A method for constructing iodoalkenyl sulfide from olefin, iodine and dimethyl sulfoxide

Abstract

The present invention discloses a method for constructing iodoalkenyl sulfide from olefins, iodine and dimethyl sulfoxide. This method uses olefins, iodine and sulfoxide as raw materials. Under heating conditions, iodine and sulfoxide simultaneously undergo substitution reactions on the same carbon atom of the olefin. Without adding other catalysts or additives, through a one-pot reaction, an α-iodoalkenyl sulfide 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.

Description

Technical Field

[0001] The present invention relates to a method for constructing iodoalkenyl sulfide from olefin, iodine and dimethyl sulfoxide, and particularly relates to a method for synthesizing α-iodoalkenyl sulfide derivatives by double substitution reaction of sulfoxide and iodine on olefin carbon atoms, belonging to the field of organic synthesis. Background Art

[0002] Halogenated alkenyl sulfides are compounds with important synthetic value. They contain multiple reactive sites in their molecules and are often used as synthetic intermediates to construct biomedicine molecules and photochemical material molecules. Halogenated alkenyl sulfides, due to the simultaneous presence of halogen and thioalkyl groups in the molecule, are popular research materials in the fields of organic synthetic chemistry and organic materials science, attracting the research interest of many 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). Such haloalkenyl sulfide 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, yielding various derivatives. Additionally, the thioalkyl group in the molecule is also an important group, which not only has important significance for biomolecules but also is easily replaced by other groups or undergoes self-oxidation-reduction transformation in chemical reactions (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). Therefore, iodoalkenyl sulfides 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] In the past few decades, the method for synthesizing such iodoalkenyl sulfides has been through the addition difunctionalization reaction of iodo-thioalkylation of alkynes. Currently, several research groups have reported the synthesis of β-iodoalkenyl sulfones from alkynes and alkylsulfonyl hydrazides under the condition that iodine sources are provided by I2, KI or CuI. (Wan J-P, Hu D, Bai F, et al. Stereoselective Z-halosulfonylation of terminal alkynes using sulfonohydrazides and CuX(X=Cl, Br, I). RSC Advances, 2016, 6(77):73132-73135; Yang L, Hu D, Wei L, et al. KI as iodine source for the synthesis of E-iodovinylsulfones via metal-free iodosulfonylation of terminal alkynes. Phosphorus, Sulfur, and Silicon and the Related Elements, 2017, 192(12):1301-1304; Hou Y, Zhu L, Hu H, et al. Iodine promoted iodosulfonylation of alkynes with sulfonylhydrazides in an aqueous medium: highly stereoselective synthesis of (E)-β-iodovinylsulfones. New Journal of Chemistry, 2018, 42(11):8752-8755; Ma Y, Wang K, Zhang D, et al. Solvent Controlled Transformation between Sulfonyl Hydrazides and Alkynes: Divergent Synthesis of Benzo[b]thiophene-1,1-dioxides and (E)-b-iodo Vinylsulfones. Advanced Synthesis & Catalysis, 2018, 361(3):597-602.). The reaction is shown as follows.

[0004]

[0005] Synthesis of β-iodo vinyl sulfones by the reaction of reactive 1-alkynes with alkylsulfonyl hydrazides

[0006] In addition, the Jiang research group and Sun, Liu et al. also reported the synthesis of such β-iodo vinyl sulfones based on the reaction of alkynes with sodium alkylsulfonates (Gao Y, Wu W, Huang Y, et al. NBS-promoted halosulfonylation of terminal alkynes: highly regio- and stereoselective synthesis of (E)-β-halo vinylsulfones. Organic Chemical Frontiers, 2014, 1(4): 361-364); Sun Y, Abdukader A, Lu D, et al. Synthesis of (E)-β-iodo vinylsulfones via iodine-promoted iodosulfonylation of alkynes with sodium sulfinates in an aqueous medium at room temperature. Green Chemistry, 2017, 19(5): 1255-1258). The reaction is shown in Reaction Scheme 2.

