esters derived from 1- (1′-adamantyl) -1-methylethanol are produced at a yield of about 65.2 to 90.5%. . However, the esters produced in Examples 1 to 6 are those in which R ^A and R ^B are both methyl groups in the above general formula (I). Therefore, the esters produced in these Examples are bulky tertiary compounds. It is not an alcohol-derived ester. The present inventors used a bulky tertiary alcohol in which R ^A and R ^B are both isobutyl groups as starting materials, and used the above Grignard reagent and organolithium reagent to produce a bulky tertiary alcohol-derived ester. Production was attempted, but bulky esters derived from tertiary alcohol could only be produced in low yield (see Comparative Examples 1 and 2 below). It was also found that by this method, a Grignard reagent and an organolithium reagent produce by-products due to side reactions such as reaction with an acid anhydride or acid halide. That is, the method of Patent Document 2 has a drawback that a bulky tertiary alcohol-derived ester cannot be selectively produced with good yield. Further, the method of Patent Document 2 uses a Grignard reagent or an organolithium reagent in the form of a solution, and therefore has an industrial disadvantage that it cannot be concentrated to a certain concentration or more.

JP 2002-105022 A JP 2002-173466 A

Chemistry Letters, Vol.27, p.3, 1998 Chemistry Letters, Vol.32, p.300, 2003 Organic Letters, Vol.13, p.426, 2011 Journal of Synthetic Organic Chemistry, Vol.67, p.1274, 2009

  The subject of this invention is providing the industrially advantageous manufacturing method of the ester derived from a bulky tertiary alcohol without the fault of said (1)-(3).

  Another object of the present invention is to provide a method for producing a bulky tertiary alcohol-derived ester in a high yield.

  As a result of intensive research to develop an industrially advantageous production method for esters derived from bulky tertiary alcohols that have solved the above problems, the present inventors have used bulky tertiary alcohols as starting materials. Then, by reacting the tertiary alcohol with metal strontium and an alkyl halide, and then reacting the resulting reaction product with an acid halide and / or an acid anhydride, an ester derived from the desired bulky tertiary alcohol is produced. Has been found to be advantageous. In addition, the present inventors can use a bulky phenol as a starting material instead of a bulky tertiary alcohol and perform a reaction similar to the above to produce a bulky phenol-derived ester industrially. I found it. The present invention has been completed based on such findings.

  The present invention provides a method for producing an ester derived from a bulky tertiary alcohol or a bulky phenol according to the following items 1 to 14.

  Item 1. General formula (1)

[Wherein R ¹ , R ² and R ³ represent any one of the following (i) to (iv).
(I) R ¹ , R ² and R ³ are the same or different and represent a C _1-20 saturated or unsaturated hydrocarbon group. However, at least one of R ^{1 to} R ³ is a hydrocarbon group having 4 or more carbon atoms.
(Ii) R ¹ and R ² are bonded to each other to form a C _3-20 saturated or unsaturated hydrocarbon ring together with adjacent carbon atoms. R ³ represents a C _1-20 saturated or unsaturated hydrocarbon group.
(Iii) R ¹ , R ² and R ³ together with the adjacent carbon atoms form a C _3-20 saturated or unsaturated hydrocarbon ring.
(Iv) R ¹ , R ² and R ³ together with adjacent carbon atoms form a phenyl group, and each of the 2 ortho positions of the phenyl group has a C _3-9 branched carbonization Has a hydrogen group. ]
In addition to bulky tertiary alcohols or bulky phenols represented by the formula, metal strontium and general formula (2)
R ⁴ X ¹ (2)
[Wherein, R ⁴ represents a C _1-9 linear or branched alkyl group. X ¹ represents a halogen atom. ]
A general formula (3) produced by reacting an alkyl halide represented by

[Wherein, R ¹ , R ² , R ³ and X ¹ are the same as above. ]
In the compound represented by general formula (4)
R ⁵ COX ² (4)
[Wherein, R ⁵ represents a C _1-20 saturated or unsaturated hydrocarbon group. X ² represents a halogen atom. ]
An acid halide represented by the general formula (5)
(R ⁵ CO) ₂ O (5)
[Wherein, R ⁵ is the same as defined above. ]
Is reacted with an acid anhydride represented by the general formula (6)

[Wherein, R ¹ , R ² , R ³ and R ⁵ are the same as above. ]
A process for producing an ester derived from a bulky tertiary alcohol or a bulky phenol represented by the formula:

Item 2. The method for producing an ester according to item 1, wherein R ¹ , R ² and R ³ in the general formula (1) represent the above (i).

