阅读说明：本技术 1,4,2-氧杂噻唑类衍生物及其制备方法 (1,4, 2-oxathiazole derivatives and preparation method thereof ) 是由 程斌 李慧 刘豆 汪太民 孙海燕 翟宏斌 于 2020-11-02 设计创作，主要内容包括：本发明涉及化学合成领域,具体为1,4,2-氧杂噻唑类衍生物及其制备方法；本发明涉及的方法是由α-烯醇二硫代酯和肟氯类化合物为起始原料,原料易于制备,反应采用不同的反应溶剂,可在室温条件反应制备合成1,4,2-氧杂噻唑类衍生物。反应中没有使用贵重金属催化剂,反应条件温和,操作简单,后处理方便,产率高,且在制备过程中无需惰性气体保护。(The invention relates to the field of chemical synthesis, in particular to a 1,4, 2-oxathiazole derivative and a preparation method thereof; the method uses alpha-enol dithioester and oxime chloride compounds as starting materials, the raw materials are easy to prepare, different reaction solvents are adopted in the reaction, and the 1,4, 2-oxathiazole derivatives can be prepared and synthesized by the reaction at room temperature. No noble metal catalyst is used in the reaction, the reaction condition is mild, the operation is simple, the post-treatment is convenient, the yield is high, and the inert gas protection is not needed in the preparation process.)

1,4, 2-oxathiazole derivatives, which are characterized in that the structural formula is shown as III or III',

wherein: r¹Is phenyl or alkyl substituent; r²Is phenyl or substituted phenyl, alkyl substituent.

2. The 1,4, 2-oxathiazole derivative according to claim 1, wherein: the substituted phenyl group includes 4-methoxy, 4-methyl, 2-naphthalene, 4-fluoro and 3-chloro.

A process for producing 1,4, 2-oxathiazole derivatives, which comprises the following steps:

in the formula, the preparation method of the compound III comprises the following steps: dissolving the compound I and the compound II in a methanol solvent, adding triethylamine for reaction, removing the methanol solvent after the reactant I disappears completely, and eluting by column chromatography to obtain a compound III.

The preparation method of the compound III' comprises the following steps: dissolving a compound I and a compound II in a 1, 4-dioxane solvent, adding triethylamine for reaction, completely removing a reactant I, removing the 1, 4-dioxane solvent, and eluting by column chromatography to obtain a compound III'.

4. A process for preparing 1,4, 2-oxathiazole derivatives according to claim 3, which comprises the steps of: dissolving the compound I and the compound II in a methanol solvent or a 1, 4-dioxane solvent at room temperature, wherein the conditions of removing the methanol solvent and removing the 1, 4-dioxane solvent are reduced pressure.

5. A process for preparing 1,4, 2-oxathiazole derivatives according to claim 3, which comprises the steps of: when the compound III is prepared, the molar ratio of the compound I to the compound II to triethylamine is I: II: 1:1.5, and the concentration of a methanol solution is 0.1M.

6. A process for preparing 1,4, 2-oxathiazole derivatives according to claim 3, which comprises the steps of: in the preparation of the compound III', the molar ratio of the compound I to the compound II to the triethylamine is I: II: 1:1:1, and the concentration of the 1, 4-dioxane solution is 0.1M.

7. A process for preparing 1,4, 2-oxathiazole derivatives according to claim 3, which comprises the steps of: the eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the eluent to the ethyl acetate is V_{Petroleum ether}:V_{Ethyl acetate}＝30:1～10:1。

8. A1, 4, 2-oxathiazole derivative composition, which is characterized by comprising the 1,4, 2-oxathiazole derivative.

Technical Field

The invention relates to the field of chemical synthesis, in particular to a 1,4, 2-oxathiazole derivative and a preparation method thereof.

