JPH02262554A - Production of 4-aromatic ring-thio substituted phenol compound - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as a synthetic intermediate for dyes, pharmaceuticals and agricultural chemicals and having a wide application field with few production steps in high yield by reacting a phenolic compound with a disulfide in the presence of a base. CONSTITUTION:The objective compound of formula IV or formula V can be produced by reacting a phenolic compound of formula l or formula II (R1 is group which can be substituted to aromatic group but does not substitute the 4-site of phenol and naphthol (m) is 0-4; (n) is 0-6) with a symmetric or asymmetric disulfide of formula III (X is O, S, Se, Te, imino or methine; Y is N or methine; Z is non-metal forming a 5- or 6-membered ring together with X and Y and may have condensed ring) in the presence of a base (e.g. NaOH) in a solvent such as N,N-dimethylformamide at -78 to +250 deg.C.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to a method for producing 4-aromatic ring thio-1-phenol and 4-aromatic ring thio-1-naphthol derivatives, which are 4-thio substituted phenol compounds. .

(Prior Art) 4-aromatic ring thio-1-phenol and 4-aromatic ring thio-1-naphthol derivatives are important as synthetic intermediates for dyes and physiologically active compounds (medicines, agricultural chemicals, etc.).

Furthermore, 4-thio-substituted-1-phenol and 4-thio-substituted-1-naphthol derivatives are known in the field of photographic chemistry as two-equivalent cyan color-forming couplers8, e.g., U.S. Pat. No. 3,227,554; Japanese Patent Publication No. 60-5053
Examples can be found in No. 3, No. 60-91355, No. 61-201247, and No. 62-173467.

On the other hand, 4 of 1-phenol and 1-naphthol derivatives
There are only two known methods for introducing an aromatic ring thio group into the position.

(U.S. Patent No. 3.227.551;
No. 554) When 1-phenol or 1-naphthol derivatives are reacted with arylsulfenyl chloride, the 4-position is arylthiolated. Arylsulfenyl chloride can be synthesized by reacting the corresponding aryl mercaptan with sulfuryl chloride, chlorine, N-chlorosuccinimide, or the like.

■ (New Experimental Chemistry Course 14-r, 423; JP-A-61-
No. 201247) By iodizing the 4-position of 1-naphthol and subsequently reacting with an aryl mercaptan, the 4-position can be arylthiolated.

(Problems to be Solved by the Invention) However, each of the two methods described above has several drawbacks.

Method (2) cannot be used when the reaction molecule is sensitive to acids, because separation occurs during the synthesis of sulfenyl chloride and the reaction with phenol and naphthols. Also,
There is a drawback that it is difficult to use reaction solvents that react with sulfenyl chloride, such as alcohols.

Furthermore, this method cannot be used if the mercaptan used has a functional group that reacts with sulfenyl chloride in its molecule.

Method (2) has the drawback that the yield of iodination at the 4-position of naphthol is not very high, and the yield is not high when looking at the entire process.

Therefore, it is desired to develop a reaction that has a wide range of applications (and can obtain the desired product in high yield).

Therefore, an object of the present invention is to provide a general synthetic method for synthesizing 4-aromatic ring-substituted thio-1-phenol and 4-aromatic ring-substituted thio-1-naphthol derivatives from the corresponding 1-phenol or 1-naphthol derivatives in good yield. It's about doing.

(Means for Solving the Problems) As a result of various studies aimed at developing a general synthesis method that overcomes the drawbacks of these conventional methods, the present inventors found that 1-phenol or 1-naphthol was synthesized in the presence of a base. It is possible to synthesize the desired 4-substituted thio-1-phenol or 4-substituted thio-1-naphthol derivative in high yield by reacting the derivative with the compound represented by the general formula (It). Based on this knowledge, it was our turn to develop the present invention.In other words, the present invention provides a phenol compound represented by the formula (I-a) or (1-b) (I=a) (I-b) A symmetric or asymmetric disulfide represented by the general formula (TI) is reacted with the general formula (III-a) or (II[-b) (+U-a
) (III-b) Provides a method for producing a 4-thio substituted phenol compound, which is characterized by obtaining a 4-thio substituted phenol compound represented by the following formula.

