JPH02286655A - Synthesis of catechols having thioether group - Google Patents

Abstract

PURPOSE:To selectively produce the subject compound useful as a synthetic intermediate for photographic chemicals, antiseptic agent, rust-proofing agent, pharmaceuticals, etc., by reacting catechols with a sulfenylation agent in the presence of a trivalent phosphorus compound, an organic base and a halogenation agent. CONSTITUTION:The objective catechol having thioether group and expressed by formula II can be produced by reacting a compound of formula I (R1 is group which can be substituted to benzene ring; n is 0-3: etc.) with a compound of formula X-S-R2 (R2 is aliphatic, aromatic or heterocyclic group; X is halogen or imide) in the presence of a trivalent phosphorus compound of formula P(Y)3 (Y is halogen, aliphatic group, aromatic group, alkoxy, amino, etc.), an organic base and a halogenation agent in a solvent (e.g. THF) at -15-+10 deg.C. The objective compound can be produced under mild condition in high yield while minimizing the amount of the sulfenylation agent.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for selectively synthesizing catechols having a thioether group in high yield.

(Prior Art) Catechols having a thioether group are useful compounds as photographic compounds. For example, its usefulness is described in JP-A-23371/-/. Furthermore, it is a compound that is expected to be used as an intermediate for preservatives, rust preventives, preservatives, and pharmaceuticals.

Conventionally, when introducing all sulfenyl groups into catechols,
For example, methods using sulfenyl chlorides are known. However, when a nulphenyl group is introduced into catechols having an electron-withdrawing group, the reaction often does not proceed even if sulfenyl chlorides are used because the reactivity thereof decreases.

At that time, it was known to use aluminum chloride as a catalyst, an example of which is described in JP-A-2337-7. However, when the compound of the general formula (V) described in claim (2) of the present specification is reacted with sulfenyl chloride in the presence of aluminum chloride, reaction points are formed in the catechol moiety. It has been found that because of the presence of sulfides in different positions, one has a nulphite introduced at each position, and the other has a sulfide introduced at a - position. Therefore, in order to obtain the product introduced at the desired position, some sort of separation operation was required, which naturally resulted in a decrease in yield. In addition, when using aluminum chloride, extremely low temperatures (-100C to -
The reaction temperature was 100C), and the troublesome reaction operation was undeniable. For these reasons, a method of selectively introducing nulphites into catechols has been desired.

As one method to solve this problem, a method of reacting catechols and sulfenyl chlorides in the presence of a trivalent glue/compound is proposed in JP-A-Sho 3-. 2 was disclosed in the Hiro/J issue. In fact, when a compound represented by the general formula (V) of the present specification is reacted with sulfenyl chloride in the presence of triphenylphosphine according to the method described in JP-A No. 3-3-λr≠/3, Compared to reactions that do not use triphenylphosphine or reactions that use aluminum chloride instead of triphenylphosphine, the yield of the target compound with the general formula (■) is higher! - I found out that there is something wrong. However, in the synthesis examples in this specification, in most cases 3 mol to 1 mol of catechols
The reaction is carried out using j moles or more of sulfenyl chloride. If the reaction is carried out under such conditions, a large amount of thiol and disulfide, which are thought to be decomposition products of the excess nulfenyl chloride, will be produced, resulting in the formation of crystals of the target compound of general formula (■), etc. It was found that these substances tend to remain as impurities. When the compound represented by the general formula (■) is a photographic compound added to a silver halide photographic light-sensitive material, these impurities cause a fatal deterioration of performance, so thiols and disulfides are generated. Less is. In other words, it has been strongly desired to develop a method capable of synthesizing the compound represented by the general formula (■) in a high yield using as little amount of sulfur chloride as possible. Unexamined Japanese Patent Publication 1973
−． 2r Hirol! In the synthesis examples in the specification of No. 2, the general formula (
There are 7 examples in which the compound represented by the formula V) is reacted with a small amount of sulfenyl chloride in the presence of carbon tetrachloride and triphenylphosphine to obtain the l- compound represented by the general formula (■). However, carbon tetrachloride is a deleterious substance and highly toxic, so it has been difficult to use it for industrial large-scale synthesis.