Item 3. The C _1-20 saturated or unsaturated hydrocarbon group represented by R ¹ , R ² and R ³ in the above (i) is an aryl group which may have a substituent or an aryl C _{1 which} may have a substituent. _{A -9} alkyl group, an _optionally substituted aryl C _2-9 alkenyl group, an _optionally substituted aryl C _2-9 alkynyl group, a C _1-20 saturated or unsaturated aliphatic hydrocarbon group, Or the method of manufacturing the ester of said claim | item 2 which is a _C3-20 saturated or unsaturated alicyclic hydrocarbon group.

Item 4. Item 4. The method for producing an ester according to Item 2 or 3, wherein R ² and R ³ in the general formula (1) are each a C _3-9 branched alkyl group.

Item 5. The ester according to any one of Items 2 to 4, wherein R ¹ in the general formula (1) is an aryl group which may have a substituent or an aryl C _1-9 alkyl group which may have a substituent. How to manufacture.

Item 6. The method for producing an ester according to item 1, wherein R ¹ , R ² and R ³ in the general formula (1) represent the above (ii).

Item 7. The hydrocarbon ring formed by combining R ¹ and R ² in (ii) together with adjacent carbon atoms is a C _5-10 cycloalkane ring, a C _5-10 cycloalkene ring or an adamantane ring. The method for producing an ester according to Item 6.

Item 8. The method for producing an ester according to item 1, wherein R ¹ , R ² and R ³ in the general formula (1) represent the above (iii).

Item 9. The ring formed by combining R ¹ , R ² and R ³ with the adjacent carbon atom in (iii) is a bicyclo [2,2,1] heptane ring, a bicyclo [2,2,2] octane ring or Item 9. The method for producing an ester according to Item 8, which is an adamantane ring.

Item 10. ^{How R} 1, ^{R 2} and ^{R 3} in formula (1) wherein indicating the (iv), to produce the esters according to the claim 1.

Item 11. The phenyl group formed by R ¹ , R ² and R ³ in the above (iv) is represented by the general formula (7)

[Wherein, R ⁶ and R ⁷ are the same or different and represent a C _3-9 branched hydrocarbon group. R ⁸ represents a C _1-9 alkyl group. ]
Item 11. The method for producing an ester according to Item 10, wherein the ester is a bulky phenyl group.

Item 12. R ⁵ in the general formulas (4) and (5) is an aryl group that may have a substituent, an aryl C _1-9 alkyl group that may have a substituent, an aryl C ₂₋ that may have a substituent. ₉ alkenyl group, aryl C _2-9 alkynyl group which may have a substituent, C _1-20 saturated or unsaturated aliphatic hydrocarbon group, or C _3-20 saturated or unsaturated alicyclic hydrocarbon group The method for producing an ester according to any one of Items 1 to 11, wherein:

Item 13. In the above item 12, wherein R ⁵ is a C _1-9 alkyl group, an aryl C _1-9 alkyl group, an aryl group which may have a substituent, or an aryl C _2-9 alkenyl group which may have a substituent. A process for producing the described ester.

  Item 14. The use amount of the metal strontium is 1 to 2 equivalents relative to the bulky tertiary alcohol or bulky phenol represented by the general formula (1), A method for producing an ester.

Examples of the C _1-20 saturated or unsaturated hydrocarbon group represented by R ¹ , R ² and R ³ include an aryl group which may have a substituent and an aryl C _{1-9 which} may have a substituent. An alkyl group, an optionally substituted aryl C _2-9 alkenyl group, an _optionally substituted aryl C _2-9 alkynyl group, a C _1-20 saturated or unsaturated aliphatic hydrocarbon group, C _{3 -20} saturated or unsaturated alicyclic hydrocarbon group and the like.

