阅读说明：本技术 过渡金属催化的卡宾***/环合反应高效合成氨基噻唑衍生物的绿色合成新方法 (Novel green synthesis method for efficiently synthesizing aminothiazole derivative through carbene insertion/cyclization reaction under catalysis of transition metal ) 是由 海俐 吴勇 赖睿智 徐莹莹 黄鑫 于 2020-06-30 设计创作，主要内容包括：本发明涉及一种过渡金属催化的卡宾插入/环合反应高效合成氨基噻唑衍生物的绿色合成新方法。该方法以硫叶立德作为卡宾供体,过渡金属催化卡宾发生插入/环合反应,高效形成C-S键以及构建2-氨基噻唑衍生物。与传统方法相比,本方法原料易得,步骤简单,以温和的硫叶立德试剂代替了传统合成方法中需要用到的卤代试剂,是一种温和、快速、简便、有效、环境友好的制备2-氨基噻唑及其衍生物的方法,具有广阔的应用前景。(The invention relates to a novel green synthesis method for efficiently synthesizing aminothiazole derivatives by transition metal catalyzed carbene insertion/cyclization reaction. According to the method, sulfur ylide is used as a carbene donor, and transition metal is used for catalyzing carbene to perform insertion/cyclization reaction, so that a C-S bond is efficiently formed and the 2-aminothiazole derivative is constructed. Compared with the traditional method, the method has the advantages of easily obtained raw materials and simple steps, replaces a halogenated reagent required in the traditional synthetic method with a mild sulfur ylide reagent, is a mild, rapid, simple, convenient, effective and environment-friendly method for preparing the 2-aminothiazole and the derivatives thereof, and has wide application prospect.)

1. a novel green synthesis method for efficiently synthesizing C-S bond and cyclization to construct thiazole derivatives based on insertion/cyclization reaction catalyzed by transition metal is characterized in that thiourea is used as an initial raw material, a sulfur ylide compound is used as a carbene donor, and the chemical reaction formula is as follows:

R₁is an aromatic ring or a heterocyclic ring such as phenyl, thienyl, furyl, pyridyl, naphthyl, pyrrolyl, indolyl, etc., C₁~C₂₀Unsubstituted or substituted alkyl of C₁~C₂₀Unsubstituted or substituted chain hydrocarbon group of C₃~C₁₀Unsubstituted or substituted cycloalkyl of C₁~C₂₀One of unsubstituted or substituted acyl groups of (a);

R₂is an aromatic ring or a heterocyclic ring such as hydrogen, phenyl, thienyl, furyl, pyridyl, naphthyl, pyrrolyl, indolyl, etc., C₁~C₂₀Unsubstituted or substituted alkyl of C₁~C₂₀Unsubstituted or substituted chain hydrocarbon group of C₃~C₁₀Unsubstituted or substituted cycloalkyl of C₁~C₂₀Or one of unsubstituted or substituted acyl groups.

2. A process for preparing thiazole derivatives according to claim 1, characterized by comprising the following steps:

sequentially adding a sulfur ylide compound, a thiourea compound, a catalyst and 1, 2-dichloroethane into a clean reactor, and stirring for 24 hours in an oil bath kettle at the temperature of 80 ℃;

after the reaction is finished, collecting reaction liquid, decompressing to remove the solvent, and separating and purifying residues by silica gel column chromatography to obtain the product.

