CN106986843A - A kind of preparation method of α heterocycles thioether ketone compounds - Google Patents

A kind of preparation method of α heterocycles thioether ketone compounds Download PDF

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CN106986843A
CN106986843A CN201710274947.5A CN201710274947A CN106986843A CN 106986843 A CN106986843 A CN 106986843A CN 201710274947 A CN201710274947 A CN 201710274947A CN 106986843 A CN106986843 A CN 106986843A
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周从山
杨赞
杨涛
李姣
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Hunan Institute of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles 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 in position 2
    • C07D277/70—Sulfur atoms
    • C07D277/74—Sulfur atoms substituted by carbon atoms
    • 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
    • C07D213/60—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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles 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 in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical

Abstract

The method containing different heterocycle thioether ketones derivants is efficiently synthesized the invention provides a kind of, it uses KI as catalyst, potassium peroxydisulfate is oxidant, and at ambient temperature using carbonyl complex and benzheterocycle mercaptan as reaction substrate, reaction system adds DMSO as solvent.The advantage of this method：Catalyst is cheap and easy to get；Reaction condition is gentle, can occur under room temperature condition, safe and reliable；Gained target product yield is up to 94%.It this method solve traditional heterocycle thioetherification reaction substrate expensive, it is necessary to multistep reaction, and the deficiency such as severe reaction conditions, with good prospects for commercial application.

Description

A kind of preparation method of α-heterocycle thioether ketone compounds
Technical field
The present invention relates to the synthesis field of heterocycle thioether ketone compounds, one kind is related in particular to KI catalysis of carbonyl The method that class compound prepares heterocycle thioether ketone compounds with heterocyclic thiol class compound under oxidizing effect.
【Background technology】
Heterocyclic thiol class compound is the important organic compound of a class, such compound have important pharmacological activity and Bioactivity, due to the excellent chemical property of this quasi-molecule so that it has a wide range of applications in terms of biological, medicine [Chem. Rev., 2013, 113, 2958]。
Due to the extensive uses of such nitrogenous, oxygen, the Benzoheterocyclic compounds of sulphur, there is provided efficiently synthesize nitrogenous, oxygen, sulphur The method of Benzoheterocyclic compounds is significant.Traditional synthetic method mainly includes：With carbon disulfide, thioether or The organic sulfide such as mercaptan reagent realizes the synthesis [J. Org. Chem., 1999,64,1029] of heterocycle thioether；Two be with The inorganic sulfurs such as sulphur simple substance, potassium sulfide or vulcanized sodium introduce S atom, realize C-S couplings [Tetrahedron. Lett., 2012, 53, 2511]。
In recent years, the thio-ether type compounds of the benzheterocycles such as nitrogenous, oxygen and sulphur are constructed in synthesisization by C-S coupling reactions It is significant in.With the development of oxidative dehydrogenation coupling reaction, realize that C-S couplings are anti-by direct c h bond functionalization It should be with a wide range of applications, also receive the concern of more and more organic chemists, in the related thioether class reported in recent years In the synthetic method of compound, by the S-H of mercaptan with others C-H functionalizations come synthesize be main flow synthesis path [J. Am. Chem. Soc., 2010, 132, 15531]。
In the document reported, realizing α-thioetherification of ketone compounds mainly includes：One is, α-halogenation ketone and mercaptan Nucleophilic substitution；Two are, under the conditions of strong acid and strong base, the direct coupling reaction of ketone compounds and mercaptan or disulfide；Three Be, the oxidative dehydrogenation coupling reaction under the temperate condition of developed recently.And C-S keys are directly introduced by mercaptobenzothiazoler Synthetic method is relatively fewer, in the synthetic system with report, mainly there is K2S2O8/HClO4[Org. Biomol. Chem., , and Cu (acac) 2016,14,7665]2/O2[Eur. J. Org. Chem., 2016,1963] catalyst system and catalyzing, based on this Can a little work, it is contemplated that find a kind of new catalyst system and catalyzing, realize ketone compounds and sulfydryl benzo in a mild condition The direct C-S coupling reactions of thiazole.
【The content of the invention】
Raw material is used as by carbonyl complex cheap and easy to get and heterocyclic thiol class compound it is an object of the invention to provide a kind of The method for efficiently synthesizing corresponding heterocycle thioether ketone compounds, to overcome defect of the prior art.
