KR101893515B1 - Novel Method for Preparing 4-hydroxy-3-sulfanylcoumarin Derivatives or 4-hydroxy-3-sulfanylquinoline Derivatives and Their Compounds Made Thereby, and Its Use - Google Patents

Abstract

The present invention relates to 4-hydroxy-3-sulfanylcoumarin derivatives represented by chemical formula 1, 4-hydroxy-3-sulfanylquinolinone derivatives represented by chemical formula 2, novel preparation methods thereof, and uses thereof. According to the present invention, the preparation methods can reduce the preparation cost by utilizing inexpensive catalysts, and at the same time, can yield desired products with high yield. In the chemical formula 1, R_1 to R_4 are as described in the present invention. In the chemical formula 2, R_5 to R_7 are as described in the present invention.

Description

Hydroxy-3-sulfanylcoumarin derivative or a 4-hydroxy-3-sulfanylquinolinone derivative using a copper catalyst and a derivative compound prepared therefrom, and a use thereof. [0002] The present invention relates to novel methods for preparing 4-hydroxy- 3-sulfanylcoumarin Derivatives or 4-hydroxy-3-sulfanylquinoline Derivatives and Their Compounds Made Thereby, and Its Use}

The present invention relates to a novel process for producing a 4-hydroxy-3-sulfanylcoumarin derivative or a 4-hydroxy-3-sulfanylquinolinone derivative using a copper catalyst, a derivative compound produced thereby, The present invention relates to a composition for detecting cadmium.

Molecules containing C-S bonds can be found in natural products, pharmaceuticals, and functional materials that are bio-active. These sulfanylated coumarin and quinolinone derivatives exhibit a wide range of life and pharmacological activities including antifungal, antibacterial, antimicrobial and anti-HCV activities. Because of their importance and utility, various synthetic methods for sulfanylation of 4-hydroxy coumarin and hydroxy quinoline have been developed by forming C-S bonds between 3-coumarin or quinolinone and sulfanylating reagents. Representative synthetic methods for synthesizing 3-sulfanyl coumarin or 3-sulfanyl quinolinone include reacting hydrocoumarin and hydroquinolinone with the corresponding thiol or disulfide. Recently, Peddinti group has reported an iodine-catalyzed method using arylthiol as a sulfanylating reagent to synthesize 3-sulfanyl coumarin derivatives. Traditionally, sulfamide, sulfanyl halide, disulfide, thiol and sulfanate esters have been used as thiolating reagents.

Thus far, although many synthesis methods have been reported for the sulfanylation of 4-hydroxyquinolines and 4-hydroxyquinolines, most of these synthesis steps are odorous and volatile, such as thiol, disulfide and thiolate The band exhibits several drawbacks, such as the use of sulfanylating reagents, or the need for too slow reaction conditions. Therefore, a more effective and easy method is still required.

On the other hand, in recent years, aryl sulfonyl hydrazide compounds have been used as ideal and useful sulfanylation reagents for CS bond formation. In addition, copper-catalyzed direct CH functionalization has attracted considerable attention over the past decade due to the ease of accessibility and cost-effectiveness as well as the suitability of high-functionality copper metals. However, the CuBr 占 S ₂ S-catalyzed sulfanylation reaction using 4-hydroxy coumarin and 4-hydroxyquinolinone and arylsulfonyl hydrazide has not yet been reported.

1. Korean Registered Patent No. 10-0456685 (registered on November 2, 2004) 2. Korean Registered Patent No. 10-0636423 (registered on October 12, 2006)

It is an object of the present invention to provide novel 4-hydroxy-3-sulfanylcoumarin derivatives.

Another object of the present invention is to provide a novel 4-hydroxy-3-sulfanylquinolinone derivative.

It is another object of the present invention to provide a composition for detecting cadmium in water exhibiting excellent cadmium detection activity.

It is still another object of the present invention to provide a novel method for preparing a 4-hydroxy-3-sulfanyl coumarin derivative or a 4-hydroxy-3-sulfanylquinolinone derivative.

In order to achieve the above object, the present invention provides a 4-hydroxy-3-sulfanyl coumarin derivative represented by the following formula (1).

In order to accomplish the above other objects, the present invention provides a 4-hydroxy-3-sulfanyl quinolinone derivative represented by the following general formula (2).

In order to accomplish still another object of the present invention, the present invention provides a 4-hydroxy-3-sulfanylcoumarin derivative represented by the following general formula (1) or a 4-hydroxy-3-sulfanylquinolinone derivative represented by the general formula The present invention provides a composition for detecting cadmium in water.

In order to achieve the above another object, the present invention provides a process for the production of a compound of formula (I), comprising the steps of: a) reacting 4-hydroxy coumarin or 4-hydroxyquinolinone and b) sulfonyl hydrazide with CuBr.Me ₂ S as a catalyst Hydroxy-3-sulfanylcoumarin or a 4-hydroxy-3-sulfanylquinolinone derivative.

[Chemical Formula 1]

Wherein R ₁ is selected from the group consisting of hydrogen, (C ₁ -C 4) alkyl and halogen, R ₂ and R ₃ are each independently selected from hydrogen or halogen, and R ₄ is a substituted or unsubstituted phenyl group , A substituted naphthyl group and an unsubstituted thienyl group, and the substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with a (C1-C4) alkyl group, and the substituted naphthyl group is Di (C1 to C4 alkyl) amine group;

(2)

Wherein R ₅ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen, R ₆ is (C 1 -C 4) alkyl or hydrogen, and R ₇ is a substituted or unsubstituted phenyl group And substituted naphthyl groups, wherein the substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups, and the substituted naphthyl group is selected from the group consisting of di To C4 alkyl) amine groups.

According to the novel production method of the present invention, it is possible to cause a sulfanylation reaction on 4-hydroxy coumarin or 4-hydroxyquinolinone using inexpensive copper, thereby improving the production efficiency and reducing the reaction time and cost The 4-hydroxy-3-sulfanyl coumarin derivative or 4-hydroxy-3-sulfanyl quinolinone derivative thus prepared can also be used as a reactant for other useful compounds, And thus can be usefully used as a composition for detecting cadmium in water.

1 and 2 show structural formulas of the compounds prepared by the method according to an embodiment of the present invention.
FIG. 3 is a diagram illustrating the mechanism of the manufacturing method of the present invention.
FIG. 4 and FIG. 5 show the detection activity of cadmium in the water of the compound prepared by the preparation method according to an embodiment of the present invention (FIG. 4A: selective detection activity of cadmium in compound 3f, FIG. 4b: 5a: Confirmation of fluorescence intensity according to cadmium concentration at 442 nm of Compound 3f, FIG. 5b: Confirmation of the ratio of cadmium ion reacting with compound 3f)

Based on the characteristic reactivity of aryl sulfonyl hydrazide as a sulfanylating reagent, the inventors of the present invention have investigated the formation of a CS bond using a copper-catalyst, using CuBr 占_{2 2} S as a catalyst, Hydroxy-3-sulfanylquinoline and 4-hydroxy-3-sulfanylquinolinone derivatives by directly sulfanylating 4-hydroxyquinolinone and 4-hydroxyquinolinone, Hydroxy-3-sulfanylcoumarin and 4-hydroxy-3-sulfanylquinolinone derivatives prepared by the above method have an activity of detecting cadmium in water, thereby completing the present invention.

Accordingly, the present invention provides a 4-hydroxy-3-sulfanylcoumarin derivative represented by the following formula (1);

[Chemical Formula 1]

Wherein R ₁ is selected from the group consisting of hydrogen, (C ₁ -C 4) alkyl and halogen, R ₂ and R ₃ are each independently selected from hydrogen or halogen, and R ₄ is a substituted or unsubstituted phenyl group , A substituted naphthyl group and an unsubstituted thienyl group, and the substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with a (C1-C4) alkyl group, and the substituted naphthyl group is Di (C1 to C4 alkyl) amine group.

Preferably, in Formula 1, R ₁ is selected from the group consisting of hydrogen, methyl, fluoro, and chloro, and R ₂ and R ₃ are each independently selected from the group consisting of hydrogen, bromo, fluoro, and chloro And R ₄ can be selected from the group consisting of phenyl, p -tolyl, mesityl, 5- (dimethylamino) naphthalen-1-yl and 2-thienyl.

More preferably, the 4-hydroxy-3-ylsulfanyl coumarin derivatives is 4-hydroxy-3- (phenylthio) -2H- chromen-2-one, 4-hydroxy-3- (p - tolyl 2-one, 3 - ((5- (dimethylamino) naphthalen-1-yl) thiophene- Hydroxy-6-methyl-3- (phenylthio) -2H-chromen-2-one, 4-hydroxy-6-methyl 3- (p - tolyl thio) -2H- chromen-2-one, 4-hydroxy-3 (mesityl thio) -6-methyl -2H- chromen-2-one, 6-chloro-4 Chloro-4-hydroxy-3- ( p -tolylthio) -2H-chromen-2-one, 6-chloro- (Phenylthio) -2H-chromen-2-one, 6-fluoro-4-hydroxy-3- (mesitylthio) (Methylthio) -2H-chromen-2-one, 7-bromo-4-hydroxy-3- On, 7-fluoro-4-hydroxy-3 2-one, 6,8-dichloro-4-hydroxy-3- (phenylthio) -2H- Hydroxy-3- (mesitylthio) -2H-chromen-2-one and 4-hydroxy-3- (thiophen-2-ylthio) -2H-chromen- .

The present invention also provides a 4-hydroxy-3-sulfanylquinolinone derivative represented by the following formula (2);

(2)

Wherein R ₅ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen, R ₆ is (C 1 -C 4) alkyl or hydrogen, and R ₇ is a substituted or unsubstituted phenyl group And substituted naphthyl groups, wherein the substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups, and the substituted naphthyl group is selected from the group consisting of di To C4 alkyl) amine groups.

