CN105294601B - Thioamide analog compound and its synthetic method - Google Patents

Thioamide analog compound and its synthetic method Download PDF

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CN105294601B
CN105294601B CN201510725463.9A CN201510725463A CN105294601B CN 105294601 B CN105294601 B CN 105294601B CN 201510725463 A CN201510725463 A CN 201510725463A CN 105294601 B CN105294601 B CN 105294601B
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aldehyde
analog compound
synthetic method
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CN105294601A (en
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姜雪峰
魏建朋
李鸣
李一鸣
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East China Normal University
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    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/194—Radicals derived from thio- or thiono carboxylic acids
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/38—Amides of thiocarboxylic acids
    • C07C327/40—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C327/44—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
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    • C07C327/46—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/38—Amides of thiocarboxylic acids
    • C07C327/48—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to carbon atoms of six-membered aromatic rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
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    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

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Abstract

The invention discloses the synthetic method of the thioamide analog compound shown in a kind of formula (II), using aldehyde and formoxyl fatty amine as reaction raw materials, with Na2S·9H2O is sulfiding reagent, under oxidant effect, is reacted in aqueous phase and obtains thioamide analog compound.The synthetic method raw material of the present invention is cheap and easy to get, solvent is green, operation is simple, mild condition, substrate universality is wide, and yield is higher, and functional group tolerance is good, and it is successfully realized the thioamidesization modification of natural aldehyde and bioactive molecule, the method that efficiently structure thioamide analog compound is provided for pharmaceutical chemistry, bio-orthogonal chemical research.

Description

Thioamide analog compound and its synthetic method
Technical field
The invention belongs to organic compound technique synthesis and applied technical field, and in particular to thioamide analog compound and Its synthetic method.
Background technology
Thioamide analog compound is a kind of very important compound, is widely used as various kinds of drug and bioactivity point Son, as shown in formula (i)~formula (iii).Therefore, from some simple in construction, commercial compounds that can largely obtain, structure Thioamide analog compound is built to be particularly important.
Medicine fractionated molecule containing thio amide structure
Synthesize thioamide analog compound conventional method mainly by acid amides and lawesson reagent or phosphorus pentasulfide come Prepare.In such method, used lawesson reagent is unstable, and costly, Atom economy is low for price, and stink is big, and right Environment and human body have different degrees of injury, and required acid amides will be prepared beforehand through carboxylic acid (or acyl chlorides) and amine condensation, step Economy is low.In recent years, developed using Willgerodt-Kindler reactions to prepare the method for thioamide analog compound, This method is used as raw material by the use of sulphur simple substance as sulphur source, aryl aldehyde, aryl groups per alkyl group ketone, aryl ethane, benzylamine, Arylacetic acids etc. To synthesize thioamide analog compound, compared to conventional method, atom utilization and step economy, but substrate the method increase Universality is not wide, and part substrate severe reaction conditions, reaction temperature is up to 320 DEG C, and many raw materials are not readily available, and The use of organic solvent also limit its practicality.Many deficiencies constrain such method in technical study and pharmaceutical chemistry above The profound application of research field.
" Green Chemistry " is as one of main target of chemical developer of 21 century, it is desirable to is engaged in the researcher of chemistry Raw material should be effectively utilized when developing and chemically reacting, avoids the use of harmful reagent and solvent.In consideration of it, a kind of green of development is high The method that effect synthesizes thioamides turns into the vertical topic foundation of the present invention and technical problem to be solved.
The content of the invention
Instant invention overcomes the drawbacks described above of prior art, innovatively proposes a kind of efficiently structure thioamide analog The method of compound.The method of the present invention is raw material using aldehyde compound and formoxyl fatty amine, with Na2S·9H2O tries for vulcanization Agent, under oxidant effect, using water as reaction dissolvent, the thioamide analog compound as shown in formula (II) is prepared.This The synthetic method of invention, raw material is cheap and easy to get, and solvent is green, and operation is simple, mild condition, and substrate universality is wide, Yield is high, can compatible alcoholic extract hydroxyl group, phenolic hydroxyl group, pi-allyl, alkenyl, electron donating group, electron withdraw group and steric group, and Stereocpecificity is kept.
The present invention proposes a kind of synthetic method of thioamide analog compound, wherein, using aldehyde and formoxyl fatty amine as Reaction raw materials, with Na2S·9H2O is sulfiding reagent, in the presence of oxidant (including crossing peroxygen oxidising agent), in 25~100 DEG C of bars Under part, reacted 3~24 hours in reaction dissolvent and obtain the thioamide analog compound as shown in formula (II)；The course of reaction As shown in formulas below (a).
In the reaction equation (a), R is alkyl or aryl；R1/R2It is alkyl, containing aryl alkyl or hydrogen.In the present invention, R, R1/R2Include but are not limited to above-mentioned group.
Wherein, in the reaction equation (a), R is isobutyl group, 2- phenylethyls, benzyl, cyclohexyl, 2,6- dimethyl -5- alkene Base heptyl, 1- methyl -2- (4- tert-butyl-phenyls) ethyl, 1,5 dimethyl -4- alkenyls hexyls, phenyl, 2- aminomethyl phenyls, 3- first Base phenyl, 4- aminomethyl phenyls, 3- fluorophenyls, 3- chlorphenyls, 3- bromophenyls, 4- methoxyphenyls, 3,4,5- trimethoxyphenyls, 3- trifluoromethyls, 4- trifluoromethyls, 4- chlorphenyls, 4- bromophenyls, 4- hydroxy phenyls, 2- hydroxy phenyls, 2- naphthyls, 2- thiophene, 2- pyridines, 2- benzofurans, cholesterol derivative or estrone derivative；R1/R2It is methyl/methyl, 2- phenyl second Base/hydrogen, 2- hydroxyethyls/hydrogen, propyl group/hydrogen, benzyl/hydrogen, pi-allyl/hydrogen,
In the present invention, the reaction temperature is 25~100 DEG C, it is preferable that is carried out under the conditions of 100 DEG C.
In the present invention, aldehyde compound (substrate 1) and sulfiding reagent Na of the initiation material as shown in formula (I)2S· 9H2O dosage mol ratio is 1:1~7.Preferably, both dosage mol ratios are 1:3.5.
In the present invention, aldehyde compound and formoxyl fatty amine (substrate 2) dosage of the initiation material as shown in formula (I) Mol ratio is 1:1~10.Preferably, both dosage mol ratios are 1:5.
In the present invention, the oxidant is selected from Isosorbide-5-Nitrae-benzoquinones, dibenzoyl peroxide, potassium peroxydisulfate, oxygen, m-chloro peroxide Benzoic acid, iodobenzene diacetate, ferric nitrate, peroxide list potassium sulfonate etc., it is preferable that the oxidant be dibenzoyl peroxide or Potassium peroxydisulfate, the dosage mol ratio of raw material aldehyde and the oxidant as shown in formula (I) is 1:1~5.When the oxidant was When aoxidizing dibenzoyl, it is preferable that the dosage mol ratio of raw material aldehyde and the dibenzoyl peroxide as shown in formula (I) is 1: 2.5.When the oxidant is potassium peroxydisulfate, it is preferable that the dosage of raw material aldehyde and the potassium peroxydisulfate as shown in formula (I) is rubbed You are than being 1:1.8.
The oxidant of the present invention act as promoting formoxyl fatty amine to produce amine free radical, and aoxidizes finally thio Acid amides free radical obtains final thioamide product.
In the present invention, in the synthetic method, additive can further include.The additive is pyridine, three second Amine, tetrabutylammonium chloride, TBAB or tetrabutylammonium iodide, it is preferable that the additive is pyridine.The additive Mole be up to 5 times of aldehyde as shown in formula (I)；Preferably, the mole of the additive is the aldehyde as shown in formula (I) 5 times.
The additive of the present invention act as increasing the solubility of aldehyde (substrate 1) in a solvent.
In the present invention, the reaction dissolvent is DMF, dimethyl sulfoxide, DMA, N- Methyl pyrrolidone, nitromethane, ethylene glycol, acetonitrile, 1,4- dioxane, paraxylene or water are arbitrarily a kind of.Preferably, The solvent is water.
In synthetic method of the present invention, when substrate aldehyde and formoxyl fatty amine are liquid, methods described includes following step Suddenly：Sulfiding reagent is first added in reaction vessel, then adds the substrate aldehyde, formoxyl fatty amine and additive that are dissolved in solvent In reaction vessel, oxidant is eventually adding, after being reacted 3~24 hours under the conditions of 25~100 DEG C, obtains the sulphur shown in formula (II) For amides compound.
In synthetic method of the present invention, when aldehyde is liquid, formoxyl fatty amine is solid, methods described includes following step Suddenly：The formoxyl fatty amine of sulfiding reagent and solid is first added in reaction vessel, then by the substrate aldehyde for being dissolved in solvent and is added Add agent to add in reaction vessel, be eventually adding oxidant, after being reacted 3~24 hours under the conditions of 25~100 DEG C, obtain formula (II) Shown thioamide compound；
In synthetic method of the present invention, when aldehyde is solid, formoxyl fatty amine is liquid, methods described includes following step Suddenly：Sulfiding reagent, the aldehyde of solid are first added in reaction vessel, then adds the formoxyl fatty amine and additive that are dissolved in solvent Enter in reaction vessel, be eventually adding oxidant, after being reacted 3~24 hours under the conditions of 25~100 DEG C, obtain shown in formula (II) Thioamide compound；
In synthetic method of the present invention, when aldehyde and formoxyl fatty amine are solid, it the described method comprises the following steps：First Sulfiding reagent, aldehyde and formoxyl fatty amine are added in reaction vessel, the additive for being dissolved in solvent is then added into reaction vessel In, oxidant is eventually adding, after reacting 3-24 hours under the conditions of 25~100 DEG C, obtains the thioamides shown in formula (II) Compound.