[0007]

[0008] Reaction Scheme 2 Synthesis of β-iodo vinyl sulfones by the reaction of alkynes with sodium alkylsulfonates

[0009] Pan, Liu et al. used the popular synthon dimethyl sulfoxide (DMSO) to provide a sulfur source, and reacted with alkynes and elemental iodine I2 in a mixed solvent formed with H2O to also obtain β-iodo vinyl sulfones (Zhou P, Pan Y, Tan H, et al. I2-DMSO-H2O: A Metal-Free Combination System for the Oxidative Addition of Alkynes to Access (E)-alpha-Iodo-beta-methylsulfonylalkenes. The Journal of Organic Chemistry, 2019, 84(23): 15662-15668).

[0010]

[0011] Synthesis of β-iodoalkenyl sulfones by the reaction of reactive 3-alkynes with DMSO and H2O. In addition, the literature also reports a method for preparing β-iodoalkenyl thioethers by the reaction of 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 respectively located on the two carbon atoms of the double bond.

[0012]

[0013] Reaction Scheme 4: Synthesis of β-iodoalkenyl thioethers by the reaction of ketones with sulfonyl hydrazides

[0014] α-Iodoalkenyl sulfur compounds are more prone to substitution reactions than β-iodoalkenyl sulfur compounds in which the iodine and sulfur atoms are respectively located on two carbon atoms. Therefore, they are a class of iodoalkenyl sulfides with better reaction performance and biological properties. In 2001, Jin et al. reported a method for preparing α-iodoalkenyl thioethers by the addition reaction of alkynyl thioethers 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 thioether needs to be prepared in advance by the reaction of alkynes with thioalkanes, and then reacted with TMS-I to obtain the final product α-iodoalkenyl thioether through two-step reactions, as shown in Reaction Scheme 5 below.

[0015]

[0016] Synthesis of α-iodovinyl sulfides through multi-step reactions of reactive alkynes, thioalkanes, and trimethylsilyl iodide In 2006, Cai et al. reported a multi-step method for synthesizing α-iodovinyl sulfides. 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 (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). Finally, the obtained alkynyl sulfide is reacted with TMS-I to obtain the target product α-iodovinyl sulfide, as shown in Reaction Scheme 6.

[0017]

[0018] Reaction Scheme 6 Synthesis of α-iodovinyl sulfides through multi-step reactions of alkynes, chloro thioalkanes, and trimethylsilyl iodide

[0019] In 2008, Guerrero et al. reacted diisobutylaluminum reagent with a pre-prepared alkynyl sulfide to obtain a metal vinyl sulfide intermediate (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). Subsequently, the intermediate can remove the metal group under the condition of elemental iodine to obtain α-iodovinyl sulfide products, and the reaction is shown in Reaction Scheme 7.

[0020]

[0021] Reaction Scheme 7 Synthesis of α-iodovinyl sulfides through multi-step reactions of alkynyl sulfides, diisobutylaluminum, and iodine

[0022] In addition, in 2006, Cai et al. reported a method for synthesizing α-iodoalkenyl sulfide compounds by using stannane-substituted alkenyl sulfide compounds as substrates to undergo iodode-stannylation reaction with elemental iodine (Turchi I J, Dewar M JS. Chemistry of oxazoles. Chemical Reviews, 1975, 75(4): 389-437), as shown in Reaction Scheme 8. Similarly, in this method, the starting stannane-substituted alkenyl sulfide needs to be prepared in advance.

[0023]

[0024] Reaction Scheme 8 Synthesis of α-iodoalkenyl sulfide by the reaction of stannane-substituted alkenyl sulfide with iodine

[0025] According to the above overview of the synthesis methods, although a series of target compounds, α-iodoalkenyl sulfides, can be synthesized by existing methods, there are still some problems with these reactions. In particular, the reactions require the use of special synthetic reagents that are difficult to synthesize as raw materials, such as substituted alkynyl sulfide compounds or metal alkenyl compounds, and these special reagents need to be prepared in advance. Therefore, in terms of the reaction steps, the synthesis of α-iodoalkenyl sulfides 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

[0026] Aiming at the defects of the existing synthesis methods of α-iodoalkenyl sulfur compounds, such as requiring two or even multiple steps of reaction, the participation of organometallic compounds, and high requirements for reaction conditions, the purpose of the present invention is to provide a method for directly synthesizing (Z)-α-iodoalkenyl sulfide from terminal olefins, sulfoxides, iodine and other easily available raw materials without using metal organic compounds.

