CN105017209B - A kind of 3 ketone compounds of polysubstituted dihydro-thiophene and its synthetic method - Google Patents

A kind of 3 ketone compounds of polysubstituted dihydro-thiophene and its synthetic method Download PDF

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CN105017209B
CN105017209B CN201510393628.7A CN201510393628A CN105017209B CN 105017209 B CN105017209 B CN 105017209B CN 201510393628 A CN201510393628 A CN 201510393628A CN 105017209 B CN105017209 B CN 105017209B
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thiophene
ketone compounds
thiocarbamide
alkynyl
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CN105017209A (en
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姜雪峰
张泽光
代志洪
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East China Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/32—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

The invention discloses a kind of synthetic method of 3 ketone compounds of polysubstituted dihydro-thiophene, is, in ethanol, under room temperature condition, with alkynyl diketone as reaction raw materials, to be implanted into reagent by sulphur atom of thiocarbamide, reaction obtains 3 ketone compounds of polysubstituted dihydro-thiophene.Advantage of the present invention includes：Reaction is efficient, and yield is higher；Thiocarbamide is as sulphur atom transfering reagent, cheap economical；Reaction condition only needs room temperature, without the need for strong acid and strong base；Without the need for the participation of catalyst；Reaction substrate is easily prepared.

Description

A kind of polysubstituted dihydro-thiophene -3- ketone compounds and its synthetic method
Technical field
The invention belongs to organic compound technique applied technical field, and in particular to the polysubstituted dihydro-thiophene -3- ketone of a class Class compound and its green synthesis method.
Background technology
Polysubstituted dihydro-thiophene -3- ketone structure not only can be to all kinds of thiophene, and thienone enters accommodating conversion, while its work Can build including the various natural products including biotin and its derivative for important organic synthesis intermediate.Therefore it is many Substituted-dihydro thiophene -3- ketone compounds have important synthesis meaning.But the existing synthesis with regard to this kind of compound is reported It is relatively fewer, and generally require by complicated raw material, or loaded down with trivial details synthesis step is realizing, cause its synthesis difficulty compared with Greatly.
Therefore a kind of simple, green, high efficiency low cost, the good, environmental friendliness of compatibility, mild condition and economic and practical are found The new method for building polysubstituted dihydro-thiophene -3- ketone compounds just seems and is even more important.The present inventor is it has been investigated that alkynyl Diketone is the unique compounds that a class has how electrophilic site, and the thinking that combination atom implantation is reacted conveniently can build a series of miscellaneous Cycle compound.In consideration of it, the present invention is devised with alkynyl diketone and thiocarbamide prepares polysubstituted two by sulphur atom implantation as raw material The reaction of hydrogen thiophene -3- ketone compounds.
The content of the invention
Instant invention overcomes the shortcomings of conventional construction method, innovatively realize that one kind efficiently builds polysubstituted dihydro The method of thiophene -3- ketone compounds.The present invention is implanted into reagent by sulphur atom of thiocarbamide with alkynyl diketone as raw material, in reaction Corresponding conversion is have effectively achieved in solvent under room temperature condition, prepare polysubstituted dihydro-thiophene as shown in formula (II)- 3- ketone compounds.
Wherein, the course of reaction is as shown in formulas below.
In above reaction equation,
Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle.R is straight chained alkyl, branched paraffin or aryl.
Preferably, Ar be phenyl, 4- aminomethyl phenyls, 4- methoxyphenyls, 4- phenyls, 4- fluorophenyls, 4- chlorphenyls, 4- bromophenyls, 4- iodophenyls, 2- naphthyls, 2- thienyls, 2- benzothienyls, 2- furyls, 4- nitrobenzophenones；Preferably, R is Phenyl, 4- aminomethyl phenyls, normal-butyl, cyclopropyl.
In the present invention, Ar, R include but are not limited to above-mentioned group.
Such as above reaction equation, of the invention by the use of the alkynyl diketone shown in formula (I) as initiation material, former as sulphur using thiocarbamide Son implantation reagent, is reacted in reaction dissolvent, is synthesized the polysubstituted dihydro-thiophene -3- ketone chemical combination as shown in formula (II) Thing.
