JP2000336081A - Production of benzothiazole derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce the subject compound useful as a synthetic intermediate for functional coloring matters, medicines, functional materials, etc. in good yield by using a readily available specific substituted phenol as a starting substance. SOLUTION: A compound represented by formula I (R1 to R5 are each H, a monofunctional substituent group or may mutually be bound to form a ring) (e.g. 4-phenylphenol) is derivatized into a compound represented by formula II [R11 to R15 have each the same meaning as that of R1 to R5; and R16 is a (substituted) aliphatic group, a (substituted) aromatic group or the like], which is then converted into a compound represented by formula III (R21 to R25 have each the same meaning as that of R1 to R5; X2 is S or the like; and L is H, a monofunctional substituent group or the like). The resultant compound represented by formula III is subsequently converted into a compound represented by formula IV (R31 to R35 have each the same meaning as that of R1 to R5; R37 is H or a monofunctional substituent group; and X3 is S or the like) (e.g. 2-methyl-5-phenylbenzothiazole) to thereby produce the compound represented by formula IV. The R15 and R25 in the compounds represented by formulae II and III are preferably nitro groups and the compound represented by formula III is preferably a compound represented by formula V.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel method for synthesizing a benzoazole derivative, which is used as an intermediate for synthesizing functional dyes, pharmaceuticals, functional materials and the like.

[0002]

2. Description of the Related Art At present, dyes having various structures are used as functional dyes. Among them, cyanine dyes, merocyanine dyes or rhodanine dyes are often used as typical dye structures. For specific structures and typical synthetic methods of these dyes, for example,
"Heterocyclic Compounds-Cya", by FM Hamer, "Heterocyclic Compounds-Cyanine Dye and Relatively Compounded Compounds-"
nine dyes and related compounds-) "(John Wiley & Sons, New York, London, 1964), T.H.
"The Theory of
Photographic process (Tha Theory of Photog)
raphic Process "(Macmillan, New York, 1977).

[0003] The chromophores of these dyes include a structure containing a nitrogen atom in common. In many dyes, the nitrogen atom forms a part of the heterocyclic ring and forms a part of the chromophore. are doing. Numerous structures are known as such a nitrogen-containing heterocyclic ring to date, for example, oxazoline, thiazoline, oxazole, thiazole, benzoxazole, benzothiazole, benzimidazole,
Benzoselenazole, benzotellurazole, naphthoxazole, naphthothiazole, quinoline, indole,
Pyridine and the like can be mentioned, and are appropriately selected from these heterocycles according to the purpose.

A cyanine dye, a merocyanine dye or a rhodocyanine dye having a benzothiazole ring, a benzoselenazole ring or a benzotellurazole ring as a chromophore is
As can be seen from the fact that it is widely used as a spectral sensitizing dye for photography because it is relatively stable, has a large molar absorption intensity, and has a high oxidation-reduction potential, benzothiazole,
Benzoselenazole and benzotellurazole derivatives are useful as synthetic intermediates such as functional dyes.

[0005] In addition, many compounds having a heterocyclic ring are known among pharmaceuticals and functional materials, and benzothiazole, benzoselenazole and benzotellurazole derivatives having a desired substituent introduced at an arbitrary position include: It is also useful as a synthetic intermediate for these compounds.

Examples of known methods for producing benzothiazole derivatives are described in, for example, Hiroshi Yamanaka et al., “Chemistry of Heterocyclic Compounds,” pp. 78-80 (Kodansha Scientific, 1988), Heterocyclic Compounds-Special Topics in Heterocyclic Chemistry, by DM Sturmer
topics in heterocyclic chemistry-) ", Chapters 8 and 4
Verses 482-515 (John Willie and
It is described in documents such as Johns Wiley & Sons, New York, London, 1977.

For example, in a production method using a substituted aniline as a raw material, a reaction of forming a benzothiazole ring by an oxidative cyclization reaction of a thioamide compound is known. However, in this case, in order to obtain a 5-substituted benzothiazole useful as a synthetic intermediate of a photographic spectral sensitizing dye, a 3-substituted aminobenzene is required as a raw material, and its synthesis may not be easy, and The selectivity of the cyclization position must also be considered.

Further, in a reaction in which a carbon-sulfur bond is formed in advance on a benzene ring to form a benzothiazole ring, a production method using a substituted 2-halonitrobenzene as a raw material is known. However, in order to obtain the useful synthetic intermediate described above, the substitution 2
-Halonitrobenzene may not be easily available.

The reaction of easily obtaining a substituted halobenzene by converting a hydroxyl group of a substituted phenol to a halogen in a readily available substituted phenol is described in, for example, “New Experimental Chemistry Course 14” edited by The Chemical Society of Japan.
Synthesis and Reaction of Organic Compounds I ", Chapter 2, Halogen Compounds,
369-374 (Maruzen, 1977), R.
Comprehensive Organic Transformations by RC Larock, "Comprehensive Organic Transformations-A Guide to Functional Group Preparations"
-A Guide to Functional Group Preparations-) "3rd
65 pages (Buy Seat Publishers (VCH
Publishers, Inc., New York, 1989), but it is difficult to replace the hydroxyl group of phenol with a halogen by a usual method, and there are only a few applications that can be successfully applied using a phosphorus halide. It is stated that there is.