Examples of the aryl group which may have a substituent represented by R ¹ , R ² and R ³ include, for example, an aryl group such as a phenyl group and a naphthyl group, and C _{1-6 at} an arbitrary position on the aryl group. Examples include those in which 1 to 3 substituents such as an alkyl group, a C _1-6 alkoxy group, a nitro group, a cyano group, an amino group, a carboxyl group, and a C _1-6 alkanoyl group are substituted.

The aryl _{C 1-9} alkyl group which may have a substituent represented by R ^{1, R 2} and ^{R 3,} the other aryl _{C 1-9} alkyl group such as 2-phenylethyl group, on the aryl group A compound in which 1 to 3 substituents such as C _1-6 alkyl group, C _1-6 alkoxy group, nitro group, cyano group, amino group, carboxyl group, C _1-6 alkanoyl group are substituted at an arbitrary position, etc. Can be mentioned.

R ^1, the aryl _{C 2-9} alkenyl group which may have a ^{R 2} and substituents represented by ^{R 3,} for example, 2-phenylethenyl group, 2- naphthylethenyl aryl _{C 2-9} alkenyl groups such as In addition, a substituent such as a C _1-6 alkyl group, a C _1-6 alkoxy group, a nitro group, a cyano group, an amino group, a carboxyl group, a C _1-6 alkanoyl group or the like is 1 at any position on the aryl group. -3 substituted ones can be mentioned. The alkenyl group in the aryl C _2-9 alkenyl group has, for example, 1 to 3 double bonds.

R ^1, the aryl _{C 2-9} alkynyl group which may have a substituent represented by ^{R 2} and ^{R 3,} for example, 2-phenylethynyl group, aryl _{C 2-9} alkynyl groups such as 2-naphthylethynyl group In addition, a substituent such as a C _1-6 alkyl group, a C _1-6 alkoxy group, a nitro group, a cyano group, an amino group, a carboxyl group, a C _1-6 alkanoyl group or the like is 1 at any position on the aryl group. -3 substituted ones can be mentioned. The alkynyl group in the aryl C _2-9 alkynyl group has, for example, 1 to 3 triple bonds.

The saturated or unsaturated aliphatic hydrocarbon group of _{C 1-20} shown by R ^{1, R 2} and ^{R 3,} for _example, an alkyl _group, an alkenyl group of _{C 2-20} of _{C 1-20, C 2-20} And the like. More specifically, examples of the C _1-20 alkyl group include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n- Examples thereof include linear or branched alkyl groups such as a pentyl group, isopentyl group, neopentyl group, n-hexyl group, isohexyl group, and n-nonyl group. _Examples of the C _2-20 alkenyl group include an ethenyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, and a nonenyl group. Examples of the alkynyl group include ethynyl group, propynyl group, butynyl group, pentynyl group, hexynyl group, and noninyl group.

Examples of the C _3-20 saturated or unsaturated alicyclic hydrocarbon group represented by R ¹ , R ² and R ³ include, for example, a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, an adamantyl group, a bicyclo [2,2, 1] heptyl group, bicyclo [2,2,2] octyl group, cyclopropenyl group, cyclopentenyl group, cyclohexenyl group and the like.

R ¹ in the above (i) is an aryl group that may have a substituent, an aryl C _1-9 alkyl group that may have a substituent, an aryl C _2-9 alkenyl group that may have a substituent, It may be an aryl C _2-9 alkynyl group, a C _1-20 saturated or unsaturated aliphatic hydrocarbon group, or a C _3-20 saturated or unsaturated alicyclic hydrocarbon group, which may have a substituent. Preferably, it is an aryl group that may have a substituent or an aryl C _1-9 alkyl group that may have a substituent.

R ² in the above (i) is an aryl group that may have a substituent, an aryl C _1-9 alkyl group that may have a substituent, an aryl C _2-9 alkenyl group that may have a substituent, It may be an aryl C _2-9 alkynyl group, a C _1-20 saturated or unsaturated aliphatic hydrocarbon group, or a C _3-20 saturated or unsaturated alicyclic hydrocarbon group, which may have a substituent. Preferably, it is a C _1-9 alkyl group, more preferably a C _3-9 branched alkyl group. Examples of the C _3-9 branched alkyl group include an isopropyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, and a neopentyl group.

