CN106167459B - A method of synthesis alkenyl thiocyanates derivative - Google Patents

Abstract

The invention belongs to the technical field of pharmaceutical chemical synthesis and discloses a method for synthesizing alkenyl thiocyanate derivatives. The method comprises the following steps: adding alkyne halide and thiocyanate into a reaction vessel as raw materials, heating and reacting with silver salt as catalyst and organic solvent as solvent, cooling the obtained reaction solution to room temperature after the reaction, and then purifying , to obtain the described alkenyl thiocyanate derivatives; the present invention uses alkyne halides and thiocyanates as raw materials, and under the catalysis of silver salts, a thiocyanation reaction occurs to synthesize alkenyl thiocyanate derivatives in one step. things. The use of dangerous goods such as concentrated sulfuric acid and mercury salts is avoided. The reaction raw materials are simple and easy to obtain, the reaction operation is safe and convenient, the reaction process is environmentally friendly, the substrate has wide applicability, strong functional group compatibility, high separation yield, good product configuration selectivity, can be scaled up to gram scale, and the product retention The halogen can facilitate further transformation.

Description

A kind of method of synthesizing alkenyl thiocyanate derivative

technical field

The invention belongs to the technical field of pharmaceutical chemical synthesis, in particular to a new method for synthesizing alkenyl thiocyanate derivatives.

Background technique

Thiocyanate compounds have a wide range of biomedical activities and are important structural units of many bioactive molecules and natural products. And studies have shown that thiocyanate compounds show excellent application potential in electrochemical reduction. In addition, thiocyanate compounds are important synthetic intermediates, which can be converted into sulfonic acid, sulfonyl chloride, thiocarbamate, thiol, sulfonyl nitrile and other compounds. For this reason, scientific researchers have conducted a lot of research on these compounds, and found that many thiocyanate compounds have strong inhibitory effects on parasites, bacteria and viruses. Although such compounds have such important applications, unfortunately there are few synthetic methods for thiocyanate compounds, and even fewer methods for constructing alkenyl thiocyanate compounds.

The traditional synthetic method of constructing alkenyl thiocyanate derivative generally will use dangerous goods such as concentrated sulfuric acid, mercury salt (Giffard M, Cousseau J, Chemical Communications, 1979 (22): 1026-1027; Giffard M, Cousseau J, Gouin L, Tetrahedron, 1985, 41(4): 801-810; Giffard M, Cousseau J, Gouin L, et al., Journal of organometallic chemistry, 1985, 287(3): 287-303). The biggest problem with this type of method is that it is easy to pollute the environment during the production process, and has a certain poisonous effect on the experimental operator; in addition, the configuration selectivity of the product is not strong, and the poor compatibility of functional groups is also a practical problem. Therefore, the development of environmentally friendly synthetic methods for the construction of alkenyl thiocyanate derivatives has been widely concerned by the scientific and industrial circles.

In organic synthetic chemistry, alkyne halide is a kind of organic synthesis building block with great research significance and practical value. In recent years, functionalization reactions based on alkyne halides have received extensive attention. (Trofimov A, Chernyak N, Gevorgyan V., Journal of the American Chemical Society, 2008, 130(41): 13538-13539; Yun S Y, Kim M, Lee D, et al., Journal of the American Chemical Society, 2008 , 131(1):24-25; Usanov D L, Yamamoto H, Journal of the American Chemical Society, 2011, 133(5): 1286-1289; Murali R, Rao N N, Cha J K, Organic letters, 2015, 17( 15):3854-3856; Tan H, Li H, Ji W, et al., Angewandte Chemie International Edition, 2015, 54(29): 8374-8377; Lehnherr D, Alzola J M, Lobkovsky E B, et al., Chemistry –A European Journal, 2015, 21(50): 18122-18127). However, there is no report on the direct synthesis of alkenyl thiocyanate derivatives using alkyne halides as raw materials.

Contents of the invention

In order to overcome the shortcomings and deficiencies of the above-mentioned prior art, the primary purpose of the present invention is to provide a new method for synthesizing alkenyl thiocyanate derivatives.

