(Z)-β-Iodo-β-methylthioalkene synthesis method

Abstract

The present invention discloses (Z)-β-iodo-β-methylthio olefins and their synthesis method. In the disclosed compounds, iodine and methylthio are located on the same carbon atom of the carbon-carbon double bond, and they are formed by the double substitution reaction of olefins with iodine and sulfoxide on the terminal carbon atom. The reaction does not require other catalysts or additives, and only through a one-pot reaction under heating conditions, (Z)-β-iodo-β-alkylthio styrene can be selectively obtained; this method has mild reaction conditions, simple operation, no need for external catalysts or additives, good selectivity and high yield, which is conducive to industrial production.

Description

Technical Field

[0001] The present invention relates to (Z)-β-iodo-β-methylthio olefins and their synthesis methods, and particularly relates to a method for synthesizing (Z)-β-iodo-β-methylthio olefins by reacting simple terminal olefins with sulfoxides and iodine, belonging to the field of organic synthesis. Background Art

[0002] Sulfur-containing haloalkenes are a class of organic compounds that contain halogen, organic sulfur, and a C=C double bond in the molecule, and have important synthetic value in organic chemical reactions. The halogen groups in sulfur-containing haloalkenyl molecules, especially bromine and iodine, are good leaving groups. In organic reactions, more complex and valuable products can be obtained by coupling with other molecules through dehalogenation substitution. Sulfur-containing haloalkenyl molecules contain multiple reaction sites and are often used as synthetic intermediates to construct biomedicine molecules and photochemical material molecules. For example, in recent years, the research focus has been on aggregation-induced emission materials (Leung N L, Xie N, Yuan W, et al. Restriction of intramolecular motions: the general mechanism behind aggregation-induced emission. Chemistry, 2014, 20(47): 15349-15353; Mei J, Hong Y, Lam J W, et al. Aggregation-induced emission: the whole is more brilliant than the parts. Advanced Materials, 2014, 26(31): 5429-5479; Bu F, Wang E, Peng Q, et al. Structural and theoretical insights into the AIE attributes of phosphindole oxide: the balance between rigidity and flexibility. Chemistry, 2015, 21(11): 4440-4449; Mei J, Leung N L, Kwok R T, et al. Aggregation-Induced Emission: Together We Shine, United We Soar! Chemical Reviews, 2015, 115(21): 11718-11940). As a special type of haloalkylthioarylalkene, these iodoalkylthioaryl ethylene molecules contain halogen groups, especially iodine groups, which are good leaving groups in chemical reactions. The iodine atom on the double bond carbon is more easily replaced by other groups than other halogen atoms, resulting in various derivatives. In addition, the thioalkyl group in the molecule is also an important group, and the thioalkyl chain is a common structural unit in biological protein molecules (Palmer J T, Rasnick D, Klaus J L, et al.Vinyl Sulfones as Mechanism-Based Cysteine Protease Inhibitors. Journal of Medicinal Chemistry, 1995, 38(17): 3193 - 3196; Meadows D C, Sanchez T, Neamati N, et al. Ring substituent effects on biological activity of vinyl sulfones as inhibitors of HIV-1. Bioorganic Medicinal Chemistry, 2007, 15(2): 1127 - 1137; Leung N L, Xie N, Yuan W, et al. Restriction of Intramolecular Motions: the General Mechanism Behind Aggregation-Induced Emission. Chemistry A European Journal, 2014, 20(47): 15349 - 15353). Therefore, sulfur-containing haloalkenes are not only of great significance to biomolecules (Ettari R, Nizi E, Di Francesco M E, et al. Development of peptidomimetics with a vinyl sulfone warhead as irreversible falcipain-2 inhibitors. Journal of Medicinal Chemistry, 2008, 51(4): 988 - 996; Palmer J T, Rasnick D, Klaus J L, et al. Vinyl sulfones as mechanism-based cysteine protease inhibitors. Journal of Medicinal Chemistry, 1995, 38(17): 3193 - 3196; Meadows D C, Sanchez T, Neamati N, et al. Ring substituent effects on biological activity of vinyl sulfones as inhibitors of HIV-1.Bioorganic Medicinal Chemistry, 2007, 15(2): 1127 - 1137), and it is also easily substituted by other groups or undergoes self - redox transformation in chemical reactions. Because of this, iodoalkylthioaryl ethene, as a popular research material in the fields of organic synthetic chemistry and organic materials science, has attracted the research interest of numerous scientists (Wang B W, Jiang K, Li J X, et al. 1,1 - Diphenylvinylsulfide as a Functional AIEgen Derived from the Aggregation - Caused - Quenching Molecule 1,1 - Diphenylethene through Simple Thioetherification. Angewandte Chemie International Edition, 2020, 59(6): 2338 - 2343; Gu X - X, Xie M - H, Zhao X - Y, et al. An Efficient Synthesis of Polysubstituted 1,3 - Enynes from (E)-β - Iodovinyl Sulfones and Terminal Alkynes. Chinese Journal of Chemistry, 2008, 26(9): 1625 - 1629; Li X, Shi X, Fang M, et al. Iron halide - mediated regio - and stereoselective halosulfonylation of terminal alkynes with sulfonylhydrazides: synthesis of (E)-beta - chloro and bromo vinylsulfones. The Journal of Organic Chemistry, 2013, 78(18): 9499 - 9504; Iwasaki M, Fujii T, Nakajima K, et al. Iron - induced regio - and stereoselective addition of sulfenyl chlorides to alkynes by a radical pathway.Angewandte Chemie International Edition, 2014, 53(50): 13880 - 13884; Iwasaki M, Fujii T, Yamamoto A, et al. Palladium-catalyzed regio- and stereoselective chlorothiolation of terminal alkynes with sulfenyl chlorides. Chemistry An Asian Journal, 2014, 9(1): 58 - 62). In recent years, iodoalkylthioaryl ethenes and their synthetic methods have become very important research contents in the field of organic synthesis, and many organic synthesis and materials application scientists have carried out a large amount of research work.

