阅读说明：本技术 一种新型科里–柴可夫斯基试剂的合成方法 (Synthesis method of novel Kerrico-Chaokski reagent ) 是由 曾庆乐 康晓康 于 2021-09-03 设计创作，主要内容包括：科里–柴可夫斯基试剂作为一种重要的碳卡宾有机环化试剂,在有机合成、药物化学、天然产物方面具有重要的作用。本专利开发了一种水介导的环状科里–柴可夫斯基试剂的合成方法,在碳酸铯碱性条件下,以乙腈和水为混合溶液,苯甲酰亚甲基二甲基溴化硫通过分子内环氧化反应,以中等至良好的收率在广泛的底物范围内合成五元环状科里–柴可夫斯基试剂。该方法具有反应条件温和,操作简单,无金属,具有极大的潜在价值等优点。(The Kerrico-Chagowski reagent is used as an important carbon carbene organic cyclization reagent and has important functions in the aspects of organic synthesis, medicinal chemistry and natural products. The patent develops a water-mediated synthesis method of a cyclic Cory-Chakowski reagent, under the alkaline condition of cesium carbonate, acetonitrile and water are used as mixed solution, benzoyl methylene dimethyl sulfur bromide is subjected to intramolecular epoxidation reaction, and the five-membered cyclic Cory-Chakowski reagent is synthesized in a wide substrate range with medium to good yield. The method has the advantages of mild reaction conditions, simple operation, no metal, great potential value and the like.)

1. A novel synthesis method of Kerri-Chaokuski reagent is characterized in that: in a mixed solution of acetonitrile and water, cesium carbonate is taken as alkali, and benzoyl methylene dimethyl sulfur bromide is subjected to intramolecular cyclization reaction to synthesize a cyclic Kelly-Chakowski reagent in one step; the formyl methylene dimethyl sulfur bromide is 2- (methoxyl) benzoyl methylene dimethyl sulfur bromide, 3- (methoxyl) benzoyl methylene dimethyl sulfur bromide, 4- (methoxyl) benzoyl methylene dimethyl sulfur bromide, 2,5- (dimethoxy) benzoyl methylene dimethyl sulfur bromide, 4- (methyl) benzoyl methylene dimethyl sulfur bromide, naphthoyl methylene dimethyl sulfur bromide, dibenzoyl methylene dimethyl sulfur bromide, 3- (fluorine) benzoyl methylene dimethyl sulfur bromide, 2- (fluorine) benzoyl methylene dimethyl sulfur bromide, 4- (trifluoromethyl) benzoyl methylene dimethyl sulfur bromide, 2,4- (difluoro) benzoyl methylene dimethyl sulfur bromide, 4- (fluorine) benzoyl methylene dimethyl sulfur bromide, 2- (dimethyl sulfur bromide, 3- (dimethyl sulfur bromide, 2- (dimethyl sulfur bromide, 4- (fluorine) benzoyl methylene dimethyl sulfur bromide, 2- (dimethyl sulfur bromide, 4- (fluorine) benzoyl methylene bromide, 2- (dimethyl sulfur, 4- (dimethyl sulfur bromide, 2-dimethyl sulfur, 4- (fluorine) benzoyl methylene bromide, 2-methyl sulfur, 2-dimethyl sulfur bromide, 4- (dimethyl sulfur bromide, 4-methyl) benzoyl methylene sulfur, 2-methyl sulfur, 4-methyl sulfur bromide, 2-methyl sulfur bromide, 4-methyl sulfur, 4-methyl-bromide, 2-methyl-sulfide, 2-methyl bromide, 2-methyl bromide, sodium-methyl bromide, 2, 3- (chloro) benzoylmethylene dimethyl sulfur bromide, 4- (chloro) benzoylmethylene dimethyl sulfur bromide, 2- (chloro) benzoylmethylene dimethyl sulfur bromide, 4- (bromo) benzoylmethylene dimethyl sulfur bromide, 3- (bromo) benzoylmethylene dimethyl sulfur bromide, 4- (cyano) benzoylmethylene dimethyl sulfur bromide and thiophenecarboxylmethylene dimethyl sulfur bromide.

2. The method for synthesizing a novel Cochlikovisky reagent as claimed in claim 1, wherein the mixed solution of acetonitrile and water is a mixed solution of acetonitrile and water in a volume ratio of 4: cesium carbonate is used in an amount of 3 equivalents.