The object of the present invention is achieved through the following schemes:

A new method for synthesizing alkenyl thiocyanate derivatives, mainly comprising the following steps:

In the reaction vessel, add alkyne halide and thiocyanate as raw materials, heat the reaction under the conditions of silver salt as catalyst and organic solvent as solvent, after the reaction, the obtained reaction solution is cooled to room temperature and then purified to obtain the Alkenyl thiocyanate derivatives.

Its reaction is shown in the following formula:

Wherein, R is aryl or aliphatic alkyl, X is chlorine, bromine or iodine.

The thiocyanate can be potassium thiocyanate or ammonium thiocyanate.

The alkyne halide can be aryl alkyne chloride, aryl alkyne bromide, aryl alkyne iodide, alkyl alkyne chloride, alkyl alkyne bromide or alkyl alkyne iodide.

Preferably, the alkyne chloride is an aryl alkyne bromide or an alkyl alkyne bromide.

More preferably, the aryl alkyne bromide includes phenylacetylene bromide, 2-chlorophenylacetylene bromide, 2-bromophenylacetylene bromide, 2,4-dimethylphenylacetylene bromide, 3-chlorophenylacetylene bromide, 3- Fluorophenylacetylene bromide, 3-methylphenylacetylene bromide, 3-methoxyphenylacetylene bromide, 3-bromophenylacetylene bromide, 3-acetylene bromothiophene, 3,5-difluorophenylacetylene bromide, 4-chlorophenylacetylene bromide Bromine, 4-methoxyphenylacetylene bromide, 4-ethoxyphenylacetylene bromide, 4-methylphenylacetylene bromide, 4-ethylphenylacetylene bromide, 4-trifluoromethylphenylacetylene bromide, 4-n-propane Phenylacetylene bromide; the alkyl alkyne halides include: 1,4-decadiynyl bromide, 1,6-heptadiynyl bromide, 1-hexyne bromide, 1-heptyne bromide, 1-octyne bromide, 1-nonyne bromide, 1-decyne bromide, 1-ethynylbromcyclohexene, 3-cyclohexyl-1-propyne bromide, 3-phenyl-1-propyne bromide, 3-cyclopentyl-1 -propyne bromide, 4-phenyl-1-butyne bromide, 5-chloro-1-pentyne bromide, 5-phenyl-1-pentyne bromide, 5-methyl-1-hexyne bromide, 5- Cyano-1-pentyne bromide, cyclopentylacetylene bromide.

The molar ratio of alkyne halide and thiocyanate used is 1:(1~4).

The silver salt can be at least one of silver chloride, silver bromide, silver nitrate, silver oxide, silver trifluoromethanesulfonate, silver carbonate, silver tetrafluoroborate, silver acetate and silver trifluoroacetate. Above-mentioned silver salt catalyst is all solid, and they can be dissolved in the organic solvent that reaction needs.

Preferably, the silver salt is silver acetate.

The molar ratio of silver salt to alkyne halide used was 0.1:1.

The organic solvent is at least one of glacial acetic acid and ethanol.

The heating reaction refers to a stirring reaction at 80-100° C. for 1-24 hours.

The purification refers to filtering the reaction solution, adding sodium bicarbonate solution and extracting three times with ethyl acetate, collecting the organic phase, drying with magnesium sulfate, and then distilling off the organic solvent under reduced pressure to obtain a crude product, and then to obtain the crude product The product was subjected to column chromatography.

Wherein, the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate; the volume ratio of petroleum ether and ethyl acetate is (10-200):1.

Preferably, the volume ratio of the petroleum ether and ethyl acetate is 100:1.

Mechanism of the present invention is:

Using alkyne halides and thiocyanates as raw materials, under the catalysis of silver salts, a thiocyanation reaction occurs to synthesize alkenyl thiocyanate derivatives in one step.