[0003] Iodoalkylthioaryl ethenes can be divided into α-iodo-β-alkylthioaryl ethenes and β-iodo-β-alkylthioaryl ethenes according to the position of the iodine atom on the double bond.

[0004] The literature reported a method for preparing α-iodo-β-alkylthioaryl ethenes by reacting ketone compounds with alkylsulfonyl hydrazides and I2, followed by deoxidation (Bao Y, Yang X, Zhou Q, et al. Iodine-Promoted Deoxygenative Iodization / Olefination / Sulfenylation of Ketones with Sulfonyl Hydrazides: Access to beta-Iodoalkenyl Sulfides. Organic Letters, 2018, 20(7): 1966 - 1969). In the product, the iodine atom and the sulfur atom are located on two carbon atoms of the double bond respectively.

[0005]

[0006] Reaction Scheme 1 Synthesis of α-iodo-β-alkylthioaryl ethene from ketone and sulfonyl hydrazide

[0007] β-Iodo-β-alkylthioaryl ethene compounds are more prone to substitution reactions than α-iodo-β-alkylthioaryl ethene compounds in which the iodine atom and the sulfur atom are located on two carbon atoms respectively. Therefore, they are a class of iodoalkenyl sulfides with better reaction performance and biological performance. Currently, the method for synthesizing such iodoalkylthioaryl ethenes is through the addition difunctionalization reaction of iodo-thioalkylation of alkynes.

[0008] In 2001, Jin et al. reported a method for preparing α-iodoalkenyl sulfides by the addition reaction of alkynyl sulfides as substrates with trimethylsilyl iodide (TMS-I) (Bao Y, Yang X, Zhou Q, et al. Iodine-Promoted Deoxygenative Iodization / Olefination / Sulfenylation of Ketones with Sulfonyl Hydrazides: Access to beta-Iodoalkenyl Sulfides. Organic Letters, 2018, 20(7): 1966-1969). In this method, the substrate alkynyl sulfide needs to be prepared in advance by the reaction of alkyne with thioalkane, and then reacted with TMS-I to obtain the final product β-iodo-β-alkylthioaryl ethylene through two-step reactions as shown in Reaction Scheme 2 below.

[0009]

[0010] Reaction Scheme 2 Synthesis of β-iodo-β-alkylthioaryl ethylene from alkyne, thioalkane, and trimethylsilyl iodide

[0011] In 2006, Cai et al. reported a multi-step method for synthesizing β-iodo-β-alkylthioaryl ethylene. This method first reacts a terminal alkyne with a Grignard reagent to obtain an alkynylmagnesium bromide intermediate, which is then coupled with one molecule of chloro thioalkane to obtain an alkynyl sulfide intermediate. Finally, the obtained alkynyl sulfide is reacted with TMS-I to obtain the target product β-iodo-β-alkylthioaryl ethylene (Zhao Q, Liu S, Li Y, et al. Design, synthesis, and biological activities of novel 2-cyanoacrylates containing oxazole, oxadiazole, or quinoline moieties. Journal of Agricultural and Food Chemistry, 2009, 57(7): 2849-2855), as shown in Reaction Scheme 3.

