JPWO2005087753A1 - Reagent for reaction - Google Patents

Abstract

An object of the present invention is to provide a method for efficiently performing a dealkylation reaction, a Corey-Kim oxidation reaction, and a Swern oxidation reaction without causing an irritating odor or an unpleasant odor. The general formula [1] (wherein R1 Represents a tertiary amino group, a group derived from a quaternary ammonium salt or a cyclic amino group, R2 represents a thiol group, an alkylsulfenyl group or an alkylsulfinyl group, and n represents a case where R1 is a cyclic amino group Represents an integer of 5 or more, and when R1 is a tertiary amino group or a group derived from a quaternary ammonium salt, the total of n and the number of carbon atoms, nitrogen atoms and oxygen atoms of the amino group is 10 or more. A reagent for dealkylation reaction or oxidation reaction comprising the compound represented by formula (2), a method for oxidizing an alcohol compound using the reaction reagent, and a carbonyl compound using the reaction reagent. Production method on.

Description

  The present invention relates to a reaction reagent comprising a thiol compound that has no irritating odor or unpleasant odor peculiar to sulfur-containing compounds and can be applied to various reactions.

  The thiol compound used in various reactions is a lower aliphatic or aromatic thiol compound and has an irritating odor or an unpleasant odor. Therefore, special consideration must be given to the working environment when using it. Therefore, although the use of thiol compounds is useful for the synthesis of various compounds, the use thereof has been apt to be avoided in the past.

  Accordingly, the present inventors have developed a reaction reagent comprising a thiol compound that has little irritating odor and unpleasant odor and has the same reactivity as a conventionally used lower aliphatic or aromatic thiol compound (patent) Document 1 and Patent document 2).

  These reaction reagents are useful because they do not have an unpleasant odor that poses a problem in use, but they require a slightly complicated operation to be removed from the reaction system after use. Improvement was desired.

JP 2002-265434 JP JP2003-313151

  The present invention provides a method for performing a dealkylation reaction, a Corey-Kim oxidation reaction, and a Swern oxidation reaction more efficiently without worrying about deterioration of the working environment due to an irritating odor or unpleasant odor in the reaction process. Let it be an issue.

The present invention relates to a general formula [1]

(Wherein R ¹ represents a tertiary amino group, a group derived from a quaternary ammonium salt or a cyclic amino group, R ² represents a thiol group, an alkylsulfenyl group or an alkylsulfinyl group, and n represents that R ¹ is When it is a cyclic amino group, it represents an integer of 5 or more, and when R ¹ is a tertiary amino group or a group derived from a quaternary ammonium salt, n and the carbon atom, nitrogen atom and oxygen atom of the amino group Represents an integer such that the sum of the number and the number of the deoxygenating agent is 10 or more).

  Further, the invention is an invention of an oxidation method of an alcohol compound, characterized in that the reaction reagent and an alcohol compound are brought into contact with each other.

  Furthermore, the invention is a method for producing a carbonyl compound corresponding to the alcohol compound, wherein the reagent for reaction is brought into contact with the alcohol compound.

Furthermore, the general formula [2]

(Wherein m represents an integer of 5 or more, and R ² is the same as described above).

  The reaction reagent of the present invention has a weak odor despite being a sulfur-containing compound, and has an amino group in its structure, so that it is dealkylated, Corey-Kim oxidation reaction or When used in the Swern oxidation reaction, the reaction reagent can be easily separated from the reaction solution by only acid washing after the reaction without worrying about deterioration of the working environment due to irritating odors and unpleasant odors in the reaction process. The troublesome post-treatment process after the reaction can be reduced.

In the present invention, the general formula [1]

(Wherein R ¹ represents a tertiary amino group, a group derived from a quaternary ammonium salt or a cyclic amino group, R ² represents a thiol group, an alkylsulfenyl group or an alkylsulfinyl group, and n represents that R ¹ is When it is a cyclic amino group, it represents an integer of 5 or more, and when R ¹ is a tertiary amino group or a group derived from a quaternary ammonium salt, n and the carbon atom, nitrogen atom and oxygen atom of the amino group The tertiary amino group represented by R ¹ of the compound represented by formula (3) is a general formula [3].

(Wherein R ⁴ and R ⁵ each independently represents an alkyl group, aryl group or aralkyl group optionally having an oxygen atom).

The alkyl group which may have an oxygen atom represented by R ⁴ and R ⁵ of the group represented by the general formula [3] may be linear, branched or cyclic, but A chain is preferable, usually having 1 to 12, preferably 1 to 6, more preferably 1 to 4, more preferably 1 or 2 carbon atoms. Specific examples include, for example, a methyl group and an ethyl group. , N-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, tert-pentyl, neopentyl, n- Hexyl, isohexyl, sec-hexyl, tert-hexyl, n-heptyl, isoheptyl, sec-heptyl, tert-heptyl, n-octyl, sec-octyl, tert-octyl, nonyl Group, decyl group, undecyl group, dodecyl group Group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl group, cyclodecyl group, cycloundecyl group, cyclododecyl group, and the like.

As the alkyl group having an oxygen atom represented by R ⁴ and R ⁵ , usually 1 to 5, preferably 1 to 3 oxygen atoms in the chain of the alkyl group having 2 to 12 carbon atoms. Specific examples include, for example, —CH ₂ —O—CH ₃ , —CH ₂ CH ₂ —O—CH ₃ , —CH ₂ —O—CH ₂ CH ₃ , —CH (CH ₃ ) -O-CH ₃ , -CH ₂ -CH (CH ₃ ) -O-CH ₃ , -CH ₂ CH ₂ -O-CH ₂ CH ₃ , -CH ₂ CH ₂ -OC (CH ₃ ) ₃ , -CH ₂ CH ₂ CH ₂ -O-CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₂ -O-CH (CH ₃ ) CH ₃ , -CH ₂ CH (CH ₃ ) -O-CH ₂ CH (CH ₃ ) CH ₃ , -CH ₂ -O-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ -O-CH ₃ , -CH ₂ CH ₂ -O-CH (CH ₂ CH ₃ ) CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ -O-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₂ CH ₂ -OC (CH ₃ ) _{3, -CH 2 CH 2 CH 2} -O-CH 2 CH 2 CH 2 -O-CH 2 CH 2 CH 3, -CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH ₂ -O-CH ₃ , -CH ₂ CH ₂ -O-CH ₂ CH ₂ -O-CH ₂ CH ₂ -O-CH ₂ CH ₃ , -CH ₂ CH ₂ -O-CH ₂ CH ₂ -O-CH ₂ CH ₂ -O-CH ₂ CH ₂ -O-CH ₂ CH ₂ CH ₃ , -CH ₂ CH ₂ -O-CH ₂ CH ₂ -O-CH ₂ CH (CH ₃ ),

Etc.

Examples of the aryl group represented by R ⁴ and R ⁵ usually include those having 6 to 14 carbon atoms. Specific examples include a phenyl group, a naphthyl group, an anthryl group, and a phenanthryl group.

Examples of the aralkyl group represented by R ⁴ and R ⁵ usually include those having 7 to 10 carbon atoms, and specific examples include a benzyl group, a phenylethyl group, a phenylpropyl group, and a phenylbutyl group. .

Preferably at least one of such R ⁴ and R ⁵ above is an alkyl group, and more preferably R ⁴ and R ⁵ are both the same group, R ⁴ and R ⁵ are both the same alkyl group More preferably it is.

  Specific examples of the group represented by the general formula [3] include, for example, dimethylamino group, diethylamino group, methylethylamino group, di-n-propylamino group, diisopropylamino group, 1-phenylethylamino group, and the like. It is done.

Examples of the group derived from the quaternary ammonium salt represented by R ¹ in the general formula [1] include the following general formula [4].

(Wherein R ⁶ represents an alkyl group, and R ⁴ and R ⁵ are the same as described above).

The alkyl group represented by R ⁶ in the general formula [4] is the same as the alkyl group of the alkyl group optionally having an oxygen atom represented by R ⁴ and R ⁵ as described above. Can be mentioned.