A method for directly converting a substituted phenol to a substituted thiophenol is disclosed in US Pat. No. 2,438,838.
The high temperature (525 ° C) high pressure (260
(00 Torr), and the production is not easy. A reaction for temporarily converting a substituted phenol into an O-arylthiocarbamate and converting it to an S-arylthiocarbamate by a thermal reaction to obtain a substituted thiophenol is described in J. Am. Org. Chem. 1966, 31
Vol. 3, page 3980, etc., but it is not general when a reaction temperature is as high as 200 ° C. or higher and a substrate that is not stable to heat is used.

As described above, in the conventionally known method for producing a benzoazole derivative, it is difficult to synthesize a raw material, a problem occurs in the regioselectivity of ring formation, and the number of steps is large. In some cases, the development of a general production method that does not include such a problem has been desired.

[0012]

The problem to be solved by the present invention is to use a readily available substituted phenol as a raw material.
An object of the present invention is to provide a general production method for obtaining a benzoazole derivative in a good yield.

[0013]

The above-mentioned problems have been solved by the following manufacturing method as a result of intensive studies. (1) A compound represented by the following general formula (I) is derived into a compound represented by the general formula (II), and is converted into a compound represented by the general formula (III).
A process for producing a compound represented by the general formula (IV) from a compound represented by the general formula (I) by converting the compound represented by V). General formula (I)

[0014]

Embedded image

In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ each independently represent a hydrogen atom or a monovalent substituent, and these may be bonded to each other to form a ring. General formula (II)

[0016]

Embedded image

In the formula, R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ¹⁵ each independently represent a hydrogen atom or a monovalent substituent, and these may be bonded to each other to form a ring. R ¹⁶
Represents a substituted or unsubstituted aliphatic group, aromatic group and heterocyclic group. General formula (III)

[0018]

Embedded image

In the formula, R ²¹ , R ²² , R ²³ , R ²⁴ and R ²⁵ each independently represent a hydrogen atom or a monovalent substituent, and these may be bonded to each other to form a ring. X ²
Represents a sulfur atom, a selenium atom, or a tellurium atom. L represents a hydrogen atom, a monovalent substituent or a metal and nonmetal cation. General formula (IV)

[0020]

Embedded image

In the formula, R ³¹ , R ³² , R ³³ and R ³⁴ each independently represent a hydrogen atom or a monovalent substituent, and these may be bonded to each other to form a ring. R ³⁷ represents a hydrogen atom or a monovalent substituent. X ³ represents a sulfur atom, a selenium atom, or a tellurium atom. (2) In (1), the general formula (I) and the general formula (I
I), R ¹ , R ² , R ⁴ , R ¹¹ , R ¹² , R ¹⁴ , R ^{14 of} the compounds represented by the general formulas (III) and (IV)
²¹ , R ²² , R ²⁴ , R ³¹ , R ³² and R ³⁴ represent a hydrogen atom, and R ³ , R ¹³ , R ²³ and R ³³ are monovalent substituents, (1) A method for producing a compound represented by the general formula (IV) from a compound represented by the general formula (I) described in (1). (3) The compound represented by the general formula (I) according to (1), wherein R ¹⁵ and R ²⁵ of the compounds represented by the general formulas (II) and (III) are nitro groups. A) producing a compound represented by the general formula (IV) from the compound represented by the formula: (4) In (1), R ^{37 of the} compound represented by the general formula (IV) is a methyl group,
A method for producing a compound represented by the general formula (IV) from a compound represented by the general formula (I) described in (1). (5) The compound represented by the general formula (I) according to the above (1), wherein the compound represented by the general formula (III) is a compound represented by the general formula (III) ′. A production method for producing a compound represented by the general formula (IV). General formula (III) ′

[0022]

Embedded image

In the formula, R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , X ²
Has the same meaning as in formula (III). (6) A compound represented by the general formula (I) for producing a compound represented by the general formula (III) from the compound represented by the general formula (II)
Production method of II).

[0024]

DETAILED DESCRIPTION OF THE INVENTION The general formulas (I), (II) and (II)
I) and (IV) will be specifically described. R ¹ , R ² ,
R ³ , R ⁴ , R ⁵ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R
^{21, R 22, R 23,} R 24, R 25, R 31, R 32, R 33, and R ³⁴ represents a hydrogen atom or a monovalent substituent independently for each of these, taken together A ring may be formed. The monovalent substituent is not particularly restricted but includes, for example, a halogen atom (for example, chlorine, bromine, iodine, fluorine), a mercapto group, a cyano group, a carboxyl group, a phosphoric acid group, a phosphoric acid group, a sulfo group, a hydroxy group, To 10, preferably 2 to 8, more preferably 2 to 5 carbamoyl groups (eg methylcarbamoyl, ethylcarbamoyl, morpholinocarbonyl), 0 carbon atoms
To 10, preferably 2 to 8 carbon atoms, more preferably 2 to 5 carbon atoms (eg, methylsulfamoyl, ethylsulfamoyl, piperidinosulfonyl), nitro group, 1 to 20 carbon atoms, preferably Is an alkoxy group having 1 to 10 carbon atoms, more preferably 1 to 8 carbon atoms (for example, methoxy, ethoxy, 2-methoxyethoxy, 2-phenylethoxy), and 6 to 2 carbon atoms.
An aryloxy group having 0, preferably 6 to 12 carbon atoms, more preferably 6 to 10 carbon atoms (eg, phenoxy, p-methylphenoxy, p-chlorophenoxy, naphthoxy);