Compared with the prior art, the present invention has the following advantages and beneficial effects:

The present invention constructs the synthetic method of alkenyl thiocyanate, avoids the use of dangerous goods such as concentrated sulfuric acid, mercury salt. The reaction raw materials are simple and easy to obtain, the reaction operation is safe and convenient, the reaction process is environmentally friendly, the substrate has wide applicability, strong functional group compatibility, high separation yield, good product configuration selectivity, can be scaled up to gram scale, and the product retention The halogen can facilitate further transformation. The synthesis of such compounds is widely used in the synthesis of pesticides, medicines and natural products.

Description of drawings

Fig. 1 is the NOE nuclear magnetic resonance spectrum of the product obtained in embodiment 1-16.

Fig. 2 is the proton nuclear magnetic resonance spectrogram of the product obtained in embodiment 43.

Fig. 3 is the carbon nuclear magnetic resonance spectrogram of the product obtained in Example 43.

Fig. 4 is the proton nuclear magnetic resonance spectrogram of the product obtained in embodiment 53.

Fig. 5 is the carbon nuclear magnetic resonance spectrogram of the product obtained in Example 53.

Detailed ways

The present invention will be further described in detail below with reference to the examples and drawings, but the implementation of the present invention is not limited thereto.

All the reagents used in the examples can be purchased routinely from the market.

Example 1

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of phenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir and react for 3 hours at 100°C , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was a mixed solvent of petroleum ether: ethyl acetate with a volume ratio of 100:1, and the yield was 84%.

The structural characterization data of the resulting product are as follows:

IR(KBr):3065,2924,2854,2357,2120,735,692cm ^-1 .

¹ H NMR (400MHz, CDCl ₃ ): δ7.49-7.43 (m, 5H), 6.79 (s, 1H).

¹³ C NMR (100MHz, CDCl ₃ ): δ135.3, 134.4, 130.2, 128.9, 128.1, 110.6, 108.3ppm.

HRMS (ESI) m/z: Calcd. for _C9H6BrNS [M+Na] ⁺ : 261.9297 _; Found: 261.9294.

According to the above data, the structure of the obtained product is deduced as: It shows that the target product was successfully synthesized.

Example 2

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver chloride, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours After that, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The eluent of the column chromatography was petroleum ether with a volume ratio of 100:1: ethyl acetate mixed solvent, and the yield was 56%.

Example 3

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver bromide, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours After that, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent is petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield is 53%.

Example 4

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver nitrate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, stir and react at 100°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 73%.

Example 5

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver oxide, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 49%.

Example 6

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver trifluoromethanesulfonate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir at 100°C After reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target Product, the column chromatography eluent used is petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield is 62%.

Example 7

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver carbonate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 50%.

Example 8

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol phenylacetylene bromide, 0.02 mmol silver tetrafluoroborate, 0.4 mmol potassium thiocyanate and 2 ml glacial acetic acid, and stir the reaction at 100°C 3 Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 51%.

Example 9

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of phenylacetylene bromide, 0.02mmol of silver trifluoroacetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir at 100°C for reaction 3 Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 63%.

Example 10

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of ammonium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 68%.

Example 11

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver acetate, 0.2 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 73%.

Example 12

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver acetate, 0.8 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 81%.

Example 13

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of phenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir and react at 80°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 74%.

Example 14

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of phenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir and react at 90°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 77%.

Example 15

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of phenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction for 1 hour at 100°C , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 56%.

Example 16

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir and react at 100°C for 24 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 69%.

The NOE nuclear magnetic resonance spectra of the products obtained in Examples 1-16 are all shown in FIG. 1 . It shows that the thiocyanate and bromine atoms in the obtained product are on the same side of the double bond, which is a cis structure.

Example 17

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene chloride, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 56%.

Example 18

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene iodine, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C for 3 hours , stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The column chromatography eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 21%.

Example 19

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of phenylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of ethanol, and stir and react at 100°C for 3 hours. Stop heating and stirring, cool to room temperature, filter, add aqueous sodium bicarbonate and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product. The chromatographic eluent was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 64%.

Example 20

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 1,4-decadiynyl bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain For the target product, the column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 88%.