[0027]

[0028] Reaction Scheme 9 Synthesis of (Z)-α-iodoalkenyl sulfide by the reaction of olefin with sulfoxide and I2

[0029] This method involves a double substitution reaction of the C=C double bond of the terminal olefin with iodine and sulfoxide at the terminal carbon atom simultaneously. Without adding other catalysts or additives, only through a one-pot reaction under heating conditions, a (Z)-α-iodoalkenyl sulfide product is selectively obtained; this method has mild reaction conditions, simple operation, no need for external catalysts or additives, good selectivity, high yield, and is conducive to industrial production.

[0030] The (Z)-α-iodoalkenyl sulfide derivative has the structure of Formula 1:

[0031]

[0032] The terminal olefin structure has the structure of Formula 2:

[0033]

[0034] The sulfoxide has the structure of Formula 3:

[0035]

[0036] Wherein,

[0037] R1 is an alkyl group such as methyl, ethyl, propyl, butyl, pentyl, hexyl, dodecyl or their substituted alkyl groups, or is phenyl and their substituted derivatives.

[0038] R2 is methyl, ethyl, propyl, butyl, benzyl.

[0039] The iodine is elemental iodine or an iodine salt such as sodium iodide, potassium iodide, etc.

[0040] In the terminal olefin of the present invention, when R1 is an aryl group, it includes a simple aryl group or a substituted aryl group. The substituted aryl group contains 1 to 2 substituents, and the substituents are selected from at least one of halogen substituents, alkyl groups, hydroxyl groups, amino groups, and carboxyl groups. Halogen substituents such as fluorine, chlorine, bromine, iodine, etc. The alkyl group is a C1-C 10 alkyl group; more preferably a short-chain alkyl group of C1-C5, such as methyl, ethyl, propyl, etc., and can also be a branched-chain alkyl group, such as isopropyl, isobutyl, etc.

[0041] In the terminal olefin of the present invention, when R1 is an alkyl group, it includes a simple alkyl group and a substituted alkyl group. When R1 is selected from substituted alkyl groups, the substituents include at least one of halogen, hydroxyl, amino, cyano, ester group, nitro, and hydroxyl.

[0042] In a preferred embodiment, the ratio of iodine to the terminal olefin is 0.5 to 3:1. More preferably 0.8 to 1.2:1.

[0043] In a preferred embodiment, the ratio of the sulfoxide to the terminal olefin is 3 to 10:1. More preferably 5 to 6:1.

[0044] The sulfoxide mainly plays two roles. On the one hand, it acts as a benign solvent, and on the other hand, as a reaction substrate, the sulfoxide provides an alkylthio group as the sulfur-containing group in the product.

[0045] In a preferred embodiment, the reaction conditions are: in an air atmosphere, at a temperature of 80 to 150 °C, for 2 to 12 h. More preferred conditions are: in an air atmosphere, at a temperature of 110 to 130 °C, for 3 to 5 h.

[0046] The present invention uses the reaction of styrene with dimethyl sulfoxide and elemental iodine to synthesize (Z)-α-iodostyryl methyl sulfide (a) to illustrate the reaction mechanism. After consulting and referring to relevant literature, a series of mechanism research experiments were designed. First, under standard conditions, a series of free radical inhibition experiments were conducted using styrene as a substrate, and the results are shown as follows:

[0047]

[0048] Response inhibition test

[0049] Two free radical inhibitors, TEMPO and BHT, were used to test the reaction by adding gradient equivalents of inhibitors. When the inhibitor dosage was 0.5 equivalents, the yield of α-iodovinyl methyl sulfide decreased compared with the previous one; when it was added to 1.0 equivalents, the yield of α-iodovinyl methyl sulfide decreased significantly. When we added 2.0 equivalents of inhibitor, the results of both sets of experiments showed that the product α-iodovinyl methyl sulfide had become very small, see (1). Through the two sets of free radical inhibition experiments, it is speculated that the di-substitution reaction of the olefin may have undergone a free radical process. If 2.0 equiv of BHT is added under standard conditions and the reaction is monitored by GC-MS, the product α-iodovinyl methyl sulfide is basically undetectable, and the free radical capture product BHT-SCH3 can be detected, see (2). In addition, the reaction was monitored at different reaction times under standard reaction conditions. The results showed that the intermediate product β-iodostyrene could be detected in the reaction, see (3).