In the present invention, the mole dosage ratio of alkynyl diketone and thiocarbamide of the initiation material as shown in formula (I) is 1:1- 1:15.Preferably, both usage ratios are 1:1.
In the present invention, the reaction dissolvent be methyl alcohol, ethanol, isopropanol, the tert-butyl alcohol, water, DMSO, DMF, DMA, acetonitrile, Any one or any combination of acetone, tetrahydrofuran, toluene, dichloromethane, 1,2- dichloroethanes, chloroform.Preferably, it is described Solvent is ethanol.
Synthetic reaction of the present invention is comprised the following steps：Alkynyl diketone, thiocarbamide, solvent are added in reaction vessel, in nitrogen In atmosphere, react in room temperature to stirred at reflux condition, obtain the polysubstituted dihydro-thiophene -3- ketone chemical combination shown in formula (II) Thing.Preferably, step is reacted at ambient temperature.
In an instantiation, synthetic reaction of the present invention is, in reaction bulb A, to add alkynyl dione compounds (X Mmol), thiocarbamide (Y mmol), solvent (V mL), reaction system stir 4-24 hours in nitrogen atmosphere, at ambient temperature. Monitoring reaction process.After completion of the reaction, direct Jing column chromatography for separation obtains the polysubstituted dihydro thiophene shown in target product formula (II) Fen -3- ketone compounds.
The invention allows for prepare according to above-mentioned synthetic method of the invention as shown in formula (II) polysubstituted two Hydrogen thiophene -3- ketone compounds,
Wherein, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle.R is straight chained alkyl, branched paraffin or aryl.
Preferably, Ar be phenyl, 4- aminomethyl phenyls, 4- methoxyphenyls, 4- phenyls, 4- fluorophenyls, 4- chlorphenyls, 4- bromophenyls, 4- iodophenyls, 2- naphthyls, 2- thienyls, 2- benzothienyls, 2- furyls, 4- nitrobenzophenones；Preferably, R is Phenyl, 4- aminomethyl phenyls, normal-butyl, cyclopropyl.
The invention allows for new alkynyl dione compounds, shown in its structural formula such as formula (II),
Wherein, Ar is phenyl, 4- aminomethyl phenyls, 4- methoxyphenyls, 4- phenyls, 4- fluorophenyls, 4- chlorphenyls, 4- Bromophenyl, 4- iodophenyls, 2- naphthyls, 2- thienyls, 2- benzothienyls, 2- furyls, 4- nitrobenzophenones.R is phenyl, 4- first Base phenyl, normal-butyl, cyclopropyl.
The present invention has advantages below：Reaction is efficient, and yield is higher；Thiocarbamide is as sulphur atom transfering reagent, cheap economical； Reaction condition only needs room temperature, without the need for strong acid and strong base；Without the need for the participation of catalyst；Reaction substrate is easily prepared.The present invention is with easy The alkynyl diketone of preparation is reaction raw materials, is implanted into reagent as sulphur atom with thiocarbamide, without the need for metal catalytic, directly carries out sulphur atom Implantation reaction obtains polysubstituted dihydro-thiophene -3- ketone compounds.Operation is simple, and reaction condition is extremely gentle, is adapted to big Technical scale metaplasia is produced.
Specific embodiment
With reference to specific examples below, the present invention is described in further detail, and the content of protecting of the present invention is not limited to In following examples.Under the spirit and scope without departing substantially from inventive concept, those skilled in the art it is conceivable that change and excellent Point is all included in the present invention, and with appending claims as protection domain.Implement the present invention process, condition, Reagent, experimental technique etc., in addition to the following content for specially referring to, are the universal knowledege and common knowledge of this area, this It is bright that content is not particularly limited.Data given by following examples include concrete operations and reaction condition and product.Product is pure Degree is identified by nuclear-magnetism.
The synthetic reaction of the polysubstituted dihydro-thiophene -3- ketone compounds of the present invention, comprises the following steps：In reaction vessel Alkynyl diketone, thiocarbamide, solvent are added, in nitrogen atmosphere, is reacted in room temperature to stirred at reflux condition, is obtained shown in formula (II) Polysubstituted dihydro-thiophene -3- ketone compounds.Jing column chromatography for separation obtains purpose product again.
