JP2018104430A - Production method of glycidic acid ester - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel glycidic acid ester that can be efficiently recovered during production and can be expected to be applied as a synthesis intermediate body, and a production method thereof.SOLUTION: Provided are a novel glycidic acid ester represented by the formula (I) having a step of oxidatively esterifying a compound represented by the formula (II) with a compound selected from organic nitroxyl radical, its N-hydroxy and its oxoammonium cation-containing salt, an oxidant and a base and its production method. (Rand Reach independently represents a monovalent hydrocarbon group or are mutually bonded to represent a divalent hydrocarbon group forming a ring structure, except for the case where Rand Rare simultaneously a methyl group.)SELECTED DRAWING: None

Description

  The present invention relates to a method for producing a novel glyceric acid ester.

Compounds having a glyceric acid skeleton in which the hydroxyl groups at the 2-position and 3-position are protected as cyclic acetal groups include, for example, synthetic intermediates such as glyceric acid and esters thereof that are used as raw materials for various pharmaceuticals, cosmetics, detergents, polymers, etc. Useful as a body.
As examples of compounds having a glyceric acid skeleton in which the hydroxyl groups at the 2-position and 3-position are protected as cyclic acetal groups, for example, Non-Patent Documents 1 to 4 include 4-hydroxymethyl-2,2 that can be produced from glycerol and acetone. -2,2-dimethyl-1,3-dioxolane-4-carboxylic acid by dimerization reaction of dimethyl-1,3-dioxolane or its oxidized 4-formyl-2,2-dimethyl-1,3-dioxolane A preparation example of acid (2,2-dimethyl-1,3-dioxolan-4-yl) methyl ester is described.

Synlett, Vol. 10, pp. 1565-1566, 2001 The Journal of Organic Chemistry, Vol. 69, p. 5116-5119, 2004. The Journal of Organic Chemistry (The Journal of Organic Chemistry), Vol. Tetrahedron, 63, 11325-11340, 2007 Synlett, Vol. 23, 2261-2265, 2012

  The method for producing 2,2-dimethyl-1,3-dioxolane-4-carboxylic acid (2,2-dimethyl-1,3-dioxolan-4-yl) methyl ester described in Non-Patent Documents 1 to 4 is as follows. Is as follows.

However, the compounds having a glyceric acid skeleton in which the hydroxyl groups at positions 2 and 3 described in Non-Patent Documents 1 to 4 are protected as cyclic acetal groups are only compounds derived from acetone.
Non-patent documents 1 to 4 are documents describing the development of a novel dimerization reaction method or a dimer compound obtained as a by-product, and the 2- and 3-position hydroxyl groups are protected as cyclic acetal groups. There is no description on substrate selection and reaction conditions for realizing the production of a compound having a glyceric acid skeleton or industrialization of subsequent derivative development.
In various reactions using an organic solvent, a step of washing the organic layer with water is generally performed for the purpose of efficiently removing byproducts such as catalysts and inorganic salts derived from the auxiliary materials. On the other hand, if the water solubility of the target compound is high, the yield decreases in the washing step, which is economically disadvantageous, or the work load for recovering the target compound from the aqueous phase increases.
The present invention relates to providing a novel glyceric acid ester that is expected to be applied as a synthetic intermediate and has a high recovery rate in a washing step after the reaction, and that requires little work during production, and a method for producing the same.

The present invention relates to the following <1> and <2>.
<1> A method for producing a compound represented by the following formula (I), comprising a step of oxidative esterification of the compound represented by the following formula (II).

(In formula (II), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.)

(In formula (I), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.)

  <2> A compound represented by the following formula (I).

(In formula (I), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.)

  ADVANTAGE OF THE INVENTION According to this invention, the recovery rate in the washing process after reaction is high, there are few work additions at the time of manufacture, and the novel glyceric acid ester with which application as a synthetic intermediate is anticipated and its manufacturing method can be provided. .

[Compound represented by formula (I)]
The compound represented by the following formula (I) of the present invention is a novel glyceric acid ester (hereinafter also referred to as “the glyceric acid ester of the present invention” or “the ester dimer of the present invention”).
Glyceric acid and its ester form can be produced from the glyceric acid ester of the present invention. In addition, the glyceric acid ester of the present invention has an excellent effect that the recovery rate in the water washing step after the reaction is high and the work addition during the production is small.

(In formula (I), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.)

In formula (I), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² represent a divalent hydrocarbon group that is bonded to each other to form a ring structure. Represent.
As a preferred embodiment of R ¹ and R ^{2, from} the viewpoints of availability and reactivity of raw materials, stability of dioxolane and the ester dimer of the present invention, and ease of recovery of ketones by-produced by acetal decomposition of the ester dimer of the present invention. Preferably, R ¹ is a monovalent hydrocarbon group having 1 to 8 carbon atoms, and R ² is a monovalent hydrocarbon group having 2 to 8 carbon atoms, more preferably R ¹ has 1 to 8 carbon atoms. An alkyl group and R ² is an alkyl group having 2 to 8 carbon atoms, more preferably R ¹ is an alkyl group having 1 or 2 carbon atoms and R ² is an alkyl group having 2 to 6 carbon atoms, more preferably R ¹ is An alkyl group having 1 or 2 carbon atoms and R ² having 2 or more and 4 or less carbon atoms, more preferably R ¹ is a methyl group and R ² is an ethyl group.
As another preferred embodiment of R ¹ and R ^2, R ¹ and R ² is a divalent hydrocarbon group that forms a ring structure with each other, from the point of view, preferably 2 or more carbon atoms 7 The following divalent hydrocarbon group, more preferably a divalent hydrocarbon group having 3 to 6 carbon atoms, more preferably a divalent hydrocarbon group having 4 to 5 carbon atoms, still more preferably 5 carbon atoms. These are divalent hydrocarbon groups. That is, the ring structure containing R ¹ and R ² is preferably a 3- to 8-membered ring, more preferably a 4- to 7-membered ring, still more preferably a 5- to 6-membered ring, and even more preferably a 6-membered ring. The ring structure containing R ¹ and R ² is preferably a cycloalkane structure, more preferably a ring structure having 5 or 6 carbon atoms (cyclopentane ring or cyclohexane ring), and a cyclohexane ring. More preferably it is.

In formula (I), when R ¹ and R ² are bonded to each other to form a ring structure, formula (I) becomes formula (I ′).

(In the formula (I ′), R ^A represents a divalent hydrocarbon group forming a ring structure.)

In the formula (I ′), the ring structure containing R ^A is preferably a 3- to 8-membered ring, more preferably a 4- to 7-membered ring, still more preferably a 5- to 6-membered ring, and even more preferably a 6-membered ring. . The ring structure containing R ^A is preferably a cycloalkane structure, more preferably a cyclopentane ring or a cyclohexane ring as described above, and a cyclohexane ring formed. Is more preferable.
That is, ^RA preferably represents an ethylene group (— (CH ₂ ) ₂ —), a trimethylene group (— (CH ₂ ) ₃ —), a tetramethylene group (— (CH ₂ ) ₄ —), a pentamethylene group (— (CH ₂ ) ₅ —), hexamethylene group (— (CH ₂ ) ₆ —) or heptamethylene group (— (CH ₂ ) ₇ —), more preferably trimethylene group, tetramethylene group, pentamethylene group or hexamethylene More preferably a tetramethylene group or a pentamethylene group, still more preferably a pentamethylene group.

Since the compound represented by the formula (I) has two or more asymmetric carbon atoms, when the number of asymmetric carbon atoms is n, the mixture is a maximum of 2 ⁿ (2 to the power of n) stereoisomer mixture. . In the present invention, the compound represented by the formula (I) may be a stereoisomer mixture and is not particularly limited.

<Method for Producing Compound Represented by Formula (I)>
The method for producing the ester dimer of the present invention is not particularly limited, but is preferably produced by subjecting a compound represented by the following formula (II) (hereinafter also referred to as “dioxolane”) to an oxidative esterification reaction.

(In formula (II), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.)

  In the present invention, as dioxolane, the compound represented by the above formula (II) may be used alone, and the compound represented by formula (II) and the compound represented by formula (V) described below (hereinafter, A mixture with “dioxane”) may also be used. In addition, the mixture of the compound represented by the formula (II) and the compound represented by the formula (V) may be a commercially available product, or, as described later, in the formula (II) A mixture of the compound represented by formula (V) and the compound represented by formula (V) may be produced and used, but is not particularly limited. From the viewpoint of producing at a low cost, a mixture of dioxolane and dioxane is produced (synthesized). , Preferably used.