Preferably, in Formula 2, R ₅ is any one selected from the group consisting of hydrogen, methyl, isopropyl, bromo, and chloro, R ₆ is methyl or hydrogen, R ₇ is phenyl, p- , A mesityl group and a 5- (dimethylamino) naphthalen-1-yl group.

More preferably, the 4-hydroxy-3-sulfanylquinolinone derivative is 4-hydroxy-1-methyl-3- (phenylthio) quinolin- 3 - ((5-tert-butoxycarbonylamino) methyl) -3- ( p -tolylthio) quinolin- (4-hydroxy-3- (phenylthio) quinolin-2 (1H) -one, 4-hydroxy -3- (p - tolyl thio) quinolin -2 (1H) - one, 4-hydroxy-6-methyl -3- (p - tolyl thio) quinolin -2 (1H) - one, 4- Hydroxy-6-isopropyl-3- (phenylthio) quinolin-2 (1H) -one, 4- hydroxy-6-isopropyl -3- (p - tolyl thio) quinolin -2 (1H) - one, 6-bromo-4-hydroxy -3- (p - tolyl thio) quinolin -2 (1H) - (LH) -one and 6-chloro-4-hydroxy-3- ( p -tolylthio) quinolin-2 )-On ≪ / RTI >

Furthermore, the present invention provides a method for detecting cadmium in water comprising, as an active ingredient, a 4-hydroxy-3-sulfanylcoumarin derivative represented by the following formula (1) or a 4-hydroxy-3-sulfanylquinolinone derivative represented by the following formula ≪ / RTI >

[Chemical Formula 1]

Wherein R ₁ is selected from the group consisting of hydrogen, (C ₁ -C 4) alkyl and halogen, R ₂ and R ₃ are each independently selected from hydrogen or halogen, and R ₄ is a substituted or unsubstituted phenyl group , A substituted naphthyl group and an unsubstituted thienyl group, and the substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with a (C1-C4) alkyl group, and the substituted naphthyl group is Di (C1 to C4 alkyl) amine group;

(2)

Wherein R ₅ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen, R ₆ is (C 1 -C 4) alkyl or hydrogen, and R ₇ is a substituted or unsubstituted phenyl group And substituted naphthyl groups, wherein the substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups, and the substituted naphthyl group is selected from the group consisting of di To C4 alkyl) amine groups.

Preferably, in Formula 1, R ₁ is selected from the group consisting of hydrogen, methyl, fluoro, and chloro, and R ₂ and R ₃ are each independently selected from the group consisting of hydrogen, bromo, fluoro, and chloro And R ₄ can be selected from the group consisting of phenyl, p -tolyl, mesityl, 5- (dimethylamino) naphthalen-1-yl and 2-thienyl.

In Formula 2, R ₅ is any one selected from the group consisting of hydrogen, methyl, isopropyl, bromo and chloro, R ₆ is methyl or hydrogen, R ₇ is phenyl, p -tolyl, Yl group and a 5- (dimethylamino) naphthalene-1-yl group.

More preferably, the 4-hydroxy-3-ylsulfanyl coumarin derivatives is 4-hydroxy-3- (phenylthio) -2H- chromen-2-one, 4-hydroxy-3- (p - tolyl 2-one, 3 - ((5- (dimethylamino) naphthalen-1-yl) thiophene- Hydroxy-6-methyl-3- (phenylthio) -2H-chromen-2-one, 4-hydroxy-6-methyl 3- (p - tolyl thio) -2H- chromen-2-one, 4-hydroxy-3 (mesityl thio) -6-methyl -2H- chromen-2-one, 6-chloro-4 Chloro-4-hydroxy-3- ( p -tolylthio) -2H-chromen-2-one, 6-chloro- (Phenylthio) -2H-chromen-2-one, 6-fluoro-4-hydroxy-3- (mesitylthio) (Methylthio) -2H-chromen-2-one, 7-bromo-4-hydroxy-3- On, 7-fluoro-4-hydroxy-3 2-one, 6,8-dichloro-4-hydroxy-3- (phenylthio) -2H- Hydroxy-3- (mesitylthio) -2H-chromen-2-one and 4-hydroxy-3- (thiophen-2-ylthio) -2H-chromen- .

The 4-hydroxy-3-sulfanylquinolinone derivative can also be obtained by reacting 4-hydroxy-1-methyl-3- (phenylthio) quinolin- - (p-tolyl thio) quinolin -2 (1H) - one, 4-hydroxy-3 (mesityl thio) -1-methyl-quinolin -2 (1H) - one, 3 - ((5- (dimethylamino ), 4-hydroxy-3- (phenylthio) quinolin-2 (1 H) -one, 4-hydroxynaphthalene- hydroxy -3- (p-tolyl thio) quinolin -2 (1H) - one, 4-hydroxy-6-methyl -3- (p-tolyl thio) quinolin -2 (1H) - one, 4-hydroxy- Hydroxy-6-isopropyl-3- (phenylthio) quinolin-2 (1H) -one, 4-hydroxy- 6-isopropyl -3- (p - tolyl thio) quinolin -2 (1H) - one, 6-bromo-4-hydroxy -3- (p - tolyl thio) quinolin -2 (1H) - one, 6 Hydroxy-3- ( p -tolylthio) quinolin-2 (1H) -one and 6-chloro-4-hydroxy- Composed of Can be selected from the group.

In one embodiment of the present invention the 4-hydroxy-3-ylsulfanyl coumarin is 4-hydroxy-6-methyl-3 can be turned on chromen -2 - (p - tolyl thio) -2 H.

In addition, the present invention relates to a process for the preparation of 4-hydroxy-4-hydroxyquinoline, which comprises the reaction of a) 4-hydroxycoumarin or 4-hydroxyquinolinone and b) sulfonylhydrazide, using CuBrMe ₂ S as catalyst, Sulfanyl coumarin or a 4-hydroxy-3-sulfanyl quinolinone derivative.

Preferably, the reaction may be carried out using DABCO as an additive and 1,4-dioxane as a solvent, and may be carried out at 80 ° C to 120 ° C for 3 hours to 8 hours.

At this time, the 4-hydroxy coumarin may be represented by the following formula 3;

(3)

In Formula 3, R ₈ is selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen, and R ₉ and R ₁₀ are each independently selected from hydrogen or halogen.

Preferably, in Formula 3, R ₈ is selected from the group consisting of hydrogen, methyl, fluoro, and chloro, and R ₉ and R ₁₀ are each independently selected from the group consisting of hydrogen, bromo, fluoro, and chloro .

Also, the 4-hydroxyquinolinone may be represented by the following general formula (4);

[Chemical Formula 4]

In Formula 4, R ₁₁ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen, and R ₁₂ is (C 1 -C 4) alkyl or hydrogen.

Preferably, in Formula 4, R ₁₁ may be selected from the group consisting of hydrogen, methyl, isopropyl, bromo, and chloro, and R ₁₂ is selected from the group consisting of phenyl, p -tolylyl, mesityl and 5- ) Naphthalene-1-yl group.

In one embodiment of the present invention, the 4-hydroxy-3-sulfanyl coumarin derivative may be represented by the following formula (1);

[Chemical Formula 1]

Wherein R ₁ is selected from the group consisting of hydrogen, (C ₁ -C 4) alkyl and halogen, R ₂ and R ₃ are each independently selected from hydrogen or halogen, and R ₄ is a substituted or unsubstituted phenyl group , A substituted naphthyl group and an unsubstituted thienyl group, and the substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with a (C1-C4) alkyl group, and the substituted naphthyl group is Di (C1-C4 alkyl) amine group.

More preferably, in Formula 1, R ₁ is selected from the group consisting of hydrogen, methyl, fluoro, and chloro, and R ₂ and R ₃ are each independently selected from the group consisting of hydrogen, bromo, fluoro, and chloro And R ₄ may be selected from the group consisting of phenyl, p -tolyl, mesityl, 5- (dimethylamino) naphthalen-1-yl and 2-thienyl.

In one embodiment of the present invention, the 4-hydroxy-3-sulfanyl quinolinone derivative may be represented by the following general formula (2);

(2)

Wherein R ₅ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen, R ₆ is (C 1 -C 4) alkyl or hydrogen, and R ₇ is a substituted or unsubstituted phenyl group And substituted naphthyl groups, wherein the substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups, and the substituted naphthyl group is selected from the group consisting of di To C4 alkyl) amine groups.

In more preferably, the formula 2, R ₅ is any one selected from the group consisting of hydrogen, methyl, isopropyl, bromo or chloro, R ₆ is methyl or hydrogen, R ₇ is phenyl, p - tolyl A mesyl group, and a 5- (dimethylamino) naphthalen-1-yl group.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. It is to be understood that both the foregoing description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed. no.

< Preparation Example > Preparation of reagents and compounds

All experiments according to the invention were carried out in air contact. 4-hydroxy-coumarin, 4-hydroxy quinolinone and aryl sulfonyl hydrazide, Al ^{+ 3,} Ca ^{+ 2,} Co ^{+ 2,} Cr ^3+, Cu ^{2 +,} Fe ^{2 +,} Fe ^{3 +,} Hg ^{+ 2,} Ni ^{+ 2} and Zn ^{2 +} chloride salt, nitrate, lead (Pb ^{+ 2)} and cadmium acetate (Cd ²⁺⁾ was used as purchased from Sigma-Aldrich or receive the.

TLC for analysis was performed using a pre-coated silica gel plate (Art. 5554) with a fluorescence indicator from Merck, Inc. The melting points of each compound were determined using a Fisher-Johns melting point apparatus containing a micro- And were not calibrated. ¹ H NMR analysis and ¹³ C NMR analysis was measured by using CDCl _3, DMSO-d ₆ and acetone-VNS Varian spectrometer at -d ₆ or DPX spectrometer (600 MHz and 300 MHz). IR analysis (infrared analysis) was recorded with a JASCO FTIR 5300 spectrophotometer, and high-resolution mass spectra were performed using a JOEL JMS-700 spectrometer (Korea Basic Science Institute).