Wherein, polysubstituted dihydro-thiophene -3- ketone compounds as shown in table 1, are and are synthesized by the inventive method The product for arriving, there is not yet open source literature discloses these compounds.As dihydro-thiophene -3- ketone compounds can be used as important Organic synthesis intermediate converted to the various natural products including including biotin and its derivative, therefore in table These new dihydro-thiophene -3- ketone compounds can be used to synthesize all kinds of brand-new biotins containing different substituents group Deng natural products analog, so as to realize various sex modification of these natural products, and then probe into the aspects such as its pharmaceutically active Property and rule.
New dihydro-thiophene -3- the ketone compounds of 1 present invention of table
Embodiment 1
The synthesis of compound 2a：
Alkynyl diketone 1a (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2a after direct column chromatography for separation, is obtained.Yield：84%；1H NMR(400MHz,CDCl3)δ7.75–7.69 (m,2H),7.62–7.54(m,3H),7.53–7.45(m,2H),7.39–7.29(m,3H),6.48(s,1H),4.10(s,1H) ；13C NMR(101MHz,CDCl3)δ203.4,176.7,138.8,132.9,132.3,129.1,128.8,128.6,126.9, 125.4,112.7,91.9；IR(film)2924,1671,1626,1519,1465,1389,1274,1178,988,934,839, 791,749,713,660cm-1.HRMS(EI)Calcd for C16H12O2S 268.0558,Found 268.0556。
Embodiment 2
The synthesis of compound 2b：
Alkynyl diketone 1b (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2b after direct column chromatography for separation, is obtained.Yield：86%；1H NMR(400MHz,CDCl3)δ7.76–7.65 (m, 2H), 7.60-7.52 (m, 1H), 7.52-7.42 (m, 4H), 7.14 (d, J=8.1Hz, 2H), 6.45 (s, 1H), 4.59 (s, 1H),2.33(s,3H)；13C NMR(101MHz,CDCl3)δ203.6,176.7,138.6,135.9,132.8,132.3, 129.2,129.0,126.9,125.3,112.7,92.2,21.1；IR(film)2927,1675,1621,1525,1483, 1374,1225,1134,1092,1032,795,760,719,668cm-1.HRMS(EI)Calcd for C17H14O2S 282.0715,Found 282.0716。
Embodiment 3
The synthesis of compound 2c：
Alkynyl diketone 1c (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2c after direct column chromatography for separation, is obtained.Yield：93%；1H NMR(400MHz,CDCl3)δ7.70(d,J =7.9Hz, 2H), 7.62-7.41 (m, 5H), 6.86 (d, J=8.7Hz, 2H), 6.44 (s, 1H), 4.19 (s, 1H), 3.78 (s, 3H)；13C NMR(101MHz,CDCl3)δ203.5,176.4,159.8,132.8,132.3,130.8,129.0,126.9, 126.9,113.9,112.7,92.2,55.3；IR(film)3366,1661,1607,1539,1510,1487,1446,1304, 1250,1174,1091,1031,916,821,768,733,684cm-1.HRMS(EI)Calcd for C16H11O2S 298.0664,Found 298.0663。
Embodiment 4
The synthesis of compound 2d：
Alkynyl diketone 1d (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2d after direct column chromatography for separation, is obtained.Yield：91%；1H NMR(300MHz,DMSO)δ8.08(s, 1H),7.97–7.86(m,2H),7.71–7.62(m,5H),7.61–7.54(m,4H),7.51–7.42(m,2H),7.41–7.32 (m,1H),6.87(s,1H)；13C NMR(101MHz,DMSO)δ202.4,174.1,140.1,139.6,139.3,132.9, 132.2,129.3,129.0,127.6,126.9,126.7,126.0,113.4,92.8；IR(film)1674,1620,1597, 1525,1483,1374,1227,1155,784,573cm-1.HRMS(EI)Calcd for C22H16O2S 344.0871,Found 344.0873。
