KR101896611B1 - Manufacturing method of compound having sulfonyl group - Google Patents

Abstract

The present invention relates to a process for preparing a sulfonyl group containing compound comprising reacting thiosulfonates with a electrophile in a solvent comprising nucleophilic bases. Accordingly, by using the thiosulfonate as a nucleophile, the present invention can produce a sulfonyl group-containing compound having a variety of structures at a high efficiency and a high yield through a simpler process than before.

Description

TECHNICAL FIELD [0001] The present invention relates to a method for producing a sulfonyl group-containing compound,

The present invention relates to a method for preparing a sulfonyl group-containing compound, and more particularly, to a method for producing a sulfonyl group-containing compound such as sulfones, sulfonamides and the like using a thiosulfonate as a nucleophile.

The sulfonyl group is composed of two oxygen atoms and one sulfur atom, and the sulfonyl group-containing compound is collectively referred to as an organic compound containing a sulfonyl group in its structure. Examples of such sulfonyl group-containing compounds are sulfones, sulfonamides, and the like.

Sulfones, sulfonamides, etc. have recently become known due to their pharmacological and chemical usefulness. As a result, there is a growing interest in a method for easily preparing sulfonyl group-containing compounds having various structures have.

For example, conventionally, a method of preparing a sulfonyl group-containing compound through the oxidation reaction of sulfides with a precursor, or a transition metal catalyst cross-coupling reaction of a sulfinate with a precursor, A method for producing a sulfonyl group-containing compound having a useful substituent, and the like are known.

In the case of using a sulfinate as a precursor, it is necessary to supply a large amount of organic sulfonate compounds having various structures in order to industrially mass-produce a sulfonyl group-containing compound. In the early days when sulfinate compounds were known, sodium sulfinates and SO ₂ gas-derived sulfinates were mainly used. However, a large amount of toxic sulfur dioxide (SO ₂ ) was produced in the production of sodium sulfite There was a problem and it was difficult to use it industrially.

Recently, DABCO (DABCO (SO ₂ ) ₂ ; DABCO = 1,4-diazabicyclo [2.2.2] octane) and potassium methoxide were synthesized using a coupling reaction by metal catalysts by Willis and Mascitti A method of producing sulfinate without directly treating toxic sulfur dioxide (SO ₂ ) gas using potassium metabisulfite (K ₂ S ₂ O ₅ ) has been reported.

As such, it becomes possible to provide a variety of sulfinate derivatives, and thus there is a growing demand for a technique capable of industrially mass-producing sulfone group-containing compounds using sulfinate as a precursor.

A related art is Korean Patent Laid-Open Publication No. 10-1992-0007989.

An object of the present invention is to provide a process for producing a sulfonyl group-containing compound which produces sulfonyl group-containing compounds having various structures at high efficiency and high yield.

One embodiment of the present invention is directed to a method for preparing a sulfonyl group containing compound comprising reacting a thiosulfonate compound with an electrophile in a solvent comprising nucleophilic bases.

The sulfonyl group-containing compound may include at least one of a sulfon compound and a sulfonamide compound.

The thiosulfonate compound may be a compound represented by the following general formula (1).

[Chemical Formula 1]

R ¹ -S (= O) ₂ -SR ²

In Formula 1, R ¹ and R ² each independently represent a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, a substituted or unsubstituted 3 to 20 carbon atom A substituted or unsubstituted aryl group having 6 to 20 carbon atoms, or a substituted or unsubstituted heteroaryl group having 3 to 20 carbon atoms.

The nucleophilic base may comprise an amidine-type bases.

The amidine type base may include at least one of triazabicyclodecene, diazabicyclodecene, tetramethylguanidine, and methyltrijabaiycyclodecene.

The nucleophilic base may comprise amine-type bases.

The amine type base may include diisopropylethylamine.

The nucleophilic base may include a carbonate.

The carbonate may include at least one of potassium carbonate (K ₂ CO ₃ ) and cesium carbonate (Cs ₂ CO ₃ ).

The sulfonyl group-containing compound may be a sulfonate compound, and the electrophile may be a compound represented by the following formula (2A).

(2A)

R ³ -X

In Formula 2A, R ³ represents a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 20 carbon atoms, A substituted or unsubstituted aryl group having 6 to 20 carbon atoms; X may be hydrogen or halogen.

Specifically, in Formula 2A, R ³ is a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms or a substituted or unsubstituted aryl group having 6 to 20 carbon atoms; X may be halogen.

The sulfonyl group-containing compound may be a sulfonamide compound, and the electrophile may be a compound represented by the following formula (2B).

(2B)

A-X

In Formula 2B, A is a substituted or unsubstituted amine group; X may be hydrogen or halogen.

The solvent may include at least one of toluene, ethanol, tetrahydrofuran, acetylacetone, dimethylsulfoxide, dimethylformamide, dichloroethane and acetonitrile.

The equivalent ratio of the thiosulfonate to the electrophile may be from 1: 0.5 to 1: 5.

In one embodiment, the nucleophilic base is cesium carbonate and the solvent may be ethanol.

In one embodiment, the nucleophilic base is cesium carbonate and the solvent may be toluene.

In one embodiment, the nucleophilic base is triazabicyclo-decene, and the solvent may be tetrahydrofuran.

In one embodiment, the nucleophilic base is triaza bicyclodecene, and the solvent may be acetonitrile.

In one embodiment, the nucleophilic base is cesium carbonate and the solvent may be acetylacetone and ethanol.

The present invention can provide a method for producing a sulfonyl group-containing compound having a variety of structures at a high efficiency and a high yield by using a thiosulfonate as a nucleophile through a simpler process than the conventional process.

One embodiment of the present invention is directed to a method for preparing a sulfonyl group containing compound comprising reacting a thiosulfonate compound with an electrophile in a solvent comprising nucleophilic bases. Accordingly, by using the thiosulfonate as a nucleophile, the present invention can produce a sulfonyl group-containing compound having a variety of structures at a high efficiency and a high yield through a simpler process than before.

The method for preparing a sulfonyl group-containing compound comprises contacting a thiosulfonate compound with a solvent containing a nucleophilic base to form sulfinate anions at a high efficiency through a nucleophilic base, wherein the -sulfinate anion To prepare a sulfonyl group-containing compound in which the organic thio group of the thiosulfonate is substituted by the electrophile.

The sulfonyl group-containing compound may be one containing at least one of sulfones and sulfonamides.

For example, the method for preparing a sulfonyl group-containing compound can be carried out by using a toxic sulfur dioxide gas, anaerobic cryogenic photolytic condition, and N-hydroxy-2-thiopyridone esters A sulfone group-containing compound such as a sulfone compound or a sulfonamide compound can be produced in an excellent yield.

The thiosulfonate compound is not limited as long as it is an organic thiosulfonate compound, and may be, for example, a compound represented by the following formula (1).

[Chemical Formula 1]

R ¹ -S (= O) ₂ -SR ²

In Formula 1, R ¹ and R ² each independently represent a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, a substituted or unsubstituted 3 to 20 carbon atom A substituted or unsubstituted aryl group having 6 to 20 carbon atoms, or a substituted or unsubstituted heteroaryl group having 3 to 20 carbon atoms. In this case, it is possible to prepare chemically useful sulfonyl group-containing compounds having various types of organic substituent groups, and the formation of sulfinate anions is further promoted, so that the yield of sulfonyl group-containing compounds can be improved.

As used herein, the term " substituted or unsubstituted " means that the chemical structure of the compound is substituted with at least one substituent, and examples of the substituent include an alkyl group, an alkoxy group, an alkenyl group, A hydrocarbon group having 1 to 10 carbon atoms such as an acryloyl group, an acryloyl group, an acryloyl group, a methacryloyl group, an acryloyloxy group, a methacryloyloxy group or an aryl group, or a halogen group.

