CN110804012B - Method for reducing mercaptal or thioketone for desulfurization - Google Patents
Method for reducing mercaptal or thioketone for desulfurization Download PDFInfo
- Publication number
- CN110804012B CN110804012B CN201911045776.4A CN201911045776A CN110804012B CN 110804012 B CN110804012 B CN 110804012B CN 201911045776 A CN201911045776 A CN 201911045776A CN 110804012 B CN110804012 B CN 110804012B
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- hydrazine hydrate
- mercaptal
- reducing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
The invention provides a method for reducing mercaptal or thioketone for desulfurization, which takes hydrazine hydrate as a reducing agent to reduce mercaptal or thioketone into methyl or methylene. The method has the advantages of simple and convenient process, environmental protection, capability of safely converting in a gram-level or above scale, suitability for the field of chemical and medical engineering and realization of large-scale production.
Description
Technical Field
The invention relates to the technical field of pharmaceutical chemicals, in particular to a method for reducing mercaptal or thioketone for desulfurization.
Background
The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.
The reduction of mercaptal or thioketal to desulfurize and prepare methyl or methylene is an important chemical transformation, and is widely used in the synthesis of medicines and intermediates. The applicant has found through research that the current reduction desulfurization reaction can be roughly divided into the following types: (1) taking active metal as a reducing agent, wherein the representative agent is Raney nickel, and nickel derivatives NiCrAs (prepared from nickel acetate, sodium hydride and tertiary amyl alcohol) and Ni2B (nickel chloride and sodium borohydride preparation) and an ammonia solution of metallic sodium or lithium. The reagent is most widely used, has better functional group compatibility and yield, but needs several times of equivalent of Raney nickel, because the Raney nickel is expensive and extremely flammable, great potential safety hazard exists in gram-level reaction scale, and a large amount of waste residues with high activity and difficult treatment are generated, and the reaction scale is difficult to safely amplify; (2) metal hydride is used as a reducing reagent, for example, under the condition of azodiisobutyronitrile as a free radical initiator, tri-n-butyltin hydride is used as a reducing agent to carry out reduction desulfurization reaction. The reaction condition is mild, but tri-n-butyltin hydride has high toxicity and is not suitable for being applied to pharmaceutical chemical production; (3) non-metal compounds such as diphosphorus tetraiodide and sodium ethyl mercaptide are used as reducing agents. This type of reducing agent has poor functional group compatibility and is limited only to compounds of relatively simple structure.
Disclosure of Invention
Therefore, the invention aims to provide a method for reducing mercaptal or thioketal and desulfurizing, which can be produced in an enlarged way.
Specifically, the invention has the following technical scheme:
in a first aspect of the invention, the invention provides a method for reducing desulfurization, wherein hydrazine hydrate is used as a reducing agent to reduce mercaptal or thioketal into methyl or methylene.
In an embodiment of the present invention, the mercaptal or thione refers to a compound obtained by reacting a carbonyl compound with an alcohol or thiol, which is generally referred to as having
And/or
A compound of the group in which n is 0 or 1 and when n is 0, it is a five-membered ring
Or
When n is 1, it is a six-membered ring
Or
In an embodiment of the present invention, the method comprises mixing mercaptal or thione with a reaction solvent, adding an alkaline reagent, and heating under nitrogen with hydrazine hydrate as a reducing agent to reduce mercaptal or thione to methyl or methylene.
In an embodiment of the present invention, the reaction solvent is diethylene glycol and/or ethylene glycol.
In an embodiment of the invention, the alkaline agent is selected from cesium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
In an embodiment of the invention, the molar ratio of mercaptal or thioketal to hydrazine hydrate is from 1:5 to 1: 15.
In an embodiment of the invention, the molar ratio of mercaptal or thione to alkaline agent is from 1:5 to 1: 15.
In some embodiments of the invention, mercaptal or thioketal is added to a reaction flask with an agitated reflux condenser, dissolved in an organic solvent, and hydrazine hydrate (5-15eq.) and alkaline reagent (5-15eq.) are added sequentially. Stirring, placing in 80-180 deg.C oil bath (nitrogen atmosphere), reacting for 2-8h, cooling to room temperature after reaction, adding water to quench reaction, extracting water phase with ethyl acetate for three times, combining organic phases, washing organic phases with water and saturated salt water, concentrating organic solvent, and performing flash column chromatography to obtain desired methyl or methylene product. Unless otherwise specified, the eq. in the present invention means a chemical equivalent.