[0012]

[0013] Reaction Scheme 3 Synthesis of β-iodo-β-alkylthioaryl ethylene from alkyne, chloro thioalkane, and trimethylsilyl iodide

[0014] In 2008, Guerrero et al. reacted diisobutylaluminum reagent with pre-prepared alkynyl thioether to obtain a metal vinyl thioether intermediate. Subsequently, the intermediate can be de-metallated under the condition of elemental iodine to obtain β-iodo-β-alkylthioaryl ethylene (Yang W S, Shimada K, Delva D, et al. Identification of Simple Compounds with Microtubule-Binding Activity That Inhibit Cancer Cell Growth with High Potency. ACS Medicinal Chemical Letters, 2012, 3(1): 35-38). The reaction is shown in Reaction Scheme 4.

[0015]

[0016] Reaction Scheme 4 Synthesis of β-iodo-β-alkylthioaryl ethylene from alkynyl thioether, diisobutylaluminum, and iodine

[0017] In addition, in 2006, Cai et al. reported a method for synthesizing β-iodo-β-alkylthioaryl ethylene compounds by iodode-stannylation reaction of stannane-substituted vinyl thioether compounds with elemental iodine (Turchi I J, Dewar M J S. Chemistry of oxazoles. Chemical Reviews, 1975, 75(4): 389-437), as shown in Reaction Scheme 8. Similarly, in this method, the starting material stannane-substituted vinyl thioether needs to be prepared in advance.

[0018]

[0019] Reaction Scheme 5 Synthesis of β-iodo-β-alkylthioaryl ethylene from stannane-substituted vinyl thioether and iodine

[0020] According to the above overview of the synthesis methods, although a series of target compounds β-iodo-β-alkylthioaryl ethylene can be synthesized by existing methods, due to the need to use special synthetic reagents that are difficult to synthesize as raw materials in the reaction, such as substituted alkynyl thioether compounds or metal vinyl compounds. These special reagents are difficult to prepare. Therefore, so far, few β-iodo-β-alkylthioaryl ethylene compounds have been reported, and the synthesis of these β-iodo-β-alkylthioaryl ethylene requires two or more steps to obtain the product, and it is impossible to achieve one-step or one-pot synthesis. Summary of the Invention

[0021] Aiming at the defects that there are few reported β-iodo-β-alkylthioaryl ethylene compounds, the synthesis methods require two or even multiple steps of reaction, need to involve organometallic compounds, and have high requirements for reaction conditions, etc., the purpose of the present invention is to provide a method for synthesizing β-iodo-β-methylthio olefins in one step from simple terminal olefins, sulfoxides, iodine and other readily available raw materials without using organometallic compounds, and disclose 16 unreported (Z)-β-iodo-β-methylthio olefins that can only be synthesized by this method, and the structures of the products have all been characterized.

[0022] The 16 disclosed β-iodo-β-alkylthioaryl ethylene have the following structures:

[0023]

[0024] In Formula 1, R is phenyl, p-tolyl, p-tert-butylphenyl, p-fluorophenyl, p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, β-naphthyl, o-ethylphenyl, p-bromophenyl, m-bromophenyl, n-hexyl, dodecyl, cyclohexyl, α-pyridyl, α-thienyl.

[0025] The compounds shown in Formula 1 are synthesized by the following reaction:

[0026]

[0027] Reaction Scheme 6: Olefins react with sulfoxides and I2 to synthesize (Z)-β-iodo-β-methylthio olefins

[0028] This method is a double substitution reaction on the terminal carbon atoms of the C=C double bond of the olefin with iodine and sulfoxide simultaneously. No other catalysts or additives are added in the reaction. Only through a one-pot reaction under heating conditions, a (Z)-β-iodo-β-methylthio olefin product is selectively obtained; this method has mild reaction conditions, simple operation, does not require external catalysts or additives, has good selectivity and high yield, and is conducive to industrial production.

[0029] The iodine mentioned above is elemental iodine or iodine salts such as sodium iodide and potassium iodide.

[0030] In a preferred embodiment, the ratio of iodine to aryl ethylene is 0.5 - 3:1. More preferably, it is 0.8 - 1.2:1.

[0031] In a preferred embodiment, the ratio of sulfoxide to aryl ethylene is 3 - 10:1. More preferably, it is 5 - 6:1.

[0032] Sulfoxide mainly plays two roles. On the one hand, it acts as a benign solvent, and on the other hand, as a reaction substrate, sulfoxide provides an alkylthio group as the sulfur-containing group in the product.

[0033] Preferably, the reaction conditions are as follows: in an air atmosphere, at a temperature of 80-150 °C, for 2-12 h. More preferably, the conditions are: in an air atmosphere, at a temperature of 110-130 °C, for 3-5 h.