In an instantiation, synthetic reaction of the present invention is in reaction bulb A：
(1) when substrate aldehyde and formoxyl fatty amine are liquid, then sulfiding reagent Na is added in reaction vessel2S·9H2O (X mmol), it is then that substrate aldehyde (Formulas I, Y mmol), formoxyl fatty amine (Z mmol) and additive pyridine (W mmol) is molten In solvent H2O (V mL) is added in reaction vessel, adds oxidant dibenzoyl peroxide (U mmol) or potassium peroxydisulfate (S mmol)；
(2) when aldehyde is solid, formoxyl fatty amine is liquid, then sulfiding reagent Na is added in reaction vessel2S· 9H2O (X mmol), substrate aldehyde (Formulas I, Y mmol), then by formoxyl fatty amine (Z mmol) and additive pyridine (W Mmol) it is dissolved in solvent H2O (V mL) is added in reaction vessel, adds oxidant dibenzoyl peroxide (U mmol) or over cure Sour potassium (S mmol)；
(3) when aldehyde is liquid, formoxyl fatty amine is solid, then sulfiding reagent Na is added in reaction vessel2S· 9H2O (X mmol), formoxyl fatty amine (Z mmol), then by substrate aldehyde (Formulas I, Y mmol) and additive pyridine (W Mmol) it is dissolved in solvent H2O (V mL) is added in reaction vessel, adds oxidant dibenzoyl peroxide (U mmol) or over cure Sour potassium (S mmol)；
(4) when substrate aldehyde and formoxyl fatty amine are solid, then sulfiding reagent Na is added in reaction vessel2S·9H2O(X Mmol), substrate aldehyde (Formulas I, Y mmol), formoxyl fatty amine (Z mmol), then additive pyridine (W mmol) is dissolved in molten Agent H2O (V mL) is added in reaction vessel, adds oxidant dibenzoyl peroxide (U mmol) or potassium peroxydisulfate (S mmol)；
Reaction system stirs 3-24 hours at 60-100 DEG C；After thin-layer chromatography monitoring reaction terminates, by reaction system Room temperature is cooled to, H is added into system2O (10mL) dilutes, and is extracted with ethyl acetate (10mL*3), anhydrous sodium sulfate drying, mistake Filter, concentration, target product Formula II is obtained through column chromatography for separation；
The invention also provides the thioamides as shown in formula (II) being prepared according to the above-mentioned synthetic method of the present invention Class compound,
Wherein, R is alkyl, aryl；R1/R2It is alkyl, containing aryl alkyl or hydrogen.
Preferably, R be isobutyl group, 2- phenylethyls, benzyl, cyclohexyl, 2,6- dimethyl -5- alkenyls heptyl, 1- methyl - 2- (4- tert-butyl-phenyls) ethyl, 1,5 dimethyl -4- alkenyls hexyls, phenyl, 2- aminomethyl phenyls, 3- aminomethyl phenyls, 4- methylbenzenes Base, 3- fluorophenyls, 3- chlorphenyls, 3- bromophenyls, 4- methoxyphenyls, 3,4,5- trimethoxyphenyls, 3- trifluoromethyls, 4- trifluoromethyls, 4- chlorphenyls, 4- bromophenyls, 4- hydroxy phenyls, 2- hydroxy phenyls, 2- naphthyls, 2- thiophene, 2- pyridines, 2- benzofurans, cholesterol derivative or estrone derivative；R1/R2It is methyl/methyl, 2- phenylethyls/hydrogen, 2- hydroxyl second Base/hydrogen, propyl group/hydrogen, benzyl/hydrogen, pi-allyl/hydrogen,
New compound prepared by the present invention, it is characterised in that shown in its structural formula such as formula (II),
Wherein, R is isobutyl group, cyclohexyl, 2,6- dimethyl -5- alkenyls heptyl, 1- methyl -2- (4- tert-butyl-phenyls) second Base, 1,5 dimethyl -4- alkenyls hexyls, phenyl, 3- chlorphenyls, 3- bromophenyls, 2- benzofurans, cholesterol derivative or female phenol Ketone derivatives；
R1/R2It is methyl/methyl, 2- phenylethyls/hydrogen, 2- hydroxyethyls/hydrogen,
Preferably, the new thioamide analog compound includes：
The advantages of synthetic method of the present invention, includes：Used each raw material is industrialization commodity, and simple and easy to get, source is wide It is general, and performance is highly stable, it is not necessary to special preservation condition；The present invention uses inorganic salts Na2S·9H2O as sulfiding reagent, With the characteristic that cost is low, yield is high, simple to operate, Atom economy is high, industrialization large-scale production is completely suitable for；This hair The solvent that bright synthetic method uses is pollution-free, can especially use water as reaction dissolvent, green, the post processing letter of product It is single；Inventive substrate universality is wide, functional group tolerance is good, and is successfully realized natural products aldehyde and bioactive molecule Thioamidesization modifies (for example, embodiment 5,6,10,11,12,13,14,42,43), is ground for pharmaceutical chemistry, bio-orthogonal chemistry Study carefully the method for providing efficiently structure thioamide analog compound.
Embodiment
In embodiment 1~13, embodiment 15~42, solvent for use is water.
In embodiment 14 and embodiment 43, solvent for use is water：Ethylene glycol=1:1 (volume ratio).
In embodiment 1~15, embodiment 17~19, embodiment 21, embodiment 23~24 is used in embodiment 41~43 Na2S·9H2O moles are 3.5 times of aldehyde；Oxidant used is potassium peroxydisulfate, and mole is 1.8 times of aldehyde.Formoxyl used The mole of fatty amine is 5 times of aldehyde.
In embodiment 16, embodiment 20, embodiment 22, embodiment 25, embodiment 27~32, in embodiment 37~40, institute Use Na2S·9H2O moles are 3.5 times of aldehyde；Oxidant used is dibenzoyl peroxide, and mole is 2.5 times of aldehyde；Institute Mole with formoxyl fatty amine is 5 times of aldehyde.
In embodiment 26, embodiment 33~36, Na used2S·9H2O moles are 7 times of aldehyde；Oxidant used was Dibenzoyl is aoxidized, mole dosage is 5 times of aldehyde；The mole of formoxyl fatty amine used is 10 times of aldehyde.
In embodiment 1~12, embodiment 14~23, embodiment 31, embodiment 35~36, in embodiment 41~43, reaction Temperature is 100 DEG C.
It it is 60 DEG C in embodiment 13, embodiment 24~30, embodiment 32~34, embodiment 37~40, reaction temperature.
In embodiment 1~15, embodiment 17~19, embodiment 21, embodiment 23~24, in embodiment 41~43, addition Pyridine, pyridine mole used are 5 times of aldehyde.
With reference to specific examples below, the present invention is described in further detail, and of the invention protects content not limit to In following examples.Under the spirit and scope without departing substantially from inventive concept, those skilled in the art it is conceivable that change and excellent Point is all included in the present invention, and using appended claims as protection domain.Implement the present invention process, condition, Reagent, experimental method etc., it is the universal knowledege and common knowledge of this area in addition to the following content specially referred to, this hair It is bright that content is not particularly limited.Data given by following examples include concrete operations and reaction condition and product.Product is pure Degree is identified by nuclear-magnetism.
The synthetic reaction of arylalkyl thioethers compound of the present invention, comprises the following steps：When substrate aldehyde and formoxyl fat When amine is liquid, sulfiding reagent is first added in reaction vessel, then will be dissolved in the substrate aldehyde of solvent, formoxyl fatty amine and Additive is added in reaction vessel, is eventually adding oxidant, after being reacted 3~24 hours under the conditions of 25~100 DEG C, is obtained formula (II) thioamide analog compound shown in；When aldehyde is liquid, formoxyl fatty amine is solid, first added in reaction vessel The formoxyl fatty amine of sulfiding reagent and solid, then the substrate aldehyde for being dissolved in solvent and additive are added in reaction vessel, most After add oxidant, after being reacted 3~24 hours under the conditions of 25~100 DEG C, obtain the thioamide compound shown in formula (II)； When aldehyde is solid, formoxyl fatty amine is liquid, sulfiding reagent, the aldehyde of solid are first added in reaction vessel, then will be molten Added in the formoxyl fatty amine and additive of solvent in reaction vessel, be eventually adding oxidant, it is anti-under the conditions of 25~100 DEG C After answering 3~24 hours, the thioamide compound shown in formula (II) is obtained；When aldehyde and formoxyl fatty amine are solid, first Sulfiding reagent, aldehyde and formoxyl fatty amine are added in reaction vessel, the additive for being dissolved in solvent is then added into reaction vessel In, oxidant is eventually adding, after reacting 3-24 hours under the conditions of 25~100 DEG C, obtains the thioamides shown in formula (II) Compound.Thioamide compound prepared by above-mentioned steps again through extracting, drying, filtering, concentrating, what column chromatography for separation was purified Purpose product.
