CN105272935A - New method for simple synthesis of thiazole from anhydride and beta-azide disulfide - Google Patents
New method for simple synthesis of thiazole from anhydride and beta-azide disulfide Download PDFInfo
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- CN105272935A CN105272935A CN201410341512.4A CN201410341512A CN105272935A CN 105272935 A CN105272935 A CN 105272935A CN 201410341512 A CN201410341512 A CN 201410341512A CN 105272935 A CN105272935 A CN 105272935A
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Abstract
The present invention provides a new method for efficient one-pot synthesis of a thiazole compound directly from anhydride and beta-azide disulfide as substrates under the combined action of neutral organic phosphine, an organic alkali agent and an oxidizing agent, and the thiazole compound is as shown in Formula I; and the method is simple, and economical, and can easily accomplish synthesis of the thiazole compound without adding of any coupling reagent by use of market-available anhydride as the substrate under mild alkaline conditions.
Description
Technical field
The present invention relates to a kind of is substrate with acid anhydrides, and the novel method of easy synthetizing thiazolium compound, belongs to technical field of organic chemistry.
Background technology
Thiazole is the important five member ring heterocyclic compound of a class, and in daily life, also play more and more important effect.Azoles and derivative thereof all have a wide range of applications (J.SulfurChem.2005,26,429-449.) in fields such as polymer, sterilant, photonuclease, pharmaceutical synthesis, liquid crystal material, antioxidant, fluorescence dyes.That does not exaggerate says, this compounds just quietly changes production, the life of people.
Just in view of the application prospect that thiazole compound is wide, the synthesis of thiazole compound, applied research work were never interrupted.Especially to development efficiently, succinctly, the research of thiazoline and thiazole new synthetic method safely, always be the focus that scientific circles are studied.Many existing thiazole synthetic methods, although achieved many useful achievements, efficiently, method that is easy, green, that efficiently prepare on a large scale thiazole compound has been still in short supply.
Synthesis at present for thiazole is broadly divided into following three approach: 1. by using the oxidising agent method of fractional steps, by the method for thiazoline or thiazolidine oxidative synthesis thiazole, is also a kind of conventional strategy building thiazole; 2. reacted the method building thiazole ring by Hantzsch, remain selecting the most at large of organic chemists, through groping of century more than one, the method becomes better and approaching perfection day by day, reliably ripe; 3. in recent years, use the multi-component reactions such as Ugi reaction to prepare the novel method of thiazole, have also been obtained deep research and development.
1, from thiazolidine, the preparation of thiazoline substrate oxidation
Thiazolidine and thiazoline are the five-membered heterocycles very similar with thiazole structure, they be usually considered to thiazolium compounds precursor.
1981, Badr group utilized bromo-succinimide and Benzoyl Peroxide that thiazolidine oxidation is obtained thiazole (Bull.Chem.Soc.Jpn.1981,54,1844-1847.).
2011, Reginatio group utilized activated manganese dioxide that thiazolidine oxidation is obtained thiazole (Tetrahedron2011,67,267-274.).
2010, China Yao and group of army reported a kind of neomethodology (TetrahedronLett.2010,51,1751-1753.) using dioxygen oxidation thiazoline to generate thiazole.
1997, Williams group utilized BrCCl
3/ DBU, under ice-water bath condition, completes the synthesis (TetrahedronLett.1997,38,331-334.) of thiazoline to thiazolium compounds.
2, Hantzsch Reactive Synthesis thiazole
1888, a research thioamide analog compound (thiocarbamide) and α-halogenatedcarbonylcompounds (ethyl bromide acetone) are under acid catalysis, can the generation thiazole (LiebigsAnn.Chem.1888,249,31-33.) of high yield.
The method so far, is still thiazole and synthesizes one of foremost method.
3, the multi-component reaction such as Ugi reaction prepares thiazole
2000, Domling group completed the synthesis (TetrahedronLett.2002,43,6897-6901.) of thiazolium compounds by polycomponent Ugi reaction.
Our group also once reported a kind of novel method (patent No.: 201410113814.6) of one pot process thiazole
Summary of the invention
The object of the invention is to prepare the shortcomings such as loaded down with trivial details, step is tediously long for existing thiazole synthetic method substrate, is substrate first with acid anhydrides, the simple and direct chemosynthesis completing thiazolium compounds efficiently.
The present invention relates to a kind of is substrate with acid anhydrides, and one kettle way efficiently prepares the novel method of thiazolium compounds, belongs to technical field of organic chemistry.As shown in general formula I, acid anhydrides substrate, under the effect of organic bases and organic phosphine reagent, reacts with β-nitrine disulphide, has synthesized target thiazoles compound simply, efficiently.
Beneficial effect of the present invention: adopt acid anhydrides substrate synthetizing thiazolium first, and step is brief, simple to operate, effectively prevent the loaded down with trivial details last handling process needed for polystep reaction.Without the need to adding expensive coupling reagent, can effectively save synthesis cost.Adopt the stable mercaptan compound of disulphide replacement needed for polystep reaction, directly utilize carboxylic acid cheap and easy to get as reaction substrate, significantly improve combined coefficient.Reaction can be carried out under relatively mild condition, and has good suitability to multiple substrate.
Embodiment:
(1)
Step one: get 25ml flask, under the condition of lucifuge, adds β-nitrine disulphide 200mg and dissolves with 15ml tetrahydrofuran (THF).
Step 2: slowly add diacetyl oxide 240mg and triethylamine 300mg in system, and continue to stir half an hour.
Step 3: add 276mg tributylphosphine in system, maintains normal-temperature reaction 1 hour.
Step 4: then add 1.2g triphenylphosphine in system, and be heated to reflux and maintain 8 hours.