[0034] The present invention illustrates the reaction mechanism by synthesizing (Z)-β-iodo-β-methylthio styrene (a) from styrene, dimethyl sulfoxide and elemental iodine. After consulting and referring to relevant literature, a series of mechanism research experiments were designed. First, under standard conditions, a series of radical inhibition experiments were carried out with styrene as the substrate, and the results are shown in Reaction Scheme 7:

[0035]

[0036] Reaction Scheme 7 Reaction inhibition experiment

[0037] Two radical inhibitors TEMPO and BHT were used respectively, and the reaction was tested by adding gradient equivalents of the inhibitors. When the dosage of the inhibitor was 0.5 equivalent, the yield of (Z)-β-iodo-β-methylthio styrene decreased compared with before; when it was added to 1.0 equivalent, the yield of (Z)-β-iodo-β-methylthio styrene decreased significantly. When we added 2.0 equivalents of the inhibitor, the results of both groups of experiments showed that the product (Z)-β-iodo-β-methylthio styrene had become very few (see (1) in Reaction Scheme 7). It was speculated from the two groups of radical inhibition experiments that the double substitution reaction of this olefin might undergo a radical process. If 2.0 equiv BHT was added under standard conditions and the reaction was monitored by GC-MS, the product (Z)-β-iodo-β-methylthio styrene could hardly be detected, and the radical capture product BHT-SCH3 could be detected (see (2) in Reaction Scheme 7). In addition, the reaction was monitored at different reaction times under standard reaction conditions, and the results showed that the product β-iodostyrene could be detected in the reaction.

[0038] Based on the results of the above control experiments and literature reports, we propose a reasonable reaction mechanism for this reaction, as shown in Reaction Scheme 8. First, dimethyl sulfoxide (sulfoxide) slowly breaks down under heating conditions to produce one molecule of methanethiol and one molecule of formaldehyde. At the same time, I2 homolytically cleaves under heating conditions to generate monatomic iodine radicals (I·). The monatomic iodine radicals interact with methanethiol, and radical transfer occurs to produce methylthio radicals (CH3S·) and hydrogen iodide HI. On the other hand, the terminal olefin reacts with elemental iodine to obtain a β-iodoolefin intermediate through β-iodo substitution reaction. Subsequently, the methylthio radical (CH3S·) attacks the β-iodoolefin intermediate to obtain a radical addition intermediate. Finally, the intermediate reacts under the action of iodine to obtain the final product (Z)-β-iodo-β-methylthio styrene with the double bond retained. At the same time, in the reaction, HI can be oxidized back to iodine under oxidative conditions such as DMSO, completing the recycling of iodine.

[0039]

[0040] Reaction Scheme 8 Reaction mechanism

[0041] Compared with the prior art, the beneficial technical effects brought by the technical solution of the present invention are as follows:

[0042] 1) The present invention discloses 16 kinds of β-iodo-β-methylthio olefins that have not been reported and their synthesis methods.

[0043] 2) The raw materials used in the method for synthesizing β-iodo-β-methylthio olefins proposed by the present invention are simple terminal olefins, sulfoxides, and iodine, all of which are common ordinary chemical raw materials with low cost and wide sources, which is conducive to industrial production.

[0044] 2) In the synthesis process of β-iodo-β-methylthio olefins proposed by the present invention, no catalyst is required, and the product is formed in a one-pot reaction under an atmospheric atmosphere. The process is simple and convenient for industrial application.

[0045] 3) The synthesis process of β-iodo-β-methylthio olefins proposed by the present invention uses a one-pot reaction method, and the reaction conditions are mild, the operation is simple, and it meets the requirements of industrial production.

[0046] 4) In the synthesis process of β-iodo-β-methylthio olefins proposed by the present invention, the scope of adaptation of the substrate raw materials is relatively wide, and β-iodo-β-alkylthio olefins with various substituents can be constructed. Detailed implementation mode

[0047] The following examples are intended to further illustrate the content of the present invention rather than limit the protection scope of the claims of the present invention.

[0048] Unless otherwise specified, all reactions were carried out in Schlenk tubes.

[0049] All reaction raw materials and solvents were obtained from commercial sources and used without further purification.

[0050] Product separation was carried out using a silica gel column chromatography, with silica gel (particle size 300 mesh - 400 mesh).

[0051] 1H NMR (400 MHz), 13C NMR (100 MHz) and 19F NMR (376 MHz) were detected using a Bruker ADVANCEIII spectrometer, with CDCl3 as the solvent and TMS as the internal standard. Chemical shifts were measured in parts per million (ppm), with 0.0 ppm of tetramethylsilane as the reference shift. The following abbreviations (or combinations thereof) were used to interpret multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad peak. The coupling constant J was in units of Hertz (Hz). Chemical shifts were expressed in ppm, referring to the center line of the triplet of deuterated chloroform at 77.0 ppm or the center line of the heptet of deuterated DMSO at 39.52 ppm.