(In the formula, R1 represents a group that can be substituted on the aromatic ring, and is not substituted at the 4-position of phenol or the 4-position of naphthol.)
represents an integer from 0 to 4, n represents an integer from 0 to 6, X represents an oxygen atom, a sulfur atom, a selenium atom, a tellurium atom, an imino group or a methine group, and Y represents a nitrogen atom or a methine group. , Z is 5-membered or 6-membered with X and Y
Z represents a group of nonmetallic atoms constituting a member ring, and Z may further have a fused ring. ) Next, the compounds represented by the general formulas (I-a), (I-b) and (II) and the bases used in the reaction will be described in detail.

In the compound represented by general formula (I-a) or (I-b), R1 is a group that can be substituted on an aromatic ring, such as a halogen atom, an alkyl group, an aralkyl group, an alkenyl group, an aryl group, a carboxyl group. , sulfo group, hydroxyl group, cyano group, carbamoyl group, sulfamoyl group, ureido group, carbonamide group, sulfonamide group, alkoxy group, aryloxy group, heterocyclic group, amino group, alkylsulfonyl group, arylsulfonyl group,
There are alkoxycarbonyl groups, aryloxycarbonyl groups, alkoxysulfonyl groups, aryloxysulfonyl groups, sulfamoylamino groups, alkoxycarbonylamino groups, acyl groups, nitro groups, etc. 0m is an integer from O to 4, and m is an integer from O to 4. When there is a plurality of R1s, the R1s may be the same or different, and the R1s may be bonded to each other to form an aromatic hydrocarbon ring, an aliphatic ring, or a heterocycle, and n is from 0 to is an integer up to 6, and when n is multiple, multiple R1s may be the same or different, and multiple R1s are bonded to each other to form an aromatic hydrocarbon ring, an aliphatic ring, or a heterocycle. It's okay.

More specifically, the exemplified groups for R1 above include those having further substituents, such as halogen atoms, alkyl groups, aralkyl groups, alkenyl groups, and aryl groups. , carboxyl group, sulfo group, hydroxyl group, cyano group, carbamoyl group,
Sulfamoyl group, ureido group, carbonamide group, sulfonamide group, alkoxy group, aryloxy group, heterocyclic group, amino group, alkylsulfonyl group, arylsulfonyl group, alkoxycarbonyl group, aryloxycarbonyl group, alkoxysulfonyl group, aryl Examples include oxysulfonyl group, sulfamoylamino group, alkoxycarbonylamino group, acyl group, and nitro group.

The substituents preferably used in the present invention for the compound represented by formula (I-a) or (1-b) are as follows. That is, R1 is a halogen atom (
fluorine atom, chlorine atom, bromine atom, iodine atom), alkyl groups having 1 to 19 carbon atoms (e.g. methyl, ethyl, i
-propyl, t-butyl, trifluoromethyl, n-dodecyl, n-octadecyl), aralkyl group having 1 to 19 carbon atoms (e.g. benzyl, phenethyl), carboxyl group, sulfo group, hydroxyl group, cyano group, 1 carbon number ~
37 carbamoyl groups (e.g. carbamoyl, N, N
-dimethylcarbamoyl, N.

