CN111303079A - Method for aqueous phase synthesis of thioamide by promoting elemental sulfur with mixed alkali - Google Patents
Method for aqueous phase synthesis of thioamide by promoting elemental sulfur with mixed alkali Download PDFInfo
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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
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- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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
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- 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
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- 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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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
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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
Abstract
The invention provides a method for promoting elemental sulfur to synthesize thioamide compounds by using aqueous phase mixed alkali, belonging to the field of organic synthesis; the method takes aldehyde compounds and amide compounds as substrates and S8Adding a certain equivalent of alkali into water as a sulfur source and water as a solvent to react at the temperature of between 60 and 120 ℃ under the atmosphere of nitrogenThe time is 4-24 h; the method does not need to add transition metal as a catalyst, has simple synthesis steps, simple and easy operation, high product yield up to 99 percent and wide substrate range, and provides a new idea for the synthesis of thioamide compounds; the reaction is carried out in a water phase, the use of an organic solvent is avoided, the reaction efficiency is high, few byproducts are generated, the environment is friendly, the reaction can be amplified to 10 g level, and the method has a strong industrial application prospect.
Description
Technical Field
The invention relates to the technical field of synthesis of thioamide compounds, in particular to a method for synthesizing thioamide by promoting elemental sulfur with mixed alkali in a water phase.
Background
Thioamides are important compounds with biological activity and medicinal value, are widely present in medicine and natural product molecules, and can be used for preparing various biologically-related heterocyclic stent materials and protein chemical polypeptides. It is also one of the most important precursors for the construction of various sulfur-containing heterocycles (e.g., thiazoles, thiazolines, thiazolones, etc.).
There are many methods for synthesizing thioamides, and conventional methods for synthesizing thioamides include reactions between amides and phosphorus pentasulfide or Lawesson reagents; Willgeodt-Kindler reaction; Friedel-Crafts thioacylation of aromatic hydrocarbons with isothiocyanates. Most of the synthesis processes use high-boiling-point organic solvents, so that the pollution is large, the waste is more, and the conversion rate is low.
Other methods for preparing thioamides have been developed in recent years, and in 2016, Jiangxue project group reported a method for synthesizing thioamides by combining three components of aldehyde, N-substituted formamide and sodium sulfide in aqueous phase [ Jiangx]The method has the advantages of green and environment-friendly solvent, simple reaction operation, relatively mild conditions and high yield, but a large amount of oxidant and additive are used in the reaction, so that more waste is generated in the reaction process, the atom economy is poor, and inconvenience is brought to the post-treatment. In 2018, Wu project group reported a method for selectively synthesizing two thioamides from olefin, amine and sulfur three components by selecting alkali [ Wu H.J.org.chem.2018,83, 14269-14276-]Using KF and K3PO42-phenylethane thioamides and benzothioamides are obtained selectively. This scheme provides a simple and efficient method for the synthesis of thioamides, but in this method an amine substrate is reacted with S8The proportion of the organic solvent is required to be kept at 1:4, the atom economy is poor, the organic solvent with high boiling point is used in the reaction, the environmental hazard is great, and the reaction cost is increased by dangerous waste treatment. In 2018, Wang topic group reports that aromatic alkyne, amide and S are cracked by carbon-carbon triple bonds through alkali8Method for synthesizing thioamide by three components [ Wang M.org.Lett.2018,20, 2228-one 2231]The reaction ofTaking DMF as a solvent, an aromatic alkyne substrate and S8The ratio of (A) to (B) is 1:24, the atom economy is poor and the reaction time is long.
Disclosure of Invention
The invention provides a method for promoting aldehydes, amides and S by alkali in aqueous phase8The method for synthesizing thioamide by three components is a reaction in a water phase, and the thioamide product can be obtained without adding an organic solvent, an oxidant and a catalyst, so that the subsequent treatment is simple, and the green and environment-friendly effects are realized to a great extent.
The invention adopts the following technical scheme:
alkali-promoted aldehydes, amides and S in water phase8A process for synthesizing thioamide from aldehyde compound and S8And dispersing the amide compounds in an alkaline aqueous solution, and stirring and reacting for 4-24h at 60-120 ℃ in the presence of nitrogen to obtain the thioamide compounds.