R ³ in the above (i) is an aryl group that may have a substituent, an aryl C _1-9 alkyl group that may have a substituent, an aryl C _2-9 alkenyl group that may have a substituent, It may be an aryl C _2-9 alkynyl group, a C _1-20 saturated or unsaturated aliphatic hydrocarbon group, or a C _3-20 saturated or unsaturated alicyclic hydrocarbon group, which may have a substituent. Preferably, it is a C _1-9 alkyl group, more preferably a C _3-9 branched alkyl group. Examples of the C _3-9 branched alkyl group include an isopropyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, and a neopentyl group.

Examples of the C _3-20 saturated or unsaturated ring in which R ¹ and R ² in (ii) above are bonded to each other and formed together with adjacent carbon atoms include, for example, a C _3-20 cycloalkane ring, A C _3-20 cycloalkene ring and the like can be mentioned, and a C _5-10 cycloalkane ring, a C _5-10 cycloalkene ring and the like are preferable. Here, the cycloalkane ring and the cycloalkene ring may form two or more rings by having a bridge portion. Specifically, cyclopropane ring, cyclopentane ring, cyclohexane ring, adamantane ring, bicyclo [2,2,1] heptane ring, bicyclo [2,2,2] octane ring, cyclopentene ring, cyclohexene ring, bicyclo [2 , 2,1] heptene ring, bicyclo [2,2,2] octene ring, and the like.

^R 1, ^{R 2} and ^{R 3} in (iii) above, as the saturated or unsaturated ring _{C 3-20} which they are formed together with the carbon atom adjacent, for _example, bicyclo _{C 3-20} Examples include an alkane ring and a C _3-20 bicycloalkene ring. Here, the bicycloalkane ring and the bicycloalkene ring may form a further ring by further having a bridge. In this case, the hydroxyl group of the tertiary alcohol is bonded to the carbon atom at the bridge head. Specifically, bicyclo [2,2,1] heptane ring, bicyclo [2,2,2] octane ring, adamantane ring, bicyclo [2,2,1] heptene ring, bicyclo [2,2,2] octene A ring etc. are mentioned.

Examples of the C _1-20 saturated or unsaturated hydrocarbon group represented by R ⁵ include an aryl group that may have a substituent, an aryl C _1-9 alkyl group that may have a substituent, and a substituent. An aryl C _2-9 alkenyl group which may have, an aryl C _2-9 alkynyl group which may have a substituent, a C _1-20 saturated or unsaturated aliphatic hydrocarbon group, or a C _3-20 saturated or An unsaturated alicyclic hydrocarbon group is mentioned.

Examples of the aryl group which may have a substituent represented by R ⁵ include an aryl group such as a phenyl group and a naphthyl group, a C _1-6 alkyl group, a C _1- Examples include those in which 1 to 3 substituents such as ₆ alkoxy group, nitro group, cyano group, amino group, carboxyl group, C _1-6 alkanoyl group are substituted.

The aryl C _1-9 alkyl group which may have a substituent represented by R ^5, for example, the other aryl C _1-9 alkyl group such as 2-phenylethyl group, at any position on the aryl group Examples include those in which 1 to 3 substituents such as C _1-6 alkyl group, C _1-6 alkoxy group, nitro group, cyano group, amino group, carboxyl group, C _1-6 alkanoyl group are substituted. .

The aryl C _2-9 alkenyl group which may have a substituent represented by R ^5, for example, 2-phenylethenyl group, the other aryl C _2-9 alkenyl groups such as 2-naphthylethenyl group, the aryl group 1 to 3 substituents such as C _1-6 alkyl group, C _1-6 alkoxy group, nitro group, cyano group, amino group, carboxyl group, C _1-6 alkanoyl group, etc. substituted at any position above Etc. The alkenyl group in the aryl C _2-9 alkenyl group has, for example, 1 to 3 double bonds.