[0050] Based on the results of the above control experiments and literature reports, we proposed a reasonable path for the reaction mechanism of this reaction, as shown below. First, dimethyl sulfoxide (sulfoxide) slowly breaks under heating conditions to generate a molecule of methyl mercaptan and a molecule of formaldehyde. At the same time, I2 is homolytically split under heating conditions to produce a monoiodine radical (I·). The monoiodine radical interacts with methyl mercaptan, and free radical transfer occurs to produce methyl sulfenyl radical (CH3S·) and hydrogen iodide HI. On the other hand, the terminal olefin reacts with elemental iodine to obtain a β-iodinated olefin intermediate through a β-iodination substitution reaction. Then, the methyl sulfenyl radical (CH3S·) attacks the β-iodinated olefin intermediate to obtain a free radical addition intermediate. Finally, the intermediate obtains a final product with double bonds retained under the action of iodine. At the same time, in the reaction, HI can be oxidized back to elemental iodine under oxidizing conditions such as DMSO, completing the iodine cycle.

[0051]

[0052] Reaction mechanism

[0053] Compared with the prior art, the technical solution of the present invention brings the following beneficial technical effects:

[0054] 1) The raw materials used in the method for constructing iodoalkenyl sulfide from olefins, iodine and dimethyl sulfoxide proposed by the present invention are terminal olefins, sulfoxides and iodine, which are all common ordinary chemical raw materials with low cost and wide sources, facilitating industrial production.

[0055] 2) The method for constructing iodoalkenyl sulfide from olefins, iodine and dimethyl sulfoxide proposed by the present invention does not require the use of a catalyst and forms the product in a one-pot reaction under an atmospheric atmosphere, with a simple process and convenient for industrial application.

[0056] 3) The method for constructing iodoalkenyl sulfide from olefins, iodine and dimethyl sulfoxide proposed by the present invention adopts a one-pot reaction with mild reaction conditions and simple operation, meeting the requirements of industrial production.

[0057] 4) The method for constructing iodoalkenyl sulfide from olefins, iodine and dimethyl sulfoxide proposed by the present invention has a wide range of adaptability to substrate raw materials and can construct α-iodoalkenyl sulfides with various substituents. Detailed implementation mode

[0058] 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.

[0059] Unless otherwise specified, all reactions were carried out in Schlenk tubes.

[0060] All reaction raw materials and solvents were obtained from commercial sources and used without further purification.

[0061] Product separation was carried out using a silica gel chromatography column with silica gel (particle size 300 mesh - 400 mesh).

[0062] 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 explain multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad peak. The unit of coupling constant J is hertz (Hz). Chemical shifts are expressed in ppm, referring to the center line of the triplet of deuterated chloroform at 77.0 ppm or the center line of the septet of deuterated DMSO at 39.52 ppm.

[0063] GC-MS was detected using a GC-MS QP2010 device, HRMS was measured using the electron ionization (EI) method, the type of mass analyzer was TOF, and EI was detected using an Esquire 3000plus instrument.

[0064] 1. Conditional optimization experiment:

[0065] Taking the synthesis of (Z)-(1-iodo-2-phenylethylene)(methyl)sulfide (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.

[0066]

[0067] Reaction formula 9: Synthesis of (Z)-(1-iodo-2-phenylethylene)(methyl)sulfide from styrene, DMSO and I2

[0068] 1.1 Screening of the types and amounts of iodine reagents

[0069] First, the types and amounts of iodine reagents used in the reaction were screened and optimized. I2, KI and NaI were screened, and the results are shown in Table 1 below. The reaction with the addition of 1.0 equivalent (0.5 mmol) of I2 could finally obtain a with a yield of 81%, but the effects of changing to KI or NaI were far less 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% could be obtained. However, when the usage amount was further increased, other polyiodo-substituted by-products would appear, 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.