Preferably, the aldehyde group compound has the following structural general formula:
At-CHO
wherein, the functional group represented by Ar is: any of benzene ring, naphthalene ring, and heterocycle (heterocycle such as thiophene, pyridine, pyrrole, imidazole, etc.) having various substituents (such as methyl group, methoxy group, hydroxyl group, isopropyl group, halogen group, aldehyde group, nitrile group, etc.).
Preferably, the amide compound has the following structural formula:
wherein R is1Represents an aromatic ring, a heterocyclic ring, an aliphatic hydrocarbon group or a cycloalkyl group, etc., R2Represents an aromatic ring, a heterocyclic ring, an aliphatic hydrocarbon group or a cycloalkyl group, etc., R3Represents methyl or ethyl.
Preferably, the alkaline aqueous solution is prepared by adding a base into water, wherein the base is an equal proportion mixed base of an inorganic base (any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide and potassium phosphate) and triethylamine, and the total molar weight of the mixed base is 1-10 times of the molar weight of the aldehyde compound or amide compound substrate.
Preferably, said S8The dosage of the aldehyde group compound or the amide compound is 1:1.
Preferably, the dosage of the amide compound is 3-10 times of the molar weight of the aldehyde compound.
Preferably, the reaction temperature is 60-120 ℃, and the reaction stirring time is 4-24 h.
Compared with the prior art, the synthesis method of the invention has the following advantages:
in the invention, the reaction is carried out in a water phase, so that the method is safe and pollution-free, simple and safe in post-treatment, free of organic waste liquid, free of organic solvent, catalyst and oxidant, more green and environment-friendly, and S is prepared8Is a source of sulfur and is in S8The molar weight ratio of the aldehyde group substrate to the aldehyde group substrate is 1:1, the reaction yield can still reach 99%, the method conforms to the concept of atom economy, the synthesis process is simple and convenient, the product selectivity is high, the byproducts are few, the wastes are few, and the method has a strong industrial application prospect.
Drawings
FIG. 1 is a drawing of (4-methoxyphenyl) (morpholino) thione prepared in example 11H NMR spectrum;
FIG. 2 is a drawing of (4-methoxyphenyl) (morpholino) thione prepared in example 113C NMR spectrum.
FIG. 3 is a photograph of (4-chlorophenyl) (morpholino) thione prepared in example 21H NMR spectrum;
FIG. 4 is a photograph of (4-chlorophenyl) (morpholino) thione prepared in example 213C NMR spectrum.
FIG. 5 is a drawing of morpholino (naphthalen-2-yl) thiones prepared in example 31H NMR spectrum;
FIG. 6 is a drawing of morpholino (naphthalen-2-yl) thiones prepared in example 313C NMR spectrum.
FIG. 7 is a drawing of morpholino (thiophen-2-yl) thiones prepared in example 41H NMR spectrum;
FIG. 8 is a drawing of morpholino (thiophen-2-yl) thiones prepared in example 413C NMR spectrum.
FIG. 9 is a drawing of morpholino (pyridin-2-yl) thione prepared in example 51H NMR spectrum;
FIG. 10 is a photograph of morpholino (pyridin-2-yl) thione prepared in example 513C NMR spectrum.
FIG. 11 is a photograph of 4-methyl-N- (p-tolyl) thiobenzoyl prepared in example 61H NMR spectrum;
FIG. 12 is a photograph of 4-methyl-N- (p-tolyl) thiobenzoyl prepared in example 613C NMR spectrum.
FIG. 13 is a photograph of 4-methyl-N- (phenyl) thiobenzoyl prepared in example 71H NMR spectrum;
FIG. 14 is a photograph of 4-methyl-N- (phenyl) thiobenzoyl prepared in example 713C NMR spectrum.
FIG. 15 is a photograph of 4-methyl-N- (p-fluorophenyl) thiobenzoyl prepared in example 81H NMR spectrum;
FIG. 16 is a photograph of 4-methyl-N- (p-fluorophenyl) thiobenzoyl prepared in example 813C NMR spectrum.
FIG. 17 is a photograph of 4-methyl-N- (p-bromophenyl) thiobenzoyl prepared in example 91H NMR spectrum;
FIG. 18 is a photograph of 4-methyl-N- (p-bromophenyl) thiobenzoyl prepared in example 913C NMR spectrum.