Step 5: ice-water bath is cooled to 0 DEG C, slowly adds activated manganese dioxide 1.2g and continues back flow reaction 1 hour in system.Aftertreatment: under frozen water condition, in system, add saturated ammonium chloride solution cancellation react and stir 0.5 hour, extraction into ethyl acetate three times, after saturated common salt washing, separate organic phase with separating funnel, organic phase is after anhydrous sodium sulfate drying, evaporated under reduced pressure, obtain yellow oil, silicagel column obtains white solid 136mg (productive rate is 70%) after being separated (ethyl acetate/petroleum ether=1:3), and nuclear-magnetism confirms as target thiazoles product
1hNMR (400MHz): δ 2.77 (s, 3H), 3.94 (s, 3H), 8.05 (s, 1H);
13cNMR (100MHz) δ 19.3,52.4,127.4,146.5,161.8,166.9.
Claims (7)
1. the invention provides a kind of directly with acid anhydrides and β-nitrine disulphide for substrate, by the novel method of one kettle way multistep processes synthetizing thiazolium compound.As shown in general formula I, this method with acid anhydrides cheap and easy to get for substrate, easy and simple to handle, economical and practical, under the condition without the need to using coupling reagent, only under the existence of organic phosphine reagent and organic bases, complete the synthesis of thiazolium compounds, and the method have good substrate applicability and expansion.
Acid anhydrides substrate and β-nitrine disulphide are dissolved in organic solvent, organic bases and tributylphosphine and triphenylphosphine is added in reaction system, under the condition of reflux, by Staudinger-Aza-Wittig reaction in molecule, complete the synthesis of five yuan of thiazoline intermediate products, finally by adding oxidising agent, one kettle way complete thiazolium compounds easy, efficiently synthesize.
In general formula I:
R
1can be CH
3, OCH
3, OCH
2cH
3, OC (CH
3)
3, N (CH
3)
2, N (CH
2cH
3)
2, NCH
3(OCH
3), or other group.
R
2can be CH
3, C
2h
5, C
3h
7, C
4h
9, C
5h
11, C
6h
13, COCH
3, C
6h
5, CH (CH
3)
2,-CH
2-, 2-C
4h
3s, 2-C
4h
3o, m-CH
3-C
6h
4, CH
2(CH
2)
4c (CH
3)
3, CH
2c (CH
3)
3, m-(N (CH
3)
2) C
6h
4, p-CH
3-C
6h
4or other group.
2. method according to claim 1, is characterized in that, the reaction conditions of thiazole synthesis is: organic phosphine reagent, alkali, oxidising agent, organic solvent.
3. method according to claim 1, is characterized in that, temperature of reaction is between-20 DEG C-100 DEG C.
4. method according to claim 1, is characterized in that, the reaction times is between 5 minutes-200 hours.
5. method according to claim 1, it is characterized in that, reaction solvent can be ethyl acetate, ether, t-butyl methyl ether, n-butyl ether, tetrahydrofuran (THF), N, dinethylformamide, glycol dimethyl ether, methylene dichloride, trichloromethane, 1,2-ethylene dichloride, toluene, pyridine, benzene.
6. method according to claim 1, it is characterized in that, organic alkali agents can be pyridine, triethylamine, Trimethylamine 99, Tetramethyl Ethylene Diamine, I-hydroxybenzotriazole, quinoline, imidazoles, DMAP, diisopropyl ethyl amine, 1,8-diazabicyclo [5.4.0] 11 carbon-7-alkene etc., preferred DMAP.
7. method according to claim 1, is characterized in that, oxidising agent can be potassium permanganate, CuBr/Cu (OAc)
2/ t-BuOOCOPh, DBU/NIS, DBU/BrCCl
3, activated manganese dioxide, NiO
2, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, NaH/DBU, oxygen etc.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410341512.4A CN105272935A (en) | 2014-07-17 | 2014-07-17 | New method for simple synthesis of thiazole from anhydride and beta-azide disulfide |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105753937A (en) * | 2016-03-21 | 2016-07-13 | 中国科学院生态环境研究中心 | Synthesis method for marine cyclopeptide compound 27-Deoxylyngbyabellin A and derivative of marine cyclopeptide compound 27-Deoxylyngbyabellin A |
| CN110204538A (en) * | 2019-06-04 | 2019-09-06 | 烟台大学 | Aryl thiazole-tryptamines class marine red tide algae algicide and its preparation method and application |
| CN111454230A (en) * | 2020-04-26 | 2020-07-28 | 深圳市老年医学研究所 | Synthesis method of key intermediate Tuv of natural anticancer drug Tubulysins |
-
2014
- 2014-07-17 CN CN201410341512.4A patent/CN105272935A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105753937A (en) * | 2016-03-21 | 2016-07-13 | 中国科学院生态环境研究中心 | Synthesis method for marine cyclopeptide compound 27-Deoxylyngbyabellin A and derivative of marine cyclopeptide compound 27-Deoxylyngbyabellin A |
| CN110204538A (en) * | 2019-06-04 | 2019-09-06 | 烟台大学 | Aryl thiazole-tryptamines class marine red tide algae algicide and its preparation method and application |
| CN110204538B (en) * | 2019-06-04 | 2022-02-08 | 烟台大学 | Aryl thiazole-tryptamine ocean red tide algae algicide and preparation method and application thereof |
| CN111454230A (en) * | 2020-04-26 | 2020-07-28 | 深圳市老年医学研究所 | Synthesis method of key intermediate Tuv of natural anticancer drug Tubulysins |
| CN111454230B (en) * | 2020-04-26 | 2021-12-14 | 深圳市老年医学研究所 | Synthesis method of key intermediate Tuv of natural anticancer drug Tubulysins |
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