An acyl group having 1 to 20 carbon atoms, preferably 2 to 12 carbon atoms, more preferably 2 to 8 carbon atoms (eg, acetyl, benzoyl, trichloroacetyl), 1 to 20 carbon atoms, preferably 2 to 20 carbon atoms 1
2, more preferably an acyloxy group having 2 to 8 carbon atoms (eg, acetyloxy, benzoyloxy), an acylamino group having 1 to 20, preferably 2 to 12, and more preferably 2 to 8 carbon atoms (eg, acetyl Amino), a sulfonyl group having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 8 carbon atoms (for example, methanesulfonyl, ethanesulfonyl, benzenesulfonyl and the like), 1 to 20 carbon atoms, preferably 1 carbon atom To 10, more preferably a sulfinyl group having 1 to 8 carbon atoms (eg, methanesulfinyl, benzenesulfinyl), a sulfonylamino group having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 8 carbon atoms (eg, Methanesulfonylamino, ethanesulfonylamino, ben Such emission sulfonylamino)

An amino group, a substituted amino group having 1 to 20 carbon atoms, preferably 1 to 12 carbon atoms, more preferably 1 to 8 carbon atoms (eg, methylamino, dimethylamino,
Benzylamino, anilino, diphenylamino), an ammonium group having 0 to 15 carbon atoms, preferably 3 to 10 carbon atoms, more preferably 3 to 6 carbon atoms (for example, trimethylammonium group, triethylammonium group);
A hydrazino group having 0 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms (for example, trimethylhydrazino group), 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms
(E.g., ureido group, N, N-dimethylureido group), an imide group having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms (e.g., succinimide group), An alkyl or arylthio group having 1 to 20, preferably 1 to 12 carbon atoms, more preferably 1 to 8 carbon atoms (eg, methylthio, ethylthio, carboxyethylthio, sulfobutylthio, phenylthio, etc.), 2 to 20 carbon atoms, preferably 2 to 12 carbon atoms, more preferably 2 to 8 carbon atoms
An alkoxycarbonyl group (e.g., methoxycarbonyl, ethoxycarbonyl, benzyloxycarbonyl) having 6 to 20 carbon atoms, preferably 6 to 12 carbon atoms;
More preferably, an aryloxycarbonyl group having 6 to 8 carbon atoms (for example, phenoxycarbonyl),

An unsubstituted alkyl group having 1 to 18 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 5 carbon atoms (eg, methyl, ethyl, propyl, butyl), and 1 to 18 carbon atoms, preferably 1 to 1 carbon atoms
0, more preferably a substituted alkyl group having 1 to 5 carbon atoms (hydroxymethyl, trifluoromethyl, benzyl,
Carboxyethyl, ethoxycarbonylmethyl, acetylaminomethyl, and here, preferably, an unsaturated hydrocarbon group having 2 to 18 carbon atoms, more preferably 3 to 10 carbon atoms, and particularly preferably 3 to 5 carbon atoms (for example, vinyl group Ethynyl group, 1-cyclohexenyl group, benzylidine group, benzylidene group) are also included in the substituted alkyl group. ), A substituted or unsubstituted aryl group having 6 to 20 carbon atoms, preferably 6 to 15 carbon atoms, more preferably 6 to 10 carbon atoms (eg, phenyl, naphthyl, p-carboxyphenyl, p-nitrophenyl,
3,5-dichlorophenyl, p-cyanophenyl, m-
Fluorophenyl, p-tolyl, p-bromophenyl),

An optionally substituted heterocyclic group having 1 to 20, preferably 2 to 10, more preferably 4 to 6 carbon atoms (eg, pyridyl, 5-methylpyridyl, thienyl, furyl, morpholino, tetrahydro Furfuryl).

These substituents may be bonded to each other to form a ring, and the ring may be either saturated or unsaturated, preferably an aromatic ring and a heterocyclic ring, more preferably an aromatic ring, Particularly preferred is a benzene ring.

Preferably, a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group having 1 to 3 carbon atoms (eg, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and a trifluoromethyl group), 3 is an alkoxy group (for example, methoxy group, ethoxy group, propoxy group, isopropoxy group), substituted or unsubstituted phenyl group, nitro group, substituted or unsubstituted amino group.

More preferably, R ¹ , R ² , R ⁴ , R
^{11, R 12, R 14,} R 21, R 22, R 24, R 31, R 32, R 34
Is a hydrogen atom, and R ³ , R ¹³ , R ²³ , and R ³³ are a halogen atom, an alkyl group having 1 to 3 carbon atoms (eg, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl) Alkenyl group having 1 to 3 carbon atoms (for example, methoxy group, ethoxy group, propoxy group, isopropoxy group), phenyl group, substituted phenyl group and benzene condensed ring. More preferred are a phenyl group and a substituted phenyl group (for example, p-bromophenyl), and most preferred is a phenyl group.