3. The production method according to claim 2, wherein the catalyst in the step (1) is palladium on carbon, tetrakis (triphenylphosphine) palladium, palladium acetate, palladium chloride, bis (acetonitrile) palladium dichloride, bis (benzonitrile) palladium dichloride, 1, 1' -bis (diphenylphosphino) ferrocene palladium dichloride, bis (triphenylphosphine) palladium dichloride, bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) dipalladium, allylpalladium (II) chloride dimer, (1, 5-cyclooctadiene) palladium (II) dichloride, rhodium on carbon, rhodium trichloride, rhodium acetate, triphenylphosphine rhodium acetylacetonate, bicyclo-octene rhodium chloride dimer, pentamethylcyclopentadienyl-rhodium (III) dichloride dimer, (bis (hexafluoroantimonic acid) triacetonitrile (pentamethylcyclopentadienyl) rhodium (III)), triphenylphosphine rhodium chloride, ruthenium trichloride, or a mixture thereof, One or more of triphenylphosphine ruthenium chloride, dichlorodicarbonyl bistriphenylphosphine ruthenium, bis (2-methylallyl) (1, 5-cyclooctadiene) ruthenium (II), p-cymene ruthenium dichloride dimer, cobalt chloride, acetoacetic cobalt, octacarbonyldicobalt, dichloro (pentamethylcyclopentadienyl) cobalt (III) dimer, pentamethylcyclopentadienylcarbonyl cobalt diiodide, (bis (hexafluoroantimonic acid) triacetonitrile (pentamethylcyclopentadienyl) cobalt (III)), iridium trichloride, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, bis (1, 5-cyclooctadiene) iridium chloride (I) dimer, and methoxy (cyclooctadiene) iridium dimer.

4. The preparation method according to claim 2, wherein the molar ratio of the sulfoylide compound to the thiourea compound to the catalyst in the step (1) is 1 (1.5-2.0) to (0.02-0.05).

Technical Field

The invention relates to a novel green synthesis method for efficiently forming a C-S bond and constructing 2-aminothiazole and derivatives thereof by taking sulfur ylide as a carbene donor and carrying out transition metal catalyzed carbene insertion/cyclization reaction, belonging to the technical field of organic synthetic chemistry.

Background

Thiazole and its derivatives are important heterocyclic structural units, which are present in the structure of many drugs, natural products, such as vitamin B₁Fanetizole, abafungin^1-4At present, it is a compoundThe method for forming aminothiazole and derivatives thereof comprises Hantzsch, Cook Heilborn and Tchernic synthesis reaction⁵. The Hantzsch's synthesis method is a common method for synthesizing aminothiazole, and the method mainly uses alpha-halogenated ketone or alpha-halogenated aldehyde and thiourea as substrates to perform condensation cyclization under acidic conditions. However, the conventional method usually requires the use of an acidic system and a halide, which causes a large pollution to the environment during the post-treatment process, and therefore, many researchers have made many improvements on the synthesis method of 2-aminothiazole ring compounds based on the classical synthesis method. Mainly comprises the methods of using a non-acidic solvent system, a green solvent system, a solvent-free system, an immobilized reagent, metal catalysis, a microwave method, substrate diversification and the like⁶The synthesis method of the 2-aminothiazole ring compound is greatly enriched and developed. Metal-catalyzed carbene insertion X-H bond (X = C, N, O, S) reactions have long been recognized as a method for building important organic building blocks gently and efficiently. Diazo compounds are commonly used metal carbene precursors, and are widely used in carbene insertion reactions due to their good reactivity and applicability^7-11. 2008, Yadav et al¹²A method for synthesizing 2-aminothiazole derivatives by the reaction of copper trifluoromethanesulfonate-catalyzed alpha-diazoketone with thiourea is reported. However, diazo compounds are difficult to synthesize, unstable, difficult to store and even potentially dangerous. The sulfur ylide is also used as a carbene precursor compound, has the advantages of safety, stability, easy synthesis and the like compared with a diazo compound, and is recently taken as a research hotspot of carbene chemistry^13-17. Thiobesite, which is also a carbene precursor, has been reported only rarely as a method for synthesizing 2-aminothiazole derivatives using it as a substrate¹⁸. Sheppeck et al reported a process for the preparation of thiazole derivatives using a thioylide, but still required a large amount of hydrochloric acid catalysis, and the yields were not high, the examples were too few, and there were no examples of the reaction of a thioylide with a substituted thiourea. Therefore, the method for synthesizing the C-S bond and constructing the aminothiazole, which is economic, efficient, safe, green and wide in substrate applicability, is developed by taking the sulfur ylide as a carbene donor, and has great research significance.

Disclosure of Invention

The invention takes sulfur ylide as a carbene donor, simply, rapidly and efficiently performs carbene insertion reaction with thiourea through transition metal catalysis, and constructs a new synthesis method of the thiazole and the derivative thereof through cyclization, thereby solving the defects of large environmental pollution, complicated steps, harsh conditions and the like of the traditional method. The method has the advantages of easily obtained raw materials, simple steps, wide applicability, avoidance of use of halogenated matters, mildness, rapidness, simplicity, convenience, effectiveness and environmental friendliness, and has a wide application prospect.