Technical Field

The patent relates to the research field of organic synthesis, pharmaceutical synthesis and organic chemical industry, in particular to a five-membered cyclic Cory-Chakowski reagent synthesized by one step through intramolecular cyclization reaction of benzoyl methylene dimethyl sulfur bromide under the action of water and alkali.

Background

The Kery-Chakowski reagent was derived from dimethyl sulfoxide by E.J.Corey et al in 1962 (E.J.Corey, M.Chaykovsky, J.Am.chem.Soc.1962,84, 867-containing 868.), and was often added to a ketone, aldehyde, imine and a, β -unsaturated carbonyl compound to form the corresponding three-membered ring product ((a) L.F.Hsu, C.P.Chang, M.C.Li, N.C.Chang, J.org.chem.1993,58, 4756-containing 4757 (b) S.K.Thompson; C.H.Heathcock, J.org.1992, 57, 5979-containing 5989 (c) A.H.Li, L.X.Dai, V.K.Aggarwal, Chemg.1997, 231, 72). The Kerich-Chaokussy reagent is widely used as a cyclization reagent in organic synthesis ((a) S.Hajra, S.Roy, S.A.Saleh, Org.Lett.2018,20, 4540-containing 4544- (b) M.M Heravi, S.Asadi, N.Nazari, B.Malekzadeh Lashkariani, Curr.Org.Synth.2016,13, 308-containing 333-containing), pharmaceutical chemistry ((a) J.D.Burch, M.Belley, R.Fortin, D.Deschenne, M.Girard, J.Colluci, J.Farand, A.G.Therien, M.C.Mathieu, D.Denis, E.Vitulat, J.F.Lesre, S.Gagnne, M.T.T. Cheng.T. Cheng. Cheng.J.J.J.C.J.Cheng.J.J.J.J.Cheng.J.J.J.J.J.J.Cheng.J.J.J.Shi, C.Cheng.J.J.J.J.J.J.Shi, C.J.Cheng.J.J.J.J.J.Cheng.J.J.J.J.J.C.J.J.J.J.Cheng.S.J.J.S.J.J.S.J.J.C.J.J.J.J.J.J.J.J.Cheng.J.J.Cheng.Shi, D.C.J.J.C.J.J.J.J.J.C.C.J.J.J.J.J.J.J.J.C.J.J.J.Cheng.J.J.J.C.C.J.J.J.J.J.J.J.J.J.J.J.J.J.J.J.Shi, D.C.C.J.J.C.C.J.C.C.J.J.J.J.J.J.J.J.C.J.J.J.J.J.C.J.J.J.C.C.No. Shi.No. Shi, D.No. Shi, D.C.No. Shi, D.C.C.C.C.C.C.C.No. Shi, D.C.C.C.C.C.C.C.C.S.C.C.D.No. Shi, D.No. Shi.S.No. Shi.S.S.S.S.S.S.S.S.S.S.S.S.S.D.D.S.D.S.S.S.D.S.S.C.C.C.C.C.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.D.S.S.D.S.S.S.S.C.C.S.S.S.S.C.C.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.No. Shih, D.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S.S. Based on this importance, the development of novel Cory-Chakowski reagents is of great value.

We report here a water-mediated intramolecular cyclization of phenacylidene dimethylbromide sulfur to give a novel five-membered cyclic Cory-Chagowski reagent.

To the best of our knowledge, no literature reports are found which are the same as the present application.

Disclosure of Invention

The invention provides a synthesis method of a novel Kerrico-Chaokski reagent.

The synthesis method of the Kelly-Chakowski reagent disclosed by the invention is completed in one step, namely, in a mixed solution of acetonitrile and water, cesium carbonate is used as alkali, and benzoyl methylene dimethyl sulfur bromide is subjected to intramolecular cyclization reaction to synthesize the annular Kelly-Chakowski reagent in one step, wherein the reaction equation is shown as follows.

The present invention is illustrated in more detail by the following examples, which are not to be construed as limiting the scope of the invention.