Formulas (I), (II), (III),
Through (IV), the set of R ¹ , R ¹¹ , R ²¹ , R ³¹
A set of R ² , R ¹² , R ²² , R ³² , R ³ , R ¹³ , R ²³ , R ³³
And the group of R ⁴ , R ¹⁴ , R ²⁴ , and R ³⁴ preferably represent the same, but may be different depending on the reaction conditions. In addition, it may be different in the middle to use an arbitrary protecting group, but may finally show the same one.

R ⁵ , R ¹⁵ and R ²⁵ are a hydrogen atom or 1
It represents a valent substituent, and is preferably a hydrogen atom, a nitro group or a monovalent substituent which can be easily converted to a nitro group. Particularly preferred are a hydrogen atom, a nitro group, and a substituted or unsubstituted amino group. In addition, R ¹⁵
And R ²⁵ is particularly preferably a nitro group.

R ¹⁶ represents a substituted or unsubstituted aliphatic group, aromatic group or heterocyclic group. Examples of the substituent include C1 to C18, preferably C1 to C10,
More preferably, an unsubstituted alkyl group having 1 to 5 carbon atoms (eg, methyl, ethyl, propyl, butyl), a substituted alkyl group having 1 to 18 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 5 carbon atoms. Groups (hydroxymethyl, trifluoromethyl, pentafluoroethyl,
Benzyl, carboxyethyl, ethoxycarbonylmethyl, acetylaminomethyl, here also preferably have 2 to 18 carbon atoms, more preferably 3 to 1 carbon atoms.
An unsaturated hydrocarbon group having 0, particularly preferably 3 to 5 carbon atoms (for example, a vinyl group, an ethynyl group, a 1-cyclohexenyl group, a benzylidine group, and a benzylidene group) is also included in the substituted alkyl group. ), A substituted or unsubstituted aryl group having 6 to 20 carbon atoms, preferably 6 to 15 carbon atoms, more preferably 6 to 10 carbon atoms (for example, phenyl, naphthyl, 4-carboxyphenyl, 3,5-dichlorophenyl, -Cyanophenyl, 3-fluorophenyl, 4-methylphenyl, 4-chlorophenyl group, 4
-Nitrophenyl group, 2,4-dinitrophenyl group,
2,4,5-trichlorophenyl group), having 1 to 2 carbon atoms
Examples thereof include an optionally substituted heterocyclic group having 0, preferably 2 to 10 carbon atoms, and more preferably 4 to 6 carbon atoms (eg, pyridyl, 5-methylpyridyl, thienyl, furyl, morpholino, and tetrahydrofurfuryl). Particularly preferred are a methyl group, a phenyl group, a 4-methylphenyl group, a 4-chlorophenyl group, a 2,4-dinitrophenyl group, and a 2,4,5-trichlorophenyl group. Most preferably, it is a 2,4,5-trichlorophenyl group.

R ³⁷ represents a hydrogen atom or a monovalent substituent. Examples of the monovalent substituent include the substituents described above as examples of R ^{1 and the} like. Preferably, a mercapto group, a halogen atom (eg, fluorine, chlorine, bromine, iodine), an unsubstituted alkyl group having 18 or less carbon atoms (eg, methyl, ethyl, propyl), a substituted alkyl group (eg, a halogen atom , An alkoxy group, a cyano group,
Sulfo group, hydroxy group, acylamino group, aryloxy group, alkyl group substituted with arylamino group), unsubstituted alkenyl group having 18 or less carbon atoms (eg, vinyl, propenyl, butenyl, isopropenyl, isobutenyl)
And a substituted alkenyl group (for example, a halogen atom, an alkoxy group, a cyano group, a sulfo group, a hydroxy group, an acylamino group, an aryloxy group, an alkenyl group substituted with an arylamino group), an unsubstituted aryl having 18 or less carbon atoms Group (eg, phenyl, naphthyl) and substituted aryl group (eg, halogen atom, alkoxy group, cyano group, sulfo group, hydroxy group, acylamino group, aryloxy group, aryl group substituted with arylamino group), carbon An unsubstituted alkylthio group of the number 18 or less (for example, methylthio, ethylthio, propylthio,
Butylthio, pentylthio) and substituted alkylthio groups (for example, a halogen atom, an alkoxy group,
Cyano group, sulfo group, hydroxy group, acylamino group,
An aryloxy group, an alkylthio group substituted by an arylamino group, an alkenylthio group having 18 or less carbon atoms (for example, vinylthio, propenylthio, butenylthio) and a substituted alkenylthio group (for example, a halogen atom, an alkoxy group, a cyano group) Group, sulfo group, hydroxy group, acylamino group, aryloxy group, alkenylthio group substituted with arylamino group), unsubstituted arylthio group having 18 or less carbon atoms (eg, phenylthio, naphthylthio) and substituted arylthio group (as a substituent) Examples thereof include a halogen atom, an alkoxy group, a cyano group, a sulfo group, a hydroxy group, an acylamino group, an aryloxy group, and an arylthio group substituted with an arylamino group.