N-diethylcarbamoyl, N-methylcarbamoyl,
N-butylcarbamoyl, N-cyclohexylcarbamoyl, N,N-diethylcarbamoyl, N-(2-carboxylethyl)carbamoyl, N-hexadecylcarbamoyl, N-dodecylcarbamoyl, N-(3-dodecyloxypropyl) Carbamoyl, N-[3-(2,
4-di-1-pentylphenoxy)propyl]carbamoyl, N-[4-(2,4-di-t-pentylphenoxy)butylcarbamoyl), sulfamoyl group having 0 to 36 carbon atoms (e.g. sulfamoyl, N-methylsulfamoyl), moyl, N-butylsulfamoyl, N,N-diethylcarbamoyl, N,N-diethylsulfamoyl, N-
dodecylsulfamoyl, N-octadecylsulfamoyl), carbon amide groups having 1 to 36 carbon atoms (e.g. formamide group, acetamide group, trifluoroacetamide group, propionamide group, benzamide group, p-nitrobenzamide, n-dodecane) amide, n-octadecanamide, i-butanamide, t-butanamide, 2
-Ethylhexanamide, 2-(2,4-di-t-pentylphenoxy)butanamide, trichloroacetamide, p-chlorobenzamide, pentafluorobenzamide, 2-(2,4-di-t-pentylphenoxy)
Hexaneamide, 2-(2,4-di-7-pentylphenoxy)octanamide, 2-(3-pentadecylphenoxy)butanamide, 2-(4-dodecylphenylthio)octanamide, 2-(4-butanesulfonamide) phenoxy)tetradecanamide, 2-(2,4-
di-t-octylphenoxy)octanamide, 2-
(2,4-di-t-pentylphenoxy)tetradecanamide, 2-(4-(p-hydroxybenzenesulfonyl)phenoxy)tetradecanamide, 2-(2-chloro-4-(3'-chloro-4'- hydroxybenzenesulfonyl)phenoxy)dodecanamide, 2-(2-chloro-4-carboxylphenoxy)tetradecanamide, 2-(3-t-butyl-4-hydroxyphenoxy)tetradecanamide), sulfonamide having 1 to 36 carbon atoms groups (e.g. methanesulfonamide, ethanesulfonamide, n-butanesulfonamide, trifluoromethanesulfonamide, benzenesulfonamide, p-toluenesulfonamide, phenylmethanesulfonamide, n-hexadecanesulfonamide, n-octadecanesulfonamide, m - nitromethanesulfonamide,
p-dodecylbenzenesulfonamide), carbon number 6-3
6 aryloxy groups (e.g. phenoxy, p-methylphenoxy, p-methoxyphenoxy, p-nitrophenoxy, 0-chlorophenoxy), alkoxy groups having 1 to 36 carbon atoms (e.g. methoxy, ethoxy, methoxyethoxy, benzyloxy, 2-pyranoxy, n-butoxy, n-dodecyloxy, n-octadecyloxy), alkoxycarbonyl groups having 2 to 36 carbon atoms (e.g. methoxycarbonyl, ethoxycarbonyl, n-octylcarbonyl, n-octadecylcarbonyl), amino groups , an alkylamino group having 1 to 36 carbon atoms (e.g. methylamine, dimethylamino, morpholino, n-octylamino)
, nitro group, acyl group having 1 to 36 carbon atoms (e.g. formyl, acetyl, benzoyl, propionyl, n-butyryl, cyclohexanecarbonyl, n-decanoyl, n-
octadecanoyl), alkoxycarbonylamino groups having 1 to 36 carbon atoms (e.g. methoxycarbonylamino, ethoxycarbonylamino, i-butoxycarbonylamino, benzyloxycarbonylamino, n-butoxycarbonylamino, t-butoxycarbonylamino, n-
octyloxycarbonylamino, n-dodecyloxycarbonylamino, n-octadecyloxycarbonylamino), ureido groups having 1 to 36 carbon atoms (e.g. ureido, N-methylureido, N-ethylureido, N
-Phenylureido, N-(p-cyanophenyl)ureido, N-(m-chloro-p-cyanophenyl)ureido, N-propanesulfonylphenylureido, N-
Butanesulfonylphenylureido, N-(m,p-dichlorophenyl)ureido, N-(o-chloro-p-cyanophenyl)ureido, N-(4-cyanonaphthyl)
ureido, N-(m-cyanophenyl)ureido, N
-methanesulfonylphenylureido, N-(p-chlorophenyl)ureido, N-(p-methylphenyl)ureido, and N-(m-methanesulfonamidophenyl)ureido) are each preferred.

The substituent R1 is preferably introduced at least at the 2- and 5-positions in the compounds of formulas (1-a) and (I-b).

Among the compounds represented by the general formula (I-a) or (I-b), those having the following structures (V), (Vl
) is preferred.