[Method for producing dioxolane]
The production method of dioxolane (a compound represented by the formula (II)) used in the present invention is not particularly limited, and glycerol and a compound represented by the following formula (III) are generally well-known methods. (Hereinafter also referred to as “ketone”) Method of acetalization in the presence of an acid catalyst (Method 1), or Method of exchanging glycerol and a compound represented by the following formula (IV) in the presence of an acid catalyst (Method 2) From the viewpoint of availability of raw materials, yield, and ease of reaction operation.
That is, it is preferable that the manufacturing method of the glycerol ester of this invention includes the following process 1 and process 2.
Step 1: Step of acetalizing glycerol and a compound represented by the following formula (III) in the presence of an acid catalyst (Step 1-1), or glycerol and a compound represented by the following formula (IV) in the presence of an acid catalyst Step of exchanging acetal with (step 1-2)
Step 2: Oxidative esterification of a mixture of a compound represented by the following formula (II) and a compound represented by the following formula (V)

(In the formula (III) and formula (IV), ^{R 1} and ^{R 2} are each ^{R 1} and ^{R 2} synonymous in formula (I), wherein (IV), ^{R 3} is independently a monovalent Represents a hydrocarbon group of

R ³ in formula (IV) is each independently a monovalent hydrocarbon group, preferably from 1 to 8 carbon atoms, from the viewpoint of availability of raw materials, and by-produced by an acetal exchange reaction. From the viewpoint of accelerating the reaction by distilling alcohol out of the reaction system, more preferably a monovalent hydrocarbon group having 1 to 3 carbon atoms, still more preferably a monovalent alkyl group having 1 to 3 carbon atoms, Even more preferred is a methyl group.

Usually, the dioxolane obtained by the acetalization or acetal exchange method is obtained as a mixture with a compound (dioxane) represented by the following formula (V) as shown in the following reaction formula.
In particular, dioxolane obtained from the compound represented by the formula (III) and the compound represented by the formula (IV) has an isomerization ratio of 95% or more.

A mixture of dioxolane (compound represented by formula (II)) and dioxane (compound represented by formula (V)) obtained by the above method 1 (step 1-1) or method 2 (step 1-2) is It can be used as a raw material for the next step as it is or after purification, but it is preferable to purify the mixture and remove unreacted raw materials from the viewpoint of the yield in the next step, and distillation purification from the viewpoint of ease of purification. More preferably.
In addition, since it is difficult to separate dioxolane and dioxane by purification, it is preferable to use as a raw material for the next step in the state of a mixture of dioxolane and dioxane.

[Oxidative esterification]
The glyceric acid ester of the present invention can be obtained by oxidative esterification of the above dioxolane (compound represented by the formula (II)).
Oxidative esterification is a kind of oxidation reaction for obtaining an ester from a primary alcohol and an alcohol in a broad sense, and more generally a reaction for obtaining one molecule of an ester dimer from two molecules of the same primary alcohol. There are also other names such as quantification. In the present invention, oxidative esterification means carrying out a reaction for obtaining the ester dimer (compound represented by formula (I)) of the present invention from dioxolane (compound represented by formula (II)).
Examples of the oxidative esterification method include a method using a homogeneous or heterogeneous metal catalyst, and 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium described in Non-Patent Document 2. A method using tetrafluoroborate and pyridine, a catalytic amount of 2,2,6,6-tetramethylpiperidine-1-oxyl (hereinafter also referred to as “TEMPO”), an oxidizing agent and pyridine described in Non-Patent Document 4. There is a method of using.
In addition, when the mixture of the said dioxolane (compound represented by Formula (II)) and dioxane (compound represented by Formula (V)) is oxidatively esterified, the following reactions typically occur.

(Wherein R ¹ and R ² are as described above.)

  As described above, the dioxolane used in the present invention is usually a mixture with dioxane, but in the oxidative esterification step, formyl dioxolane (a compound represented by the formula (VII)) is by-produced from dioxolane depending on the reaction conditions. There is. Although there is no limitation on the amount of by-produced formyldioxolane, from the viewpoint of obtaining the ester dimer of the present invention in a high yield, the yield of formyldioxolane produced from dioxolane is preferably 20% or less, more preferably 10% or less. More preferably, it is 5% or less, still more preferably substantially 0%, and still more preferably 0%. In order to reduce the amount of by-produced formyldioxolane, a preferable production method described later may be followed.

  Similarly, in the step of oxidative esterification of a mixture of dioxolane and dioxane, a compound represented by the above formula (VI) from dioxane (hereinafter also referred to as “dioxanone”) in which dioxane does not react depending on the reaction conditions. May be produced, or a compound other than dioxanone may be produced, or a mixture of these compounds may be obtained. However, as long as it does not adversely affect the purification process of the ester dimer of the present invention, the production amount and production ratio of these compounds are affected. There is no limit.

  In the present invention, any oxidative esterification method can be used as long as the compound represented by the formula (I) is obtained. From the viewpoint of obtaining high reaction activity, an organic compound as described in Non-Patent Document 2 is used. From the oxidative esterification method using a nitroxyl radical-containing salt containing an oxoammonium cation and a base, as well as the organic nitroxyl radical, its N-hydroxy form, and salts containing those oxoammonium cations as in Non-Patent Document 4. An oxidative esterification method selected from oxidative esterification methods (hereinafter also referred to as “nitroxyl radical methods”) using a selected compound, an oxidizing agent, and a base is preferable, and the yield of the ester dimer of the present invention is The nitroxyl radical method is preferable from the viewpoint of high yield and low yield of formyldioxolane. An oxidative esterification method using a radical and / or its N-hydroxy form, an oxidizing agent, and a base is more preferred.

(Nitroxyl radical method)
[Nitroxyl radical species]
In this reaction, the nitroxyl radical species is selected from any organic nitroxyl radical that has an oxidative esterification activity for dioxolane in combination with an oxidizing agent, its N-hydroxy form, and salts containing their oxoammonium cations. Compounds can be used.
That is, as the nitroxyl radical species, it is preferable to use at least one compound selected from organic nitroxyl radicals, N-hydroxy isomers thereof, and salts containing oxoammonium cations thereof.
From the viewpoint of obtaining high oxidative esterification activity, the organic nitroxyl radical is a compound represented by the following formula (VIII), a compound represented by the following formula (IX) or a compound represented by the following formula (X). It is preferable that That is, the nitroxyl radical species includes a compound represented by the following formula (VIII), a compound represented by the following formula (IX) or a compound represented by the following formula (X), an N-hydroxy form thereof, and It is preferable that it is a compound chosen from the salt containing the oxoammonium cation.

(In the formula (VIII), R ⁴ is a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group, an acyloxy group, an alkoxycarbonyl group, an amino group, an acylamino group, a sulfonyloxy group, an N-alkylcarbamoyloxy group, a carboxy group, a cyano group. Represents an isocyanato group, an isothiocyanato group, or an oxo group, and in formula (IX), R ⁵ and R ⁶ each independently represents a hydrogen atom or a methyl group, and in formula (X), R ⁷ and R ⁸ represent Each independently represents a hydrogen atom or a methyl group.)

In the formula (VIII), R ⁴ is a hydrogen atom, a halogen atom, a hydroxyl group (—OH), an alkoxy group, an acyloxy group, an alkoxycarbonyl group, an amino group, an acylamino group, a sulfonyloxy group, an N-alkylcarbamoyloxy group, or a carboxy group. (—C (═O) —OH), cyano group (—C≡N), isocyanato group (—N═C═O), isothiocyanato group (—N═C═S), or oxo (═O) group. Represent. In formula (VIII), R ⁴ is preferably an alkoxy group, an acyloxy group, or an acylamino group from the viewpoint of availability and high yield of the ester dimer of the present invention.

Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a fluorine atom, a chlorine atom, or a bromine atom is preferable from the viewpoint of easy acquisition or preparation and low molecular weight.
The alkoxy group is represented by —OR ⁹ , R ⁹ represents a monovalent hydrocarbon group, and is preferably an alkyl group having 1 to 12 carbon atoms or a carbon number from the viewpoint of easy acquisition or preparation and low molecular weight. An alkenyl group having 2 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, or an aryl group having 6 to 20 carbon atoms, more preferably an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, and 2 carbon atoms. -6 alkynyl group, or aryl group having 6 to 14 carbon atoms, more preferably alkyl group having 1 to 4 carbon atoms, alkenyl group having 2 to 4 carbon atoms, alkynyl group having 2 to 4 carbon atoms, or 6 carbon atoms. Is an aryl group of from 10 to 10, more preferably a methyl group. In R ⁹ , part of the hydrogen atoms may be substituted with a halogen atom.

The acyloxy group is represented by —O (C═O) —R ¹⁰ , and R ¹⁰ is preferably a hydrogen atom, an alkyl group having 1 to 12 carbon atoms from the viewpoint of easy acquisition or preparation and low molecular weight. C1-C12 alkenyl group, or C6-C20 aryl group, More preferably, a hydrogen atom, C1-C8 alkyl group, or C6-C14 aryl group, More preferably, a hydrogen atom , An alkyl group having 1 to 4 carbon atoms, or an aryl group having 6 to 10 carbon atoms, more preferably a methyl group, an ethyl group, or a phenyl group, and still more preferably a phenyl group.
The acylamino group is represented by —NH (C═O) —R ¹¹ , and R ¹¹ is preferably a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, from the viewpoint of easy acquisition or preparation and low molecular weight. Or an aryl group having 6 to 20 carbon atoms, more preferably a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an aryl group having 6 to 14 carbon atoms, still more preferably a hydrogen atom, an alkyl group having 1 to 4 carbon atoms. Or an aryl group having 6 to 10 carbon atoms, more preferably a methyl group, an ethyl group, or a phenyl group, and still more preferably a methyl group.
The sulfonyloxy group is represented by —O (O═S═O) —R ¹² , and R ¹² is preferably an alkyl group having 1 to 12 carbon atoms from the viewpoint of easy acquisition or preparation and low molecular weight. Or an aryl group having 6 to 20 carbon atoms, more preferably an alkyl group having 1 to 8 carbon atoms, or an aryl group having 6 to 14 carbon atoms, still more preferably an alkyl group having 1 to 4 carbon atoms, or 6 to 6 carbon atoms. 10 aryl groups, more preferably a methyl group, an ethyl group, or a paratolyl group, still more preferably a methyl group or a paratolyl group.