Detailed Description

Example one

To a 25mL glass tube equipped with a stirrer were added benzoylmethylen dimethylsulfide bromide (1mmol), cesium carbonate (3 equiv.), 2mL acetonitrile and 0.5mL water, and finally plugged with a rubber stopperAnd sealing and grinding the test tube. The tube was stirred in a pre-heated oil bath at 80 ℃ for 18h and the reaction mixture was cooled to room temperature. The reaction mixture was then quenched by the addition of saturated sodium chloride solution (10mL), extracted 3 times with ethyl acetate (15mL), and the combined organic layers were dried over anhydrous MgSO4 and then adsorbed on a rotary evaporator with basic alumina. The residue was purified by basic alumina flash column chromatography (petroleum ether: ethyl acetate 100: 1 as eluent) to give, after purification, 3-methyl-5-phenyl-2, 5-dihydro-1, 3 λ as a colorless oil⁶-thiazole-3-oxide in 55% yield.

The product 3-methyl-5-phenyl-2, 5-dihydro-1, 3 lambda⁶The structural characterization data of the 3-oxathiolate are as follows:

¹H NMR(400MHz,Chloroform-d)δ7.52(d,J＝1.5Hz,2H),7.28–7.18(m,3H),4.93(s,1H),4.72(d,J＝3.1Hz,1H),4.19(d,J＝3.1Hz,1H),2.18(s,3H).

¹³C NMR(101MHz,CDCl₃)δ158.45,136.13,128.69,128.23,125.50,85.04,71.97,15.14.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₀H₁₂NaO₂S⁺219.0450,found 219.0446.

example two

2- (methoxy) Benzylmethylene Dimethylthio bromide instead of Benzylmethylene Dimethylthio bromide as in example one, to give 5- (2-methoxy) -3-methyl-5-phenyl-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 67%.

¹H NMR(400MHz,Chloroform-d)δ7.52(dd,J＝7.6,1.8Hz,1H),7.32(ddd,J＝8.3,7.6,1.8Hz,1H),7.02–6.91(m,2H),5.01(s,2H),4.84(d,J＝2.3Hz,1H),4.56(d,J＝2.3Hz,1H),3.86(s,3H),2.31(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ157.10,156.46,129.76,125.72,120.36,111.21,90.00,71.71,55.60,14.91.

HRMS(ESI)m/z[M+Na]+Calcd for C11H14NaO3S+249.0556,found 249.0552.

EXAMPLE III

3- (methoxy) benzeneFormylmethylene dimethyl Sulfur Bromide instead of benzoylmethylene dimethyl Sulfur Bromide in example one, to give 5- (3-methoxy) -3-methyl-5-phenyl-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 78%.

¹H NMR(400MHz,Chloroform-d)δ7.33–7.26(m,2H),7.26–7.24(m,1H),6.91(dt,J＝7.1,2.4Hz,1H),5.06(s,2H),4.88(d,J＝3.1Hz,1H),4.34(d,J＝3.1Hz,1H),3.84(s,3H),2.31(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ159.58,158.21,137.63,129.24,118.06,114.11,111.29,85.40,72.03,55.22,15.08.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₁H₁₄NaO₃S⁺249.0556,found 249.0553.

Example four

4- (methoxy) Benzylmethylene Dimethylthio bromide instead of Benzylmethylene Dimethylthio bromide as in example one, to give 5- (4-methoxy) -3-methyl-5-phenyl-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 78%.

¹H NMR(400MHz,Chloroform-d)δ7.48(d,J＝9.0Hz,2H),6.79(d,J＝8.9Hz,2H),4.94(s,2H),4.63(d,J＝3.0Hz,1H),4.12(d,J＝3.0Hz,1H),3.74(s,3H),2.21(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ160.02,158.29,128.76,126.80,113.53,83.43,71.88,55.29,15.12.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₁H₁₄NaO₃S⁺249.0556,found 249.0557.

EXAMPLE five

2,5- (dimethoxy) benzoylmethylene dimethyl sulphur bromide instead of the benzoylmethylene dimethyl sulphur bromide from example one, to give a colourless oil, 5- (2, 5-methoxy) -3-methyl-5-phenyl-2, 5-dihydro-1, 3. lambda⁶The yield of the-thiazole-3-oxide was 81%.

¹H NMR(400MHz,Chloroform-d)δ6.95–6.92(m,1H),6.65(d,J＝2.0Hz,2H),4.81(s,2H),4.72(d,J＝2.3Hz,1H),4.36(d,J＝2.3Hz,1H),3.59(d,J＝9.5Hz,6H),2.09(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ155.91,153.31,151.36,126.43,115.31,114.24,112.66,90.22,71.72,56.19,55.58,14.83.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₂H₁₆O₄S⁺279.0662,found 279.0658.