The aryl C _2-9 alkynyl group which may have a substituent group which may have a substituent represented by R ^5, for example, 2-phenylethynyl group, aryl C _2-9 alkynyl such as 2-naphthylethynyl group In addition to the group, a substituent such as a C _1-6 alkyl group, a C _1-6 alkoxy group, a nitro group, a cyano group, an amino group, a carboxyl group, a C _1-6 alkanoyl group or the like is present at any position on the aryl group. Examples include one to three substituted. The alkynyl group in the aryl C _2-9 alkynyl group has, for example, 1 to 3 triple bonds.

The saturated or unsaturated aliphatic hydrocarbon group of _{C 1-20} shown by R ^5, for _example, include an alkyl group of _{C 1-20,} alkenyl group _{C 2-20,} alkynyl groups _{C 2-20} etc. It is done. More specifically, examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, and an isopentyl group. , A linear or branched alkyl group such as a neopentyl group, an n-hexyl group, an isohexyl group, and an n-nonyl group. Examples of the alkenyl group include those having 1 to 10 double bonds, and more specific examples include an ethenyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, and a nonenyl group. Examples of the alkynyl group include those having 1 to 10 triple bonds, and more specific examples include an ethynyl group, a propynyl group, a butynyl group, a pentynyl group, a hexynyl group, and a noninyl group.

Examples of the C _3-20 saturated or unsaturated alicyclic hydrocarbon group represented by R ⁵ include a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, an adamantyl group, a bicyclo [2,2,1] heptyl group, and a bicyclo group. [2,2,2] octyl group, cyclopropenyl group, cyclopentenyl group, cyclohexenyl group and the like.

R ⁵ includes an aryl group that may have a substituent, an aryl C _1-9 alkyl group that may have a substituent, an aryl C _2-9 alkenyl group that may have a substituent, and a substituent. aryl _{C 2-9} alkynyl group which is _preferably a saturated or unsaturated aliphatic hydrocarbon group, or a saturated or unsaturated alicyclic hydrocarbon group having _{C 3-20} of _{C 1-20, C 1-} It is more preferably a ₉ alkyl group, an aryl C _1-9 alkyl group, an aryl group that may have a substituent, or an aryl C _2-9 alkenyl group that may have a substituent.

In the above (iv), R ¹ , R ² and R ³ together with adjacent carbon atoms form a phenyl group, and each of the 2 ortho positions of the phenyl group has a C _3-9 branched chain. The bulky tertiary alcohol or bulky phenol represented by the above general formula (1) in the case of having a hydrocarbon group is represented by the general formula (8)

The bulky phenol represented by these is included.

Examples of the C _3-9 branched hydrocarbon group in R ⁶ and R ⁷ include isopropyl group, tert-butyl group, sec-butyl group, 1-methylbutyl group, 1,1-dimethylpropyl group, 1 -A methylpentyl group, a 1, 1-dimethylbutyl group, etc. are mentioned.

The C _1-9 alkyl group for R ⁸ is preferably a C _1-6 alkyl group.

Examples of the halogen atom represented by X ¹ and X ² include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

R ⁴ is preferably an alkyl group having 1 to 6 carbon atoms, more preferably an alkyl group having 1 to 3 carbon atoms, and particularly preferably a methyl group.

  Reaction in which a metal strontium and an alkyl halide represented by the general formula (2) are allowed to act on a bulky tertiary alcohol or bulky phenol represented by the general formula (1) (this reaction is hereinafter referred to as “A reaction”). Is carried out in a suitable solvent.

  Here, as the solvent, a solvent that does not adversely influence the reaction can be widely used, and examples thereof include ether solvents such as diethyl ether, tetrahydrofuran, and dioxane. Of these, tetrahydrofuran is preferred.

  The amount of metal strontium used is usually 1 to 2 equivalents, preferably 1.2 to 1.7 equivalents, relative to the bulky tertiary alcohol or bulky phenol of the general formula (1). ) Of the halogenated alkyl is usually 1 to 2 equivalents, preferably 1.2 to 1.7 equivalents, relative to the bulky tertiary alcohol or bulky phenol of the general formula (1).