Specific examples of the nitroxyl radical species include TEMPO, 4-hydroxy TEMPO, 4-amino-TEMPO, 4-methoxy-TEMPO (hereinafter also referred to as “4-OMe-TEMPO”), 4-ethoxy-TEMPO. 4-phenoxy-TEMPO, 4-acetoxy-TEMPO, 4-benzoyloxy-TEMPO (hereinafter also referred to as “4-OBz-TEMPO”), 4-methacrylate-TEMPO, 4-acetamido-TEMPO (hereinafter referred to as “4”). -NHAc-TEMPO "), 4-methylsulfonyloxy-TEMPO (hereinafter also referred to as" 4-OMs-TEMPO "), 4-paratoluenesulfonyloxy-TEMPO, 4-oxo-TEMPO, 2-aza Adamantane-N-hydroxyl (hereinafter referred to as “AZADOL (Also referred to as Nissan Chemical Industries, Ltd., trademark)), 2-azaadamantane-N-oxyl (hereinafter also referred to as “AZADO”), 1-methyl-2-azaadamantane-N-oxyl (hereinafter referred to as “trademark”). 1-Me-AZADO ”), 9-azanoradamantane-N-oxyl (hereinafter also referred to as“ nor-AZADO ”), 1,5-dimethyl-9-azanoradamantane-N-oxyl (hereinafter referred to as“ nor-AZADO ”). , Also referred to as “DMM-AZADO”).
From the viewpoint of availability and high yield of the ester dimer of the present invention, nitroxyl radical species include 4-methoxy-TEMPO, 4-benzoyloxy-TEMPO, 4-acetamido-TEMPO, 4-methylsulfonyloxy-TEMPO. And a compound selected from AZADOL, and a compound selected from 4-benzoyloxy-TEMPO, 4-acetamido-TEMPO, 4-methylsulfonyloxy-TEMPO, and AZADOL is more preferable.
Preferred compounds are exemplified below, but in the present invention, the nitroxyl radical species is not limited to these compounds.

  From the viewpoint of ensuring sufficient oxidative esterification activity, the amount of the compound selected from the organic nitroxyl radical, its N-hydroxy form, and salts containing their oxoammonium cations is used with respect to dioxolane or a mixture of dioxolane and dioxane. The molar ratio is preferably 0.0001 or more, more preferably the molar ratio is 0.0002 or more, and still more preferably the molar ratio is 0.0005 or more. From the viewpoint of economy, the molar ratio is preferably 0.1 or less, more preferably the molar ratio is 0.05 or less, and still more preferably the molar ratio is 0.02 or less.

〔Oxidant〕
In this reaction, an oxidizing agent is preferably used together with the above-described nitroxyl radical species from the viewpoint of reactivity. As the oxidizing agent, any oxidizing agent capable of oxidizing an organic nitroxyl radical or its N-hydroxy form to an oxoammonium cation can be used, but a decrease in yield due to hydration or hydrolysis of dioxanone or ester dimer is suppressed. Therefore, an oxidizing agent composed of a halogen-containing compound that can be used in an organic solvent (hereinafter also referred to as “halogen-containing oxidizing agent”) is preferable. Examples of the halogen-containing oxidizing agent include sodium hypochlorite pentahydrate, metachloroperbenzoic acid, trichloroisocyanuric acid (hereinafter, also referred to as “TCCA”), tertiary butyl hypochlorite (hereinafter, “ ^t BuOCl”). ), An oxidizing agent comprising a chlorine-containing compound such as N-chlorosuccinimide (hereinafter also referred to as “chlorine-containing oxidizing agent”), and an oxidizing agent comprising a bromine-containing compound such as N-bromosuccinimide ( Hereinafter, the halogen-containing oxidizing agent having a plurality of halogen elements such as “bromine-containing oxidizing agent” and (dichloroiodo) benzene is exemplified. Halogen-containing oxidizing agent, oxidizing the viewpoint of obtaining an ester dimers of the present invention in high yield, stability of the oxidizing agent, from the viewpoint of safety and ease of handling, the chlorine-containing oxidizing agent is preferably selected from TCCA and ^t BuOCl An agent is more preferable, and TCCA is more preferable from the viewpoint of availability.
The oxidizing agent of the present invention includes a compound represented by the formula (VIII), a compound represented by the formula (IX), or an oxoammonium cation obtained by one-electron oxidation of the compound represented by the formula (X). The organic nitroxyl radical or its N-hydroxy oxoammonium cation is excluded.
From the viewpoint of achieving both a high reaction conversion rate of dioxolane or a mixture of dioxolane and dioxane and a reduction in the amount of formyl dioxolane produced, the molar ratio of the oxidizing active species to dioxolane or a mixture of dioxolane and dioxane is preferably 1.0 or more, more preferably. Is 1.1 or more. Further, from the viewpoint of economy and reduction of waste amount, the molar ratio is preferably 2.0 or less, more preferably 1.5 or less.
The oxidation active species means a chlorine atom in the case of a chlorine-containing oxidant, and in the case of TCCA, there are 3 mol of oxidation active species in 1 mol of the molecule.

〔base〕
In this reaction, a base is used for the purpose of neutralizing an acid produced as a by-product due to consumption of the oxidizing agent. Any base can be used as long as it does not interfere with the desired oxidation reaction, but it is weakly basic and side reactions are suppressed as it causes a direct side reaction with dioxolane or a mixture of dioxolane and dioxane, a catalyst or an oxidizing agent. From the viewpoint, a heterocyclic aromatic amine having a pyridine skeleton is preferable. The heterocyclic aromatic amine having a pyridine skeleton may be used in combination with an inorganic base in order to suppress the amount used, but has a pyridine skeleton from the viewpoint of obtaining the ester dimer of the present invention in a high yield. More preferably, the heterocyclic aromatic amine is used alone.
Examples of the heterocyclic aromatic amine having a pyridine skeleton include pyridine, alkyl-substituted pyridines, polycyclic quinolines, bipyridyls that are pyridine dimers, and the like. Specifically, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2-ethylpyridine, 3-ethylpyridine, 4-ethylpyridine, 2,6-lutidine, 3,5-lutidine, 2 , 3,5-collidine, 2,4,6-collidine, 5-ethyl-2-methylpyridine, 3,5-diethylpyridine, 2,2′-bipyridyl, 2,4′-bipyridyl, 4,4′- Bipyridyl, quinoline and the like can be mentioned.
Among the heterocyclic aromatic amines having a pyridine skeleton, it is preferable to select and use a heterocyclic aromatic amine having a pyridine skeleton that has a large boiling point difference from dioxanone and the ester dimer of the present invention and is easily separated by distillation. From the viewpoint of availability, an amine selected from pyridine and 5-ethyl-2-methylpyridine is preferable. From the viewpoint of easy recovery when the amine is regenerated from the amine salt after the reaction is completed, a water-insoluble pyridine skeleton is formed. Preferred is a heterocyclic aromatic amine having, from the viewpoint of yield, selected from pyridine, 3,5-lutidine, 2,6-lutidine, 3-ethylpyridine, 4-ethylpyridine and 5-ethyl-2-methylpyridine. Preferred amines are pyridine, 3,5-lutidine, 3-ethylpyridine, 4-ethylpyridine and 5-ethyl-2. Amines selected from methyl pyridine is more preferred.

  From the viewpoint of completely neutralizing the acid derived from the oxidizing agent and suppressing the decomposition of the acetal group of dioxolane and the ester dimer of the present invention, the molar ratio of the base to dioxolane or a mixture of dioxolane and dioxane is preferably 1.0 or more. More preferably, it is 1.1 or more, More preferably, it is 1.2 or more, More preferably, it is 1.3 or more. In addition, from the viewpoints of economy and ease of recovery of excess base, the molar ratio is preferably 2.5 or less, more preferably 2.0 or less, and even more preferably 1.7 or less.

〔solvent〕
In this reaction, it can be carried out either in the absence of a solvent or under the conditions of use of a solvent. From the viewpoint of lowering the viscosity of the resin and facilitating stirring, solvent use conditions are preferred. Any solvent can be used as long as it is inert to dioxolane or a mixture of dioxolane and dioxane, an oxidizing agent, and a base. For example, when TCCA is used as an oxidizing agent, TCCA solubility and availability are considered. And preferably a solvent selected from acetone, 2-butanone, cyclopentanone, acetonitrile and dichloromethane, more preferably a solvent selected from acetone, 2-butanone, acetonitrile and dichloromethane, still more preferably selected from acetone and 2-butanone. Solvent. Moreover, acetonitrile is more preferable from the viewpoint of the productivity of the ester dimer of the present invention.