  Specific examples of the group represented by the general formula [4] include a trimethylammonium group, a triethylammonium group, a dimethylethylammonium group, and a dimethylphenylammonium group.

The cyclic amino group represented by R ¹ in the general formula [1] is derived from a tertiary amino group represented by the general formula [3] and a quaternary ammonium salt represented by the general formula [4]. R ⁴ and R ^{5 in} the above group are combined to form an alkyl chain, and the alkyl chain and the nitrogen atom are usually 3 to 15 members, preferably 3 to 12 members, more preferably 3 to 7 members, still more preferably 5 Or what forms the 6-membered saturated heterocyclic ring is mentioned.

The alkyl chain formed by bonding R ⁴ and R ^{5 as} described above usually has 1 to 15 carbon atoms, preferably 2 to 13 carbon atoms, and may have an oxygen atom and / or a nitrogen atom in the chain. More preferred are 2 to 10, further preferred are 2 to 6, particularly preferred are 3 to 5 linear or branched ones, and among these, linear ones are preferred.

  When the alkyl chain has an oxygen atom and / or a nitrogen atom in the chain, the total number of these atoms is usually 1 to 3, preferably 1 to 2, and more preferably 1.

  Examples of the cyclic amino group include amino groups in which the cyclic portion is usually a 3- to 12-membered ring, preferably a 5- to 6-membered ring. Specifically, for example, a 3-membered ring such as aziridine, for example, pyrrolidine Groups having a 5-membered ring such as imidazoline and pyrazolidine, for example, a 6-membered ring such as piperidine, morpholine and piperazine, for example, a bicyclo ring such as quinuclidine, among which the cyclic part is morpholine, piperazine and pyrrolidine Among them, those having a 5- to 6-membered ring are preferable, and among them, an amino group (morpholino group) in which the cyclic portion is a morpholine ring is particularly preferable. Among the specific examples of the cyclic amino group, preferred examples include cyclic tertiary amino groups such as piperazino group, imidazolidino group, morpholino group, piperidino group, pyrrolidino group, such as N-methylmorpholino group and N-ethylmorpholino group. N-propylmorpholino group, N-methylpiperidino group, N-ethylpiperidino group, N-propylpiperidino group, N-methylpyrrolidino group, N-ethylpyrrolidino group, N-propylpyrrolidino group, etc. A class ammonium group etc. are mentioned.

The alkylsulfenyl group represented by R ² of the compound represented by the general formula [1] according to the present invention may be linear, branched or cyclic at one bond of a divalent sulfur atom. A straight chain is preferable but usually has 1 to 12, preferably 1 to 6, more preferably 1 to 4, more preferably 1 or 2, and particularly preferably 1 or 2 alkyl groups. Specifically, for example, methylsulfenyl group, ethylsulfenyl group, n-propylsulfenyl group, isopropylsulfenyl group, n-butylsulfenyl group, isobutylsulfenyl group, sec-butylsulfenyl group, tert-butylsulfenyl group, Phenyl group, n-pentylsulfenyl group, isopentylsulfenyl group, sec-pentylsulfenyl group, tert-pentylsulfenyl group, neopentylsulfenyl group, n- Xylsulfenyl, isohexylsulfenyl, sec-hexylsulfenyl, tert-hexylsulfenyl, n-heptylsulfenyl, isoheptylsulfenyl, n-octylsulfenyl, etc. n-nonylsulfenyl Group, n-decylsulfenyl group, n-undecylsulfenyl group, n-dodecylsulfenyl group, cyclopropylsulfenyl group, cyclopentylsulfenyl group, cyclohexylsulfenyl group, cycloheptylsulfenyl group, cyclooctylsulfenyl group Group, cyclononylsulfenyl group, cyclodecylsulfenyl group, cycloundecylsulfenyl group, cyclododecylsulfenyl group and the like.

Further, the alkylsulfinyl group represented by R ² may be linear, branched or cyclic at one bond of the sulfinyl group, but is preferably linear, usually having 1 to 12 carbon atoms, preferably 1 to 6, more preferably 1 to 4, more preferably 1 or 2, particularly preferably 1 is an alkyl group bonded thereto. Specific examples include methylsulfinyl group, ethylsulfinyl group, n-propyl. Sulfinyl group, isopropylsulfinyl group, n-butylsulfinyl group, isobutylsulfinyl group, sec-butylsulfinyl group, tert-butylsulfinyl group, n-pentylsulfinyl group, isopentylsulfinyl group, sec-pentylsulfinyl group, tert-pentylsulfinyl group Group, neopentylsulfinyl group, n-hexylsulfinyl group, isohexyl Rufinyl group, sec-hexylsulfinyl group, tert-hexylsulfinyl group, n-heptylsulfinyl group, isoheptylsulfinyl group, n-octylsulfinyl group, n-nonylsulfinyl group, n-decylsulfinyl group, n-undecylsulfinyl group N-dodecylsulfinyl group, cyclopropylsulfinyl group, cyclopentylsulfinyl group, cyclohexylsulfinyl group, cycloheptylsulfinyl group, cyclooctylsulfinyl group, cyclononylsulfinyl group, cyclodecylsulfinyl group, cycloundecylsulfinyl group, cyclododecylsulfinyl group Etc.

N of the compound represented by the general formula [1] according to the present invention is usually 5 or more, preferably 5 to 18, more preferably 6 to 18, more preferably 6 to 6 when R ¹ is a cyclic amino group. When R ¹ is a tertiary amino group or a group derived from a quaternary ammonium salt, the total of n and the number of carbon atoms, nitrogen atoms and oxygen atoms contained in these amino groups is usually 10 or more. , Preferably 10 to 18, more preferably 11 to 18, and still more preferably 12 to 16.

  Although the compound represented by the general formula [1] according to the present invention has a thiol group, an alkylsulfenyl group or an alkylsulfinyl group in the molecule, there is almost no irritating odor or unpleasant odor.

  The compound represented by the general formula [1] as described above can be obtained, for example, as follows.

That is, for example, the following general formula [11]

(Wherein R ¹ is the same as above) and the following general formula [12]

Wherein X represents a halogen atom selected from chlorine, bromine or iodine, a p-toluenesulfonyloxy group, a methanesulfonyloxy group or a trifluoromethanesulfonyloxy group, and n is the same as above. , Without solvent or using a suitable solvent, usually at -78 to 250 ° C, preferably 0 to 200 ° C, more preferably 50 to 150 ° C, usually 0.1 to 24 hours, preferably 0.5 to 15 hours, more preferably 1 to 1 General formula [13] obtained by reacting for 10 hours

(Wherein R ¹ and n are the same as above) and a sulfurizing agent of usually 1 to 10 times equivalent, preferably 1 to 2 equivalents, more preferably 1 to 1.1 equivalents, relative to the compound. (For example, thiourea, sodium sulfide, sodium hydrogen sulfide, diphosphorus pentasulfide, etc.) in the presence of an acid catalyst such as hydrobromic acid, usually in a suitable solvent at −78 to 250 ° C., preferably 0 to When the reaction is carried out at 200 ° C., more preferably 50 to 150 ° C., usually for 0.1 to 24 hours, preferably 0.5 to 16 hours, more preferably 1 to 12 hours, the compound represented by the general formula [1] according to the present invention can be obtained. Among them, a compound in which R ² is a thiol group is obtained.

  Among the above reactions, suitable solvents used in the reaction of the compound represented by the general formula [11] and the compound represented by the general formula [12] include aliphatic hydrocarbons such as hexane and cyclohexane. Aromatic hydrocarbons such as benzene, toluene, xylene, etc., alcohols such as methanol, ethanol, isopropyl alcohol, etc., ethers such as diethyl ether, tetrahydrofuran, isopropyl ether, dioxane, diethoxyethane, eg acetone, methyl ethyl ketone, etc. Ketones such as halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, such as dimethylformamide, etc., and the amount used is usually 0.1 to 40 times weight, preferably 0.2-10 times weight, more The weight is preferably 0.5 to 5 times.