Embodiment 5
The synthesis of compound 2e：
Alkynyl diketone 1e (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2e after direct column chromatography for separation, is obtained.Yield：81%；1H NMR(400MHz,Acetone)δ7.92– 7.84(m,2H),7.70–7.61(m,3H),7.61–7.54(m,2H),7.20–7.09(m,2H),6.86(s,1H),6.63(s, 1H)；13C NMR(101MHz,Acetone)δ202.4,174.8,163.3(d,1JCF=245.5Hz), 137.0 (d,4JCF= 3.0Hz),133.5,133.5,130.0,128.7(d,3JCF=8.6Hz), 127.6,115.8 (d,2JCF=21.9Hz), 113.7,92.9；19F NMR(376MHz,Acetone)δ61.97(s,1F)；IR(film)2927,1673,1617,1523, 1479,1371,1204,1131,1090,1022,830,794,737,698,668cm-1.HRMS(EI)Calcd for C16H11FO2S 286.0464,Found 286.0463。
Embodiment 6
The synthesis of compound 2f：
Alkynyl diketone 1f (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2f after direct column chromatography for separation, is obtained.Yield：85%；1H NMR(400MHz,Acetone)δ7.88 (d, J=7.8Hz, 2H), 7.64 (t, J=8.8Hz, 3H), 7.58 (t, J=7.5Hz, 2H), 7.41 (d, J=8.4Hz, 2H), 6.91(s,1H),6.62(s,1H)；13C NMR(101MHz,Acetone)δ202.2,175.0,139.9,134.4,133.5, 133.5,130.1,129.1,128.4,127.6,113.8,92.9；IR(film)1597,1523,1464,1423,1374, 1263,1207,1169,1127,1091,1026,865,774,746,617cm-1.HRMS(EI)Calcd for C16H11ClO2S 302.0168,Found 302.0174。
Embodiment 7
The synthesis of compound 2g：
Alkynyl diketone 1g (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2g after direct column chromatography for separation, is obtained.Yield：76%；1H NMR(400MHz,DMSO)δ8.11(s, 1H), 7.89 (d, J=7.7Hz, 2H), 7.65 (t, J=7.1Hz, 1H), 7.57 (t, J=7.4Hz, 4H), 7.43 (d, J= 7.9Hz,2H),6.83(s,1H)；13C NMR(101MHz,DMSO)δ202.0,174.1,139.6,133.0,132.1,131.3, 129.3,127.7,126.9,121.4,113.2,92.2；IR(film)2929,1675,1622,1525,1472,1374, 1220,1092,1044,945,794,719,668cm-1.HRMS(EI)Calcd for C16H11BrO2S 345.9663,Found 345.9666。
Embodiment 8
The synthesis of compound 2h：
Alkynyl diketone 1h (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2h after direct column chromatography for separation, is obtained.Yield：78%；1H NMR(300MHz,DMSO)δ8.10(s, 1H), 7.94-7.84 (m, 2H), 7.73 (d, J=8.4Hz, 2H), 7.68-7.61 (m, 1H), 7.61-7.53 (m, 2H), 7.27 (d, J=8.5Hz, 2H), 6.84 (s, 1H)；13C NMR(101MHz,DMSO)δ202.0,174.1,140.0,137.1,132.9, 132.1,129.3,127.7,126.9,113.2,94.5,92.3；IR(film)2925,1648,1565,1522,1445, 1373,1336,1261,1202,1103,992,872,781,748,718,671cm-1.HRMS(EI)Calcd for C16H11IO2S 393.9524,Found393.9526。
Embodiment 9
The synthesis of compound 2i：
Alkynyl diketone 1i (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2i after direct column chromatography for separation, is obtained.Yield：73%；1H NMR(400MHz,DMSO)δ8.22(s, 1H), 8.11 (s, 1H), 8.01-7.95 (m, 1H), 7.93 (d, J=7.7Hz, 2H), 7.88 (d, J=8.5Hz, 2H), 7.65 (t, J=7.2Hz, 1H), 7.58 (t, J=7.5Hz, 2H), 7.52 (p, J=4.6Hz, 2H), 7.47 (d, J=8.7Hz, 1H), 6.93(s,1H)；13C NMR(126MHz,DMSO)δ202.4,174.2,137.5,132.8,132.6,132.4,132.2, 129.3,128.2,128.1,127.4,126.9,126.5,124.1,123.4,113.6,92.9；IR(film)2926,1666, 1618,1581,1528,1504,1459,1370,1312,1236,1197,1120,1085,1029,912,851,813,790, 758,723,691,666,629cm-1.HRMS(EI)Calcd for C20H14O2S 318.0715,Found 318.0716。