EXAMPLE six

4- (methyl) benzoylmethylen dimethylthio bromide instead of the benzoylmethylen dimethylthio bromide from example one, to give 3-methyl-5-p-tolyl-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 64%.

¹H NMR(400MHz,Chloroform-d)δ7.60(d,J＝8.1Hz,2H),7.22(d,J＝7.9Hz,2H),5.09(s,2H),4.85(dd,J＝2.9,1.2Hz,1H),4.32(d,J＝3.0Hz,1H),2.42(s,3H),2.35(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ158.57,138.54,133.39,128.93,125.43,84.29,71.92,21.28,15.12.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₁H₁₄NaO₂S⁺233.0607,found 233.0605.

EXAMPLE seven

Naphthalenemethylene dimethyl Sulfur Bromide instead of benzoylmethylene dimethyl Sulfur Bromide in example one, to give 3-methyl-5-naphthyl-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 59%.

¹H NMR(400MHz,Chloroform-d)δ8.27(s,1H),8.00–7.93(m,1H),7.89(dd,J＝8.8,5.0Hz,2H),7.82(d,J＝8.7Hz,1H),7.56(q,J＝5.1,3.9Hz,2H),5.16(s,2H),5.07(d,J＝3.1Hz,1H),4.49(d,J＝3.1Hz,1H),2.39(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ158.42,133.68–133.18(m),128.69,127.85(d,J＝21.6Hz),126.43(d,J＝5.6Hz),124.66,123.60,85.88,72.24,15.31.

HRMS(ESI)m/z[M+H]⁺Calcd for C₁₄H₁₅O₂S⁺247.0787,found 247.0785.

Example eight

Bibenzoylmethylen dimethylsulfur bromide was substituted for the benzoylmethylen dimethylsulfur bromide of example one to give 3-methyl-5-biphenyl-2, 5-dihydro-1, 3. lambda⁶The yield of the-thiazole-3-oxide was 61%.

¹H NMR(400MHz,Chloroform-d)δ7.62(d,J＝8.3Hz,2H),7.54–7.47(m,4H),7.35(t,J＝7.6Hz,2H),7.26(t,J＝7.3Hz,1H),4.97(s,2H),4.78(d,J＝3.1Hz,1H),4.24(d,J＝3.1Hz,1H),2.22(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ158.14,141.42,140.63,135.03,128.84,127.48,126.99(d,J＝15.7Hz),125.88,85.08,72.01,15.17.

HRMS(ESI)m/z[M+H]⁺Calcd for C₁₆H₁₇O₂S⁺273.0944,found 273.0941.

Example nine

3- (fluoro) Benzylmethylene Dimethylthio bromide instead of Benzylmethylene Dimethylthio bromide as in example one, to give 5- (3-fluoro) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 40%.

¹H NMR(400MHz,Chloroform-d)δ7.30(dt,J＝7.8,1.1Hz,1H),7.25–7.14(m,2H),6.94–6.87(m,1H),4.92(s,2H),4.73(d,J＝3.3Hz,1H),4.22(d,J＝3.3Hz,1H),2.17(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ164.03,161.60,157.10(d,J＝2.7Hz),138.39(d,J＝7.8Hz),129.66(d,J＝8.3Hz),121.07(d,J＝2.9Hz),115.42(d,J＝21.3Hz),112.47(d,J＝23.2Hz),85.88,72.09,15.12.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₀H₁₂NaO₂S⁺237.0356,found 237.0356.

Example ten

2- (fluoro) benzoylmethylidene dimethyl sulphur bromide instead of benzoylmethylidene dimethyl sulphur bromide in example one, to give 5- (2-fluoro) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda⁶The yield of the-thiazole-3-oxide was 33%.

¹H NMR(400MHz,Chloroform-d)δ7.46(td,J＝7.7,1.6Hz,1H),7.15(dtd,J＝9.1,5.0,1.7Hz,1H),7.03–6.90(m,2H),4.88(s,2H),4.76(d,J＝2.8Hz,1H),4.42(d,J＝2.0Hz,1H),2.15(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ161.28,158.79,153.58(d,J＝3.0Hz),129.95(d,J＝8.6Hz),129.14(d,J＝2.7Hz),124.37(d,J＝11.4Hz),124.02–123.74(m),116.07(d,J＝23.0Hz),90.43(dd,J＝8.5,4.2Hz),72.25–71.49(m),15.02(d,J＝5.6Hz).