  Among the above reactions, suitable solvents used in the reaction of the compound represented by the general formula [13] with the sulfurizing agent include aromatic hydrocarbons such as benzene, toluene and xylene, for example, Examples thereof include dimethylformamide, and dimethylformamide is particularly preferable. The usage-amount of a solvent is 0.5-40 times weight normally with respect to the compound shown by General formula [13], Preferably it is 1-10 times weight, More preferably, it is 2-5 times weight.

In addition, for example, among the compounds represented by the general formula [1] obtained by the above reaction, R ² is a thiol group, and usually 1 to 10 equivalents, preferably 1 to 2 equivalents, more preferably the compound. 1 to 1.1 equivalents of an alkylating agent (for example, methyl iodide, methyl bromide, dimethyl sulfate, methyl trifluoromethanesulfonate, methyl p-toluenesulfonate, etc.) in the presence of an aqueous sodium hydroxide solution, for example. In a solvent, usually -78 to 200 ° C, preferably -20 to 150 ° C, more preferably 0 to 100 ° C, usually 0.1 to 24 hours, preferably 0.5 to 10 hours, more preferably 1 to 5 hours. Among the compounds represented by the general formula [1] according to the present invention, a compound in which R ² is an alkylsulfenyl group is obtained.

Examples of suitable solvents used in the reaction of the compound represented by the general formula [1] wherein R ² is a thiol group with an alkylating agent include aliphatic hydrocarbons such as hexane and cyclohexane, such as benzene. Aromatic hydrocarbons such as toluene and xylene, alcohols such as methanol, ethanol and isopropyl alcohol, ethers such as diethyl ether, tetrahydrofuran, isopropyl ether, dioxane and diethoxyethane, and ketones such as acetone and methyl ethyl ketone , For example, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, and the like, such as dimethylformamide, etc., and the amount used is usually relative to the compound in which R ^{2 in the} general formula [1] is a thiol group 0.5 to 40 times weight, preferably 1 to 10 times weight More preferably, the weight is 2 to 5 times.

Furthermore, for example, among the compounds represented by the general formula [1] obtained by the above reaction, R ² is an alkylsulfenyl group, and usually 1 to 10 equivalents, preferably 1 to 2 equivalents, relative to the compound. More preferably, 1 to 1.1 equivalents of an oxidizing agent (for example, m-chloroperbenzoic acid, hydrogen peroxide, hypochlorite, etc.), if necessary, activity of so-called oxidation reaction such as acetyl chloride or sodium tungstate In the presence of an agent, a suitable solvent is used, usually at -100 to 200 ° C, preferably -78 to 100 ° C, more preferably at -50 to 50 ° C, usually for 0.1 to 24 hours, preferably 0.2 to 10 hours, and more. Preferably, by reacting for 0.3 to 5 hours, a compound in which R ² is an alkylsulfinyl group among the compounds represented by the general formula [1] is obtained.

Of the cyclic amino groups, R ^{1 of the} compound represented by the general formula [1] according to the present invention is the following general formula [2].

(In the formula, m represents an integer of 5 or more, and R ² is the same as described above).

  In the general formula [2], m represents an integer of usually 5 or more, preferably 5 to 18, more preferably 6 to 18, and still more preferably 6 to 16.

  The reagent for reaction comprising the compound represented by the general formula [1] according to the present invention is prepared by (i) reacting an asymmetric sulfide compound with an amino group-containing sulfur compound and cleaving the sulfide group of the sulfide compound. Reaction to produce a thiol group-containing sulfur compound, (ii) reaction to react an alkoxy group-containing compound with an amino group-containing sulfur compound to produce a corresponding hydroxyl group-containing compound, (iii) an amino group to an aralkyloxy group-containing compound It is useful for various reactions such as a so-called dealkylation reaction such as a reaction in which a containing sulfur compound is allowed to act to produce a corresponding hydroxyl group-containing compound.

For example, a reaction reagent comprising a compound in which R ² in the general formula [1] is a thiol group can be handled by (1) cleaving the sulfide group of the sulfide compound if this is applied to an asymmetric sulfide compound. The thiol group-containing compound is obtained, and (2) the reaction reagent is allowed to act on the alkoxy group-containing compound to obtain the corresponding hydroxyl group-containing compound. When it is allowed to act on an aralkyloxy group-containing compound, a corresponding hydroxyl group-containing compound is obtained.

Further, for example, the reaction reagent comprising a compound represented by the general formula [1] wherein R ² is an alkylsulfenyl group or an alkylsulfinyl group includes (4) an oxidation reaction of an alcohol compound and (5) a reaction. It is useful as a reaction reagent used in a method for producing a carbonyl compound corresponding to an alcohol compound to be produced.

As described above, a reaction reagent comprising a compound in which R ^{2 of the} compound represented by the general formula [1] is a thiol group is allowed to act on the asymmetric sulfide compound to obtain a corresponding thiol group-containing compound (above In the reaction (1), the asymmetric sulfide compound may be any compound having two organic groups with different sulfur atoms present in the molecule. For example, the following general formula [5]

(In the formula, R ⁷ represents an alkyl group which may have a substituent, and R ⁸ and R ⁹ each independently represents an alkyl group, an aryl group, or an optionally substituted hydrogen atom or substituent. Represents an aralkyl group, A represents a group represented by —N (R ^{9 ′} ) — or an oxygen atom, R ^{9 ′} represents a hydrogen atom or an optionally substituted alkyl group, R ⁹ and R ^{9 ′} may be bonded to each other to form a ring.), For example, a compound represented by the general formula [6]

(Wherein R ¹⁰ , R ¹¹ and R ¹² each independently represents a hydrogen atom, an alkyl group and an aryl group, and R ⁷ is the same as described above), and the like. When the reaction reagent of the present invention is allowed to act in the presence of a catalyst, if necessary, the corresponding general formula [7]

(Wherein R ⁸ , R ⁹ and A are as defined above) or a compound represented by the general formula [8]

(Wherein R ¹⁰ , R ¹¹ and R ¹² are the same as described above), and a thiol group-containing compound such as a compound represented by

  As described above, since the compound represented by the general formula [1] according to the present invention has almost no irritating odor or unpleasant odor, the reaction reagent containing the compound is used as the reaction of the above (1) to (5). There is no need to give special consideration to the odor when used for the odor.

In the general formulas [5] and [6], the alkyl group of the alkyl group which may have a substituent represented by R ⁷ may be linear, branched or cyclic, In the case of a ring, it may be monocyclic or polycyclic, and usually includes those having 1 to 20 carbon atoms, preferably 5 to 12 carbon atoms. Specific examples thereof include a methyl group, an ethyl group, an n-propyl group, and an isopropyl group. , N-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, n-hexyl group, isohexyl group, sec- Hexyl, tert-hexyl, n-heptyl, isoheptyl, sec-heptyl, tert-heptyl, n-octyl, sec-octyl, tert-octyl, nonyl, decyl, undecyl, Dodecyl group, tridecyl group, tetradecyl group , Pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, icosyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl group, cyclodecyl group, cycloundecyl group, cyclododecyl group Group, cyclotridecyl group, cyclohexadecyl group, cyclooctadecyl group, cycloicosyl group, bicyclo [2.1.0] pentyl group, bicyclo [2.2.1] heptyl group, bicyclo [3.2.1] octyl group, bicyclo [5.2. 0] nonyl group, bicyclo [4.3.1] decyl group, tricyclo [5.4.0.0 ^2.9 ] undecyl group, tricyclo [5.3.1.1] dodecyl group, tricyclo [7.3.2.0 ^5.13 ] tetradecyl group, spiro [3.4] octyl group, Spiro [3.3] heptyl group, spiro [4.5] decyl group, etc. For example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, tert-pentyl group, neopentyl group, n-hexyl group, isohexyl group, 2,2-dimethylbutyl group, cyclopentyl group, cyclohexyl group and other linear, branched, and cyclic alkyl groups having 1 to 6 carbon atoms, oxo group, carbonyl group, hydroxyl group Groups and the like.