[0052] GC-MS was detected using a GC-MS QP2010 device, HRMS was measured using the electron ionization (EI) method, the mass analyzer type was TOF, and EI was detected using an Esquire 3000plus instrument.

[0053] 1. Condition optimization experiments:

[0054] Taking the synthesis of (Z)-β-iodo-β-(methylthio)styrene (a) from styrene, dimethyl sulfoxide and iodine as an example, the types and amounts of iodine reagents used in the reaction, reaction additives, reaction time and temperature were screened to seek the best reaction conditions.

[0055]

[0056] Reaction Scheme 7: Synthesis of (Z)-β-iodo-β-(methylthio)styrene from styrene, DMSO and I2

[0057] 1.1 Screening of the types and amounts of iodine reagents

[0058] First, the types and amounts of iodine reagents used in the reaction were screened and optimized. The results of screening I2, KI, and NaI are shown in Table 1 below. The reaction with 1.0 equivalent (0.5 mmol) of I2 finally gave a in a yield of 81%, but the effects of changing to KI or NaI were much worse than that of I2. Therefore, the simplest elemental iodine I2 was finally selected as the iodine reagent. Subsequently, the amount of I2 used was investigated. When I2 was added at 0.5 equivalent (0.25 mmol) according to the reaction stoichiometry, the yield of a was only 57%. When it was increased to 0.8 equivalent (0.4 mmol), the yield of a increased. When 1.2 equivalents (0.6 mmol, 150 mg) of I2 were used, the highest yield of 86% was obtained. However, when the usage amount was further increased, other polyiodinated by-products appeared, which had an obvious impact on the yield of a. Finally, 1.2 equivalents (0.6 mmol, 150 mg) of I2 were selected for use.

[0059] Table 1. Screening of the types and amounts of iodine reagents

[0060]

[0061] 1.2 Screening of reaction additives

[0062] Under the above optimal conditions, a could be obtained in a yield of 86%. Then, an attempt was made to continue adding a certain additive to promote and improve the reaction yield. A variety of common small-molecule compounds were selected and added to the original reaction system. The results were monitored by GC-MS, as shown in Table 2. First, alkaline substances, Na2CO3, NaOH, and DBU, were tried, but it was found that the alkaline conditions had a great impact on the target reaction and greatly reduced the reaction yield. Then, acidic substances H3PO4 and HCl (0.1 M) were tried, and it was found that the acids also had a negative impact on this reaction. Subsequently, some oxidants were added in the hope of promoting the reaction. The addition of H2O2, TBHP, and K2S2O8 had a great impact on the reaction, and PhI(OAc)2 also had no obvious effect. Based on the analysis of a series of experimental results, finally no additive was selected.

[0063] Table 2. Screening of reaction additives

[0064]

[0065]

[0066] 1.3 Screening of reaction temperature and time

[0067] The reaction temperature and time are important factors affecting the reaction yield. The effects of gradient temperature and different reaction times on this reaction were further studied, and the results are shown in Table 3 below. We know that the reaction can obtain a with a maximum yield of 86% when reacting at 120 °C for 4 h. Continuing to increase the temperature has a slight impact on the reaction, while decreasing the temperature has a great impact on the reaction. When the temperature is below 80 °C, the reaction yield becomes very poor. We continued to study the reaction time factor at 120 °C. When the reaction time is 2 - 3 h, the yield continuously increases. However, after more than 6 h or after overnight reaction for 12 h, the reaction yield does not increase. Therefore, we finally chose to react for 4 h under heating in an oil bath at 120 °C.

[0068] Table 3. Screening of reaction temperature and time

[0069]

[0070] 1.4 Standard reaction procedure

[0071] The standard reaction procedure obtained after the above optimization is as follows: Add 4 ml of DMSO to a 25 ml Schlenk tube, weigh 0.5 mmol of styrene, and 0.6 mmol (about 150 mg) of elemental iodine I2. After mixing evenly, seal the reaction tube with a sealing plug and place it in a magnetic stirring oil bath at 120 °C for heating and stirring. After reacting for 4 h, stop heating. After the reaction tube cools, add about 5 ml of ethyl acetate, and transfer the mixture to a separatory funnel. Add 10 ml of saturated brine and an appropriate amount of sodium thiosulfate Na2S2O3. Shake the separatory funnel to extract the reaction solution. Take the upper organic layer and drain the lower aqueous layer, repeating twice. Transfer the organic layer to a beaker and add anhydrous Na2SO4 for drying. Finally, evaporate the solvent under vacuum. The dried sample is separated by silica gel column chromatography using petroleum ether / ethyl acetate as the eluent, and finally the product (Z)-β-iodo-β-methylthio styrene is obtained. After vacuum drying, it is characterized by NMR, MS, etc.

