JPH0227972B2 - JIFURUOROMECHIRUCHIOEETERURUINOSEIZOHO - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for producing thiols of the general formula RSH (wherein R represents an aromatic or heterocyclic residue) by reacting them with chlorodifluoromethane.
A method for producing difluoromethylthioethers represented by RSCHF ₂ (wherein R is the same as above), particularly characterized in that the reaction is carried out in an aprotic, strongly polar solvent in the presence of a basic catalyst. .

As a method for producing corresponding difluoromethylthioethers by reacting thiols with chlorodifluoromethane, for example, the Journal of
American Chemical Society, Volume 79 (1957)
The method described on pages 5493-5496 has been used. According to this method, thiophenols are reacted with chlorodifluoromethane in methanol in the presence of a large excess of sodium methoxide for a long period of time. Additionally, in this manner, the sodium salt of thiophenol is produced using an equivalent amount of sodium methoxide and similarly reacted with chlorodifluoromethane in methanol.
The reaction is extremely slow and has little practical use, and the presence of a large excess of sodium methoxide, which is a strong base, is practically essential. Furthermore, it has been stated that under such conditions, chlorodifluoromethane reacts with methanol at a considerable rate, and difluoromethyl-methyl ether is produced as a by-product. This is not necessarily an advantageous method.

Under these circumstances, we investigated various methods for producing difluoromethylthioethers and found that a large excess of strong base is required to react thiols with chlorodifluoromethane to produce the desired difluoromethylthioethers. The inventors have now invented a method in which this reaction proceeds extremely well in a substantially non-aqueous system.

In other words, we have found that when a highly polar aprotic solvent is used as a solvent in the reaction, the desired reaction proceeds extremely well in the coexistence of an equimolar or small excess of a basic substance. . The highly polar aprotic solvent mentioned here has a dielectric constant (ε) of 15 or more, a dipole efficiency (μ) of 2.5D or more, and an E _T (30) value, which is one of the solvent polarity parameters. is 40 to 47. Typical examples of these solvents include dimethyl sulfoxide (DMSO), dimethylformamide (DMF), diethylformamide, dimethylacetamide, diethylacetamide, propylene carbonate, ethylene carbonate, acetonitrile, sulfolane, and dimethylsulfolane. , dimethylsulfone, acetone, acetophenone, nitrobenzene, benzonitrile, 1-methyl-2-pyrrolidinone, tetramethylurea, and the like. Even if these solvents contain a small amount of water or other organic solvents, it will not have a major effect, and usually 50 to 100% content can be used. As the basic substance, alkali metal hydroxides, carbonates, and bicarbonates are used. For example, relatively weak bases such as potassium carbonate, sodium carbonate, potassium bicarbonate, and sodium bicarbonate can be used, and strong bases such as caustic soda and caustic potash can also be used. Although there are no strict restrictions on the amount used, it is usually advisable to use 1 to 4 moles of the basic substance relative to the thiol.

Chlorodifluoromethane may be directly blown into the above-mentioned solvent, thiols, and a mixture of basic substances, or may be pressurized into an autoclave and raised to the reaction temperature for reaction. The reaction may be carried out using a reaction tank. In either case, the amount used is not particularly limited, but it is preferable to use chlorodifluoromethane in an amount of 1 to 10 times the mole of the thiol.

Although reaction conditions depend on the type of thiols and basic substances used, the reaction generally proceeds in the range of room temperature to 150°C, preferably in the range of 50°C to 120°C.

The method of the present invention can be applied to the production of a very wide range of difluoromethylthioethers. For example, as the organic residue represented by R- of the thiol represented by the general formula R-SH, aromatic Examples of the group include phenyl group, naphthalene group, and their nuclear substituents; when R- is a heterocycle, the heterocycle ranges widely; examples include R-SH; 2-mercaptoonasazoline; Thiohydantoin, 2-mercaptothiazole, 2-mercaptobenzothiazole, 2-mercapto-2-thiazoline, 2-mercaptoimidazole, 2-mercaptobenzothiazole, 2-mercapto-1,
3,4-oxa-diazole, 5-mercapto-
1,2,4-thiadiazole, 2-mercapto-
Examples include 1,3,4-thiadiazole, 3-mercapto-1,2,4-triazole, 5-mercapto-tetrazole, mercaptopyridine, mercaptoquinoline, 3-mercaptopyridazine, 4-mercaptopyrimidine, and the like.