A solvent may be used individually by 1 type and may use the above together.
The amount of the solvent used is not particularly limited, but from the viewpoint of operability and the viewpoint of obtaining the ester dimer of the present invention in a high yield, the amount of the solvent used is preferably 20% by mass or more, more preferably 30%, based on the entire reaction system. % By mass or more, more preferably 40% by mass or more, still more preferably 50% by mass, and still more preferably 60% by mass or more. From the viewpoint of productivity, the amount of solvent used for the entire reaction system is preferably 90% by mass. % Or less, More preferably, it is 85 mass% or less, More preferably, it is 80 mass% or less.

[Reaction procedure]
In this reaction, there is no limitation on the order of charging the raw materials, but since the oxidative esterification reaction is an exothermic reaction, raw materials other than the oxidizing agent are used from the viewpoint of ease of temperature control of the reaction solution and safety. The method of dripping an oxidizing agent or an oxidizing agent solution in a mixture or a mixed solution is preferable.
The temperature of the reaction solution during dropping of the oxidant or oxidant solution is preferably −15 ° C. or higher, more preferably −10 ° C. or higher, from the viewpoint of equipment load and suppression of viscosity increase of the reaction solution. Moreover, from the viewpoint of suppressing side reactions such as decomposition at high temperature and obtaining the ester dimer of the present invention in a high yield, it is preferably 25 ° C. or less, more preferably 10 ° C. or less. After the addition of the oxidizing agent or oxidizing agent solution, the reaction is continued until the total amount of dioxolane reacts or the decrease in the residual amount stops. The temperature of the reaction solution is preferably −10 from the viewpoint of promoting the reaction of dioxolane. From the viewpoint of suppressing side reactions, it is preferably 50 ° C. or lower, more preferably 30 ° C. or lower.

At the end of the reaction, from the viewpoint of side reaction suppression and safety, it is preferable to add a reaction terminator that completely consumes the residual oxidizing agent. As the reaction terminator, any compound can be used as long as it does not easily react with the reaction product such as the ester dimer of the present invention and reacts with the oxidizing agent. From the viewpoint of making it, alcohol is preferable. The alcohol is preferably a primary or secondary alcohol, and more preferably a secondary alcohol from the viewpoint of suppressing transesterification with the ester dimer of the present invention. Moreover, C1-C12 alcohol is preferable.
The addition amount of the reaction terminator is not particularly limited.

[Separation of compound represented by formula (I)]
In the present invention, it is preferable to have a step of separating the ester dimer of the present invention (compound represented by the formula (I)) after the step of oxidative esterification of dioxolane or preferably a mixture of dioxolane and dioxane.
In the step of separating the ester dimer of the present invention, from the viewpoint of efficiency, solids such as salts and reduced products of oxidants are separated by filtration or oil-water extraction, and dioxanone, formyldioxolane and residual base are distilled or column chromatography. It is preferable to separate by. With respect to water-soluble by-products such as salts and reduced products of oxidizing agents, it is preferable to perform a water washing step of removing the water-soluble by-products by water washing from the viewpoint of removal efficiency. Regarding the removal of water-soluble by-products, the washing step and the filtration step may be used in combination, or only the washing step may be performed.
In the separation of dioxanone and the ester dimer of the present invention, separation by distillation is more preferable from the viewpoint of easy separation utilizing a large boiling point difference. Separation by distillation can be carried out under either simple distillation conditions or rectification conditions, but it is preferable to carry out under rectification conditions from the viewpoint of obtaining a high-purity ester dimer of the present invention with a high distillation yield. As the rectification conditions, from the viewpoint of increasing the purity of the ester dimer of the present invention, the number of theoretical columns of the rectification column is preferably 2 or more, more preferably 5 or more, and the reflux ratio is preferably 0.1 or more. More preferably, it is 0.5 or more. Further, from the viewpoint of productivity of the ester dimer purification of the present invention, the number of theoretical columns of the rectifying column is preferably 20 or less, more preferably 10 or less, and the reflux ratio is preferably 20 or less, more preferably 10 or less. It is.

  The novel glyceric acid ester of the present invention (the ester dimer of the present invention) is a glyceric acid ester in which the hydroxyl groups at the 2nd and 3rd positions are protected as cyclic acetal groups, and is a raw material for various pharmaceuticals, cosmetics, detergents, polymers, etc. It is useful as a synthetic intermediate for glyceric acid, glycerate and deprotected glyceric acid esters used as

[Method for producing glyceric acid, glycerate or deprotected glyceric acid ester]
Glyceric acid, glycerate, or deprotected glyceric acid ester can be produced by hydrolysis or alcoholysis of the acetal group and ester group of the ester dimer of the present invention obtained as described above. The method of hydrolysis or alcoholysis is not particularly limited, but the method of decomposing using an excess amount of water or alcohol in the presence of an acid catalyst is the simplest and preferred.
The alcohol used for the alcoholysis is preferably a primary alcohol from the viewpoint of reactivity (particularly the decomposition of the acetal group), and more preferably from the viewpoint that the deprotected glyceric acid ester has a low boiling point and can be easily purified by distillation. It is a primary alcohol having 1 to 3 carbon atoms.
Further, from the viewpoint of easily reducing the polarity of the deprotected glyceric acid ester and separating and purifying the deprotected glyceric acid ester and glycerin by an oil-water extraction method, more preferably a straight chain having 4 to 8 carbon atoms. It is a chain or branched primary alcohol.

  The obtained glyceric acid, glycerate, or deprotected glyceric acid ester is preferably separated from a by-product (glycerin, aldehyde or acetal thereof) by distillation or column chromatography.

  The present invention further discloses the following [1] to [36].

  [1] A process for producing a compound represented by the following formula (I), comprising a step of oxidative esterification of the compound represented by the following formula (II).

(In formula (I), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.)

(In formula (II), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.)

  [2] The production method according to [1], including a step of oxidative esterification of a mixture of a compound represented by the following formula (II) and a compound represented by the following formula (V).

(In Formula (II) and Formula (V), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Represents a valent hydrocarbon group, except that R ¹ and R ² are simultaneously methyl groups.)

  [3] A mixture of a compound represented by the formula (II) and a compound represented by the formula (V) is obtained by converting glycerol and a compound represented by the following formula (III) or a multimer thereof in the presence of an acid catalyst into an acetal. The production method according to [2], which is produced by a method (Method 1) or a method (Method 2) in which glycerol and a compound represented by the following formula (IV) are acetal exchanged in the presence of an acid catalyst.

(In the formula, R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² represent a divalent hydrocarbon group which is bonded to each other to form a ring structure. However, the case where R ¹ and R ² are simultaneously methyl groups is excluded, and R ³ is independently a monovalent hydrocarbon group, preferably a hydrocarbon group having 1 to 8 carbon atoms, more preferably carbon. A monovalent hydrocarbon group having a number of 1 or more and 3 or less, more preferably a monovalent alkyl group having a carbon number of 1 or more and 3 or less, and still more preferably a methyl group.

[4] The production method according to [2] or [3], including the following step 1 and step 2.
Step 1: Step of acetalizing glycerol and a compound represented by the following formula (III) in the presence of an acid catalyst (Step 1-1), or glycerol and a compound represented by the following formula (IV) in the presence of an acid catalyst Step of exchanging acetal with (step 1-2)
Step 2: Oxidative esterification of a mixture of a compound represented by the following formula (II) and a compound represented by the following formula (V)

(In the formula, R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² represent a divalent hydrocarbon group which is bonded to each other to form a ring structure. However, the case where R ¹ and R ² are simultaneously methyl groups is excluded, and R ³ is independently a monovalent hydrocarbon group, preferably a hydrocarbon group having 1 to 8 carbon atoms, more preferably carbon. A monovalent hydrocarbon group having a number of 1 or more and 3 or less, more preferably a monovalent alkyl group having a carbon number of 1 or more and 3 or less, and still more preferably a methyl group.

[5] The yield of the formula formyldioxolane produced from the compound represented by the formula (II) is preferably 20% or less, more preferably 10% or less, still more preferably 5% or less, and still more preferably substantially. The production method according to any one of [1] to [4], which is 0%, more preferably 0%.
[6] In the oxidative esterification step, preferably, an oxidative esterification method using a salt containing an oxoammonium cation of an organic nitroxyl radical and a base, an organic nitroxyl radical, an N-hydroxy form thereof, and the like Using an oxidative esterification method selected from an oxidative esterification method (hereinafter also referred to as “nitroxyl radical method”) using a compound selected from salts containing an oxoammonium cation, an oxidizing agent, and a base; [1] The production method according to any one of [5].
[7] In the above [6], the organic nitroxyl radical is a compound represented by the following formula (VIII), a compound represented by the following formula (IX), or a compound represented by the following formula (X). The manufacturing method as described.

(In the formula (VIII), R ⁴ is a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group, an acyloxy group, an alkoxycarbonyl group, an amino group, an acylamino group, a sulfonyloxy group, an N-alkylcarbamoyloxy group, a carboxy group, a cyano group. Represents an isocyanato group, an isothiocyanato group, or an oxo group, preferably an alkoxy group, an acyloxy group, or an acylamino group, wherein R ⁵ and R ⁶ each independently represent a hydrogen atom or a methyl group; In formula (X), R ⁷ and R ⁸ each independently represents a hydrogen atom or a methyl group.)