More preferable specific examples of the group represented by R ^{7 as} described above include, for example,

Etc.

In the general formulas [5] and [7], the alkyl group of the alkyl group which may have a substituent represented by R ⁸ and R ⁹ may be linear, branched or cyclic, Examples thereof usually include those having 1 to 6 carbon atoms, specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, Examples include n-pentyl group, isopentyl group, tert-pentyl group, neopentyl group, n-hexyl group, isohexyl group, 2,2-dimethylbutyl group, cyclopentyl group, cyclohexyl group and the like.

  Examples of the aryl group of the aryl group which may have a substituent usually include those having 6 to 14 carbon atoms, and specific examples include a phenyl group, a naphthyl group, a phenanthryl group, and an anthryl group. .

  Examples of the aralkyl group of the aralkyl group which may have a substituent usually include those having 7 to 10 carbon atoms. Specifically, for example, a benzyl group, a phenylethyl group, a phenylpropyl group, a phenylbutyl group, etc. Is mentioned.

  Examples of the substituent for the alkyl group, aryl group and aralkyl group include halogen atoms such as chlorine, fluorine, bromine and iodine, for example, the alkyl group as described above, and the number of substituents is usually 1 to 5, Preferably it is 1-2.

Examples of the alkyl group which may have a substituent represented by R ^{9 ′} include those similar to the alkyl group which may have a substituent represented by R ⁸ and R ⁹ as described above. It is done.
In the general formulas [5] and [7], when R ⁹ and R ^{9 ′} are bonded to each other to form a ring, the ring may be monocyclic or polycyclic and may be 5-membered or 6-membered. Specific examples include heterocycles, and specific examples include monocyclic heterocycles such as pyrrolidine rings and piperidine rings.

  These rings may have a substituent which does not participate in the reaction with the thiol compound. Specific examples of the substituent include, for example, an alkyl group such as a methyl group, an ethyl group, and a propyl group, an aryl group such as a phenyl group and a naphthyl group, an aralkyl group such as a benzyl group, such as a methoxy group, an ethoxy group, and a propoxy group. Alkoxy groups such as dimethylamino group, diethylamino group and other dialkylamino groups such as methyloxycarbonyl group, ethyloxycarbonyl group, propyloxycarbonyl group and other alkyloxycarbonyl groups such as phenyloxycarbonyl group, tert-butyldiphenyl An aryloxycarbonyl group such as an oxycarbonyl group, an aralkyloxycarbonyl group such as a benzyloxycarbonyl group, an alkylsilyloxycarbonyl group such as a tert-butyldimethylsilyloxycarbonyl group, and the like.

In the general formulas [6] and [8], the alkyl group and aryl group represented by R ¹⁰ , R ¹¹ and R ¹² may be an alkyl which may have a substituent represented by R ^9. Examples thereof are the same as the alkyl group and aryl group of the group and aryl group.

Examples of the catalyst used as needed include Lewis acid catalysts such as BF ₃ .O (CH ₂ CH ₃ ) ₂ and aluminum chloride, such as triethylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1 And tertiary amines such as 5-diazabicyclo [4.3.0] non-5-ene.

  The usage-amount of the reagent for reaction of this invention is 1-10 equivalent normally with respect to an asymmetric sulfide compound, Preferably it is 2-5 equivalent, More preferably, it is 1.2-2 equivalent.

  If necessary, the amount of the catalyst used is usually 0.1 to 10% by weight, preferably 1 to 5% by weight, more preferably 1.2 to 1.5% by weight, based on the asymmetric sulfide compound.

  In the reaction (1), a reaction solvent may be used. Examples of the reaction solvent include hydrocarbons such as hexane, aromatic hydrocarbons such as benzene and toluene, such as dichloromethane, chloroform, Examples thereof include halogenated hydrocarbons such as carbon tetrachloride, halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene, and ethers such as diethyl ether, tetrahydrofuran and dioxane.

  The amount of the reaction solvent used is usually 2 to 100 times, preferably 5 to 50 times, more preferably 5 to 10 times the weight of the asymmetric sulfide compound.

  The reaction temperature varies depending on the type and amount of the reaction reagent of the present invention and the asymmetric sulfide compound to be used, but is usually 5 to 50 ° C, preferably 15 to 30 ° C.

  While the reaction time varies depending on the type and amount of the reaction reagent of the present invention and the asymmetric sulfide compound used, the reaction time and the like, it is generally 30 minutes to 15 hours, preferably 1 to 10 hours.

  After completion of the reaction (1), for example, the reaction solution may be extracted and washed with water or acid, and then the target product may be extracted with a suitable organic solvent.

  As the acid used for the purpose of the post-treatment after the reaction, any acid can be used as long as it is a normal acid. Examples thereof include carboxylic acids such as acids, organic acids such as sulfonic acids such as p-toluenesulfonic acid and methanesulfonic acid, and hydrochloric acid is particularly preferable.

  The organic solvent used for the extraction of the target product may be any organic solvent that is usually used for the extraction operation and can dissolve the target product. Specifically, for example, methyl acetate, ethyl acetate, etc. Esters, for example, ethers such as dimethyl ether, diisopropyl ether, and diethyl ether, aromatic hydrocarbons such as toluene, and halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride.

  In addition, post-treatment and purification after the reaction other than the above may be performed according to a method known per se.

In addition, depending on the combination of R ¹⁰ , R ¹¹ and R ¹² of the compound represented by the general formula [6], the thiol group-containing compound represented by the general formula [8] has an asymmetric carbon. These reaction reagents can also be used for asymmetric reactions.

Further, the reaction reagent comprising the compound of the present invention represented by the general formula [1] wherein R ² is a thiol group can act on, for example, an alkoxy group-containing compound or an aralkyloxy group-containing compound, if necessary in the presence of an acid. To produce a corresponding hydroxyl group-containing compound (reaction (2) or (3) above).

  Such an alkoxy group-containing compound or aralkyloxy group-containing compound may be one having at least one alkoxy group or aralkyloxy group in the molecule, and having two or more. However, the reaction similar to the compound having one occurs, and a compound having two or more corresponding hydroxyl groups is obtained.

As the alkoxy group-containing compound or aralkyloxy group-containing compound as described above, for example, the following general formula [9]

(Wherein R ¹³ represents an alkyl group, aryl group, aralkyl group or natural terpenoid which may have a substituent, and R ¹⁴ represents an alkyl group or aralkyl which may have a substituent. A compound represented by the following formula:

The alkyl group which may have a substituent represented by R ¹³ in the general formula [9] may be linear, branched or cyclic, and usually has 2 to 6 carbon atoms, preferably 2 to 2 carbon atoms. Specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, Examples include an isopentyl group, a tert-pentyl group, a neopentyl group, an n-hexyl group, an isohexyl group, a 2,2-dimethylbutyl group, a cyclopentyl group, and a cyclohexyl group. Examples of the substituent include alkyl having 1 to 4 carbon atoms. Group, an aryl group having 6 to 10 carbon atoms, a hydroxyl group, an acetoxyl group, an amino group, an amide group, and the like.