  The reaction A is usually performed at about 0 to 35 ° C., preferably near room temperature, and the reaction is generally completed in about 20 minutes to 1 hour.

  A reaction in which an acid halide of the general formula (4) and / or an acid anhydride of the general formula (5) is allowed to act on the compound of the general formula (3) generated by the A reaction (this reaction is hereinafter referred to as “B reaction”) is Is carried out in a suitable solvent. The solvent used in the B reaction may be the same as the solvent used in the A reaction. Therefore, from the viewpoint of reaction efficiency, it is preferable to add the acid halide of the general formula (4) and / or the acid anhydride of the general formula (5) to the reaction solution after the completion of the A reaction, and continue the B reaction.

  Either one of the acid halide of the general formula (4) and the acid anhydride of the general formula (5) may be used, or both may be used in combination.

  The amount of the acid halide of the general formula (4) or the acid anhydride of the general formula (5) is usually 1 to 2 equivalents, preferably 1.2 to 1.7 equivalents, relative to the compound of the general formula (3). It is.

  The reaction B is usually performed at about 0 to 35 ° C., preferably at about room temperature, and the reaction is generally completed in about 40 minutes to 2 hours. Thus, the bulky tertiary alcohol represented by the general formula (6) or the bulky phenol-derived ester is produced in a high yield.

  In isolating and purifying the ester of the general formula (6) from the reaction mixture obtained above, known isolation means and purification means can be employed. For example, in order to remove unreacted acid halide of the general formula (4) and / or acid anhydride of the general formula (5) from the reaction mixture, the reaction mixture is washed with aqueous ammonia and then extracted with diethyl ether. Next, the diethyl ether extract is dried, concentrated, and then purified using an aluminum column, whereby the ester of the general formula (6) can be obtained with high purity.

  According to the method of the present invention, an ester derived from a bulky hydroxyl group-containing compound represented by the general formula (6) can be produced with high yield and high purity.

  The method of the present invention has no problems as shown in the above (1) to (3), and is extremely advantageous as an industrial production method of an ester derived from a bulky hydroxyl group-containing compound represented by the general formula (6). .

  The present invention will be further clarified by the following examples.

Example 1
In a sufficiently dried two-diameter reaction vessel, 132 mg (1.51 mmol) of metal strontium and 1-phenyl-1- (2-methylethyl) -3-methyl as a bulky hydroxyl group-containing compound represented by the general formula (1) 224 mg (1.02 mmol) of -1-propanol and 5 ml of tetrahydrofuran as a solvent were added. Under stirring at room temperature, 214 mg (1.51 mmol) of methyl iodide as an alkyl halide represented by the general formula (2) was added and stirred for 30 minutes to produce a strontium alkoxide represented by the general formula (3). It was. Thereafter, 210 mg (1.49 mmol) of benzoyl chloride was added as an acid chloride represented by the general formula (4) and reacted for 60 minutes. The reaction was stopped by adding 2 ml of 14N concentrated aqueous ammonia. 150 ml of diethyl ether was divided into three portions, and organic substances were extracted from the aqueous layer. The organic layers were collected, washed with 5% aqueous sodium hydrogen sulfite solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent; n-hexane: ethyl acetate = 4: 1) to obtain the target compound (1) which is a bulky ester represented by the general formula (6). 276 mg of (benzyloxy-1-phenyl-1- (2-methylethyl) -3-methylpropane) was obtained with a yield of 84%.

Examples 2-16
Using appropriate starting materials, esters derived from bulky hydroxyl group-containing compounds shown in the following Tables 1 to 6 were produced in the same manner as in Example 1. When an acid anhydride was used, an acid anhydride was used in place of the benzoyl chloride of Example 1. In each table, Ph means a phenyl group, and t-Bu means a tert-butyl group.

Example 17
A bulky hydroxyl-containing compound-derived ester was produced in the same manner as in Example 1 except that the bulky hydroxyl-containing compound used was replaced with 2,6-di-tert-butyl-4-methylphenol, which is a bulky phenol. .

