CN106083690A - 一种多取代3‑亚甲基吲哚酮的制备方法 - Google Patents
一种多取代3‑亚甲基吲哚酮的制备方法 Download PDFInfo
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- 229910052801 chlorine Inorganic materials 0.000 claims description 6
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- 239000003054 catalyst Substances 0.000 claims description 3
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- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
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- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000011630 iodine Substances 0.000 claims 1
- 238000010189 synthetic method Methods 0.000 abstract description 8
- 238000004440 column chromatography Methods 0.000 abstract description 3
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
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- MUTCAPXLKRYEPR-ITWZMISCSA-N methyl (e,3r,5s)-7-[4-bromo-2,3-bis(4-fluorophenyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyhept-6-enoate Chemical compound COC(=O)C[C@H](O)C[C@H](O)\C=C\N1C(C(C)C)=C(Br)C(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 MUTCAPXLKRYEPR-ITWZMISCSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
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- XEYMRFSIZINEEF-AATRIKPKSA-N CC/C=C(\C(C)(C)O)/N Chemical compound CC/C=C(\C(C)(C)O)/N XEYMRFSIZINEEF-AATRIKPKSA-N 0.000 description 1
- KVMXTGQGDYPPRC-JXMROGBWSA-N CCOC(/C=C(\c1cc(C)ccc1N1)/C1=O)=O Chemical compound CCOC(/C=C(\c1cc(C)ccc1N1)/C1=O)=O KVMXTGQGDYPPRC-JXMROGBWSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
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- DORMTBIPKNPJPY-UHFFFAOYSA-N acetic acid;iodobenzene Chemical compound CC(O)=O.IC1=CC=CC=C1 DORMTBIPKNPJPY-UHFFFAOYSA-N 0.000 description 1
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- 125000001246 bromo group Chemical group Br* 0.000 description 1
- GUPWNYUKYICHQX-UHFFFAOYSA-N carbonobromidic acid Chemical compound OC(Br)=O GUPWNYUKYICHQX-UHFFFAOYSA-N 0.000 description 1
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- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
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Abstract