[8] One or more compounds selected from the organic nitroxyl radical, its N-hydroxy form, and a salt containing an oxoammonium cation thereof are preferably TEMPO, 4-hydroxy TEMPO, 4-amino-TEMPO, 4 -Methoxy-TEMPO (hereinafter also referred to as "4-OMe-TEMPO"), 4-ethoxy-TEMPO, 4-phenoxy-TEMPO, 4-acetoxy-TEMPO, 4-benzoyloxy-TEMPO (hereinafter referred to as "4-OBz"). -TEMPO "), 4-methacrylate-TEMPO, 4-acetamido-TEMPO (hereinafter also referred to as" 4-NHAc-TEMPO "), 4-methylsulfonyloxy-TEMPO (hereinafter" 4-OMs-TEMPO "). Also called 4-paratoluenesulfonylo. Xi-TEMPO, 4-oxo-TEMPO, 2-azaadamantane-N-hydroxyl (hereinafter also referred to as “AZADOL”), 2-azaadamantane-N-oxyl (hereinafter also referred to as “AZADO”), 1- Methyl-2-azaadamantane-N-oxyl (hereinafter also referred to as “1-Me-AZADO”), 9-azanoradamantane-N-oxyl (hereinafter also referred to as “nor-AZADO”), 1,5 -Dimethyl-9-azanoradamantane-N-oxyl (hereinafter also referred to as "DMM-AZADO"), more preferably 4-methoxy-TEMPO, 4-benzoyloxy-TEMPO, 4-acetamido-TEMPO, 4-methyl Compound selected from sulfonyloxy-TEMPO and AZADOL, more preferably 4-benzo Yloxy-TEMPO, 4-acetamido-TEMPO, a compound selected 4-methylsulfonyloxy-TEMPO, and the AZADOL, production method according to [6] or [7].
[9] The amount of the compound selected from the organic nitroxyl radical, its N-hydroxy form, and a salt containing the oxoammonium cation is represented by the compound represented by the formula (II) or the formula (II). Preferably, the molar ratio is 0.0001 or more, more preferably the molar ratio is 0.0002 or more, and still more preferably the molar ratio is 0.0005 with respect to the mixture of the compound represented by formula (V). The molar ratio is 0.1 or less, more preferably the molar ratio is 0.05 or less, and still more preferably the molar ratio is 0.02 or less. Manufacturing method.

[10] The oxidizing agent is preferably an oxidizing agent (halogen-containing oxidizing agent) made of a halogen-containing compound, more preferably an oxidizing agent (chlorine-containing oxidizing agent) made of a compound containing chlorine, more preferably trichloroisocyanuric. The manufacturing method according to any one of [6] to [9], wherein the oxidizing agent is selected from an acid and tertiary butyl hypochlorite, more preferably trichloroisocyanuric acid.
[11] The molar ratio of the oxidizing active species of the oxidizing agent to the compound represented by the formula (II) or the mixture of the compound represented by the formula (II) and the compound represented by the formula (V) However, Preferably it is 1.0 or more, More preferably, it is 1.1 or more, Preferably it is 2.0 or less, More preferably, it is 1.5 or less, The manufacture in any one of [6]-[10] Method.

[12] The production method according to any one of [6] to [11], wherein the base is a heterocyclic aromatic amine having a pyridine skeleton.
[13] The heterocyclic aromatic amine having a pyridine skeleton is preferably pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2-ethylpyridine, 3-ethylpyridine, 4-ethylpyridine, 2,6-lutidine, 3,5-lutidine, 2,3,5-collidine, 2,4,6-collidine, 5-ethyl-2-methylpyridine, 3,5-diethylpyridine, 2,2'-bipyridyl , 2,4′-bipyridyl, 4,4′-bipyridyl, and quinoline, more preferably pyridine, 3,5-lutidine, 2,6-lutidine, 3-ethylpyridine, 4- At least one selected from ethylpyridine and 5-ethyl-2-methylpyridine, more preferably pyridine, 3,5-lutidine, 3-ethylpyridine, 4- The production method according to [12], which is at least one selected from ethylpyridine and 5-ethyl-2-methylpyridine.
[14] The molar ratio of the base to the compound represented by the formula (II) or the mixture of the compound represented by the formula (II) and the compound represented by the formula (V) is preferably 1.0 or more, more preferably 1.1 or more, still more preferably 1.2 or more, still more preferably 1.3 or more, preferably 2.5 or less, more preferably 2.0 or less, still more preferably The production method according to any one of [6] to [13], which is 1.7 or less.

[15] Preferably, a solvent is used in the oxidative esterification step, and the solvent is preferably a solvent selected from acetone, 2-butanone, cyclopentanone, acetonitrile and dichloromethane, more preferably acetone, 2-butanone. , A solvent selected from acetonitrile and dichloromethane, more preferably a solvent selected from acetone and 2-butanone, [1] to [14].
[16] The amount of the solvent used in the entire reaction system is preferably 20% by mass or more, more preferably 30% by mass or more, still more preferably 40% by mass or more, still more preferably 50% by mass or more, and still more preferably. It is 60 mass% or more, Preferably it is 90 mass% or less, More preferably, it is 85 mass% or less, More preferably, it is 80 mass% or less, The manufacturing method as described in [15].

[17] The production according to any one of [6] to [16], wherein in the oxidative esterification step, the oxidant or the oxidant solution is preferably added dropwise to a mixture or mixed solution of raw materials other than the oxidant. Method.
[18] The temperature of the reaction solution during dropping of the oxidizing agent or oxidizing agent solution is preferably −15 ° C. or higher, more preferably −10 ° C. or higher, preferably 25 ° C. or lower, more preferably 10 ° C. or lower. [17] The manufacturing method according to the above.
[19] The production method according to [17] or [18], wherein the reaction is continued until the total amount of dioxolane has reacted or the decrease in the residual amount has stopped after completion of the dropping of the oxidizing agent or oxidizing agent solution.
[20] The process according to [19], wherein the temperature of the reaction solution is preferably −10 ° C. or higher, more preferably −5 ° C. or higher, preferably 50 ° C. or lower, more preferably 30 ° C. or lower. .

[21] The production method according to any one of [1] to [20], wherein alcohol is preferably used as a reaction terminator.
[22] The production method according to [21], wherein the reaction terminator is preferably a primary or secondary alcohol, and more preferably a secondary alcohol.
[23] The production method according to [21] or [22], wherein the reaction terminator is preferably an alcohol having 1 to 12 carbon atoms.

[24] After the step of oxidative esterification of the compound represented by the formula (II) or preferably a mixture of the compound represented by the formula (II) and the compound represented by the formula (V) The manufacturing method in any one of [1]-[23] which has the process of isolate | separating the compound represented by Formula (I).
[25] The production method according to [24], wherein the separation in the step of separating the compound represented by the formula (I) is separation by distillation.
[26] The production method according to [25], wherein the separation by distillation is preferably performed under rectification conditions.
[27] The rectification conditions are such that the theoretical plate number of the rectification column is preferably 2 or more, more preferably 5 or more, and the reflux ratio is preferably 0.1 or more, more preferably 0.5 or more. The production method according to [26], wherein the number of theoretical plates of the rectification column is preferably 20 or less, more preferably 10 or less, and the reflux ratio is preferably 20 or less, more preferably 10 or less.
[28] Glyceric acid, glycerate, or deprotected glyceric acid ester, which hydrolyzes or alcoholates the compound represented by the formula (I) separated in any one of [24] to [27] Production method.
[29] A process for producing the compound represented by the formula (I) by the production method according to any one of [1] to [27], and the process represented by the formula (I) produced in the process. The manufacturing method of the glycerol acid, glycerol salt, or deprotected glycerol ester which has the process of hydrolyzing or alcohololyzing the compound which carries out.
[30] The production method according to [28] or [29], wherein the alcohol used for the alcoholysis is preferably a primary alcohol, more preferably a primary alcohol having 1 to 3 carbon atoms.
[31] The production method according to [28] or [29], wherein the alcohol used for the alcoholysis is more preferably a linear or branched primary alcohol having 4 to 8 carbon atoms.
[32] In Formula (I) and Formula (II), R ¹ and R ² are preferably a monovalent hydrocarbon group in which R ¹ has 1 to 8 carbon atoms and R ² has 2 to 8 carbon atoms. monovalent hydrocarbon group, more preferably R ¹ is 1 or more carbon atoms 8 an alkyl group and R ² is 2 to 8 of the alkyl group carbon atoms, more preferably an alkyl R ¹ is 1 or 2 carbon atoms R ² is an alkyl group having 2 to 6 carbon atoms, more preferably R ¹ is an alkyl group having 1 or 2 carbon atoms, and R ² is an alkyl group having 2 to 4 carbon atoms, more preferably R ¹ is it is a methyl group and ^{R 2} is an ethyl group, the process according to any one of [1] to [31].
[33] In formula (I) and formula (II), R ¹ and R ² represent a divalent hydrocarbon group which is bonded to each other to form a ring structure, preferably a divalent hydrocarbon group having 2 to 7 carbon atoms. A hydrocarbon group, more preferably a divalent hydrocarbon group having 3 to 6 carbon atoms, still more preferably a divalent hydrocarbon group having 4 to 5 carbon atoms, still more preferably a divalent carbon group having 5 carbon atoms. The production method according to any one of [1] to [31], which is a hydrogen group.
[34] A compound represented by the following formula (I).