FIG. 19 is a photograph of N, N, 4-trimethylbenzothioamides prepared in example 101H NMR spectrum;
FIG. 20 is a photograph of N, N, 4-trimethylbenzothioamides prepared in example 1013C NMR spectrum.
Detailed Description
In order to make the technical purpose, technical solutions and advantages of the present invention clearer, the technical solutions of the present invention are further described below with reference to the accompanying drawings and specific embodiments.
Example 1
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added 0.2mmol (28mg) of substrate 4-methoxybenzaldehyde, S80.2mmol (51mg), 1mmol (115mg) of N-formylmorpholine, 32mg (1.5eq.), 31mg (1.5eq.), and 1mL of water, and adding magneton, displacing nitrogen, heating to 120 deg.C, and stirring for reaction for 12 h. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 99% yield. Target product characterization data: yellow solid is at 96-100 deg.c.1H NMR(400MHz,CDCl3)δ＝7.21(d,J＝8.7Hz,2H),6.80(d,J＝8.7Hz,2H),4.35(s,2H),3.80(s,2H),3.74(s,3H),3.59(s,4H).13C NMR(100MHz,CDCl3)δ＝200.13,159.26,133.82,127.08,112.70,65.74,65.53,54.42,51.78,48.98.LRMS(EI)m/z calcd forC12H15NO2S[M]+,237；found,237.
Example 2
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 4-chlorobenzaldehyde 0.2mmol (29mg), S80.2mmol (51mg), 1.4mmol (161mg) of N-formylmorpholine, 56mg (2eq.), 41mg (2eq.), and 1mL of triethylamine were added to the mixture, and then the mixture was heated to 100 ℃ under stirring for 6 hours with replacement of nitrogen. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 98% yield.Target product characterization data: yellow solid is between 133 and 140 ℃.1H NMR(400MHz,CDCl3)δ＝7.27(d,J＝8.4Hz,2H),7.16(d,J＝8.5Hz,2H),4.38-4.31(m,2H),3.84-3.78(m,2H),3.55(m,4H).13C NMR(100MHz,CDCl3)δ＝199.51,140.74,134.94,128.81,127.44,66.69,66.51,52.61,49.62.LRMS(EI)m/z calcd for C11H12ClNOS[M]+,241；found,241.
Example 3
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 2-naphthaldehyde 0.2mmol (32mg), S80.2mmol (51mg), 0.8mmol (104mg) of 4-acetylmorpholine, 228mg (3.5eq.) of cesium carbonate, 71mg (3.5eq.) of triethylamine and 1mL of water were added with magneton, replaced with nitrogen, heated to 80 ℃ and stirred for 17 hours. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 93% yield. Target product characterization data: yellow solid is 110-115 ℃.1H NMR(400MHz,CDCl3)δ＝7.7-7.72(m,3H),7.68(d,J＝1.1Hz,1H),7.46-7.39(m,2H),7.34-7.29(m,1H),4.43-4.37(m,2H),3.86-3.80(m,2H),3.55(s,4H).13C NMR(100MHz,CDCl3)δ＝200.91,139.67,133.17,132.76,128.47,128.41,127.80,127.01,126.94,125.04,123.87,66.81,66.59,52.69,49.65.LRMS(EI)m/z calcd for C15H15NOS[M]+,257；found,257.
Example 4
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 2-thiophenecarboxaldehyde 0.2mmol (23mg), S80.2mmol (51mg), 0.6mmol (75mg) of 4-acetylmorpholine, 20mg (2.5eq.), 51mg (2.5eq.), and 1mL of water were added with magnetons, replaced with nitrogen, heated to 120 ℃ and stirred for 4 hours. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 95% yield. Target product characterization data: yellow solid.74-78 ℃.1H NMR(400MHz,CDCl3)δ＝7.38-7.32(m,1H),7.03-6.98(m,1H),6.94-6.89(m,1H),4.09(s,4H),3.73(s,4H).13C NMR(100MHz,CDCl3)δ＝191.83,144.33,129.43,126.66,126.23,66.69.LRMS(EI)m/z calcd for C9H11NOS2[M]+,213；found,213.