The technical route of the invention takes thiourea compounds as substrates and sulphur ylide as carbene donors, and the chemical reaction formula is shown as follows:

wherein:

R₁is an aromatic ring or a heterocyclic ring such as phenyl, thienyl, furyl, pyridyl, naphthyl, pyrrolyl, indolyl, etc., C₁~C₂₀Unsubstituted or substituted alkyl of C₁~C₂₀Unsubstituted or substituted chain hydrocarbon group of C₃~C₁₀Unsubstituted or substituted cycloalkyl of C₁~C₂₀Or one of unsubstituted or substituted acyl groups.

R₂Is an aromatic ring or a heterocyclic ring such as hydrogen, phenyl, thienyl, furyl, pyridyl, naphthyl, pyrrolyl, indolyl, etc., C₁~C₂₀Unsubstituted or substituted alkyl of C₁~C₂₀Unsubstituted or substituted chain hydrocarbon group of C₃~C₁₀Unsubstituted or substituted cycloalkyl of C₁~C₂₀Or one of unsubstituted or substituted acyl groups.

The preparation method comprises the following steps:

(1) sequentially adding a thioylide compound, a thiourea compound, a catalyst and 1, 2-dichloroethane into a clean reactor, and stirring for 24 hours in an oil bath kettle at the temperature of 80 ℃.

(2) After the reaction is finished, collecting reaction liquid, decompressing to remove the solvent, and separating and purifying residues by silica gel column chromatography to obtain the product.

In the step (1), the catalyst is palladium on carbon, tetrakis (triphenylphosphine) palladium, palladium acetate, palladium chloride, bis (acetonitrile) palladium dichloride, bis (benzonitrile) palladium dichloride, 1, 1' -bis (diphenylphosphino) ferrocene palladium dichloride, bis (triphenylphosphine) palladium dichloride, bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) dipalladium, allylpalladium (II) chloride dimer, (1, 5-cyclooctadiene) palladium (II) dichloride, rhodium on carbon, rhodium trichloride, rhodium acetate, acetylacetonatocarbonyltriphenylphosphine rhodium, dicyclooctenylrhodium chloride dimer, dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, (bis (hexafluoroantimonic acid) triacetonitrile (pentamethylcyclopentadienyl) rhodium (III)), triphenylphosphine rhodium chloride, ruthenium trichloride, triphenylphosphine ruthenium chloride, dichlorodicarbonylditriphenylphosphine ruthenium chloride, bistriphenylphosphine ruthenium chloride, ruthenium trichloride, One or more of bis (2-methallyl) (1, 5-cyclooctadiene) ruthenium (II), p-cymene ruthenium dichloride dimer, cobalt chloride, cobalt acetoacetoxide, dicobalocarbonyl, dichloro (pentamethylcyclopentadienyl) cobalt (III) dimer, pentamethylcyclopentadienyl cobalt diiodide, (bis (hexafluoroantimonate) triacetonitrile (pentamethylcyclopentadienyl) cobalt (III)), iridium trichloride, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, bis (1, 5-cyclooctadiene) iridium (I) chloride dimer, and methoxy (cyclooctadiene) iridium dimer.

A sulfoylide compound in the step (1): thiourea compounds: the molar ratio of the catalyst is 1 (1.5-2.0) to 0.02-0.05.

Compared with the traditional reaction, the invention is a method for efficiently forming C-S bonds and constructing 2-aminothiazole and derivatives thereof by using the sulfur ylide as a carbene donor transition metal for transition metal catalytic carbene insertion/cyclization reaction. The method is a simple, convenient and efficient method for preparing the 2-aminothiazole derivative, provides an experimental basis for synthesizing the thiazole derivative with bioactivity in the future, and has wide application prospect.

By nuclear magnetic resonance hydrogen spectroscopy (¹H NMR), carbon spectrum (¹³C NMR) and high resolution mass spectroscopy confirmed the formation of C-S bonds on the aryl heterocycles and the structure of the 2-aminothiazole derivatives. Wherein the NMR chart is measured by Varian INOVA-400 NMR spectrometer, Tetramethylsilane (TMS) is used as an internal standard (0 ppm), and deuterated dimethyl sulfoxide is used as a solvent; high resolution mass spectra were determined using an Agilent 1946B mass spectrometer.