Thioamide analog compound as shown in table 1, it is that obtained product is synthesized by the inventive method, there is not yet Open source literature discloses these compounds.
The thioamide analog compound of the synthetic method synthesis of the present invention of table 1
Embodiment 1
Compound 2a synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by isopentyl aldehyde (0.3mmol, 25.8mg), N- first Acylpiperidine (1.5mmol, 169.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, then will K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 8 hours at 100 DEG C, and TLC is detected after completion of the reaction, drop To room temperature, water 10mL dilutions are added into system, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, Concentration, yellow liquid 2a (33.8mg, 61%), R are obtained through column chromatography for separationf=0.55 (PE:EA=10:1)；1H NMR (400MHz,CDCl3) δ 4.38-4.25 (m, 2H), 3.76-3.68 (m, 2H), 2.80 (d, J=7.3Hz, 2H), 2.24-2.07 (m, 1H), 1.78-1.60 (m, 6H), 1.00 (d, J=6.7Hz, 6H)13C NMR(100MHz,CDCl3)δ201.4,52.0, 51.6,51.1,28.9,26.9,25.4,24.1,22.4；IR(film)2937,2361,1487,1440,1265,1149, 1079,1002,852cm-1；HRMS(EI)Calcd for C10H19NS 185.1238,Found 185.1235.
Embodiment 2
Compound 2b synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by isopentyl aldehyde (0.3mmol, 25.8mg), N- first Acyl group morpholine (1.5mmol, 172.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, then By K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 9 hours at 100 DEG C, and TLC is detected after completion of the reaction, Room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, mistake Filter, concentration, weak yellow liquid 2b (32.0mg, 57%), R are obtained through column chromatography for separationf=0.6 (PE:EA=5:1)；1H NMR (400MHz,CDCl3) δ 4.44-4.25 (m, 2H), 3.86-3.62 (m, 6H), 2.76 (d, J=7.3Hz, 2H), 2.17-2.06 (m, 1H), 0.99 (d, J=6.7Hz, 6H)；13C NMR(100MHz,CDCl3)δ203.2,66.6,66.5,51.6,50.4, 50.1,29.1,22.3；IR(film)2961,2925,2866,1478,1431,1259,1115,1021,797cm-1；MS(EI) M/z (%) 187 (100), 144 (80), 86 (85)
Embodiment 3
Compound 2c synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by 3-phenylpropion aldehyde (0.3mmol, 40.2mg), N, Dinethylformamide (1.5mmol, 109.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and add reaction tube In, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 8 hours at 100 DEG C, and TLC detections have been reacted Bi Hou, room temperature is dropped to, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate is done It is dry, filter, concentration, orange liquid 2c (48.0mg, 83%), R are obtained through column chromatography for separationf=0.4 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ7.32-7.27(m,2H),7.24-7.20(m,3H),3.48(s,3H),3.14(s,3H),3.13- 3.09(m,2H),3.09-3.03(m,2H)；13C NMR(100MHz,CDCl3)δ203.1,140.6,128.5,128.4, 126.4,44.9,44.6,41.5,35.7；IR(film)3025,2963,1514,1496,1393,1260,1093,1017, 798,700cm-1；MS (EI) m/z (%) 193 (100), 88 (90)
Embodiment 4
Compound 2d synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by 3-phenylpropion aldehyde (0.3mmol, 40.2mg), N- Formyl morpholine (1.5mmol, 172.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, Again by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 3 hours at 100 DEG C, and TLC detection reactions finish Afterwards, room temperature is dropped to, water 10mL dilutions are added into system, ethyl acetate (10mL*3) is added and extracts, anhydrous sodium sulfate drying, Filtering, concentration, orange liquid 2d (58.5mg, 83%), R are obtained through column chromatography for separationf=0.4 (PE:EA=5:1)；1H NMR (400MHz,CDCl3)δ7.30-7.27(m,2H),7.23-7.20(m,3H),4.32-4.30(m,2H),3.70-3.68(m, 2H),3.54-3.51(m,2H),3.39-3.36(m,2H),3.12-3.10(m,4H)；13C NMR(100MHz,CDCl3)δ 202.6,140.1,128.5,128.5,126.5,66.3,66.0,50.0,49.8,44.1,35.7；IR(film)3302, 3060,3028,2962,2862,1531,1488,1453,1384,1261,1093,1027,943,802,767,695cm-1；MS (EI) m/z (%) 235 (45), 144 (100), 91 (60).
Embodiment 5
Compound 2e synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by citronellal (0.3mmol, 46.2mg), N- first Acyl group -2- ethylaminoethanols (1.5mmol, 133.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and add reaction tube In, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 5 hours at 100 DEG C, and TLC detections have been reacted Bi Hou, room temperature is dropped to, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate is done It is dry, filter, concentration, yellow solid 2e (34.4mg, 50%), R are obtained through column chromatography for separationf=0.50 (PE:EA=1:1).1H NMR(400MHz,CDCl3) δ 7.72 (br, 1H), 5.10-5.07 (m, 1H), 3.94-3.83 (m, 4H), 2.70 (dd, J= 13.2,6.1Hz, 1H), 2.41 (dd, J=13.1,8.5Hz, 1H), 2.20-2.12 (m, 1H), 2.08-1.94 (m, 2H), 1.67 (s, 3H), 1.59 (s, 3H), 1.27-1.14 (m, 2H), 0.92 (d, J=6.6Hz, 3H)；13C NMR(100MHz,CDCl3)δ 205.7,131.6,124.2,60.6,54.9,47.8,36.5,33.5,25.7,25.4,18.9,17.7；IR(film)3266, 2957,2926,1534,1457,1404,1318,1052,718cm-1；HRMS(EI)Calcd for C12H23NOS 229.1500,Found 229.1501.
Embodiment 6
Compound 2f synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by citronellal (0.3mmol, 46.2mg), N- first Acyl group morpholine (1.5mmol, 172.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, then By K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 10 hours at 100 DEG C, and TLC detection reactions finish Afterwards, room temperature is dropped to, water 10mL dilutions are added into system, ethyl acetate (10mL*3) is added and extracts, anhydrous sodium sulfate drying, Filtering, concentration, weak yellow liquid 2f (46.7mg, 61%), R are obtained through column chromatography for separationf=0.4 (PE:EA=5:1)；1H NMR (400MHz,CDCl3) δ 5.06 (t, J=7.0Hz, 1H), 4.36-4.34 (m, 2H), 3.86-3.65 (m, 6H), 2.86 (dd, J =13.4,6.2Hz, 1H), 2.73 (dd, J=13.4,8.5Hz, 1H), 2.09-1.92 (m, 3H), 1.66 (s, 3H), 1.59 (s, 3H), 1.51-1.39 (m, 1H), 1.34-1.25 (m, 1H), 0.98 (d, J=6.6Hz, 3H)；13C NMR(100MHz,CDCl3)δ 203.1,131.7,124.2,66.6,66.5,50.4,50.2,50.1,36.7,33.1,25.7,25.3,19.2,17.7；IR (film)2963,2906,1477,1432,1259,1084,1012,792.702cm-1；HRMS(EI)Calcd for C14H25NOS255.1657,Found 255.1655.
Embodiment 7
Compound 2g synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by phenylacetaldehyde (0.3mmol, 36.0mg), N- first Acyl group morpholine (1.5mmol, 172.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, then By K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 9 hours at 100 DEG C, and TLC is detected after completion of the reaction, Room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, mistake Filter, concentration, yellow solid 2g (30.6mg, 46%), R are obtained through column chromatography for separationf=0.35 (PE:EA=5:1)；1H NMR (400MHz,CDCl3)δ7.31-7.17(m,5H),4.33-4.27(m,4H),3.71-3.66(m,2H),3.60-3.54(m, 2H),3.36-3.30(m,2H)；13C NMR(100MHz,CDCl3)δ200.0,135.7,128.9,127.7,127.1,66.3, 66.1,50.7,50.6,50.1；IR(film)3407,3059,3026,2964,2855,1602,1487,1433,1296, 1254,1109,1030,959,751,705cm-1；MS (EI) m/z (%) 221 (70), 130 (75), 91 (100)
Embodiment 8
Compound 2h synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by hexahydrobenzaldehyde (0.3mmol, 33.7mg), N- formyl morpholines (1.5mmol, 172.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and add reaction tube In, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 4 hours at 100 DEG C, and TLC detections have been reacted Bi Hou, room temperature is dropped to, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate is done It is dry, filter, concentration, faint yellow solid 2h (32.6mg, 51%), R are obtained through column chromatography for separationf=0.6 (PE:EA=10:1)；1H NMR(400MHz,CDCl3) δ 4.45-4.30 (m, 2H), 3.92-3.64 (m, 6H), 2.69 (t, J=10.9Hz, 1H), 1.83- 1.74(m,4H),1.70-1.67(m,3H),1.32-1.24(m,3H)；13C NMR(100MHz,CDCl3)δ209.2,66.7, 66.6,50.0,49.5,47.3,33.2,26.1,25.6；IR(film)2956,2925,2852,1462,1429,1261, 1119,1030,797cm-1；MS (EI) m/z (%) 213 (80), 126 (25), 86 (100)
Embodiment 9
Compound 2i synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), N- formoxyl -2- phenylethylamines (1.5mmol, 223.5mg), by hexahydrobenzaldehyde (0.3mmol, 33.7mg), pyridine (1.5mmol, 118.5mg) is dissolved in water (0.6mL) addition In reaction tube, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 8 hours at 100 DEG C, TLC detections After completion of the reaction, room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous sulphur Sour sodium is dried, and is filtered, and concentration, yellow liquid 2i (40.7mg, 55%), R is obtained through column chromatography for separationf=0.50 (PE:EA= 10:1).1H NMR(400MHz,CDCl3) δ 7.37-7.17 (m, 5H), 7.12 (br, 1H), 3.95 (dd, J=12.5,6.8Hz, 2H), 2.98 (t, J=6.9Hz, 2H), 2.46-2.38 (m, 1H), 1.88-1.74 (m, 4H), 1.69-1.66 (m, 1H), 1.55- 1.47(m,2H),1.27-1.18(m,3H)；13C NMR(100MHz,CDCl3)δ210.4,138.3,128.8,128.7, 126.8,55.0,46.3,33.7,32.8,25.9,25.6；IR(film)3243,2928,2853,1524,1450,1280, 1131,979,698cm-1；HRMS(EI)Calcd for C15H21NS 247.1395,Found 247.1392.