One object of the present invention offer is a kind of to contain carbonyl complex and heterocyclic thiol class compound by cheap and easy to get The method for efficiently synthesizing corresponding heterocycle thioether ketone compounds, includes following step：Take the carbonyl complex, miscellaneous of reacting dose Epithio alcohol compound, catalyst, oxidant and organic solvent are placed in reaction vessel under air atmosphere and mixed, in room The lower stirring reaction of temperature 24 hours, that is, be made the corresponding heterocycle thioether ketones derivant containing different substitution functional groups.Specific reaction Formula is as follows：
Wherein, R1It is to be selected from from hydrogen, methyl, phenyl, 4- fluorophenyls, 4- chlorphenyls, 3- chlorphenyls, 4- aminomethyl phenyls, 2,4- bis- The groups such as aminomethyl phenyl, 3,4- 3,5-dimethylphenyls, 2- thienyls, naphthyl；
R2It is selected from groups such as hydrogen, methyl, ethyl, phenyl；
Het is the heterocycles such as benzothiazole, benzoxazole, imidazoles, tetrazole, thiadiazoles, pyridine.
In the method for above-mentioned synthesizing heterocyclic thioether ketone compounds, the carbonyl complex described in reactions steps is choosing From acetophenone, 4- fluoro acetophenones, 4- methyl acetophenones, 2,4- dimethyl acetophenones, propiophenone, phenyl propyl ketone, 2- acetonaphthones, hexichol Base ethyl ketone, 1- indones, 1- (2- thienyls) -1- acetone, acetone, 1- butyraldehyde etc..
In the method for above-mentioned synthesizing heterocyclic thioether ketone compounds, heterocyclic thiol class compound is to be selected from 2- sulfydryl benzo thiophenes Azoles, 2- mercaptobenzoxazoles, 5- dredge base -1- phenyl-tetrazole, 5- and dredge base -1- methyl-tetrazole, 2- sulfydryl -5- methyl isophthalic acids, 3,4- thiadiazoles, 2- mercaptopyridines.
In the method for above-mentioned synthesizing heterocyclic thioether ketone compounds, catalyst is to be selected from iodine, cuprous iodide, KI, iodine Change sodium, KBr, tetrabutyl sodium iodide, N- N-iodosuccinimides.
In the method for above-mentioned synthesizing heterocyclic thioether ketone compounds, organic solvent refers to ethyl acetate, dimethyl sulfoxide, N, N- bis- NMF, 1,2- dichloroethanes, acetonitrile.
In the method for above-mentioned synthesizing heterocyclic thioether ketone compounds, oxidant is potassium peroxydisulfate, hydrogen peroxide, the tertiary fourth of peroxide Alcohol, di-t-butyl peroxide or ammonium persulfate-sodium bisulfate.
In the method for above-mentioned synthesizing heterocyclic thioether ketone compounds, carbonyl complex rubs with heterocyclic thiol class compound You are than being 2：1, the mol ratio of carbonyl complex and oxidant is 1：0.6.
The side provided by the present invention that beta-nitrostyrene class compound is efficiently synthesized by the compound of class containing alpha, beta-unsaturated acid Method, course of reaction is gently easy to control.While higher yields are obtained, this method is simple and easy to apply, and used catalyst is cheap It is easy to get, prepares simply, with good prospects for commercial application.
【Embodiment】
With reference to embodiments of the invention, the present invention will be further described：
First, test and analysis
The structural analysis of reaction product uses the Bruker Avance-III that Bruker companies produce in the following embodiments of the present invention 400 magnetic nuclear resonance analyzers.
2nd, embodiment
Embodiment 1
By 1.0 mmol acetophenone, 0.5 mmol mercaptobenzothiazoler, 0.3 mmol potassium peroxydisulfate, 1 mlDMSO exists Under air ambient add Schlenk pipes in, added under air ambient 20 mol% catalyst (iodine, cuprous iodide, KI, Sodium iodide, KBr, tetrabutyl sodium iodide, N- N-iodosuccinimides), stirring reaction 24 hours at room temperature.Pass through post layer Analysis purifying, when KI is as catalyst, the yield of the thioetherification reaction can reach 92%.