The structural characterization data of the resulting product are as follows:

IR(KBr):3074,2935,2863,2357,2160,1738,1599,1459,819,766cm ^-1 .

¹ H NMR (400MHz, CDCl ₃ ): δ6.87(s, 1H), 3.40(d, J=2.0Hz, 2H), 2.21(tt, J=7.1, 2.1Hz, 2H), 1.56-1.48(m ,2H),1.39-1.29(m,4H),0.91(t,J＝7.0Hz,3H).

¹³ C NMR (100MHz, CDCl ₃ ): δ128.6, 109.2, 108.0, 86.7, 77.3, 31.0, 28.2, 27.5, 22.1, 18.6, 13.9ppm.

HRMS ₍ ESI) m/z: Calcd. for _C11H14BrNS [M+Na] ⁺ : 293.9923; found: 293.9928.

According to the above data, the structure of the obtained product is deduced as: It shows that the target product was successfully synthesized.

Example 21

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 1,6-heptadiynyl bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain For the target product, the column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 74%.

Example 22

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 1-heptyne bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C. Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 96%.

Example 23

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of cyclopentylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100° C. Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 89%.

Example 24

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 1-hexyne bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C. Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 95%.

Example 25

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 1-nonyne bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid, and stir the reaction at 100°C. Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 92%.

Example 26

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 1-octyne bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C. Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 95%.

Example 27

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 1-ethynylbromocyclohexene, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir at 100°C After reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target Product, the column chromatography eluent used is petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield is 79%.

Example 28

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 2,4-dimethylphenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid. After stirring and reacting under the same conditions for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography , to obtain the target product, the column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 57%.

The structural characterization data of the resulting product are as follows:

IR(KBr):3069,2988,2924,2860,2357,2160,1763,1242,1053,818,746, 698cm ^-1 .

¹ H NMR (400MHz, CDCl ₃ ): δ7.09(dd, J=14.8, 8.8Hz, 3H), 6.48(s, 1H), 2.34(s, 6H).

¹³ C NMR (100MHz, CDCl ₃ ): δ140.6, 136.6, 134.8, 132.0, 131.5, 129.8, 127.0, 108.3, 107.9, 21.3, 19.4ppm.

HRMS (ESI) m/z: Calcd. for _C11H10BrNS [M+Na] ⁺ : 289.9610; _found : 289.9612.

According to the above data, the structure of the obtained product is deduced as: It shows that the target product was successfully synthesized.

Example 29

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 2-chlorophenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C After 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product , the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 52%.

Example 30

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 2-bromophenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C After 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product , the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 61%.

Example 31

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 3,5-difluorophenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography. To obtain the target product, the column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 62%.

Example 32

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 3-phenyl-1-propynyl bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, at 100°C After stirring and reacting under the same conditions for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography , to obtain the target product, the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 82%.

Example 33

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 3-fluorophenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C After 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product , the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 76%.

Example 34

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 3-cyclohexyl-1-propynyl bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid. After stirring and reacting under the same conditions for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography , to obtain the target product, the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 87%.

Example 35

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 3-cyclopentyl-1-propyne bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid at 100 After stirring and reacting at ℃ for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate by column chromatography Purify to obtain the target product, the column chromatography eluent used is petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield is 89%.

Example 36

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 3-methylphenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir at 100°C After reacting for 3 hours, stop heating and stirring, cool to room temperature, filter the aqueous sodium bicarbonate solution and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product , the column chromatography eluent used was petroleum ether in a volume ratio of 100:1: ethyl acetate mixed solvent, and the yield was 57%.

Example 37

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 3-methoxyphenylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain For the target product, the column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 75%.

Example 38

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 3-chlorophenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C After 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product , the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 71%.

Example 39

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 3-bromophenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C After 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product , the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 78%.

Example 40

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 3-acetylene bromothiophene, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C for 3 Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 75%.

Example 41

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 4-phenyl-1-butyne bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, at 100°C After stirring and reacting under the same conditions for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography , to obtain the target product, the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 76%.

