JPS62201862A - Production of aromatic thiol - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to a compound of the formula The present invention relates to a novel method for producing aromatic thiols represented by a phenyl group, a phenyl group, a halogen atom, or a hydrogen atom. This compound is useful in industrial applications as a raw material for agricultural chemicals, medicines, dyes, antioxidants, resin stabilizers, and the like.

[Prior art] Conventionally, alkyl halides and thiourea were reacted to form S.
Methods are known for synthesizing an -alkyl-isothiuronium salt and then hydrolyzing this salt to produce aliphatic alkylthiols.

(Organic Chemistry Volume 2, p. 367, Organic Chemistry of Vivalent Sulfur
c Chemistry of Bivalcnt
(5ulfur) Vol. 1, p. 32) This method is based on the good reactivity of alkyl halides and thiourea.

On the other hand, as is well known, the use of aryl halides in organic synthesis is considerably limited due to the low reactivity of the sp2cm halogen bond.

Therefore, when an aryl halide is reacted with thiourea instead of the alkyl halide described above, the aryl halide is inert to the nucleophilic substitution reaction, so almost no reaction proceeds, and S-aryl-isothiuronium salt Because of the inability to produce aromatic thiols, a method for producing aromatic thiols using aryl halides and thiourea as raw materials has not yet been completed.

[Problems to be Solved by the Invention] As a result of research conducted in view of such conventional techniques, the present inventors found that among aryl halides, in particular, in the reaction between aryl iodide and a thiourea compound, the catalyst It was discovered that by using a transition metal complex as an S-aryl-isothiuronium salt, one reaction can easily proceed,
The inventors discovered that aromatic thiols with high purity and high yield can be obtained by hydrolyzing the same, and this led to the completion of the present invention.

Means for Solving Problems c] That is, the present invention provides a method for solving problems of the formula represents a phenyl group, a halogen atom or a hydrogen atom) and an aryl iodide represented by the formula (in the formula, flr, R2, R3 and R4 represent the same or different lower alkyl group, phenyl group or hydrogen atom) A thiourea compound is reacted in the presence of a transition metal complex to produce an S-aryl-inchuronium salt represented by the formula (wherein R, R1, R'', R' and R4 have the above meanings) This is a method for producing aromatic thiols represented by the formula (wherein R represents the above-mentioned meaning), characterized in that the salt is hydrolyzed.

The present invention will be explained in detail below.

The method for producing aromatic thiols according to the present invention is expressed by the following reaction formula.

NR'R” (■) (I)・・・・・・
(A) The present invention produces an S-aryl-inchuronium salt by reacting an aryl iodide and a thiourea compound in a solvent in the presence of a transition metal complex using the reaction represented by the above formula (A). This is a method for producing aromatic thiols by producing aromatic thiols and then hydrolyzing the salts.

As is clear from the reaction formula of formula (A) above, in the present invention, it is desirable to carry out the reaction by specifying the amounts of the aryl iodide and thiourea compound in the raw material system at a constant ratio, and the molar ratio Per mole of aryl iodide,
The thiourea compound is added in an amount of 1 to 3.0 moles, preferably 1.0 to 3.0 moles.
It is preferable to use 0 to 1.5 moles, and by reacting the raw material system at this specific ratio, S-aryl-isothiuronium salt can be selectively produced.

Iodinated aryl hydroxyl group used as a raw material of the present invention,
Amino group, aldehyde group, acyl group, carboxyl group,
an alkoxyl group having 1 to 3 carbon atoms, a lower alkyl group,
Indicates substituents such as a phenyl group, a halogen atom, or a hydrogen atom, but also substituents such as a substituted carbonyl group, an ester group, a substituted amino group, a substituted amide group, a hydroxymethyl group, a heteroaromatic group (furyl group, chenyl group, pyridyl group, morpholyl group, etc.) It may be substituted with a substituent such as a methyl trifluoride group, a vinyl group, or a substituted ethynyl group. Moreover, the positions of the above-mentioned substituents can be provided at any position among the 0-position, m-position and p-position depending on the substituent. Specific examples of the substituent include 1 to 3 carbon atoms.
Examples of alkoxyl groups include methoxy, ethoxy,
Propoxy, isopropoxy, lower alkyl groups include methyl, ethyl, propyl, butyl, amyl and their isomers; substituted amino groups include methylamino,
Dimethylamino, ethylamino, diethylamino, pro-ruamino, butylamino.

Phenylamino and substituted amide groups include N-methylamide, N-ethylamide, and N-phenylamide.

N,N-dimethylamide, N-methyl-N-phenylamide, the acyl group is acetyl, propionyl, butyryl, benzoyl, the substituted ethynyl group is allyl, impropenyl, 1-propenyl, the substituted carboxy group is methoxycarbonyl, Ethoxycarbonyl, propoxycarbonyl.

Examples include, but are not limited to, phenoxycarbonyl and the like.