The thiosulfonate compound represented by the above formula (1) is, for example, S-phenyl benzenesulfonothiolate, S-4-methoxyphenyl 4-methoxybenzenesulfonate thiolate (S-4 4-methoxybenzenesulfonothiolate, Sp-tolyl 4-methylbenzenesulfonothioate, S-4-fluorophenyl 4-fluorobenzenesulfonate thiolate (S-4-fluorophenyl 4 S-4-chlorobenzenesulfonothioate, S-4-chlorophenyl 4-chlorobenzenesulfonothioate, S-octyl octane-1-sulfonothiolate, And so on.

The nucleophilic base is included in the solvent to effect the mediation of the thiosulfonate compound being converted to a sulfinate anion. When a nucleophilic base is used as described above, the formation of a radical compound in which the electrophile is directly reacted with the thiosulfonate and the organic thio group is trapped in the electrophile can be remarkably reduced.

The nucleophilic base may be a compound comprising at least one of an organic base and an inorganic base. In this case, the efficiency of the mediation action can be improved to further improve the efficiency of conversion of the thiosulfonate to the sulfinate anion.

Specifically, the organic base may include guanidine-type bases rather than amidine-type bases.

The guanidine base may be, for example, 1,5-triazabicyclo [4.4.0] dec-1-ene (TBD), 1,8-diazabicyclo [5.4.0] undec-7-ene, DBU, 1,1,3,3-tetramethylguanidine, 7-methyl-1,5,7-triazabicyclo [4.4.0] dec- 5-enem Me-TBD) and the like. One of the above examples may be used alone, or two or more of them may be used in combination.

Specifically, the organic base may include aliphatic amine-type bases rather than amine-type bases.

The amine type base may include an aliphatic amine having 1 to 30 carbon atoms, such as diisopropylethyl amine (DIPEA). The aliphatic amine may be of a chain type, a branched type, a cyclic type, and the like.

The chain or cyclic aliphatic amines include, for example, piperidine, pyrrolidine, N-benzylmethylamine, benzylamine, butylamine, / Day < / RTI > / secondary amine.

In one embodiment, when an aliphatic amine is used as the amine-type base, a heteroaromatic amine (e.g., N, N-dimethylaminopyridine (DMAP) and 1,4-diazabicyclo [2.2. 2] octane (DABCO)) can be realized.

Specifically, the inorganic base may include a carbonate. In this case, formation of a radical including an organic thio group can be further reduced.

The carbonate may be, for example, potassium carbonate (K ₂ CO ₃ ), cesium carbonate (Cs ₂ CO ₃ ), or the like. One of the above examples may be used alone, or two or more of them may be used in combination.

In one embodiment, when cesium carbonate (Cs ₂ CO ₃ ) is used as the nucleophilic base, the formation of radicals containing organic thio groups is further reduced and the efficiency of conversion of the thiosulfonate to the sulfinate anion is further enhanced The yield of the sulfone compound can be further increased.

The electrophile is trapped in the sulfinate anion to introduce the desired organic functional group into the sulfonyl group-containing compound.

The electrophile is not particularly limited, but may be specifically a compound represented by the following formula (2).

(2)

R-X

In Formula 2, R represents a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 20 carbon atoms, a substituted or unsubstituted An aryl group having 6 to 20 carbon atoms or a substituted or unsubstituted amide group; X is hydrogen or halogen. In this case, the R group in the above formula (2) is converted into an R + cation group during the reaction to improve the coupling efficiency with the sulfinate anion, and industrially useful substituents can be introduced into various types.

Specifically, the sulfonyl group-containing compound may be a sulfonate compound, and the electrophile may be a compound represented by the following formula (2A).

(2A)

R ³ -X

In Formula 2A, R ³ represents a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 20 carbon atoms, A substituted or unsubstituted aryl group having 6 to 20 carbon atoms; X may be hydrogen or halogen.

More specifically, in Formula 2A, R ³ is a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms or a substituted or unsubstituted aryl group having 6 to 20 carbon atoms; X may be halogen. In this case, the yield of the sulfone compound can be further improved.

The compound represented by the formula (2A) may be, for example, benzyl bromide, 3-methoxybenzyl bromide, 4-fluorobenzyl bromide, 3,5-bis Benzyl bromide, 3,5-bis (trifluoromethyl) benzyl bromide, 2-nitrobenzyl bromide, octyl bromide, methyl iodide, allyl bromide, It is also possible to use allyl bromide, 2-bromoacetophenone, 2-bromopropiophenone, benzyl bromoacetate, 2-chlorobenzothiazole ), Diphenyliodonium trifluoromethanesulfonate, and the like.

Specifically, the sulfonyl group-containing compound may be a sulfonamide compound, and the electrophile may be a compound represented by the following formula (2B). In this case, the yield of the sulfonamide compound can be further improved.

(2B)

A-X

In Formula 2B, A is a substituted or unsubstituted amine group; X may be hydrogen or halogen.

More specifically, when the compound of Formula 2B X is hydrogen, a halogenating agent may be added as an additive to proceed the reaction. In this case, the yield of sulfonamide can be further improved.

The halogenating agent is not particularly limited and may be, for example, N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), iodine . ≪ / RTI >

In one embodiment, when X of the compound of Formula 2B is hydrogen, the compound may be morpholine and may be converted to a halogenating agent to replace the hydrogen of the morpholine (X of the 2B compound) with a halogen. N-chlorosuccinimide (NCS), bromosuccinimide (NBS), iodine (I2) and the like can be added during the reaction to form sulfonamide in a more excellent yield.

The chain or cyclic amine may be, for example, piperidine, pyrrolidine, N-benzylmethylamine, benzylamine, butylamine or the like. / Day < / RTI > / secondary amine.

The solvent may include at least one of toluene, ethanol, tetrahydrofuran, acetylacetone, dimethylsulfoxide, dimethylformamide, dichloroethane, and acetonitrile. In this case, it is possible to reduce the formation of radicals by the action of the electrophile directly on the thiosulfonate, and to improve the efficiency of the nucleophilic base mediated action, thereby further improving the yield of the sulfonyl group-containing compound.

Specifically, when a mixture of toluene, ethanol, tetrahydrofuran, acetylacetone, acetylacetone, and ethanol is used as a solvent, the efficiency with which the nucleophilic base mediates the action is improved to further improve the yield of the sulfonyl group-containing compound .

More specifically, when the acetylacetone and ethanol are mixed, they can be mixed at an equivalent ratio of 1: 1 to 7: 1, for example, 4: 1. In this case, the acetylacetone reacts rapidly with the organic thio group which is removed when the sulfinate anion is generated from the thiosulfonate, so that the efficiency of reacting the sulfinate anion formed during the reaction with the electrophile introduced into the reactant is improved, and the yield of the desired product Can be further improved.

In one embodiment, acetylacetone and ethanol may be used as the solvent in an equivalent ratio of 4: 1. In this case, the solvent has a possibility that the organic thio group liberated as the sulfinate anion is generated in the thiosulfonate during the reaction acts competitively with the electrophile (Formula 2, Formula 2A, Formula 2B, etc.) It is possible to further improve the efficiency of the reaction.

In the method for producing a sulfonyl group-containing compound of the present invention, the equivalence ratio of the thiosulfonate compound to the electrophile may be appropriately changed depending on the kind of the electrophile, but it is specifically 1: 0.5 to 1: 5, more specifically 1: To 1: 2. Within this range, the reaction efficiency between the sulfinate anion formed through the nucleophilic base and the electrophile may be further improved.

In the method for producing a sulfonyl group-containing compound of the present invention, the equivalence ratio of the thiosulfonate compound to the nucleophilic base may be specifically 1: 0.5 to 1: 5, more specifically 1: 1 to 1: 2. Within this range, the reaction efficiency between the sulfinate anion formed through the nucleophilic base and the electrophile may be further improved.

In the method for producing a sulfonyl group-containing compound of the present invention, the content of the nucleophilic base may be appropriately changed according to the content of the thiosulfonate compound, but may be specifically 0.1 M to 5 M, more specifically 0.5 M to 3 M. Within this range, the reaction efficiency between the sulfinate anion formed through the nucleophilic base and the electrophile may be further improved.