Examples of the aryl group of the aryl group which may have a substituent represented by R ¹³ usually include those having 6 to 14 carbon atoms. Specifically, for example, a phenyl group, a naphthyl group, a phenanthryl group, an anthryl group Among them, a phenyl group is preferable, and examples of the substituent of the aryl group include alkyl groups having 1 to 4 carbon atoms such as a methyl group, an ethyl group, a propyl group, and a butyl group, such as a methoxy group and an ethoxy group. An alkoxy group having 1 to 4 carbon atoms such as a propoxy group or a butoxy group, for example, an aryloxy group such as a phenyloxy group or a naphthyloxy group, for example, an acyl group having 2 to 5 carbon atoms such as an acetyl group, a propionyl group or a butyryl group May have an aralkyl group having 7 to 10 carbon atoms such as a benzyl group, an ethylphenyl group or a propylphenyl group, for example, a substituent. Examples thereof include saturated aliphatic groups having 5 to 7 carbon atoms such as cyclopentyl group, cyclohexyl group, and cycloheptyl group. An aryl group having a saturated aliphatic group having a substituent as a substituent includes an aryl group formed by forming a condensed ring with 1 to 5 saturated aliphatic rings having a substituent, or a nitrogen atom. A saturated cyclic group which may have a substituent or a quinone ring and an aryl group which are condensed or bonded as a ring-forming isomer atom are also included. The saturated aliphatic group, the saturated aliphatic ring, the saturated cyclic group containing a nitrogen atom as a ring-forming isomer atom, and the substituent that the quinone ring may have, for example, a methyl group, an ethyl group, C1-C4 alkyl groups, such as a propyl group and a butyl group, for example, C1-C4 alkoxy groups, such as a methoxy group, an ethoxy group, a propyloxy group, a butoxy group, for example, an acetyl group, a propionyl group, a butyryl group, etc. And an acyl group having 2 to 5 carbon atoms.

When the reaction reagent of the present invention is allowed to act on a compound in which the group represented by R ¹³ is an aryl group having one or more alkoxy groups or aryloxy groups as substituents, the reaction reagent has two or more hydroxyl groups. In some cases, one of the hydroxyl groups of the compound forms a new ring containing an oxygen atom as a ring-forming isomer atom with another ring fused or bonded to the aryl group.

As the aralkyl group of the aralkyl group which may have a substituent, represented by R ¹³ in the general formula [9], those having 7 to 10 carbon atoms are usually mentioned. Specifically, for example, phenylethyl Group, phenylpropyl group, phenylbutyl group and the like. Examples of the substituent include alkyl groups such as methyl group, ethyl group and propyl group, for example, dialkylamino groups such as dimethylamino group and diethylamino group, such as methyloxycarbonyl. Group, alkyloxycarbonyl group such as ethyloxycarbonyl group, propyloxycarbonyl group and the like.

Examples of natural terpenoids represented by R ¹³ in the general formula [9] include monovalent organic residues derived from diterpenoids, triterpenes, steroids, alkaloids, and the like.

In addition, examples of the alkyl group of the alkyl group which may have a substituent represented by R ¹⁴ in the general formula [9] include those similar to those represented by R ^{13 as} described above. Examples of the group include an alkoxy group having 2 to 5 carbon atoms such as a methoxy group, an ethoxy group, a propyloxy group, and a butoxy group.

Examples of the aralkyl group optionally having a substituent represented by R ¹⁴ in the general formula [9] include the same groups as those represented by R ^{13 as} described above.

Examples of specific examples of the alkoxy group-containing compound or the aralkyloxy group-containing compound represented by the general formula [9] according to the present invention include

(Hereinafter, Bn represents a benzyl group.)

(Wherein X represents an acyl group having 2 to 5 carbon atoms such as acetyl group, propionyl group and butyryl group, and Y ₁ and Y ₂ are each independently carbon such as benzyloxy group and phenylethyloxy group. Z represents a hydrogen atom or an acyl group having 1 to 5 carbon atoms such as a formyl group, an acetyl group, a propionyl group, and a butyryl group).

As a specific example of the reaction for producing the hydroxyl group-containing compound as described above, an example in which the reaction reagent of the present invention is used and a compound having one alkoxy group or one aralkyloxy group in the molecule is used. ] Is shown below.

In addition, using the reaction reagent of the present invention,

(In the formula, X, Y ₁ , Y ₂ and Z are the same as above.) The reaction formula in the case of hydroxylating the compound shown below is shown below.

(Wherein X, Y ₁ , Y ₂ and Z are the same as above)
In the reaction (2) or (3) such as the reaction represented by the reaction formula [10], the reaction reagent of the present invention is used in the same amount as the reaction solvent of the present invention. In some cases, it is used in a large excess, but it is usually 1 to 10 equivalents, preferably 2 to 3 equivalents, relative to the alkoxy group-containing compound or aralkyloxy group-containing compound to be reacted.

  Examples of the acid used as needed include organic acids such as trifluoroacetic acid and methanesulfonic acid, Lewis acids such as aluminum chloride, and the like. The amount used is an alkoxy group-containing compound or an aralkyloxy group-containing compound. The amount is usually 0.1 to 10 equivalents, preferably 1 to 5 equivalents, more preferably 1 to 2 equivalents.

  In addition, the reaction of the above (2) or (3) such as the reaction represented by the reaction formula [10] may use a reaction solvent different from the reaction reagent. As such a reaction solvent, for example, Hydrocarbons such as hexane, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride, halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene, Examples include ethers such as diethyl ether and tetrahydrofuran, and nitriles such as acetonitrile, and the amount used is usually 1 to 100 times the weight of the alkoxy group-containing compound or aralkyloxy group-containing compound, preferably 5 to 5 times. The weight is 50 times, more preferably 5 to 10 times.

  The reaction temperature is usually −10 to 100 ° C., preferably −5 to 30 ° C.

  The reaction time is usually 30 minutes to 80 hours, preferably 1 to 10 hours.

  The post-treatment after the reactions (2) and (3) may be performed in the same manner as the post-treatment after the reaction (1). That is, the target product can be easily isolated from the reaction solution by treatment with an acid.

Further, among the compounds represented by the general formula [1], a compound in which R ² is an alkylsulfinyl group is reacted with an alcohol compound using a base and a co-oxidant in the presence of a solvent, if necessary. A carbonyl compound corresponding to the compound is obtained (reactions (4) and (5) above).

In addition, when an oxidation reaction of alcohol (production of a carbonyl compound) is performed by the above reaction, R ^{2 of the} compound represented by the general formula [1] is an alkylsulfenyl group simultaneously with the carbonyl compound corresponding to the alcohol compound. Can be obtained.

In addition, a compound in which R ² is an alkylsulfenyl group among the compounds represented by the general formula [1] is reacted with an alcohol compound using a base and a co-oxidant in the presence of a solvent, if necessary. A carbonyl compound corresponding to the compound is obtained.

As an alcohol compound used when producing a carbonyl compound using a compound in which the compound R ² represented by the general formula [1] is an alkylsulfinyl group or an alkylsulfenyl group as described above, a compound having a hydroxyl group is used. For example, the general formula [10]

(In the formula, R ¹⁵ and R ¹⁶ each independently represent a hydrogen atom, an alkyl group, an aryl group, an aralkyl group or an acyl group, and R ¹⁵ and R ¹⁶ may combine to form a ring. ).

In the general formula [10], the alkyl group represented by R ¹⁵ and R ¹⁶ may be linear, branched or cyclic, and usually has 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, and more preferably. Include those of 1 to 6, specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n- Pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, n-hexyl group, isohexyl group, 2,2-dimethylbutyl group, n-heptyl group, isoheptyl group, sec-heptyl group, tert- Heptyl group, n-octyl group, isooctyl group, n-nonyl group, isononyl group, sec-nonyl group, n-decyl group, n-undecyl group, n-dodecyl group n-tridecyl group, n-tetradecyl group, n-pentadecyl group, n-hexadecyl group, n-heptadecyl group, n-octadecyl group, n-nonadecyl group, n-icosyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, Cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl, cyclohesadecyl, cycloheptadecyl, cyclononadecyl, cycloicosyl, bicyclo [2.1.0] pentyl Group, bicyclo [2.2.1] heptyl group, bicyclo [3.2.1] octyl group, bicyclo [5.2.0] nonyl group, bicyclo [4.3.1] decyl group, tricyclo [5.4.0.0 ^2.9 ] undecyl group, tricyclo [ 5.3.1.1] dodecyl group, tricyclo [7.3.2.0 ^5.13] tetradecyl, spiro [3.4 Octyl, spiro [3.3] heptyl group, spiro [4.5] decyl group.

The alkyl group is, for example, a halogen atom such as chlorine, bromine, iodine or fluorine, for example, an alkoxy group having 1 to 4 carbon atoms such as a methoxy group, an ethoxy group, a propyloxy group or a butoxy group, a carbonyl group or an oxo group. And may have a double bond at an arbitrary position. Among the substituents and alkyl groups having a double bond, specific examples of preferable ones include, for example,

Etc.