In a second aspect of the invention, the invention provides a method for reducing mercaptal or thioketal for desulfurization, the method comprising reducing compound 1 to compound 2:
compound 1:
compound 2:
in an embodiment of the present invention, the method comprises dissolving compound 1 in an organic solvent, adding an alkaline reagent, using hydrazine hydrate as a reducing agent, and heating under nitrogen to reduce compound 1 to compound 2.
In an embodiment of the present invention, the organic solvent is diethylene glycol and/or ethylene glycol.
In an embodiment of the invention, the alkaline agent is cesium carbonate. In the implementation process of preparing the compound 2 from the compound 1, the invention discovers that when hydrazine hydrate is used as a reducing agent, potassium carbonate, sodium hydroxide and potassium hydroxide are used as alkaline substances, the reaction is difficult to carry out, the yield is low, and particularly when potassium tert-butoxide is used as the alkaline substance, only a trace amount of product can be generated.
In an embodiment of the invention, the molar ratio of compound 1 to hydrazine hydrate is from 1:5 to 1: 15.
Preferably, the molar ratio of compound 1 to alkaline agent is from 1:5 to 1: 15.
In an embodiment of the present invention, the hydrazine hydrate is preferably 80% to 98% hydrazine hydrate, more preferably 98% hydrazine hydrate.
In some embodiments, the concentration of hydrazine hydrate can affect the choice of alkaline material, such as when 80% hydrazine hydrate is used, the alkaline material is potassium hydroxide and the reaction is not as easy as with 98% hydrazine hydrate.
In some embodiments, when the alkaline reagent is cesium carbonate, the reaction can occur under a wider range of reaction conditions and can be performed more easily, and therefore, cesium carbonate is a preferred alkaline reagent in the present invention. For example, when hydrazine hydrate is used as a catalyst, cesium carbonate is used as an alkaline reagent, and diethylene glycol is used as an organic solvent (reaction solvent), the reaction can be carried out within the range of 140 ℃ to 180 ℃, and the reaction time is 2 to 6 hours. When the reaction temperature is lower than 140 ℃, the reaction is difficult to proceed.
Further, in some embodiments, when the basic agent is cesium carbonate, the reaction yield increases significantly as the reaction temperature increases, such as from 140 ℃ to 170 ℃, but decreases as the temperature continues to increase to 180 ℃, but the yield at 180 ℃ is still higher than the yield at 140 ℃; in still other embodiments, when the basic agent is cesium carbonate, the reaction yield increases significantly with increasing reaction time, such as when the reaction time increases from 2 hours to 4 hours, but continues to increase to 6 hours, the reaction yield decreases, but the yield at 6 hours is still higher than the yield at 2 hours.
Therefore, in some embodiments of the present invention, the reductive desulfurization method uses hydrazine hydrate as a reducing agent to reduce mercaptal or thioketone into corresponding methyl or methylene, the alkaline reagent is cesium carbonate, the organic solvent is diethylene glycol, the reaction temperature is 170-. And, in some embodiments, a reaction temperature of 170 ℃ and a reaction time of 4 hours is more preferred.
In the embodiment of the invention, the experiment is amplified to be more than gram level, the reaction yield is still stable, and no obvious reduction is caused. For example, in some embodiments of the present invention, the amount of compound 1 (i.e., substrate) is increased from 120mg to 5.3g (i.e., 5300mg) under the same conditions, i.e., the molar ratio of compound 1 to hydrazine hydrate is 1:15, the alkaline reagent is cesium carbonate, the molar ratio of compound to cesium carbonate is 1:15, the reaction temperature is 170 ℃, and the reaction time is 4 hours, the reaction is safe and the yield is stable without significant decrease.
In the embodiment of the present invention, in the reaction of reducing and desulfurizing compound 1 to produce compound 2, hydrazine hydrate is used as a reducing agent, and the applicant tried to set the reaction temperature to be lower than 140 ℃, for example, 80 ℃, 100 ℃ and 135 ℃, and the reaction is difficult to proceed, and no compound 2 is produced.
In the embodiment of the present invention, in the reaction of reducing and desulfurizing compound 1 to produce compound 2, hydrazine hydrate is used as a reducing agent, and the applicant tried to replace the catalyst with potassium carbonate, sodium hydroxide or potassium hydroxide, and found that the reaction is difficult to proceed, and even if the reaction temperature and the amount of the reactant are adjusted on the basis of the catalyst, the reaction is still difficult to proceed, and the yield is low, and can reach 4% at the minimum.