本发明公开了一种多取代3‑亚甲基吲哚酮的制备方法，属于有机合成化学技术领域。所述方法为：向反应器中，加入取代靛红和异氰基乙酸乙酯，铜盐，配体，在溶剂中加热至反应完毕；体系冷却后，转移至单口瓶旋干，用柱层析分离得到产品。本发明所提供的多取代3‑亚甲基吲哚酮的合成方法具有科学合理，合成方法简单，产品易于纯化等特点。其反应方程式如下：
Description
技术领域
本发明属于有机合成化学技术领域，本发明涉及一种多取代3-亚甲基吲哚酮的制备方法。
背景技术
3-亚甲基吲哚酮是合成具有生物活性和潜在药用价值的吲哚螺环化合物的一类重要的中间体，多年以来一直作为最有效的合成吲哚螺环化合物的中间体活跃在有机合成化学领域(Org.Biomol.Chem.2015,13,pp 8669-8675；Chem.Commun.2016,52,pp 2473-2476；Angew.Chem.Int.Ed.2013,52,pp 585-588.)。吲哚螺环化合物是一类重要的在自然界中广泛存在的杂环骨架化合物。很多吲哚螺环化合物具有广泛的生理活性和药理活性，如抗肿瘤，抗艾滋病病毒，抗疟疾和抗糖尿病等(Int.J.Pharm.Sci.Drug Res.2010,2,pp229-235；Science 2010,329,pp 1175-1180.)。
作为合成吲哚螺环化合物的重要中间体，3-亚甲基吲哚酮的合成具有特别重要的意义。
3-亚甲基吲哚酮的制备方法有：
1)Brandman合成法：取代靛红和乙基(三苯基膦)乙酸酯，醋酸作溶剂，发生Wittig反应，脱掉三苯基膦，得到3-亚甲基吲哚酮。
2)Javad合成法：取代靛红和溴代羧酸酯在三苯基膦，吗啉和无溶剂条件下发生Wittig反应，得到3-亚甲基吲哚酮。
3)Griffin合成法：取代靛红和丙酮在二乙胺，60℃条件下反应16h，得到β-羟基酮，然后在酸性条件下脱水得到3-亚甲基吲哚酮。
4)王乃兴合成法：取代N,3-二苯基丙炔酰胺和醋酸在醋酸碘苯，醋酸钯，80℃条件下，发生钯催化氧化反应生成3-亚甲基吲哚酮。
利用上述方法在实验室中制备3-亚甲基吲哚酮，具有明显的缺点：1)合成方法局限于使用磷叶立德，发生Wittig反应由羰基化合物合成烯烃，反应中脱掉分子量大的三苯基膦分子；2)反应分步进行，反应时间长；3)需要贵金属催化，反应成本高。
发明内容
为了克服上述现有技术的不足，本发明提供了一种多取代3-亚甲基吲哚酮的制备方法。
一种多取代3-亚甲基吲哚酮的制备方法，所述多取代3-亚甲基吲哚酮具有式I所示的结构：
式I中，其中R1在4位,7位选自氢原子、氯原子；R1在5位选自氢原子，氟原子，氯原子，溴原子、硝基、三氟甲氧基，甲基、甲氧基；R1在6位选自氢原子，氯原子，甲氧基；R2选自氢原子、甲基、苯基、苄基、叔丁氧羰基；向反应容器中，加入取代靛红，异氰基乙酸乙酯，催化剂碘化亚铜，配体邻菲罗啉，溶剂甲苯，加热至反应完毕，体系冷却后，转移至单口瓶旋干，用柱层析分离得到产品，该制备方法见反应方程式II:
选用的铜盐催化剂为碘化亚铜，碘化亚铜的用量为取代靛红摩尔量的10％，取代靛红和异氰基乙酸乙酯的摩尔比值为1:1.2，根据权利要求1所述的制备方法，其特征在于所选用的溶剂是甲苯，反应温度为110℃，反应时间为6h。
本发明的有益效果为：本发明提供的多取代3-亚甲基吲哚酮的制备方法科学合理，可以合成得到具有多种取代基的3-亚甲基吲哚酮；而且还具有合成方法简单，产品易于纯化等特点。
附图说明
图1为实施例3制备的化合物3c的1H NMR谱图；
图2为实施例3制备的化合物3c的13C NMR谱图；
图3为实施例4制备的化合物3d的1H NMR谱图；
图4为实施例4制备的化合物3d的13C NMR谱图；
图5为实施例8制备的化合物3h的1H NMR谱图；
图6为实施例8制备的化合物3h的13C NMR谱图。
具体实施方式
下面结合附图和具体的实施例对本发明进一步详细的说明：
下述实施例中所述试验方法，如无特殊说明，均为常规方法；所述试剂和材料，如无特殊说明，均可从商业途径获得。
实施例1
1)7-氯-3-亚甲基吲哚酮3a的制备
在15mL厚壁耐压管中加入7-氯靛红1a(0.5mmol,90.6mg)，CuI(10mol％,9.5mg)，邻菲罗啉(10mol％,9.0mg)，和异氰基乙酸乙酯2(0.6mmol,67.2mg)，加入2mL甲苯作为溶剂，油浴110℃，TLC跟踪反应至反应完全。反应结束后，停止加热，转移至单口瓶旋干，用PE:EA＝4:1柱层析得到黄色固体产物，经NMR,HRMS证实为7-氯-3-亚甲基吲哚酮3a，其收率为75％。
谱图解析数据3a:
1H NMR(CDCl3,500MHz):δ1.38(t,J＝7.1Hz,3H),4.34(q,J＝7.1Hz,2H),6.39(s,1H),7.01(t,J＝8.0Hz,1H),7.32(d,J＝8.2Hz,1H),7.94(s,1H),8.48(d,J＝7.8Hz,1H)；13CNMR(CDCl3,125MHz):δ14.1,61.4,115.2,121.7,123.5,124.3,127.3,132.0,137.7,140.7,165.2,167.7；HRMS(ESI–TOF):calcd for C12H11NO3Cl[M+H]+252.0427,found 252.0420.