In the method for producing a sulfonyl group-containing compound of the present invention, the concentration of the solvent may be appropriately varied depending on the content and type of the thiosulfonate compound and the nucleophilic base, but is specifically in the range of 0.1 M to 5 M, Lt; / RTI > Within this range, the reaction efficiency between the sulfinate anion formed through the nucleophilic base and the electrophile may be further improved.

In the method for producing a sulfonyl group-containing compound of the present invention, the reaction temperature may be appropriately changed depending on the content and type of the thiosulfonate compound, the nucleophilic base and the electrophile, but is specifically from 50 ° C to 150 ° C, more specifically from 65 Deg.] C to 100 [deg.] C. Within this range, the yield of the sulfonyl group-containing compound can be further improved.

In one embodiment, the nucleophilic base is cesium carbonate and the solvent may be ethanol. In this case, the intermediates in the reaction with the halide electrophiles themselves, particularly with the electrophiles including alkyl halides, can be improved, and the yield of the sulfonyl group-containing compounds can be further improved while reducing the equivalence of the nucleophilic bases introduced.

In one embodiment, the nucleophilic base is cesium carbonate and the solvent may be toluene. In this case, the intermediates are excellent in the reaction with the halide electrophiles themselves, especially the electrophiles including aryl halides, so that the yield of sulfonyl group-containing compounds can be further improved while reducing the equivalence of nucleophilic bases introduced.

In one embodiment, the nucleophilic base is triazabicyclo-decene, and the solvent may be tetrahydrofuran. In such a case, the yield of the sulfonyl group-containing compound can be further improved because of its excellent intermediacy in the reaction with the electrophiles including halide electrophiles themselves, particularly aryl halides.

In one embodiment, the nucleophilic base is triaza bicyclodecene, and the solvent may be acetonitrile. In such a case, the yield of the sulfonyl group-containing compound can be further improved because of its excellent intermediacy in the reaction with the electrophiles including halide electrophiles themselves, particularly aryl halides.

In one embodiment, the nucleophilic base is cesium carbonate and the solvent may be acetylacetone and ethanol. In this case, the intermediates are excellent in the reaction with the halide electrophiles themselves, especially the electrophiles including aryl halides, so that the yield of sulfonyl group-containing compounds can be further improved while reducing the equivalence of nucleophilic bases introduced.

Example

Hereinafter, the structure and operation of the present invention will be described in more detail with reference to specific examples of the present invention. It should be understood, however, that the present invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover various modifications and similarities.

The contents not described here are sufficiently technically inferior to those skilled in the art, and a description thereof will be omitted.

Production Example 1

Preparation of Thiosulfonates Compounds

(4.8 mg, 0.025 mmol) and triaza bicyclodecene (TBD, 7.1 mg, 0.05 mmol) were dissolved in tetrahydrofuran (THF, 1 mL) was added thiophenol (159 μL, 1.5 mmol) and benzyl alcohol (52 μL, 0.50 mmol). The resulting solution was stirred at 65 [deg.] C for 18 hours under 1 atmosphere of oxygen. Thereafter, the product was decanted and the solvent was removed. The residue was purified by column chromatography on silica gel eluting with hexane and ethyl acetate to give the desired thiosulfonate compound.

Examples 1 to 16

(Example 1)

Benzyl bromide (60 μl, 0.50 mmol) was added to a solution of S-phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol), which is a thiosulfonate compound, and cesium carbonate (Cs ₂ CO ₃ ) Was added to the seal tube containing the mixture. To proceed the reaction, 0.5 ml (0.5 M) of ethanol (EtOH) was added and the vessel was closed and stirred at 90 ° C for 16 hours. The product was cooled and then diluted with dichloromethane (DCM) and filtered. The filtrate was concentrated by rotary evaporation and the residue was purified by column chromatography (silica gel, 3% ethyl acetate in hexane) to produce the desired sulfones.

(Examples 2 to 16)

The reaction was carried out in the same manner as in Example 1, except that the kind, content and reaction conditions of the reactants were changed as shown in Table 1 below.

However, when THF is used as a solvent, the product is not diluted with dichloromethane (DCM) and filtered immediately after cooling.

Thiosulfonate
(Equivalent ratio) An invitation itself
(Equivalent ratio) Nucleophilic base
(Equivalent ratio) menstruum Reaction temperature
(° C) product Yield (%) Example 1 Ph-S (= O) _2- SPh (1) BnBr (2) TBD (2) Toluene 100 C1 89 Example 2 Ph-S (= O) _2- SPh (1) BnBr (2) DBU (2) Toluene 100 C1 81 Example 3 Ph-S (= O) _2- SPh (1) BnBr (2) TMG (2) Toluene 100 C1 70 Example 4 Ph-S (= O) _2- SPh (1) BnBr (2) Me-TBD (2) Toluene 100 C1 73 Example 5 Ph-S (= O) _2- SPh (1) BnBr (2) DIPEA (2) Toluene 100 C1 71 Example 6 Ph-S (= O) _2- SPh (1) BnBr (2) TBD (2) CH ₃ CN 80 C1 91 Example 7 Ph-S (= O) _2- SPh (1) BnBr (2) TBD (2) THF 65 C1 99 Example 8 Ph-S (= O) _2- SPh (1) BnBr (2) TBD (2) EtOH 90 C1 87 Example 9 Ph-S (= O) _2- SPh (1) BnBr (2) TBD (1) THF 65 C1 81 Example 10 Ph-S (= O) _2- SPh (1) BnBr (2) Cs ₂ CO ₃ (2) Toluene 100 C1 97 Example 11 Ph-S (= O) _2- SPh (1) BnBr (2) Cs ₂ CO ₃ (2) EtOH 90 C1 99 Example 12 Ph-S (= O) _2- SPh (1) BnBr (2) Cs ₂ CO ₃ (2) THF 65 C1 91 Example 13 Ph-S (= O) _2- SPh (1) BnBr (2) Cs ₂ CO ₃ (1) EtOH 90 C1 99 Example 14 Ph-S (= O) _2- SPh (1) BnBr (2) Cs ₂ CO ₃ (0.5) EtOH 90 C1 61 Example 15 Ph-S (= O) _2- SPh (1) BnBr (2) K ₂ CO ₃ (2) EtOH 90 C1 89 Example 16 Ph-S (= O) _2- SPh (1) BnBr (2) Cs ₂ CO ₃ (1) EtOH r.t. C1 88 Ph-S (= O) _2- SPh: S-phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol)
BnBr: benzyl bromide (BnBr, 60 [mu] L, 0.50 mmol)
C1: (Benzylsulfonyl) benzene
TBD: 1,5,7-triazabicyclo [4.4.0] dec-1-ene
DBU: 1,8-diazabicyclo [5.4.0] undec-7-ene
TMG: 1,1,3,3-tetramethylguanidine
Me-TBD: 7-methyl-1,5,7-triazabicyclo [4.4.0] dec-5-ene
DIPEA: Diisopropylethyl amine
DMAP: N, N-dimethylaminopyridine
DABCO: 1,4-diazabicyclo [2.2.2] octane
rt: room temperature
EtOH: ethanol
THF: tetrahydrofuran

(Identification of the compounds prepared in Examples 1 to 16)

It was confirmed that benzylsulfonyl benzene (C1, (benzylsulfonyl) benzene) was formed as a white solid sulfone compound (Mp: 148-150 ° C)

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.63-7.56 (3H, m), 7.45-7.41 (2H, m), 7.33-7.22 (3H, m), 7.08 (2H, d, J = 8.0 Hz), 4.30 (2 H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz)?: 137.7, 133.6, 130.7, 128.8, 128.7, 128.6, 128.5, 128.0, 63.0. HRMS (EI, m / z) : calcd for C 13 H 12 O 2 S [M] +, 232.0558; found, 232.0555. FTIR (neat): 3030, 2963, 1302, 1152, 1126 cm < ^{-1 &} gt ;.