[0070] Table 1. Screening of the types and amounts of iodine reagents

[0071]

[0072] 1.2 Screening of reaction additives

[0073] Under the above optimal conditions, a can be obtained with a yield of 86%. Subsequently, attempts were made to further add a certain additive to promote 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 significantly reduced the reaction yield. Then, acidic substances H3PO4 and HCl (0.1 M) were tried, and it was found that the acid 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, it was finally decided not to add any additives.

[0074] Table 2. Screening of reaction additives

[0075]

[0076]

[0077] 1.3 Screening of reaction temperature and time

[0078] The reaction temperature and time are important factors affecting the reaction yield. The effects of gradient temperatures and different times on this reaction were further studied, and the results are shown in Table 3 below. We already know that the reaction can obtain a with a best 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, but after more than 6 h or overnight for 12 h, the reaction yield does not increase. Therefore, we finally chose to react for 4 h under an oil bath heating at 120 °C.

[0079] Table 3. Screening of reaction temperature and time

[0080]

[0081] 1.4 Standard reaction procedure

[0082] The standard reaction process obtained after the above optimization is as follows: Add 4 ml of DMSO to a 25 ml Schlenk tube, weigh 0.5 mmol of terminal olefin, 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 120 °C oil bath 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, drain the lower aqueous layer, and repeat twice. Transfer the organic layer to a beaker and dry it with anhydrous Na₂SO₄. Finally, spin-dry the solvent under vacuum. The spun-dried sample is separated by silica gel column chromatography using petroleum ether / ethyl acetate as the eluent. Finally, the product is obtained, vacuum-dried, and characterized by NMR, MS, etc.

[0083] 2. Substrate expansion

[0084] 2.1 Substrate expansion of simple substituted styrene derivatives

[0085] Under the standard reaction conditions, the applicability of substituted styrene derivatives in the present invention was investigated, and the results are shown in Table 4 below. The corresponding product a of styrene was finally isolated in a yield of 83%. We replaced the solvent reactant dimethyl sulfoxide with deuterated dimethyl sulfoxide (DMSO-d6), and finally successfully obtained the corresponding deuterated product d 3 -a, with a yield of 70%. When there is a -Me or -tBu substitution at the para position of styrene, the yields of the corresponding products b and c can also reach over 82%. When there is an -F substitution at the para position, the product yield is also 81%. We continued to investigate the reaction of styrene with different positions of -Cl substitution on the benzene ring. The results showed that the yields of the three substrates with -Cl substitution at different positions were 86%, 78%, and 74% respectively. When we used 2-vinylnaphthalene instead of styrene, the corresponding product h was also isolated in a yield of 71%.

[0086] Table 4 Applicability study of substrates of substituted styrene derivatives

[0087]

[0088] Reaction conditions: Substituted styrene (0.5 mmol), I₂ (1.2 equiv, 0.6 mmol), DMSO (3 ml), heated in a pressure-resistant tube at 120 °C for 4 h. The yield is the isolated yield.

[0089] 2.2 Substrate expansion of aliphatic and aromatic heterocyclic olefins

[0090] Through the study of the substrate applicability of simple substituted styrene derivatives, it was found that this method has good effects on aromatic terminal olefins and good applicability to different substituents. Subsequently, other terminal olefins were further investigated. First, we studied the reaction of aliphatic olefins. 1-Octene could obtain the corresponding product i in a yield of 41% under this reaction condition. Another straight-chain olefin, tetradecene, could also be converted into the corresponding product j under this condition. The target product k could also be detected for 3-Br propene under the same conditions. For the alicyclic olefin, cyclohexylethylene, the corresponding iodoalkenyl sulfide product l could be obtained in a moderate yield of 48%. Then, the heterocyclic olefins were also studied. 2-Vinyl furan and 2-vinyl thiophene could be converted to obtain the corresponding substrates m and n. For the substrates containing pyridine rings, 2-vinyl pyridine and 4-vinyl pyridine could also obtain the final products o and p, but the yields of the corresponding products were relatively low.