< Example  1> Optimization of reaction conditions

(1) Optimization of reaction conditions

Direct coupling between 1 mmol of 4-hydroxy coumarin compound (1a) and 1.5 mmol of benzene sulfonyl hydrazide (2a) was carried out under different catalyst and solvent conditions to find the optimal reaction conditions. At this time, the reaction of the compounds was as shown in Reaction Scheme 1 below, and the reaction conditions were as shown in Table 1 below.

[Reaction Scheme 1]

First, 10 mol% of Ag ₂ O, Cu (OTf) ₂ or Cu (OAc) ₂ catalyst and 1.0 equivalent of DABCO were used as base additive in 1,4-dioxane solvent, but the coupling product 3a was produced (Entry 1-3). Further, when the compounds 1a and 2a were reacted in the presence of 10 mol% of I ₂ , CuI and CuBr, the product 3a was produced at the yields of 68%, 65% and 70% respectively (Entry 4-6). The best results (yield of 88%) were shown in a reaction carried out with 10 mol% CuBr · Me ₂ S as a catalyst and with 1 equivalent of DABCO in reflux with 1,4-dioxane for 5 h (Entry 7) . Product 3a was not produced in reactions without copper catalyst (Entry 8). Without additional DABCO addition, the yield of 3a was only 10% (Entry 9).

To improve the yield of this sulfamic carbonylation reaction, using the yield was high is CuBr · Me ₂ S catalyst, were screened with different base additive, such as DBU, and Et ₃ N. As a result, in the combination of 10 mol% of CuBr 占_{2 2} S and DBU (1 equivalent) or Et ₃ N, the yield of 3a was reduced to 60% and 50%, respectively (Entry 10 and 11). In addition, when the loading amount of the catalyst was reduced to 15 mol% or 3 mol%, the yield of the product was not improved (Entry 12 and 13). On the other hand, in polar solvents such as acetonitrile, DMSO and DMF, 3a was obtained at 45, 58 and 66%, respectively, whereas in the non-polar solvent toluene, 3a was produced with a yield of only 10% (Entry 14-17). The structure of product 3a was determined through analysis of spectral data and comparison with previously reported values.

Under the optimum reaction conditions as described above, the substrate scope of the reaction substrate was tested using various 4-hydroxycoumarin 1a-1g and sulfonyl hydrazide 2a-2f as shown in the following Reaction Scheme 2 .

[Reaction Scheme 2]

As a result, it succeeded in synthesizing the compounds (3b to 3r) shown in Fig. More specifically, substituents such as methyl, bromo, chloro and fluoro located in the benzene ring of coumarin have been reacted well and substituents such as p -tolyl, mesityl and 5- (dimethylamino) naphthalen- The multiple sulfonyl hydrazides involved also coupled well with the corresponding 4-hydroxycoumarin to yield the desired product in high yield. More specifically, reaction of 1a and 2b to 2d for 5 hours produced the desired product 3b-3d with yields of 90, 91 and 62%, respectively.

The 4-hydroxycoumarin (1b) containing the electron-donating group methyl group at the 6-position of the benzene ring was reacted with the sulfonyl hydrazide 2a-2c to give 3e-3g of the product with a yield of 90-93% While reaction of 1c-1f compounds containing electron attracting groups 6-Cl, 6-F, 7-Br, 7-F produced product 3h-3n with a yield of 78-86%. For 1 g of hydroxy coumarin containing two electron-withdrawing substituents in the benzene ring, the desired products 3o and 3p were obtained with a yield of 78% and 84%, respectively.

Subsequently, in order to confirm the possibility of using heteroarylsulfonyl hydrazide and alkenesulfonyl hydrazide, thiophene-2-sulfono hydrazide (2e) and ( p -tolyl) ethene-1- Additional reaction of the Drazide (2f) was carried out. In the 1,4-dioxane solvent, the reaction of the compounds 1a and 2e at 100 DEG C for 5 hours gave the desired compound 3q in a yield of 65%. On the other hand, the reaction with 2f did not produce the desired product 3r, and in this case, the two starting materials 1a and 2f were regenerated. In addition, the reaction of 2 H -chromen-2-one with benzenesulfonyl hydrazide in a 4-dioxane solvent at 100 &lt; 0 &gt; C for 12 h did not produce the desired product, Zydes were degraded and unreacted 2 H -chromen-2-one recovered.

At this time, NMR data of ( p -tolyl) ethene-1-sulfonohydrazide (2f) was as follows; White crystalline solid with a melting point of 140-143 [deg.] C; ^{1 H NMR (600 MHz, CDCl} 3 _{+ DMSO- d 6): δ 9.12} (1H, s), 7.37 (1H, d, J = 15.6 Hz), 7.30 (2H, d, J = 7.8 Hz), 7.09 (2H, d, J = 7.8 Hz) , 6.71 (1H, d, J = 16.2 Hz), 2.29 (3H, s); ^{13 C NMR (150 MHz, CDCl} 3 + DMSO- d ₆ ):? 142.5, 140.8, 129.3, 129.2, 127.9, 122.5, 20.9; IR: 3223, 3034, 2920, 1610, 1511, 1395, 1325 cm &lt; ^{-1 &} gt ;.

In order to confirm the versatility of the sulfanylation reaction as described above, additional reactions of various 4-hydroxyquinolinones with sulfonylhydrazides were tested. At this time, the reactants and reaction schemes were as shown in Reaction Scheme 3 below. At this time, 1.0 mmol of the 4-hydroxy coumarin compound, 1.5 mmol of the sulfonyl hydrazide, 10 mol% of CuBr · Me ₂ S and 1.0 equivalent of DABCO were used, and the solvent was 5 mL of 1,4-dioxane And reacted at 100 ° C.

[Reaction Scheme 3]

As a result, the compounds disclosed in Fig. 2 could be synthesized. Specifically, in the reaction of 4-hydroxy-1-methylquinolone (4a) with 2a-2d, the desired products 5a-5d were obtained with a yield of 70-90%, while in the reaction of 4b with 2a and 2b, 5f were obtained with yields of 80% and 83%, respectively. In addition, the reaction of 4-hydroxyquinolinone 4c-4f, including the electron-donating group or electron-attracting group, on the benzene ring was also successfully carried out. In the reactions of 4c and 4d and 2a-2c containing electron-donating groups such as 6-methyl and 6-isopropyl groups, the desired product 5g-5j was produced with a yield of 82-88% Reaction of 4e and 4f with 2b and 2c, including electron-attracting groups such as chloro, gave product 5k-5m with yields of 80, 82 and 77%.

(2) Identification of mechanism

Then, in order to clarify the mechanism of the sulfanylation reaction, a control experiment was carried out, wherein the reactants, products and reaction schemes were as shown in Reaction Scheme 4 below.

[Reaction Scheme 4]

First, under optimal reaction conditions obtained above, without S-hydroxy coumarin or 4-hydroxyquinolinone, S-phenylbenzenesulfonothioate (6) and diphenyl sulfide (7) Separated (Eq. (1)). On the other hand, when the arylsulfonyl hydrazide was refluxed in the 1,4-dioxane solvent for 24 hours without the copper (I) complex, no product 6 or 7 was found. Importantly, in the reaction of product 6 or 7 with 4-hydroxy coumarin under optimum reaction conditions, product 3a was produced by 80% and 82%, respectively (Eq. (2) and (3)). These results clearly show that S-phenylbenzenesulfonothiotate (6) or disulfide (7) is an intermediate product in the sulfanylation reaction. On the other hand, when the reaction of 1a and 2a was carried out under optimum reaction conditions and addition of TEMPO, the effect of the radical scavenger did not appear. This result means that the reaction does not occur through the radical pathway (Eq. (4)).

On the basis of the above results, as shown in FIG. 3, the mechanism of formation of the products 3a and 5a through sulfanylation was confirmed. Specifically, the sulfanylation reaction is initiated first through Cu (I) -catalyzed anaerobic oxidation and the intermediate products thiosulfonate (6) and disulfide (7) are separated from the other intermediates (8) and It is produced through redox decomposition process. The copper catalyst then reacts with compounds 6 and 7 to form the copper (III) complex 10, which undergoes DABCO-mediated metal exchange at position 3 of 4-hydroxy coumarin or 4-hydroxyquinoline (III) complex 11, which is another intermediate product, is formed. Next, the reductive removal of the copper (III) complex 11 leads to the formation of 3a ', 5a' and copper (I) complexes 12. The exchange of copper (I) complex 12 with HBr forms sulfinic acid 13 or thiol 14 and restores the copper (I) catalyst. Finally, keto-enol tautomerization of intermediate products 3a 'and 5a' forms the final products 3a and 5a.

< Synthetic example  1> Synthesis of Compound 3a-3r, 5a-5m

Is a general procedure for the synthesis of various 3-arylsulfanyl-4-hydroxycoumarin and 3-arylsulfanyl-4-hydroxyquinolinone derivatives. First, a 4-hydroxy coumarin / 4-hydroxy quinolinone (1.0 mmol), aryl sulfonyl hydrazide (1.5 mmol), CuBr · Me 2 S (10 mol%) and DABCO (1 eq.) 5 mL Of 1,4-dioxane solvent and stirred well under reflux conditions. After the completion of the reaction, the solvent was evaporated under vacuum, and the residue was purified by column chromatography on a mixture of ethyl acetate and hexane as eluent to give pure 3-aryl sulfamide (3a-3r) and 3-arylsulfanyl-4-hydroxyquinolinone derivatives (5a-5m) were obtained.