Embodiment 10
Compound 2j synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by lilial (0.3mmol, 61.3mg), N- first Acyl group morpholine (1.5mmol, 172..5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, Again by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 20 hours at 100 DEG C, and TLC detection reactions finish Afterwards, room temperature is dropped to, water 10mL dilutions are added into system, ethyl acetate (10mL*3) is added and extracts, anhydrous sodium sulfate drying, Filtering, concentration, faint yellow solid 2j (59.5mg, 65%), R are obtained through column chromatography for separationf=0.3 (PE:EA=5:1)；1H NMR (400MHz,CDCl3) δ 7.28 (d, J=8.3Hz, 2H), 7.14 (d, J=8.3Hz, 2H), 4.82-4.74 (m, 1H), 3.88- 3.82(m,1H),3.73-3.69(m,1H),3.57-3.53(m,1H),3.48-3.39(m,3H),3.35-3.28(m,1H), 3.09 (dd, J=13.1,8.9Hz, 1H), 2.83 (dd, J=13.1,5.6Hz, 1H), 2.66-2.60 (m, 1H), 1.34 (d, J =6.4Hz, 3H), 1.29 (s, 9H)；13C NMR(100MHz,CDCl3)δ208.8,149.5,136.6,128.8,125.2, 66.3,65.9,50.3,49.8,43.8,43.6,34.3,31.3,22.2；IR(film)3024,2862,1510,1471, 1433,1274,1233,1113.1024,983,872,837,805cm-1；HRMS(EI)Calcd for C18H27NOS 305.1813,Found 305.1814.
Embodiment 11
Compound 2k synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by lilial (0.3mmol, 61.3mg), N- first Acylpiperidine (1.5mmol, 169.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, then will K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 24 hours at 100 DEG C, and TLC is detected after completion of the reaction, Room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, mistake Filter, concentration, yellow solid 2k (47.3mg, 52%), R are obtained through column chromatography for separationf=0.50 (PE:EA=10:1).1H NMR (400MHz,CDCl3) δ 7.27 (d, J=8.6Hz, 2H), 7.15 (d, J=8.3Hz, 2H), 4.70-4.59 (m, 1H), 3.89- 3.80 (m, 1H), 3.68-3.62 (m, 1H), 3.47-3.38 (m, 1H), 3.38-3.28 (m, 1H), 3.13 (dd, J=13.1, 7.9Hz, 1H), 2.80 (dd, J=13.2,6.3Hz, 1H), 1.65-1.60 (m, 1H), 1.59-1.51 (m, 2H), 1.50-1.42 (m,1H),1.45-1.35(m,1H),1.30-1.27(m,12H),0.92-0.75(m,1H)；13C NMR(100MHz,CDCl3)δ 207.3,149.1,137.0,128.9,125.1,51.8,50.3,43.8,43.6,34.3,31.3,26.4,25.2,24.2, 21.7；IR(film)2962,2933,2858,1487,1444,1282,1254,874,833,802cm-1；HRMS(EI)Calcd for C19H29NS 303.2021,Found 303.2023.
Embodiment 12
Compound 2l synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), N- formoxyl -2- phenylethylamines (1.5mmol, 223.5mg), by lilial (0.3mmol, 61.3mg), pyridine (1.5mmol, 118.5mg) is dissolved in water (0.6mL) and adds reaction Guan Zhong, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 24 hours at 100 DEG C, and TLC detections are anti- After answering, room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous slufuric acid Sodium is dried, and is filtered, and concentration, yellow liquid 2l (63.0mg, 62%), R is obtained through column chromatography for separationf=0.50 (PE:EA=10: 1).1H NMR(400MHz,CDCl3) δ 7.33-7.27 (m, 3H), 7.26-7.19 (m, 2H), 7.11 (d, J=8.2Hz, 2H), 7.01 (d, J=6.9Hz, 2H), 6.82 (br, 1H), 4.01-3.87 (m, 1H), 3.70-3.62 (m, 1H), 3.00 (dd, J= 13.2,8.4Hz,1H),2.82-2.75(m,2H),2.74-2.64(m,1H),2.62-2.52(m,1H),1.30(s,9H), 1.27 (d, J=6.6Hz, 3H)；13C NMR(100MHz,CDCl3)δ209.2,149.3,138.2,136.6,128.7,128.7, 128.6,126.7,125.2,52.8,46.2,42.9,34.4,33.7,31.4,20.7；IR(film)3283,2963,2868, 1519,1454,1268,1108,981,700cm-1；HRMS(EI)Calcd for C22H29NS 339.2021,Found 339.2024.
Embodiment 13
Compound 2m synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by melonal (0.3mmol, 42.1mg), N- first Acyl group morpholine (1.5mmol, 172.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, then By K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 20 hours at 60 DEG C, and TLC is detected after completion of the reaction, Room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, mistake Filter, concentration, colourless oil liquid 2m (48.2mg, 67%), R are obtained through column chromatography for separationf=0.5 (PE:EA=5:1)；1H NMR (400MHz,CDCl3)δ5.15-4.96(m,1H),4.54-4.29(m,2H),3.84-3.78(m,2H),3.77-3.75(m, 2H), 3.73-3.67 (m, 2H), 2.98 (dd, J=13.2,6.6Hz, 1H), 2.03-1.86 (m, 3H), 1.66 (s, 3H), 1.57 (s, 3H), 1.56-1.49 (m, 1H), 1.21 (d, J=6.6Hz, 3H)；13C NMR(100MHz,CDCl3)δ209.9,132.2, 123.8,66.6,66.6,50.2,49.7,40.8,37.4,25.7,25.6,21.2,17.7；IR(film)2963,2926, 2856,1468,1432,1260,1085,1017,795cm-1；HRMS(EI)Calcd for C13H23NOS 241.1500, Found241.1501.
Embodiment 14
Compound 2n synthesis：
Na is added in reaction tube2S·9H2O (0.7mmol, 168mg), cholesterol derivative (aldehyde) (0.2mmol, 91.2mg), N- formyl morpholines (1.0mmol, 115mg), pyridine (1.0mmol, 79mg) are dissolved in water (0.3mL) and second two Alcohol (0.3mL) is added in reaction tube, then by K2S2O8(0.36mmol, 97.3mg) is added in reaction system, is stirred at 100 DEG C 12 hours, TLC was detected after completion of the reaction, drops to room temperature, and water 10mL dilutions are added into system, add ethyl acetate (10mL* 3) extract, anhydrous sodium sulfate drying, filter, concentration, pale yellow oily liquid 2n (60mg, 54%) is obtained through column chromatography for separation, Rf=0.4 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ5.37–5.29(m,1H),4.39-4.29(m,2H),3.84- 3.69 (m, 6H), 3.52 (t, J=5.9Hz, 2H), 3.17-3.08 (m, 1H), 2.94 (dd, J=8.7,6.8Hz, 2H), 2.34- 2.28(m,1H),2.20-2.10(m,1H),2.03-1.91(m,4H),1.88-1.79(m,3H),1.60-1.29(m,12H), 1.16-1.00 (m, 9H), 0.97 (s, 3H), 0.90 (d, J=6.5Hz, 3H), 0.86 (d, J=1.7Hz, 3H), 0.84 (d, J= 1.7Hz,3H),0.66(s,3H)；13C NMR(100MHz,CDCl3)δ203.7,140.7,121.6,79.2,66.6,66.5, 66.5,56.7,56.1,50.2,50.1,49.9,42.3,40.1,39.8,39.5,39.2,37.2,36.8,36.2,35.7, 31.9,31.9,29.8,28.5,28.2,28.0,24.3,23.8,22.8,22.5,21.0,19.3,18.7,11.8；IR(KBr) 3455,2958,1633,1434,1383,1261,1109,1021,804；HRMS(ESI)Calcd for C35H59NO2S[M+H]+ 558.4345,Found558.4339.
Embodiment 15
Compound 3a synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by benzaldehyde (0.3mmol, 31.8mg), N- first Acyl group propylamine (1.5mmol, 130.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, then will K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 10 hours at 100 DEG C, and TLC is detected after completion of the reaction, Room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, mistake Filter, concentration, yellow liquid 3a (34.5mg, 64%), R are obtained through column chromatography for separationf=0.50 (PE:EA=5:1)；1H NMR (400MHz,CDCl3) δ 7.72 (d, J=7.3Hz, 2H), 7.60 (br, 1H), 7.45 (t, J=7.3Hz, 1H), 7.37 (t, J= 7.5Hz, 2H), 3.78 (dd, J=13.6,6.4Hz, 2H), 1.96-1.68 (m, 2H), 1.04 (t, J=7.4Hz, 3H)；13C NMR(100MHz,CDCl3)δ199.2,142.0,130.9,128.4,126.5,48.4,21.4,11.5；IR(film)3259, 2963,2931,2873,1523,1486,1449,1390,1347,1261,1223,1064,1013,946,767,693cm-1；MS (EI) m/z (%) 179 (60), 121 (100), 77 (65)
Embodiment 16
Compound 3b synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), N- formoxyl -2- phenylethylamines (2.5mmol, 372.5mg), by benzaldehyde (0.5mmol, 53mg) be dissolved in water (1mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 10 hours at 100 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, to system Middle addition water 10mL dilutions, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filter, concentration, through column chromatography Isolated yellow solid 3b (98.9mg, 82%), Rf=0.40 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ 7.56-7.54(m,2H),7.47(br,1H),7.37-7.33(m,1H),7.28-7.25(m,4H),7.20-7.18(m,3H), 4.02 (q, J=6.3Hz, 2H), 3.01 (t, J=6.9Hz, 2H)；13C NMR(100MHz,CDCl3)δ199.2,141.9, 138.2,131.0,128.9,128.7,128.5,126.9,126.5,47.4,33.8；IR(film)3032,2963,1531, 1488,1452,1261,1095,1027,802,695cm-1；MS (EI) m/z (%) 241 (25), 121 (40), 104 (100)
Embodiment 17
Compound 3c synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), N- formoxyls benzylamine (1.5mmol, 202.5mg), by benzaldehyde (0.3mmol, 31.8mg), pyridine (1.5mmol, 118.5mg) is dissolved in water (0.6mL) and adds reaction Guan Zhong, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 21 hours at 100 DEG C, and TLC detections are anti- After answering, room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous slufuric acid Sodium is dried, and is filtered, and concentration, yellow solid 3c (38.9mg, 57%), R is obtained through column chromatography for separationf=0.30 (PE:EA=5: 1).1H NMR(400MHz,CDCl3)δ7.80-7.67(m,3H),7.51-7.43(m,1H),7.43-7.34(m,7H),5.00 (d, J=5.1Hz, 2H)；13C NMR(100MHz,CDCl3)δ199.1,141.6,136.2,131.1,129.0,128.5, 128.4,128.2,126.7,51.1；IR(film)2963,2925,1521,1451,1380,1262,1097,1026,802, 696cm-1；MS (EI) m/z (%) 227 (60), 121 (50), 91 (90)
Embodiment 18
Compound 3d synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by benzaldehyde (0.3mmol, 31.8mg), N- first Acyl group nafoxidine (1.5mmol, 148.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, Again by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 8 hours at 100 DEG C, and TLC detection reactions finish Afterwards, room temperature is dropped to, water 10mL dilutions are added into system, ethyl acetate (10mL*3) is added and extracts, anhydrous sodium sulfate drying, Filtering, concentration, orange oily liquids 3d (49.3mg, 86%), R are obtained through column chromatography for separationf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3) δ 7.47-7.28 (m, 5H), 3.96 (t, J=7.1Hz, 2H), 3.45 (t, J=6.8Hz, 2H), 2.14-2.00(m,2H),1.99-1.92(m,2H)；13C NMR(100MHz,CDCl3)δ197.2,143.9,128.6,128.2, 125.5,53.7,53.3,26.4,24.6；IR(film)2963,2875,1495,1449,1327,1263,1078,1034, 800,762,698cm-1；MS (EI) m/z (%) 191 (80), 121 (80), 77 (65)
Embodiment 19
Compound 3e synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by benzaldehyde (0.3mmol, 31.8mg), N- first Acylpiperidine (1.5mmol, 169.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, then will K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 4 hours at 100 DEG C, and TLC is detected after completion of the reaction, drop To room temperature, water 10mL dilutions are added into system, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, Concentration, yellow oily liquid 3e (40.1mg, 65%), R are obtained through column chromatography for separationf=0.60 (PE:EA=5:1)；1H NMR (400MHz,CDCl3) δ 7.33-7.19 (m, 5H), 4.30 (t, J=5.2Hz, 2H), 3.46 (t, J=5.6Hz 2H), 1.77 (dt, J=11.1,5.5Hz, 2H), 1.70 (dt, J=11.3,5.4Hz, 2H), 1.52 (dt, J=11.5,5.7Hz, 2H)；13C NMR(100MHz,CDCl3)δ199.5,143.3,128.3,128.3,125.3,53.1,50.5,26.8,25.4,24.1；IR (film)2939,2857,1494,1478,1444,1294,1261,1244,1136,1013,801,759,698cm-1；MS(EI) M/z (%) 205 (80), 204 (100), 121 (95)
Embodiment 20
Compound 3f synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by benzaldehyde (0.5mmol, 53mg), N- formyls Base morpholine (2.5mmol, 287.5mg) is dissolved in water (1mL) and added in reaction tube, then BPO (1.25mmol, 302.5mg) is added Enter in reaction system, stirred 12 hours at 100 DEG C, TLC is detected after completion of the reaction, drops to room temperature, water is added into system 10mL dilutes, and adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filters, concentration, is obtained through column chromatography for separation Yellow liquid 3f (77.4mg, 75%), Rf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ7.29-7.20(m, 5H),4.53-4.24(m,2H),3.95-3.72(m,2H),3.56-3.54(m,4H)；13C NMR(100MHz,CDCl3)δ 201.0,142.5,128.8,128.5,125.8,66.7,66.5,52.5,49.5；IR(film)2962,2923,2853, 1495,1479,1434,1291,1260,1228,1112,1026,873,803,760,696cm-1；MS (EI) m/z (%) 207 (65),121(100).
Embodiment 21
Compound 3g synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by benzaldehyde (0.3mmol, 31.8mg), N- first Acyl thiocarbamates morpholine (1.5mmol, 196.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and add reaction tube In, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 8 hours at 100 DEG C, and TLC detections have been reacted Bi Hou, room temperature is dropped to, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate is done It is dry, filter, concentration, yellow liquid 3g (44.8mg, 67%), R are obtained through column chromatography for separationf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ7.34-7.22(m,3H),7.20-7.12(m,2H),4.78-4.48(m,2H),3.78-3.75 (m,2H),2.93-2.72(m,2H),2.65-2.37(m,2H)；13C NMR(100MHz,CDCl3)δ201.3,142.8, 128.6,128.5,125.3,54.4,51.8,28.4,27.2；IR(film)3053,2961,2910,1470,1433,1361, 1296,1236,1189,1037,950,800,758,698cm-1；HRMS(EI)Calcd for C11H13NS2223.0489, Found 223.0487.
Embodiment 22
Compound 3h is synthesized：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by benzaldehyde (0.5mmol, 53mg), N, N- bis- NMF (2.5mmol, 182.5mg) be dissolved in water (0.5mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 12 hours at 100 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, to system Middle addition water 10mL dilutions, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filter, concentration, through column chromatography Isolated yellow liquid 3h (71.3mg, 86%), Rf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ 7.37-7.28(m,5H),3.60(s,3H),3.16(s,3H)；13C NMR(100MHz,CDCl3)δ200.0,142.6,127.8, 127.5,125.0,43.5,42.5；IR(film)3055,2932,1514,1485,1442,1390,1292,1139,760, 698cm-1；MS (EI) m/z (%) 165 (65), 164 (85), 121 (100), 77 (70)
Embodiment 23
Compound 3i synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by benzaldehyde (0.3mmol, 31.8mg), N- first Acyl group -2- ethylaminoethanols (1.5mmol, 133.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and add reaction tube In, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 5 hours at 100 DEG C, and TLC detections have been reacted Bi Hou, room temperature is dropped to, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate is done It is dry, filter, concentration, faint yellow solid 3i (40.2mg, 74%), R are obtained through column chromatography for separationf=0.30 (PE:EA=2:1).1H NMR(400MHz,CDCl3)δ8.08(br,1H),7.78-7.75(m,2H),7.48-7.45(m,1H),7.40-7.37(m, 2H),4.02-4.00(m,2H),3.97-3.96(m,2H),2.12(br,1H)；13C NMR(100MHz,CDCl3)δ199.9, 141.7,131.2,128.5,126.7,60.6,48.5；IR(film)3367,3263,2963,1528,1450,1262,1098, 1026,802,696cm-1；MS (EI) m/z (%) 181 (70), 121 (100)
Embodiment 24
Compound 3j synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by benzaldehyde (0.3mmol, 31.8mg), N- first Acyl group allyl amine (1.5mmol, 127.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, Again by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 12 hours at 60 DEG C, and TLC detection reactions finish Afterwards, room temperature is dropped to, water 10mL dilutions are added into system, ethyl acetate (10mL*3) is added and extracts, anhydrous sodium sulfate drying, Filtering, concentration, weak yellow liquid 3j (42.0mg, 79%), R are obtained through column chromatography for separationf=0.50 (PE:EA=5:1).1H NMR(400MHz,CDCl3) δ 7.73 (d, J=7.8Hz, 2H), 7.65 (br, 1H), 7.45 (t, J=7.3Hz, 1H), 7.37 (t, J=7.7Hz, 2H), 6.09-5.92 (m, 1H), 5.31 (dd, J=22.0,13.7Hz, 2H), 4.45 (td, J=5.9,1.1Hz, 2H)；13C NMR(100MHz,CDCl3)δ199.3,141.7,131.8,131.1,128.5,126.6,118.7,49.0；IR (film)3260,3080,3028,2963,2911,1517,1486,1448,1374,1261,1218,1066,1029,933, 800,769,692cm-1；MS (EI) m/z (%) 177 (20), 162 (100), 121 (60), 77 (60)；
Embodiment 25
Compound 3k synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by 2- tolyl aldehydes (0.5mmol, 60mg) ,-DMF (2.5mmol, 182.5mg) is dissolved in water (0.5mL) and added in reaction tube, then by BPO (1.25mmol, 302.5mg) is added in reaction system, is stirred 12 hours at 60 DEG C, and TLC is detected after completion of the reaction, drops to room Temperature, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filter, it is dense Contracting, yellow oily liquid 3k (69.0mg, 77%), R are obtained through column chromatography for separationf=0.50 (PE:EA=5:1)；1H NMR (400MHz,CDCl3) δ 7.33-7.27 (m, 1H), 7.18 (d, J=5.9Hz, 2H), 7.12 (d, J=7.6Hz, 1H), 3.64 (s,3H),3.21(s,3H),2.40(s,3H)；13C NMR(100MHz,CDCl3)δ201.4,143.3138.0,129.2, 128.1,126.2,122.5,44.0,43.0,21.2；IR(film)3033,2929,1513,1453,1390,1296,1139, 1024,787,702cm-1；MS (EI) m/z (%) 179 (70), 178 (85), 135 (100), 91 (65)
Embodiment 26
Compound 3l synthesis：
Na is added in reaction tube2S·9H2O (3.5mmol, 840mg), by 3- tolyl aldehydes (0.5mmol, 60mg), N, N-- dimethylformamide (5mmol, 365mg) are dissolved in water (1mL) and added in reaction tube, then by BPO (2.5mmol, 605mg) Add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, drops to room temperature, water is added into system 10mL dilutes, and adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filters, concentration, is obtained through column chromatography for separation Yellow oily liquid 3l (71.6mg, 80%), Rf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ7.35- 7.25 (m, 1H), 7.18 (d, J=6.0Hz, 2H), 7.12 (d, J=7.5Hz, 1H), 3.64 (s, 3H), 3.21 (s, 3H), 2.40 (s,3H)；13C NMR(100MHz,CDCl3)δ201.2,143.2,138.0,129.1,128.0,126.1,122.4,44.0, 43.0,21.2；IR(film)3031,2961,2931,1583,1453,1389,1296,1260,1138,1022,786, 702cm-1；MS (EI) m/z (%) 179 (80), 178 (90), 135 (100), 91 (55)
Embodiment 27
Compound 3m synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by 4- tolyl aldehydes (0.5mmol, 60mg), N, N-- dimethylformamide (2.5mmol, 182.5mg) be dissolved in water (0.5mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, into system Water 10mL dilutions are added, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, concentration, through column chromatography point From obtaining yellow oily liquid 3m (58.2mg, 65%), Rf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ 7.19 (d, J=8.0Hz, 2H), 7.13 (d, J=8.3Hz, 2H), 3.57 (d, J=0.9Hz, 3H), 3.16 (d, J=0.8Hz, 3H),2.33(s,3H)；13C NMR(100MHz,CDCl3)δ201.4,140.4,138.6,128.8,125.8,44.1,43.2, 21.1；IR(film)3024,2924,2870,1517,1502,1453,1388,1291,1137,996,884,814cm-1；MS (EI) m/z (%) 179 (75), 178 (100), 135 (98), 91 (65)
Embodiment 28
Compound 3n synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by 3- fluorobenzaldehydes (0.5mmol, 62mg), N, Dinethylformamide (2.5mmol, 182.5mg) be dissolved in water (0.5mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 3 hours at 60 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, into system Water 10mL dilutions are added, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, concentration, through column chromatography point From obtaining yellow oily liquid 3n (59.5mg, 65%), Rf=0.60 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ 7.34-7.28(m,1H),7.08-6.99(m,3H),3.57(s,3H),3.15(s,3H)；13C NMR(100MHz,CDCl3)δ 199.2 (s), 162.2 (d, J=247.8Hz), 145.0 (d, J=7.4Hz), 130.1 (d, J=8.5Hz), 121.3 (d, J= 3.0Hz), 115.4 (d, J=21.0Hz), 113.1 (d, J=23.1Hz), 44.0,43.1；19F NMR(377MHz,CDCl3)δ- 112.10；IR(film)3054,2931,1583,1515,1481,1428,1391,1294,1137,826,786,695cm-1；MS (EI) m/z (%) 183 (70), 182 (80), 139 (100), 95 (50)
Embodiment 29
Compound 3o synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by 3- chlorobenzaldehydes (0.5mmol, 70.3mg), DMF (2.5mmol, 182.5mg) be dissolved in water (0.5mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, into system Water 10mL dilutions are added, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, concentration, through column chromatography point From obtaining pale yellow oily liquid 3o (51.9mg, 52%), Rf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ 7.28-7.22(m,3H),7.14-7.12(m,1H),3.54(s,3H),3.13(s,3H)；13C NMR(100MHz,CDCl3)δ 199.1,144.7,134.2,129.6,128.5,125.8,123.7,44.0,43.1；IR(film)3053,2961,2934, 1591,1564,1514,1470,1389,1286,1141,1078,1014,786,751,694cm-1；HRMS(EI)Calcd for C9H10ClNS 199.0222,Found 199.0221.
Embodiment 30
Compound 3p synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by 3- bromobenzaldehydes (0.5mmol, 92.5mg), DMF (2.5mmol, 182.5mg) be dissolved in water (0.5mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, into system Water 10mL dilutions are added, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, concentration, through column chromatography point From obtaining yellow oily liquid 3p (69.2mg, 57%), Rf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ 7.46-7.43(m,2H),7.22-7.21(m,2H),3.57(s,3H),3.16(s,3H)；13C NMR(100MHz,CDCl3)δ 199.0,144.9,131.5,129.9,128.6,124.2,122.3,44.1,43.1；IR(film)3051,2931,1559, 1514,1468,1390,1285,1141,1072,1010,894,785,728,693cm-1；HRMS(EI)Calcd for C9H10BrNS 242.9717,Found 242.9715.
Embodiment 31
Compound 3q synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by 4-methoxybenzaldehyde (0.5mmol, 68mg), DMF (2.5mmol, 182.5mg) is dissolved in water (0.5mL) and added in reaction tube, then by BPO (1.25mmol, 302.5mg) is added in reaction system, is stirred 12 hours at 100 DEG C, and TLC is detected after completion of the reaction, drops to room Temperature, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filter, it is dense Contracting, yellow oily liquid 3q (75.0mg, 77%), R are obtained through column chromatography for separationf=0.40 (PE:EA=5:1)；1H NMR (400MHz,CDCl3) δ 7.29 (d, J=8.7Hz, 2H), 6.85 (d, J=8.7Hz, 2H), 3.81 (s, 3H), 3.58 (s, 3H), 3.21(s,3H)；13C NMR(100MHz,CDCl3)δ201.3,160.0,135.8,127.9,113.5,55.4,44.3,43.5； IR(film)2962,2928,2857,1505,1457,1391,1261,1097,1031,801cm-1；MS (EI) m/z (%) 195 (85),151(100),107(65).