Background

Organic sulfur compounds show increasingly wide application prospects in the aspects of medicines, pesticides, biology, organic functional materials and the like. The sulfur-containing heterocyclic ring is an important intermediate for synthesizing a plurality of biological and medical active molecules, and particularly has potential biological activity after being modified by functional groups. Thiazole compounds are an important classification of sulfur-containing heterocyclic compounds, thiazole and derivatives thereof are heterocyclic compounds with a plurality of biological activities, and the structural units of the thiazole and the derivatives thereof contain five-membered ring structural frameworks of oxygen, nitrogen and sulfur, and the five-membered ring structural frameworks are chemically modified to possibly obtain the derivatives with higher biological activities. Scientists have reported the synthesis of 1,4, 2-oxathiazole derivatives. In 1961, HuI sgen and Mack et al first reported the 1, 3-dipolar cycloaddition of thiocarbonyl-containing compounds with nitrile oxides to give 1,4, 2-oxathiazoles (1, 3-DII polar add I tons I ons of nI trI oxi I des to C-e bases, R.Hu I sgen; W.Mack and Anneser, E.E.Angew.chem., 1961,73, 656-657). In 2015, B.C.LemerI er and J.G.PIerce constructed 1,4, 2-oxathiazole five-membered ring skeleton by DDQ oxidation using thiohydroxamic acid derivatives were simple and efficient, but the reaction conditions were complicated and severe (Synthesis of 1,4,2-Oxath Iozole va Iot cycle Iot ion of Th Iohydrox Iom Io Ac I ds, B.C.LemerI er and J.G.PIerce, org.Lett.2015,17,4542 + 4545).

Although chemists have made relevant reports on the synthesis of 1,4, 2-oxathiazole derivatives, problems still exist in the synthesis of the compounds, such as the application of excessive catalyst, small substrate application range, difficult preparation of raw materials and the like. Based on the above, the development of an indirect, efficient and green method for synthesizing 1,4, 2-oxathiazole derivatives is urgent.

Disclosure of Invention

One of the objects of the present invention is to provide 1,4, 2-oxathiazole derivatives, which have the structural formula III or III',

wherein: r¹Is phenyl or alkyl substituent; r²Is phenyl or substituted phenyl (substituted phenyl includes 4-methoxy, 4-methyl, 2-naphthalene, 4-fluoro and 3-chloro), alkyl substituent.

Another object of the present invention is to provide a process for preparing 1,4, 2-oxathiazole derivatives, which comprises the following steps:

in the formula, the preparation method of the compound III comprises the following steps: dissolving the compound I and the compound II in a methanol solvent, adding triethylamine for reaction, removing the methanol solvent after the reactant I disappears completely, and eluting by column chromatography to obtain a compound III.

The preparation method of the compound III' comprises the following steps: dissolving a compound I and a compound II in a 1, 4-dioxane solvent, adding triethylamine for reaction, completely removing a reactant I, removing the 1, 4-dioxane solvent, and eluting by column chromatography to obtain a compound III'.

Dissolving the compound I and the compound II in a methanol solvent or a 1, 4-dioxane solvent at room temperature, wherein the conditions of removing the methanol solvent and removing the 1, 4-dioxane solvent are reduced pressure.

When the compound III is prepared, the molar ratio of the compound I to the compound II to triethylamine is I: II: 1:1.5, and the concentration of a methanol solution is 0.1M.

In the preparation of the compound III', the molar ratio of the compound I to the compound II to the triethylamine is I: II: 1:1:1, and the concentration of the 1, 4-dioxane solution is 0.1M.

The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the eluent to the ethyl acetate is V_{Petroleum ether}:V_{Ethyl acetate}＝30:1～10:1。

The invention also provides an application mode, namely a 1,4, 2-oxathiazole derivative composition, wherein the composition comprises the 1,4, 2-oxathiazole derivative.

The invention has the beneficial effects that: the method uses alpha-enol dithioester and oxime chloride compounds as starting materials, the raw materials are easy to prepare, different reaction solvents are adopted in the reaction, and the 1,4, 2-oxathiazole derivatives can be prepared and synthesized by the reaction at room temperature. No noble metal catalyst is used in the reaction, the reaction condition is mild, the operation is simple, the post-treatment is convenient, the yield is high, and the inert gas protection is not needed in the preparation process.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of a product III-1 obtained in an example of the present invention;

FIG. 2 is a nuclear magnetic carbon spectrum of a product III-1 obtained in an example of the present invention;

FIG. 3 is a nuclear magnetic hydrogen spectrum of a product III' -1 obtained in an example of the present invention;

FIG. 4 shows the nuclear magnetic carbon spectrum of the product III' -1 obtained in the example of the present invention.