(V) (W) Here, R has the same meaning as R1 described above. Ar represents an alkylcarbonamide, and the alkyl may be substituted; R'-N- represents a monosubstituted amino group; more specifically, alkylcarbonamide, arylcarbonamide, alkoxycarbonylamino, aryloxycarbonylamino, It represents alkanesulfonamide, arylsulfonamide, etc., and alkyl and aryl may be substituted.

In the compound represented by general formula (II), X, Y and Z are as described above, and in the formula, X and X, Y and Y, and Z
and Z may be the same or different.

In general formula (It), when X and Y are both methine groups, typical preferred groups are phenyl and naphthyl groups, and when X and Y are not methine groups, specific examples are pyridyl, pyrrolyl, oxasilyl, thiazolyl, benzoxasilyl, benzthiazolyl, quinolyl,
These include furyl, thienyl, indolyl, pyrazinyl, and pyrimidinyl. These groups include halogen atoms, nitro,
cyano, alkyl, hydroxy, alkoxy, aryloxy, acyloxy, sulfonyloxy, carboxy, carboxylic acid ester, carbamoyl, sulfo, sulfonic acid ester, sulfamoyl, alkylth5arylthio, sulfonyl, acyl, amino, acylamino,
Sulfonamide, ureido, urethane, sulfenyl,
It may be substituted with mercapto, aryl, heterocyclic groups, etc.

Moreover, it is preferable to use a symmetric disulfide, which has only one reaction site due to symmetry, because it is easier to control the reaction, than to use an asymmetric disulfide, which has two reaction sites.

As the base used in the present invention, bases used in ordinary organic reactions can be used6. For example, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, carbonate Potassium hydrogen, sodium hydride, potassium hydride, lithium hydride, sodium amide, t-
Butoxypotassium, guanidine, 1□8-diazabicyclo[5,4,'O]-7-undecene (DBU), 1.
5-Diazabicyclo[4,3,0]-5-nonene (D
BN), n-butyllithium, n-methyllithium 1.
5ec-butyllithium, i-butyllithium, t-butyllithium, i-propyllithium, methylmagnesium bromide, trimethylsilyloxypotassium,
Examples include sodium acetate, triethylamine, pyridine, sodium methoxide, potassium methoxide, lithium methoxide, and sodium ethoxide. Among these bases, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, DBU
, trimethylsilyloxypotassium, etc. are preferred.

Next, the reaction conditions of the present invention will be described in detail.

Solvents used in the reaction of the present invention include methylene chloride, chloroform, l,2-dichloroethane, acetonitrile, N,N-dimethylformamide F, N,N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, tetrahydrofuran, dioxane, Dimethoxyethane, diglyme, diethyl ether, benzene, toluene, hexamethylphosphoric triamide, sulfolane, diethyl carbonate, 1. , Is-dimethyl-2
-imidazolitone, methanol, ethanol, isopropyl alcohol, ethyl acetate, butyl acetate, acetone,
Examples include methyl ethyl ketone, xylene, acetic acid, and water, among which N.

Preferred are N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, tetrahydrofuran, methanol, ethanol, and the like.

The general formula (I-a) or (I-b) of the symmetric or asymmetric disphites represented by the general formula (n) in the present invention
) is 0.01 to 100.
0, preferably o, i~20. More preferably, it is 0.5 to 1O90.

The reaction temperature is -78 to 250°C, preferably -20 to 20°C.
The temperature is 0°C, more preferably -4 to 160°C.

The reaction time is 1 minute to 72 hours, preferably 20 minutes to 36 hours, more preferably 30 minutes to 24 hours.

(Specific examples of compounds) Specific examples of compounds to which the method of the present invention is applied are shown below.
It is not limited to these.

- Shows specific examples of compounds represented by formula (I-a) or (I-b). In addition, in the following structural formula, (t)(:
5H1□ is -C(CH3)2C2H5 (t)C8H1
□ is -C(CI+3)2CIl. Each represents C(CH3) 3.