In the embodiment of the present invention, in the reaction of reducing and desulfurizing compound 1 to produce compound 2, the applicant has tried to replace hydrazine hydrate with other commonly used reducing agents (such as diphosphorus tetraiodide, sodium ethanethiol, tri-n-butyltin hydride, etc.), and the reaction system is disturbed except for raney nickel, so that the desired reduction product compound 2 cannot be obtained; even if applicants attempted to adjust other reaction conditions, compound 2, the desired product, was not obtained.
In the embodiment of the present invention, in the reaction of producing compound 2 by reductive desulfurization of compound 1, the applicant has tried to change hydrazine hydrate to raney nickel and the reaction proceeds, but the yield is unstable, the reaction scale can be maintained only at about 100mg, and the reaction cannot be scaled up, and it is difficult to industrially produce the hydrazine hydrate.
In some embodiments of the present invention, the method for obtaining compound 2 by reductive desulfurization of compound 1 comprises dissolving compound 1 in diethylene glycol and/or ethylene glycol (diethylene glycol is more preferred) as an organic solvent, adding hydrazine hydrate and cesium carbonate, and reacting in nitrogen at 140-180 ℃ for 2-6 hours to generate compound 2, wherein the molar ratio of compound 1 to hydrazine hydrate is 1:5-1: 15; the molar ratio of the compound 1 to the alkaline reagent is 1:5-1: 15. After the reaction is finished, adding water to quench the reaction, separating and purifying to obtain the compound 2.
And, in an embodiment of the present invention, the present invention provides an amplification method for reductive desulfurization of compound 1 to compound 2, the method comprising: dissolving a compound 1 in an organic solvent diethylene glycol, adding hydrazine hydrate and cesium carbonate, and reacting for 3-6 hours in nitrogen at 170-180 ℃ to generate a compound 2, wherein the molar ratio of the compound 1 to the hydrazine hydrate is 1:5-1: 15; the molar ratio of the compound 1 to the alkaline reagent is 1:5-1: 15. After the reaction is finished, adding water to quench the reaction, separating and purifying to obtain the compound 2.
Compared with the prior art, the invention has the following advantages:
the invention creatively adopts hydrazine hydrate as a reducing agent to carry out reduction desulfurization on mercaptal and thioketone, compared with the prior conventional method, such as compared with the prior conventional method that uses active metal such as Raney nickel, NiCras and Ni2B. The ammonia solution of metal sodium or lithium is a reducing reagent, the reagent cost of hydrazine hydrate is cheaper, taking Raney nickel as an example, the price difference of the two is 30-50 times, and the Raney nickel has larger activity difference and unstable yield according to the difference of a preparation method, and belongs to high-risk materials and is extremely flammable, large-scale reaction above gram level has larger potential safety hazard, and generates a large amount of waste residues with high activity and difficult treatment, the post-treatment is difficult, the reaction scale is difficult to realize safe amplification, and the scale is only about 100 mg; for example, compared with metal hydride as a reducing agent (such as tri-n-butyl tin hydride), tri-n-butyl tin hydride is a highly toxic substance although the reaction temperature is moderate, is colorless and tasteless, and is not suitable for pharmaceutical chemical production; for example, compared with a non-metal compound as a reducing agent (such as diphosphorus tetraiodide or sodium ethyl mercaptide), the reducing agent of the type has poor functional group compatibility, and is only limited to a compound with a simpler structure, such as the compound 1 shown in the invention, so that the compound 2 cannot be obtained under the reducing agent.
The invention uses cheap and easily obtained hydrazine hydrate as a reducing reagent, conveniently converts mercaptal or thioketone into corresponding methyl or methylene, has simple and convenient process and environmental protection, can safely convert on a scale of more than gram level, is suitable for the field of chemical engineering and medicine, and can realize large-scale production.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The reagents or starting materials used in the present invention can be purchased from conventional sources, and unless otherwise specified, the reagents or starting materials used in the present invention can be used in a conventional manner in the art or in accordance with the product specifications. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.