[0091] Table 5 Study on the applicability of aliphatic and heterocyclic olefin substrates

[0092]

[0093] Reaction conditions: olefin (0.5 mmol), I2 (1.2 equiv, 0.6 mmol), DMSO (3 ml), heated in a pressure-resistant tube at 120 °C for 4 h, and the yield is the isolated yield.

[0094] 2.3 Study on the applicability of sulfoxide substrates

[0095] In addition to dimethyl sulfoxide containing methyl, the sulfoxides containing ethyl, propyl, butyl, pentyl, and benzyl are applicable to this invention, but the yield of the product obtained from dimethyl sulfoxide is the highest (see Table 6).

[0096] Table 6 Study on the applicability of sulfoxide substrates

[0097]

[0098] Structural characterization of some α-iodoalkenyl sulfides

[0099] a(Z)-(1-iodo-2-phenylvinyl)(methyl)sulfane:

[0100]

[0101] Yellow oil, yield 83%, 114.5 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 11H 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 13C{ 1 1H} NMR (101 MHz, CDCl3) δ 141.61, 137.50, 128.31, 127.92, 127.85, 97.01, 16.64. GC-MS (m / z) = 276

[0102] d 3 -a(Z)-(1-iodo-2-phenylvinyl)(methyl-d3)sulfane:

[0103]

[0104] Yellow oil, yield 70%, 97.6 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H NMR (400 MHz, CDCl3) δ 7.45–7.43 (m, 3H), 7.25–7.22 (m, 2H), 6.85 (s, 1H). 13 13C{ 1 1H} NMR (101 MHz, CDCl3) δ 141.66, 137.48, 128.32, 127.87, 125.67, 96.99. GC-MS (m / z) = 279.

[0105] b(Z)-(1-iodo-2-(p-tolyl)vinyl)(methyl)sulfane:

[0106]

[0107] Bright yellow oil, yield 82%, 119 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 1H 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 13C{ 1 1H} 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

[0108] c(Z)-(2-(4-(tert-butyl)phenyl)-1-iodovinyl)(methyl)sulfane:

[0109]

[0110] Dark yellow oil, yield 85%, 141 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H NMR(400MHz,CDCl3)δ7.37(d,J = 7.9Hz,2H),7.31(d,J = 7.8Hz,2H),6.80(s,1H),2.49(s,3H),1.32(s,12H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ151.09,138.86,136.63,127.52,125.24,97.24,34.51,31.22,16.61.GC-MS(m / z)=332.

[0111] d(Z)-(2-(4-fluorophenyl)-1-iodovinyl)(methyl)sulfane:

[0112]

[0113] Light yellowish white oil, yield 81%, 119 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 HNMR(400MHz,CDCl3)δ7.44 - 7.30(m,2H),6.98(t,J = 8.5Hz,2H),6.77(s,1H),2.50(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ162.35(d,J = 248.4Hz),138.01(d,J = 3.2Hz),137.62,129.44(d,J = 8.1Hz),115.13(d,J = 21.8Hz),95.19,16.60.GC-MS(m / z)=294.

[0114] e(Z)-(2-(4-chlorophenyl)-1-iodovinyl)(methyl)sulfane:

[0115]

[0116] Pale yellow oil, yield 86%, 133 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H NMR(400MHz,CDCl3)δ7.36(d,J=7.9Hz,2H),7.25(d,J=7.7Hz,2H),6.85(s,1H),2.50(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ140.13,138.33,133.75,129.01,128.40,95.07,16.65.GC-MS(m / z)=310.f(Z)-(2-(3-chlorophenyl)-1-iodovinyl)(methyl)sulfane:

[0117]

[0118] Pale yellow oil, yield 78%, 121 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H NMR(400MHz,CDCl3)δ7.42(s,1H),7.31(m,1H),7.21(m,2H),6.92(s,1H),2.52(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ143.23,139.18,134.17,129.49,127.82,127.73,126.20,94.40,16.67.GC-MS(m / z)=310.