Embodiment 2
By 1.0 mmol acetophenone, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 1 mlDMSO is in sky Added under compression ring border in Schlenk pipes, 0.3 mmol oxidant (potassium peroxydisulfate, hydrogen peroxide, mistake is added under air ambient The oxygen tert-butyl alcohol, di-t-butyl peroxide or ammonium persulfate-sodium bisulfate), stirring reaction 24 hours at room temperature.Pass through column chromatography Purifying, when potassium peroxydisulfate is as oxidant, the yield of the thioetherification reaction can reach 92%.
Embodiment 3
By 1.0 mmol acetophenone, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol over cure Sour potassium is added in Schlenk pipes under air ambient, and 1 ml solvent (ethyl acetate, diformazan Asia are added under air ambient Sulfone, DMF, 1,2- dichloroethanes, acetonitrile), stirring reaction 24 hours at room temperature.Purified by column chromatography, When dimethyl sulfoxide is as solvent, the yield of the thioetherification reaction can reach 92%.
Embodiment 4
By 1.0 mmol acetophenone, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol over cure Sour potassium, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response terminates Afterwards, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- Phenyl ethyl ketones of 92% separation yield.Pass through1H、13C NMR identifies the product.
1H NMR (400 MHz, CDCl3) δ 8.07 – 8.05 (m, 2 H), 7.82 – 7.80 (m, 1 H), 7.54 – 7.22 (m, 1 H), 7.61 (t, J = 7.6 Hz, 2 H), 7.52 – 7.39 (m, 2 H), 7.31 – 7.28 (m, 2 H), 4.97 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 192.9, 165.2, 152.8, 135.5, 135.4, 133.8, 128.8, 128.5, 126.0, 124.4, 121.5, 121.0, 41.0.
Embodiment 5
By 1.0 mmol 4- fluoro acetophenones, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol's Potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response knot Shu Hou, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- (4- fluorophenyls) ethyl ketone that 76 % separate yield. Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.11 – 8.07 (m, 2 H), 7.79 (d, J = 8.0 Hz, 1 H), 7.72 (d, J = 8.0 Hz, 1 H), 7.38 (t, J = 7.8 Hz, 1 H), 7.27 (t, J = 8.2 Hz, 1 H), 7.15 (t, J = 8.0 Hz, 2 H), 4.90 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 191.4, 167.3, 165.0, 164.7, 152.7, 135.4, 131.8, 131.8, 131.3, 131.2, 125.92, 124.4, 121.3, 121.0, 115.9, 115.7, 40.5.
Embodiment 6
By 1.0 mmol 4- methyl acetophenones, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol Potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response After end, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- (p-methylphenyl) second that 70 % separate yield Ketone.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.0 Hz, 1 H), 7.75 (d, J = 9.6 Hz, 1 H), 7.40 (t, J = 8.0 Hz, 1 H), 7.31 – 7.26 (m, 3 H), 4.96 (s, 2 H), 2.44 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 192.4, 165.3, 152.8, 144.7, 135.4, 132.9, 129.4, 128.6, 125.9, 124.3, 121.4, 120.9, 40.9, 21.6.
Embodiment 7
By 1.0 mmol 2,4- dimethyl acetophenones, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 Mmol potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Treat After reaction terminates, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- (2,4- diformazans that 87 % separate yield Base phenyl) ethyl ketone.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 7.78 (dd, J = 7.9, 3.1 Hz, 2H), 7.72 (d, J = 7.9 Hz, 1H), 7.37 (ddd, J = 8.4, 7.2, 1.3 Hz, 1H), 7.31 – 7.20 (m, 1H), 7.09 (d, J = 8.6 Hz, 2H), 4.82 (s, 2H), 2.50 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 195.3,165.5,153.0,143.0,139.7,135.6,133.2,129.6,126.5, 126.1,124.4,121.5,43.2,21.6,21.6.