The invention can be carried out according to the following reaction:
EXAMPLE 1 preparation of Compound 3
Compound 1: (1S,2S,4aS,5S,6R,8aR) -1- ((E) -2- (5- (2-fluorophenyl) pyridin-2-yl) vinyl) -6-hydroxy-5, 8 a-dimethyloctahydro-1H-spiro- [ naphthalene-2, 2' -oxirane ] -5-carbaldehyde
(1S,2S,4aS,5S,6R,8aR)-1-((E)-2-(5-(2-Fluorophenyl)pyridin-2-yl)vinyl)-6-hydroxy-5,8a-dimethyloctahydro-1H-spiro-[naphthalene-2,2’-oxirane]-5-car baldehyde
The compound alcohol (236mg,0.88mmol) was dissolved in dichloromethane (15mL), cooled in an ice-water bath, and TEMPO (28mg,0.18mmol),15mL of 0.05M K were added sequentially2CO3-0.5M NaHCO3Buffer solution, TBAI (65mg,0.18mmol) and NCS (235mg,1.76 mmol). Vigorously stirred at room temperature for 7 h. After the reaction was completed, the aqueous phase was separated from the organic phase, the aqueous phase was extracted three times with methylene chloride (20 ml. times.3), and the organic phases were combined. The organic phase was washed with water, saturated brine, dried over sodium sulfate, filtered and concentrated to give compound 3(213mg, 90%): white powder, mp241-243 ° C, 1H NMR (400MHz, DMSO) δ 10.01(s,1H),8.85(d, J ═ 2.2Hz,1H),8.06(dd, J ═ 8.2,2.4Hz,1H),7.67-7.45(m,4H),7.31-7.18(m,1H),6.57-6.38(m,2H),5.15(s,1H),3.36(dd, J ═ 11.8,4.8Hz,1H),2.79(d, J ═ 4.2Hz,1H),2.54(d, J ═ 4.5Hz,1H),2.43(d, J ═ 8.8Hz,1H),2.06-1.69(m,4H),1.60-1.44(m,1H), 1H (m, 44, 1H), 3.35 (d, 13H), 3.13 (d, 13H), 3.35 (d, 13H), 3.35H, 13 (d, 13H), 3.9, 13H, 3.35H, 13H), 129.8,123.2(d, J2.5 Hz),121.7,115.2(d, J21.2 Hz),113.8(d, J22.4 Hz),75.5,58.6,56.9,54.5,53.1,50.2,39.3,37.6,35.4,27.8,22.0,21.5,16.2 ESI-HRMS (M/z): calcd for C27H31FNO3[ M + H3: (M/z) ]]+,436.2243；found,436.2277.
EXAMPLE 2 preparation of Compound 1
Compound 1: (1S,2R,4aS,5R,6R,8aS) -1, 6-bis (1, 3-dithiolan-2-yl) -5- ((E) -2- (5- (2-fluorophenyl) pyridin-2-yl) ethenyl) -1,4 a-dimethyldecalin-2-ol
(1S,2R,4aS,5R,6S,8aS)-1,6-di(1,3-dithiolan-2-yl)-5-((E)-2-(5-(2-fluoroph enyl)pyridin-2-yl)vinyl)-1,4a-dimethyldecahydronaphthalen-2-ol
Compound 3(50mg,0.12mmol) was dissolved in dry dichloromethane (3ml) and BF was added under nitrogen in sequence3·Et2O (37. mu.L, 0.30mmol) and 1, 2-ethanedithiol (46. mu.L, 0.6 mmol). Stirring was carried out overnight at room temperature. After the reaction is finished, adding water to quench the reaction. The aqueous phase was extracted three times with dichloromethane (10 ml. times.3) and the organic phases were combined. The organic phase was washed with water, saturated brine, dried over sodium sulfate, filtered, concentrated and flash column chromatographed to give compound 1(59.5mg, 88%): yellow power, mp 145 ℃.1H NMR (400MHz, CDCl3) δ 8.76(d, J ═ 2.1Hz,1H),7.80(dd, J ═ 8.1,2.4Hz,1H),7.43(td, J ═ 8.0,5.9Hz,1H),7.38-7.33(m,1H),7.31(d, J ═ 8.0Hz,1H),7.29-7.23(m,1H),7.13-7.03(m,1H),6.67(dd,J＝15.5,10.2Hz,1H),6.54(d,J＝15.5Hz,1H),4.98(s,1H),4.74(d,J＝3.1Hz,1H),3.46(td,J＝10.2,5.1Hz,1H),3.30-2.86(m,8H),2.34(d,J＝7.0Hz,1H),2.28-2.18(m,1H),2.03(tt,J＝11.5,3.3Hz,1H),1.87(ddd,J＝16.4,12.6,3.3Hz,2H),1.81-1.74(m,1H),1.73-1.62(m,3H),1.35(dd,J＝12.4,4.7Hz,1H),1.30(s,3H),1.19(dd,J＝12.1,3.0Hz,1H),1.14(s,3H).13C NMR(101MHz,CDCl3)δ163.4(d,J＝246.5Hz),154.6,148.1,140.1(d,J＝7.7Hz),135.0,134.2,133.7,133.2,130.8(d,J＝8.4Hz),122.7(d,J＝2.8Hz),121.9,114.9(d,J＝21.1Hz),113.9(d,J＝22.2Hz),81.5,62.0,58.0,57.6,57.5,46.7,42.8,40.3,39.3,39.0,38.2,37.8,37.4,27.3,26.7,23.5,20.0,16.3.ESI-HRMS(m/z):calcd for C31H39FNOS4[M+H]+,588.1854；found,588.1889.