(1) 4- Hydroxy -3- ( Phenylthio )-2 H - Kromen One (4- Hydroxy -3- ( 메틸THIO ) -2H-chromen-2-one; 3a)

This compound was obtained as a white crystalline solid melting at 198-200 [deg.] C through a common reaction. Yield: 88% (237 mg); ^{1 H NMR (600 MHz, Acetone-} d 6): δ 7.99 (1H, d, J = 7.2 Hz), 7.74 (1H, t, J = 8.4 Hz), 7.42 (1H, t, J = 8.4 Hz), 7.39 (1H, d, J = 8.4Hz), 7.30-7.26 (4H, m), 7.19-7.17 (1H, m); ^{13 C NMR (150 MHz, Acetone-} d 6): δ 168.4, 161.2, 154.6, 136.3, 134.6, 129.9, 128.1, 128.0, 126.9, 125.2, 125.0, 117.4, 115.9, 96.8; IR: 3067, 1671, 1602, 1538, 1423, 1187 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 15 H 10 O 3 S: 270.0351, Found: 270.0349.

(2) 4- Hydroxy -3- ( p - Tolylthio )-2 H - Kromen One (4- Hydroxy -3- ( p -tolylthio) -2 H -chromen-2-one; 3b)

This compound was obtained as a white crystalline solid melting at 210-212 [deg.] C through a common reaction. Yield: 90% (256 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 7.95 (1H, d, J = 7.2 Hz), 7.69 (1H, t, J = 7.2 Hz), 7.42-7.38 (2H, m), 7.13-7.08 (4 H, m), 2.23 (3 H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 167.9, 160.8, 152.9, 135.2, 133.6, 133.5, 132.2, 129.7, 126.9, 124.3, 124.2, 116.5, 116.4, 115.6, 95.2, 20.5; IR: 3220, 1681, 1598, 1544, 1489, 1187 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 16 H 12 O 3 S: 284.0507, Found: 284.0510.

(3) 4- Hydroxy -3- ( Meshil tithio )-2 H - Kromen One (4- Hydroxy -3- (mesitylthio) -2 H -chromen-2-one; 3c)

The above compound was obtained as a white crystalline solid having a melting point of 187-190 DEG C through a general reaction. Yield: 91% (284 mg); ^{1 H NMR (600 MHz, Acetone-} d 6): δ 7.97 (1H, dd, J = 7.8, 1.2 Hz), 7.64 (1H, td, J = 9.0, 1.8 Hz), 7.38 (1H, td, J = 8.4, 1.2 Hz), 7.28 (1H, d, J = 8.4 Hz), 6.89 (2H, s), 2.49 (6H, s), 2.20 (3H, s); ^{13 C NMR (150 MHz, Acetone-} d 6): δ 164.6, 160.1, 153.8, 143.4, 138.9, 133.6, 130.0, 129.9, 127.8, 124.9, 124.6, 117.2, 117.0, 115.9, 99.7, 21.9, 20.8; IR: 3186, 1677, 1603, 1547, 1385, 1281, 1147 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 18 H 16 O 3 S: 312.0820, Found: 312.0822.

(4) Synthesis of 3 - ((5- (dimethylamino) naphthalen-1-yl) Thio )-4- Hydroxy -2 H - Kromen (3 - ((5- (Dimethylamino) naphthalen-1-yl) thio) -4-hydroxy-2 H -chromen-2-one; 3d)

The above compound was obtained as a white crystalline solid having a melting point of 232-234 DEG C through a general reaction. Yield: 62% (225 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 7.98-7.96 (3H, m), 7.70 (1H, td, J = 9.0, 1.8 Hz); 7.53 (1H, t, J = 7.2 Hz), 7.42-7.38 (2H, m), 7.35 (1H, t, J = 7.8 Hz), 7.21 (1H, d, J = 7.2 Hz), 7.13 (1H, d , &Lt; / RTI &gt; J = 7.2 Hz), 2.84 (6H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 169.4, 161.0, 153.1, 150.5, 133.7, 133.4, 131.7, 128.5, 126.1, 125.1, 124.4, 124.0, 122.7, 121.2, 118.5, 116.5, 116.4, 114.6, 92.6, 44.9; IR: 3030, 1677, 1598, 1532, 1463, 1369 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 21 H 17 NO 3 S: 363.0929, Found: 363.0927.

(5) 4- Hydroxy -6- methyl -3- ( Phenylthio )-2 H - Kromen One (4- Hydroxy -6-methyl-3- (phenylthio) -2 H -chromen-2-one; 3e)

This compound was obtained as a white crystalline solid melting at 172-174 [deg.] C through a common reaction. Yield: 90% (256 mg); ^{1 H NMR (600 MHz, CDCl} 3): δ 8.21 (1H, s), 7.66 (1H, s), 7.40 (1H, dd, J = 8.4, 2.4 Hz), 7.28 (2H, d, J = 8.4 Hz ), 7.23-7.20 (3H, m), 7.16 (1H, t, J = 7.8 Hz), 2.40 (3H, s); ¹³ C NMR (150 MHz, CDCl ₃ ):? 167.0, 161.0, 151.7, 134.9, 134.2, 133.2, 129.3, 128.2, 127.1, 123.9, 116.6, 113.5, 96.8, 20.7; IR: 3163, 1685, 1603, 1538, 1433, 1159 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 16 H 12 O 3 S: 284.0507, Found: 284.0505.

(6) 4- Hydroxy -6- methyl -3- ( p - Tolylthio )-2 H - Kromen One (4- Hydroxy -6-methyl-3- ( p -tolylthio) -2 H -chromen-2-one; 3f)

This compound was obtained as a white crystalline solid melting at 182-185 [deg.] C through a common reaction. Yield: 90% (268 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 7.72 (1H, s), 7.49 (1H, d, J = 8.4 Hz), 7.29 (1H, d, J = 9.0 Hz), 7.11-7.08 (4H , &lt; / RTI &gt; m), 2.38 (3H, s), 2.23 (3H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 167.9, 160.9, 151.1, 135.1, 134.4, 133.5, 132.2, 129.7, 126.9, 123.8, 116.2, 115.2, 95.1, 20.4, 20.3; IR: 3222, 1688, 1590, 1540, 1498, 1150 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 17 H 14 O 3 S: 298.0664, Found: 298.0661.

(7) 4- Hydroxy -3- ( Meshil tithio ) -6- methyl -2 H - Kromen One (4- Hydroxy -3- (mesitylthio) -6-methyl-2 H -chromen-2-one; 3g)

The above compound was obtained as a white crystalline solid having a melting point of 193-195 DEG C through a general reaction. Yield: 93% (303 mg); ^{1 H NMR (600 MHz, CDCl} 3): δ 7.72 (1H, s), 7.61 (1H, s), 7.33 (1H, dd, J = 8.4, 1.8 Hz), 7.16 (1H, d, J = 9.0 Hz ), 6.90 (2H, s), 2.49 (6H, s), 2.40 (3H, s), 2.23 (3H, s); ¹³ C NMR (150 MHz, CDCl ₃ ):? 163.4, 159.9, 151.1, 142.6, 139.1, 133.9, 133.8, 129.7, 125.3, 123.3, 116.5, 113.7, 99.2, 21.9, 20.9, 20.8; IR: 3273, 1675, 1562, 1376, 1277, 1172 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 19 H 18 O 3 S: 326.0977, Found: 326.0977.

(8) 6- Chloro -4- Hydroxy -3- ( Phenylthio )-2 H - Kromen One (6- Chloro -4-hydroxy-3- (phenylthio) -2 H -chromen-2-one; 3h)

This compound was obtained as a white crystalline solid melting at 168-170 [deg.] C through a common reaction. Yield: 83% (253 mg); ^{1 H NMR (600 MHz, CDCl} 3): δ 8.17 (1H, s), 7.82 (1H, d, J = 2.4 Hz), 7.50 (1H, dd, J = 9.0, 2.4 Hz), 7.28-7.16 (6H , m); ¹³ C NMR (150 MHz, CDCl ₃ ):? 165.7, 160.2, 151.9, 133.8, 132.6, 129.9, 129.4, 128.7, 127.5, 123.8, 118.5, 114.9, 98.4; IR: 3207, 1704, 1601, 1538, 1477, 1150 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 15 H 9 ClO 3 S: 303.9961, Found: 303.9958.

(9) 6- Chloro -4- Hydroxy -3- ( p - Tolylthio )-2 H - Kromen One (6- Chloro -4-hydroxy-3- ( p -tolylthio) -2 H -chromen-2-one; 3i)

This compound was obtained as a white crystalline solid melting at 195-198 [deg.] C through a common reaction. Yield: 85% (271 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 7.89 (1H, s), 7.71 (1H, d, J = 8.4 Hz), 7.44 (1H, dd, J = 8.4, 1.2 Hz), 7.11-7.07 (4 H, m), 2.23 (3 H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 167.2, 160.7, 151.7, 135.2, 133.0, 132.2, 129.7, 128.2, 126.9, 123.4, 118.7, 117.6, 95.8, 20.5; IR: 3080, 1683, 1603, 1542, 1487, 1219, 1117 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 16 H 11 ClO 3 S: 318.0117, Found: 318.0115.

(10) 6- Chloro -4- Hydroxy -3- ( Meshil tithio )-2 H - Kromen One (6- Chloro -4-hydroxy-3- (mesitylthio) -2 H -chromen-2-one; 3j)

This compound was obtained as a white crystalline solid melting at 218-221 [deg.] C through a common reaction. Yield: 86% (298 mg); ^{1 H NMR (600 MHz, CDCl} 3): δ 7.80 (1H, d, J = 2.4 Hz), 7.72 (1H, s), 7.47 (1H, dd, J = 9.0, 2.4 Hz), 7.21 (1H, d , J = 9.0 Hz), 6.91 (2H, s), 2.49 (6H, s), 2.23 (3H, s); ¹³ C NMR (150 MHz, CDCl ₃ ):? 162.0, 159.2, 151.2, 142.7, 139.4, 132.7, 129.8, 129.6, 124.7, 123.2, 118.2, 115.2, 100.5, 21.9, 20.9; IR: 3214, 1703, 1597, 1537, 1153 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 18 H 15 ClO 3 S: 346.0430, Found: 346.0433.