(I-7) (I-8) H 0H H (l-17) (I-19,) (I-20) H CF3CONH U-22) (I-24) 0H rt2 rt3 (I-26) (I-28) (I-29) (■ (I OH OH OH (I (I (I-40) (I-45) (I=48) Ct) 150CQNH Of( OH Shitt3buzNtt (■ (I-42) (I-49) R OH +1]c4H90CONH (“I.M. OH (I-54) (I-55) (i-56) CI=61) (I-62) OH OH 02CH3 (■ (I-60) (■ Next, specific examples of the compound represented by the general formula (I) will be shown.

CH2COOH N02 COOH H 0■ (II-9) (■ (llf (III-12) (II[-13) (II-14) R CH2COOH (II-16) CH2CH2COOH (IW-17) CH2CH20H OH (IN-25 ) OH2 Shii2L-i3 H 0H (In-29) Hat-38) (III-40) H (■ (I-34) (]l[-36) (■ AND) (■ (I-44) 0H 0M OH (■ (III-47) (II[-53) (II-55) (IN-56) (1![-49) OH CH2COOH (Ii[-51) OH (■ OH CH2CH20H (M 57) OH ( II[-58) OH (II[-60) 2H5 (II-65) 0 Sweet (III-66) H (II[-68) The compound represented by the general formula (1) is disclosed in U.S. Pat.
No. 74.293, No. 4,333,999 and No. 4,
It can be synthesized by the method described in No. 690.889 and the like.

The compound represented by general formula (II) can be synthesized by a conventionally known method described in Shin Jikken Kagaku Koza 14-III, 1735, etc.

(Effects of the Invention) According to the present invention, a desired 4-aromatic ring thio-substituted phenol compound can be produced in good yield by introducing an aromatic ring thio group into the 4-position of a phenol compound such as a l-phenol or -naphthol derivative. Obtainable. Furthermore, the method of the present invention requires fewer synthesis steps and has a wide range of application, so it is suitable as a method for industrial implementation (Examples) Next, the present invention will be explained in more detail based on Examples.

Example 1 (Synthesis of Exemplified Compound ■-56) I'-56 (5.28 g, 10.0 m) under a nitrogen stream
Potassium carbonate (1.40 g, 20.0 mmol) was added to a solution of 5 mol) of tetrahydrofuran at room temperature.
After stirring for a minute, compound II-41 (3.48 g, 1
0.0 mmol) and heated under reflux for 10 hours. Add water and extract three times with ethyl acetate. The organic layer is washed with saturated aqueous sodium bicarbonate solution, water, and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and column chromatography (developing solvent; hexane: ethyl acetate =
After purification with 3:1), compound 1-56 (5.19 g 74%) was obtained.

Example 2 (Synthesis of Exemplified Compound ■-62) I-62 (4.61g, 10.0m) under nitrogen stream
Potassium carbonate (2.76 g, 20.mol) was added to an 80% ethanol solution of
mmol) and heated under reflux for 1 hour. Add water and extract three times with ethyl acetate.

The organic layer was washed with a saturated aqueous sodium bicarbonate solution, water, and saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and purified by column chromatography (developing solvent: hexane: ethyl acetate = 4:1). Then the compound lll
-62 (4.09 g, 65%) was obtained.

Claims (1)

[Claims] General formula ( I -a) or ( I -b) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( I - a) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( I - b) A phenol compound represented by the general formula (II) ▼There are mathematical formulas, chemical formulas, tables, etc.▼ (II) A symmetrical or asymmetrical disulfide represented by is reacted in the presence of a base ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III -a) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (III-b) A method for producing a 4-thio substituted phenol compound, which is characterized by obtaining a 4-thio substituted phenol compound represented by the following. (In the formula, R_1 represents a group that can be substituted on the aromatic ring, and is not substituted at the 4-position of phenol or the 4-position of naphthol. m represents an integer from 0 to 4, and n represents an integer from 0 to 6. , X represents an oxygen atom, a sulfur atom, a selenium atom, a tellurium atom, an imino group or a methine group, Y represents a nitrogen atom or a methine group, and Z constitutes a 5- or 6-membered ring together with X and Y. Represents a nonmetallic atomic group. Also, Z may further have a fused ring.)