Example 5
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 2-pyridinecarboxaldehyde 0.2mmol (22mg), S80.2mmol (51mg), 1.2mmol (155mg) of 4-acetylmorpholine, 45mg (4eq.), 81mg (4eq.), and 1mL of water, and magnetons were added and replaced with nitrogen, and the mixture was heated to 90 ℃ and stirred for reaction for 8 hours. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 97% yield. Target product characterization data: yellow solid.105-109 ℃.1H NMR(400MHz,CDCl3)δ＝8.44(d,J＝4.6Hz,1H),7.67(t,J＝7.7Hz,1H),7.53(d,J＝7.8Hz,1H),7.23-7.16(m,1H),4.40-4.33(m,2H),3.87-3.80(m,2H),3.67-3.62(m,2H),3.56-3.50(m,2H).13C NMR(100MHz,CDCl3)δ＝197.52,158.71,148.18,137.08,123.77,123.49,66.74,66.40,52.40,49.55.HRMS(ESI):m/z calcd for C10H13N2OS[M+H]+,209.0743；found,209.0740.
Example 6
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 4-methylbenzaldehyde 0.2mmol (24mg), S80.2mmol (51mg), 1.8mmol (244mg) of 4-formanilide, 43mg (1eq.), 43mg of potassium phosphate, 21mg (1eq.), and 1mL of water were added with magneton, replaced with nitrogen, heated to 70 ℃ and stirred for reaction for 22 hours. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 97% yield. Target product characterization data: yellow solid.169-171 deg.C.1H NMR(400MHz,CDCl3)δ＝8.91(br,1H),7.68(d,J＝7.9Hz,2H),7.51(d,J＝8.0Hz,2H),7.20-7.10(m,4H),2.30(d,J＝9.8Hz,6H).13C NMR(100MHz,CDCl3)δ＝198.20,141.90,140.22,136.95,136.60,129.62,129.26,126.78,124.01,21.44.LRMS(EI)m/z calcd forC15H15NS[M]+,241；found,241.
Example 7
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 4-methylbenzaldehyde0.2mmol(24mg),S80.2mmol (51mg), 2mmol (243mg) of formanilide, 5mg (0.5eq.), 11mg (0.5eq.), and 1mL of water, magnetons are added, nitrogen is replaced, the temperature is raised to 120 ℃, and the reaction is stirred for 24 hours. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 96% yield. Target product characterization data: yellow solid is at 144-146 deg.c.1H NMR(400MHz,CDCl3)δ＝8.94(br,1H),7.67(s,4H),7.34(s,2H),7.25-7.08(m,3H),2.31(s,3H).13C NMR(100MHz,CDCl3)δ＝198.31,141.97,140.35,139.14,129.27,129.05,126.91,126.78,123.84,21.43.LRMS(EI)m/z calcd for C14H13NS[M]+,227；found,227.
Example 8
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 4-methylbenzaldehyde 0.2mmol (24mg), S80.2mmol (51mg), 1.6mmol (223mg) of N- (4-fluorophenyl) formamide, 35mg (3eq.), 61mg (3eq.), and 1mL of water were added with magneton and replaced with nitrogen, heated to 110 ℃ and stirred for reaction for 16 hours. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 94% yield. Target product characterization data: yellowsolid is between 166 and 168 ℃.1H NMR(400MHz,DMSO)δ＝11.67(br,1H),7.84-7.76(m,4H),7.32-7.23(m,4H),2.37(s,3H).13C NMR(100MHz,DMSO)δ＝197.98,160.21(d,J＝242Hz),141.47,139.97,136.91(d,J＝3Hz),129.01,128.03,127.06(d,J＝9Hz),115.66(d,J＝22Hz),21.38.LRMS(EI)m/z calcd for C14H12FNS[M]+,245；found,245.
Example 9
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 4-methylbenzaldehyde 0.2mmol (24mg), S80.2mmol (51mg), 1mmol (200mg) of N-4- (bromophenyl) formamide, 152mg (5eq.), 101mg (5eq.), and 1mL of water, and then, magnetons and nitrogen were added to the mixture, and the mixture was heated to 100 ℃ and stirred for reaction for 15 hours. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 93% yield. Target product characterization data: yellowsolid is between 192 and 195 ℃.1H NMR(400MHz,DMSO)δ＝11.72(br,1H),7.83(d,J＝8.7Hz,2H),7.78(d,J＝8.1Hz,2H),7.63(d,J＝8.7Hz,2H),7.28(d,J＝8.0Hz,2H),2.37(s,3H).13C NMR(100MHz,DMSO)δ＝198.06,141.57,140.14,139.88,131.82,129.02,128.06,126.71,118.72,21.42.LRMS(EI)m/z calcd for C14H12BrNS[M]+,305；found,305.