(Objective of the Invention) Therefore, the object of the present invention is to provide a method for synthesizing industrially useful catechols having a thioether group in good yield under mild conditions using as little sulfenylating agent as possible. be.

Means for Solving Problem c) The above-mentioned object of the present invention is to combine the catechols represented by the following general formula (I) and the compound represented by the following general formula (n) into the following general formula ( A method for synthesizing catechols having a thioether group represented by the general formula (In), characterized by reacting in the presence of a trivalent phosphorus compound, an organic base, and a halogenating agent as described in IV) achieved by.

General formula (I) General formula (I) General formula (II [
) General formula (JV) -R2 In the formula, R□ represents a substituent 1-[I, and n represents an integer from O to 3. When n is one or more, multiple R1s harm the same or different things. R2 represents an aliphatic group, an aromatic group or a heterocyclic group, and X represents a halogen atom or an imide group. Y#'i represents a halogen/atom, an aliphatic group, an aromatic group, an alkoxy group, an aryloxy group, or an amino group.

The present invention will be explained in more detail below.

In the general formula (1), □ is a halogen atom (e.g., salt atom, bromine atom), linear or branched, chain or cyclic, saturated or unsaturated, substituted or unsubstituted, aliphatic hydrocarbon. groups, i.e. alkyl groups, alkenyl groups, alkynyl groups (for example, methyl, propyl, t-butyl, trifluoromethyl, tridecyl, J-(2, Hiro-di-t-amylphenoxy)propyl, -1-dodecyloxyethyl, 3-phenoxyprobyl, -hexylsulfonylethyl, cyclopentyl, benzyl], aryl 1 (flJ engineering ld' phenyl, pt-butylphenyl, kutetradeca/amidophenyl), heteday 31i (
flit, -furyl, -thenyl, -pyrimidyl, copenzothiazolyl), cyano group, alkoxy group (e.g., methoxy, ethoxy, λ-methoxyethoxy, -1dodecyloxyethoxy, -1methanesulfonyl) ethoxy), aryloxy groups (e.g. phenoxy,
comethylphenoxy, a-ty' tylphenoxy)
, hetexyloxy groups (e.g. Kobe/zimidazolyloxy), acyloxy groups (e.g. acetoxy, hexadecanoyloxy), carbamoyloxy groups (N-ethylcarbamoyloxy), silyloxy groups (e.g.
trimethylsilyloxy), sulfonyloxy groups (e.g., dodecylsulfonyloxy), acylamino groups (e.g., acetamide, benzamide, tetradecanamide, α-ter(-,ter-t-amylphenoxy)butyramide,
-, tertiary-t-amylphenoxyacetamide, α-
(+-(l/L-hydroxyphenylnulfonyl)phenoxy))decaneamide, impentadecanamide),
Anilino groups (e.g., phenylamino, -1chloroanilino, -1chloro3-tetradecanamideanilino,
- One Roro! -dodecyloxycarbonylanilino,
N-acetylanilino, -1chloro3-(α-(--
(t-butyl-hydroxyphenoxy)dodecanamido)anilino), ureido groups (e.g., phenylureido, methylureido, N,N-dibutylureido), imide groups (e.g., N-nuccinimide, 3-penzylhydantoinyl) , Hiro-(j-ethylhexanoylamine)
phthalimide), null-7 amoylamino group (e.g. N
, N-dipropylsulfamoylamino, N-methyl-
N-decylsulfamoylamino), alkylthio group (
9'Il is a methylthio, octylthio, tetradecylthio, -monophenoxyethylthio, 3-phenoxydipropylthio, 3-(4L-1-7''f-ruphenoxy)propylthio), arylthio group (e.g. Phenylthio, Coptoxy 1-1-octylphenylthio, 3-
pentadecylphenylthio, λ-carboxyphenylthio, Hiro-tetradecanamidophenylthio), heterocyclic thio groups (e.g. cobenzothiazolylthio), alkoxycarbonylamino groups (e.g. methoxycarpolamino, tetradecyloxycarbonylamino) ), aryloxycarbonylamino groups (e.g., phenoxycarbonylamino 1,2.4t-di-tert-butylphenoxycarbonylamino), sulfonamide groups (e.g., methanesulfonamide, hexadecanesulfo/amide, benzenesulfonamide, 1 )-4 Rue/sulfonamide, octadecane-nulphonamide, -1-methyloxy-3-1-butylbenzene-nulphonamide), carbamoyl group (13'Ltld, N-ethylcarbamoyl,
N-,'rovylcarbamoyl, N-dibutylcarbamoyl, N-(,2-dodecyloxyethyl)carbamoyl, N-methyl-N-dodecylcarbamoyl, N-(
,? -(,2,F-G-tert-7 milk enoxy)
(propyl)carbamoyl), acyl groups (e.g., acetyl groups (2, tert-amylphenoxy)acetyl, benzoyl), nurfinyl groups (e.g., N-ethylcarbamoyl, N,N-dibutylcarbamoyl, N
-(,2-dodecyloxyethyl)sulfamoyl, N
silsulfamoyl, N,N-dibutylcarbamoyl], sulfonyl group (?Lt, methanesulfonyl, octanesulfonyl, benzenesulfonyl, toluenesulfonyl), nulfinyl group (e.g. octane sulfonyl, dodecylnurfinyl, phenylsulfinyl], alkoxycarbonyl groups (e.g., methoxycarbonyl, butyloxycarbonyl, dodecylcarbonyl, octadecylcarbonyl), aryloxycarbonyl groups (e.g., phenyloxycarbonyl, 3--!'ntadecylmexyl), Carbonyl) Woiwasu.