Detailed Description

The technical scheme of the invention is further explained by specific embodiments in the following with the accompanying drawings:

the preparation method comprises the steps of dissolving the compound I and the compound II in an organic solvent for reaction, removing the solvent after the reaction is finished, and then obtaining the target compound by using a column chromatography method. Experiments show that the preferable organic solvents of the invention are methanol and 1, 4-dioxane, the yield of the reaction product is generally high, and when the target compound III is prepared, the molar ratio of the raw materials is that the molar ratio of the compound I to the compound II to the triethylamine is I: II: triethylamine 1:1:1.5, the optimal concentration of the solution is 0.1M; when the target compound III' is prepared, the molar ratio of the raw materials is that the compound I, the compound II and triethylamine are in a molar ratio of I: II: triethylamine is 1:1:1, and the optimal concentration of the solution is 0.1M. In all of the following examples, nuclear magnetic spectroscopy was performed by Bruker 400, JEOL 400 instrument in CDCl₃To obtain the compound. Delta values are internal standard relative values (CDCl)₃Scaling delta 7.26¹H NMR and 77.16¹³C NMR). High Resolution Mass Spectrometry (HRMS) was obtained using a 4G quadrupole t I me-of-fl I light (QTof) mass spectrometer.

The invention is illustrated below with reference to specific embodiments.

The first embodiment is as follows:

the reaction scheme of example 1, the compounds I-1, II-1 and the product III-1 used in particular have the following structures

The specific experimental steps are as follows: 63mg (0.30mmol, 1.0 equivalent) of Compound I-1 and 47mg (0.3mmol, 1.0 equivalent) of Compound II-1 were dissolved in 3mL of methanol, and triethylamine (0.45mmol, 1.5 equivalents) was added thereto and reacted at room temperature for 15 min. After the reaction was completed, the reaction mixture was evaporated under reduced pressure by a water pump to remove the solvent. The residue was washed with 200-mesh 300-mesh silica gel and eluted with a volume ratio of V_{Petroleum ether}:V_{Ethyl acetate}30: 1-10: 1) to obtain a compound shown as III-1, and identifying a product through nuclear magnetism and high-resolution mass spectrometry, wherein the product is shown as figure 1 and figure 2.

Preparation of the target Compound III' -1: 63mg (0.30mmol, 1.0 equivalent) of Compound I-1 and 47mg (0.3mmol, 1.0 equivalent) of Compound II-1 were dissolved in 3mL of 1, 4-dioxane, and triethylamine (0.3mmol, 1.0 equivalent) was added and reacted at room temperature. After the reaction was completed, the reaction mixture was evaporated under reduced pressure by a water pump to remove the solvent. The residue was washed with 200-mesh 300-mesh silica gel and eluted with a volume ratio of V_{Petroleum ether}:V_{Ethyl acetate}30: 1-10: 1) to obtain a compound shown as III' -1, and identifying a product by nuclear magnetism and high-resolution mass spectrometry, wherein the product is shown in fig. 3 and 4.

Product III-1 was a white solid in 89% yield.¹H NMR(400MHz,CDCl₃)δ8.01(d,J＝7.2Hz,2H),7.83(d,J＝7.2Hz,2H),7.59–7.46(m,6H),7.19(s,1H)；¹³C NMR(100MHz,CDCl₃)δ186.5,176.0,160.9,137.5,132.6,132.4,129.5,128.8,128.0,127.8,126.2,91.0；ESⅠ-HRMS m/z calcd for C₁₆H₁₂NO₂S[M+H]⁺282.0583,found 282.0588.

The product III' -1 is a yellow solid in 85% yield.¹H NMR(400MHz,CDCl₃)δ8.02(d,J＝7.6Hz,2H),7.72(d,J＝6.8Hz,2H),7.63(t,J＝7.6Hz,1H),7.56–7.39(m,5H),4.48(d,J＝17.6Hz,1H),3.98(d,J＝17.6Hz,1H),2.29(s,3H)；¹³C NMR(100MHz,CDCl₃)δ194.0,157.9，135.9,134.2，131.3,129.0，128.4,127.8,127.7,109.4,49.9,13.8(1C mⅠssⅠng)；ESⅠ-HRMS m/z calcd for C₁₇H₁₅NO₂S₂Na[M+Na]⁺352.0436,found 352.0444.

Example 2

The procedure used in the examples for preparing the other compounds of the invention (compounds III-2 to III-8 and III '-2 to III' -8) was the same as in example 1, with the following reaction conditions: compound I (0.30mmol, 1.0 equiv.), Compound II (0.30mmol, 1.0 equiv.) were dissolved in 3mL of methanol (or 1, 4-dioxane), followed by addition of triethylamine, and reacted at room temperature for 15 minutes to 2 hours.