EXAMPLE 3 preparation of Compound 2
Compound 2: (1S,2R,4aS,5R,6R,8aS) -5- ((E) -2- (5- (2-fluorophenyl) pyridin-2-yl) ethenyl) -1,4a, 6-tetramethyldecahydronaphthalen-2-ol
(2R,4aS,5S,6S,8aS)-5-((E)-2-(5-(2-fluorophenyl)pyridin-2-yl)vinyl)-1,4a,6-tetramethyldecahydronaphthalen-2-ol
Dissolving the compound 1(5.3g,9mmol) in diethylene glycol (180ml), and adding hydrazine hydrate (6.8ml,135mmol,15eq.) and cesium carbonate (44g,135mmol,15eq.) in sequence; the reaction was placed in an oil bath at 170 ℃ for 4 hours (nitrogen atmosphere). After the reaction was completed, the reaction system was cooled to room temperature. The reaction was quenched by the addition of water (200ml), extracted three times with ethyl acetate (400 ml. times.3), and the organic phases were combined. The organic phase was washed with water, saturated brine, dried over sodium sulfate, filtered, concentrated and flash column chromatographed (PE: EA ═ 3:1) to afford the title compound (1.15g, 31%):1H NMR(400MHz,CDCl3)δ8.75(d,J＝2.1Hz,1H),7.78(dd,J＝8.2,2.4Hz,1H),7.43(td,J＝7.9,6.0Hz,1H),7.38-7.30(m,2H),7.29-7.24(m,1H),7.11-7.03(m,1H),6.57(dd,J＝15.6,9.9Hz,1H),6.43(d,J＝15.6Hz,1H),3.25(dd,J＝11.2,4.5Hz,1H),1.90(ddd,J＝13.0,6.7,3.7Hz,1H),1.70-1.38(m,8H),1.29-1.23(m,1H),1.14(td,J＝14.3,5.9Hz,1H),1.00(s,3H),0.98(s,3H),0.90(dd,J＝12.3,2.5Hz,1H),0.82(s,3H),0.79(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3)δ163.3,155.2,147.8,140.1,136.9,134.7,133.2,131.5,130.6,122.5,121.0,114.7,113.7,79.1,63.2,53.9,39.1,38.7,37.6,36.2,31.1,28.3,27.4,21.6,21.5,15.6,15.3.ESI-HRMS(m/z):calcd for C27H35FNO[M+H]+,408.2658；found,408.2697.
EXAMPLES 4-18 preparation of Compound 2
Dissolving the compound 1 (substrate) in an organic solvent, and sequentially adding hydrazine hydrate (6.8ml,135mmol,15eq.) and an alkaline reagent; the reaction mixture was placed in an oil bath for reaction (nitrogen atmosphere). After the reaction was completed, the reaction system was cooled to room temperature. The reaction was quenched by the addition of water (200ml), extracted three times with ethyl acetate (400 ml. times.3), and the organic phases were combined. The organic phase is washed with water and saturated brine, dried over sodium sulfate, filtered, concentrated and subjected to flash column chromatography (PE: EA ═ 3:1) to obtain the target compound. Wherein the molar ratio of the compound 1 to the hydrazine hydrate is 1:15, the hydrazine hydrate, the amount of the compound 1, the kind and amount of the organic solvent, the kind and amount of the alkaline reagent, the oil bath temperature, and the reaction time are shown in table 1. The reaction results and yield information are detailed in table 1.