More preferably, a hydrogen atom, a mercapto group, a halogen atom, an unsubstituted alkyl group having 8 or less carbon atoms (eg, methyl, ethyl, propyl) and an unsubstituted aryl group having 8 or less carbon atoms (eg, phenyl, naphthyl) And an unsubstituted alkylthio group having 8 or less carbon atoms (eg, methylthio, ethylthio, propylthio, butylthio, pentylthio) and an unsubstituted arylthio group having 10 or less carbon atoms (eg, phenylthio, naphthylthio). Particularly preferably, a hydrogen atom, a mercapto group, a halogen atom, and a carbon number of 3
The following unsubstituted alkyl groups (eg, methyl, ethyl, propyl) and unsubstituted alkylthio groups having 3 or less carbon atoms (eg, methylthio, ethylthio, propylthio).

X ² and X ³ are a sulfur atom, a selenium atom,
Represents a tellurium atom. Preferred are a sulfur atom and a selenium atom, and particularly preferred is a sulfur atom.

L represents a hydrogen atom, a monovalent substituent or a metal and nonmetal cation. Examples of the monovalent substituent include the substituents described above as examples of R ^{1 and the} like. As L, a monovalent substituent is preferably a mercapto group, an unsubstituted alkylthio group having 18 or less carbon atoms (eg, methylthio, ethylthio, propylthio, butylthio, pentylthio) and a substituted alkylthio group (eg, a halogen atom, Alkoxy group, cyano group,
A sulfo group, a hydroxy group, an acylamino group, an aryloxy group, an alkylthio group substituted by an arylamino group), an alkenylthio group having 18 or less carbon atoms (for example, vinylthio, propenylthio, butenylthio) and a substituted alkenylthio group (as a substituent) For example, a halogen atom,
An alkoxy group, a cyano group, a sulfo group, a hydroxy group, an acylamino group, an aryloxy group, an alkenylthio group substituted with an arylamino group), an unsubstituted arylthio group having 18 or less carbon atoms (eg, phenylthio, naphthylthio) and a substituted arylthio group (For example, a halogen atom, an alkoxy group, a cyano group, a sulfo group, a hydroxy group, an acylamino group, an aryloxy group, an arylthio group substituted with an arylamino group).

Examples of metal and nonmetal cations in L include inorganic ammonium ions and organic ammonium ions (for example, tetraalkylammonium ion,
Pyridinium ion), alkali metal ion (for example,
Sodium ion, potassium ion), and alkaline earth metal ion (eg, calcium ion).
Preferably, sodium ion, potassium ion, ammonium ion, triethylamine and the like can be mentioned.

L is preferably a hydrogen atom, a mercapto group, an unsubstituted alkylthio group having 8 or less carbon atoms (for example,
Methylthio, ethylthio, propylthio, butylthio,
Pentylthio), a substituted or unsubstituted arylthio group having 18 or less carbon atoms (eg, phenylthio, naphthylthio, p-phenylphenyl), sodium ion, potassium ion, and ammonium ion.

Particularly preferably, a hydrogen atom, a mercapto group,
A substituted arylthio group having 18 or less carbon atoms, a sodium ion and an ammonium ion. In particular, in the case of a substituted arylthio group, when L is a substituted arylthio group formed by a portion of the compound represented by the general formula (III) except for L, that is, when the general formula (II
Preferred is a symmetric disulfide compound represented by I) ′.

The compound represented by the general formula (I) may be any available substituted phenol. Preferred are those in which the ortho position is previously substituted with a nitro group, that is, those in which R ^{5 in the} general formula (I) is a nitro group. However, in the process of converting a readily available substituted phenol to the general formula (II), orthomono is preferred. It may be nitrated. Further, in order to obtain a desired substituted phenol, the compound may be synthesized from another available substituted phenol, and in this case, the hydroxyl group may be protected with an optional protecting group.

As a method for synthesizing the compound represented by the general formula (II), any method may be selected according to available raw materials. For example, when a 4-substituted phenol is used as a raw material, the synthesis is preferably performed in the order of (1) orthomononitration (2) sulfonic acid esterification.

The ortho-mononitration may be carried out by any method. For example, see "Organic Functional Group Preparations No. 1" by SR Sandler and W. Karo. 2nd edition (Organic Functional Group Prepara
tions Second Edition) ", Chapter 16, Chapters 529-548
Page (Academic Press, New York, 1983), Bull. Soc. Ch
im. Fr. The method described in 1994, vol. 131, p. 27, etc. can be used.

The reaction conditions for the nitration of phenol will be described in detail. The reaction is carried out by reacting (I) with a nitrating agent such as nitric acid, acyl nitric acid, nitronium salt and the like. The reaction temperature can be selected from the range of -100 ° C to 270 ° C. A range from -20 ° C to 100 ° C is preferred. Water, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMS)
Any solvent may be used, from a polar solvent such as O), sulfolane and methanol to a non-polar solvent such as hexane and xylene, but is preferably water, acetic acid or ethyl acetate. Further, a mixed solvent of an arbitrary combination of these may be used, or a multiphase solvent that is not mixed may be used. The feed ratio ((I) / nitrifying agent) of the raw materials can be selected from the range of 0.5 to 20. Preferably it is in the range of 0.75 to 10. In the reaction, an acid may or may not be added as a catalyst.