In the general formula (n), R2 has the number of carbon atoms/~! aliphatic, aromatic or heterocyclic group.

An aliphatic group is a linear or branched, chain or cyclic, saturated or unsaturated, substituted or unsubstituted aliphatic hydrocarbon. Substitutional examples include ethyl, butyl, methyl, (i) propyl, besylyl, cyclohexyl, (S)butyl, heptyl or 2-ethylhexyl.

The aromatic group is a substituted or unsubstituted phenyl group or a substituted or unsubstituted naphthyl group.

Among these, a substituted phenyl group is a preferred example. The substituent may include, for example, an aliphatic group (for example, a liptyl group), an alkoxy group, a nitro group, a cyan group, or a halogen atom (for example, a chlorine atom).

A heterocyclic group is a double purple atom selected from nitrogen, sulfur, or oxygen atoms! or g-membered substituted or unsubstituted heterocyclic group. Examples of substitute heterocyclic groups include z=(/,,+,3,4t-tetrazolyl) group,
t-(/,,2.≠-trialyl) group, J-(/,3
．． 41-thiadiazolyl) group, -1 (/, 3.II-oxadiazolyl) group, benzimidazolyl group, benzoxasilyl group, benzthiazolyl group, and the like.

Substituents for heterocyclic groups include phenyl group, aliphatic group (e.g. methyl group), aliphatic thio group (e.g. methylthio group)
, or an acylamino group (eg an acetamido group) are alternative examples.

In the general formula (n), X represents a halogen atom (eg, fluorine atom, chlorine atom, bromine atom, iodine atom) or an imide group (eg, succinimide, phthalimide).

Among the compounds represented by general formula (I), preferred compounds are represented by general formula (V).

In the formula, R3, 几. is a substituent t- that can be substituted on the benzene ring
R5 is the σ of the metal that can be substituted on the benzene ring.
Represents an electron-withdrawing group included in the value O to /, 0,
i represents an integer from O to 3.

Here, when n is plural. may be the same or different, and R4 may be bonded to each other to form a ring. For Hammett's σ value, see Jerry Mar
ch, “Advanced Organic Ch.
emistry”, page 233.

For more information, see Substituents)? +3 and R14 represent the same as R1 described above.

R5 represents an electron-withdrawing group included in the Hammett's σ value of 0 to 0, which can be substituted in the be/ze/ring; cyan group, -tro group, aryloxy group (e.g. phenoxy), acyloxy group (e.g. acetoxy), carbamoyloxy group, nulfonyloxy group, acylamino group (e.g. acetamide, propylamide, (t)-butylamide), sulfonamide group, A carbamoyl group, an acyl group (ffl, acetyl, benzoyl), a sulfonyl group, an alkoxycarbonyl group (eg, methoxycarbonyl, butyloxycarbonyl), an aryloxycarbonyl group, etc. can be used.