Embodiment 32
Compound 3r synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), 3,4,5-Trimethoxybenzaldehyde (0.5mmol, 98.1mg), DMF (2.5mmol, 182.5mg) is dissolved in into water (0.5mL) to add in reaction tube, then by BPO (1.25mmol, 302.5mg) is added in reaction system, is stirred 12 hours at 60 DEG C, and TLC is detected after completion of the reaction, drops to room Temperature, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filter, it is dense Contracting, yellow solid 3r (117.0mg, 92%), R are obtained through column chromatography for separationf=0.40 (PE:EA=3:1)；1H NMR (400MHz,CDCl3)δ6.51(s,2H),3.84(s,6H),3.83(s,3H),3.58(s,3H),3.19(s,3H)；13C NMR (100MHz,CDCl3)δ201.0,153.1,138.8,138.1,103.1,60.8,56.2,44.2,43.2；IR(film) 2962,2937,2835,1581,1502,1453,1409,1334,1260,1235,1123,1006,915,799,730cm-1；MS (EI) m/z (%) 255 (100), 211 (25)
Embodiment 33
Compound 3s synthesis：
Na is added in reaction tube2S·9H2O (3.5mmol, 840mg), by 3- trifluoromethylated benzaldehydes (0.5mmol, 87mg), DMF (5mmol, 365mg) be dissolved in water (1mL) add reaction tube in, then by BPO (2.5mmol, 605mg) add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, drops to room temperature, is added into system Enter water 10mL dilutions, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filter, concentration, through column chromatography for separation Obtain yellow oily liquid 3s (73.1mg, 63%), Rf=0.40 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ 7.56-7.47(m,4H),3.59(s,3H),3.15(s,3H)；13C NMR(100MHz,CDCl3)δ199.0,143.8,130.70 (q, J=32.6Hz), 129.0,128.9,125.1 (q, J=3.7Hz), 123.5 (q, J=271Hz), 122.6 (q, J= 3.9Hz),44.1,43.1；19F NMR(376MHz,CDCl3)δ-62.75；IR(film)2937,1518,1393,1334, 1263,1125,1072,1015,908,803,700cm-1；MS (EI) m/z (%) 233 (70), 232 (100), 189 (75), 145 (30).
Embodiment 34
Compound 3t synthesis：
Na is added in reaction tube2S·9H2O (3.5mmol, 840mg), by 4- trifluoromethylated benzaldehydes (0.5mmol, 87mg), DMF (5mmol, 365mg) be dissolved in water (1mL) add reaction tube in, then by BPO (2.5mmol, 605mg) add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, drops to room temperature, is added into system Enter water 10mL dilutions, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filter, concentration, through column chromatography for separation Obtain yellow oily liquid 3t (84.2mg, 72%), Rf=0.40 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ7.61 (d, J=8.2Hz, 2H), 7.40 (d, J=8.1Hz, 2H), 3.60 (s, 3H), 3.15 (s, 3H)；13C NMR(100MHz, CDCl3) δ 199.2,146.5,130.4 (q, J=32.8Hz), 126.0,125.5 (q, J=3.7Hz), 123.7 (q, J= 270.5Hz),44.0,43.0；19F NMR(376MHz,CDCl3)δ-62.83；IR(film)2962,2934,1525,1504, 1395,1324,1294,1260,1106,1066,1020,837,796,691cm-1；MS (EI) m/z (%) 233 (70), 232 (100),189(70),145(40).
Embodiment 35
Compound 3u synthesis：
Na is added in reaction tube2S·9H2O (3.5mmol, 840mg), 4- chlorobenzaldehydes (0.5mmol, 70.2mg) will DMF (5mmol, 365mg) is dissolved in water (1mL) and added in reaction tube, then BPO (2.5mmol, 605mg) is added Enter in reaction system, stirred 12 hours at 100 DEG C, TLC is detected after completion of the reaction, drops to room temperature, water is added into system 10mL dilutes, and adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filters, concentration, is obtained through column chromatography for separation Yellow oily liquid 3u (88.5mg, 89%), Rf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ7.31(d,J =8.6Hz, 2H), 7.24 (d, J=8.6Hz, 2H), 3.57 (s, 3H), 3.15 (s, 3H)；13C NMR(100MHz,CDCl3)δ 199.3,141.4,134.1,128.2,127.0,43.9,43.0；IR(film)2962,2931,1591,1513,1486, 1392,1288,1261,1140,1090,996,823,729cm-1；MS (EI) m/z (%) 199 (70), 198 (100), 155 (85).
Embodiment 36
Compound 3v synthesis：
Na is added in reaction tube2S·9H2O (3.5mmol, 840mg), 4- bromobenzaldehydes (0.5mmol, 92.6mg) will DMF (5mmol, 365mg) is dissolved in water (1mL) and added in reaction tube, then BPO (2.5mmol, 605mg) is added Enter in reaction system, stirred 12 hours at 100 DEG C, TLC is detected after completion of the reaction, drops to room temperature, water is added into system 10mL dilutes, and adds ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filters, concentration, is obtained through column chromatography for separation Yellow solid 3v (116.0mg, 95%), Rf=0.50 (PE:EA=5:1)；1H NMR(400MHz,CDCl3) δ 7.45 (d, J= 8.3Hz, 2H), 7.15 (d, J=8.3Hz, 2H), 3.54 (s, 3H), 3.13 (s, 3H)；13C NMR(100MHz,CDCl3)δ 199.5,141.9,131.3,127.3,122.5,44.0,43.1；IR(film)3024,2961,2932,1584,1514, 1482,1391,1287,1140,1070,993,820,711cm-1；MS (EI) m/z (%) 245 (60), 244 (100), 243 (60),242(100),201(55),199(55),120(80).
Embodiment 37
Compound 3w synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), 2- naphthaldehydes (0.5mmol, 78mg), by N, N- Dimethylformamide (2.5mmol, 182.5mg) be dissolved in water (0.5mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, into system Water 10mL dilutions are added, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, concentration, through column chromatography point From obtaining yellow oily liquid 3w (98.6mg, 92%), Rf=0.40 (PE:EA=5:1)；1H NMR(400MHz,CDCl3)δ 7.84-7.82 (m, 3H), 7.77 (d, J=1.2Hz, 1H), 7.54-7.47 (m, 2H), 7.43 (dd, J=8.5,1.7Hz, 1H), 3.65(s,3H),3.21(s,3H)；13C NMR(100MHz,CDCl3)δ201.2,140.5,133.0,132.7,128.3, 128.1,127.7,126.7,126.7,124.7,123.9,44.2,43.2；IR(film)2962,1515,1392,1259, 1087,1013,793,689cm-1；MS (EI) m/z (%) 215 (100), 171 (85), 127 (65)
Embodiment 38
Compound 3x synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by 2 thiophene carboxaldehyde (0.5mmol, 56mg), N, Dinethylformamide (2.5mmol, 182.5mg) be dissolved in water (0.5mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, into system Water 10mL dilutions are added, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, concentration, through column chromatography point From obtaining yellow oily liquid 3x (81.0mg, 95%), Rf=0.60 (PE:EA=10:1)；1H NMR(400MHz,CDCl3)δ 7.37 (d, J=5.1Hz, 1H), 7.09 (d, J=3.6Hz, 1H), 6.95 (t, J=4.4Hz, 1H), 3.55 (s, 3H), 3.41 (s,3H)；13C NMR(100MHz,CDCl3)δ191.4,145.1,129.2,126.4,126.3,44.5；IR(film)3071, 2962,2928,2869,1503,1453,1386,1354,1262,1124,1048,794,707cm-1；MS (EI) m/z (%) 171 (65),127(100).
Embodiment 39
Compound 3y synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by 2- pyridine carboxaldehydes (0.5mmol, 53.5mg), DMF (2.5mmol, 182.5mg) be dissolved in water (0.5mL) add reaction tube in, then by BPO (1.25mmol, 302.5mg) add in reaction system, stirred 12 hours at 60 DEG C, TLC is detected after completion of the reaction, room temperature is dropped to, into system Water 10mL dilutions are added, ethyl acetate (10mL*3) extraction is added, anhydrous sodium sulfate drying, filters, concentration, through column chromatography point From obtaining pale yellow oily liquid 3y (43.9mg, 53%), Rf=0.40 (PE:EA=1:1)；1H NMR(400MHz,CDCl3)δ 8.49 (d, J=4.8Hz, 1H), 7.72 (t, J=7.7Hz, 1H), 7.56 (d, J=7.9Hz, 1H), 7.26-7.19 (m, 1H), 3.59(s,3H),3.17(s,3H)；13C NMR(100MHz,CDCl3)δ198.0,159.4,148.0,136.9,123.2, 123.1,43.7,43.2；IR(film)3048,2961,2929,1585,1524,1464,1427,1393,1300,1145, 1014,785,745,702cm-1；MS (EI) m/z (%) 166 (45), 123 (100), 79 (75)；
Embodiment 40
Compound 3z synthesis：
Na is added in reaction tube2S·9H2O (1.75mmol, 420mg), by benzofuran -2- formaldehyde (0.5mmol, 73.1mg), DMF (2.5mmol, 182.5mg) is dissolved in water (0.5mL) and added in reaction tube, then by BPO (1.25mmol, 302.5mg) is added in reaction system, is stirred 12 hours at 60 DEG C, and TLC is detected after completion of the reaction, drops to room Temperature, water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extraction, anhydrous sodium sulfate drying, filter, it is dense Contracting, yellow oily liquid 3z (71.7mg, 70%), R are obtained through column chromatography for separationf=0.40 (PE:EA=10:1)；1H NMR (400MHz,CDCl3) δ 7.58 (d, J=7.8Hz, 1H), 7.44 (d, J=8.3Hz, 1H), 7.33 (t, J=7.7Hz, 1H), 7.29 (s, 1H), 7.23 (t, J=7.5Hz, 1H), 3.55 (s, 3H), 3.42 (s, 3H)；13C NMR(100MHz,CDCl3)δ 186.7,154.2,153.3,127.4,126.3,123.5,122.0,112.1,111.6,44.3,44.1；IR(film)2962, 2931,1567,1507,1447,1390,1295,1258,1127,1005,934,818,751cm-1；HRMS(EI)Calcd for C11H11NOS 205.0561,Found 205.0560.