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₀H₁₁FNaO₂S⁺237.0356,found 237.0357.

EXAMPLE eleven

4- (trifluoromethyl) benzoylmethylidene dimethyl sulphur bromide was used instead of the benzoylmethylidene dimethyl sulphur bromide of example one to give 3-methyl-5- (4- (trifluoromethyl) benzene) -2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 32%.

¹H NMR(400MHz,Chloroform-d)δ7.75(d,J＝8.2Hz,2H),7.62(d,J＝8.3Hz,2H),5.08(s,2H),4.93(d,J＝3.4Hz,1H),4.43(d,J＝3.4Hz,1H),2.32(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ157.04,139.45,130.49(d,J＝32.4Hz),125.69,125.16(q,J＝3.8Hz),86.77,72.18,15.14.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₁H₁₁F₃NaO₂S⁺287.0324,found 287.0325.

Example twelve

2,4- (difluoro) benzoylmethylidene dimethyl sulfur bromide was substituted for the benzoylmethylidene dimethyl sulfur bromide in example one to give a colorless oil of 5- (2, 4-difluoro) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda⁶The yield of the-thiazole-3-oxide was 32%.

¹H NMR(400MHz,Chloroform-d)δ7.51–7.43(m,1H),6.81–6.70(m,2H),4.92(s,2H),4.73(d,J＝3.0Hz,1H),4.43(d,J＝2.6Hz,1H),2.19(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ163.92(d,J＝11.2Hz),161.47(dd,J＝11.7,6.3Hz),158.98(d,J＝12.4Hz),152.81(d,J＝3.3Hz),130.11(dd,J＝9.6,4.2Hz),120.74(dd,J＝11.6,3.9Hz),111.12(d,J＝3.8Hz),110.91(d,J＝3.8Hz),104.61,104.35(d,J＝1.3Hz),104.09,90.10(d,J＝9.4Hz),71.91,15.05.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₀H₁₀F₂NaO₂S⁺255.0262,found 255.0257.

EXAMPLE thirteen

4- (fluoro) benzoylmethylidene dimethyl sulphur bromide instead of benzoylmethylidene dimethyl sulphur bromide in example one, to give 5- (4-fluoro) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda⁶The yield of the-thiazole-3-oxide was 37%.

¹H NMR(400MHz,Chloroform-d)δ7.66–7.59(m,2H),7.09–7.01(m,2H),5.05(s,2H),4.77(d,J＝3.2Hz,1H),4.30(d,J＝3.2Hz,1H),2.31(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ164.27,161.81,157.58,132.26(d,J＝3.2Hz),127.29(d,J＝8.2Hz),115.06(d,J＝21.6Hz),84.70(d,J＝1.3Hz),72.04,15.13.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₀H₁₁FNaO₂S⁺237.0356,found 237.0352.

Example fourteen

3- (chloro) benzoylmethylidene dimethyl sulfur bromide was used in place of the benzoylmethylidene dimethyl sulfur bromide in example one to give 5- (3-chloro) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda. as a colorless oil⁶The yield of the-thiazole-3-oxide was 43%.

¹H NMR(400MHz,Chloroform-d)δ7.64(s,1H),7.52(dt,J＝7.1,1.7Hz,1H),7.34–7.28(m,2H),5.05(s,2H),4.85(d,J＝3.4Hz,1H),4.36(d,J＝3.4Hz,1H),2.31(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ157.04,137.91,134.24,129.44,128.63,125.63,123.61,85.99,72.14,15.19.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₀H₁₁ClNaO₂S⁺253.0060,found 253.0058.

Example fifteen

4- (chloro) benzoylmethylidene dimethyl sulfur bromide was used in place of the benzoylmethylidene dimethyl sulfur bromide in example one to give 5- (4-chloro) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda. as a colorless oil⁶The yield of the-thiazole-3-oxide was 45%.

¹H NMR(400MHz,Chloroform-d)δ7.60–7.56(m,2H),7.35–7.31(m,2H),5.05(s,2H),4.82(d,J＝3.3Hz,1H),4.33(d,J＝3.3Hz,1H),2.31(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ157.38,134.51(d,J＝8.3Hz),128.36,126.76,85.33,72.07,15.17.