TABLE 1 optimization of reaction conditions and results
In this example, it was also tried to use other catalysts, respectively, diphosphorus tetraiodide, sodium ethanethiol, tri-n-butyltin hydride and raney nickel, and with respect to diphosphorus tetraiodide, sodium ethanethiol and tri-n-butyltin hydride, it was difficult to perform the reaction without adjusting the reaction temperature, the reaction amount and changing the basic substance, and no compound 2 was produced.
Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (1)
1. A method for reducing mercaptal for desulfurization is characterized by comprising the steps of dissolving a compound 1 in an organic solvent, adding an alkaline reagent, using hydrazine hydrate as a reducing agent, and heating under the condition of nitrogen to reduce the compound 1 into a compound 2:
formula 1:
formula 2:
wherein the organic solvent is diethylene glycol and/or ethylene glycol;
the alkaline reagent is cesium carbonate;
the molar ratio of the compound 1 to the hydrazine hydrate is 1:5-1: 15;
the molar ratio of the compound 1 to the alkaline reagent is 1:5-1: 15;
the reaction temperature is 140 ℃ and 180 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911045776.4A CN110804012B (en) | 2019-10-30 | 2019-10-30 | Method for reducing mercaptal or thioketone for desulfurization |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911045776.4A CN110804012B (en) | 2019-10-30 | 2019-10-30 | Method for reducing mercaptal or thioketone for desulfurization |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110804012A CN110804012A (en) | 2020-02-18 |
| CN110804012B true CN110804012B (en) | 2021-06-08 |
Family
ID=69489553
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911045776.4A Active CN110804012B (en) | 2019-10-30 | 2019-10-30 | Method for reducing mercaptal or thioketone for desulfurization |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110804012B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112759548B (en) * | 2020-12-31 | 2021-11-02 | 山东大学 | PAR-1 inhibitor and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105732595B (en) * | 2015-12-22 | 2018-08-28 | 山东大学 | PAR-1 inhibitor based on terpene derivant and preparation method thereof and the purposes in treating thrombotic diseases |
-
2019
- 2019-10-30 CN CN201911045776.4A patent/CN110804012B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110804012A (en) | 2020-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108033922B (en) | Preparation method of 3-acyl quinoxalinone derivative | |
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| CN110804012B (en) | Method for reducing mercaptal or thioketone for desulfurization | |
| CN106977415B (en) | Intermediate of shakubiqu and preparation method thereof | |
| CN111362880B (en) | Synthesis method of alkyl and aryl-containing pyrimidine compound | |
| CN108689901A (en) | A kind of synthetic method of aziridine class compound | |
| CN111646964B (en) | Novel method for synthesizing 2H-pyran-2-one derivative by base catalysis | |
| CN113061077B (en) | Alpha, alpha-dideuteroalcohol compounds, deuterated drugs and preparation method thereof | |
| IL178918A (en) | Process for producing pentacyclic taxane | |
| CN106892928A (en) | A kind of synthetic method of the carboxylate of 8 hydroxyl of the tert-butyl group, 5 oxa- 2 azaspiro [3.5] nonane 2 | |
| CN105693778B (en) | The method of N- methoxymethylamide guiding synthesis ferrocene and Pyridione derivatives | |
| CN115093372A (en) | Synthesis method of imidazole derivative | |
| CN106966948A (en) | A kind of synthetic method together with difluoro substituted pyrrolidone compound | |
| CN109942432B (en) | Triaryl methanol compound and synthetic method thereof | |
| CN111793047B (en) | Preparation method of eribulin intermediate | |
| CN113372353A (en) | Difluoroalkylated dihydrofuranoquinolinone derivative and preparation method thereof | |
| CN108530510A (en) | A kind of C19- is acylated the preparation method of triptolide | |
| CN106046028A (en) | Synthesis of natural products with inhibitory activity of histone demethylase | |
| CN108299466B (en) | Improved dolutegravir synthesis method | |
| Ando et al. | Novel reactions of sterically protected fused 1, 2, 3‐selenadiazole. A new aspect of reactivity of organoselenium intermediates | |
| CN103382208B (en) | The preparation method of Arglabin | |
| CN110698422A (en) | Synthetic method of aromatic mercapto-diazole derivative | |
| CN113461632B (en) | Preparation method of methyl 3- ((4-fluorophenyl) sulfonyl) -4-hydroxy-2-methylthiazolidine-2-carboxylate | |
| CN114437106B (en) | Method for preparing 1, 3-oxazine-2-ketone derivative by continuous one-pot method | |
| CN113135931B (en) | Synthesis method of cytochalasin compound flaviperine A |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |