CN105017209A - Polysubstituted dihydrothiophene-3-one compound and synthetic method therefor - Google Patents

Polysubstituted dihydrothiophene-3-one compound and synthetic method therefor Download PDF

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CN105017209A
CN105017209A CN201510393628.7A CN201510393628A CN105017209A CN 105017209 A CN105017209 A CN 105017209A CN 201510393628 A CN201510393628 A CN 201510393628A CN 105017209 A CN105017209 A CN 105017209A
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reaction
thiophene
phenyl
ketone compounds
polysubstituted
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CN105017209B (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 synthetic method of a polysubstituted dihydrothiophene-3-one compound. The synthetic method comprises: carrying out a reaction in methanol under a room temperature condition to obtain the polysubstituted dihydrothiophene-3-one compound by taking alkynyl diketone as a reaction raw material and thiourea as a sulfur atom implanting reagent. The synthetic method disclosed by the invention has the advantages of efficient reaction and relatively high yield; thiourea taken as a sulfur atom transfer reagent is low in price and economical; the reaction condition only needs room temperature without strong acids and strong alkali; no catalysts participate in; and reaction substrates are easily prepared.

Description

A kind of polysubstituted dihydro-thiophene-3-ketone compounds and synthetic method thereof
Technical field
The invention belongs to organic compound process application technical field, be specifically related to the polysubstituted dihydro-thiophene of a class-3-ketone compounds and green synthesis method thereof.
Background technology
Polysubstituted dihydro-thiophene-3-ketone structure not only can to all kinds of thiophene, and thienone carries out convenience and transforms, and it can build the multiple natural product comprising vitamin H and derivative thereof as important organic synthesis intermediate simultaneously.Therefore polysubstituted dihydro-thiophene-3-ketone compounds has important synthesis meaning.But the existing report of the synthesis about this compounds is relatively less, and often need the raw material by complexity, or loaded down with trivial details synthesis step realizes, cause its synthesis difficulty larger.
Therefore find that a kind of simple, green, high efficiency low cost, compatibility are good, the novel method of environmental friendliness, mild condition and the economic and practical polysubstituted dihydro-thiophene of structure-3-ketone compounds just seems and be even more important.The present inventor finds that alkynyl diketone is the unique compounds that a class has how close potential point after deliberation, and the thinking that combination atom implants reaction can conveniently build a series of heterogeneous ring compound.Given this, the present invention devises with alkynyl diketone and thiocarbamide as the reaction of the polysubstituted dihydro-thiophene-3-ketone compounds of preparation to be implanted by raw material by sulphur atom.
Summary of the invention
Instant invention overcomes the shortcomings of conventional construction method, realize the method for the polysubstituted dihydro-thiophene of a kind of efficient structure-3-ketone compounds innovatively.The present invention for raw material with alkynyl diketone, is that sulphur atom implants reagent with thiocarbamide, in reaction solvent, have effectively achieved corresponding conversion under room temperature condition, prepares such as formula the polysubstituted dihydro-thiophene-3-ketone compounds shown in (II).
Wherein, described reaction process is as shown in following reaction formula.
In above reaction formula,
Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle.R is straight chained alkyl, branched paraffin or aryl.
Preferably, Ar is phenyl, 4-aminomethyl phenyl, 4-p-methoxy-phenyl, 4-phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 4-bromophenyl, 4-iodophenyl, 2-naphthyl, 2-thienyl, 2-benzothienyl, 2-furyl, 4-nitrophenyl; Preferably, R is phenyl, 4-aminomethyl phenyl, normal-butyl, cyclopropyl.
In the present invention, Ar, R include but are not limited to above-mentioned group.