The sulfonic acid esterification may be carried out by any method. For example, TW Greene, PGM Utz (P.
GMWuts) "Protective Groups in Organic Synthesis 2nd Edition (Protective Groups)
in Organic Synthesis Second Edition ”, p. 168 (John Wiley & Sons)
ons), New York, 1991), supervised by Toshio Goto et al.
The method described on page 1 (Chemical Doujin, 1990) can be used.

The reaction conditions for sulfonic acid esterification of phenol will be described in detail. The reaction is carried out by reacting (I) or a substituted phenol derived from (I) with any sulfonic acid halide or sulfonic anhydride in the presence of a base. As the base, any of inorganic bases such as potassium carbonate, sodium hydrogencarbonate, sodium hydroxide and potassium hydroxide, and any organic base such as triethylamine and pyridine may be used.
Preferred are potassium carbonate, sodium hydroxide and triethylamine. The reaction temperature can be selected from the range of -70 ° C to 270 ° C. The range is preferably from -40 ° C to 100 ° C, more preferably from -20 ° C to 60 ° C. As the reaction solvent, any solvent may be used, from aprotic polar solvents such as N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO) and sulfolane to nonpolar solvents such as hexane and xylene. Preferably, acetone and methylene chloride are used. Further, a mixed solvent of an arbitrary combination of these may be used, or a multiphase solvent that is not mixed may be used. The feed ratio (substituted phenol / sulfonic acid derivative) of the raw materials can be selected from the range of 0.5 to 20.
The range of 0.75 to 5 is preferable, and the range of 1 to 1.25 is more preferable. During the reaction, an activating agent such as 4-dimethylaminopyridine may or may not be added.

The step of converting the compound represented by the general formula (II) to the compound represented by the general formula (III) will be described in detail. The reaction is carried out with (II) and a sulfide salt, disulfide salt or water selenide salt. As the sulfide salt, sodium hydrogen sulfide, sodium sulfide, potassium sulfide, ammonium sulfide, or the like can be used. As the disulfide salt, sodium disulfide, potassium disulfide, or the like can be used. As the water selenide salt, sodium water selenide can be used. The disulfide salt may be prepared from a sulfide salt such as sodium sulfide or potassium sulfide and sulfur, but it is preferable to use commercially available sodium disulfide. Water, N, N-
Any solvent may be used from a polar solvent such as dimethylformamide (DMF), dimethylsulfoxide (DMSO), sulfolane or methanol to a non-polar solvent such as hexane or xylene.
Alcohols such as ethanol. Further, a mixed solvent of an arbitrary combination of these may be used, or a multiphase solvent that is not mixed may be used. The reaction temperature is-
It can be selected from the range of 20 ° C to 270 ° C. 0 ° C
To 150.degree. C., and particularly preferably 25 to 100.degree. The raw material charging ratio (sulfonic acid ester / sulfide salt, etc.) can be selected from the range of 0.5 to 10. A range of 1 to 5 is preferred, and a range of 1.5 to 3 is more preferred.

The compound represented by the general formula (III) is
The step of converting into a compound represented by the general formula (IV) comprises:
For example, as described in Hirokazu Yamanaka et al., “Chemistry of Heterocyclic Compounds”, page 79 (Kodansha Scientific, 1988), when R ²⁵ is a nitro group, the nitro group is first reduced and then acid anhydride is obtained. It is preferable to form a thiazole ring by reacting with a compound, a carboxylic acid derivative such as an acid halide or an orthoester, or carbon disulfide. Alternatively, it is preferable to reduce the nitro group and form a selenazole ring in the same manner as described in Pharmaceutical Magazine, 1947, Vol. 67, p. 138. Furthermore, when the general formula (III) is a disulfide or diselenide compound, the reduction of these functional groups is required in addition to the reduction of the nitro group, and the reduction can be carried out before, simultaneously with, or after the reduction of the nitro group. Although it may be performed, it is preferable to perform simultaneously.

The reaction conditions for the first-stage reduction reaction will be described in detail. The reaction is carried out by reacting (III) with a reducing agent. The reaction may be performed under any conditions. For example, M. Hudlicky, "Reductions in Organic Chemistry Second Edition"
ACS Monograph 188 (ACS Monograph
188) "Chapter 8 (American Chemical Society, Washington, DC, 19
1996) can be used. In the case where the compound of the general formula (III) is represented by the general formula (III) ′, reduction of a disulfide group or both of a diselenide group and a nitro group is required. The reaction may be carried out, and it is more preferable to carry out the reaction under conditions that allow simultaneous reduction.
It is preferable to use zinc, sodium sulfide, and ammonium sulfide as the reducing agent. The reaction temperature ranges from -20 ° C to 2
It can be selected from the range of 70 ° C. 0 ° C to 150 ° C
Is more preferable, and the range of 25 ° C to 100 ° C is more preferable. Water, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMS)
Any solvent may be used, from polar solvents such as O), sulfolane and methanol, to non-polar solvents such as hexane and xylene, but water and acetic acid are preferred. Further, a mixed solvent of an arbitrary combination of these may be used, or a multiphase solvent that is not mixed may be used. The raw material charging ratio ((III) / reducing agent) can be selected from the range of 0.5 to 20. The range is preferably from 0.75 to 10, more preferably from 1 to 5.