[0119] g(Z)-(2-(2-chlorophenyl)-1-iodovinyl)(methyl)sulfane:

[0120]

[0121] Yellow oil, yield 74%, 115 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H NMR(400MHz,CDCl3)δ7.42(s,1H),7.31(m,1H),7.21(m,2H),6.92(s,1H),2.52(s,3H). 13 C{ 11H 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.

[0122] h(Z)-(2-(4-bromophenyl)-1-iodovinyl)(methyl)sulfane:

[0123]

[0124] 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.

[0125] i(Z)-(2-(3-bromophenyl)-1-iodovinyl)(methyl)sulfane:

[0126]

[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] j(Z)-(2-(2-ethylphenyl)-1-iodovinyl)(methyl)sulfane:

[0129]

[0130] Yellow oil, yield 57%, 86 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H 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.

[0131] k(Z)-(1-iodo-2-(naphthalen-2-yl)vinyl)(methyl)sulfane:

[0132]

[0133] Brownish-yellow oil, yield 85%, 53 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H 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.

[0134] l(Z)-(1-iodooct-1-en-1-yl)(methyl)sulfane:

[0135]

[0136] Pale yellow oil, yield 41%, 53 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H NMR(400MHz,CDCl3)δ6.32(s,1H),2.36(s,3H),1.63(m,2H),1.24(m,7.2Hz,8H),0.95(t,J=7.4Hz,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ133.09,100.79,31.55,29.62,27.89,22.55,19.19,18.42,14.06.GC-MS(m / z)=284.

[0137] m(Z)-(1-iodotetradec-1-en-1-yl)(methyl)sulfane:

[0138]

[0139] Orange-yellow oil, yield 47%, 86 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H NMR(400MHz,CDCl3)δ6.32(s,1H),2.37(s,3H),2.04(s,2H),1.26(m,20H),0.96(t,J=7.4Hz,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ133.08,103.47,33.91,30.57,29.65,29.62,29.53,29.29,28.22,22.68,18.07,16.28,14.10,13.70.GC-MS(m / z)=368.

[0140] o(Z)-(2-cyclohexyl-1-iodovinyl)(methyl)sulfane:

[0141]

[0142] Yellow oil, yield 48%, 53 mg, eluent ratio: petroleum ether / ethyl acetate = 100 / 1. 1 H NMR(400MHz,CDCl3)δ6.38(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 C{1 1H NMR (101 MHz, CDCl3) δ 131.46, 111.60, 50.92, 33.76, 25.93, 16.32. GC-MS (m / z) = 282.

[0143] q(Z)-2-(2-iodo-2-(methylthio)vinyl)thiophene

[0144]

[0145] 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 C{ 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.

[0146] s(Z)-2-(2-iodo-2-(methylthio)vinyl)pyridine::

[0147]

[0148] 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 C{ 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 constructing iodoalkenyl sulfide from olefin, iodine and dimethyl sulfoxide, characterized in that: An olefin and iodine are subjected to a one-pot stirring and heating reaction in a dimethyl sulfoxide solution system under an atmospheric atmosphere to obtain a stereospecific (Z)-α-iodoalkenyl sulfide derivative; The (Z)-α-iodoalkenyl sulfide derivative has the structure of Formula 1: Formula 1; The olefin structure has the structure of Formula 2: Formula 2 wherein, R1 is methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclohexyl or dodecyl, or their bromo-substituted alkyl groups; or is phenyl and substituted benzene, and the substituents in the substituted benzene are: methyl, ethyl, isopropyl or halogen; the positions of the substituents in the substituted benzene are ortho, para or meta positions of the benzene ring; R2 is methyl; the iodine is elemental iodine, sodium iodide or potassium iodide.

2. A method for constructing iodoalkenyl sulfide from olefin, iodine and dimethyl sulfoxide according to claim 1, characterized in that: The reaction conditions are: under an atmospheric atmosphere, at a temperature of 80-150 °C, and the reaction is carried out for 2-12 h.

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