Examples of the aryl group represented by R ¹⁵ and R ¹⁶ usually include those having 6 to 14 carbon atoms, preferably 6 to 10 carbon atoms, specifically phenyl group, naphthyl group, anthryl group and the like. Halogen atoms such as chlorine, bromine, iodine and fluorine, for example, alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, propyl group and butyl group, such as methoxy group, ethoxy group, propyloxy group and butoxy group Or a C1-C4 alkoxy group such as an aryloxy group of benzyloxy group as a substituent. Among the specific examples of the aryl group having such a substituent, preferred examples include 2-methylphenyl group, 4-methylphenyl group, 2-chlorophenyl group, 2-bromophenyl group, 4-bromophenyl group,

Etc.

As the aralkyl group represented by R ¹⁵ and R ¹⁶ , the alkyl portion may be linear or branched, and generally includes those having 7 to 14 carbon atoms as a whole. These have, for example, halogen atoms such as chlorine, bromine, iodine and fluorine, for example, alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, propyl group and butyl group as substituents of the aromatic ring. In addition, for example, a halogen atom such as chlorine, bromine, iodine, or fluorine, a carbonyl group, or the like may be included as a substituent of the alkyl moiety. The aralkyl group may have a double bond at an arbitrary position.

Specific examples of the aralkyl group include, for example, benzyl group, phenylethyl group, 1-methyl-2-phenylethyl group, 1-phenyl-1-methylethyl group, phenylpropyl group, 1-methyl-3-phenylpropyl group. , Phenylbutyl group,

Etc.

Examples of the acyl group represented by R ¹⁵ and R ¹⁶ include an aliphatic acyl group having 2 to 10 carbon atoms and an aromatic acyl group having 7 to 14 carbon atoms. Specifically, for example, an acetyl group, a propionyl group, Examples include butyryl group, isobutyryl group, valeryl group, pivaloyl group, benzoyl group, naphthoyl group, and toluoyl group.

The ring formed by combining R ¹⁵ and R ¹⁶ may be monocyclic or polycyclic. For example, an alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group, a propyl group, or a butyl group is substituted with a substituent. You may have as. Specific examples of these rings include, for example, cyclopentane ring, cyclohexane ring, cycloheptane ring, cyclooctane ring, cyclononane ring, cyclodecane ring, cycloundecane ring, cyclododecane ring,

And the like.

Among the compounds represented by the general formula [1] as described above, as a co-oxidant used for producing a carbonyl compound using a compound in which R ² is an alkylsulfinyl group, for example, acetic anhydride, trifluoroacetic anhydride, Acid anhydrides such as methanesulfonic anhydride, organic dehydrating agents such as dicyclohexylcarbodiimide, inamine, keteneimine, such as oxalyl chloride, thionyl chloride, phosphorus oxychloride, benzoyl chloride, acetyl bromide, methanesulfonyl chloride, ethyl chloroformate, etc. Examples of the acid halide include inorganic acids such as phosphorus pentoxide, phosphorus oxychloride, sulfur trioxide, and chlorine, and isothiocyanate. Of these, oxalyl chloride is preferable in that there are few by-products.

  Examples of the base include tertiary amines such as triethylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene, and the like. Triethylamine is preferred.

  Examples of solvents that can be used include ethers such as diethyl ether, tetrahydrofuran, and dioxane, esters such as ethyl acetate, aliphatic hydrocarbons such as hexane, and aromatic hydrocarbons such as toluene and xylene. Examples thereof include halogenated hydrocarbons such as chloroform, dichloromethane and carbon tetrachloride, nitriles such as acetonitrile, and polar solvents such as N, N-dimethylformamide and the like.

Among the compounds represented by the general formula [1], the amount of the compound represented by the general formula [1] used for producing the carbonyl compound using the compound in which R ² is an alkylsulfinyl group is the amount of the alcohol compound to be reacted. The amount is usually 1 to 10 equivalents, preferably 1 to 3 equivalents, more preferably 1 to 2 equivalents with respect to the hydroxyl group.

  The usage-amount of a co-oxidant is the quantity used normally as 1-5 equivalent with respect to the hydroxyl group of the alcohol compound made to react, Preferably it is 1-3 equivalent, More preferably, it is 1.1-2 equivalent.

  The usage-amount of a base is a quantity used normally as 1-30 equivalent with respect to the hydroxyl group of an alcohol compound, Preferably it is 1-10 equivalent, More preferably, it is 3-6 equivalent.

  When the reaction is carried out using a solvent, the amount of the solvent used is usually 1 to 300 mL, preferably 1 to 150 mL, more preferably 5 to 100 mL with respect to 1 g of the alcohol compound.

The reaction temperature when producing a carbonyl compound using a compound in which R ² is an alkylsulfinyl group among the compounds represented by the general formula [1] is usually −100 to 50 ° C., preferably −60 ° C. to room temperature. is there.

  The reaction time varies depending on the compound to be reacted, the amount of the co-oxidant to be used, or the reaction temperature, but is usually 10 minutes to 10 hours, preferably 10 minutes to 5 hours, more preferably 30 minutes to 2 hours. .

Moreover, as a co-oxidant used when manufacturing a carbonyl compound using the compound in which R ² is an alkylsulfenyl group among the compounds represented by the general formula [1], for example, isothiocyanate, chlorine, N-bromo Examples thereof include succinimide, N-chlorosuccinimide, hypochlorite, and the like. Among them, N-chlorosuccinimide is preferable.

Examples of the base and, if necessary, the solvent used are the same as those used when producing a carbonyl compound using a compound in which R ^{2 of the} compound represented by the general formula [1] is an alkylsulfinyl group. It is done.

The amount of the compound represented by the general formula [1] used in the production of the carbonyl compound using the compound represented by the general formula [1] wherein R ² is an alkylsulfenyl group is the alcohol compound to be reacted. Is usually 1 to 10 equivalents, preferably 2 to 5 equivalents, more preferably 2 to 3 equivalents.

The amounts of the co-oxidant, the base and the solvent used are the same as in the case where the compound represented by the general formula [1] wherein R ² is an alkylsulfinyl group is used.

The reaction temperature for producing a carbonyl compound using a compound represented by the general formula [1] wherein R ² is an alkylsulfenyl group is usually −60 to 50 ° C., preferably −40 ° C. to room temperature. .

  The reaction time varies depending on the compound to be reacted, the amount of the co-oxidant used, or the reaction temperature, but is usually 30 minutes to 20 hours, preferably 1 to 10 hours, more preferably 2 to 6 hours.

  The post-treatment after the reactions (4) and (5) may be performed in the same manner as the post-treatment after the reactions (1), (2) and (3). That is, the target product can be easily isolated from the reaction solution by treatment with an acid.

The compound represented by the general formula [1] used or generated in the oxidation reaction of the alcohol of the present invention as described above, wherein R ² is an alkylsulfenyl group, is an irritating odor or unpleasant odor peculiar to a sulfur-containing compound. Therefore, the compound is used as an oxidizing agent, or a compound represented by the general formula [1] wherein R ² is an alkylsulfinyl group so that the compound is formed after the reaction. As a result, it is possible to carry out the oxidation reaction of alcohol without special consideration for the working environment.

  In addition, the compound represented by the general formula [1] has a tertiary amino group, a group derived from a quaternary ammonium salt or a cyclic amino group in its molecule, and therefore is used for various reactions as described above. Even after being used as a reagent, it is a very industrially useful reaction reagent that can be easily separated from a reaction solution only by an acid washing operation.