Examples 17 to 42

Except that the type of nucleophilic base, the kind of the electrophile, the content, and the reaction conditions were changed as shown in Table 2 below.

Thiosulfonate compound (equivalent ratio) An invitation itself
(Equivalent ratio) Nucleophilic base
(Equivalent ratio) menstruum Reaction temperature (캜) product Yield (%) Example 17 Ph-S (= O) _2- SPh (1) B2 (2) Cs ₂ CO ₃ (2) EtOH 90 C2 99 Example 18 Ph-S (= O) _2- SPh (1) B2 (2) TBD (2) THF 65 C2 94 Example 19 Ph-S (= O) _2- SPh (1) B3 (2) Cs ₂ CO ₃ (2) EtOH 90 C3 96 Example 20 Ph-S (= O) _2- SPh (1) B3 (2) TBD (2) THF 65 C3 95 Example 21 Ph-S (= O) _2- SPh (1) B4 (2) Cs ₂ CO ₃ (2) EtOH 90 C4 74 Example 22 Ph-S (= O) _2- SPh (1) B4 (2) TBD (2) THF 65 C4 49 Example 23 Ph-S (= O) _2- SPh (1) B5 (2) Cs ₂ CO ₃ (1) EtOH 90 C5 (D5) 54 (36) Example 24 Ph-S (= O) _2- SPh (1) B5 (2) TBD (2) THF 65 C5 (D5) 26 (73) Example 25 Ph-S (= O) _2- SPh (1) B5 (2) Cs ₂ CO ₃ (1) AcAcH: EtOH 90 C5 (D5) 94 (0) Example 26 Ph-S (= O) _2- SPh (1) B6 (2) Cs ₂ CO ₃ (1) EtOH 90 C6 97 Example 27 Ph-S (= O) _2- SPh (1) B6 (2) TBD (2) THF 65 C6 87 Example 28 Ph-S (= O) _2- SPh (1) B7 (2) Cs ₂ CO ₃ (1) EtOH 90 C7 96 Example 29 Ph-S (= O) _2- SPh (1) B7 (2) TBD (2) THF 65 C7 71 Example 30 Ph-S (= O) _2- SPh (1) B8 (2) Cs ₂ CO ₃ (1) EtOH 90 C8 (D8) 33 (47) Example 31 Ph-S (= O) _2- SPh (1) B8 (2) TBD (1) THF 65 C8 (D8) 65 (2) Example 32 Ph-S (= O) _2- SPh (1) B8 (2) Cs ₂ CO ₃ (1) AcAcH: EtOH 90 C8 (D8) 86 (0) Example 33 Ph-S (= O) _2- SPh (1) B9 (2) Cs ₂ CO ₃ (1) EtOH 90 C9 (D9) 34 (51) Example 34 Ph-S (= O) _2- SPh (1) B9 (2) TBD (2) THF 65 C9 (D9) 20 (75) Example 35 Ph-S (= O) _2- SPh (1) B9 (2) Cs ₂ CO ₃ (1) AcAcH: EtOH 90 C9 (D9) 71 (12) Example 36 Ph-S (= O) _2- SPh (1) B10 (2) Cs ₂ CO ₃ (1) EtOH 90 C10 48 Example 37 Ph-S (= O) _2- SPh (1) B10 (2) TBD (1) THF 65 C10 57 Example 38 Ph-S (= O) _2- SPh (1) B11 (2) TBD (1) THF 65 C11 63 Example 39 Ph-S (= O) _2- SPh (1) B12 (2) Cs ₂ CO ₃ (1) EtOH 90 C12 59 Example 40 Ph-S (= O) _2- SPh (1) B12 (2) TBD (2) THF 65 C12 83 Example 41 Ph-S (= O) _2- SPh (1) B13 (2) Cs ₂ CO ₃ (1) EtOH 90 C13 61 Example 42 Ph-S (= O) _2- SPh (1) B13 (2) TBD (2) THF 65 C13 42 Ph-S (= O) _2- SPh: S-phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol)
B2: 3-methoxybenzyl bromide (71 L, 0.50 mmol)
B3: 4-Fluorobenzyl bromide (63 [mu] L, 0.50 mmol)
B4: 3,5-Bis (trifluoromethyl) benzyl bromide (96 L, 0.50 mmol)
B5: 2-nitrobenzyl bromide (110 mg, 0.50 mmol)
B6: octyl bromide (88 [mu] L, 0.50 mmol)
B7: methyl iodide (32 [mu] L, 0.50 mmol)
B8: allyl bromide (45 [mu] L, 0.50 mmol)
B9: 2-Bromoacetophenone (102 mg, 0.50 mmol)
B10: 2-Bromopropiophenone (78 [mu] L, 0.50 mmol)
B11: benzyl bromoacetate (81 [mu] L, 0.50 mmol)
B12: 2-chlorobenzothiazole (67 [mu] L, 0.50 mmol)
B13: diphenyliodonium trifluoromethanesulfonate (220 mg, 0.50 mmol)
TBD: 1,5,7-triazabicyclo [4.4.0] dec-1-ene
EtOH: ethanol
THF: tetrahydrofuran
AcAcH: EtOH = acetylacetone (eq.1): ethanol (eq.4)

(Identification of the compounds prepared in Examples 17 to 18)

1-Methoxy-3 - ((phenylsulfonyl) methyl) benzene) was generated as a white solid sulfone compound (Mp: 112-114 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.66-7.58 (3H, m), 7.47-7.44 (2H, m), 7.15 (1H, t, J = 8.0 Hz), 6.86-6.83 (1H, m), 6.65-6.60 (2H, m), 4.28 (2H, s), 3.71 (3H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 159.4, 137.8, 133.6, 129.5, 129.3, 128.8, 128.6, 123.1, 115.9, 114.7, 62.9, 55.3 ppm. HRMS (FAB, m / z) : calcd for C 14 H 15 O 3 S [M + H] +, 263.0742; found, 263.0741. FTIR (neat): 3061, 2977, 1299, 1132 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 19-20)

It was confirmed that 1-fluoro-4 - ((phenylsulfonyl) methyl) benzene (C3: 1-Fluoro-4- (phenylsulfonyl) methyl) benzene was generated as a solid white sulfone compound (Mp: 167-168 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.65-7.59 (3H, m), 7.49-7.45 (2H, m), 7.08-7.04 (2H, m), 6.97-6.93 (2H, m), 4.28 (2H , s). ^{13 C {1 H} NMR (} CDCl 3, 100 MHz): 164.2 (d, J = 246 Hz), 137.7, 133.8, 132.6 (d, J = 9.1 Hz), 129.0, 128.6, 124.0, 115.8 (d, J = 22 Hz), 62.1. HRMS (FAB, m / z) : calcd for C 13 H 12 FO 2 S [M + H] +, 251.0542; found, 251.0540. FTIR (neat): 3061, 2945, 1303, 1150 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 21 to 22)

1 - ((phenylsulfonyl) methyl) -3,5-bis (trifluoromethyl) benzene (C4) was used as a white solid sulfone compound. ) (Mp: 147 ~ 149 ° C).

¹ H NMR (CDCl ₃ , 400 MHz): 7.84 (1H, s), 7.69-7.64 (3H, m), 7.53-7.49 (4H, m), 4.41 (2H, s). ^{13 C {1 H} NMR (} CDCl 3, 100 MHz): 137.0, 134.4, 132.0 (q, J = 33.4 Hz), 130.9 (2C), 129.3, 128.5, 122.8 (q, J = 271 Hz), 122.7 ( m), 62.1. HRMS (FAB, m / z) : calcd for C 15 H 11 F 6 O 2 S [M + H] +, 369.0384; found, 369.0385. FTIR (neat,): 3061, 2932, 1330, 1128 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 23 to 25)

(C5; 1-Nitro-2- (phenylsulfonyl) methyl) benzene, (Mp: 114-116 占 폚) as a light yellow solid solid sulfone compound and by- ((2-nitrophenyl) (phenylsulfonyl) methyl) (phenyl) sulfane, (Mp: 116-118 ° C) Was generated.