The structures of the starting materials used for the preparation of compounds III-2 to III-8 and III '-2 to III' -8 are as follows:

the preparation method of the compound I-2 comprises the following steps: to a suspension of sodium hydride (58.8mmol) in tetrahydrofuran (20.0mL) was added dropwise a solution of imidazole (2.0g) in tetrahydrofuran (40.0mL) under ice-bath over about five minutes, the mixture becoming viscous with the addition of imidazole. Then a solution of carbon disulfide (11.0mmol, 2.7mL) in tetrahydrofuran (20.0mL) was added dropwise and the reaction mixture was stirred at 0-5 ℃ for 15 min. The reaction mixture became clear and dark yellow, to which was added dropwise a solution of methyl iodide (38.2mmol, 2.4mL) in tetrahydrofuran (20.0mL) over 2 minutes, and then the reaction mixture was stirred at 0-5 ℃ for 10 minutes. The excess sodium hydride was quenched by addition of distilled water. The system was extracted with ethyl acetate (10.0mL) and dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure with a water pump to give the crude product without purification.

Acetone (5mmol) in N, N-dimethylformamide (10mL) was added to a mixture of sodium hydride (12.5mmol) in DMF-hexane (4:1, 10mL) at 0 deg.C, and the mixture was reacted at 0 deg.C for 1 hour, after 1 hour, the yellow oily substance (5mmol) obtained above was slowly added to the system and reacted at room temperature for 10 hours, after the reaction was completed, 25 mL of 0.1M HCl was added to quench the reaction, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue is taken up in 200-300 mesh silica gel, eluent (volume ratio V)_{Petroleum ether}:V_{Ethyl acetate}100:1-50:1) column chromatography to obtain i-2.

The preparation method of the compounds II-3 to II-8 comprises the following steps: a50 mL round bottom flask was charged with aldehyde (1 eq.), hydroxylamine hydrochloride (1.2 eq.), H₂O and methanol. Then, K is added₂CO₃(1.5 equiv.) was added slowly to the solution. The reaction was stirred at rt overnight. After the reaction was completed, methanol was removed, and the aqueous layer was extracted three times with ethyl acetate. The organic layers were combined over anhydrous Na₂SO₄And (5) drying. After removal of the solvent, the crude aldoxime was used for the next step. A50 mL round bottom flask was charged with the first step crude aldoxime and N, N-dimethylformamide. Then, a solution of N-chlorosuccinimide (1.1 equivalent) in N, N-dimethylformamide was slowly added dropwise to the system over 10 minutes. The reaction was stirred at room temperature for 4 hours. After completion, the reaction mixture was poured into water, extracted three times with ethyl acetate, and the combined organic layers were washed with water and brine, and with anhydrous Na₂SO₄And (5) drying. After removal of the solvent, the residue is chromatographed (petroleum ether: ethyl acetate: 30:1-5:1) to give the desired oxime.

The structures and data of the products III-2 to III-8 obtained are characterized as follows:

product III-2 was a white solid in 91% yield.¹H NMR(400MHz,CDCl₃)δ8.01(d,J＝6.8Hz,2H),7.71(d,J＝8.0Hz,2H),7.58–7.46(m,3H),7.31(d,J＝8.0Hz,2H),7.17(s,1H),2.43(s,3H)；¹³C NMR(100MHz,CDCl₃)δ186.4,176.2,160.8,143.1,137.5,132.6,130.2,128.8,127.9,127.8,123.2,90.9,21.7；ESI-HRMS m/z calcd for C₁₇H₁₄NO₂S[M+H]⁺296.0740,found 296.0745.

Product III-3 was a yellow solid in 84% yield.¹H NMR(400MHz,CDCl₃)δ8.00(d,J＝7.6Hz,2H),7.77(d,J＝8.0Hz,2H),7.60–7.45(m,5H),7.20(s,1H)；¹³C NMR(100MHz,CDCl₃)δ186.5,175.7,160.0,138.7,137.4,132.7,129.9,129.2,128.8,127.8,124.6,91.2；ESI-HRMS m/z calcd for C₁₆H₁₀ClNO₂SNa[M+Na]⁺338.0013,found 338.0017.

