CN109824573A - N-烯丙基苯胺氰烷基化合成氰烷基吲哚啉的方法 - Google Patents
N-烯丙基苯胺氰烷基化合成氰烷基吲哚啉的方法 Download PDFInfo
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Abstract
本发明提供一种N‑烯丙基苯胺氰烷基化合成氰烷基吲哚啉的方法,使用廉价烷基腈与特定非活化烯烃在DTBP作用,在无金属和中性条件下,N‑烯丙基苯胺类化合物发生exo选择性的氰烷基化/环化级联反应,生成3‑氰烷基吲哚啉。本发明方法反应无需金属和强碱、底物范围广,即使是化合物中存在磺酰基保护基时反应也能顺利发生;而且使用本发明方法,一级、二级和三级腈产物都可以顺利合成,同时反应条件温和、操作简单,适合工业化推广。
Description
技术领域
本发明属于有机合成技术领域,具体涉及一种N-烯丙基苯胺氰烷基化合成氰烷基吲哚啉的方法。
背景技术
吲哚啉是一类非常重要的含氮杂环化合物,普遍存在于生物碱和其他天然产物中,其在染料工业、香料、有机中间体合成、医药、农药合成方面有着巨大的应用。由于以吲哚啉为母核结构化合物多样的生物活性和临床应用,反过来又要求科学家合成更多结构多样的吲哚啉衍生物作为药物先导分子。利用C-H键官能团化反应直接从廉价烷基腈合成高价值的氰烷基吲哚啉极具吸引力,因为这类过程避免了反应原料的预先卤代和剧毒氰化物的使用;然而,由于极性小、键能大,惰性C(sp3)-H键的官能团化反应极具挑战。这不仅在于吲哚化学中吲哚啉骨架要比其它吲哚类结构更难构建(吲哚啉的合成主要依赖吲哚的去芳香化反应,但该类反应一般生成2-位取代的吲哚啉),更是因为作为传统离子型反应溶剂的烷基腈非常稳定,在缺乏合适催化剂的条件下反应很难发生。刘国生等人于2011年开发了强大的Pd(OAc)2/PhI(O2Ct-Bu)2/AgF催化剂体系,从而合成了3-氰烷基氧化吲哚和吲哚啉,如下式:
这两个反应都是使用乙腈为氰烷基源,但为了活化乙腈的C-H键需要使用钯催化剂、大大过量的AgF和高碘试剂的组合,成本非常高。此外,该方法3-氰烷基吲哚啉合成反应中,由于只有乙腈是可用的氰烷基源,因此产物局限于一级腈;同时磺酰基保护基在该反应中不被兼容。中国专利CN108440373A报道了铁催化的偶氮二异丁腈(AIBN)作为氰烷基化试剂合成3-氰烷基吲哚啉的反应,然而受限于偶氮试剂的结构,该反应只能用于合成三级腈。尽管在合成氰烷基吲哚啉等高价值腈类分子的研究中取得了一些进展,但通过C-H键官能团化反应直接从廉价烷基腈合成氰烷基吲哚啉等高价值腈类分子还主要依赖于强碱或特定的昂贵金属催化剂。
发明内容
为了解决现有技术中的问题,本发明的目的在于提供一种N-烯丙基苯胺氰烷基化合成氰烷基吲哚啉的方法,该方法不使用强碱和金属催化剂,官能团耐受性能好,能用于合成一级、二级和三级吲哚啉-3-烷基腈,通用且经济,具有明显的实用价值。
本发明的目的是这样实现的:
一种N-烯丙基苯胺氰烷基化合成氰烷基吲哚啉(式II化合物)的方法,其特征在于,反应路线如下:
其中:
R1是氢、卤素、C1-6烷基或苯基;
R2是氢或C1-6烷基;
R3是COR6或SO2R7;
R4是氢或C1-6烷基;
R5是氢或C1-6烷基;
R6是C1-17烷基或-O-C1-6烷基;
R7是C1-6烷基、N,N-二甲基、噻吩基或
R8是氢、卤素、羟基、C1-6烷基或-O-C1-6烷基。
所述催化剂选自DTBP、DCP、BPO、TBHP、Oxone、TBPB或K2S2O8。
本文所用的术语“卤素”是指氟、氯、溴或碘,优选为氟、氯或溴。
本文所用的术语“C1-6烷基”是指具有1-6个碳原子的饱和的直链或支链烃基,例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基、异己基等,优选甲基、乙基、丙基、异丙基、叔丁基或异丁基。
本文所用的术语“C1-17烷基”是指具有1-17个碳原子的饱和的直链或支链烃基,例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基、异己基、n-C7H15、n-C9H19、n-C11H23、n-C17H35。
本发明所用的术语“-O-C1-6烷基”,是指具有1-6个碳原子的饱和的直链或支链烷氧基,例如甲氧基、乙氧基、叔丁氧基等。
进一步,本发明中R1选自氢、甲基、氟、氯、溴或苯基;R2选自氢或甲基;R4是氢、甲基或乙基;R5选自氢、甲基或乙基;R6选自甲基、乙基、n-C7H15、n-C9H19、n-C11H23、n-C17H35、t-Bu或叔丁氧基;R7选自甲基、乙基、N,N-二甲基、噻吩基。
进一步,本发明所述催化剂优选二叔丁基过氧化物(DTBP),其用量优选1.5-2.0当量。
本发明的一个实施方案包括其中R1是苯基的化合物(如式I),所述苯基是未取代的或被一个或多个下列基团取代:氢、甲基、氯、溴或苯基;式I化合物中,R1可以独立的为邻位、间位或对位,可以邻位、间位或/和对位同时取代,也可以单独取代。同样的,本发明的一个实施方案包括其中R8是苯基的化合物,所述苯基是未取代的或被一个或多个下列基团取代:氢、甲基、卤素、-OCH3或-OH;R8可以独立的为邻位、间位或对位,可以邻位、间位或/和对位同时取代,也可以单独取代。