When this manufacturing method is compared with conventional methods, it has the following advantages and is an extremely superior method industrially.

First, the reaction is possible in a non-aqueous system, and
The solvent itself is inert to the reaction, and by distilling off and recovering the solvent after the reaction, it can be reused as it is, and the solvent can be used efficiently.

Second, chlorodifluoromethane, which is generally used in excess, causes almost no side reactions, and the excess amount can be recovered very easily, so that expensive chlorodifluoromethane can be used effectively. Thirdly, the amount of basic substance used is extremely small compared to conventional methods, which not only improves economy but also significantly reduces the burden of wastewater treatment.

Below, typical examples of the method of the present invention will be shown, and the method of the present invention will be explained in more detail. However, these examples are merely illustrative examples of typical ones, and it goes without saying that the method of the present invention is not limited to these only, and is not limited in any way by these examples. .

Example 1 Paranitrophenylmercaptan 50g, dimethylformamide (DMF) 400ml, potassium carbonate
62g was placed in an autoclave, and 80g of chlorodifluoromethane was pressurized into it. After that, the reaction was carried out at 100℃ for 2 hours, and after the reaction was completed, the pressure was returned to normal pressure to remove excess chlorodifluoromethane, and DMF was added under reduced pressure.
After distilling off, toluene was added to the residue, the organic layer was obtained by filtration, washed with alkaline water (5% caustic soda aqueous solution) and water, the toluene was distilled off, and the product was heated at 139-141℃/ Distilled under reduced pressure at 11mmHg,
Paradifluoromethylthionitrobenzene 162g
(75% yield).

Example 2 A reaction similar to Example 1 was carried out using dimethyl sulfoxide (DMSO) instead of DMF, and paradifluoromethylthionitrobenzene was obtained with a yield of 70%.

Example 3 10 g of thiophenol was added to a mixture of 200 ml of DMF and 28 g of potassium carbonate, heated to 100°C, and reacted by introducing chlorodifluoromethane at normal pressure for 2 hours with stirring. After the reaction was completed, DMF was distilled off, 300 ml of toluene was added, the mixture was washed with alkaline water and water, and toluene was distilled off to obtain difluoromethylthiobenzene with a yield of 85%.

Example 4 4-tert-butyl-2-mercapto-
Add 4g (23mmol) of 1,3-thiazole and 7g of potassium carbonate to 60ml of DMF and heat to 90°C.
Under stirring, chlorodifluoromethane was introduced for 3 hours. After the reaction is complete, remove the solid matter,
The liquid was concentrated under reduced pressure. Dichloromethane 60 to the residue
ml was added, washed with a 5% aqueous sodium hydroxide solution and then with water, and the solvent was distilled off to obtain 3.5 g of product. This product was determined to be 4-tert-butyl-2-difluoromethylthio-1,3-thiazole by infrared spectrum and NMR spectrum measurements. Yield 63%.

NMR ( _CDCl3 )δ, 1.36 (Singlet 9H), 7.00
(Singlet 1H), 7.24 (triplet=56Hz 1H)

Claims (1)

[Claims] 1. Thiols represented by the general formula RSH (in the formula R represents an aromatic or heterocyclic residue) are chloropropyl in a strong aprotic polar solvent in the presence of a basic catalyst. A method for producing difluoromethylthioethers represented by the general formula RSCHF ₂ (wherein R is the same as above), which comprises reacting with difluoromethane. 2 The aprotic strong polar solvent has a dielectric constant (ε)
15 or more, dipole efficiency (μ) 2.5D or more, E _T (30) value, which is one of the solvent polarity parameters, is 40 to 47.
The manufacturing method according to claim 1, wherein the solvent has the following. 3. The production method according to claim 1, wherein the basic catalyst is at least one of alkali metal hydroxides, carbonates, and bicarbonates.