Example 10
A process for the preparation of thioamide compounds of the formula:
to a 25mL Schlenk tube was added the substrate 4-methylbenzaldehyde 0.2mmol (24mg), S80.2mmol (51mg), DMF 1mmol (73mg), sodium tert-butoxide 87mg (4.5eq.), triethylamine 91mg (4.5eq.), and water 1mL, magneton was added to replace nitrogenHeating to 100 deg.C, stirring and reacting for 5 h. After completion of the reaction, the reaction tube was cooled to room temperature, 50mL of saturated brine was added, extraction was performed three times with dichloromethane (3 × 50mL), and the mixture was dried for 30min with anhydrous sodium sulfate, and then the low-boiling point solvent was removed by a rotary evaporator. The reaction mixture was then separated and purified by column chromatography (30 × 300mm) (eluent: n-hexane: dichloromethane ═ 1: 2) to give the desired product in 99% yield. Target product characterization data: yellow liquid.1H NMR(400MHz,CDCl3)δ＝7.06-7.25(m,4H),3.59(s,3H),3.18(s,3H),2.35(s,3H).13C NMR(100MHz,CDCl3)δ＝201.56,140.58,138.71,128.91,125.91,44.25,43.37,21.29.LRMS(EI)m/z calcd for C10H13NS[M]+,179；found,179.
Thioamide-based compounds were synthesized in a similar manner to example 1, and their respective reaction conditions and reaction results are shown in Table 1.
TABLE 1 Synthesis of various thioamide Compounds under different conditions
From the above examples, it can be seen that the yield of the preparation method of the present invention is over 90%, the preparation method does not require an organic solvent, and the reaction efficiency is high.
Finally, it should be noted that: the above embodiments are merely illustrative and not restrictive of the technical solutions of the present invention, and any equivalent substitutions and modifications or partial substitutions made without departing from the spirit and scope of the present invention should be included in the scope of the claims of the present invention.
Claims (8)
1. A method for promoting the synthesis of thioamide compounds by using mixed alkali in a water phase is characterized by comprising the following steps: in a nitrogen atmosphere, with S8Aldehyde compounds and amide compounds are used as sulfur sourcesDispersing the product in alkaline water solution, and reacting for 4-24h at 60-120 deg.C under stirring to obtain thioamide compounds.
2. The aqueous phase mixed base accelerated thioamide synthesis method according to claim 1, characterized in that: the aldehyde group compound has the following structural general formula:
Ar-CHO
wherein, the functional group represented by Ar is: any of benzene ring, naphthalene ring, and heterocycle (heterocycle such as thiophene, pyridine, pyrrole, imidazole, etc.) having various substituents (such as methyl group, methoxy group, hydroxyl group, isopropyl group, halogen group, aldehyde group, nitrile group, etc.).
3. The aqueous phase mixed base accelerated thioamide synthesis method according to claim 1, characterized in that: the structural general formula of the amide compound is shown as follows:
wherein R is1Represents an aromatic ring, a heterocyclic ring, an aliphatic hydrocarbon group or a cycloalkyl group, etc., R2Represents an aromatic ring, a heterocyclic ring, an aliphatic hydrocarbon group or a cycloalkyl group, etc., R3Represents methyl or ethyl.
4. The aqueous phase mixed base accelerated thioamide synthesis method according to claim 1, characterized in that: the thioamide compound has the following structural general formula:
wherein, the functional group represented by Ar is: any of benzene ring, naphthalene ring, and heterocycle (heterocycle such as thiophene, pyridine, pyrrole, imidazole, etc.) having various substituents (such as methyl group, methoxy group, hydroxyl group, isopropyl group, halogen group, aldehyde group, nitrile group, etc.). R1Represents an aromatic ring, a heterocyclic ring, an aliphatic hydrocarbon group, a cycloalkyl group or the like. R2Represents an aromatic ring, a heterocyclic ring, an aliphatic hydrocarbon group, a cycloalkyl group or the like.