(In formula (I), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.)

[35] R ¹ and R ² are, preferably R ¹ is a hydrocarbon group and R ² is a hydrocarbon group of mono- 2 having 8 or more carbon atoms of the monovalent having 1 to 8 carbon atoms, more preferably R ¹ is an alkyl group having 1 to 8 carbon atoms and R ² is an alkyl group having 2 to 8 carbon atoms, more preferably R ¹ is an alkyl group having 1 or 2 carbon atoms and R ² is 2 to 6 carbon atoms. More preferably, R ¹ is an alkyl group having 1 or 2 carbon atoms and R ² is an alkyl group having 2 to 4 carbon atoms, more preferably R ¹ is a methyl group and R ² is an ethyl group. [34] The compound described in.
[36] R ¹ and R ² represent a divalent hydrocarbon group which is bonded to each other to form a ring structure, preferably a divalent hydrocarbon group having 2 to 7 carbon atoms, more preferably a carbon number. [34], which is a divalent hydrocarbon group having 3 to 6 carbon atoms, more preferably a divalent hydrocarbon group having 4 to 5 carbon atoms, still more preferably a divalent hydrocarbon group having 5 carbon atoms. The described compound.

[Identification of compounds]
Each compound obtained in the following Production Examples, Examples or Comparative Examples (hereinafter also referred to as “Examples”) is a nuclear magnetic resonance apparatus (NMR, manufactured by Agilent Technologies, Inc., Model: Agilent 400-MR). DD2), spectrum using an infrared spectrophotometer (IR, manufactured by Horiba, Ltd., model: FT-710), gas chromatograph mass spectrometer (GC-MS, manufactured by Agilent Technologies, model: Agilent 5975C) Identified by analysis.
[Purity of manufactured or purified compound]
In the following Examples and the like, the purity of the produced or purified compound was determined by analysis (GC analysis) using a gas chromatograph (manufactured by Agilent Technologies, Inc., model: Agilent 6850). Note that “%” relating to purity means “GC%”, and this value was used when converting the raw material of the reaction raw material or the high-purity sample into a pure amount.

[Units, conversion and yield]
The conversion rates of reaction raw materials and product yields shown in the following examples and the like were determined by internal standard method quantitative GC analysis. A calibration curve necessary for quantitative analysis was prepared using a high-purity sample purified from a commercially available sample or reaction mixture by distillation or silica gel column chromatography. However, the yield of formyldioxolane was calculated by substituting the corresponding calibration curve of dioxanone.

[Measurement conditions for GC and GC-MS]
Column: Ultra ALLOY-1 (MS / HT) (Frontier Labs, trademark, inner diameter 0.25 mm, film thickness 0.15 μm, length 30 m)
Carrier gas: helium, 1.0 mL / min
Injection conditions: 250 ° C., split ratio 1/50
Detection condition: FID method, 220 ° C
Column temperature condition: held at 40 ° C. for 5 minutes, then raised to 350 ° C. at 10 ° C./minute Internal standard compound: n-dodecane Ionization mode: EI
Ion source temperature: 230 ° C
Interface temperature: 350 ° C

Production Example: Production of 2,2-dialkyl-4-hydroxymethyl-2-methyl-1,3-dioxolane as a raw material The reaction carried out in the production example is as follows.

Production Example 1: Production of 2-ethyl-4-hydroxymethyl-2-methyl-1,3-dioxolane (R ¹ = Me, R ² = Et) as a raw material To a 1 L flask equipped with a Dean-Stark apparatus, glycerol 184 g (purity 100%, 2.00 mol), 2-butanone 162 g (purity 98.0%, 2.20 mol), methanesulfonic acid 981 mg (purity 98.0%, 10.0 mmol), n-hexane 50 g And refluxed for 5 hours while removing water produced as a by-product in the reaction. After cooling, the solution was neutralized with 3.50 g of a 20% ethanol solution of sodium ethoxide (700 mg as sodium ethoxide, 10.3 mmol). As a result of GC analysis of the reaction solution, the reaction yield of a mixture of cis and trans isomers of 2-ethyl-4-hydroxymethyl-2-methyl-1,3-dioxolane was 74%.
Subsequently, the reaction solution was transferred to a 500 mL flask equipped with a Claisen head, heated to 50 ° C. and then gradually reduced in pressure to distill off n-hexane and ethanol, and then further reduced under a reduced pressure of 0.13 kPa (absolute pressure). Distillation was performed to obtain 220 g of a stereoisomer mixture distilled as a colorless liquid at a fraction temperature of 91 to 94 ° C. The purity was 95.3% and the distillation yield was 97%.
<Spectral data of stereoisomer mixture>
IR (neat, cm ⁻¹ ): 3465 (br), 2993, 2935, 2883, 1466, 1375, 1190, 1078, 1041, 876.
MS (m / z): 131, 117, 57, 43.

Production Example 2: Production of 2-isobutyl-4-hydroxymethyl-2-methyl-1,3-dioxolane (R ¹ = Me, R ² = ⁱ Bu) as a raw material 221 g of 4-methyl-2-pentanone (purity 99) 0.5%, 2.20 mol) as a reaction raw material, and the same operation as in Production Example 1 was carried out to give 2-isobutyl-4-hydroxymethyl-2-methyl-1,3-dioxolane in a reaction yield of 68%. To give a mixture of cis and trans isomers.
Furthermore, simple distillation was performed under a reduced pressure of 0.13 kPa (absolute pressure) to obtain 246 g of a stereoisomer mixture distilled as a colorless liquid at a fraction temperature of 117 to 123 ° C. The purity was 97.4% and the distillation yield was 92%.
<Spectral data of stereoisomer mixture>
IR (neat, cm ⁻¹ ): 3446 (br), 2952, 2871, 1466, 1375, 1184, 1090, 1041.
MS (m / z): 159, 143, 117, 99, 85, 57, 43.

Production Example 3: Production of 2-hydroxymethyl-1,4-dioxaspiro [4.5] decane (R ¹ , R ² = — (CH ₂ ) ₅ —) as a raw material 218 g of cyclohexanone (purity 99.0%, 2 .20 mol) was used as a reaction raw material, and the same operation as in Production Example 1 was performed to obtain 2-hydroxymethyl-1,4-dioxaspiro [4.5] decane in a reaction yield of 80%.
Furthermore, simple distillation was performed under reduced pressure of 0.13 kPa (absolute pressure) to obtain 297 g of a colorless liquid distilled at a fraction temperature of 123 to 126 ° C. The purity was 97.0% and the distillation yield was 95%.
<Spectral data>
¹ H-NMR (400 MHz, CDCl ₃ , δ _ppm ): 1.37-1.42 (2H, m), 1.54-1.63 (8H, m), 2.30 (1H, s), 3.56-3.61 (1H, m), 3.70-3.80 (2H, m), 4.02-4.05 (1H, m), 4.21-4.25 (1H, m ).
^{· 13 C-NMR (100MHz,} CDCl 3, δ ppm): 23.7,24.0,25.1,34.7,36.3,63.1,65.3,75.7,110.0 .
IR (neat, cm ⁻¹ ): 3423 (br), 2933, 2860, 1448, 1365, 1281, 1163, 1097, 1039, 926.
MS (m / z): 172 (M ^<+> ), 143, 129, 116, 81, 73, 55, 41, 31.

Production Example 4: Production of raw material 2-ethyl-4-hydroxymethyl-2-pentyl-1,3-dioxolane (R ¹ = Et, R ² = Pentyl) 3-octanone 288 g (purity 98.0%, 2 .20 mol) as a reaction raw material, and the same operation as in Production Example 1 was carried out. The cis and trans isomerism of 2-ethyl-4-hydroxymethyl-2-pentyl-1,3-dioxolane was obtained in a reaction yield of 73%. A body mixture was obtained.
Further, simple distillation was carried out under a reduced pressure of 0.13 kPa (absolute pressure) to obtain 284 g of a stereoisomer mixture distilled as a colorless liquid at a fraction temperature of 143 to 146 ° C. The purity was 97.4% and the distillation yield was 85%.
<Spectral data of stereoisomer mixture>
IR (neat, cm ⁻¹ ): 3450 (br), 2933, 2871, 1963, 1464, 1165, 1047, 912.
MS (m / z, common to 2 peaks on GC): 202 (M ⁺ ), 173, 131, 99, 71, 57, 43.

Examples: Preparation of 2,2-dialkyl-1,3-dioxolane-4-carboxylic acid (2,2-dialkyl-1,3-dioxolan-4-yl) methyl ester The reactions carried out in the examples are as follows: Street.