_{^{C5: 1 H NMR (CDCl 3}} , 400 MHz): 7.97 (1H, dd, J = 8.0, 1.2 Hz), 7.69-7.66 (2H, m), 7.64-7.59 (2H, m), 7.55-7.44 (4H , < / RTI > m), 4.94 (2H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz) 隆: 149.2, 137.8, 134.2, 134.1, 133.3, 130.1, 129.2, 128.3, 125.4, 122.9, 58.7. HRMS (FAB, m / z) : calcd for C 13 H 12 NO 4 S [M + H] +, 278.0487; found, 278.0485. FTIR (neat): 3068, 2924, 1529, 1352, 1320, 1147 cm < ^{-1 &} gt ;.

_{^{D5: 1 H NMR (CDCl 3}} , 400 MHz): 7.96 (1H, d, J = 8.0 Hz), 7.92 (1H, d, J = 8.4 Hz), 7.75-7.68 (3H, m), 7.61-7.51 ( 2H, m), 7.43 (2H, t, 7.2 Hz), 7.30-7.19 (5H, m), 6.65 (1H, d, J = 1.6 Hz). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 148.6, 136.8, 134.2, 133.4, 132.5, 132.3, 132.2, 130.1, 129.3 (2C), 128.9, 128.8, 127.0, 124.9, 70.2. HRMS (FAB, m / z) : calcd for C 19 H 16 NO 4 S 2 [M + H] +, 386.0521; found, 386.0518. FTIR (neat): 3065, 2919, 1528, 1348, 1322, 1150 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 26-27)

It was confirmed that 1-fluoro-4 - ((phenylsulfonyl) methyl) benzene (C6; (octylsulfonyl) benzene) was formed as a liquid sulfone compound.

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.92 (2H, dd, J = 8.0, 1.6 Hz), 7.68-7.63 (1H, m), 7.59-7.55 (2H, m), 3.10-3.06 (2H, m ), 1.74-1.67 (2H, m), 1.36-1.23 (10H, m), 0.86 (3H, t, J = 7.2 Hz). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 139.1, 133.5, 129.2, 127.9, 56.4, 31.8, 29.1, 29.0, 28.4, 22.8, 22.7, 14.2. HRMS (FAB, m / z) : calcd for C 14 H 23 O 2 S [M + H] +, 255.1419; found, 255.1418. FTIR (neat): 3065, 2927, 1306, 1147 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 28 to 29)

(Methylsulfonyl) benzene as a white solid sulfone compound (Mp: 87-89 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.96 (2H, dd, J = 8.4, 0.8 Hz), 7.69-7.64 (1H, m), 7.60-7.56 (2H, m), 3.06 (3H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 140.4, 133.6, 129.3, 127.2, 44.6. HRMS (FAB, m / z): Calcd for C ₇ H ₉ O ₂ S [M + H] ⁺ , 157.0323; found, 157.0322. FTIR (neat): 3023, 2927, 1307, 1147 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 30 to 32)

It was confirmed that (allylsulfonyl) benzene (C8; (Allylsulfonyl) benzene) as a sulfone compound was produced in a mixed state of a solid phase and a liquid phase.

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.89 (2H, dd, J = 8.4, 1.2 Hz), 7.68-7.63 (1H, m), 7.59-7.54 (2H, m), 5.85-5.74 (1H, m ), 5.36 (1H, dd, J = 10.0,4.8 Hz), 5.18-5.12 (1H, m), 3.83 (2H, dd, J = 7.6, 0.8 Hz). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 138.1, 133.7, 128.9, 128.3, 124.7, 124.5, 60.9. HRMS (FAB, m / z): calcd for C ₉ H ₁₁ O ₂ S [M + H] ⁺ , 183.0480; found, 183.0478. FTIR (neat): 3066, 2920, 1308, 1146 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 33 to 35)

Phenyl-2- (phenylsulfonyl) ethan-1-one, (Mp: 95-97 占 폚) and 1-phenyl 2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one, (Mp: 135-136 Lt; RTI ID = 0.0 > (C)) < / RTI >

_{^{C9: 1 H NMR (CDCl 3}} , 400 MHz): 7.95-7.88 (4H, m), 7.68-7.59 (2H, m), 7.56-7.52 (2H, m), 7.50-7.45 (2H, m), 4.74 (2H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 187.8, 138.6, 135.6, 134.3, 134.1, 129.2, 129.1, 128.8, 128.4, 63.4. HRMS (FAB, m / z) : calcd for C 14 H 13 O 3 S [M + H] +, 261.0585; found, 261.0583. FTIR (neat): 3064, 2947, 1680, 1323, 1154 cm < ^{-1 &} gt ;.

_{^{D9: 1 H NMR (CDCl 3}} , 400 MHz): 8.02 (2H, dd, J = 8.4, 1.2 Hz), 7.89 (2H, d, J = 8.0 Hz), 7.70-7.44 (8H, m), 7.37- 7.28 (3 H, m), 5.79 (1 H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 189.0, 136.3, 134.9, 134.4, 134.3, 133.5, 131.9, 130.6, 129.4, 129.3, 129.1, 128.8, 128.6, 75.6. HRMS (FAB, m / z) : calcd for C 20 H 17 O 3 S 2 [M + H] +, 369.0619; found, 369.0618. FTIR (neat): 3062, 1682, 1323, 1151 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 36 to 37)

(C10; 1-Phenyl-2- (phenylsulfonyl) propan-1-one) as a white solid sulfone compound (Mp: 78 To 80 [deg.] C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.98 (2H, dd, J = 7.2, 1.2 Hz), 7.80 (2H, dd, J = 7.2, 1.2 Hz), 7.66-7.58 (2H, m), 7.54- 7.45 (4H, m), 5.19 (1H, q, J = 6.8 Hz), 1.58 (3H, d, J = 7.2 Hz). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 192.3, 136.1, 136.0, 134.2, 134.0, 129.7, 129.1, 128.9, 128.7, 65.1, 13.4. HRMS (EI, m / z) : calcd for C 15 H 14 O 3 S [M] +, 274.0664; found, 274.0667. FTIR (neat): 3064, 2941, 1682, 1309, 1149 cm ^-1 .

(Identification of the compound prepared in Example 38)

It was confirmed that benzyl 2- (phenylsulfonyl) acetate (C11; Benzyl 2- (phenylsulfonyl) acetate) was formed as a liquid sulfone compound.

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.86 (2H, d, J = 8.0 Hz), 7.64 (1H, t, J = 7.6 Hz), 7.51-7.47 (2H, m), 7.36-7.34 (3H, m), 7.27-7.25 (2H, m), 5.11 (2H, s), 4.15 (2H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz) δ: 162.1, 138.5, 134.4, 134.2, 129.2, 128.7, 128.6, 128.5, 128.4, 68.1, 61.1. HRMS (EI, m / z) : calcd for C 15 H 14 O 4 S [M] +, 290.0613; found, 290.0610. FTIR (neat): 3065, 2943, 1739, 1327, 1151 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 39-40)

It was confirmed that 2- (phenylsulfonyl) benzo [d] thiazole (C12; 2- (phenylsulfonyl) benzo [d] thiazole) was formed as a white solid sulfone compound (Mp: 159-161 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 8.17-8.13 (3H, m), 7.96 (1H, dd, J = 7.6, 0.8 Hz), 7.68-7.64 (1H, m), 7.59-7.50 (4H, m ). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 167.1, 152.8, 138.4, 137.0, 134.5, 129.5, 128.9, 127.9, 127.5, 125.5, 122.2. HRMS (FAB, m / z) : calcd for C 13 H 10 NO 2 S 2 [M + H] +, 276.0153; found, 276.0151. FTIR (neat): 3092, 3061, 1329, 1316, 1159 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 41 to 42)

It was confirmed that sulfone compound (C13: sulfonyldibenzene) was formed as a white solid sulfone compound (Mp: 123-125 ° C).