The reaction conditions for the ring formation reaction in the next step will be described in detail. The reaction is carried out by reacting a substituted aminothiophenol or a substituted aminoselenophenol obtained by reducing the general formula (III) with a carboxylic acid derivative, carbon disulfide or the like. Examples of the carboxylic acid derivative used include acid anhydrides, acid halides and orthoesters such as acetic anhydride, propionic anhydride, benzoic anhydride, acetyl chloride, propionyl chloride, benzoyl chloride, ethyl orthoacetate, methyl orthoformate, and orthopropion. Ethyl acid and the like are mentioned, and preferred are carbon disulfide, acetic anhydride, propionic anhydride, acetyl chloride, propionyl chloride and ethyl orthoacetate. Particularly preferred are carbon disulfide and acetic anhydride. Reaction temperature is -20 ° C
To 200 ° C. 0 ° C to 1
A range of 50 ° C is preferred, and a range of 20 ° C to 100 ° C is more preferred. As the reaction solvent, any solvent may be used, from a polar solvent such as water, N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), sulfolane, and methanol to a nonpolar solvent such as hexane and xylene. , Preferably water and acetic acid. Further, a mixed solvent of an arbitrary combination of these may be used, or a multiphase solvent that is not mixed may be used. The charging ratio of the raw materials (substituted aminothiophenol / carboxylic acid derivative) can be selected from the range of 0.5 to 20. The range is preferably from 0.75 to 10, more preferably from 1 to 5. It is also preferable that these reactions are continuously performed by directly adding a carboxylic acid derivative, carbon disulfide, or the like to the reaction solution in which the reduction reaction in the previous step has been performed.

In the present invention, the compounds represented by formulas (I) and (I)
Specific examples of the compounds represented by I), (III) and (IV) are shown below, but the scope of the present invention is not limited thereto. Specific examples of general formula (I)

[0053]

Embedded image

[0054]

Embedded image

Specific examples of general formula (II)

[0056]

Embedded image

[0057]

Embedded image

Specific examples of the general formula (III)

[0059]

Embedded image

[0060]

Embedded image

[0061]

Embedded image

Specific examples of general formula (IV)

[0063]

Embedded image

[0064]

Embedded image

[0065]

The present invention will be described in more detail by way of examples.

Example 1 Synthesis of 2-methyl-5-phenylbenzothiazole

[0067]

Embedded image

50 g of 4-phenylphenol and 26 g of sodium nitrate were added to 200 ml of water and 100 m of concentrated hydrochloric acid.
1, stirred in 500 ml of ethyl acetate to form a two-phase solution. 2.8 ml of acetic anhydride was added thereto, and the mixture was stirred at room temperature for 90 minutes. The organic layer was taken out, washed with water, concentrated, and then recrystallized from ethanol to obtain 2-nitro-4-phenylphenol. Yield 57 g, 90%. ¹ H
NMR (DMSO-d6) d 11.10 (s, 1H), 8.13 (s, 1H), 7.85
(d, 1H), 7.65 (d, 2H), 7.48 (t, 2H), 7.35 (t, 1H),
7.22 (d, 1H). 4.3 g of 2-nitro-4-phenylphenol and 5.6 g of 2,4,5-trichlorobenzenesulfonyl chloride are dissolved in 20 ml of acetone.
3.1 ml of triethylamine was added, and the mixture was heated under reflux for 1 hour. After cooling, the mixture was poured into 100 g of ice, and the resulting solid was recrystallized from methanol to give 2-nitro-4-phenylphenyl 2,4,5-trichlorobenzenesulfonate.
5 g were obtained. Yield 93%. ¹ H NMR (CDCl ₃ ) d 8.19 (s,
1H), 8.10 (s, 1H), 7.80 (d, 1H), 7.75 (s, 1H), 7.
35-7.60 (m, 6H). 3. 2-nitro-4-phenylphenyl 2,4,5-trichlorobenzenesulfonate
6 g is dissolved in methanol, and sodium disulfide 0.55
g, and the mixture was heated under reflux for 2 hours, cooled with ice, and the resulting solid was collected by filtration, washed with methanol, and washed with bis (2-nitro-4
1.7 g of (-phenylphenyl) disulfide were obtained. Yield 74%. FAB mass spectra: m / e 460 (M ⁺ for C ₂₄ H ₁₆
N ₂ O ₄ S ₂ ), 262, 230; ¹ H NMR (DMSO-d6) d 8.58 (s, 2
H), 8.10 (d, 2H), 7.92 (d, 2H), 7.73 (d, 4H), 7.37
-7.55 (m, 6H). Dissolve 2.3 g of bis (2-nitro-4-phenylphenyl) disulfide in 50 ml of acetic acid,
After adding 3 g of zinc dust and heating at 80 ° C. for 3 hours, 2 ml of acetic anhydride was added and the mixture was further heated for 2 hours. After cooling, the reaction solution was filtered, and the filtrate was neutralized with an aqueous sodium hydroxide solution.
The product was extracted with ethyl acetate. The solvent was distilled off and the residue was purified to give 2-methyl-5-phenylbenzothiazole.
1 g was obtained. Yield 49%. 34% yield from 4-phenylphenol.