Embodiment 10
The synthesis of compound 2j：
Alkynyl diketone 1j (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2j after direct column chromatography for separation, is obtained.Yield：72%；1H NMR(400MHz,CDCl3)δ7.74–7.69 (m, 2H), 7.61-7.55 (m, 1H), 7.53-7.47 (m, 2H), 7.33 (dd, J=5.1,1.2Hz, 1H), 7.26-7.24 (m, 1H), 6.97 (dd, J=5.1,3.7Hz, 1H), 6.44 (s, 1H), 3.96 (s, 1H)；13C NMR(101MHz,CDCl3)δ 200.8,175.2,142.5,133.0,132.2,129.2,127.1,127.1,126.9,125.9,112.0,89.5；IR (film)2931,1671,1627,1514,1463,1389,1248,1172,1032,988,837,791,748,714,669cm-1.HRMS(EI)Calcd for C14H10O2S2274.0122,Found 274.0123。
Embodiment 11
The synthesis of compound 2k：
Alkynyl diketone 1k (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2k after direct column chromatography for separation, is obtained.Yield：56%；1H NMR(300MHz,DMSO)δ8.42(s, 1H),7.96–7.87(m,3H),7.86–7.78(m,1H),7.70–7.62(m,1H),7.62–7.54(m,2H),7.49(s, 1H),7.41–7.30(m,2H),6.87(s,1H)；13C NMR(101MHz,DMSO)δ200.1,173.1,144.8,139.2, 138.9,133.0,132.0,129.3,126.9,124.8,124.5,124.0,122.4,121.5,112.6,90.8；IR (film)1632,1525,1452,1372,1317,1266,1205,1144,1094,988,860,794,757,706,670cm-1.HRMS(EI)Calcd for C18H12O2S2324.0279,Found 324.0281。
Embodiment 12
The synthesis of compound 2l：
Alkynyl diketone 1l (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2l after direct column chromatography for separation, is obtained.Yield：76%；1H NMR(400MHz,DMSO)δ8.09(s, 1H), 7.85 (d, J=7.8Hz, 2H), 7.68-7.60 (m, 2H), 7.56 (t, J=7.4Hz, 2H), 6.85 (s, 1H), 6.44 (s,2H)；13C NMR(101MHz,DMSO)δ200.0,173.1,151.8,143.5,132.9,132.0,129.3,126.8, 113.6,110.5,108.1,88.2；IR(film)3321,1710,1513,1422,1344,1282,1201,1141,1016, 850,753,682,645cm-1.HRMS(EI)Calcd for C14H10O3S 258.0351,Found 258.0344。
Embodiment 13
The synthesis of compound 2m：
Alkynyl diketone 1m (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2m after direct column chromatography for separation, is obtained.Yield：55%；1H NMR(400MHz,DMSO)δ8.36(s, 1H), 8.23 (d, J=8.3Hz, 2H), 7.91 (d, J=7.8Hz, 2H), 7.74 (d, J=8.4Hz, 2H), 7.67 (t, J= 7.2Hz, 1H), 7.59 (t, J=7.5Hz, 2H), 6.91 (s, 1H)；13C NMR(101MHz,DMSO)δ201.6,174.4, 147.3,147.2,133.1,131.9,129.4,127.0,126.8,123.7,113.3,91.6；IR(film)2924,1673, 1628,1524,1464,1370,1275,1201,1131,1097,1069,850,815,779,672,633,602cm-1.HRMS (EI)Calcd for C16H11NO4S 313.0409,Found 313.0405。
Embodiment 14
The synthesis of compound 2n：
Alkynyl diketone 1n (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2n after direct column chromatography for separation, is obtained.Yield：90%；1H NMR(400MHz,Acetone)δ7.83– 7.72(m,2H),7.67–7.57(m,2H),7.41–7.34(m,4H),7.34–7.28(m,1H),6.73(s,1H),6.58(s, 1H),2.42(s,3H)；13C NMR(101MHz,Acetone)δ202.6,174.8,144.3,141.1,130.8,130.6, 129.0,128.9,127.6,126.4,113.0,93.3,21.5；IR(film)3294,1674,1620,1406,1250, 1108,1040,847,758,716,664cm-1.HRMS(EI)Calcd for C17H14O2S 282.0715,Found 282.0717。
Embodiment 15
The synthesis of compound 2o：