¹ H NMR (CDCl ₃ , 400 MHz): 7.96-7.93 (4H, m), 7.58-7.48 (6H, m). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 141.5, 133.2, 129.3, 127.6. HRMS (FAB, m / z) : calcd for C 12 H 11 O 2 S [M + H] +, 219.0480; found, 219.0479. FTIR (neat, cm ^-1 ): 3065, 1309, 1154 cm ^-1 .

Examples 43 to 52

The procedure of Example 1 was repeated, except that the kind of nucleophilic base, kind of electrophile, content and reaction conditions were changed as shown in Table 3 below.

Thiosulfonate compound (equivalent ratio) An invitation itself
(Equivalent ratio) Nucleophilic base
(Equivalent ratio) menstruum Reaction temperature
(° C) product Yield (%) Example 43 A2 (1) BnBr (2) Cs ₂ CO ₃ (1) EtOH 90 C14 94 Example 44 A2 (1) BnBr (2) TBD (2) THF 65 C14 27 Example 45 A3 (1) BnBr (2) Cs ₂ CO ₃ (1) EtOH 90 C15 93 Example 46 A3 (1) BnBr (2) TBD (2) THF 65 C15 99 Example 47 A4 (1) BnBr (2) Cs ₂ CO ₃ (1) EtOH 90 C16 85 Example 48 A4 (1) BnBr (2) TBD (2) THF 65 C16 71 Example 49 A5 (1) BnBr (2) Cs ₂ CO ₃ (1) EtOH 90 C17 88 Example 50 A5 (1) BnBr (2) TBD (2) THF 65 C17 70 Example 51 A6 (1) BnBr (2) Cs ₂ CO ₃ (1) EtOH 90 C18 96 Example 52 A6 (1) BnBr (2) TBD (2) THF 65 C18 15 BnBr: benzyl bromide (BnBr, 60 [mu] L, 0.50 mmol)
A2: S-4-methoxyphenyl 4-methoxybenzenesulfonothiolate (77.6 mg, 0.25 mmol)
A3: Sp-tolyl 4-methylbenzenesulfonothioate (69.6 mg, 0.25 mmol)
A4: S-4-fluorophenyl 4-fluorobenzenesulfonothioate (71.6 mg, 0.25 mmol)
A5: S-4-chlorophenyl 4-chlorobenzenesulfonothioate (79.8 mg, 0.25 mmol)
A6: S-octyl octane-1-sulfonothiolate (80.6 mg, 0.25 mmol)

(Identification of the compounds prepared in Examples 43 to 44)

(Benzylsulfonyl) -4-methoxybenzene as a white solid sulfone compound (Mp: 101-103 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.53 (2H, dd, J = 6.8, 2.0 Hz), 7.31-7.24 (3H, m), 7.09 (2H, d, J = 6.8 Hz), 6.89 (2H, dd, J = 6.8, 2.0 Hz), 4.28 (2H, s), 3.85 (3H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 163.6, 130.8, 130.7, 129.3, 128.6, 128.5, 128.4, 114.0, 63.2, 55.8. HRMS (EI, m / z) : calcd for C 14 H 14 O 3 S [M] +, 262.0664; found, 262.0664. FTIR (neat): 3031, 2975, 1315, 1296, 1153 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 45 to 46)

It was confirmed that 1- (benzylsulfonyl) -4-methylbenzene (C15; 1- (Benzylsulfonyl) -4-methylbenzene) was generated as a white solid sulfone compound (Mp: 146-148 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.50 (2H, d, J = 8.4 Hz), 7.32-7.22 (5H, m), 7.09 (2H, d, J = 6.8 Hz), 4.28 (2H, s) , 2.41 (3 H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz)?: 144.6, 134.9, 130.8, 129.4, 128.6, 128.5, 128.4, 128.2, 62.9, 21.8. HRMS (EI, m / z) : calcd for C 14 H 14 O 2 S [M] +, 246.0715; found, 246.0714. FTIR (neat): 3031, 2974, 2924, 1303, 1155 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 47 to 48)

It was confirmed that 1- (benzylsulfonyl) -4-fluorobenzene (C16; 1- (Benzylsulfonyl) -4-fluorobenzene) was generated as a white solid sulfone compound (Mp: 155-157 ° C).

¹ H NMR (CDCl ₃ , 400 MHz): 7.63-7.59 (2H, m), 7.34-7.24 (3H, m), 7.13-7.06 (4H, m), 4.31 (2H, s). ^{13 C {1 H} NMR (} CDCl 3, 100 MHz): 166.9 (d, 54 Hz), 133.7 (d, J = 3.1 Hz), 131.5 (d, J = 9.1 Hz), 130.7, 128.8, 128.6, 127.9 , 116.3 (d, J = 21.9 Hz), 63.1. HRMS (EI, m / z) : calcd for C 13 H 11 FO 2 S [M] +, 250.0464; found, 250.0463. FTIR (neat): 3057, 2942, 1315, 1149, 1085 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 49 to 50)

It was confirmed that 1- (benzylsulfonyl) -4-chlorobenzene (C17; 1- (Benzylsulfonyl) -4-chlorobenzene) was produced as a white solid sulfone compound (Mp: 144-146 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.54 (2H, dd, J = 8.8, 2.0 Hz), 7.41 (2H, dd, J = 8.8, 2.4 Hz), 7.35-7.25 (3H, m), 7.09 ( 2H, d, J = 7.6Hz), 4.31 (2H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz)?: 140.4, 136.2, 130.8, 130.1, 129.2, 128.9, 128.7, 127.8, 63.0. HRMS (EI, m / z) : calcd for C 13 H 11 ClO 2 S [M] +, 266.0168; found, 266.0172. FTIR (neat): 3065, 2943, 1314, 1151 cm < ^{-1 &} gt ;.

(Identification of the compounds prepared in Examples 51 to 52)

It was confirmed that ((octylsulfonyl) methyl) benzene (C18: ((octylsulfonyl) methyl) benzene) was produced as a white solid sulfone compound (Mp: 70-72 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.41-7.38 (5H, m), 4.22-4.19 (2H, m), 2.82-2.78 (2H, m), 1.81-1.75 (2H, m), 1.36-1.25 (10H, m), 0.87 (3H, t, J = 5.6 Hz). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 130.5, 129.0, 128.9, 128.1, 59.5, 51.2, 31.9, 29.2, 29.1, 28.6, 22.8, 22.0, 14.3. HRMS (EI, m / z) : calcd for C 15 H 24 O 2 S [M] +, 268.1497; found, 268.1500. FTIR (neat): 3025, 2954, 2916, 1317, 1299, 1123 cm ^-1 .

Examples 53 to 75

(Example 52)

S-phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol), NBS (90 mg, 0.5 mmol, 0.5 M) and thiocarbamate Cesium carbonate (Cs ₂ CO ₃ ), ethanol (EtOH) Was added to the seal tube containing the mixture. The reaction vessel was closed and stirred at 80 占 폚 for 16 hours. After the reaction was completed, the product was cooled, diluted with dichloromethane (DCM) and filtered. The filtrate was concentrated by rotary evaporation and then purified by column chromatography (silica gel, 6% ethyl acetate in hexane) to obtain the desired sulfonamide compound.

(Examples 54 to 75)

The procedure of Example 53 was repeated, except that the type of nucleophilic base, the kind of electrophile, the content and the reaction conditions were changed as shown in Table 4 below.