(11) 6- Fluoro -4- Hydroxy -3- ( Phenylthio )-2 H - Kromen One (6- Fluoro -4-hydroxy-3- (phenylthio) -2 H -chromen-2-one; 3k)

The above compound was obtained as a white crystalline solid having a melting point of 185-187 DEG C through a general reaction. Yield: 80% (230 mg); ^{1 H NMR (600 MHz, CDCl} 3): δ 8.04 (1H, s), 7.43 (1H, dd, J = 9.6, 1.8 Hz), 7.21-7.19 (4H, m), 7.13 (2H, t, J = 7.8 Hz), 7.09-7.07 (1H, m); ^{13 C NMR (150 MHz, CDCl} 3): δ 166.0, 159.9 (d, J = 142.5 Hz), 157.8, 149.7 (d, J = 2.2 Hz), 132.6, 129.5, 128.7, 127.5, 121.5 (d, J = 24.2 Hz), 118.7 (d, J = 7.9 Hz), 114.6 (d, J = 9.2 Hz), 110.0 (d, J = 25.4 Hz), 98.3; ¹⁹ F NMR (564 MHz, CDCl ₃ ): d -116.40 - - 116.37; IR: 3145, 1685, 1606, 1539, 1492, 1247, 1211, 1180 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 15 H 9 FO 3 S: 288.0256, Found: 288.0256.

(12) 6- Fluoro -4- Hydroxy -3- ( Meshil tithio )-2 H - Kromen One (6- Fluoro -4-hydroxy-3- (mesitylthio) -2 H -chromen-2-one; 3l)

This compound was obtained as a white crystalline solid with melting point of 210-213 [deg.] C through a common reaction. Yield: 83% (274 mg); ^{1 H NMR (600 MHz, CDCl} 3): δ 7.71 (1H, s), 7.47 (1H, d, J = 8.4 Hz), 7.21 (2H, dd, J = 5.4, 1.8 Hz), 6.89 (2H, s ), 2.47 (6H, s), 2.21 (3H, s); ^{13 C NMR (150 MHz, CDCl} 3): δ 162.3, 159.4, 157.8, 148.9, 142.7, 139.4, 129.8, 124.7, 120.3 (d, J = 24.1 Hz), 118.3 (d, J = 9.1 Hz), 114.9 ( d, J = 9.1 Hz), 109.3 (d, J = 25.2 Hz), 100.5, 21.9, 20.9; ¹⁹ F NMR (564 MHz, CDCl ₃ ): d -118.29 - -118.26; IR: 3207, 1675, 1613, 1553, 1485, 1375, 1165 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 18 H 15 FO 3 S: 330.0726, Found: 330.0725.

(13) 7- Bromo -4- Hydroxy -3- ( Phenylthio )-2 H - Kromen One (7- Bromo -4-hydroxy-3- (phenylthio) -2 H -chromen-2-one; 3m)

This compound was obtained as a white crystalline solid melting at 224-226 [deg.] C through a common reaction. Yield: 80% (279 mg); ^{1 H NMR (300 MHz, CDCl} 3): δ 8.05 (1H, s), 7.68 (1H, d, J = 8.4 Hz), 7.45 (1H, d, J = 1.8 Hz), 7.39 (1H, dd, J = 8.7, 1.8 Hz), 7.25-7.13 (5H, m); ¹³ C NMR (75 MHz, CDCl ₃ ):? 166.4, 160.2, 153.7, 132.6, 129.5, 128.5, 128.2, 127.9, 127.5, 125.5, 120.2, 112.7, 97.4; IR: 3219, 1699, 1591, 1531, 1480, 1183 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 15 H 9 BrO 3 S: 347.9456, Found: 347.9453.

(14) 7- Fluoro -4- Hydroxy -3- ( Phenylthio )-2 H - Kromen One (7- Fluoro -4-hydroxy-3- (phenylthio) -2 H -chromen-2-one; 3n)

This compound was obtained as a white crystalline solid melting at 163-165 [deg.] C through a common reaction. Yield: 78% (225 mg); ¹ H NMR (300 MHz, CDCl ₃ ):? 8.04 (1H, s), 7.87-7.78 (1H, m), 7.22-7.10 (5H, m), 7.00-6.94 (2H, m); _{^{13 C NMR (150MHz, CDCl 3}} ): δ 166.6 (d, J = 34.5 Hz), 165.0, 160.6, 155.0 (d, J = 13.8 Hz), 132.8, 129.5, 128.5, 127.5, 126.6, 126.5, 112.9 (d , J = 22.9 Hz), 110.5 (d, J = 2.4 Hz), 104.5 (d, J = 25.2 Hz); ^{19 F NMR (564 MHz, CDCl} 3): d -102.82- -102.78; IR: 3093, 1680, 1604, 1543, 1214, 1136 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 15 H 9 FO 3 S: 288.0256, Found: 288.0258.

(15) 6,8- Dichloro -4- Hydroxy -3- ( Phenylthio )-2 H - Kromen One (6,8-Dichloro-4-hydroxy-3- (phenylthio) -2 H -chromen-2-one; 3o)

This compound was obtained as a white crystalline solid with melting point of 200-202 [deg.] C through a common reaction. Yield: 78% (264 mg); ^{1 H NMR (600 MHz, CDCl} 3): δ 8.20 (1H, s), 7.81 (1H, d, J = 2.4 Hz), 7.68 (1H, d, J = 2.4 Hz), 7.36 (2H, d, J = 7.2 Hz), 7.29 (2H, t, J = 7.2 Hz), 7.27-7.24 (1H, m); ¹³ C NMR (150 MHz, CDCl ₃ ):? 165.2, 158.9, 148.0, 133.7, 132.1, 129.7, 129.5, 129.0, 127.8, 123.0, 122.4, 115.8, 99.3; IR: 3191, 1705, 1595, 1535, 1155 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 15 H 8 Cl 2 O 3 S: 337.9571, Found: 337.9568.

(16) 6,8- Dichloro -4- Hydroxy -3- ( Meshil tithio )-2 H - Kromen One (6,8-Dichloro-4-hydroxy-3- (mesitylthio) -2 H -chromen-2-one; 3p)

This compound was obtained as a white crystalline solid melting at 213-216 [deg.] C through a common reaction. Yield: 84% (320 mg); ^{1 H NMR (300 MHz, CDCl} 3): δ 7.81 (1H, s), 7.73 (1H, d, J = 2.4 Hz), 7.57 (1H, d, J = 2.4 Hz), 6.91 (2H, s), 2.48 (6 H, s), 2.23 (3 H, s); ¹³ C NMR (75 MHz, CDCl ₃ ):? 161.5, 157.9, 147.2, 142.8, 139.6, 132.6, 129.8, 129.4, 124.2, 122.6, 121.7, 116.1, 101.3, 21.9, 20.9; IR: 3090, 1675, 1601, 1548, 1211, 1190 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 18 H 14 C l2 O 3 S: 380.0041, Found: 380.0045.

(17) 4- Hydroxy -3- (thiophen-2- Ithio )-2 H - Kromen One (4- Hydroxy -3- (thiophen-2-ylthio) -2 H -chromen-2-one; 3q)

This compound was obtained as a white crystalline solid melting at 190-193 [deg.] C through a common reaction. Yield: 65% (179 mg); ^{1 H NMR (300 MHz, CDCl} 3): δ 8.18 (1H, s), 7.89 (1H, dd, J = 8.4, 1.5 Hz), 7.59 (1H, td, J = 8.4, 1.5 Hz), 7.38 (1H , dd, J = 3.6, 0.9 Hz), 7.33-7.29 (3H, m), 6.94 (1H, dd, J = 5.1, 3.6 Hz); ¹³ C NMR (75 MHz, CDCl ₃ ): 隆 165.6, 160.6, 153.4, 134.6, 133.8, 130.0, 129.8, 127.7, 124.5, 124.3, 116.9, 113.9, 99.9; IR: 3328, 1690, 1603, 1543, 1492, 1192 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 13 H 8 O 3 S 2: 275.9915, Found: 275.9918

(18) 4- Hydroxy -One- methyl -3- ( Phenylthio ) Quinolin-2 (1 H ) -One (4- Hydroxy -1-methyl-3- (phenylthio) quinolin-2 (1 H ) -one; 5a)

This compound was obtained as a white crystalline solid melting at 238-241 [deg.] C through a common reaction. Yield: 85% (241 mg); ^{1 H NMR (600 MHz, DMSO} -d 6): δ 11.17 (1H, s), 8.03 (1H, d, J = 7.2 Hz), 7.69 (1H, t, J = 7.8 Hz), 7.51 (1H, d J = 9.0 Hz), 7.29 (1H, t, J = 7.8 Hz), 7.24 (2H, t, J = 8.4 Hz), 7.13-7.10 (3H, m), 3.60 (3H, s); ^{13 C NMR (150 MHz, DMSO} -d 6): δ 164.2, 161.1, 139.9, 136.7, 132.5, 132.4, 128.9, 126.1, 125.1, 124.3, 121.7, 115.1, 114.8, 114.7, 100.3, 29.8; IR: 3059, 1607, 1579, 1549, 1318, 1188 cm- ¹ ; ^{HRMS m / z (M +)} calcd for C 16 H 13 NO 2 S: 283.0667, Found: 283.0666.