Embodiment 41
Compound 3aa synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), 4- hydroxy benzaldehydes (0.3mmol, 36.6mg), By DMF (1.5mmol, 109.5mg), pyridine (1.5mmol, 118.5mg) is dissolved in water (0.6mL) and added instead Ying Guanzhong, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 7 hours at 100 DEG C, and TLC detections are anti- After answering, room temperature is dropped to, water 10mL dilutions are added into system, adds ethyl acetate (10mL*3) extraction, anhydrous slufuric acid Sodium is dried, and is filtered, and concentration, faint yellow solid 3aa (33.1mg, 61%), R is obtained through column chromatography for separationf=0.40 (PE:EA= 1:1)；1H NMR(400MHz,CDCl3) δ 7.19 (d, J=8.5Hz, 2H), 6.72 (d, J=8.5Hz, 2H), 5.62 (br, 1H), 3.59(s,3H),3.20(s,3H)；13C NMR(100MHz,CDCl3)δ201.4,156.4,135.6,127.9,115.2, 44.4,43.6；IR(film)3123,2925,2856,1607,1506,1457,1390,1270,1231,1138,883cm-1；MS (EI) m/z (%) 181 (85), 180 (80), 137 (100)
Embodiment 42
Compound 3ab synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), by salicylide (0.3mmol, 36.6mg), N, N- Dimethylformamide (1.5mmol, 109.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.6mL) and added in reaction tube, Again by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, is stirred 6 hours at 100 DEG C, and TLC detection reactions finish Afterwards, room temperature is dropped to, water 10mL dilutions are added into system, ethyl acetate (10mL*3) is added and extracts, anhydrous sodium sulfate drying, Filtering, concentration, pale yellow oily liquid 3ab (46.2mg, 85%), R are obtained through column chromatography for separationf=0.35 (PE:EA=2: 1)；1H NMR(400MHz,CDCl3) δ 7.95 (s, 1H), 7.12 (t, J=7.1Hz, 1H), 6.99 (d, J=7.3Hz, 1H), 6.90-6.74(m,2H),3.48(s,3H),3.13(s,4H)；13C NMR(100MHz,CDCl3)δ196.1,152.5,152.5, 130.4,127.5,127.5,126.3,119.4,117.4,44.1,42.7；IR(KBr)3412,2963,1602,1528, 1448,1396,1294,1142,1106,821,756；HRMS(ESI)Calcd for C9H11NOS[M+H]+182.0640, Found182.0648.
Embodiment 43
Compound 3ac synthesis：
Na is added in reaction tube2S·9H2O (1.05mmol, 252mg), 2- formoxyls estrone (0.3mmol, 89.5mg), N- formyl morpholines (1.5mmol, 172.5mg), pyridine (1.5mmol, 118.5mg) are dissolved in water (0.3mL) Added with ethylene glycol (0.3mL) in reaction tube, then by K2S2O8(0.54mmol, 146.0mg) is added in reaction system, at 100 DEG C Lower stirring 10 hours, TLC is detected after completion of the reaction, drops to room temperature, and water 10mL dilutions are added into system, add ethyl acetate (10mL*3) extract, anhydrous sodium sulfate drying, filter, concentration, through column chromatography for separation obtain yellow solid 3ac (84.5mg, 71%), Rf=0.4 (PE:EA=3:1)；1H NMR(400MHz,CDCl3)δ7.78(br,1H),6.88(s,1H),6.69(s, 1H), 4.17-3.90 (m, 2H), 3.85-3.65 (m, 4H), 2.83 (d, J=4.6Hz, 2H), 2.49 (dd, J=18.9, 8.6Hz,1H),2.36-1.85(m,7H),1.67-1.29(m,7H),0.89(s,3H)；13C NMR(100MHz,CDCl3)δ 220.8,197.0,151.5,140.2,131.4,124.5,123.1,117.9,66.6,50.3,47.8,43.6,38.1, 35.7,31.4,29.2,26.2,25.8,21.5,13.8；IR(KBr)3434,2962,2927,2857,1735,1616,1436, 1261,1130,1029,803；HRMS(ESI)Calcd for C23H29NO3S[M+H]+400.1946,Found 400.1931。

Claims (11)

  1. A kind of 1. synthetic method of thioamide analog compound, it is characterised in that using aldehyde and formoxyl fatty amine as reaction raw materials, With Na2S·9H2O is sulfiding reagent, in the presence of oxidant and additive, under the conditions of 25~100 DEG C, in reaction dissolvent Reaction obtains the thioamide analog compound as shown in formula (II) in 3~24 hours；The course of reaction is as shown in reaction equation；
    Wherein, R is alkyl, aryl；R1/R2It is alkyl, containing aryl alkyl or hydrogen；
    Wherein, the oxidant is dibenzoyl peroxide, potassium peroxydisulfate；The additive is pyridine.
  2. A kind of 2. synthetic method of thioamide analog compound, it is characterised in that using aldehyde and formoxyl fatty amine as reaction raw materials, With Na2S·9H2O is sulfiding reagent, in the presence of oxidant and additive, under the conditions of 25~100 DEG C, in reaction dissolvent Reaction obtains the thioamide analog compound as shown in formula (II) in 3~24 hours；The course of reaction is as shown in reaction equation；
    In the reaction equation (a), R is isobutyl group, 2- phenylethyls, benzyl, cyclohexyl, 2,6- dimethyl -5- alkenyls heptyl, 1- Methyl -2- (4- tert-butyl-phenyls) ethyl, 1,5 dimethyl -4- alkenyls hexyls, phenyl, 2- aminomethyl phenyls, 3- aminomethyl phenyls, 4- Aminomethyl phenyl, 3- fluorophenyls, 3- chlorphenyls, 3- bromophenyls, 4- methoxyphenyls, 3,4,5- trimethoxyphenyls, 3- fluoroforms Base phenyl, 4- trifluoromethyls, 4- chlorphenyls, 4- bromophenyls, 4- hydroxy phenyls, 2- hydroxy phenyls, 2- naphthyls, 2- thiophene, 2- pyridines, 2- benzofurans,R1/ R2It is methyl/methyl, 2- phenylethyls/hydrogen, 2- hydroxyethyls/hydrogen, propyl group/hydrogen, benzyl/hydrogen, pi-allyl/hydrogen,
    Wherein, the oxidant is dibenzoyl peroxide, potassium peroxydisulfate；The additive is pyridine.
  3. 3. the synthetic method of thioamide analog compound as claimed in claim 1 or 2, it is characterised in that the reaction dissolvent Be dimethyl sulfoxide, 1-METHYLPYRROLIDONE, nitromethane, ethylene glycol, acetonitrile, 1,4- dioxane, paraxylene, water or its The mixed solution of meaning combination.
  4. 4. the synthetic method of thioamide analog compound as claimed in claim 1 or 2, it is characterised in that the aldehyde with it is described Sulfiding reagent Na2S·9H2O dosage mol ratio is 1:1~7.
  5. 5. the synthetic method of thioamide analog compound as claimed in claim 1 or 2, it is characterised in that the aldehyde with it is described The dosage mol ratio of formoxyl fatty amine is 1:1~10.
  6. 6. the synthetic method of thioamide analog compound as claimed in claim 1 or 2, it is characterised in that the aldehyde with it is described The dosage mol ratio of oxidant is 1:1~5.
  7. 7. the synthetic method of thioamide analog compound as claimed in claim 1 or 2, it is characterised in that the additive Mole is up to 5 times of the aldehyde.
  8. 8. the synthetic method of thioamide analog compound as claimed in claim 7, it is characterised in that when substrate aldehyde and formoxyl When fatty amine is liquid, it the described method comprises the following steps：Sulfiding reagent is first added in reaction vessel, then will be dissolved in molten Substrate aldehyde, formoxyl fatty amine and the additive of agent are added in reaction vessel, are eventually adding oxidant and are reacted.
  9. 9. the synthetic method of thioamide analog compound as claimed in claim 7, it is characterised in that when aldehyde is liquid, formyl When base fatty amine is solid, it the described method comprises the following steps：The formyl of sulfiding reagent and solid is first added in reaction vessel Base fatty amine, then the substrate aldehyde for being dissolved in solvent and additive are added in reaction vessel, oxidant is eventually adding and is reacted.
  10. 10. the synthetic method of thioamide analog compound as claimed in claim 7, it is characterised in that when aldehyde is solid, formyl When base fatty amine is liquid, it the described method comprises the following steps：Sulfiding reagent, the aldehyde of solid are first added in reaction vessel, so The formoxyl fatty amine for being dissolved in solvent and additive are added in reaction vessel afterwards, oxidant is eventually adding and is reacted.
  11. 11. the synthetic method of thioamide analog compound as claimed in claim 7, it is characterised in that when aldehyde and formoxyl fat When fat amine is solid, it the described method comprises the following steps：Sulfiding reagent, aldehyde and formoxyl fat are first added in reaction vessel Amine, then the additive for being dissolved in solvent is added in reaction vessel, oxidant is eventually adding and is reacted.
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