The thiourea compound used as a raw material of the present invention is used as a sulfur atom donor, and formula (m) former 11192 R'm and R4 represent the same or different lower anosyl group, phenyl group, or hydrogen atom, and lower Alkyl groups include methyl, ethyl, propyl, butyl, amyl and isomers thereof. Further, specific examples of the thiourea compounds include thiourea, N-methylthiourea, N,N-dimethylthiourea, N-ethylthiourea, -N
Examples include, but are not limited to, '-phenylthiourea.

Next, the catalyst in the present invention is the following (a) or (b).
A transition metal complex prepared by either method is used.

(b) Either one of each of the following A, B, and C is combined and prepared in the reaction solution, or a complex is separately synthesized between A and B, and this one is combined with one of C. Prepare in reaction solution.

A, (transition metal species) per mole of NiX2 (X represents a halogen atom, a conjugate base of an organic acid, or acetylacetonate) and their hydrates, or Pd, Rh, Fe, Cu,
Co, Ru, Pt, Ir, Os, Re.

B, (ligand) 0 to 6 molar equivalents of thiourea per mole of the above-mentioned salts of Mn, Cr, V, Ti and rare earth elements and their hydrates.

(2) 0 to 6 molar equivalents of PR'(R' represents a methyl, ethyl, butyl, cyclohexyl, phenyl, 0-tolyl or p-dimethylaminophenyl group);

(2) 0 to 3 molar equivalents of R'2P(CHz)nPR', (R', n is phenyl, 1-3: methyl, 1-3; ethyl, 1-3);

1.0 to 3 molar equivalents of 1'-bis(diphenylphosphino)ferrocene.

■ 0 to 6 molar equivalents of P(Oph)3. (However, ph represents a phenyl group) (2) NR': 0 to 6 molar equivalents of l (Rγ represents each group of ethyl, butyl or cyclohexyl).

C, (reducing agent) NaBII<, NaBII+CN, Ai'Et2(
OEt), Ai'(1-Bu)J.

Aj) EL*, Zn, Na (fig), Mn (F
0 to 6 molar equivalents of e) (where Et is an ethyl group, B
(u represents a butyl group) (b) The following D alone or one of D
It is prepared in a reaction solution by combining one of B in (a) above per mole.

D.

N1(1,5-cyclooctadiene)2, N1((:O
),,N1(P(C,It8)yu)4,N1(Pph3
)4, Pd(Pphz)4, Pd(dibenzylideneacetone)2, [Rh(Call<)C:J] t, [RhC1'(
CJ, February 2, nhcβ(Ppt++)3 Among the transition metal complexes prepared by the above combination, a nickel complex is particularly preferred as the catalyst used in the present invention.

In addition, the method for preparing the catalyst is as described in (a) or (b) above.
A transition metal complex can be easily obtained by adjusting each compound selected by any combination of the following in a solvent under an inert gas stream. As the solvent used for preparing the catalyst, polar solvents represented by dimethylformamide (DMF), acetonitrile, acetone, 1,4-dioxane, hexamethylphosphoric triamide, etc. are preferred.

Further, the amount of the catalyst used in the present invention is o.oos to 0.5 mole, preferably 0.00 mole per 1.0 mole of aryl iodide as the raw material. O1 to 0.03 mole is desirable, and if it is less than o, oos mole, the reaction activity is weak, and it is not a good idea to use a large amount exceeding 0.5 mole.

Next, as the reaction conditions for producing the intermediate S-aryl-isothiuronium salt in the present invention, the reaction temperature varies depending on the raw materials used, but it is usually carried out at 20 to 100°C, preferably 40 to 80°C. , the pressure is usually
Although it is carried out under normal pressure, it may also be carried out under increased pressure.

The reaction time varies depending on the type of raw material and the reaction temperature, but is usually 1 to 40 hours, preferably 3 to 25 hours, but the reaction may be carried out for a long time depending on the type of raw material.

The above reaction is preferably carried out in a solvent, preferably a polar solvent similar to that used to prepare the above catalyst.

Further, the reaction is preferably carried out under an inert gas stream, and nitrogen, helium, argon, etc. can be used as the inert gas.

In the present invention, the S-aryl-isothiuronium salt is produced by adding the aryl iodide and the thiourea compound to a solvent in which the transition metal complex of the prepared catalyst is dissolved or dispersed, and then adding the aryl iodide and the thiourea compound under an inert gas flow. It can be obtained by carrying out a reaction at a predetermined temperature for a predetermined time.

After completion of the reaction, the S-aryl-isothiuronium salt of the reaction product may be isolated, or may be directly hydrolyzed to produce aromatic thiols without isolation.

When the reaction product is isolated, the S-aryl-inchuronium salt is recovered by directly cooling and crystallizing, by solvent concentration, or by treatment with sodium tetraphenylborate or the like.

Next, the target aromatic thiol can be obtained by hydrolyzing the S-aryl-isothiuronium salt.