Among the compounds represented by the general formula (It), particularly preferred compounds are represented by the general formula (Vl).

General formula (VI) α-8-R2 In the formula, R2 has the same meaning as described above.

Specific examples of the compound represented by the general formula (ml) that can be synthesized by the method of the present invention are shown below, but the present invention is not limited thereto.

H H −／　7− -+2,! − H H -, 2! − H 16- H N 2H5 H H -2 tar- The synthesis method of the present invention will be explained in detail below.

Trivalent phosphorus compounds used in the present invention include triarylphosphines (e.g., triphenylphosphine, tritolylphosphine), trialkylphosphines (e.g., tributylphosphine, tricyclohexylphosphine), phosphites ( Examples: Eva, triethyl phosphite, triphenyl phosphite], phosphite amide (
For example, hexamethylsulfur triamide), phosphorus trichloride, phosphorus tribromide, etc. can be used. Preferred trivalent phosphorus compounds are triarylphosphines and trialkylphosphines. The amount of the trivalent phosphorus compound to be used is 0.7 to 1.0 to 1 mole of the compound represented by the general formula (I).
0 mol, preferably 02 to 3.0 mol.

Examples of organic bases used in the present invention include tertiary amines (e.g., triethylamine, tripropylamine, diisopropylethylamine, dimethylcyclohexylamine),
Preferred are aromatic nitrogen-containing heterocyclic compounds with a ring or t-membered ring (for example, pyridine, 2,6-lutidine, pyrazole, imidazole), and particularly preferred are pyridine, 2.
These are t-lutidine, triethylamine, tripropylamine, and imidazole. The amount of these bases added is between 0° and 2° per mol of the compound represented by the general formula (I).
0. ．． 0 mol, preferably /, -, 0 mol.

Preferred halogenating agents used in the present invention include nurfuryl chloride, thionyl chloride, chlorine, bromine, N-chlorosuccinimide, and N-bromosuccinimide, with sulfuryl chloride and N-chlorosuccinimide being particularly preferred. The amount of these halogenating agents added is 0.7 to 3 mol, preferably 0 to 2 mol, per 1 mol of the trivalent phosphorus compound.

As the reaction solvent used in the present invention, protic or aprotic solvents can be used, but aprotic solvents are preferred.

Preferred solvents include, for example, amides (such as N,
N-dimethylformamide, N,N-dimethylacetamide, formamide, N-methylpyrrolidone), nitriles (e.g. acetonitrile, propiontrile, benzonitrile), ethers (e.g. tetrahydrofuran, dioxa/, dimethoxyethane, diethyl ether)
, aromatics (e.g. benzene, toluene), halogenated solvents (chloroform, dichloromethane, carbon tetrachloride for Horami), esters (e.g. ethyl acetate, butyl acetate)
, dimethyl nulphoxide, sulfonate 4L
- can be lost. Particularly preferred solvents among these are ethers, halog/system solvents, and esters.

In the present invention, the reaction temperature is -73°C to 100°C.
0C, preferably uo 'c to Io 0C. The reaction temperature is appropriately selected depending on the strain of the compound. The reaction time was approximately 7 to 3 hours.

(Examples) Specific examples of the present invention are shown below, but the present invention is not limited thereto.

Example 1 [Synthesis of Exemplified Compound (1)] Compound A Compound B Compound A3.0/f (4L, fmmol), triphenylphosphine/! 79 (J, mmol)'
The solution was dissolved in rTetrahydro7ran AOtd and cooled in an ice water bath. To this, N-chlorosuccinimide o, troy (
z, mmol) i was added and stirred for 30 minutes. After removing the ice-water bath and returning the reaction temperature to room temperature, 7.5 m (/jmmol) of 2,6-lutidine was added, followed by compound B2, /f (ri, 7 mmol), Stirred at room temperature for 1 hour. After reaction, 100 yt fishing
1 and about 10O- of ethyl acetate were added for extraction. The organic layer was washed once with aqueous sodium bicarbonate solution and seven times with saturated brine, and then dried over anhydrous magnesium sulfate.