Example 1: 2-Ethyl-2-methyl-1,3-dioxolane-4-carboxylic acid (2-ethyl-2-methyl-1,3-dioxolan-4-yl) methyl ester (R ¹ = Me, R ² = Et) Production Example 1-1
To a 300 mL flask equipped with a 100 mL dropping funnel, 23.0 g (purity 95.3%, 150 mmol) of 2-ethyl-4-hydroxymethyl-2-methyl-1,3-dioxolane obtained in Production Example 1; 23.4 mg of hydroxy-2-azaadamantane (AZADOL, Nissan Chemical Industries, Trademark, purity 98.0%, 150 μmol), 17.9 g of pyridine (purity 99.5%, 225 mmol), 50 g of acetonitrile The mixture was charged and stirred under cooling in a nitrogen atmosphere. A solution prepared by dissolving 14.7 g of trichloroisocyanuric acid (TCCA, purity 95.0%, 60.0 mmol) in 50 g of acetonitrile was charged into a dropping funnel, and the reaction liquid temperature in the flask was kept in the range of −2 ° C. to 10 ° C. The dropwise addition was performed over 2 hours while adjusting the dropping rate. Stirring was continued for 3 hours while cooling was stopped and the temperature of the reaction solution was raised to about 20 ° C. Finally, 1.81 g of 2-propanol (purity 99.7%, 30.0 mmol) was added, and further 20 The reaction was completed by stirring for a minute. As a result of GC analysis of the filtrate after filtering off the powdery solid produced as a by-product, the conversion of 2-ethyl-4-hydroxymethyl-2-methyl-1,3-dioxolane was 100%, and 2-ethyl-2-methyl- The yield of 1,3-dioxolane-4-carboxylic acid (2-ethyl-2-methyl-1,3-dioxolan-4-yl) methyl ester was 74%.
In order to remove the powdered solid precipitated after distilling off acetonitrile from the filtrate, 100 g of tert-butyl methyl ether and 50 g of ion-exchanged water were added for extraction. Lower layer water was extracted after the stationary separation, and 50 g of ion exchange water was added again to repeat extraction to extraction of the lower layer water. The obtained organic layer was dried over 20 g of anhydrous sodium sulfate, and after filtration, tert-butyl methyl ether was distilled off to obtain 19.8 g of a red oily crude product. As a result of GC analysis of the crude product, the yield of 2-ethyl-2-methyl-1,3-dioxolane-4-carboxylic acid (2-ethyl-2-methyl-1,3-dioxolan-4-yl) methyl ester was confirmed. The rate was 72%, and the recovery rate before and after washing with water was 92%.
Subsequently, 17.0 g of the crude product was transferred to a 50 mL flask equipped with a Claisen head, subjected to simple distillation under a reduced pressure of 0.13 kPa (absolute pressure), and distilled as a pale yellow liquid at a fraction temperature of 119 to 122 ° C. 11.6 g of 2-ethyl-2-methyl-1,3-dioxolane-4-carboxylic acid (2-ethyl-2-methyl-1,3-dioxolan-4-yl) methyl ester was obtained. The purity was 98.1% and the distillation yield was 80%. GC-MS analysis confirmed that this ester dimer was a mixture of 6 stereoisomers consisting of at least 3 racemates. For the other two sets of racemates, it is presumed that the peaks overlapped and could not be detected.
<Spectral data of stereoisomer mixture>
IR (neat, cm ⁻¹ ): 2979, 2939, 2883, 1761, 1736, 1377, 1186, 1072, 874.
MS (m / z, common to 3 peaks on GC): 287, 273, 259, 115, 57, 43.

Example 1-2
To a 50 mL flask equipped with a 20 mL dropping funnel, 4.60 g of 2-ethyl-4-hydroxymethyl-2-methyl-1,3-dioxolane obtained in Production Example 1 (purity 95.3%, 30.0 mmol) , AZADOL 4.7 mg (purity 98.0%, 30 μmol), 3,5-lutidine 4.92 g (purity 98.0%, 45.0 mmol) and acetonitrile 10 g were charged under cooling in a nitrogen atmosphere. Stir. A solution prepared by dissolving 2.94 g of TCCA (purity 95.0%, 12.0 mmol) in 10 g of acetonitrile was charged into a dropping funnel, and the dropping speed was adjusted so that the temperature of the reaction solution in the flask was within a range of −10 ° C. to 10 ° C. The solution was added dropwise over 1 hour while adjusting. Stirring was continued for another hour while cooling was stopped and the temperature of the reaction solution was raised to about 25 ° C. Finally, 0.20 g of 2-propanol (purity 99.7%, 3.3 mmol) was added, and further 10 The reaction was completed by stirring for a minute. As a result of GC analysis of the filtrate after filtering off the powdery solid produced as a by-product, the conversion of 2-ethyl-4-hydroxymethyl-2-methyl-1,3-dioxolane was 100%, and 2-ethyl-2-methyl- The yield of 1,3-dioxolane-4-carboxylic acid (2-ethyl-2-methyl-1,3-dioxolan-4-yl) methyl ester was 73%.

Example 2: 2-isobutyl-2-methyl-1,3-dioxolane-4-carboxylic acid (2-isobutyl-2-methyl-1,3-dioxolan-4-yl) methyl ester (R ¹ = Me, R using ² = ⁱ Bu) preparation example 2 obtained in 2-isobutyl-4-hydroxymethyl-2-methyl-1,3-dioxolane 26.8 g (purity 97.4% of the 150 mmol) as a reaction raw material Then, the same operation as in Example 1-1 was performed. As a result of GC analysis of the filtrate, conversion of 2-isobutyl-4-hydroxymethyl-2-methyl-1,3-dioxolane was 100% and 2-isobutyl-2-methyl-1,3-dioxolane-4-carboxylic acid The yield of (2-isobutyl-2-methyl-1,3-dioxolan-4-yl) methyl ester was 75%. The yield obtained by GC analysis of 25.9 g of dark brown crude oily product was also 75%, and it was found that there was no yield loss from the analysis of the filtrate.
Subsequently, 20.0 g of the crude product is subjected to simple distillation under reduced pressure of 40 Pa (absolute pressure), and 2-isobutyl-2-methyl-1,3-dioxolane is distilled as a yellow liquid at a fraction temperature of 116 to 124 ° C. 10.6 g of -4-carboxylic acid (2-isobutyl-2-methyl-1,3-dioxolan-4-yl) methyl ester was obtained. The purity was 98.9% and the distillation yield was 70%. GC-MS analysis revealed that the ester dimer was a mixture of 16 stereoisomers consisting of 8 racemates.
<Spectral data of stereoisomer mixture>
IR (neat, cm ⁻¹ ): 2933, 2871, 1763, 1736, 1468, 1377, 1182, 1099.
MS (m / z, common to 8 peaks on GC): 343, 329, 287, 187, 143, 115, 85, 57, 43.

Example 3: 1,4-Dioxaspiro [4.5] decane-2-carboxylic acid (1,4-dioxaspiro [4.5] decan-2-yl) methyl ester (R ¹ , R ² = — (CH ₂ ) _5- ) Production Example 3-1
Using 26.6 g (purity 97.0%, 150 mmol) of 2-hydroxymethyl-1,4-dioxaspiro [4.5] decane obtained in Production Example 3 as a reaction raw material, the same as in Example 1-1 Was performed. As a result of GC analysis of the filtrate, the conversion of 2-hydroxymethyl-1,4-dioxaspiro [4.5] decane was 100%, and 1,4-dioxaspiro [4.5] decane-2-carboxylic acid (1,4 The yield of -dioxaspiro [4.5] decan-2-yl) methyl ester was 66%. The yield obtained by GC analysis of 23.5 g of the dark orange oily crude product was 66%, and it was found that there was no yield loss from the analysis of the filtrate.
Subsequently, 6.50 g of the crude product is distilled under a reduced pressure of 40 Pa (absolute pressure) using a Kugelrohr distillation apparatus, and 1,4-dioxaspiro [4] distilled as an orange liquid at an apparatus temperature of 225 to 240 ° C. .5] 2.89 g of decane-2-carboxylic acid (1,4-dioxaspiro [4.5] decan-2-yl) methyl ester was obtained. The purity was 95.6% and the distillation yield was 60%. ^{From 13} C-NMR analysis, this ester dimer was found to be a mixture of four stereoisomers consisting of two racemates.
<Spectral data of stereoisomer mixture>
IR (neat, cm ⁻¹ ): 2933, 2862, 1761, 1738, 1448, 1367, 1161, 1097, 922.
MS (m / z): 340 (M ^<+> ), 311, 297, 242, 199, 141, 127, 55.

Examples 3-2 and 3-3
Reactions shown in Table 1 using 5.32 g (purity 97.0%, 30.0 mmol) of 2-hydroxymethyl-1,4-dioxaspiro [4.5] decane obtained in Production Example 3 as a reaction raw material The same operation as in Example 1-2 was performed except that the conditions were changed, and 1,4-dioxaspiro [4.5] decane-2-carboxylic acid (1,4-dioxaspiro [4.5] decan-2-yl ) A filtrate containing methyl ester was obtained. Table 1 shows the reaction conditions and results of Examples 3-2 and 3-3.

Example 3-4
888 g of 2-hydroxymethyl-1,4-dioxaspiro [4.5] decane obtained in Production Example 3 (purity 97.0%, 5.00 mmol), 4-acetamido-2,2,6,6-tetra 3.95 g of methyl-1-oxopiperidinium tetrafluoroborate (purity 95.0%, 12.5 mmol), 1.0 g of molecular sieve 4A previously dried under vacuum heating conditions, and 10 g of dichloromethane were added dropwise. A 50 mL flask equipped with a funnel was charged and stirred at room temperature under a nitrogen atmosphere. A solution consisting of 0.914 g of pyridine (purity 99.5%, 11.5 mmol) and 5 g of dichloromethane was placed in a dropping funnel and added dropwise over 20 minutes. Stirring was further continued at room temperature for 3 hours, and finally 0.10 g of methanol (purity 99.8%, 3.1 mmol) was added and stirred for another 10 minutes to complete the reaction. GC analysis of the filtrate after filtering the molecular sieve 4A and by-product powdered solid revealed that the conversion of 2-hydroxymethyl-1,4-dioxaspiro [4.5] decane was 100% and 1,4-dioxaspiro [ The yield of 4.5] decane-2-carboxylic acid (1,4-dioxaspiro [4.5] decan-2-yl) methyl ester was 64%.