[0072] 2. Examples

[0073] Example 1:

[0074] Add 4 ml of DMSO to a 25-ml Schlenk tube. Weigh 0.5 mmol of styrene and 0.6 mmol (about 150 mg) of elemental iodine I₂. After mixing evenly, seal the reaction tube with a sealing plug and place it in an oil bath at 120 °C for magnetic stirring and heating. After reacting for 4 h, stop heating. After the reaction tube cools, add about 5 ml of ethyl acetate, and transfer the mixture to a separatory funnel. Add 10 ml of saturated brine and an appropriate amount of sodium thiosulfate Na₂S₂O₃. Shake the separatory funnel to extract the reaction solution. Take the upper organic layer and drain the lower aqueous layer, repeating twice. Transfer the organic layer to a beaker and dry it with anhydrous Na₂SO₄. Finally, rotary evaporate the solvent under vacuum. The sample after rotary evaporation is separated by silica gel column chromatography using petroleum ether / ethyl acetate as the eluent, and finally the product (Z)-β-iodo-β-(methylthio)styrene is obtained:

[0075]

[0076] Yellow oil, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 1 H NMR (400 MHz, CDCl₃) δ 7.41 (d, J = 7.7 Hz, 2H), 7.27 (d, J = 7.5 Hz, 1H), 7.25 - 7.12 (m, 2H), 6.82 (s, 1H), 2.48 (s, 3H). 13 C{ 1 H}NMR (101 MHz, CDCl₃) δ 141.61, 137.50, 128.31, 127.92, 127.85, 97.01, 16.64. GC-MS (m / z) = 276.

[0077] Example 2:

[0078] According to the procedure of Example 1, replace DMF with deuterated DMF to obtain the target product (Z)-β-iodo-β-(methylthio)-d₃styrene:

[0079]

[0080] Yellow oil, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 1 H NMR (400 MHz, CDCl₃) δ 7.45–7.43 (m, 3H), 7.25–7.22 (m, 2H), 6.85 (s, 1H). 13 C{ 1 H}NMR (101 MHz, CDCl₃) δ 141.66, 137.48, 128.32, 127.87, 125.67, 96.99. GC-MS (m / z) = 279.

[0081] Example 3:

[0082] According to the process of Example 1, using p-methylstyrene instead of styrene to obtain the target product (Z)-β-iodo-β-methylthio-p-methylstyrene:

[0083]

[0084] p-methylthio-p-methylstyrene:

[0085] Yellow oil, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 1 H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 7.6 Hz, 2H), 7.09 (d, J = 7.8 Hz, 2H), 6.78 (s, 1H), 2.49 (s, 3H), 2.34 (s, 3H). 13 C{ 1 H}NMR (101 MHz, CDCl3) δ 138.99, 137.91, 136.51, 128.97, 127.73, 97.31, 21.02, 16.62. GC-MS (m / z) = 290

[0086] Example 4:

[0087] According to the process of Example 1, using p-tert-butylstyrene instead of styrene to obtain the target product (Z)-β-iodo-β-methylthio-p-tert-butylstyrene:

[0088]

[0089] Dark yellow oil, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 1 H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 7.9 Hz, 2H), 7.31 (d, J = 7.8 Hz, 2H), 6.80 (s, 1H), 2.49 (s, 3H), 1.32 (s, 12H). 13 C{ 1 H}NMR (101 MHz, CDCl3) δ 151.09, 138.86, 136.63, 127.52, 125.24, 97.24, 34.51, 31.22, 16.61. GC-MS (m / z) = 332.

[0090] Example 5:

[0091] According to the process of Example 1, using p-fluorostyrene instead of styrene to obtain the target product (Z)-β-iodo-β-methylthio

[0092]

[0093] Base-p-fluorostyrene:

[0094] Yellowish-white oily substance, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 1 H NMR(400 MHz, CDCl3) δ 7.44 - 7.30(m, 2H), 6.98(t, J = 8.5 Hz, 2H), 6.77(s, 1H), 2.50(s, 3H). 13 C{ 1 H}NMR(101 MHz, CDCl3) δ 162.35(d, J = 248.4 Hz), 138.01(d, J = 3.2 Hz), 137.62, 129.44(d, J = 8.1 Hz), 115.13(d, J = 21.8 Hz), 95.19, 16.60. GC-MS(m / z) = 294.