(19) 4- Hydroxy -One- methyl -3- ( p - Tolylthio ) Quinolin-2 (1 H ) -One (4- Hydroxy -1-methyl-3- ( p -tolylthio) quinolin-2 (1 H ) -one; 5b)

This compound was obtained as a white crystalline solid melting at 235-237 [deg.] C through a common reaction. Yield: 88% (261 mg); ^{1 H NMR (600 MHz, DMSO} -d 6): δ 8.02 (1H, dd, J = 8.4, 1.2 Hz), 7.68 (1H, td, J = 9.0, 1.8 Hz), 7.50 (1H, d, J = 8.4 Hz), 7.29 (1H, t, J = 7.2 Hz), 7.05 (4H, s), 3.58 (3H, s), 2.21 (3H, s); ^{13 C NMR (150 MHz, DMSO} -d 6): δ 163.9, 161.2, 139.8, 134.8, 132.9, 132.5, 129.5, 126.9, 124.3, 121.8, 115.1, 114.8, 101.2, 29.9, 20.5; IR: 3186, 1607, 1551, 1494, 1206, 1157 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 17 H 15 NO 2 S: 297.0823, Found: 297.0822.

(20) 4- Hydroxy -3- ( Meshil tithio )-One- Methylquinoline -2 (1 H ) -One (4- Hydroxy -3- (mesitylthio) -1-methylquinolin-2 (1 H ) -one; 5c)

This compound was obtained as a white crystalline solid with melting point of 132-135 [deg.] C through a common reaction. Yield: 90% (292 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 10.84 (1H, s), 8.01 (1H, dd, J = 8.4, 1.2 Hz), 7.62 (1H, td, J = 7.8, 1.2 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.27 (1H, t, J = 7.8 Hz), 6.84 (2H, s), 3.47 (3H, s), 2.40 ; ^{13 C NMR (150 MHz, DMSO-} d 6): δ 160.4, 160.3, 141.6, 138.9, 136.7, 131.5, 128.8, 128.5, 123.6, 121.5, 115.1, 114.5, 103.9, 29.5, 21.5, 20.4; IR: 3325, 1603, 1549, 1458, 1308, 1141 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 19 H 19 NO 2 S: 325.1136, Found: 325.1138.

(21) 3 - ((5- (dimethylamino) naphthalen-1-yl) Thio )-4- Hydroxy -One- Methylquinoline -2 (1 H ) -One (3 - ((5- ( Dimethylamino ) naphthalen -One- yl ) thio )-4- hydroxy -1-methylquinolin-2 (1 H ) -one; 5d)

This compound was obtained as a white crystalline solid with melting point of 132-135 [deg.] C through a common reaction. Yield: 70% (263 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 8.07 (1H, dd, J = 8.4, 1.2 Hz), 8.01 (1H, d, J = 8.4 Hz), 7.95 (1H, d, J = 8.4 Hz ), 7.71 (1H, td, J = 7.8,1.2 Hz), 7.54 (1H, d, J = 9.0 Hz), 7.51 (1H, d, J = 8.4 Hz), 7.33-7.28 (1H, d, J = 7.8 Hz), 6.97 (1H, d, J = 7.2 Hz), 3.60 (3H, s), 2.80 (6H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 164.6, 160.9, 151.1, 139.9, 134.0, 132.5, 131.9, 128.6, 126.1, 124.9, 124.2, 122.4, 121.7, 121.3, 118.4, 115.2, 114.8, 114.3, 99.8, 44.9, 29.9; IR: 2934, 1587, 1547, 1500, 1391, 1158 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 22 H 20 N 2 O 2 S: 376.1245, Found: 376.1245.

(22) 4- Hydroxy -3- ( Phenylthio ) Quinolin-2 (1 H ) -One (4- Hydroxy -3- (phenylthio) quinolin-2 (1 H ) -one; 5e)

This compound was obtained as a white crystalline solid melting at 234-236 [deg.] C through a common reaction. Yield: 80% (215 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 11.60 (1H, s), 11.16 (1H, s), 7.92 (1H, d, J = 7.2 Hz), 7.57 (1H, td, J = 7.8, 1.2 Hz), 7.32 (1H, d, J = 8.4 Hz), 7.25 (2H, t, J = 7.8 Hz), 7.20 (1H, t, J = 7.8 Hz), 7.12-7.10 (3H, m); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 165.5, 161.6, 139.1, 136.8, 132.1, 128.8, 125.9, 125.0, 123.8, 121.5, 115.2, 114.3, 100.3; IR: 3139, 2992, 1629, 1584, 1460, 1401, 1147 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 15 H 11 NO 2 S: 269.0510, Found: 269.0510.

(23) 4- Hydroxy -3- ( p - Tolylthio ) Quinolin-2 (1 H ) -One (4- Hydroxy -3- ( p -tolylthio) quinolin-2 (1 H ) -one; 5f)

This compound was obtained as a white crystalline solid melting at 295-297 [deg.] C through a common reaction. Yield: 83% (235 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 11.57 (1H, s), 11.07 (1H, s), 7.91 (1H, d, J = 7.8 Hz), 7.56 (1H, td, J = 9.6, 1.8 Hz), 7.31 (1H, d, J = 7.8 Hz), 7.19 (1H, td, J = 8.4, 1.2 Hz), 7.07-7.03 (4H, m), 2.22 (3H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 165.1, 161.6, 139.0, 134.6, 133.1, 131.9, 129.5, 126.5, 123.8, 121.5, 115.2, 114.3, 101.1, 20.4; IR: 3096, 2857, 1632, 1594, 1506, 1463, 1327, 1233 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 16 H 13 NO 2 S: 283.0667, Found: 283.0671.

(24) 4- Hydroxy -6- methyl -3- ( p - Tolylthio ) Quinolin-2 (1 H ) -One (4- Hydroxy -6-methyl-3- ( p -tolylthio) quinolin-2 (1 H ) -one; 5g)

This compound was obtained as a white crystalline solid melting at 275-279 [deg.] C through a common reaction. Yield: 85% (252 mg); ^{1 H NMR (300 MHz, DMSO-} d 6): δ 11.49 (1H, s), 10.99 (1H, s), 7.69 (1H, s), 7.39 (1H, dd, J = 8.4, 1.5 Hz), 7.20 (1H, d, J = 8.4 Hz), 7.07-6.99 (4H, m), 2.36 (3H, s), 2.22 (3H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 164.9, 161.5, 137.0, 134.5, 133.2, 133.1, 130.5, 129.4, 126.4, 123.1, 115.2, 114.1, 100.9, 20.5, 20.4; IR: 3341, 2841, 1639, 1598, 1468, 1431, 1228 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 17 H 15 NO 2 S: 297.0823, Found: 297.0823.

(25) 4- Hydroxy -3- ( Meshil tithio ) -6- Methylquinoline -2 (1 H ) -One (4- Hydroxy -3- (mesitylthio) -6-methylquinolin-2 (1 H ) -one; 5h)

This compound was obtained as a white crystalline solid melting at 295-298 [deg.] C through a common reaction. Yield: 88% (286 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 11.15 (1H, s), 10.67 (1H, s), 7.68 (1H, s), 7.31 (1H, d, J = 7.8 Hz), 7.15 (1H , d, J = 9.0 Hz), 6.84 (2H, s), 2.39 (6H, s), 2.34 (3H, s), 2.18 (3H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 161.3, 160.8, 141.4, 136.5, 136.1, 132.1, 130.2, 128.9, 128.8, 128.7, 114.9, 114.1, 104.2, 21.4, 20.5, 20.4; IR: 3294, 2836, 1643, 1598, 1424, 1235, 1195 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 19 H 19 NO 2 S: 325.1136, Found: 325.1134.

(26) 4- Hydroxy -6-isopropyl-3- ( Phenylthio ) Quinolin-2 (1 H ) -One (4- Hydroxy -6-isopropyl-3- (phenylthio) quinolin-2 (1 H ) -one; 5i)

This compound was obtained as a white crystalline solid melting at 213-215 [deg.] C through a common reaction. Yield: 82% (255 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 11.49 (1H, s), 11.03 (1H, s), 7.74 (1H, d, J = 1.8 Hz), 7.48 (1H, dd, J = 7.8, 1.8 Hz), 7.27-7.23 (3H, m), 7.12-7.09 (3H, m), 2.96 (1H, sept, J = 7.2 Hz), 1.23 (6H, d, J = 7.2 Hz); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 165.3, 161.4, 141.5, 137.4, 136.9, 130.9, 128.8, 125.9, 124.9, 120.3, 115.3, 113.9, 100.3, 32.9, 23.8; IR: 3139, 2960, 1638, 1591, 1449, 1168 cm &lt; ^{-1 &} gt ;; HRMS m / z (M ⁺ ) calcd for C ₁₈ H ₁₇ NO ₂ S: 311.0980, Found: 311.0984.

(27) 4- Hydroxy -6-isopropyl-3- ( p - Tolylthio ) Quinolin-2 (1 H ) -One (4- Hydroxy -6-isopropyl-3- ( p -tolylthio) quinolin-2 (1 H ) -one; 5j)

This compound was obtained as a white crystalline solid melting at 224-227 [deg.] C through a common reaction. Yield: 83% (270 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 11.47 (1H, s), 10.96 (1H, s), 7.74 (1H, d, J = 1.2 Hz), 7.47 (1H, dd, J = 8.4, D, J = 8.4 Hz), 7.06-7.02 (4H, m), 2.95 (1H, sept, J = 7.2 Hz), 2.21 (3H, s), 1.21 J = 7.2 Hz); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 165.0, 161.5, 141.5, 137.3, 134.4, 133.2, 130.8, 129.4, 126.5, 120.3, 115.3, 113.9, 101.0, 32.9, 23.8, 20.4; IR: 3395, 2959, 1636, 1590, 1456, 1191 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 19 H 19 NO 2 S: 325.1136, Found: 325.1135.