5. The aqueous phase mixed base accelerated thioamide synthesis method according to claim 1, characterized in that: the aldehyde group compound and S8The feed molar weight ratio of (a) to (b) is 1:1.
6. The aqueous phase mixed base accelerated thioamide synthesis method according to claim 1, characterized in that: the dosage of the amide compound substrate is 3-10 times of the molar weight of the aldehyde compound substrate.
7. The aqueous phase mixed base accelerated thioamide synthesis method according to claim 1, characterized in that: the alkaline aqueous solution is prepared by adding an alkali into water, wherein the alkali is a mixed alkali of inorganic alkali (any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide and potassium phosphate) and triethylamine in equal proportion, and the total molar weight of the mixed alkali is 1-10 times of that of an aldehyde compound or an amide compound substrate.
8. The aqueous phase mixed base accelerated thioamide synthesis method according to claim 1, characterized in that: the reaction gas atmosphere is nitrogen, the reaction temperature is 60-120 ℃, and the stirring reaction time is 4-24 h.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112500361A (en) * | 2020-12-27 | 2021-03-16 | 甘肃瀚聚药业有限公司 | Preparation method of (S) -4-phenyl-2-oxazolidinone |
| CN112521323A (en) * | 2020-12-12 | 2021-03-19 | 浙江大学衢州研究院 | Method for synthesizing thioamide compound |
| CN113831288A (en) * | 2021-08-09 | 2021-12-24 | 内蒙古工业大学 | Thioamide derivative, preparation method and application |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080044913A1 (en) * | 2006-08-17 | 2008-02-21 | Chang Suk Kyu | Novel 8-hydroxyquinoline acetamide compound, 8-hydroxy quinoline thioamide compound and use thereof |
| CN104356037A (en) * | 2014-11-05 | 2015-02-18 | 广东石油化工学院 | Method for preparing thioamide derivative |
| CN108191726A (en) * | 2018-02-06 | 2018-06-22 | 商丘师范学院 | A kind of preparation method of arylthio amide |
| CN108689895A (en) * | 2018-04-26 | 2018-10-23 | 浙江大学 | A kind of thioamide derivatives and preparation method thereof |
-
2020
- 2020-02-02 CN CN202010078016.XA patent/CN111303079A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080044913A1 (en) * | 2006-08-17 | 2008-02-21 | Chang Suk Kyu | Novel 8-hydroxyquinoline acetamide compound, 8-hydroxy quinoline thioamide compound and use thereof |
| CN104356037A (en) * | 2014-11-05 | 2015-02-18 | 广东石油化工学院 | Method for preparing thioamide derivative |
| CN108191726A (en) * | 2018-02-06 | 2018-06-22 | 商丘师范学院 | A kind of preparation method of arylthio amide |
| CN108689895A (en) * | 2018-04-26 | 2018-10-23 | 浙江大学 | A kind of thioamide derivatives and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| KAI XU, ET AL.: "Transition-Metal-Free Cleavage of C−C Triple Bonds in Aromatic Alkynes with S8 and Amides Leading to Aryl Thioamides", 《ORG. LETT.》 * |
| SAURABH KUMAR,ET AL.: "Sulfur promoted decarboxylative thioamidation of carboxylic acids using formamides as amine proxy", 《TETRAHEDRON》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112521323A (en) * | 2020-12-12 | 2021-03-19 | 浙江大学衢州研究院 | Method for synthesizing thioamide compound |
| CN112521323B (en) * | 2020-12-12 | 2022-05-13 | 浙江大学衢州研究院 | Method for synthesizing thioamide compound |
| CN112500361A (en) * | 2020-12-27 | 2021-03-16 | 甘肃瀚聚药业有限公司 | Preparation method of (S) -4-phenyl-2-oxazolidinone |
| CN112500361B (en) * | 2020-12-27 | 2023-05-12 | 甘肃瀚聚药业有限公司 | Preparation method of (S) -4-phenyl-2-oxazolidinone |
| CN113831288A (en) * | 2021-08-09 | 2021-12-24 | 内蒙古工业大学 | Thioamide derivative, preparation method and application |
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