As above reaction formula, the present invention utilizes the alkynyl diketone shown in formula (I) as starting raw material, implant reagent using thiocarbamide as sulphur atom, react in reaction solvent, synthesize such as formula the polysubstituted dihydro-thiophene-3-ketone compounds shown in (II).
In the present invention, described starting raw material is 1:1-1:15 such as formula the mole dosage ratio of the alkynyl diketone shown in (I) and thiocarbamide.Preferably, both usage ratio are 1:1.
In the present invention, described reaction solvent is any one or arbitrary combination of methyl alcohol, ethanol, Virahol, the trimethyl carbinol, water, DMSO, DMF, DMA, acetonitrile, acetone, tetrahydrofuran (THF), toluene, methylene dichloride, 1,2-ethylene dichloride, chloroform.Preferably, described solvent is ethanol.
Building-up reactions of the present invention comprises the following steps: in reaction vessel, add alkynyl diketone, thiocarbamide, solvent, in nitrogen atmosphere, reacts to stirred at reflux condition in room temperature, obtains the polysubstituted dihydro-thiophene-3-ketone compounds shown in formula (II).Preferably, step is reacted at ambient temperature.
In a specific examples, building-up reactions of the present invention is in reaction flask A, adds alkynyl dione compounds (Xmmol), thiocarbamide (Y mmol), solvent (V mL), reaction system, in nitrogen atmosphere, stirs 4-24 hour at ambient temperature.Monitoring reaction process.After completion of the reaction, directly the polysubstituted dihydro-thiophene-3-ketone compounds shown in target product formula (II) is obtained through column chromatography for separation.
The invention allows for according to the above-mentioned synthetic method of the present invention prepare such as formula the polysubstituted dihydro-thiophene-3-ketone compounds shown in (II),
Wherein, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle.R is straight chained alkyl, branched paraffin or aryl.
Preferably, Ar is phenyl, 4-aminomethyl phenyl, 4-p-methoxy-phenyl, 4-phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 4-bromophenyl, 4-iodophenyl, 2-naphthyl, 2-thienyl, 2-benzothienyl, 2-furyl, 4-nitrophenyl; Preferably, R is phenyl, 4-aminomethyl phenyl, normal-butyl, cyclopropyl.
The invention allows for new alkynyl dione compounds, its structural formula such as formula shown in (II),
Wherein, Ar is phenyl, 4-aminomethyl phenyl, 4-p-methoxy-phenyl, 4-phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 4-bromophenyl, 4-iodophenyl, 2-naphthyl, 2-thienyl, 2-benzothienyl, 2-furyl, 4-nitrophenyl.R is phenyl, 4-aminomethyl phenyl, normal-butyl, cyclopropyl.
The present invention has the following advantages: reaction is efficient, and yield is higher; Thiocarbamide is as sulphur atom transfering reagent, cheap economical; Reaction conditions only needs room temperature, without the need to strong acid and strong base; Without the need to the participation of catalyzer; Reaction substrate is easily prepared.The present invention for reaction raw materials, implants reagent with thiocarbamide as sulphur atom with the alkynyl diketone easily prepared, and without the need to metal catalytic, directly carries out sulphur atom implantation and is obtained by reacting polysubstituted dihydro-thiophene-3-ketone compounds.Operation is simple, and reaction conditions is extremely gentle, is applicable to large-scale industrial production.
Embodiment
In conjunction with following specific embodiment, the present invention is described in further detail, and protection content of the present invention is not limited to following examples.Under the spirit and scope not deviating from inventive concept, the change that those skilled in the art can expect and advantage are all included in the present invention, and are protection domain with appending claims.Implement process of the present invention, condition, reagent, experimental technique etc., except the following content mentioned specially, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.Data given by following examples comprise concrete operations and reaction conditions and product.Product purity is identified by nuclear-magnetism.
The building-up reactions of the polysubstituted dihydro-thiophene of the present invention-3-ketone compounds, comprise the following steps: in reaction vessel, add alkynyl diketone, thiocarbamide, solvent, in nitrogen atmosphere, react to stirred at reflux condition in room temperature, obtain the polysubstituted dihydro-thiophene-3-ketone compounds shown in formula (II).Object product is obtained again through column chromatography for separation.
Wherein, polysubstituted dihydro-thiophene-3-ketone compounds as shown in table 1, is and synthesizes by the inventive method the product obtained, there is not yet open source literature and disclose these compounds.Because dihydro-thiophene-3-ketone compounds can transform to the multiple natural product comprising vitamin H and derivative thereof as important organic synthesis intermediate, therefore these the novel dihydro-thiophene-3-ketone compounds in table can be used for synthesizing the natural product analogues such as all kinds of vitamin Hs containing different substituents group completely newly, thus the diversity realizing these natural products is modified, and then probe into the characer and laws of the aspects such as its pharmaceutical activity.
Table 1 new dihydro-thiophene-3-ketone compounds of the present invention
Embodiment 1
The synthesis of compound 2a:
Alkynyl diketone 1a (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2a.Yield: 84%; 1h NMR (400MHz, CDCl 3) δ 7.75 – 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, CDCl 3) δ 203.4,176.7,138.8,132.9,132.3,129.1,128.8,128.6,126.9,125.4,112.7,91.9; IR (film) 2924,1671,1626,1519,1465,1389,1274,1178,988,934,839,791,749,713,660cm -1.HRMS (EI) Calcd for C 16h 12o 2s 268.0558, Found 268.0556.
Embodiment 2
The synthesis of compound 2b:
Alkynyl diketone 1b (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2b.Yield: 86%; 1h NMR (400MHz, CDCl 3) δ 7.76 – 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, CDCl 3) δ 203.6,176.7,138.6,135.9,132.8,132.3,129.2,129.0,126.9,125.3,112.7,92.2,21.1; IR (film) 2927,1675,1621,1525,1483,1374,1225,1134,1092,1032,795,760,719,668cm -1.HRMS (EI) Calcd for C 17h 14o 2s 282.0715, Found 282.0716.
Embodiment 3
The synthesis of compound 2c:
Alkynyl diketone 1c (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2c.Yield: 93%; 1h NMR (400MHz, CDCl 3) δ 7.70 (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, CDCl 3) δ 203.5,176.4,159.8,132.8,132.3,130.8,129.0,126.9,126.9,113.9,112.7,92.2,55.3; IR (film) 3366,1661,1607,1539,1510,1487,1446,1304,1250,1174,1091,1031,916,821,768,733,684cm -1.HRMS (EI) Calcd for C 16h 11o 2s 298.0664, Found 298.0663.
Embodiment 4
The synthesis of compound 2d:
Alkynyl diketone 1d (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2d.Yield: 91%; 1h NMR (300MHz, DMSO) δ 8.08 (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) δ 202.4,174.1,140.1,139.6,139.3,132.9,132.2,129.3,129.0,127.6,126.9,126.7,126.0,113.4,92.8; IR (film) 1674,1620,1597,1525,1483,1374,1227,1155,784,573cm -1.HRMS (EI) Calcd for C 22h 16o 2s 344.0871, Found 344.0873.
Embodiment 5
The synthesis of compound 2e:
Alkynyl diketone 1e (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2e.Yield: 81%; 1h NMR (400MHz, Acetone) δ 7.92 – 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) δ 202.4,174.8,163.3 (d, 1j cF=245.5Hz), 137.0 (d, 4j cF=3.0Hz), 133.5,133.5,130.0,128.7 (d, 3j cF=8.6Hz), 127.6,115.8 (d, 2j cF=21.9Hz), 113.7,92.9; 19fNMR (376MHz, Acetone) δ 61.97 (s, 1F); IR (film) 2927,1673,1617,1523,1479,1371,1204,1131,1090,1022,830,794,737,698,668cm -1.HRMS (EI) Calcd for C 16h 11fO 2s 286.0464, Found 286.0463.
Embodiment 6
The synthesis of compound 2f:
Alkynyl diketone 1f (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2f.Yield: 85%; 1h NMR (400MHz, Acetone) δ 7.88 (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) δ 202.2,175.0,139.9,134.4,133.5,133.5,130.1,129.1,128.4,127.6,113.8,92.9; IR (film) 1597,1523,1464,1423,1374,1263,1207,1169,1127,1091,1026,865,774,746,617cm -1.HRMS (EI) Calcd for C 16h 11clO 2s 302.0168, Found 302.0174.
Embodiment 7
The synthesis of compound 2g:
Alkynyl diketone 1g (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2g.Yield: 76%; 1h NMR (400MHz, DMSO) δ 8.11 (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) δ 202.0,174.1,139.6,133.0,132.1,131.3,129.3,127.7,126.9,121.4,113.2,92.2; IR (film) 2929,1675,1622,1525,1472,1374,1220,1092,1044,945,794,719,668cm -1.HRMS (EI) Calcd for C 16h 11brO 2s 345.9663, Found 345.9666.
Embodiment 8
The synthesis of compound 2h:
Alkynyl diketone 1h (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2h.Yield: 78%; 1h NMR (300MHz, DMSO) δ 8.10 (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) δ 202.0,174.1,140.0,137.1,132.9,132.1,129.3,127.7,126.9,113.2,94.5,92.3; IR (film) 2925,1648,1565,1522,1445,1373,1336,1261,1202,1103,992,872,781,748,718,671cm -1.HRMS (EI) Calcd for C 16h 11iO 2s 393.9524, Found393.9526.
Embodiment 9
The synthesis of compound 2i:
Alkynyl diketone 1i (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2i.Yield: 73%; 1h NMR (400MHz, DMSO) δ 8.22 (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) δ 202.4,174.2,137.5,132.8,132.6,132.4,132.2,129.3,128.2,128.1,127.4,126.9,126.5,124.1,123.4,113.6,92.9; 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 C 20h 14o 2s 318.0715, Found 318.0716.
Embodiment 10
The synthesis of compound 2j:
Alkynyl diketone 1j (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2j.Yield: 72%; 1h NMR (400MHz, CDCl 3) δ 7.74 – 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, CDCl 3) 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) Calcdfor C 14h 10o 2s 2274.0122, Found 274.0123.
Embodiment 11
The synthesis of compound 2k:
Alkynyl diketone 1k (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2k.Yield: 56%; 1h NMR (300MHz, DMSO) δ 8.42 (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) δ 200.1,173.1,144.8,139.2,138.9,133.0,132.0,129.3,126.9,124.8,124.5,124.0,122.4,121.5,112.6,90.8; IR (film) 1632,1525,1452,1372,1317,1266,1205,1144,1094,988,860,794,757,706,670cm -1.HRMS (EI) Calcdfor C 18h 12o 2s 2324.0279, Found 324.0281.
Embodiment 12
The synthesis of compound 2l:
Alkynyl diketone 1l (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2l.Yield: 76%; 1h NMR (400MHz, DMSO) δ 8.09 (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) δ 200.0,173.1,151.8,143.5,132.9,132.0,129.3,126.8,113.6,110.5,108.1,88.2; IR (film) 3321,1710,1513,1422,1344,1282,1201,1141,1016,850,753,682,645cm -1.HRMS (EI) Calcd for C 14h 10o 3s 258.0351, Found 258.0344.
Embodiment 13
The synthesis of compound 2m:
Alkynyl diketone 1m (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2m.Yield: 55%; 1h NMR (400MHz, DMSO) δ 8.36 (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) δ 201.6,174.4,147.3,147.2,133.1,131.9,129.4,127.0,126.8,123.7,113.3,91.6; IR (film) 2924,1673,1628,1524,1464,1370,1275,1201,1131,1097,1069,850,815,779,672,633,602cm -1.HRMS (EI) Calcd forC 16h 11nO 4s 313.0409, Found 313.0405.
Embodiment 14
The synthesis of compound 2n:
Alkynyl diketone 1n (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2n.Yield: 90%; 1h NMR (400MHz, Acetone) δ 7.83 – 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) δ 202.6,174.8,144.3,141.1,130.8,130.6,129.0,128.9,127.6,126.4,113.0,93.3,21.5; IR (film) 3294,1674,1620,1406,1250,1108,1040,847,758,716,664cm -1.HRMS (EI) Calcd for C 17h 14o 2s 282.0715, Found 282.0717.
Embodiment 15
The synthesis of compound 2o:
Alkynyl diketone 1o (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2o.Yield: 62%; 1h NMR (400MHz, Acetone) δ 7.57 – 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) δ 202.9,183.2,141.1,129.0,128.9,126.3,116.1,93.3,34.5,31.1,22.7,13.9; IR (film) 2924,1659,1634,1527,1462,1373,1267,1211,1142,1097,864,795,758,705,673cm -1.HRMS (EI) Calcd forC 14h 16o 2s 248.0871, Found 248.0869.
Embodiment 16
The synthesis of compound 2p:
Alkynyl diketone 1p (0.2mmol, 1equiv.) and thiocarbamide (0.2mmol, 1equiv.) are joined in reaction tubes, after then adding reaction solvent ethanol (2mL), in nitrogen atmosphere, stirs 6 hours at ambient temperature.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2p.Yield: 69%; 1h NMR (400MHz, DMSO) δ 7.77 (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) δ 201.3,186.2,140.2,128.2,128.0,125.2,112.6,92.4,16.0,11.7,11.3; IR (film) 3088,1678,1546,1451,1285,1198,1115,988,865,807,752,696,583cm -1.HRMS (EI) Calcd for C 13h 12o 2s 232.0558, Found232.0558.

Claims (7)

1. the synthetic method of a polysubstituted dihydro-thiophene-3-ketone compounds, it is characterized in that, with alkynyl diketone for reaction raw materials, be sulphur atom transfering reagent with thiocarbamide, be obtained by reacting such as formula the polysubstituted dihydro-thiophene-3-ketone compounds shown in (II) in reaction solvent; Described reaction process is as shown in reaction formula;
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 characterized in that, described solvent is any one or arbitrary combination of methyl alcohol, ethanol, Virahol, the trimethyl carbinol, water, DMSO, DMF, DMA, acetonitrile, acetone, tetrahydrofuran (THF), toluene, methylene dichloride, 1,2-ethylene dichloride, chloroform.
3. the synthetic method of polysubstituted dihydro-thiophene-3-ketone compounds as claimed in claim 1, is characterized in that, in described reaction, the mole dosage ratio of described 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 characterized in that, described reaction comprises the following steps: in reaction vessel, add alkynyl diketone, thiocarbamide, solvent, in nitrogen atmosphere, react to stirred at reflux condition in room temperature, 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 characterized in that, described step is at room temperature carried out.
6. the polysubstituted dihydro-thiophene-3-ketone compounds of method synthesis as described in any one of Claims 1 to 5, it is characterized in that, its structure is such as formula shown in (II):
Wherein, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle; R is straight chained alkyl, branched paraffin or aryl.
7. a polysubstituted dihydro-thiophene-3-ketone compounds, is characterized in that, its structure is such as formula shown in (II):
Wherein, Ar is phenyl, 4-aminomethyl phenyl, 4-p-methoxy-phenyl, 4-phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 4-bromophenyl, 4-iodophenyl, 2-naphthyl, 2-thienyl, 2-benzothienyl, 2-furyl, 4-nitrophenyl; R is phenyl, 4-aminomethyl phenyl, normal-butyl, cyclopropyl.
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Citations (2)

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Publication number Priority date Publication date Assignee Title
WO2001085664A2 (en) * 2000-05-10 2001-11-15 Princeton University Compounds and methods for regulating bacterial growth and pathogenesis
CN104177241A (en) * 2014-06-23 2014-12-03 华东师范大学 Alkynyl diketone compound and synthetic method thereof

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WO2001085664A2 (en) * 2000-05-10 2001-11-15 Princeton University Compounds and methods for regulating bacterial growth and pathogenesis
CN104177241A (en) * 2014-06-23 2014-12-03 华东师范大学 Alkynyl diketone compound and synthetic method thereof

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