[0095] Example 6:

[0096] According to the procedure of Example 1, using p-chlorostyrene instead of styrene to obtain the target product (Z)-β-iodo-β-methylthio-p-chlorostyrene:

[0097]

[0098] Base-p-chlorostyrene:

[0099] Pale yellow oily substance, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 1 H NMR(400 MHz, CDCl3) δ 7.36(d, J = 7.9 Hz, 2H), 7.25(d, J = 7.7 Hz, 2H), 6.85(s, 1H), 2.50(s, 3H). 13 C{ 1 H}NMR(101 MHz, CDCl3) δ 140.13, 138.33, 133.75, 129.01, 128.40, 95.07, 16.65. GC-MS(m / z) = 310.

[0100] Example 7:

[0101] According to the procedure of Example 1, using m-chlorostyrene instead of styrene to obtain the target product (Z)-β-iodo-β-methylthio-m-chlorostyrene:

[0102]

[0103] Pale yellow oily substance, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 11H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H), 7.31 (m, 1H), 7.21 (m, 2H), 6.92 (s, 1H), 2.52 (s, 3H). 13 13C{ 1 1H} NMR (101 MHz, CDCl3) δ 143.23, 139.18, 134.17, 129.49, 127.82, 127.73, 126.20, 94.40, 16.67. GC-MS (m / z) = 310.

[0104] Example 8:

[0105] Following the procedure of Example 1, using o-chlorostyrene instead of styrene to obtain the target product (Z)-β-iodo-β-methylthio

[0106] o-chlorostyrene:

[0107] Yellow oil, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H), 7.31 (m, 1H), 7.21 (m, 2H), 6.92 (s, 1H), 2.52 (s, 3H). 13 13C{ 1 1H} NMR (101 MHz, CDCl3) δ 143.23, 139.18, 134.17, 129.49, 127.82, 127.73, 126.20, 94.40, 16.67. GC-MS (m / z) = 310.

[0108] Example 9:

[0109] Following the procedure of Example 1, using β-naphthylethylene instead of styrene to obtain the target product (Z)-β-iodo-β-methylthio

[0110]

[0111] β-naphthylethylene:

[0112] Brownish-yellow oil, yield 85%, 53 mg, eluent ratio PE / EA = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.85 - 7.77 (m, 2H), 7.74 (d, J = 8.6 Hz, 1H), 7.58 (d, J = 8.9 Hz, 1H), 7.48 (t, J = 5.4 Hz, 2H), 7.00 (s, 1H), 2.55 (s, 3H).13 C{ 1 H} NMR (101 MHz, CDCl3) δ 138.77, 137.96, 133.10, 132.85, 128.14, 127.88, 127.50, 127.23, 126.59, 126.34, 125.39, 97.26, 16.71. GC-MS (m / z) = 326

[0113] Example 10:

[0114] Following the procedure of Example 1, using o-ethylstyrene instead of styrene, the target product (Z)-β-iodo-β-

[0115]

[0116] methylthio-o-ethylstyrene was obtained:

[0117] Yellow oil, yield 57%, 86 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 7.30–7.16 (m, 3H), 7.08 (d, J = 7.3 Hz, 1H), 6.83 (s, 1H), 2.65 (dd, J = 14.7, 7.2 Hz, 2H), 2.50 (s, 3H), 1.25 (t, J = 8.0 Hz, 3H). 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 137.19, 128.83, 128.28, 127.57, 127.42, 126.15, 125.33, 97.36, 28.74, 16.63, 15.53. GC-MS (m / z) = 304.

[0118] Example 11:

[0119] Following the procedure of Example 1, using o-ethylstyrene instead of styrene, the target product (Z)-β-iodo-β-

[0120]

[0121] methylthio-p-bromostyrene was obtained:

[0122] Bright yellow oil, yield 75%, 133 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 6.87 (s, 1H), 2.50 (s, 3H). 13 C{1 1H NMR (101 MHz, CDCl3) δ 140.56, 138.42, 131.35, 129.30, 121.89, 95.08, 16.66. GC-MS (m / z) = 356.

[0123] Example 12:

[0124] Following the procedure of Example 1, using o-ethylstyrene instead of styrene to obtain the target product (Z)-β-iodo-β-

[0125]

[0126] methylthio-m-bromostyrene:

[0127] Yellow oil, yield 70%, 125 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 7.36 (d, J = 7.9 Hz, 2H), 7.16 (t, J = 7.8 Hz, 1H), 6.91 (s, 1H), 2.51 (s, 3H). 13 C{ 1 1H NMR (101 MHz, CDCl3) δ 143.49, 139.25, 130.74 (s), 130.51 (s), 129.74 (s), 126.73 (s), 122.30 (s), 94.21 (s), 16.67. GC-MS (m / z) = 356.