实施例2
用1b代替实例1中的1a,其它条件同实例1，实验结果见表1。
谱图解析数据3b:
1H NMR(CDCl3,500MHz):δ1.37(t,J＝7.1Hz,3H),4.33(q,J＝7.1Hz,2H),6.86(d,J＝1.4Hz,1H),6.88(s,1H),7.03(dd,J1＝8.4Hz,J2＝1.3Hz,1H),7.76(s,1H),8.54(d,J＝8.4Hz,1H)；13C NMR(CDCl3,125MHz):δ14.0,61.3,110.7,119.2,123.4,130.1,136.8,138.5,144.3,165.9,168.6；HRMS(ESI–TOF):calcd for C12H11NO3Cl[M+H]+252.0427,found252.0432.
实施例3
用1c代替实例1中的1a,其它条件同实例1，实验结果见表1。
谱图解析数据3c:
1H NMR(CDCl3,500MHz):δ1.39(t,J＝7.1Hz,3H),4.41(q,J＝7.1Hz,2H),6.77(d,J＝7.8Hz,1H),7.00(d,J＝8.2Hz,1H),7.20(t,J＝8.0Hz,1H),7.50(s,1H),8.7(s,1H)；13CNMR(CDCl3,125MHz):δ14.0,61.7,108.7,118.3,123.9,128.0,130.7,130.9,131.4,143.0,166.2；HRMS(ESI–TOF):calcd for C12H11NO3Cl[M+H]+252.0427,found 252.0435.
实施例4
用1d代替实例1中的1a,其它条件同实例1，实验结果见表1。
谱图解析数据3d:
1H NMR(CDCl3,500MHz):δ1.38(t,J＝7.1Hz,3H),3.83(s,3H),4.33(q,J＝7.1Hz,2H),6.74(d,J＝8.5Hz,1H),6.88(s,1H),6.90(dd,J1＝8.5Hz,J2＝2.5Hz,1H),7.65(s,1H),8.26(d,J＝2.5Hz,1H)；13C NMR(CDCl3,125MHz):δ13.2,54.9,60.2,109.3,113.5,117.9,120.2,121.8,135.9,137.5,154.8,164.6,167.8；HRMS(ESI–TOF):calcd for C13H14NO4[M+H]+248.0923,found 248.0928.
实施例5
用1e代替实例1中的1a,其它条件同实例1，实验结果见表1。
谱图解析数据3e:
1H NMR(CDCl3,500MHz):δ1.38(t,J＝7.2Hz,3H),4.36(q,J＝7.1Hz,2H),6.87(d,J＝8.5Hz,1H),6.94(s,1H),7.21-7.23(m,1H),8.54(s,1H),8.55(s,1H)；13C NMR(CDCl3,125MHz):δ14.1,61.5,110.4,121.3,122.8,124.5,125.5,137.1,141.6,144.6,165.1,168.7；HRMS(ESI–TOF):calcd for C13H11NO4F3[M+H]+302.0640,found 302.0635.
实施例6
用1f代替实例1中的1a,其它条件同实例1，实验结果见表1。
谱图解析数据3f:
1H NMR(CDCl3,500MHz):δ1.38(t,J＝7.2Hz,3H),2.35(s,3H),4.34(q,J＝7.1Hz,2H),6.74(d,J＝7.9Hz,1H),6.86(s,1H),7.13(d,J＝7.8Hz,1H),7.90(s,1H),8.38(s,1H)；13C NMR(CDCl3,125MHz):δ14.2,21.1,61.2,109.6,120.4,122.3,129.5,132.3,133.0,138.2,140.8,165.7,168.9；HRMS(ESI–TOF):calcd for C13H14NO3[M+H]+232.0974,found232,0982.
实施例7
用1g代替实例1中的1a,其它条件同实例1，实验结果见表1。
谱图解析数据3g:
1H NMR(CDCl3,500MHz):δ1.36(t,J＝7.1Hz,3H),3.85(s,3H),4.31(q,J＝7.1Hz,2H),6.40(d,J＝1.9Hz,1H),6.54(dd,J1＝8.8Hz,J2＝2.2Hz,1H),6.71(s,1H),7.94(s,1H),8.55(d,J＝8.8Hz,1H)；13C NMR(CDCl3,125MHz):δ14.2,55.6,60.9,96.8,107.9,113.9,119.2,131.2,137.8,145.3,163.7,166.0,169.9；HRMS(ESI–TOF):calcd for C13H14NO4[M+H]+248.0923,found 248.0915.