Detailed description of the invention

The present invention will be further described with reference to specific embodiments to assist in understanding the invention. It is not intended that the scope of the invention be limited thereby, but rather that the invention be defined by the claims appended hereto.

Example 1 was carried out: synthesis of Compound 1

(1) Phenyl sulfide ylide (39.2 mg, 0.2 mmol), thiourea (30.4 mg,0.4 mmol), rhodium (II) acetate dimer (2.6 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added sequentially to a clean reactor and stirred in an 80 ℃ oil bath for 24 h.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain a white solid with the yield of 85 percent.¹H NMR (400 MHz, DMSO-d ₆) 7.81 – 7.76 (m, 2H), 7.35 (t,J= 7.6 Hz, 2H), 7.27 – 7.21 (m, 1H), 7.03 (s, 2H), 6.98 (s, 1H);¹³C NMR (100MHz, DMSO-d ₆) 168.7, 150.3, 135.3, 128.9(2C), 128, 126.0(2C), 102.0. HRMS(ESI):m/zCalculated value C₉H₈N₂SH⁺177.0481, found 177.0483.

Example 2 was carried out: synthesis of Compound 2

(1) (3-methoxy) phenylthioylide (45.2 mg, 0.2 mmol), thiourea (30.4 mg,0.4 mmol), bis (1, 5-cyclooctadiene) iridium (I) chloride dimer (4.0 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added sequentially to a clean reactor and stirred in an 80 ℃ oil bath for 24 h.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain white E solid with the yield of 63 percent.¹H NMR (400 MHz, Chloroform-d) 7.28 – 7.25 (m, 2H),7.23 – 7.18 (m, 1H), 6.77 (ddd,J= 8.0, 2.5, 1.3 Hz, 1H), 6.62 (s, 1H), 5.29(s, 2H), 3.77 (s, 3H);¹³C NMR (100 MHz, Chloroform-d) 166.4, 158.8, 150.0,135.0, 128.6, 117.5, 112.7, 110.4, 102.0, 54.3. HRMS (ESI):m/zCalculated value C₁₀H₁₀N₂OSH⁺207.0587, found 207.0585.

Example 3 of implementation: synthesis of Compound 3

(1) (4-methoxy) phenylthioylide (45.2 mg, 0.2 mmol), thiourea (30.4 mg,0.4 mmol), bis (1, 5-cyclooctadiene) rhodium (I) chloride dimer (3.0 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added sequentially to a clean reactor and stirred in an 80 ℃ oil bath for 24 h.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain a white solid with the yield of 70%.¹H NMR (400 MHz, DMSO-d ₆) 7.71 (d,J= 8.8 Hz, 2H), 7.01(s, 2H), 6.91 (d,J= 8.8 Hz, 2H), 6.81 (s, 1H), 3.76 (s, 3H);¹³C NMR (100MHz, DMSO-d ₆) 168.6, 159.0, 150.0, 128.2, 127.3, 114.3, 99.8, 55.5 HRMS (ESI) calculated as m/z C₁₀H₁₀N₂OSH⁺207.0587, trueFound 207.0589.

Example 4 of implementation: synthesis of Compound 4

(1) (4-chloro) phenylthioylide (46.0 mg, 0.2 mmol), thiourea (30.4 mg,0.4 mmol), pentamethylcyclopentadienylcarbonyl cobalt diiodide (2.8 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added successively to a clean reactor and stirred in an 80 ℃ oil bath for 24 h.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain a white solid with the yield of 74 percent.¹H NMR (400 MHz, DMSO-d ₆) 7.79 (d,J= 8.4 Hz, 2H), 7.41(d,J= 8.4 Hz, 2H), 7.19 (s, 2H), 7.06 (s, 1H);¹³C NMR (100 MHz, DMSO-d ₆)168.9, 148.4,133.8, 132.1, 129.0, 127.7, 102.8 HRMS (ESI) calculated as m/z C₉H₇ClN₂SH⁺211.0091, found 211.0088.