(28) 6- Bromo -4- Hydroxy -3- ( p - Tolylthio ) Quinolin-2 (1 H ) -One (6- Bromo -4-hydroxy-3- ( p -tolylthio) quinolin-2 (1 H ) -one; 5k)

This compound was obtained as a white crystalline solid melting at 189-193 [deg.] C through a common reaction. Yield: 80% (289 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 11.69 (1H, s), 11.36 (1H, s), 7.99 (1H, s), 7.71 (1H, d, J = 9.0 Hz), 7.26 (1H , d, J = 9.0Hz), 7.07-7.03 (4H, m), 2.22 (3H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 163.9, 161.4, 137.9, 134.7, 134.4, 132.8, 129.5, 126.7, 125.7, 117.5, 116.0, 113.2, 102.4, 20.4; IR: 3290, 2838, 1644, 1593, 1465, 1220, 1112 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 16 H 12 BrNO 2 S: 360.9772, Found: 360.9775.

(29) 6- Bromo -3- Hydroxy -3- ( Meshil tithio ) Quinolin-2 (1 H ) -One (6- Bromo -4-hydroxy-3- (mesitylthio) quinolin-2 (1 H ) -one; 5l)

This compound was obtained as a white crystalline solid melting at 293-296 [deg.] C through a common reaction. Yield: 82% (320 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 11.39 (1H, s), 11.04 (1H, s), 7.99 (1H, d, J = 1.8 Hz), 7.63 (1H, dd, J = 8.4, 2.4 Hz), 7.21 (1H, d, J = 9.0 Hz), 6.85 (2H, s), 2.38 (6H, s), 2.18 (3H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 160.7, 160.1, 141.5, 137.0, 136.7, 128.8, 128.7; 128.5, 125.1, 117.3, 116.1, 113.0, 105.9, 21.4, 20.4; IR: 3273, 2824, 1643, 1597, 1471, 1108 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 18 H 16 BrNO 2 S: 389.0085, Found: 389.0082.

(30) 6- Chloro -4- Hydroxy -3- ( p - Tolylthio ) Quinolin-2 (1 H ) -One (6- Chloro -4-hydroxy-3- ( p -tolylthio) quinolin-2 (1 H ) -one; 5m)

This compound was obtained as a white crystalline solid melting at 293-295 [deg.] C through a common reaction. Yield: 77% (245 mg); ^{1 H NMR (600 MHz, DMSO-} d 6): δ 11.69 (1H, s), 11.35 (1H, s), 7.85 (1H, d, J = 1.8 Hz), 7.61 (1H, dd, J = 9.0, 2.4 Hz), 7.32 (1H, d, J = 8.4Hz), 7.07-7.03 (4H, m), 2.22 (3H, s); ^{13 C NMR (150 MHz, DMSO-} d 6): δ 163.9, 161.3, 137.6, 134.7, 132.8, 131.7, 129.4, 126.7, 125.5, 122.7, 117.2, 115.5, 102.5, 20.4; IR: 3303, 2841, 1645, 1598, 1471, 1218, 1116 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 16 H 12 ClNO 2 S: 317.0277, Found: 317.0277.

< Example  3> Identification of usefulness and activity of synthetic compounds

(1) Confirmation of availability as a reactant

In order to confirm the usefulness of the compounds synthesized in Example 1 and Synthesis Example 1, the reaction as shown in the following Reaction Scheme 5 was carried out.

Specifically, 4-hydroxy-3- ( p -tolylthio) -2H-chromen-2-one (3b, 284 mg, 1.0 mmol) was dissolved in dichloromethane (10 mL) 3-chloroperbenzoic acid (431 mg, 2.5 mmol). The reaction was terminated by TLC, and the reaction mixture was poured into 10% potassium carbonate solution, extracted with ethyl acetate (3 × 15 mL), finally washed with brine solution and dried with anhydrous sodium sulfate. The solvent was then evaporated and recrystallization using ethyl acetate gave the pure product 15.

Further, 4-hydroxy -3- (p - tolyl thio) -2H- chromen-2-one (3b; 284 mg, 1.0 mmol ), 4- methyl-benzenesulfonyl chloride (285 mg, 1.5 mmol) and tri Ethylamine (606 mg, 6.0 mmol) was stirred in dichloromethane (10 ml) at room temperature for 2 hours. After confirming the completion of the reaction using TLC, thiophenol (165 mg, 1.5 mmol) was added to the reaction mixture. After the reaction was completed, the solvent was evaporated in vacuo, and the residue was purified by column chromatography using ethyl acetate and hexane to give the pure product 16 from the eluate.

[Reaction Scheme 5]

Hydroxy-3-tosyl-2H-chromen-2-one (15) was obtained in 97% yield in the presence of m-CPBA and at room temperature for 5 hours, . &Lt; / RTI &gt; In addition, when 3b is reacted with p- TsCl and triethylamine, the addition of thiophenol leads to the formation of 4- (phenylthio) -3- ( p -tolylthio) -2H-chromen- Gt; 95% &lt; / RTI &gt; yield. These results indicate that the synthesized sulfanylated derivatives can be usefully used to prepare various coumarin derivatives containing two different sulfanyl groups at positions 3 and 4 of the coumarin ring.

(a) 4- Hydroxy -3-tosyl-2 H - Kromen One (4- Hydroxy -3- tosyl -2 H - chromen -2-one; 15)

As a white crystalline solid with a melting point of 218-221 [deg.] C. Yield: 97% (307 mg); ^{1 H NMR (300 MHz, DMSO-} d 6): δ 7.76 (2H, d, J = 8.1 Hz), 7.72 (1H, d, J = 7.8 Hz), 7.41 (1H, t, J = 7.5 Hz), 7.21 (2H, d, J = 8.1 Hz), 7.09 (1H, t, J = 7.5 Hz), 7.04 (1H, d, J = 8.1 Hz), 2.29 (3H, s); ^{13 C NMR (75 MHz, DMSO-} d 6): δ 172.6, 159.2, 153.4, 142.8, 141.3, 132.0, 128.4, 126.6, 125.2, 122.5, 122.4, 115.8, 99.2, 20.9; IR: 3491, 1657, 1605, 1556, 1462, 1350, 1291 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 16 H 12 O 5 S: 316.0405, Found: 316.0409.

(b) 4- ( Phenylthio ) -3- ( p - Tolylthio )-2 H - Kromen One (4- ( Phenylthio ) -3- ( p -tolylthio) -2 H -chromen-2-one; 16)

Lt; RTI ID = 0.0 &gt; 105-107 C. &lt; / RTI &gt; Yield: 95% (357 mg); ^{1 H NMR (300 MHz, CDCl} 3): δ 7.92 (1H, dd, J = 8.1, 1.5 Hz), 7.50 (1H, td, J = 8.4, 1.5 Hz), 7.36-7.27 (8H, m), 7.19 (1H, td, J = 8.1, 0.9 Hz), 7.11 (2H, d, J = 7.8 Hz), 2.34 (3H, s); ¹³ C NMR (75 MHz, CDCl ₃ ): δ 157.3, 152.3, 152.2, 137.3, 134.1, 131.8, 130.4, 130.3, 129.7, 129.4, 129.3, 127.8, 127.2, 124.2, 119.7, 116.7, 20.9; IR: 1724, 1578, 1496, 1267, 1179 cm &lt; ^{-1 &} gt ;; ^{HRMS m / z (M +)} calcd for C 22 H 16 O 2 S 2: 376.0592, Found: 376.0589.

(2) Confirmation of heavy metal detection activity

Several organic molecules have been applied to detect fluorescence of various toxic metal ions such as Hg ^{2 +} , Pb ^{2 +} , Cd ^{2 +} and Cu ^{2 +} . Among these toxic metal ions, cadmium (Cd ²⁺ ) is very widely used in the electroplating, metallurgy and weapons industries. Thus, wastewater from these industries contains a very high amount of Cd ^{2 +} , which causes serious health problems such as renal impairment, calcium metabolic disorders, and prostate cancer. Therefore, detection and detection of Cd ^{2 +} is a very important problem.

In this connection, the inventors of the present invention examined the compound 3f prepared according to the above Example 1 and Synthesis Example 1 to determine whether fluorescence-sensing activity for important metal ions in water was observed. Specifically, the fluorescence titration in a 4 mL quartz cuvette was carried out between 0.50 mL of compound 3a in acetonitrile and 0.50 mL of various metal ions with a concentration of 500 mu m in water. All fluorescence measurements were performed using a Hitechi-7000 at room temperature and 355 nm (emission wavelength) after incubation for 5 minutes at a scan rate of 240 nm / min using a slit width of 5 nm and a photomultiplier tube of 400 V .

As a result, as shown in Figure 4a, the compound 3f are various metal ions, that is, Al ^3+, Ca ^{+ 2,} Cd ^{+ 2,} Co ^{+ 2,} Cr ^{+ 3,} Cu ^{2 +,} Fe ^{2 +,} Fe ^{3 +} , Hg ^{2 +} , Ni ^{2 +} , Pb ^{2 +} , and Zn ^{2 +} , respectively, showed selective fluorescence reactivity to Cd ^{2 +} . This result means that compound 3f is highly selective for sensing Cd ^{2 +} ions through fluorescent enhancement among multiple screened metal ions.

Next, in order to confirm the sensitivity of the compound 3f to Cd ^{2 +} ions, experiments were carried out under the condition that Cd ^{2 +} ions were present at different concentrations. Specifically, the fluorescence titration in a 4 mL quartz cuvette was performed between 0.50 mL of compound 3a in acetonitrile and 0.50 mL of Cd ^{2 +} at various concentrations in water (0-500 urn). As described above, all fluorescence measurement was carried out using a Hitechi-7000 at room temperature and 355 nm (emission wavelength) after incubation for 5 minutes at a scanning speed of 240 nm / min using a slit width of 5 nm and a photomultiplier tube of 400 V .