Embodiment 8
By 1.0 mmol propiophenone, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol over cure Sour potassium, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response terminates Afterwards, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- phenylacetones that 94 % separate yield.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.0 Hz, 1 H), 7.73 (dd, J = 8.0 Hz, 0.4 Hz, 1 H), 7.57 (t, J = 7.8 Hz, 1 H), 7.46 (t, J = 8.0 Hz, 2 H), 7.40 (t, J = 7.8 Hz, 1 H), 7.28 (t, J = 8.0 Hz, 1 H), 5.87 (q, J = 7.4 Hz, 1 H), 1.77 (d, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 18.1, 46.9, 121.0, 122.5, 124.4, 126.0, 128.6, 128.7, 133.5, 134.8, 135.5, 152.7, 164.6,197.0.
Embodiment 9
By 1.0 mmol phenyl propyl ketone, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol over cure Sour potassium, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response terminates Afterwards, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- phenyl butanone that 82 % separate yield.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.0 Hz, 2 H), 7.81 (d, J = 8.2 Hz, 1 H), 7.72 (d, J = 8.0 Hz, 1 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.46 (t, J = 7.6 Hz, 2 H), 7.39 (t, J = 7.6 Hz, 1 H), 7.28 (t, J = 7.6 Hz, 1 H), 5.81 (t,J = 5.8 Hz, 1 H), 2.31 – 2.21 (m, 1 H), 2.13 – 2.03 (m, 1 H), 1.08 (t, J = 8.0 Hz, 3 H) ; 13C NMR (100 MHz, CDCl3) δ 197.0, 164.9, 152.7, 135.6, 135.5, 133.4, 128.7, 128.6, 125.9, 124.3, 121.4, 121.0, 52.9, 25.5, 11.4.
Embodiment 10
By 1.0 mmol 2- acetonaphthones, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol mistake Potassium sulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response terminates Afterwards, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- (2- naphthyls) ethyl ketone that 73 % separate yield.It is logical Cross1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.62 (s, 1 H), 8.07 (d, J = 8.6 Hz, 1 H), 7.97 – 7.81 (m, 4 H), 7.73 (d, J = 8.0 Hz, 1 H), 7.63 – 7.53 (m, 2 H), 7.39 (t, J = 8.0 Hz, 1 H), 7.30 – 7.24 (m, 1 H), 5.07 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 192.9, 165.3, 152.8, 135.8, 135.5, 132.7, 132.4, 130.6, 129.6, 128.8, 128.6, 127.8, 126.9, 126.0, 124.3, 123.8, 121.4, 121.0, 40.8.
Embodiment 11
By 1.0 mmol diphenylethan, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol's Potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response knot Shu Hou, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1,2- diphenylethans that 80 % separate yield.It is logical Cross1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.07 – 8.04 (m, 2 H), 7.71 – 7.66 (m, 2 H), 7.56 – 7.48 (m, 3 H), 7.41 (d, J = 8.0 Hz, 2 H), 7.39 – 7.20 (m, 5 H), 6.95 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ194.1, 164.8, 152.7, 135.5, 135.5, 134.6, 133.3, 129.1, 129.0, 128.9, 128.6, 128.5, 125.9, 124.3, 121.5, 121.1, 58.1.
Embodiment 12
By 1.0 mmol 1- indones, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol over cure Sour potassium, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response terminates Afterwards, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -2,3- dihydro -1H- indones that 65 % separate yield.It is logical Cross1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.0 Hz, 1 H), 7.74 (dd, J = 8.4, 0.5 Hz, 1 H), 7.69 – 7.62 (m, 2 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.38 – 7.32 (m, 1 H), 7.30 – 7.24 (m, 1 H), 4.70 (dd, J = 8.2, 4.6 Hz, 1 H), 3.94 (dd, J = 18.0, 8.3 Hz, 1 H), 3.43 (dd, J = 18.3, 4.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 200.6, 164.0, 152.8, 152.2, 135.8, 135.6, 135.4, 127.9, 126.3, 126.0, 124.4, 124.4, 121.6, 121.0, 50.2, 35.7.
Embodiment 13
By 1.0 mmol 3- chlorophenyl acetones, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol's Potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response knot Shu Hou, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- (3- chlorphenyls) acetone that 89 % separate yield. Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.13 (s, 1 H), 7.98 (d, J = 7.2 Hz, 1 H), 7.83 (d, J = 8.0 Hz, 1 H), 7.74 (d, J = 8.6 Hz, 1 H), 7.54 (dd, J = 8.0, 0.8 Hz, 1 H), 7.43 – 7.38 (m, 2 H), 7.30 (t, J = 8.0 Hz, 1 H), 5.80 (q, J = 8.0 Hz, 1 H), 1.74 (d, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 196.0, 164.2, 152.6, 136.6, 135.6, 134.9, 133.4, 129.9, 128.9, 126.8, 126.1, 124.5, 121.5, 121.1, 46.5, 17.8.