Product III-4 was a white solid in 76% yield.¹H NMR(400MHz,CDCl₃)δ8.18(d,J＝8.0Hz,2H),8.01(d,J＝7.2Hz,2H),7.90(d,J＝8.0Hz,2H),7.57(t,J＝7.2Hz,1H),7.50(t,J＝7.6Hz,2H),7.21(s,1H),3.96(s,3H)；¹³C NMR(100MHz,CDCl₃)δ186.5,175.6,166.0,160.2,137.4,133.5,132.8,130.6,130.1,128.8,128.0,127.9,91.2,52.7；ESI-HRMS m/z calcd for C₁₈H₁₄NO₄S[M+H]⁺340.0638,found 340.0644.

Product III-5 was a yellow solid in 90% yield.¹H NMR(400MHz,CDCl₃)δ8.22(s,1H),8.02(d,J＝7.2Hz,2H),7.98–7.86(m,4H),7.64–7.53(m,3H),7.50(t,J＝7.6Hz,2H),7.20(s,1H)；¹³C NMR(100MHz,CDCl₃)δ186.4,176.0,160.9,137.5,135.0,132.9,132.6,129.4(2C),128.9,128.8,128.5,128.1,127.8,127.5,123.5(2C),91.0；ESI-HRMS m/z calcd for C₂₀H₁₃NO₂S[M+H]⁺332.0740,found 332.0747.

Product III-6 was a yellow solid in 92% yield.¹H NMR(400MHz,CDCl₃)δ8.00(d,J＝7.2Hz,2H),7.66–7.58(m,2H),7.54(t,J＝7.6Hz,1H),7.48(t,J＝7.6Hz,2H),7.41–7.33(m,2H),7.16(s,1H),2.41(s,3H)；¹³C NMR(100MHz,CDCl₃)δ186.4,176.0,160.9,139.4,137.5,133.2,132.5,129.3,128.7,128.5,127.8,125.9,125.1,90.9,21.4；ESI-HRMS m/z calcd for C₁₇H₁₄NO₂S[M+H]⁺296.0740,found 296.0746.

Product III-7 was a yellow solid in 55% yield.¹H NMR(400MHz,CDCl₃)δ7.98(d,J＝7.2Hz,2H),7.59–7.44(m,3H),7.10(s,1H),1.44(s,9H)；¹³C NMR(100MHz,CDCl₃)δ186.5,176.6,171.2,137.7,132.5,128.7,127.7,90.5,35.5,29.7；ESI-HRMS m/z calcd for C₁₄H₁₆NO₂S[M+H]⁺262.0896,found 262.0899.

Product III-8 was a white solid in 80% yield.¹H NMR(400MHz,CDCl₃)δ7.66(d,J＝8.4Hz,2H),7.28(d,J＝8.0Hz,2H),6.43(s,1H),2.40(s,3H),2.29(s,3H)；¹³C NMR(100MHz,CDCl₃)δ193.6,173.8,160.5,143.0,130.1,127.8,123.2,94.2,29.3,21.7；ESI-HRMS m/z calcd for C₁₂H₁₂NO₂S[M+H]⁺234.0583,found 234.0588.

The structures and data of the products III '-2 to III' -8 obtained are characterized as follows:

the product III' -2 is a yellow solid with a yield of 91%.¹H NMR(400MHz,CDCl₃)δ8.02(d,J＝6.8Hz,2H),7.67–7.58(m,3H),7.51(t,J＝7.6Hz,2H),7.23(d,J＝7.6Hz,2H),4.47(d,J＝17.6Hz,1H),3.97(d,J＝17.6Hz,1H),2.39(s,3H),2.29(s,3H)；¹³C NMR(100MHz,CDCl₃)δ194.1,157.9,141.8,136.0,134.2,129.7,129.0,128.4,127.8,124.9,109.2,49.9,21.6,13.9；ESI-HRMS m/z calcd for C₁₈H₁₇NO₂S₂Na[M+Na]⁺366.0593,found 366.0599.