Example 42

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 4-methylphenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir at 100°C After reacting for 3 hours, stop heating and stirring, cool to room temperature, add ethyl acetate after filtration, dissolve sodium bicarbonate aqueous solution with sodium bicarbonate and extract with ethyl acetate three times, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then Separation and purification by column chromatography to obtain the target product, the column chromatography eluent used is petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield is 80%.

Example 43

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 4-methoxyphenylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain For the target product, the column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 67%.

The structural characterization data of the resulting product are as follows:

IR(KBr):3065,2937,2839,2357,2158,1560,1503,1456,1297,1249,1175, 1027,833,789cm ^-1 .

¹ H NMR (400MHz, CDCl ₃ ): δ7.26(d, J=8.1Hz, 2H), 7.15(d, J=8.0Hz, 2H), 6.64(s, 1H), 2.30(s, 3H), as shown in picture 2.

¹³ C NMR (100MHz, CDCl ₃ ): δ140.5, 134.5, 132.5, 129.6, 128.0, 109.6, 108.6, 21.3 ppm, as shown in FIG. 3 .

HRMS (ESI) m/z: Calcd. for _Ci0H8BrNOS [M+Na] ⁺ : 291.9402; _found : 291.9400.

According to the above data, the structure of the obtained product is deduced as: It shows that the target product was successfully synthesized.

Example 44

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 4-chlorophenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C After 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product , the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 74%.

Example 45

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 4-trifluoromethylphenylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography. To obtain the target product, the column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 67%.

Example 46

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 4-ethylphenylacetylene bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir at 100°C After reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target For the product, the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 81%.

Example 47

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 4-ethoxyphenylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain For the target product, the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 66%.

The structural characterization data of the resulting product are as follows:

IR(KBr):3067,2982,2930,2892,2158,1602,1505,1298,1250,1176,835, 793,744cm ^-1 .

¹ H NMR (400MHz, CDCl ₃ ): δ7.39-7.34(m, 2H), 6.93-6.89(m, 2H), 6.67(s, 1H), 4.05(q, J=7.0Hz, 2H), 1.42 (t,J=7.0Hz,3H).

¹³ C NMR (100MHz, CDCl ₃ ): δ160.4, 134.4, 129.5, 127.5, 114.7, 108.8, 108.7, 63.6, 14.7ppm.

HRMS (ESI) m/z: Calcd. for _C11H10BrNOS [M+Na] ⁺ : 305.9559 _; found: 305.9560.

According to the above data, the structure of the obtained product is deduced as: It shows that the target product was successfully synthesized.

Example 48

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 4-n-propylphenylacetylene bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain For the target product, the column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 81%.

Example 49

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 1-decyne bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, and stir the reaction at 100°C. Hours later, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography to obtain the target product, The column chromatography eluent used was petroleum ether:ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 89%.

Example 50

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 5-phenyl-1-pentyne bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, at 100°C After stirring and reacting under the same conditions for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography , to obtain the target product, the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 74%.

Example 51

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 5-cyano-1-pentyne bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, at 100°C After stirring and reacting for 3 hours under the same conditions, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography , to obtain the target product, the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 93%.

Example 52

In a 25ml reaction vessel equipped with a reflux condenser, add 0.2mmol of 5-methyl-1-hexyne bromide, 0.02mmol of silver acetate, 0.4mmol of potassium thiocyanate and 2ml of glacial acetic acid, at 100°C After stirring and reacting under the same conditions for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography , to obtain the target product, the column chromatography eluent used was petroleum ether: ethyl acetate mixed solvent with a volume ratio of 100:1, and the yield was 93%.

Example 53

In a 25 ml reaction vessel equipped with a reflux condenser, add 0.2 mmol of 5-chloro-1-pentyne bromide, 0.02 mmol of silver acetate, 0.4 mmol of potassium thiocyanate and 2 ml of glacial acetic acid. After stirring and reacting for 3 hours, stop heating and stirring, cool to room temperature, add aqueous sodium bicarbonate solution after filtration and extract three times with ethyl acetate, dry over magnesium sulfate, remove the solvent by rotary evaporation under reduced pressure, and then separate and purify by column chromatography. To obtain the target product, the column chromatography eluent used was a mixed solvent of petroleum ether:ethyl acetate with a volume ratio of 100:1, and the yield was 91%.