Example 18
In a sufficiently dry two-diameter reaction vessel, 137 mg (1.56 mmol) of metal strontium and 1- (2-phenylethyl) -1- (2-methylpropyl) as a bulky hydroxyl group-containing compound represented by the general formula (1) ) -3-methyl-1-butanol (236 mg, 0.95 mmol) and 5 ml of tetrahydrofuran as a solvent were added. Under stirring at room temperature, 269 mg (1.89 mmol) of methyl iodide as an alkyl halide represented by the general formula (2) was added and stirred for 30 minutes to produce a strontium alkoxide represented by the general formula (3). It was. Thereafter, 166 mg (1.46 mmol) of acetic anhydride was added as an acid anhydride represented by the general formula (5) and reacted for 60 minutes. The reaction was stopped by adding 2 ml of 14N concentrated aqueous ammonia. 150 ml of diethyl ether was divided into three portions, and organic substances were extracted from the aqueous layer. The organic layers were collected, washed with 5% aqueous sodium hydrogen sulfite solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel thin layer chromatography (developing solvent; n-hexane: ethyl acetate = 10: 1) to obtain 180 mg of the target compound which is a bulky ester represented by the general formula (6). Was obtained in a yield of 65%. Further, 84 mg (yield 35%) of a raw material which is a bulky tertiary alcohol represented by the general formula (1) was recovered.

Comparative Example 1
In a sufficiently dried two-diameter reaction vessel, 1- (2-phenylethyl) -1- (2-methylpropyl) -3-methyl-1-butanol as a bulky hydroxyl group-containing compound represented by the general formula (1) 231 mg (0.93 mmol) and 5 ml of tetrahydrofuran as a solvent were added. To this, 0.72 ml (1.20 mmol in terms of n-butyllithium) of a 1.66 mol / L n-butyllithium / hexane solution was added dropwise and stirred for 30 minutes. Thereafter, 162 mg (1.59 mmol) of acetic anhydride was added as an acid anhydride represented by the general formula (5) and reacted for 60 minutes.

  Similar to the above examples, the yield of bulky tertiary alcohol-derived ester and the recovery rate of bulky tertiary alcohol as a raw material were determined.

Comparative Example 2
The yield of bulky tertiary alcohol-derived ester and the bulky first material are the same as in Comparative Example 1 except that n-butylmagnesium chloride was used instead of n-butyllithium in Comparative Example 1 above. The recovery rate of tertiary alcohol was determined.

  Table 7 shows the results of Example 18 and Comparative Examples 1 and 2.

  As is clear from Table 7 above, the method described in Patent Document 2 cannot produce a bulky ester derived from a tertiary alcohol with good yield. In Comparative Example 1 and Comparative Example 2, the amount of metal reagent used is smaller than the amount of metal reagent used in Example 18, but this is preferable if the amount of metal reagent used is the same as that used in Example 18. This is because no side reaction occurs and the yield of the target compound is further reduced.

Furthermore, when H ¹ -NMR data on the residue before the purification step was observed, both n-butyllithium was used in Comparative Example 1 and n-butylmagnesium chloride was used in Comparative Example 2, both of which were large. It was revealed that several side reactions were in progress. This is considered to be due to a side reaction between excess n-butyllithium and n-butylmagnesium chloride and anhydride. In Comparative Examples 1 and 2, the consumption rate of the raw material by side reaction determined from the yield of the target product and the recovery rate of the raw material was 22% for n-butyllithium and 27% for n-butylmagnesium chloride.

On the other hand, in Example 18, when metal strontium was used, the H ¹ -NMR data of the residue before the purification step was observed. As a result, the spectrum containing only the target product and the raw material was not observed. . In Example 18, the sum of the yield of the target product and the recovery rate of the raw material was 100%, and it is clear that the bulky hydroxyl group-containing compound-derived ester can be produced selectively by the method of the present invention using metal strontium. is there.