The product III' -3 is a yellow oily liquid in 87% yield.¹H NMR(400MHz,CDCl₃)δ8.01(d,J＝7.2Hz,2H),7.68–7.58(m,3H),7.52(t,J＝7.6Hz,2H),7.40(d,J＝8.8Hz,2H),4.48(d,J＝17.6Hz,1H),3.97(d,J＝17.6Hz,1H),2.28(s,3H)；¹³C NMR(100MHz,CDCl₃)δ193.9,157.0,137.4,135.9,134.3,129.3,129.0(2C),128.4,126.2,109.8,49.8,13.9；ESI-HRMS m/z calcd for C₁₇H₁₄ClNO₂S₂Na[M+Na]⁺382.0047,found 382.0052.

The product III' -4 is a white solid with a yield of 86%.¹H NMR(400MHz,(CD₃)₂CO)δ8.14(d,J＝7.2Hz,2H),8.12(d,J＝6.8Hz,2H),7.88(d,J＝8.4Hz,2H),7.71(t,J＝7.2Hz,1H),7.59(t,J＝7.6Hz,2H),4.77(d,J＝17.6Hz,1H),4.09(d,J＝18.0Hz,1H),3.92(s,3H),2.25(s,3H)；¹³C NMR(100MHz,(CD₃)₂CO)δ194.7,166.4,157.8,137.0,134.8,133.3,132.8,130.8,129.7,129.2,128.5,110.6,52.7,49.5,13.7；ESI-HRMS m/z calcd for C₁₉H₁₇NO₄S₂Na[M+Na]⁺410.0491,found 410.0496.

The product III' -5 is a yellow solid with a yield of 91%.¹H NMR(400MHz,(CD₃)₂CO)δ8.22(s,1H),8.16(d,J＝7.2Hz,2H),8.12–8.06(m,1H),8.04–7.90(m,3H),7.71(t,J＝7.6Hz,1H),7.66–7.55(m,4H),4.78(d,J＝17.6Hz,1H),4.08(d,J＝17.6Hz,1H),2.27(s,3H)；¹³C NMR(100MHz,(CD₃)₂CO)δ194.8,158.7,137.1,135.4,134.8,134.0,129.7,129.6(3C),129.2,128.7,128.0,126.3,124.2,109.8,49.4,13.7,(1C peak is merged with other peaks)；ESI-HRMS m/z calcd for C₂₁H₁₇NO₂S₂Na[M+Na]⁺402.0593,found 402.0599.

The product III' -6 is a yellow oily liquid in 93% yield.¹H NMR(400MHz,(CD₃)₂CO)δ8.14(d,J＝7.2Hz,2H),7.70(t,J＝7.2Hz,1H),7.63–7.50(m,4H),7.43–7.34(m,2H),4.73(d,J＝17.6Hz,1H),4.03(d,J＝18.0Hz,1H),2.40(s,3H),2.24(s,3H)；¹³C NMR(100MHz,(CD₃)₂CO)δ194.8,158.6,139.8,137.1,134.8,132.8,129.8,129.7,129.2,128.8,128.7,125.5,109.6,49.4,21.2,13.7；ESI-HRMS m/z calcd for C₁₈H₁₇NO₂S₂Na[M+Na]⁺366.0593,found 366.0598.

The product III' -7 is a yellow solid in 76% yield.¹H NMR(400MHz,(CD₃)₂CO)δ8.10(d,J＝6.8Hz,1H),7.69(t,J＝7.2Hz,1H),7.57(t,J＝7.6Hz,2H),4.62(d,J＝17.6Hz,1H),3.88(d,J＝17.6Hz,1H),2.18(s,3H),1.29(s,9H)；¹³C NMR(100MHz,(CD₃)₂CO)δ194.8,168.4,137.2,134.6,129.7,129.2,108.8,49.4,35.8,29.4,13.6；ESI-HRMS m/z calcd for C₁₅H₁₉NO₂S₂Na[M+Na]⁺332.0749,found 332.0754.

The product III' -8 is a yellow oily liquid in 84% yield.¹H NMR(400MHz,(CD₃)₂CO)δ7.59(d,J＝8.4Hz,2H),7.31(d,J＝8.4Hz,2H),4.02(d,J＝18.0Hz,1H),3.56(d,J＝17.6Hz,1H),2.38(s,3H),2.30(s,3H),2.21(s,3H)；¹³C NMR(100MHz,(CD₃)₂CO)δ202.6,158.2,142.6,130.5,128.2,125.8,108.7,53.3,30.6,21.4,13.5；ESI-HRMS m/z calcd for C₁₃H₁₅NO₂S₂Na[M+Na]⁺304.0436,found 304.0439.

It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.