Embodiment 14
By 1.0 mmol 3,4- dimethyl benzenes acetone, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 Mmol potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Treat After reaction terminates, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- (3,4- diformazans that 85 % separate yield Base phenyl) acetone.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 7.87 – 7.83 (m, 3 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.44 – 7.39 (m, 1 H), 7.30 (t, J = 8.0 Hz, 1 H), 7.22 (d, J = 8.0 Hz, 1 H), 5.85 (q, J = 7.8 Hz, 1 H), 2.31 (s, 3 H), 2.29 (s, 3 H), 1.76 (d, J = 7.8 Hz, 3 H) ; 13C NMR (100 MHz, CDCl3) δ196.9, 164.8, 152.8, 143.3, 137.0, 135.6, 132.6, 129.9, 126.5, 125.9, 124.3, 121.5, 121.0, 47.0, 20.0, 19.7, 18.5.
Embodiment 15
By 1.0 mmol 4- chlorophenyl acetones, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol's Potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response knot Shu Hou, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- (4- chlorphenyls) acetone that 84 % separate yield. Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 8.6 Hz, 2 H), 7.82 (d, J = 8.0 Hz, 2 H), 7.75 (d, J = 7.2 Hz, 1 H), 7.43 – 7.40 (m, 3 H), 7.30 (t, J = 7.2 Hz, 1 H), 5.82 (q, J = 7.2 Hz, 1 H), 1.75 (d, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 196.0, 164.4, 152.7, 140.0, 135.7, 133.3, 130.2, 128.9, 126.1, 124.5, 121.5, 121.1, 46.5, 17.9.
Embodiment 16
By 1.0 mmol 1- (2- thienyls) -1- acetone, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes that stirring reaction 24 is small at room temperature under air ambient When.After question response terminates, separating-purifying can obtain 2- (benzo [d] thiazol-2-yl sulfenyl) -1- (2- that 67 % separate yield Thienyl) acetone.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 7.98 (dd, J = 4.0, 0.8 Hz, 1 H), 7.84 (d, J = 8.0 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.68 (dd, J = 5.2, 0.8 Hz, 1 H), 7.43 – 7.39 (m, 1 H), 7.32 – 7.28 (m, 1 H), 7.13 – 7.11 (m, 1 H), 5.71 (q, J = 8.0 Hz, 1 H), 1.79 (d, J = 8.0 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 188.9, 164.5, 152.7, 141.8, 135.6, 134.8, 133.0, 128.2, 126.0, 124.4, 121.5, 121.0, 47.5, 18.3.
Embodiment 17
By 1.0 mmol acetone, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol persulfuric acid Potassium, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.After question response terminates, Separating-purifying can obtain 1- (benzo [d] thiazol-2-yl sulfenyl) -2- acetone that 41 % separate yield.Pass through1H、13C NMR reflect The fixed product.
1H NMR (399 MHz, CDCl3) δ 7.83 (d, J = 7.8 Hz, 1H), 7.74 (d, J = 8.6 Hz, 1H), 7.44 – 7.38 (m, 1H), 7.32 – 7.25 (m, 8H), 4.23 (s, 1H), 2.39 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 201.7, 164.8, 152.7, 135.5, 126.0, 124.4, 121.5, 121.0, 43.0, 28.7.
Embodiment 18
By 1.0 mmol 1- butyraldehyde, 0.5 mmol mercaptobenzothiazoler, 20 mol% KI, 0.3 mmol over cure Sour potassium, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response terminates Afterwards, separating-purifying can obtain 1- (benzo [d] thiazol-2-yl sulfenyl) butyraldehyde that 47 % separate yield.Pass through1H、13C NMR reflect The fixed product.