Comparative Example 1 A method for producing 2-methyl-5-phenylbenzothiazole was described in US Pat.
No. 13. 4-bromo-3- as raw material
Using nitrobiphenyl, the reaction with sodium disulfide, followed by the reduction with zinc, and the reaction with acetic anhydride,
The yield is stated as 13%.

(Example 2) Synthesis of 5-methoxy-2-methylbenzothiazole Using 4-methoxy-2-nitrophenol as a raw material, 4-methoxy-2-nitrophenyl 2,4-methoxyphenyl was prepared in the same manner as in Example 1. 4,5-Trichlorobenzenesulfonate was obtained. Yield 75% ¹ H NMR (CDCl ₃ ) d 8.05 (s, 1
H), 7.72 (s, 1H), 7.45 (s, 1H), 7.25 (d, 1H), 7.10
(d, 1H), 3.85 (s, 3H). 2.0 g of 4-methoxy-2-nitrophenyl 2,4,5-trichlorobenzenesulfonate was dissolved in methanol, and 0.28 g of sodium disulfide was added. 1.4 g of (methoxy-2-nitrophenyl) disulfide were obtained. Yield 75%. FAB mass spectr
a: m / e 368 (M + for C 14 H 12 N 2 O 6 S 2). ¹ H NMR (CDCl ₃ )
d 7.65 (m, 1H), 7.28 (d, 1H), 7.17 (d, 1H), 3.85
(s, 3H). Bis (4-methoxy-2-nitrophenyl)
Disulfide was reacted in the same manner as in Example 1 to obtain 5-methoxy-2-methylbenzothiazole. Yield 83%. 47% yield from 4-methoxy-2-nitrophenol.

Comparative Example 2 A method for producing 5-methoxy-2-methylbenzothiazole was described in Zh. Obshch.
Khim. 1946, Vol. 16, p. 1071. 4-Bromo-3-nitroanisole is used as a starting material, and the yield is 32 by reaction with sodium disulfide, followed by reduction with zinc and reaction with acetic anhydride.
%.

From the above results, it was shown that in the synthesis of benzothiazole derivatives, benzothiazole derivatives can be produced in good yields by using the readily available substituted phenol as a raw material by the method of the examples.

[0073]

Industrial Applicability The present invention provides a general process for obtaining a benzothiazole derivative which is important as a synthetic intermediate for functional dyes, pharmaceuticals, functional materials, etc. in good yield from easily available substituted phenols as raw materials. provide.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) G03C 1/12 G03C 1/12

Claims (6)

[Claims] 1. A compound represented by the following general formula (I) is derived into a compound represented by the general formula (II), and is converted into a compound represented by the general formula (III). A process for producing a compound represented by the general formula (IV) from a compound represented by the general formula (I) by using the compound represented by the following formula: General formula (I) In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ each independently represent a hydrogen atom or a monovalent substituent, and these may be bonded to each other to form a ring. Formula (II) In the formula, R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ¹⁵ each independently represent a hydrogen atom or a monovalent substituent, and these may be bonded to each other to form a ring. R ¹⁶ represents a substituted or unsubstituted aliphatic group, aromatic group or heterocyclic group. General formula (III) In the formula, R ²¹ , R ²² , R ²³ , R ²⁴ and R ²⁵ each independently represent a hydrogen atom or a monovalent substituent, and these may be bonded to each other to form a ring. X ² is a sulfur atom,
Represents a selenium atom or a tellurium atom. L is a hydrogen atom,
Represents monovalent substituents or metal and non-metal cations. General formula (IV) In the formula, R ³¹ , R ³² , R ³³ and R ³⁴ each independently represent a hydrogen atom or a monovalent substituent, and these may be bonded to each other to form a ring. R ³⁷ is a hydrogen atom or 1
Represents a valent substituent. X ³ represents a sulfur atom, a selenium atom or a tellurium atom. 2. The method according to claim 1, wherein the compound represented by the general formula (I)
In formulas (II), (III) and (IV)
R of the compound represented¹, R^Two, R^Four, R¹¹, R¹²,
R¹⁴, R^{twenty one}, R^{twenty two}, R^{twenty four}, R³¹, R³²And R³⁴Is hydrogen
Represents an atom, R ^Three, R¹³, R^{twenty three}, R³³Is a monovalent substituent
The general formula according to claim 1, wherein
From the compound represented by (I), a compound represented by the general formula (IV)
Production method for producing a compound to be produced. 3. The compound according to claim 1, wherein R ¹⁵ and R of the compounds represented by the general formulas (II) and (III)
²⁵ is a compound represented by the general formula (IV), wherein the compound represented by the general formula (I) is a nitro group.
A method for producing a compound represented by the formula: 4. The method according to claim 1, wherein the general formula (IV)
R of the compound ³⁷Is a methyl group
The compound represented by the general formula (I) according to claim 1
For producing a compound represented by the general formula (IV) from
Method. 5. The compound represented by the general formula (I) according to claim 1, wherein the compound represented by the general formula (III) is represented by the general formula (III) ′ A method for producing a compound represented by the general formula (IV) from a compound. General formula (III) ′ In the formula, R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ and X ² are represented by the general formula (I
Synonymous with II). 6. A process for producing a compound represented by the general formula (III), comprising producing a compound represented by the general formula (III) from a compound represented by the general formula (II).