Alkynyl diketone 1o (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2o after direct column chromatography for separation, is obtained.Yield：62%；1H NMR(400MHz,Acetone)δ7.57– 7.51 (m, 2H), 7.39-7.26 (m, 3H), 6.56 (s, 1H), 5.92 (s, 1H), 2.75 (t, J=7.6Hz, 2H), 1.75- 1.63 (m, 2H), 1.52-1.39 (m, 2H), 0.95 (t, J=7.4Hz, 3H)；13C NMR(101MHz,Acetone)δ202.9, 183.2,141.1,129.0,128.9,126.3,116.1,93.3,34.5,31.1,22.7,13.9；IR(film)2924, 1659,1634,1527,1462,1373,1267,1211,1142,1097,864,795,758,705,673cm-1.HRMS(EI) Calcd for C14H16O2S 248.0871,Found 248.0869。
Embodiment 16
The synthesis of compound 2p：
Alkynyl diketone 1p (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are added in reaction tube, so After adding reaction dissolvent ethanol (2mL) afterwards, in nitrogen atmosphere, stir 6 hours at ambient temperature.Monitored by thin-layer chromatography After reaction terminates, product 2p after direct column chromatography for separation, is obtained.Yield：69%；1H NMR(400MHz,DMSO)δ7.77(s, 1H),7.43–7.37(m,2H),7.37–7.31(m,2H),7.31–7.26(m,1H),6.03(s,1H),2.28–2.13(m, 1H),1.32–1.15(m,2H),1.11–0.95(m,2H)；13C NMR(101MHz,DMSO)δ201.3,186.2,140.2, 128.2,128.0,125.2,112.6,92.4,16.0,11.7,11.3；IR(film)3088,1678,1546,1451,1285, 1198,1115,988,865,807,752,696,583cm-1.HRMS(EI)Calcd for C13H12O2S 232.0558, Found232.0558。

Claims (5)

1. a kind of synthetic method of polysubstituted dihydro-thiophene -3- ketone compounds, it is characterised in that former by reaction of alkynyl diketone Material, with thiocarbamide as sulphur atom transfering reagent, the reaction in reaction dissolvent obtains the polysubstituted dihydro-thiophene -3- as shown in formula (II) Ketone compounds；The course of reaction is as shown in reaction equation；
Wherein, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle；R is straight chained alkyl, branched paraffin or aryl.
2. the synthetic method of polysubstituted dihydro-thiophene -3- ketone compounds as claimed in claim 1, it is characterised in that described Solvent is methyl alcohol, ethanol, isopropanol, the tert-butyl alcohol, water, DMSO, DMF, DMA, acetonitrile, acetone, tetrahydrofuran, toluene, dichloromethane Any one or any combination of alkane, 1,2- dichloroethanes, chloroform.
3. the synthetic method of polysubstituted dihydro-thiophene -3- ketone compounds as claimed in claim 1, it is characterised in that described In reaction, the mole dosage ratio of the alkynyl diketone and thiocarbamide is 1:1-1:15.
4. the synthetic method of polysubstituted dihydro-thiophene -3- ketone compounds as claimed in claim 1, it is characterised in that described Reaction is comprised the following steps：Alkynyl diketone, thiocarbamide, solvent are added in reaction vessel, in nitrogen atmosphere, in room temperature to backflow Under the conditions of stirring reaction, obtain the polysubstituted dihydro-thiophene -3- ketone compounds shown in formula (II).
5. the synthetic method of polysubstituted dihydro-thiophene -3- ketone compounds as claimed in claim 4, it is characterised in that described Step is carried out at room temperature.
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