HRMS(ESI)m/z[M+Na]+Calcd for C₁₀H₁₁ClNaO₂S⁺253.0060,found 253.0061.

Example sixteen

2- (chloro) benzoylmethylidene dimethyl sulfur bromide was used in place of the benzoylmethylidene dimethyl sulfur bromide in example one to give 5- (2-chloro) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda. as a colorless oil⁶The yield of the-thiazole-3-oxide was 41%.

¹H NMR(400MHz,Chloroform-d)δ7.45–7.39(m,2H),7.33–7.24(m,2H),5.00(s,2H),4.55(d,J＝2.7Hz,1H),4.52(d,J＝2.8Hz,1H),2.32(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ157.78,136.22,132.81,130.95,129.87,129.74,126.54,90.06,72.19,15.22.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₀H₁₁FNaO₂S⁺253.0060,found 237.0057.

Example seventeen

4- (bromo) benzoylmethylidene dimethyl sulfur bromide was substituted for the benzoylmethylidene dimethyl sulfur bromide in example one to give 5- (4-bromo) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 49%.

¹H NMR(400MHz,Chloroform-d)δ7.43–7.33(m,4H),4.93(s,2H),4.71(d,J＝3.3Hz,1H),4.21(d,J＝3.3Hz,1H),2.18(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ157.40,135.01,131.33,127.06,122.73,85.43,72.09,15.19.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₁₀H₁₁BrNaO₂S⁺296.9555,found 296.9552.

EXAMPLE eighteen

3- (bromo) benzoylmethylidene dimethyl sulfur bromide instead of benzoylmethylidene dimethyl sulfur bromide in example one, to give 5- (3-bromo) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 51%.

¹H NMR(400MHz,Chloroform-d)δ7.67(t,J＝1.7Hz,1H),7.44(d,J＝7.9Hz,1H),7.36–7.31(m,1H),7.09(t,J＝7.9Hz,1H),4.92(s,2H),4.71(d,J＝3.4Hz,1H),4.22(d,J＝3.3Hz,1H),2.18(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ156.90,138.15,131.56,129.74,128.52,124.08,122.44,86.06(d,J＝4.5Hz),72.82–71.01(m),15.23(d,J＝4.9Hz).

HRMS(ESI)m/z[M+Na]⁺C₁₀H₁₁BrNaO₂S⁺Calcd for 296.9555,found 296.9555.

Example nineteen

4- (cyano) Benzylmethylene Dimethylthio bromide instead of Benzylmethylene Dimethylthio bromide as in example one, to give 5- (4-cyano) -3-methyl-5-benzene-2, 5-dihydro-1, 3. lambda. colorless oil⁶The yield of the-thiazole-3-oxide was 36%.

¹H NMR(400MHz,Chloroform-d)δ7.64(d,J＝8.3Hz,2H),7.55(d,J＝8.4Hz,2H),4.97(s,2H),4.87(d,J＝3.5Hz,1H),4.37(d,J＝3.6Hz,1H),2.21(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ156.45,140.26,132.05,125.91,118.75,112.04,87.73,72.32,15.20.

HRMS(ESI)m/z[M+H]⁺Calcd for C₁₁H₁₂NO₂S⁺222.0583,found 222.0581.

Example twenty

Thiophenecarboxylidene dimethyl esterThe phenylthiobromide was substituted for the benzoylmethylenedimethylthiobromide in example one to give a colorless oil, 3-methyl-5-thiophene-2, 5-dihydro-1, 3. lambda⁶The yield of the-thiazole-3-oxide was 49%.

¹H NMR(400MHz,Chloroform-d)δ7.30(dd,J＝3.6,1.1Hz,1H),7.25(d,J＝5.0Hz,1H),7.01(dd,J＝5.0,3.7Hz,1H),5.06(s,2H),4.82(d,J＝3.3Hz,1H),4.27(d,J＝3.3Hz,1H),2.31(s,3H).

¹³C NMR(101MHz,Chloroform-d)δ153.56,140.08,127.21,125.25,124.08,84.39,72.03,15.05.

HRMS(ESI)m/z[M+Na]⁺Calcd for C₈H₁₀NaO₂S₂ ⁺225.0014,found 225.0013.