实施例8
用1h代替实例1中的1a，其它条件同实例1，实验结果见表1。
谱图解析数据3h:
1H NMR(500MHz,CDCl3):δ1.36(t,J＝7.2Hz,3H),3.21(s,3H),3.88(s,3H),4.30(q,J＝7.1Hz,2H),6.34(d,J＝2.0Hz,1H),6.52-6.54(m,1H),6.75(s,1H),8.56(d,J＝8.6Hz,1H)；13C NMR(CDCl3,125MHz):δ14.2,26.2,55.6,60.9,95.9,106.4,113.1,119.0,130.7,137.6,148.1,163.6,166.1,168.4；HRMS(ESI–TOF):calcd for C14H16NO4[M+H]+262.1079,found 262.1082.
实施例9
用1i代替实例1中的1a，其它条件同实例1，实验结果见表1。
谱图解析数据3i:
1H NMR(500MHz,CDCl3):δ1.39(t,J＝7.1Hz,3H),3.21(s,3H),4.41(q,J＝7.2Hz,2H),6.72(d,J＝3.9Hz,1H),7.00(d,J＝8.3Hz,1H),7.24-7.29(m,1H),7.49(s,1H)；13C NMR(CDCl3,125MHz):δ14.0,26.1,61.8,106.8,117.6,123.9,127.7,130.2,130.7,131.2,145.6,164.6,166.3；HRMS(ESI–TOF):calcd for C13H13NO3Cl[M+H]+266.0584,found266.0578.
表1
Claims (3)
1.一种多取代3-亚甲基吲哚酮的制备方法，所述多取代3-亚甲基吲哚酮具有式Ⅰ所示的结构：
式Ⅰ中，其中R1在4位,7位选自氢原子、氯原子；R1在5位选自氢原子，氟原子，氯原子，溴原子、硝基、三氟甲氧基，甲基、甲氧基；R1在6位选自氢原子，氯原子，甲氧基；R2选自氢原子、甲基、苯基、苄基、叔丁氧羰基；其特征在于，向容器中加入取代靛红和异氰基乙酸乙酯，在碘化亚铜和邻菲罗啉作用下，在甲苯中加热，反应完毕后得到式Ⅰ所示的多取代3-亚甲基吲哚酮；该制备方法用式II表示：
2.根据权利要求1所述的制备方法，其特征在于，所选用的铜盐催化剂为碘化亚铜，碘化亚铜的用量为取代靛红摩尔量的10％，取代靛红和异氰基乙酸乙酯的摩尔比值为1:1.2。
3.根据权利要求1所述的制备方法，其特征在于所选用的溶剂是甲苯，反应温度为110℃，反应时间为6h。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108752258A (zh) * | 2018-04-04 | 2018-11-06 | 南开大学 | 镍催化高效合成吲哚酮类衍生物 |
| CN110655484A (zh) * | 2018-06-28 | 2020-01-07 | 中国科学院上海药物研究所 | 3-烯基吲哚酮类化合物的盐、其晶型、其药物组合物及其用途 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101417972A (zh) * | 2008-12-16 | 2009-04-29 | 温州大学 | 3-亚甲基-吲哚-2-酮衍生物及其制备方法 |
| CN102285909A (zh) * | 2011-08-08 | 2011-12-21 | 苏州大学 | 一种吲哚-2-酮类化合物的制备方法 |
-
2016
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101417972A (zh) * | 2008-12-16 | 2009-04-29 | 温州大学 | 3-亚甲基-吲哚-2-酮衍生物及其制备方法 |
| CN102285909A (zh) * | 2011-08-08 | 2011-12-21 | 苏州大学 | 一种吲哚-2-酮类化合物的制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| 唐林: "铜催化下3-亚甲基吲哚酮的合成及其与β-芳甲酰硫代酰胺的反应研究", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108752258A (zh) * | 2018-04-04 | 2018-11-06 | 南开大学 | 镍催化高效合成吲哚酮类衍生物 |
| CN110655484A (zh) * | 2018-06-28 | 2020-01-07 | 中国科学院上海药物研究所 | 3-烯基吲哚酮类化合物的盐、其晶型、其药物组合物及其用途 |
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