1H NMR (400 MHz, CDCl3) δ 9.71 (d, J = 2.0 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.44–7.40 (m, 1H), 7.33–7.26 (m, 1H), 4.48– 4.44(m, 1H), 2.19–2.08 (m, 1H), 1.96–1.18 (m, 1H), 1.12 (t, J = 7.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 196.4, 163.4, 152.7, 135.5, 126.1, 124.6, 121.7, 121.0, 57.0, 21.3, 11.4.
Embodiment 19
By 1.0 mmol acetophenone, 0.5 mmol 2- mercaptobenzoxazoles, 20 mol% KI, 0.3 mmol mistake Potassium sulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Question response terminates Afterwards, separating-purifying can obtain 2- (benzo [d] oxazole -2- bases sulfenyl) -1- Phenyl ethyl ketones that 75 % separate yield.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.0 Hz, 2H ), 7.65–7.43 (m, 5H), 7.29–7.22 (m, 2H), 4.96 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 192.4, 164.1, 152.0, 141.7, 135.2, 134.1, 128.9, 128.6, 124.4, 124.1, 118.4, 110.0, 41.1.
Embodiment 20
1.0 mmol acetophenone, 0.5 mmol 5- are dredged into base -1- phenyl-tetrazole, 20 mol% KI, 0.3 Mmol potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Treat After reaction terminates, separating-purifying can obtain 1- phenyl-2-((1- phenyl-1H-TETRAZOLE-5- bases) sulphur that 82 % separate yield Base) ethyl ketone.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.9 Hz, 2 H), 7.66 – 7.37 (m, 8 H), 5.07 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 192.0, 153.5, 134.8, 134.1, 133.4, 130.2, 129.8, 128.9, 128.4, 123.6, 42.4.
Embodiment 21
1.0 mmol acetophenone, 0.5 mmol 5- are dredged into base -1- methyl-tetrazole, 20 mol% KI, 0.3 Mmol potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.Treat After reaction terminates, separating-purifying can obtain 2-((1- methyl isophthalic acid H- tetrazolium-5- bases) the sulfenyl)-1- benzene that 85 % separate yield Base ethyl ketone.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.06 – 7.96 (m, 2 H), 7.73 – 7.60 (m, 1 H), 7.55 – 7.43 (m, 2 H), 4.99 (s, 2 H), 3.98 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 191.8, 153.3, 134.7, 134.2, 128.8, 128.5, 42.3, 33.5.
Embodiment 22
By 1.0 mmol acetophenone, 0.5 mmol 2- sulfydryl -5- methyl isophthalic acids, 3,4- thiadiazoles, 20 mol% KI, 0.3 mmol potassium peroxydisulfate, 1 ml DMSO adds in Schlenk pipes that stirring reaction 24 is small at room temperature under air ambient When.After question response terminates, separating-purifying can obtain 2-((5- methyl isophthalic acids, 3, the 4- thiadiazoles-2- bases) that 77 % separate yield Sulfenyl) -1- Phenyl ethyl ketones.Pass through1H、13C NMR identify the product.
1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0 Hz, 2 H), 7.60 (t, J = 11.2 Hz, 1 H), 7.48 (d, J = 8.0 Hz, 2 H), 4.95 (s, 2 H), 2.70 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 192.4, 165.2, 164.0, 135.1, 133.8, 128.7, 128.4, 41.5, 15.4.
Embodiment 23
By 1.0 mmol acetophenone, 0.5 mmol 2- mercaptopyridines, 20 mol% KI, 0.3 mmol persulfuric acid Potassium, 1 ml DMSO adds in Schlenk pipes stirring reaction 24 hours at room temperature under air ambient.After question response terminates, Separating-purifying can obtain 1- phenyl -2- (pyridine -2- bases sulfenyl) ethyl ketone that 74 % separate yield.Pass through1H、13C NMR are identified The product.
1H NMR (400 MHz, CDCl3) δ 8.36 – 8.29 (m, 1 H), 8.05 (dd, J = 7.5, 1.3 Hz, 2 H), 7.57 (t, J = 8.0 Hz, 1 H), 7.48 – 7.44 (m, 3 H), 7.26 (d, J = 5.6 Hz, 1 H), 6.98 – 6.93 (m, 1 H), 4.70 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 194.4, 156.9, 149.2, 136.1, 136.1, 133.3, 128.5, 128.5, 122.1, 119.7, 37.1.