Example 4: 2-ethyl-2-pentyl-1,3-dioxolane-4-carboxylic acid (2-ethyl-2-pentyl-1,3-dioxolan-4-yl) methyl ester (R ¹ = Et, R ² = Production of Pentyl) 31.2 g (purity 97.4%, 150 mmol) of 2-ethyl-4-hydroxymethyl-2-pentyl-1,3-dioxolane obtained in Production Example 4 was used as a reaction raw material. The same operation as in Example 1-1 was performed. As a result of GC analysis of the filtrate, conversion of 2-ethyl-4-hydroxymethyl-2-pentyl-1,3-dioxolane was 100% and 2-ethyl-2-pentyl-1,3-dioxolane-4-carboxylic acid The yield of (2-ethyl-2-pentyl-1,3-dioxolan-4-yl) methyl ester was 73%. The yield obtained by GC analysis of 33.0 g of the dark brown oily crude product was 70%, and it was found that the yield was lost by 3% from the analysis of the filtrate.
Subsequently, 6.05 g of the crude product is distilled under a reduced pressure of 40 Pa (absolute pressure) using a Kugelrohr distillation apparatus, and 2-ethyl-2-pentyl distilled as an orange liquid at an apparatus temperature of 180 to 210 ° C. 2.03 g of -1,3-dioxolane-4-carboxylic acid (2-ethyl-2-pentyl-1,3-dioxolan-4-yl) methyl ester was obtained. The purity was 90.6% and the distillation yield was 48%. GC-MS analysis revealed that the ester dimer was a mixture of 16 isomers consisting of 8 racemates.
<Spectral data of stereoisomer mixture>
IR (neat, cm ⁻¹ ): 2931, 2875, 1763, 1736, 1466, 1190, 1165, 1105, 908.
MS (m / z, common to 8 peaks on GC): 400 (M ⁺ ), 371, 329, 171, 129, 99, 71, 57, 43.

Comparative Example: Production of 2,2-dimethyl-1,3-dioxolane-4-carboxylic acid (2,2-dimethyl-1,3-dioxolan-4-yl) methyl ester (R ¹ , R ² = Me) 2 , 2-Dimethyl-4-hydroxymethyl-1,3-dioxolane 20.2 g (product of Tokyo Chemical Industry Co., Ltd., trade name 2,2-dimethyl-1,3-dioxolane-4-methanol, purity 98.0%, The same operation as in Example 1-1 was performed using 150 mmol) as a reaction raw material. As a result of GC analysis of the filtrate, the conversion rate of 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane was 100%, and 2,2-dimethyl-1,3-dioxolane-4-carboxylic acid (2,2 The yield of -dimethyl-1,3-dioxolan-4-yl) methyl ester was 70%. The yield obtained by GC analysis of 15.1 g of the dark orange oily crude product was 59%, and it was found that 11% of the yield was lost from the analysis of the filtrate.
Subsequently, a simple distillation of 14.1 g of the crude product was performed under reduced pressure of 0.13 kPa (absolute pressure), and 2,2-dimethyl-1,3-dioxolane distilled as a colorless liquid at a fraction temperature of 103 to 106 ° C. 8.20 g of -4-carboxylic acid (2,2-dimethyl-1,3-dioxolan-4-yl) methyl ester was obtained. The purity was 98.7% and the distillation yield was 97%. ^{From 13} C-NMR analysis, this ester dimer was found to be a mixture of four stereoisomers consisting of two racemates.
<Spectral data of stereoisomer mixture>
IR (neat, cm ⁻¹ ): 2987, 2939, 1759, 1734, 1371, 1192, 1153, 1099, 1066, 837.
MS (m / z): 259, 245, 186, 130, 115, 101, 73, 59, 43.

  Table 1 below shows the reaction conditions and results of Examples 1 to 4 and Comparative Examples.

Example 5: Production of ethyl glycerate The reaction carried out in Example 5 is as follows.

4. 2-ethyl-2-methyl-1,3-dioxolan-4-carboxylic acid (2-ethyl-2-methyl-1,3-dioxolan-4-yl) methyl ester obtained in Example 1-1 00 g (purity 98.1%, 17.0 mmol), methanesulfonic acid 83 mg (purity 98.0%, 0.85 mmol), ethanol 39.4 g (purity 99.5%, 850 mmol) in a 100 mL flask. The mixture was refluxed for 2 hours. After cooling, the mixture was neutralized with 290 mg of a 20% ethanol solution of sodium ethoxide (58 mg as sodium ethoxide, 0.85 mmol), and ethanol was distilled off. Subsequently, 8.75 g of the obtained orange oily crude product was purified with a Kugelrohr distillation apparatus. Under conditions of 0.13 kPa (absolute pressure) and an apparatus temperature of 150 to 155 ° C., 1.53 g of ethyl glycerate distilled as a colorless liquid was obtained. The purity was 93.5% and the yield was 63%.
<Spectral data of ethyl glycerate>
^{· 1 H-NMR (400MHz,} CDCl 3, δ ppm): 1.31 (3H, t, J = 6.8Hz), 3.82-3.92 (2H, m), 4.24-4.30 (3H, m) The ¹ H peak of the hydroxyl group was broad and could not be detected.
^{· 13 C-NMR (100MHz,} CDCl 3, δ ppm): 14.1,62.0,64.1,71.8,173.0.
IR (neat, cm ⁻¹ ): 3425 (br), 2974, 2935, 1728, 1201, 1111, 1063, 1020.
MS (m / z): 134 (M ^<+> ), 104, 76, 61, 43, 31.

  The ester dimer of the present invention (a glycerate ester in which the hydroxyl groups at the 2-position and 3-position are protected as cyclic acetal groups) has an efficient recovery rate at the time of production, for example, various pharmaceuticals, cosmetics, detergents, polymers, etc. It is useful as a synthetic intermediate for glyceric acid and deprotected glyceric acid ester used as raw materials.

Claims (13)

The manufacturing method of the compound represented by a following formula (I) which has the process of oxidatively esterifying the compound represented by a following formula (II).

(In Formula (II), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure, provided that R ¹ and Except when R ² is a methyl group at the same time.)

(In formula (I), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.) The manufacturing method of Claim 1 which has the process of carrying out the oxidative esterification of the mixture of the compound represented by the following formula (II), and the compound represented by the following formula (V).

(In Formula (II) and Formula (V), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. (However, the case where R ¹ and R ² are methyl groups at the same time is excluded.)   The said oxidative esterification process uses the compound chosen from the salt containing an organic nitroxyl radical, its N-hydroxy body, and those oxoammonium cations, an oxidizing agent, and a base of Claim 1 or 2. Manufacturing method. The production according to claim 3, wherein the organic nitroxyl radical is a compound represented by the following formula (VIII), a compound represented by the following formula (IX), or a compound represented by the following formula (X). Method.

(In the formula (VIII), R ⁴ is a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group, an acyloxy group, an alkoxycarbonyl group, an amino group, an acylamino group, a sulfonyloxy group, an N-alkylcarbamoyloxy group, a carboxy group, a cyano group. Represents an isocyanato group, an isothiocyanato group, or an oxo group, and in formula (IX), R ⁵ and R ⁶ each independently represents a hydrogen atom or a methyl group, and in formula (X), R ⁷ and R ⁸ represent Each independently represents a hydrogen atom or a methyl group.)   The manufacturing method of Claim 3 or 4 whose said oxidizing agent is an oxidizing agent which consists of a compound containing chlorine.   The production method according to claim 3, wherein the base is a heterocyclic aromatic amine having a pyridine skeleton.   The manufacturing method in any one of Claims 1-6 which has the process of isolate | separating the compound represented by Formula (I) after the process of oxidative esterification.   The production method according to claim 7, wherein the separation in the step of separating the compound represented by the formula (I) is separation by distillation.   A process for producing the compound represented by the formula (I) by the production method according to claim 1, and a hydrolysis of the compound represented by the formula (I) produced in the process Alternatively, a method for producing glyceric acid, glycerate, or deprotected glyceric acid ester, which comprises a step of alcoholysis. A compound represented by the following formula (I).

(In formula (I), R ¹ and R ² each independently represent a monovalent hydrocarbon group, or R ¹ and R ² are bonded to each other to form a ring structure. Except that R ¹ and R ² are methyl groups at the same time.) The compound according to claim 10, wherein R ¹ and R ² are monovalent hydrocarbon groups having 1 to 8 carbon atoms. The compound according to claim 10, wherein R ¹ and R ² are bonded to each other to form a cyclopentane ring or a cyclohexane ring. The compound according to claim 10 or 11, wherein R ¹ is a methyl group, and R ² is an ethyl group.