Thiosulfonate compound (equivalent ratio) An invitation itself
(Equivalent ratio) additive
(Equivalent ratio) Nucleophilic base
(Equivalent ratio) menstruum Reaction temperature
(° C) product Yield
(%) Example 53 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) DMSO 80 F1 40 Example 54 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) DMF 80 F1 74 Example 55 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) EtOH 80 F1 96 Example 56 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) CH ₃ CN 80 F1 75 Example 57 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) THF 80 F1 61 Example 58 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) DCE 80 F1 57 Example 59 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) Toluene 80 F1 46 Example 60 Ph-S (= O) _2- SPh (1) Morph
(2) I ₂ (2) Cs ₂ CO ₃ (1) EtOH 80 F1 92 Example 61 Ph-S (= O) _2- SPh (1) Morph
(2) NCS (2) Cs ₂ CO ₃ (1) EtOH 80 F1 66 Example 62 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (1) Cs ₂ CO ₃ (1) EtOH 80 F1 75 Example 63 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) EtOH 80 F1 94 Example 64 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) EtOH 80 F1 74 Example 65 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (1.5) Cs ₂ CO ₃ (1) EtOH 80 F1 98 Example 66 Ph-S (= O) _2- SPh (1) Morph
(2) NBS (2) Cs ₂ CO ₃ (1) EtOH 80 F1 84 Example 67 Ph-S (= O) _2- SPh (1) Morph
(2) N2 Cs ₂ CO ₃ (1) EtOH 90 F2 95 Example 68 Ph-S (= O) _2- SPh (1) Morph
(2) N3 Cs ₂ CO ₃ (1) EtOH 90 F3 84 Example 69 Ph-S (= O) _2- SPh (1) Morph
(2) N4 Cs ₂ CO ₃ (1) EtOH 90 F4 83 Example 70 Ph-S (= O) _2- SPh (1) Morph
(2) N5 Cs ₂ CO ₃ (1) EtOH 90 F5 65 Example 71 Ph-S (= O) _2- SPh (1) Morph
(2) N6 Cs ₂ CO ₃ (1) EtOH 90 F6 66 Example 72 A4 Morph
(2) N7 Cs ₂ CO ₃ (1) EtOH 90 F7 89 Example 73 A5 Morph
(2) N8 Cs ₂ CO ₃ (1) EtOH 90 F8 86 Example 74 A3 Morph
(2) N9 Cs ₂ CO ₃ (1) EtOH 90 F9 91 Example 75 A2 Morph
(2) N10 Cs ₂ CO ₃ (1) EtOH 90 F10 95 Ph-S (= O) _2- SPh: S-phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol)
Morph: morpholine (44 [mu] L, 0.50 mmol)
DMSO: dimethyl sulfoxide
DMF: dimethylformamide
DCE: dichoroethane
NBS: N-bromosuccinimide (90 mg, 0.5 mmol)
N2: piperidine (50 [mu] L, 0.50 mmol)
N3: pyrrolidine (42 [mu] L, 0.50 mmol)
N4: N-benzylmethylamine (65 [mu] L, 0.50 mmol)
N5: benzylamine (55 [mu] L, 0.50 mmol)
N6: butylamine (50 [mu] L, 0.50 mmol)
A4: S-4-fluorophenyl 4-fluorobenzenesulfonothioate (71.6 mg, 0.25 mmol)
A5: S-4-chlorophenyl 4-chlorobenzenesulfonothioate (79.8 mg, 0.25 mmol)
A3: Sp-tolyl 4-methylbenzenesulfonothioate (69.6 mg, 0.25 mmol)
A2: S-4-methoxyphenyl 4-methoxybenzenesulfonothiolate (77.6 mg, 0.25 mmol)

(Identification of the compounds prepared in Examples 53 to 66)

It was confirmed that 4- (phenylsulfonyl) morpholine (F1, 4- (phenylsulfonyl) morpholine) was formed as a white solid sulfonamide compound (Mp: 119-121 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.77-7.75 (2H, m), 7.65-7.61 (1H, m), 7.58-7.54 (2H, m), 3.74 (4H, t, J = 4.8 Hz), 3.00 (4H, t, J = 4.8 Hz). ^{13 C {1 H} NMR (} CDCl 3, 100 MHz): 135.0, 133.1, 129.1, 127.8, 66.2, 46.2. HRMS (EI, m / z) : calcd for C 10 H 13 NO 3 S [M] +, 227.0616; found, 227.0617. FTIR (neat): 2921, 2856, 1449, 1350, 1169 cm < ^{-1 &} gt ;.

(Identification of the compound prepared in Example 67)

It was confirmed that 1- (phenylsulfonyl) piperidine (F2, 1- (phenylsulfonyl) piperidine) was formed as a white solid sulfonamide compound (Mp: 92-94 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.77-7.74 (2H, m), 7.61-7.57 (1H, m), 7.55-7.51 (2H, m), 2.99 (4H, t, J = 5.2 Hz), 1.67-1.61 (4H, m), 1.45-1.40 (2H, m). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 136.2, 132.5, 128.9, 127.6, 47.1, 25.4, 23.7. HRMS (EI, m / z) : calcd for C 11 H 15 NO 2 S [M] +, 225.0824; found, 225.0826. FTIR (neat): 2945, 2840, 1445, 1336, 1168 cm < ^{-1 &} gt ;.

(Identification of the compound prepared in Example 68)

It was confirmed that 1- (phenylsulfonyl) pyrrolidine (Fp) was formed as a white solid sulfonamide compound (Mp: 52-54 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.86-7.81 (2H, m), 7.62-7.58 (1H, m), 7.57-7.51 (2H, m), 3.28-3.22 (4H, m), 1.79-1.72 (4H, m). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 136.7, 132.5, 128.9, 127.4, 48.1, 25.4. HRMS (EI, m / z) : calcd for C 10 H 13 NO 2 S [M] +, 211.0667; found, 211.0664. FTIR (neat): 2980, 2886, 1445, 1337, 1159 cm < ^{-1 &} gt ;.

(Identification of the compound prepared in Example 69)

It was confirmed that N-benzyl-N-methylbenzenesulfonamide (F4, N-methylbenzenesulfonamide) was formed as a white solid sulfonamide compound (Mp: 91-93 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.85-7.83 (2H, m), 7.63-7.53 (3H, m), 7.35-7.25 (5H, m), 4.14 (2H, s), 2.60 (3H, s ). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz)?: 137.2, 135.5, 132.7, 129.1, 128.6, 128.3, 127.9, 127.4, 54.3, 34.5. HRMS (EI, m / z) : calcd for C 14 H 15 NO 2 S [M] +, 261.0824; found, 261.0822. FTIR (neat): 2968, 2860, 1446, 1341, 1166 cm ^-1 .

(Identification of the compound prepared in Example 70)

It was confirmed that N-benzylbenzenesulfonamide (F5, N-benzylbenzenesulfonamide) was formed with a white solid sulfonamide compound (Mp: 86-88 DEG C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.86-7.83 (2H, m), 7.58-7.54 (1H, m), 7.50-7.45 (2H, m), 7.26-7.21 (3H, m), 7.18-7.15 (2H, m), 5.04 (1H, t, J = 6.0Hz), 4.13 (2H, d, J = 6.4Hz). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 139.8, 136.1, 132.6, 129.1, 128.6, 127.9, 127.8, 127.0, 47.4. HRMS (EI, m / z) : calcd for C 13 H 13 NO 2 S [M] +, 247.0667; found, 247.0669. FTIR (neat): 3284, 3064, 1447, 1326, 1160 cm < ^{-1 &} gt ;.

(Identification of the compound prepared in Example 71)

It was confirmed that N-butylbenzenesulfonamide (F6, N-butylbenzenesulfonamide) was formed from the sulfonamide compound of the colorless liquid phase.

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.92-7.87 (2H, m), 7.60-7.56 (1H, m), 7.54-7.49 (2H, m), 4.74 (1H, bs), 2.97-2.92 (2H m), 1.47-1.40 (2H, m), 1.33-1.24 (2H, m), 0.84 (3H, t, J = 7.2 Hz). ^{13 C {1 H} NMR (} CDCl 3, 100 MHz): 139.8, 132.6, 129.1, 127.0, 43.1, 31.8, 19.9, 13.8. HRMS (EI, m / z) : calcd for C 10 H 15 NO 2 S [M] +, 213.0824; found, 213.0821. FTIR (neat): 3284, 2960, 2873, 1447, 1325, 1161 cm < ^{-1 &} gt ;.