As a result, as shown in FIG. 4B and FIG. 5A, Compound 3f exhibited a high sensitivity to various concentrations of cadmium, exhibiting a maximum fluorescence emission intensity at 442 nm and also exhibiting various concentrations of Cd ^{2 +} ions at 442 nm , Which was identified from the linear correlation coefficient values (R ² = 0.99). The detection limit for the Cd ^{2 +} ion in water of compound 3f is 6.29 μm, which indicates that 3f has efficient fluorescence selectivity and sensitivity to Cd ^{2 +} ions. In addition, as shown in Figure 5b, according to Job's plot, the ratio of Cd ^{2 +} ions to 3f at the maximum fluorescence intensity is 1: 1, that is, the fluorescent intensity of the enhanced 3f is higher than the Cd ^{2 +} (Chelating) between the isolated electron pairs of oxygen (hydroxyl group) and photo-induced electron migration.

For comparison with thus synthesized compound 3f, the inventors of the present invention have found that the fluorescence detection activity of the currently commercially available 4-hydroxy coumarin, 4-hydroxyquinolinone and p -toluenesulfonyl hydrazide is shown in the above , None of which exhibited the cadmium (II) ion detection specificity.

That is, as described above, direct sulfanylation of 4-hydroxy coumarin and 4-hydroxy quinoline catalyzed by CuBr · Me ₂ S can be achieved using various 3-arylsulfanyl-4-hydroxy coumarins and 3- N-4-hydroxyquinolinone derivatives were obtained with very good yields, and the preparation process according to the present invention was carried out by using copper as a catalyst to convert SO and SN-bond decomposition of sulfonyl hydrazide and various 4-hydroxy coumarin or And direct cross-coupling of 4-hydroxyquinolinones. This method can provide an easy approach for direct CS bond formation, and 3-arylsulfanyl-4-hydroxycoumarin synthesized by the above method exhibits a low detection limit and a unique reversible function, Cd &lt; ^{2 + & gt ;} detection ability, it can be utilized as a composition for detecting cadmium in water.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. Do. That is, the practical scope of the present invention is defined by the appended claims and their equivalents.

Claims (12)

A 4-hydroxy-3-sulfanyl coumarin derivative represented by the following formula (1);
[Chemical Formula 1]

In Formula 1,
R &lt; ₁ &gt; is selected from the group consisting of hydrogen, (C1-C4) alkyl and halogen,
R ₂ and R ₃ are each independently selected from hydrogen or halogen,
R ₄ is selected from the group consisting of a substituted or unsubstituted phenyl group, a substituted naphthyl group and an unsubstituted thienyl group,
The substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups,
Wherein the substituted naphthyl group is substituted with a di (C1-C4 alkyl) amine group. 2. A compound according to claim 1, wherein R ₁ is selected from the group consisting of hydrogen, methyl, fluoro and chloro, R ₂ and R ₃ are each independently selected from the group consisting of hydrogen, bromo, fluoro and chloro And R ₄ is selected from the group consisting of phenyl, p -tolyl, mesityl, 5- (dimethylamino) naphthalen-1-yl and 2-thienyl. Nylcumarin derivatives. The method of claim 1 wherein the 4-hydroxy-3-ylsulfanyl coumarin derivatives is 4-hydroxy-3- (phenylthio) -2H- chromen-2-one, 4-hydroxy-3- (p - 2-one, 3 - ((5- (dimethylamino) naphthalen-1-yl Hydroxy-6-methyl-3- (phenylthio) -2H-chromen-2-one, 4-hydroxy- Methyl-3- ( p -tolylthio) -2H-chromen-2-one, 4-hydroxy-3- (mesitylthio) Chloro-4-hydroxy-3- ( p -tolylthio) -2H-chromen-2-one, 6- Chloro-4-hydroxy-3- (mesitylthio) -2H-chromen-2-one, 6-fluoro- 2-one, 7-bromo-4-hydroxy-3- (phenylthio) -2H-chromen- -7-fluoro-4-hydroxy-3- ( 2-one, 6,8-dichloro-4-hydroxy-3- (phenylthio) -2H-chromen- (Mesitylthio) -2H-chromen-2-one and 4-hydroxy-3- (thiophen-2-ylthio) -2H-chromen- 4-hydroxy-3-sulfanylcoumarin derivative. A 4-hydroxy-3-sulfanylquinolinone derivative represented by the following formula (2);
(2)

In Formula 2,
R ₅ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen,
R &lt; ₆ &gt; is (C1-C4) alkyl or hydrogen,
R ₇ is any one selected from the group consisting of a substituted or unsubstituted phenyl group and a substituted naphthyl group,
The substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups,
Wherein the substituted naphthyl group is substituted with a di (C1-C4 alkyl) amine group. The method of claim 4, wherein in the formula 2, R ₅ is any one selected from the group consisting of hydrogen, methyl, isopropyl, bromo or chloro, R ₆ is methyl or hydrogen, R ₇ is phenyl, p - (4-hydroxy-3-sulfanylquinolinone derivative) is selected from the group consisting of a thiol group, a tolyl group, a mesityl group and a 5- (dimethylamino) naphthalen-1-yl group. The method of claim 4, wherein the 4-hydroxy-3-sulfanylquinolinone derivative is 4-hydroxy-1-methyl-3- (phenylthio) quinolin- -methyl-3- (p-tolyl thio) quinolin -2 (1H) - one, 4-hydroxy-3 (mesityl thio) -1-methyl-quinolin -2 (1H) - one, 3 - ((5 - (dimethylamino) naphthalen-1-yl) thio) -4-hydroxy-1-methylquinolin-2 (1H) , 4-hydroxy -3- (p - tolyl thio) quinolin -2 (1H) - one, 4-hydroxy-6-methyl -3- (p - tolyl thio) quinolin -2 (1H) - one, 4 (4-hydroxy-6- isopropyl-3- (phenylthio) quinolin-2 (1H) -one, -hydroxy-6-isopropyl -3- (p-tolyl thio) quinolin -2 (1H) - one, 6-bromo-4-hydroxy -3- (p-tolyl thio) quinolin -2 (1H) -one, 6-bromo-3-hydroxy-3- (mesityl thio) quinoline-2 (1H) -one and 6-chloro-4-hydroxy-3- (p-tolyl thio) quinoline-2 ( 1H) - on 4-hydroxy-3-sulfanylquinolinone derivative. A composition for detecting cadmium in water, comprising a 4-hydroxy-3-sulfanyl coumarin derivative represented by the following formula (1) or a 4-hydroxy-3-sulfanyl quinolinone derivative represented by the following formula (2) as an active ingredient;
[Chemical Formula 1]

In Formula 1,
R &lt; ₁ &gt; is selected from the group consisting of hydrogen, (C1-C4) alkyl and halogen,
R ₂ and R ₃ are each independently selected from hydrogen or halogen,
R ₄ is selected from the group consisting of a substituted or unsubstituted phenyl group, a substituted naphthyl group and an unsubstituted thienyl group,
The substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups,
Wherein said substituted naphthyl group is substituted with a di (C1-C4 alkyl) amine group;

(2)

In Formula 2,
R ₅ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen,
R &lt; ₆ &gt; is (C1-C4) alkyl or hydrogen,
R ₇ is any one selected from the group consisting of a substituted or unsubstituted phenyl group and a substituted naphthyl group,
The substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups,
Wherein the substituted naphthyl group is substituted with a di (C1-C4 alkyl) amine group. The method of claim 7, wherein in Formula 1, R ₁ is hydrogen, methyl, is selected from the group consisting of fluoro and chloro, R ₂ and R ₃ is the group consisting of and chloro with hydrogen, bromo, fluoro, each independently Wherein R &lt; ₄ &gt; is selected from the group consisting of phenyl, p -tolyl, mesityl, 5- (dimethylamino) naphthalene-1-yl and 2-thienyl. The method of claim 7, wherein in the formula 2, R ₅ is any one selected from the group consisting of hydrogen, methyl, isopropyl, bromo or chloro, R ₆ is methyl or hydrogen, R ₇ is phenyl, p - And a 5- (dimethylamino) naphthalene-1-yl group. 2. The composition for detecting cadmium in water according to claim 1, to a) 4-hydroxy-coumarin and b) represented by the formula (3) a sulfonyl hydrazide, below, comprising the step of reacting using CuBr · Me ₂ S 4 as a catalyst represented by the formula (1) hydroxy -3-sulfanyl coumarin derivative: &lt; EMI ID =
(3)

In Formula 3,
R &lt; ₈ &gt; is selected from the group consisting of hydrogen, (C1-C4) alkyl and halogen,
R ₉ and R ₁₀ are each independently selected from hydrogen or halogen;
[Chemical Formula 1]

In Formula 1,
R &lt; ₁ &gt; is selected from the group consisting of hydrogen, (C1-C4) alkyl and halogen,
R ₂ and R ₃ are each independently selected from hydrogen or halogen,
R ₄ is selected from the group consisting of a substituted or unsubstituted phenyl group, a substituted naphthyl group and an unsubstituted thienyl group,
The substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups,
Wherein the substituted naphthyl group is substituted with a di (C1-C4 alkyl) amine group. a) reacting 4-hydroxyquinolinone represented by the following general formula (4) and b) sulfonylhydrazide with CuBr 占_{2 2} S as a catalyst; 4-hydroxy -3-sulfanylquinolinone &lt; / RTI &gt; derivative:
[Chemical Formula 4]

In Formula 4, R ₁₁ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen,
R &lt; ₁₂ &gt; is (C1-C4) alkyl or hydrogen;
(2)

In Formula 2,
R ₅ is any one selected from the group consisting of hydrogen, (C 1 -C 4) alkyl and halogen,
R &lt; ₆ &gt; is (C1-C4) alkyl or hydrogen,
R ₇ is any one selected from the group consisting of a substituted or unsubstituted phenyl group and a substituted naphthyl group,
The substituted phenyl group is one in which one to three hydrogens of the benzene ring are substituted with (C1-C4) alkyl groups,
Wherein the substituted naphthyl group is substituted with a di (C1-C4 alkyl) amine group. delete

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