Ethyl acetate was distilled off under reduced pressure, and methylene chloride♂d was added to the residue.
1/2 ml of hexane was added to crystallize. crystal'kF
Tori L1. l, g7fc 74t%) (D exemplified product (
1) [Melting point/6.2-/13 °C (dec, ))'t
[7'c.

Example 2 [Synthesis of Exemplified Compound (3o)] Compound C ○H Compound C, 2θ, of (,2!,!Pmmol) and triphenylphosphine//, ASi' (7g, 7mmol
1) was dissolved in 3.20 g of tetrahydrofuran and stirred while cooling in an ice water bath. Seven grams (7 grams, 7 mm) of N-chlorosuccinimide was added little by little over 20 minutes. After removing the ice water bath and stirring for 30 minutes, add triethylamine 6, tag ml (Geta, Jmm
ol) and continue with compound D/3. S? (t19.r
A solution of mmol) dissolved in 10-tetrahydrofuran was added, and the mixture was stirred at room temperature for 1 hour. I used this reaction solution for fishing.
Approximately JOOml of ethyl acetate was added for extraction.

One time with 300 rtl of organic N, 7 times with 300 rtl of 3% sodium bicarbonate solution, and 7 times with saturated salt! 0OW
After washing with Le seven times, it was dried over anhydrous sodium sulfate. Ethyl acetate was distilled off under reduced pressure, and 10 ml of methylene chloride and 1,2 ml of hexane were added to the residue, and the mixture was allowed to stand overnight. The precipitated crystals were collected at 1.20°, rr (yield 10
．． 3%) Exemplary Compound (3o) (Melting Point/31/--1
37°C).

Example 3 [Synthesis of exemplified compound (3o)] Compound Cio,
o? (/, 2.4 g mmol) and triphenylphosphine7. The mixture was added to ethyl acetate (,27, &mmol) and stirred while cooling in an ice-water bath.

To this, sulfuryl chloride J, JO7 (,27,4rmmo
l) i It was added dropwise over 10 minutes and stirred for an additional 70 minutes. The ice water bath was removed and 100 rnef of tetrahydrofurine was added. Imidazole J, ff/? (jj, Pmmo
l), followed by compound DJ, Otf in tetrahydrofuran! A solution dissolved in 0 ytl was added, and the mixture was stirred at room temperature for 7 hours. This is true fishing / j Otttl, ethyl acetate about 10
0td was added and extracted. The organic layer was washed once with Honzuri/JOynl, once with about 3 liters of sodium bicarbonate aqueous solution/JOWLl, and seven times with 100 ul of saturated sodium chloride salt, and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and to the residue were added 4tOtxl of methylene chloride and AOrnl of hexane, and the mixture was allowed to stand overnight. The precipitated crystals were counted, and the exemplified compound (30
) was obtained.

Claims (2)

[Claims] (1) Catechols represented by the following general formula (I) and compounds represented by the following general formula (II) are combined with a trivalent phosphorus compound represented by the following general formula (IV), an organic base, and a halogenating agent. 1. A method for synthesizing catechols having a thioether group represented by general formula (III), which is characterized by reacting in the presence of a thioether group. General formula (I) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (II) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (III) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (IV) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In the formula, R_1 represents a substituent that can be substituted on the benzene ring, and n represents an integer from 0 to 3. When n is 2 or more, multiple R_1's represent the same thing or different things. R_
2 represents an aliphatic group, an aromatic group or a heterocyclic group, and X represents a halogen atom or an imide group. Y represents a halogen atom, an aliphatic group, an aromatic group, an alkoxy group, an aryloxy group, or an amino group. (2) The thioether group according to claim (1), wherein the general formulas (I), (II) and (III) are the following general formulas (V), (VI) and (VII), respectively. A method for synthesizing catechols having General formula (V) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ General formula (VI) Cl-S-R_2 General formula (VII) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ In the formula, R_3 and R_4 are the benzene ring Represents a substitutable group, R_5 represents a group that can be substituted on a benzene ring and has a σ value of 0 to 1.0, and m is 0.
Represents an integer from 3 to 3. Here, when m is plural, R_4
may be the same or different, and R_4 may be bonded to each other to form a ring.