Example 5 was carried out: synthesis of Compound 5

(1) 2-Thiophenylthioylide (40.4 mg, 0.2 mmol), thiourea (30.4 mg,0.4 mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (3.7 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added in this order to a clean reactor and stirred in an oil bath at 80 ℃ for 24 hours.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain a white solid with the yield of 74 percent.¹H NMR (400 MHz, Chloroform-d) 7.31 (dd,J= 3.6, 1.2Hz, 1H), 7.21 (dd,J= 5.0, 1.2 Hz, 1H), 7.02 (dd,J= 5.1, 3.6 Hz, 1H), 6.60(s, 1H), 5.47 (s, 2H);¹³C NMR (100 MHz, Chloroform-d) 167.7, 145.5, 138.6,127.6, 124.5, 123.4, 101.4 HRMS (ESI) calculated m/z C₇H₆N₂SH⁺183.0045, found 183.0043.

Example 6 of implementation: synthesis of Compound 6

(1) In a clean reactor, thioylide (39.2 mg, 0.2 mmol), 3-methylphenylthiourea (66.4 mg,0.4 mmol), rhodium (II) acetate dimer (2.6 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added in this order, and the mixture was stirred in an oil bath at 80 ℃ for 24 hours.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain a white solid with the yield of 67%.¹H NMR (400 MHz, Chloroform-d) 7.84 (d,J= 7.6 Hz, 2H),7.39 (t,J= 7.5 Hz, 2H), 7.30 (t,J= 7.5 Hz, 1H), 7.26 – 7.23 (m, 2H), 7.15(d,J= 8.1 Hz, 2H), 6.78 (s, 1H), 2.34 (s, 3H);¹³C NMR (100 MHz, Chloroform-d) 165.5, 151.2, 134.5, 133.0, 130.0, 129.9(2C), 128.6(2C), 128.0, 127.8,126.1, 118.9, 101.4, 20.8 HRMS (ESI) calculated m/z C₇H₆N₂SH⁺267.0950, found 267.0953.

Example 7 was carried out: synthesis of Compound 7

(1) In a clean reactor, thioylide (39.2 mg, 0.2 mmol), 2-chlorophenylthiourea (74.4 mg,0.4 mmol), bis (1, 5-cyclooctadiene) rhodium (I) chloride dimer (3.0 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added in this order, and the mixture was stirred in an 80 ℃ oil bath for 24 hours.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain the wax-like substance with the yield of 90 percent.¹H NMR (400 MHz, Chloroform-d) 8.29 (d,J= 8.3 Hz, 1H),7.88 (d,J= 7.1 Hz, 2H), 7.42 (t,J= 7.7 Hz, 3H), 7.36 – 7.32 (m, 2H), 6.99(t,J= 7.0 Hz, 1H), 6.91 (s, 1H);¹³C NMR (100 MHz, Chloroform-d) 162.7,151.5, 136.9, 134.4, 129.4, 128.6(2C), 128.1, 128.0, 127.9(2C), 126.1, 122.7,117.9, 102.8 HRMS (ESI) m/z calcd C₁₅H₁₁ClN₂SH⁺287.0404, found 287.0402.

Example 8 was carried out: synthesis of Compound 8

(1) In a clean reactor, thioylide (39.2 mg, 0.2 mmol), 4-chlorophenylthiourea (74.4 mg,0.4 mmol), rhodium (II) acetate dimer (2.6 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added in this order, and the mixture was stirred in an oil bath at 80 ℃ for 24 hours.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain the wax-like substance with the yield of 74 percent.¹H NMR (400 MHz, Chloroform-d) 7.85 (d,J= 7.1 Hz, 2H),7.52 (s, 1H), 7.42 (t,J= 7.5 Hz, 2H), 7.36 – 7.26 (m, 4H), 7.04 (dt,J=6.7, 2.0 Hz, 1H), 6.87 (s, 1H);¹³C NMR (100 MHz, Chloroform-d) 163.4,151.0,141.2, 135.1, 134.0, 130.4, 128.7(2C), 128.2, 126.1(2C), 122.9, 117.9, 115.9,102.2 HRMS (ESI) m/z calculated C₁₅H₁₁ClN₂SH⁺287.0404, found 287.0401.