  The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Reference Example 1. Synthesis of 6-morpholinohexane-1-ol Morpholine (5.04 g) and 1-chloro-6-hexanol (7.90 g) were mixed and reacted at 120 ° C. for 5 hours. This was dissolved in and cooled, and then this was pulverized and washed with 15 ml of hexane. After washing, the resulting slightly pink crystals were collected by filtration and further washed with a solution of methanol: hexane (1: 5), and then the crystals were dried to obtain 10.5 g of 6-morpholinohexane-1-ol (yield). Rate 97%). The measurement results of melting point, IR, ¹ H-NMR, ¹³ C-NMR, MS and HRMS of the obtained crystals are shown below. mp: 164-165 ° C. IR (KBr): ν3415, 3395, 2945, 2925, 2710, 1430, 1310 cm ⁻¹ . ¹ H-NMR (CD ₃ OD, 400 MHz): δ 4.81 (br s, 1H, OH), 4.03 (br d, J = 12.1 Hz, 2H), 3.82 (br t, J = 12.1 Hz, 2H) , 3.55 (t, J = 6.2Hz, 2H), 3.49 (br d, J = 12.3Hz, 2H), 3.17-3.10 (m, 4H), 1.83-1.75 (m, 2H), 1.58-1.52 (m, 2H), 1.46-1.40 (m, 4H). ¹³ C-NMR (CD ₃ OD, 100 MHz): δ 65.0, 62.6, 58.4, 53.1, 33.3, 27.4, 26.4, 24.6. MS (EI) m / z 187 (M ⁺ , 2.5), 157 (3.4), 100 (100), 88 (2.8). HRMS (EI) m / z calculated for C ₁₀ H ₂₁ NO ₂ 187.1574 found 187.1572.

Example 1 Synthesis of 6-morpholinohexane-1-thiol 10.5 g of 6-morpholinohexane-1-ol obtained in Reference Example 1 and 4.69 g of thiourea were dissolved in 20 ml of water, and then 48% After slowly dropping 27.22 g of hydrobromic acid, the mixture was reacted with stirring for 8 hours while refluxing at 120 ° C. in a nitrogen atmosphere. After completion of the reaction, the reaction solution was returned to room temperature, 91% aqueous sodium hydroxide solution was added, and the mixture was further reacted for 2 hours without stirring in a nitrogen atmosphere while refluxing. After completion of the reaction, the pink reaction liquid was cooled and extracted with diethyl ether. After drying the organic layer, diethyl ether was distilled off under reduced pressure, and the resulting crude crystals were purified by silica gel column chromatography to obtain 8.34 g of colorless oily 6-morpholinohexane-1-thiol. (Yield 73%). In this experiment as a whole, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.

The measurement results of boiling point, IR, ¹ H-NMR, ¹³ C-NMR, MS and HRMS of the obtained oil are shown below. bp: 130 ° C. (1.5 mmHg). IR (CHCl ₃ ): ν3030, 2920, 2860, 2770, 2490, 1605, 1450, 1360 cm ⁻¹ . ¹ H-NMR (CDCl ₃ , 400 MHz): δ 3.70-3.68 (m, 4H), 2.50 (q, J = 7.1 Hz, 2H), 1.59 (quint, J = 7.1 Hz, 2H), 1.50-1.20 ( m, 7H). ¹³ C-NMR (CDCl ₃ , 100 MHz): δ 66.9, 59.0, 53.8, 33.9, 28.2, 26.9, 26.4, 24.5. MS (EI) m / z 203 (M ⁺ , 2.5), 170 (26.1), 100 (100), 87 (15.8). HRMS (EI) m / z calculated for C ₁₀ H ₂₁ NOS 203.1340 found 203.1344.

Example 2 Synthesis of methyl 6-morpholinohexyl sulfide 8.34 g of 6-morpholinohexane-1-thiol obtained in Example 1 was dissolved in 15 ml of ethanol, and 30 ml of 50% aqueous sodium hydroxide solution was added thereto. While the solution was cooled to 5 ° C. and stirred, 5.11 ml of methyl iodide was added dropwise, and after the dropwise addition, the reaction was stirred at room temperature for 3 hours. After completion of the reaction, ethanol in the reaction solution was distilled off under reduced pressure, 100 ml of water was added, and the mixture was extracted with diethyl ether. After drying the organic layer, the oil obtained by concentration was distilled at 1.5 mmHg at 145 ° C. to obtain 7.4 g of methyl 6-morpholinohexyl sulfide as a colorless oil (yield 83%). In this experiment as a whole, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.
The measurement results of boiling point, IR, ¹ H-NMR, ¹³ C-NMR, MS and HRMS of the obtained oil are shown below. bp: 145 ° C. (1.5 mmHg). IR (CHCl ₃ ): ν3030, 2930, 2860, 2815, 2485, 1600, 1460, 1310 cm ⁻¹ . ¹ H-NMR (CDCl ₃ , 400 MHz): δ3.71 (t, J = 4.6 Hz, 4H), 2.48 (t, J = 6.8 Hz, 4H), 2.42 (br s, 4H), 2.30 (dd, J = 7.1, 2.0 Hz, 2H), 2.08 (s, 3H), 1.52-1.28 (m, 6H). ¹³ C-NMR (CDCl ₃ , 100 MHz): δ 66.9, 59.1, 53.8, 34.2, 29.1, 28.7, 27.1, 26.5, 15.6. MS (EI) m / z 203 (M ⁺ , 3.4), 202 (20), 170 (100), 156 (9.4), 100 (98.1), 87 (19.2). HRMS (EI) m / z calculated for C ₁₁ H ₂₃ NOS 217.1503 found 217.1500.

Example 3 Synthesis of methyl 6-morpholinohexyl sulfoxide 518 mg of methyl 6-morpholinohexyl sulfide obtained in Example 2 was dissolved in 10 ml of chloroform, cooled to -78 ° C., and then 642 mg of 77% m-chloroperbenzoic acid The solution was added in portions and stirred for about 30 minutes. After completion of the reaction, the reaction solution was returned to 0 ° C. over about 10 minutes, and saturated sodium hydrogen carbonate was added thereto and extracted with chloroform. The organic layer was dried and purified by silica gel column chromatography to obtain 482 mg of colorless oily methyl 6-morpholinohexyl sulfoxide (yield 86%). In this experiment as a whole, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.

Example 4 Synthesis of methyl 6-morpholinohexyl sulfoxide 1.46 g of methyl 6-morpholinohexyl sulfide obtained in Example 2 was dissolved in 20 ml of chloroform, 0.5 ml of acetyl chloride was added thereto at room temperature, and the solution was brought to -78 ° C. After cooling, 1.81 g of 77% m-chloroperbenzoic acid was added in several portions, and the mixture was stirred for about 30 minutes. After completion of the reaction, the reaction solution was returned to 0 ° C. over about 10 minutes, and saturated sodium hydrogen carbonate was added thereto and extracted with chloroform. The organic layer was dried and purified by silica gel column chromatography to obtain 1.50 g of methyl 6-morpholinohexyl sulfoxide as a colorless oil (yield 95.5%). In this experiment as a whole, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.

The measurement results of IR, ¹ H-NMR, ¹³ C-NMR, MS and FAB-HRMS of the obtained oil are shown below. IR (CHCl ₃ ): ν3030, 2940, 2815, 2475, 1600, 1460, 1425, 1305 cm ⁻¹ . ¹ H-NMR (CDCl ₃ , 400 MHz): δ3.72 (t, J = 4.6 Hz, 4H), 2.74-2.62 (m, 2H), 2.57 (s, 3H), 2.44 (br s, 4H), 2.33 (dd, J = 7.3, 0.6 Hz, 2H), 1.78 (quint, J = 7.7 Hz, 2H), 1.56-1.34 (m, 6H). ¹³ C-NMR (CDCl ₃ , 100 MHz): δ 66.9, 58.9, 54.6, 53.7, 38.5, 28.7, 27.1, 26.3, 22.5. MS (FAB) m / z 234 (M ⁺ +1, 100), 216 (15), 170 (25), 147 (20), 100 (45). FAB-HRMSm / z calculated for C ₁₁ H ₂₃ NO ₂ S (M + H ⁺ ) 234.1540 found 234.1525.