Since S-aryl-isothiuronium salts are easily hydrolyzed in the presence of alkali, it is preferable to carry out the hydrolysis in an alkaline aqueous solution, but some salts can also be hydrolyzed in acids and water, so Hydrolysis is not limited to alkali and may be carried out using acidic solutions or water. The hydrolysis temperature is usually 100°C or lower, preferably room temperature to 80°C.

Aromatic thiols can be isolated by various methods such as hydrolysis followed by solvent extraction or steam distillation under acidic conditions, or isolation as various metal salts under alkaline conditions.

[Function] Since the present invention uses a transition metal complex as a catalyst in the reaction between an aryl iodide and a thiourea compound, the transition metal complex activates the aryl iodide, which is inactive against the nucleophilic substitution reaction. The reaction proceeds easily to produce S-aryl-inthiuronium salts, so it is presumed that high-purity aromatic thiols can be obtained in high yields by hydrolyzing the residue. be done.

[Example] Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Production of thiophenol [Preparation of catalyst] In a synthesis flask, 200 g of dimethylformamide and 0.52 g of nickel chloride (0,004 M) were placed.
The mixture was stirred and dissolved under a nitrogen stream. Next, 0.95 g (0,008 M) of triethylphosphine was added dropwise at room temperature, and further 0.38 g of sodium cyanoborohydride was added.
(0,006M), a reddish-purple dimethylformamide solution of nickel (zerovalent) triethylphosphine complex was obtained as two reactants.

[Synthesis of thiophenol] 40.80 g of iodized benzene (0.2 M
) and then 22.84 g of thiourea (0,3
M) was added and the reaction mixture was heated at 60° C. for 3 hours to react. After recovering dimethylformamide under reduced pressure, benzene 100ti), 10% caustic soda aqueous solution 100■β
1a Salt M
Add 25 ml, make it acidic for t, separate the benzene layer, recover the benzene under reduced pressure and obtain crude thiophenol 21.
59 g (yield 98%) was obtained. Then bp 10:
Vacuum distillation was performed at 1 to 104° C./100 s+mHg to obtain 20.93 g (yield 95%) of purified thiophenol.

The structure was confirmed by gas chromatography mass spectrometry, infrared absorption spectrum, etc.

Example 2 Production of various thiophenols yA'! in the same manner as in Example 1 but using different solvents ! i
To the various solvents shown in Table 1 of the prepared nickel (zerovalent) triethylphosphine complex catalyst, 0.2M equivalent of various aryl iodide compounds and 0.3M equivalent of thiourea were added, and after reacting under the conditions shown in Table 1, After recovering the solvent under reduced pressure, benzene 100mj), 10% caustic soda aqueous solution 100iβ
After heating at 30-40℃ for 30 minutes, add 25ml of concentrated hydrochloric acid.
j) was added, the benzene layer was separated, and the yield was determined by analyzing the concentration of each thiophenol using gas chromatography internal standard method.

In addition, a part of the obtained benzene solution of thiophenols was purified by concentration, distillation, reconsolidation, etc., and the structure was confirmed using gas chromatography mass spectrometer, infrared absorption spectrum, etc., and the physical properties were measured. The results are shown in Table 1 below.

[Effect of the invention] Next, the effects of the present invention are listed below.

(1) In the prior art, a method for producing aliphatic thiols via an aliphatic S-alkyl-inchuronium salt is known, but a method for producing aromatic thiols by a similar method is known. However, with the novel method of the present invention, aromatic S-aryl-isothiuronium salts are easily produced using a transition metal complex catalyst, and then highly purified aromatic thiols can be easily obtained by first hydrolysis. can be produced with high yield.

(2) The reaction is easily carried out under normal pressure and mild conditions from room temperature to 100°C, and the desired product can be obtained.

(3) When the aryl iodide of the present invention, which is an iodide among halogenated aryl compounds, is used as a raw material, the desired product can be obtained in high yield. With bromide, the desired product can be obtained, but the yield is poor, and with chloride and fluoride, the desired product cannot be obtained.

(4) The target aromatic thiols are industrially useful compounds, including agricultural chemicals, medicines, dyes, and antioxidants.

The industrial value of the present invention is extremely high because it can be used as a raw material for useful compounds such as resin stabilizers, and the desired product can be obtained in high yield.

Claims (2)

[Claims] (1) Formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R is a hydroxyl group, an amino group, an aldehyde group, an acyl group, a carboxyl group, an alkoxyl group having 1 to 3 carbon atoms, a lower alkyl group, a phenyl group) , halogen atom or hydrogen atom) and the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1, R^2, R^3 and R^4 are the same or different types. A thiourea compound represented by a lower alkyl group, a phenyl group, or a hydrogen atom) is reacted in the presence of a transition metal complex, and the formula ▲ has a mathematical formula, a chemical formula, a table, etc. ▼ (in the formula, R, R＾ Formula ▲Mathematical formula, chemical formula, There are tables, etc. ▼ Method for producing aromatic thiols represented by (wherein R indicates the above meaning). (2) The manufacturing method according to claim 1, wherein the transition metal complex is a nickel complex.