Claims (9)

General formula (1)

[Wherein R ¹ , R ² and R ³ represent any one of the following (i) to ( iii ).
(I) R ¹ , R ² and R ³ are the same or different and represent a C _1-20 saturated or unsaturated hydrocarbon group. However, at least one of R ^{1 to} R ³ is a hydrocarbon group having 4 or more carbon atoms.
(Ii) R ¹ and R ² are bonded to each other to form a C _3-20 saturated or unsaturated hydrocarbon ring together with adjacent carbon atoms. R ³ represents a C _1-20 saturated or unsaturated hydrocarbon group.
^{(Iii) R} 1, R ² and ^{R 3} together with the carbon atom to which they are adjacent to form a bicycloalkane ring or _{C 3-20} bicycloalkyl cycloalkene ring _{C 3-20.} ]
Or general formula (8)

[Wherein, R ⁶ and R ⁷ are the same or different and represent a C _3-9 branched hydrocarbon group. R ⁸ represents a C _1-9 alkyl group. ]
In addition to the bulky tertiary alcohol or bulky phenol represented by the formula, the metal strontium and the general formula (2)
R ⁴ X ¹ (2)
[Wherein, R ⁴ represents a C _1-9 linear or branched alkyl group. X ¹ represents a halogen atom. ]
A general formula (3) produced by reacting an alkyl halide represented by

[Wherein, R ¹ , R ² , R ³ and X ¹ are the same as above. ]
Or general formula (9)

[Wherein, R ⁶ , R ⁷ , R ⁸ and X ¹ are the same as above. ]
In the compound represented by the general formula (4)
R ⁵ COX ² (4)
[Wherein, R ⁵ represents a C _1-20 saturated or unsaturated hydrocarbon group. X ² represents a halogen atom. ]
An acid halide represented by the general formula (5)
(R ⁵ CO) ₂ O (5)
[Wherein, R ⁵ is the same as defined above. ]
Is reacted with an acid anhydride represented by the general formula (6)

[Wherein, R ¹ , R ² , R ³ and R ⁵ are the same as above. ]
Or general formula (10)

[Wherein R ⁶ , R ⁷ , R ⁸ and R ⁵ are the same as above. ]
A process for producing an ester derived from a bulky tertiary alcohol or a bulky phenol represented by the formula: The method for producing an ester according to claim 1, wherein R ¹ , R ² and R ³ in the general formula (1) represent the above (i). The C _1-20 saturated or unsaturated hydrocarbon group represented by R ¹ , R ² and R ³ in the above (i) is an aryl group which may have a substituent or an aryl C _{1 which} may have a substituent. _{A -9} alkyl group, an _optionally substituted aryl C _2-9 alkenyl group, an _optionally substituted aryl C _2-9 alkynyl group, a C _1-20 saturated or unsaturated aliphatic hydrocarbon group, Or the method of manufacturing ester of Claim 2 which is a _C3-20 saturated or unsaturated alicyclic hydrocarbon group. The method for producing an ester according to claim 2 or 3, wherein R ² and R ³ in the general formula (1) are each a C _3-9 branched alkyl group. The ester according to any one of claims 2 to 4, wherein R ¹ in the general formula (1) is an aryl group which may have a substituent or an aryl C _1-9 alkyl group which may have a substituent. How to manufacture. Formula (1) or the general formula bulky represented by (8) a tertiary alcohol or hindered phenols are the hindered phenols represented by the general formula (8), according to claim 1 A method for producing an ester. R ⁵ in the general formulas (4) and (5) is an aryl group that may have a substituent, an aryl C _1-9 alkyl group that may have a substituent, an aryl C ₂₋ that may have a substituent. ₉ alkenyl group, aryl C _2-9 alkynyl group which may have a substituent, C _1-20 saturated or unsaturated aliphatic hydrocarbon group, or C _3-20 saturated or unsaturated alicyclic hydrocarbon group The method for producing an ester according to any one of claims 1 to 6 . Wherein ^{R 5} is _{C 1-9} alkyl, aryl _{C 1-9} alkyl group, an aryl _{C 2-9} alkenyl group which may have an aryl group or a substituent which may have a substituent, in claim 7 A process for producing the described ester. The usage-amount of the said metal strontium is 1-2 equivalent with respect to the bulky tertiary alcohol or bulky phenol represented by the said General formula (1) or the said General formula (8) . A method for producing the ester according to any one of 8 .