Example 5 FIG. Corey-Kim oxidation reaction Under a nitrogen atmosphere, 63.76 mg of N-chlorosuccinic acid was dissolved in 2 ml of dehydrated methylene chloride, and this was cooled to −40 ° C. Then, 104 mg of methyl 6-morpholinohexyl sulfide obtained in Example 2 was added thereto. Of methylene chloride (2 ml) was added dropwise, and the mixture was stirred at -40 ° C for 30 minutes. To the reaction solution, a methylene chloride (2 ml) solution of 59 mg of diphenylmethanol was added dropwise and reacted with stirring at −40 ° C. for 2 hours. Then, 0.14 ml of triethylamine was further added dropwise and stirred for 2.5 hours. Next, the temperature of the reaction solution was raised to room temperature over 8 hours, the reaction solution was poured into 60 ml of 1N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid and brine, dried, and the solvent was distilled off to obtain 56 mg of the desired product, benzophenone (yield 96%). In this experiment as a whole, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.

Example 6 Corey-Kim oxidation reaction In a nitrogen atmosphere, 85.01 mg of N-chlorosuccinic acid was dissolved in 3 ml of dehydrated toluene, cooled to −40 ° C., and 69.3 mg of methyl 6-morpholinohexyl sulfide obtained in Example 2 here. Of toluene (3 ml) was added dropwise, and the mixture was stirred at -40 ° C for 30 minutes. To the reaction solution, a solution of 59 mg of diphenylmethanol in toluene (3 ml) was added dropwise and reacted with stirring at −40 ° C. for 2 hours. Then, 0.14 ml of triethylamine was further added dropwise and stirred for 2.5 hours. Next, the temperature of the reaction solution was raised to room temperature over 8 hours, poured into 60 ml of 1N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid and brine and then dried, and the solvent was distilled off to obtain 56.6 mg of the desired product, benzophenone (yield 97%). In this experiment as a whole, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.

Example 7 Swern oxidation reaction Under a nitrogen atmosphere, 20.5 μl of oxalyl chloride was dissolved in 5 ml of dehydrated methylene chloride, cooled to −60 ° C., and then, 73.25 mg of methyl 6-morpholinohexyl sulfoxide obtained in Example 3 was added thereto. (2 ml) The solution was added dropwise and stirred at -60 ° C for 20 minutes. A methylene chloride (2 ml) solution of 29.5 mg of diphenylmethanol was added dropwise to the reaction solution, and the mixture was stirred at -60 ° C. for 1 hour. Then, 66 μl of triethylamine was further added dropwise and stirred for 2 hours. Next, the temperature of the reaction solution was raised to room temperature and stirred for 1 hour, 5 ml of water was added to the reaction solution, washed with 1N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water and brine, dried, and the solvent was distilled off to obtain 27.4 mg of the target product, benzophenone (yield 94%). In this experiment as a whole, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.

Reference Example 2
After the reaction of Examples 5, 6 and 7, 1N hydrochloric acid from which the reaction solution was washed was collected and adjusted to pH 10 with 10% sodium hydroxide. This solution was extracted with diethyl ether, and the organic layer was dried, followed by rectification (145 ° C., 1.5 mmHg) with Kugelrohr to recover methyl 6-morpholinohexyl sulfide (yield 80 to 90%). In this recovery operation, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.

Example 8 FIG. Dealkylation reaction At room temperature, 118 mg of sodium hydride (60% oily sodium hydride) and 2 ml of dimethylformamide were suspended in dimethylformamide (416 mg of 6-morpholinohexane-1-thiol obtained in Example 1). 2 ml) solution was added dropwise and stirred for 5 minutes. Next, a solution of m-methylanisole 50 mg in dimethylformamide (2 ml) was added to the reaction solution, and the mixture was stirred at 120 ° C. for 3 hours. After completion of the reaction, the reaction solution was poured into 50 ml of 1N hydrochloric acid, and this was extracted with diethyl ether. The organic layer was washed with 1N hydrochloric acid and brine, then dried, and diethyl ether was distilled off, followed by purification by silica gel column chromatography to obtain 36 mg of the desired product, m-cresol (yield 81%). In this experiment as a whole, no irritating odor or unpleasant odor peculiar to sulfur-containing compounds was felt.

  As is apparent from Examples 5 and 6, by using the reaction reagent of the present invention, the Corey-Kim oxidation reaction can be efficiently performed without considering odors such as irritating odors and unpleasant odors in the reaction process. I understand that I can do it. It can also be seen that the reaction reagent can be easily separated from the reaction solution by treatment with an acid such as hydrochloric acid after the Corey-Kim oxidation reaction.

  As is clear from Example 7, it can be seen that by using the reaction reagent of the present invention, the Swern oxidation reaction can be performed efficiently without considering odors such as irritating odors and unpleasant odors in the reaction process. . It can also be seen that the reaction reagent can be easily separated from the reaction solution by treatment with an acid such as hydrochloric acid after the Swern oxidation reaction.

  Further, as is clear from Example 8, by using the reaction reagent of the present invention, the dealkylation reaction can be efficiently performed without considering odors such as irritating odors and unpleasant odors in the reaction process. I understand that. It can also be seen that the reaction reagent can be easily separated from the reaction solution by treatment with an acid such as hydrochloric acid after the dealkylation reaction.

  Further, as is clear from Reference Example 2, the reaction reagent of the present invention can be easily separated by acid treatment of the reaction solution after being used in various reactions, and an acid solution containing the separated reaction reagent can be obtained. It can be seen that the reaction reagent of the present invention can be easily recovered with good yield by treating with alkali.

The reaction reagent of the present invention has a weak odor despite being a sulfur-containing compound, and has an amino group in its structure, so that it is dealkylated, Corey-Kim oxidation reaction or When used in the Swern oxidation reaction, the reaction reagent can be easily separated from the reaction solution by only acid washing after the reaction without worrying about deterioration of the working environment due to irritating odors and unpleasant odors in the reaction process. The troublesome post-treatment process after the reaction can be reduced.

Claims (12)

General formula [1]

(In the formula, R ¹ is tertiary amino group, a quaternary ammonium salt derived group or a cyclic amino group, R ² represents a thiol group, alkylsulfenyl group or an alkylsulfinyl group, n represents, R ¹ is When it is a cyclic amino group, it represents an integer of 5 or more, and when R ¹ is a tertiary amino group or a group derived from a quaternary ammonium salt, n and the carbon atom, nitrogen atom and oxygen atom of the amino group And a reagent for dealkylation reaction or oxidation reaction comprising a compound represented by the following formula: The reaction reagent according to claim 1, wherein the compound represented by the general formula [1] is used in a dealkylation reaction in which a corresponding thiol group-containing compound is generated by cleavage of a sulfide group of an asymmetric sulfide compound. The reaction reagent according to claim 1, wherein the compound represented by the general formula [1] is used in a dealkylation reaction for producing a hydroxyl group-containing compound from an alkoxy group-containing compound. The reaction reagent according to claim 1, wherein the compound represented by the general formula [1] is used in a dealkylation reaction for producing a hydroxyl group-containing compound from an aralkyloxy group-containing compound.   The reaction reagent according to claim 1, wherein the compound represented by the general formula [1] is used for an oxidation reaction of an alcohol compound. The reaction reagent of claim 1 R ² is a thiol group of the general formula [1]. The reagent for reaction of Claim ¹ whose R <1> of General formula [1] is a cyclic amino group. A method for oxidizing an alcohol compound, comprising contacting the reaction reagent according to claim 1 with an alcohol compound. 9. The oxidation method according to claim 8, wherein the reaction reagent according to claim 1 comprises a compound in which R ^{2 in the} general formula [1] is an alkylsulfenyl group or an alkylsulfinyl group. 9. The oxidation method according to claim 8, wherein the reaction reagent according to claim 1 comprises a compound in which R ^{1 in the} general formula [1] is a cyclic amino group. 9. The oxidation method according to claim 8, wherein the compound produced by oxidation is a carbonyl compound corresponding to the alcohol compound. General formula [2]

(Wherein R ² represents a thiol group, an alkylsulfenyl group or an alkylsulfinyl group, and m represents an integer of 5 or more).