As can be seen from the above-described embodiment, it is of the present invention to utilize different carbonyl complexs and heterocyclic thiol class chemical combination The method of the corresponding heterocycle thioether ketones derivant containing different substitution functional groups of thing synthesis has that reaction condition is gentle, catalyst It is cheap and easy to get and the advantages of prepare simple.In addition, this method also has the advantages that substrate applicability is wide, yield it is higher there is provided A kind of method for efficiently synthesizing the heterocycle thioether ketones derivant containing different substitution functional groups.
Embodiment described above only expresses the several embodiments of the present invention, and it describes more specific and detailed, but simultaneously Therefore the limitation to the scope of the claims of the present invention can not be interpreted as.It should be pointed out that for one of ordinary skill in the art For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention Protect scope.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.

Claims (8)

1. one kind has structural formula（I）Heterocycle thioether ketones derivant preparation method,
（I）
Characterized in that, including following step：
Carbonyl complex, heterocyclic thiol class compound, catalyst, oxidant and the organic solvent of reacting dose are taken in air atmosphere Under be placed in reaction vessel and mixed, reaction 24 hours is stirred at room temperature, that is, is made and contains different substitution functional groups accordingly Heterocycle thioether ketones derivant；
Wherein,
R1Be selected from hydrogen, methyl, phenyl, 4- fluorophenyls, 4- chlorphenyls, 3- chlorphenyls, 4- aminomethyl phenyls, 2,4- 3,5-dimethylphenyls, The groups such as 3,4- 3,5-dimethylphenyls, 2- thienyls, naphthyl；
R2It is selected from groups such as hydrogen, methyl, ethyl, phenyl；
Het is selected from heterocycles such as benzothiazole, benzoxazole, imidazoles, tetrazole, thiadiazoles, pyridines.
2. preparation method according to claim 1, it is characterised in that the carbonyl complex is to be selected from acetophenone, 4- Fluoro acetophenone, 4- methyl acetophenones, 2,4- dimethyl acetophenones, propiophenone, phenyl propyl ketone, 2- acetonaphthones, diphenylethan, 1- indenes Ketone, 1- (2- thienyls) -1- acetone, acetone, 1- butyraldehyde etc..
3. preparation method according to claim 1, it is characterised in that described heterocyclic thiol class compound is to be selected from 2- mercaptos Base benzothiazole, 2- mercaptobenzoxazoles, 5- dredge base -1- phenyl-tetrazole, 5- and dredge base -1- methyl-tetrazole, 2- sulfydryls -5- Methyl isophthalic acid, 3,4- thiadiazoles, 2- mercaptopyridines.
4. preparation method according to claim 1, it is characterised in that the catalyst is to be selected from iodine, cuprous iodide, iodate Potassium, sodium iodide, KBr, tetrabutyl sodium iodide, N- N-iodosuccinimides.
5. preparation method according to claim 1, it is characterised in that the organic solvent refer to ethyl acetate, dimethyl sulfoxide, N,N-dimethylformamide, 1,2- dichloroethanes, acetonitrile.
6. preparation method according to claim 1, it is characterised in that the oxidant is potassium peroxydisulfate, hydrogen peroxide, peroxide The tert-butyl alcohol, di-t-butyl peroxide or ammonium persulfate-sodium bisulfate.
7. preparation method according to claim 1, it is characterised in that the carbonyl complex and heterocyclic thiol class chemical combination The mol ratio of thing is 2：1.
8. preparation method according to claim 1, it is characterised in that the mol ratio of the carbonyl complex and oxidant For 1：0.6.
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CN107805232A (en) * 2017-10-31 2018-03-16 沅江华龙催化科技有限公司 A kind of synthetic method of the derivative containing thiomethylfuran
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CN111116436A (en) * 2020-01-17 2020-05-08 信阳师范学院 Synthetic method of thioether compound containing 1, 4-naphthoquinone structure
CN113735750A (en) * 2021-10-15 2021-12-03 常州大学 Method for preparing S-substituent-cysteine derivative by NBS (N-bromosuccinimide) at room temperature
CN114874157A (en) * 2022-06-20 2022-08-09 常州大学 Method for preparing 3- ((arylmercapto/alkylmercapto) methyl) oxirane
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