[0128] Example 13:

[0129] Following the procedure of Example 1, using o-ethylstyrene instead of styrene to obtain the target product (Z)-β-iodo-β-

[0130]

[0131] methylthio-1-octene:

[0132] Pale yellow oil, yield 41%, 53 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 6.32 (s, 1H), 2.36 (s, 3H), 1.63 (m, 2H), 1.24 (m, 7.2 Hz, 8H), 0.95 (t, J = 7.4 Hz, 3H). 13 C{ 11H NMR (101 MHz, CDCl3) δ 133.09, 100.79, 31.55, 29.62, 27.89, 22.55, 19.19, 18.42, 14.06. GC-MS (m / z) = 284.

[0133] Example 14:

[0134] Following the procedure of Example 1, using o-ethylstyrene instead of styrene to obtain the target product (Z)-β-iodo-β-

[0135]

[0136] methylthio-1-tetradecene:

[0137] Orange-yellow oil, yield 47%, 86 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 6.32 (s, 1H), 2.37 (s, 3H), 2.04 (s, 2H), 1.26 (m, 20H), 0.96 (t, J = 7.4 Hz, 3H). 13 13C{ 1 1H} NMR (101 MHz, CDCl3) δ 133.08, 103.47, 33.91, 30.57, 29.65, 29.62, 29.53, 29.29, 28.22, 22.68, 18.07, 16.28, 14.10, 13.70. GC-MS (m / z) = 368.

[0138] Example 15:

[0139] Following the procedure of Example 1, using o-ethylstyrene instead of styrene to obtain the target product (Z)-β-iodo-β-

[0140]

[0141] methylthio-cyclohexene:

[0142] Yellow oil, yield 48%, 53 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 6.38 (s, 1H), 2.37 (s, 3H), 1.99–1.93 (m, 1H), 1.87–1.71 (m, 5H), 1.33–1.28 (m, 5H), 1.21–1.04 (m, 1H). 13 13C{ 11H NMR (101 MHz, CDCl3) δ 131.46, 111.60, 50.92, 33.76, 25.93, 16.32. GC-MS (m / z) = 282.

[0143] Example 16:

[0144] Following the procedure of Example 1, using o-ethylstyrene instead of styrene to obtain the target product (Z)-β-iodo-β-

[0145]

[0146] (methylthio)-α-thienylethylene:

[0147] Orange oil, yield 49%, 55 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 7.10 (s, 1H), 6.67–6.50 (m, 2H), 6.37 (s, 1H), 2.37 (s, 3H). 13 13C{ 1 1H}NMR (101 MHz, CDCl3) δ 148.31, 137.31, 126.81, 124.71, 117.55, 89.70, 14.92. GC-MS (m / z) = 282.

[0148] Example 17:

[0149] Following the procedure of Example 1, using o-ethylstyrene instead of styrene to obtain the target product (Z)-β-iodo-β-

[0150]

[0151] (methylthio)-α-pyridylethylene:

[0152] Yellow oil, yield 35%, 48 mg, eluent ratio: petroleum ether / ethyl acetate = 5 / 1. 1 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 7.95 (s, 1H), 7.66 - 7.56 (m, 2H), 7.09 (s, 1H), 2.56 (s, 3H). 13 13C{ 1 1H}NMR (101 MHz, CDCl3) δ 155.32, 148.76, 142.85, 137.04, 122.58, 121.85, 95.45, 16.78. GC-MS (m / z) = 277.

Claims

1. A method for synthesizing (Z)-β-iodo-β-methylthio olefin, characterized in that: The (Z)-β-iodo-β-methylthio olefin has the structure of Formula 1: Formula 1; In Formula 1, R is phenyl, p-tolyl, p-tert-butylphenyl, p-fluorophenyl, p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, β-naphthyl, o-ethylphenyl, p-bromophenyl, m-bromophenyl, α-pyridyl or α-thienyl; Synthesis method of the (Z)-β-iodo-β-methylthio olefin: Aryl ethylene, iodine and dimethyl sulfoxide are used as raw materials to react in one step in an atmospheric atmosphere to obtain stereospecific (Z)-β-iodo-β-methylthio olefin. Dimethyl sulfoxide is both a reactant and a reaction solvent; the iodine is elemental iodine, sodium iodide or potassium iodide.

2. The synthetic method of (Z)-β-iodo-β-methylthio olefin according to claim 1, characterized in that: The reaction conditions are: in an atmospheric atmosphere, at a temperature of 80-150 °C, react for 2-12 h.

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