Example 9 was carried out: synthesis of Compound 9

(1) 2-Furothioylide (37.2 mg, 0.2 mmol), thiourea (30.4 mg,0.4 mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (3.7 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added successively to a clean reactor and stirred in an oil bath at 80 ℃ for 24 h.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain a white solid with the yield of 53 percent.¹H NMR (400 MHz, Chloroform-d) 7.39 (d,J= 1.7 Hz, 1H),6.68 (s, 1H), 6.61 (d,J= 3.3 Hz, 1H), 6.43 (t,J= 2.5 Hz, 1H), 5.27 (s,2H);¹³C NMR (100 MHz, Chloroform-d) 167.8, 150.1, 142.5, 141.8, 111.3,106.3, 102.1 HRMS (ESI) calculated m/z C₇H₆N₂OSH⁺167.0274, found 167.0275.

Example 10 of implementation: synthesis of Compound 10

(1) 1-phenylpropylthioylide (47.6 mg, 0.2 mmol), thiourea (30.4 mg,0.4 mmol), pentamethylcyclopentadienylcarbonyl cobalt diiodide (2.8 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added in this order to a clean reactor and stirred in an 80 ℃ oil bath for 24 hours.

(2) After the reaction is finished, collecting reaction liquid, removing the solvent under reduced pressure, and separating and purifying residues by silica gel column chromatography to obtain waxy substances with the yield of 40%.¹H NMR (400 MHz, Chloroform-d) 7.33 – 7.23 (m, 4H), 7.22 –7.15 (m, 1H), 6.10 (d,J= 0.9 Hz, 1H), 3.74 – 3.63 (m, 1H), 2.17 – 1.82 (m,2H), 0.87 (t,J= 7.3 Hz, 3H);¹³C NMR (100 MHz, Chloroform-d) 167.5, 155.5,143.2, 128.3(2C), 128.1(2C), 126.3, 102.6,50.0, 28.0, 12.5 HRMS (ESI) m/z calcd for C₁₂H₁₄N₂SH⁺219.0950, found 219.0951.

Example 11 of implementation: synthesis of Compound 11

(1) 1-Phenylvinylthioylide (44.4 mg, 0.2 mmol), thiourea (30.4 mg,0.4 mmol), rhodium (II) acetate dimer (2.6 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added sequentially to a clean reactor and stirred in an 80 ℃ oil bath for 24 h.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain the wax-like substance with the yield of 37%.¹H NMR (400 MHz, Chloroform-d) 7.48 (d,J= 7.1 Hz, 2H),7.33 (t,J= 7.5 Hz, 2H), 7.27 – 7.22 (m, 2H), 6.87 (d,J= 15.9 Hz, 1H),6.44 (s, 1H), 5.17 (s, 2H);¹³C NMR (100 MHz, Chloroform-d) 167.2, 150.2,137.1, 130.4, 128.6(2C), 127.6, 126.5(2C), 121.4, 106.6 HRMS (ESI): m/z calculated value C₁₁H₁₀N₂S H⁺203.0637, found 203.0638.

Example 12 of implementation: synthesis of Compound 12

(1) Phenyl thioylide (39.2 mg, 0.2 mmol), N-methylthiourea (36.1 mg,0.4 mmol), rhodium (II) acetate dimer (2.6 mg, 0.006 mmol) and 1, 2-dichloroethane (2mL) were added sequentially to a clean reactor and stirred in an 80 ℃ oil bath for 24 h.

(2) After the reaction is finished, the reaction liquid is collected, the solvent is removed under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain the wax-like substance with the yield of 71 percent.¹H NMR (400 MHz, Chloroform-d) 7.83 – 7.74 (m, 2H), 7.37(t,J= 7.6 Hz, 2H), 7.29 (d,J= 7.3 Hz, 1H), 6.69 (s, 1H), 6.09 (s, 1H),2.96 (s, 3H).¹³C NMR (100 MHz, Chloroform-d) 171.1, 151.5, 134.9, 128.6,127.7, 126.1, 100.7, 32.3. HRMS (ESI): m/z calculated for C₁₀H₁₀N₂SH⁺:191.0637, found: 191.0635。

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