(Identification of the compound prepared in Example 72)

It was confirmed that 4 - ((4-fluorophenyl) sulfonyl) morpholine (F7, 4 - (4-Fluorophenyl) sulfonyl) morpholine was formed as a white solid phase sulfonamide compound (Mp: .

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.80-7.76 (2H, m), 7.28-7.22 (2H, m), 3.75 (4H, t, J = 4.8 Hz), 3.00 (4H, t, J = 4.8 Hz). ^{13 C {1 H} NMR (} CDCl 3, 100 MHz): 166.5 (d, J = 253 Hz), 131.2 (d, J = 3.8 Hz), 130.5 (d, J = 9.1 Hz), 116.5 (d, J = 22 Hz), 66.1, 46.1. HRMS (EI, m / z) : calcd for C 10 H 12 FNO 3 S [M] +, 245.0522; found, 245.0523. FTIR (neat): 2962, 2858, 1347, 1158 cm < ^{-1 &} gt ;.

(Identification of the compound prepared in Example 73)

It was confirmed that 4 - ((4-chlorophenyl) sulfonyl) morpholine (F8, 4 - ((4-Chlorophenyl) sulfonyl) morpholine was formed as a white solid phase sulfonamide compound (Mp: 149-151 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.71-7.69 (2H, m), 7.55-7.53 (2H, m), 3.74 (4H, t, J = 4.8 Hz), 3.00 (4H, t, J = 4.8 Hz). ^{13 C {1 H} NMR (} CDCl 3, 100 MHz): 139.6, 133.5, 129.4, 129.2, 66.1, 46.1. HRMS (EI, m / z) : calcd for C 10 H 12 ClNO 3 S [M] +, 261.0226; found, 261.0229. FTIR (neat): 2978, 2866, 1453, 1350, 1163 cm < ^{-1 &} gt ;.

(Identification of the compound prepared in Example 74)

It was confirmed that 4-tosylmorpholine (F9, 4-Tosylmorpholine) was formed as a white solid sulfonamide compound (Mp: 149-115 ° C).

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.64 (2H, d, J = 8.0 Hz), 7.35 (2H, d, J = 8.0 Hz), 3.73 (4H, t, J = 4.8 Hz), 2.98 (4H , t, J = 4.8 Hz), 2.44 (3H, s). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz)?: 143.8, 131.8, 129.7, 127.8, 66.1, 46.1, 21.7. HRMS (EI, m / z) : calcd for C 11 H 15 NO 3 S [M] +, 241.0773; found, 241.0775. FTIR (neat): 2972, 2851, 1452, 1346, 1165 cm < ^{-1 &} gt ;.

(Identification of the compound prepared in Example 75)

It was confirmed that 4 - ((4-methoxyphenyl) sulfonyl) morpholine (F10, 4 - ((4-Methoxyphenyl) sulfonyl) morpholine was formed as a white solid phase sulfonamide compound (Mp: 112-113 ° C) .

_{^{1 H NMR (CDCl 3, 400}} MHz): 7.70 (2H, d, J = 9.2 Hz), 7.02 (2H, d, J = 8.8 Hz), 3.88 (3H, s), 3.73 (4H, t, J = 4.8 Hz), 2.97 (4H, t, J = 4.8 Hz). ¹³ C { ¹ H} NMR (CDCl ₃ , 100 MHz): 163.0, 129.9, 126.3, 114.2, 66.1, 55.8, 46.1. HRMS (EI, m / z) : calcd for C 11 H 15 NO 4 S [M] +, 257.0722; found, 257.0719. FTIR (neat): 2974, 2852, 1454, 1347, 1162 cm < ^{-1 &} gt ;.

It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (19)

A process for preparing a sulfonic acid compound comprising reacting a thiosulfonate compound with an electrophile in a solvent comprising nucleophilic bases,
The thiosulfonate compound is a compound represented by the following formula (1)
The nucleophilic base includes amidine-type bases including at least one of triazabicyclodecene, diazabicyclodecene, tetramethylguanidine, and methyltrijabaiycyclodecene; Amine-type bases comprising diisopropylethylamine; Or a carbonate base containing at least one of potassium carbonate (K ₂ CO ₃ ) and cesium carbonate (Cs ₂ CO ₃ )
The solvent includes at least one of toluene, ethanol, tetrahydrofuran, acetylacetone, dimethylsulfoxide, dimethylformamide, dichloroethane, and acetonitrile,
Wherein the electrophile is a compound represented by the following formula (2A): < EMI ID =
[Chemical Formula 1]
R ¹ -S (= O) ₂ -SR ²
In Formula 1, R ¹ and R ² each independently represent a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, a substituted or unsubstituted 3 to 20 carbon atom A substituted or unsubstituted aryl group having 6 to 20 carbon atoms, or a substituted or unsubstituted heteroaryl group having 3 to 20 carbon atoms;
(2A)
R ³ -X
In Formula 2A, R ³ represents a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 20 carbon atoms, A substituted or unsubstituted aryl group having 6 to 20 carbon atoms; X is hydrogen or halogen.
The method according to claim 1,
In Formula 2A, R ³ is a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms or a substituted or unsubstituted aryl group having 6 to 20 carbon atoms; And X is halogen.
The method according to claim 1,
Wherein the equivalent ratio of the thiosulfonate to the electrophile is from 1: 0.5 to 1: 5.
The method according to claim 1,
Wherein the nucleophilic base is cesium carbonate and the solvent is ethanol.
The method according to claim 1,
Wherein the nucleophilic base is cesium carbonate and the solvent is toluene.
The method according to claim 1,
Wherein the nucleophilic base is triazabicyclo-decene, and the solvent is tetrahydrofuran.
The method according to claim 1,
Wherein the nucleophilic base is triazabicyclo-decene, and the solvent is acetonitrile.
The method according to claim 1,
Wherein the nucleophilic base is cesium carbonate and the solvent is acetylacetone and ethanol.
A process for preparing sulfonamides comprising reacting thiosulfonates with a electrophile in a solvent comprising nucleophilic bases,
The thiosulfonate compound is a compound represented by the following formula (1)
The nucleophilic base includes amidine-type bases including at least one of triazabicyclodecene, diazabicyclodecene, tetramethylguanidine, and methyltrijabaiycyclodecene; Amine-type bases comprising diisopropylethylamine; Or a carbonate base containing at least one of potassium carbonate (K ₂ CO ₃ ) and cesium carbonate (Cs ₂ CO ₃ )
The solvent includes at least one of toluene, ethanol, tetrahydrofuran, acetylacetone, dimethylsulfoxide, dimethylformamide, dichloroethane, and acetonitrile,
Wherein the electrophile is a compound represented by the following Formula 2B:
[Chemical Formula 1]
R ¹ -S (= O) ₂ -SR ²
In Formula 1, R ¹ and R ² each independently represent a substituted or unsubstituted alkyl group having 1 to 20 carbon atoms, a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, a substituted or unsubstituted 3 to 20 carbon atom A substituted or unsubstituted aryl group having 6 to 20 carbon atoms, or a substituted or unsubstituted heteroaryl group having 3 to 20 carbon atoms;
(2B)
AX
In Formula 2B, A is a substituted or unsubstituted amine group; X is hydrogen or halogen.
10. The method of claim 9,
Wherein the equivalent ratio of the thiosulfonate to the electrophile is from 1: 0.5 to 1: 5.
10. The method of claim 9,
Wherein the nucleophilic base is cesium carbonate and the solvent is ethanol.
10. The method of claim 9,
Wherein the nucleophilic base is cesium carbonate and the solvent is toluene.
10. The method of claim 9,
Wherein the nucleophilic base is triaza bicyclodecane, and the solvent is tetrahydrofuran.
10. The method of claim 9,
Wherein the nucleophilic base is triazabicyclo-decene, and the solvent is acetonitrile.
10. The method of claim 9,
Wherein the nucleophilic base is cesium carbonate and the solvent is acetylacetone and ethanol. delete delete delete delete