The structural characterization data of the resulting product are as follows:

IR(KBr):3070,2957,2855,2357,2159,1835,1241,1057cm ^-1 .

¹ H NMR (400MHz, CDCl ₃ ): δ6.55(s, 1H), 3.59(t, J=6.1Hz, 2H), 2.79(t, J=7.2Hz, 2H), 2.15-2.07(m, 2H ),As shown in Figure 4.

¹³ C NMR (100MHz, CDCl ₃ ): δ132.2, 108.6, 107.7, 43.1, 33.9, 29.9ppm, as shown in FIG. 5 .

ESI _- HRMS m/z: Calcd. for _C6H7BrClNS [M+Na] ⁺ : 261.9063, found: 261.9060.

According to the above data, the structure of the obtained product is deduced as: It shows that the target product was successfully synthesized.

The above-mentioned embodiment is a preferred embodiment of the present invention, but the embodiment of the present invention is not limited by the above-mentioned embodiment, and any other changes, modifications, substitutions, combinations, Simplifications should be equivalent replacement methods, and all are included in the protection scope of the present invention.

Claims (6)

1. a kind of method of synthesis alkenyl thiocyanates derivative, it is characterised in that include the following steps:

In the reaction vessel, alkynes halogen, rhodanate is added for raw material, in the condition that silver salt is catalyst, organic solvent is solvent Gained reaction solution is cooled to room temperature then to purify and spread out to get the alkenyl thiocyanates by lower heating reaction after reaction Biology；

Its reaction is shown below:

Wherein, R is aryl or fatty alkyl, and X is chlorine, bromine or iodine；The rhodanate is potassium rhodanide or ammonium thiocyanate；

The alkynes halogen is arylalkyne chlorine, arylalkyne bromine, arylalkyne iodine, alkyl alkynes chlorine, alkyl alkynes bromine or alkyl alkynes iodine；

The silver salt be silver chlorate, silver bromide, silver nitrate, silver trifluoromethanesulfonate, silver carbonate, silver tetrafluoroborate, silver acetate and At least one of silver trifluoroacetate；

The organic solvent is at least one of glacial acetic acid and ethyl alcohol.

2. the method for synthesis alkenyl thiocyanates derivative according to claim 1, it is characterised in that：

The alkynes halogen is arylalkyne bromine or alkyl alkynes bromine.

3. the method for synthesis alkenyl thiocyanates derivative according to claim 2, it is characterised in that：

The arylalkyne bromine includes phenylacetylene bromine；

The alkyl alkynes bromine includes：1- hexin bromines, 1- heptyne bromines, 1- octyne bromines, 1- n-heptylacetylene bromines, 1- decine bromines, 5- methyl-1s- Hexin bromine.

4. the method for synthesis alkenyl thiocyanates derivative according to claim 1, it is characterised in that：

The molar ratio of alkynes halogen and rhodanate used is 1:(1~4)；

The molar ratio of silver salt used and alkynes halogen is 0.1:1.

5. the method for synthesis alkenyl thiocyanates derivative according to claim 1, it is characterised in that：

The described heating reaction refer to be stirred to react 1 at 80~100 DEG C~for 24 hours.

6. the method for synthesis alkenyl thiocyanates derivative according to claim 1, it is characterised in that：

The purifying refers to filtering reaction solution, and sodium bicarbonate solution is added and is extracted with ethyl acetate three times, collects organic Phase is dried with magnesium sulfate, and then vacuum distillation removes organic solvent, obtains crude product, then carries out column to the crude product of gained Chromatography；

Wherein, the eluent of column chromatography is the mixed solvent of petroleum ether and ethyl acetate；The volume ratio of petroleum ether and ethyl acetate For (10~200):1.