本发明式II化合物选自2a1-2n化合物,具体如下表1。
表1 2a1-2n化合物
有益效果
不意图为任何理论所束缚,认为尽管利用C-H键官能团化反应直接从廉价烷基腈合成高价值的氰烷基吲哚啉极具吸引力,然而,由于极性小、键能大,惰性C(sp3)-H键的官能团化反应极具挑战。这不仅在于吲哚化学中吲哚啉骨架要比其它吲哚类结构更难构建,更是因为作为传统离子型反应溶剂的烷基腈非常稳定,在缺乏合适催化剂的条件下反应很难发生。大量研究显示,通过C-H键官能团化反应直接从廉价烷基腈合成氰烷基吲哚啉等高价值腈类分子主要依赖于强碱或/和特定的昂贵金属催化剂。
本发明人进行了N-烯丙基苯胺与烷基腈的氰烷基化/环合反应的实验,并且出人意料地发现,使用廉价烷基腈与特定非活化烯烃在DTBP作用,在无金属和中性条件下,N-烯丙基苯胺类化合物发生exo选择性的氰烷基化/环化级联反应,生成3-氰烷基吲哚啉。本发明方法反应无需金属和强碱、底物范围广,即使是化合物中存在磺酰基保护基时反应也能顺利发生;而且使用本发明方法,一级、二级和三级腈产物都可以顺利合成,同时反应条件温和、操作简单,适合工业化推广。
具体实施方式
为了使本发明的目的和技术方案更加清楚,下面对本发明的优选实施例进行详细的描述。要说明的是:以下实施例只用于对本发明进行进一步的说明,而不能理解为对本发明保护范围的限制。本领域的技术人员根据本发明的上述内容做出的一些非本质的改进和调整均属于本发明的保护范围。
实施例1
非活化烯烃类式I化合物的合成(以1a2合成为例),反应路线如下:
操作步骤:向一个放有磁力搅拌子的100mL圆底烧瓶中依次加入对甲苯胺(1.607g,15.0mmol)、CH2Cl2(50.0mL),和Et3N(4.170mL,30.0mmol),最后加入乙酰氯(1.273mL,18.0mmol)。反应混合液在室温用磁力搅拌器进行搅拌。TLC显示原料对甲苯胺消耗完毕后,用饱和NaHCO3溶液(100mL)淬灭反应,然后用CH2Cl2(100.0mL)萃取3次。合并的有机相用食盐水(50mL)洗涤2次。蒸除有机溶剂得到的固体用石油醚/乙酸乙酯(5:1,体积比)混合液洗涤,得到白色固体对甲基乙酰苯胺(2.104g,94%产率)。向保持搅拌的对甲基乙酰苯胺(1.492g,10.0mmol)和NaOH(600mg,15.0mmol)的DMF(30mL)溶液中加入2-甲基-3-溴丙烯(1.311mL,13.0mmol),得到的混合液用磁力搅拌器在室温搅拌反应。TLC显示对甲基乙酰苯胺消耗完毕后,用食盐水(60mL)淬灭反应并用CH2Cl2(100.0mL)萃取3次。蒸除有机溶剂得到的残留物用硅胶进行柱层析(石油醚-乙酸乙酯=20:1,体积比),得到无色油状物N-(2-甲基烯丙基)-N-对甲苯基乙酰胺1a2(1.830g,90%产率)。
参照文献(文献1:D.Liang,Q.Dong,P.Xu,Y.Dong,W.Li,Y.Ma,J.Org.Chem.2018,83,11978-11986.;文献2:S.O'Sullivan,E.Doni,T.Tuttle,J.A.Murphy.Angew.Chem.Int.Ed.2014,53,474–478;Angew.Chem.2014,126,484–488;文献3:Z.Wu,S.Li,H.Xu.Angew.Chem.Int.Ed.2018,57,14070–14074;Angew.Chem.2018,130,14266–14270.;文献4:CN201811634880.2)及上述实施例1制备得到以下表1式I化合物。
表1式I化合物
。
实施例2
N-烯丙基苯胺氰烷基化合成氰烷基吲哚啉(以2a1的合成为例),反应路线如下:
操作步骤:氩气保护下向装有磁力搅拌子的Schlenk管中依次加入N-烯丙基苯胺衍生物1a1(57mg,0.3mmol)、催化剂DTBP(88mg,0.6mmol)和乙腈溶剂(3.0mL)。该混合液在140℃加热搅拌6h,冷却后用饱和Na2S2O3水溶液(1.0mL)和水(10.0mL)淬灭。得到的混合液用二氯甲烷(10.0mL)萃取3次,合并有机相。蒸除有机溶剂,残余物使用300-400目硅胶进行柱层析(石油醚和乙酸乙酯作为洗脱剂),得到3-氰烷基吲哚啉产物2a1。
参照上述实施例2,考察催化剂、温度对反应的影响,具体情况见表2。
表2催化剂、温度对反应的影响a
a反应条件:1a1(0.3mmol),催化剂(0.6mmol),乙腈(3.0mL),Ar,6h。
b加入CuCl(10mol%)作为复合催化剂。
c5.0-6.0mol/L的癸烷溶液。
如表2所示,N-(2-甲基丙烯基)乙酰苯胺1a1和乙腈的反应被选为模型反应用于反应条件优化。1a1在10mol%CuI和2当量二叔丁基过氧化(DTBP)的作用下与120℃的乙腈发生反应,以28%的产率生成3-氰乙基吲哚啉2a1(序号1)。令人惊喜的是,去掉金属催化剂后产率提高到61%(序号2),可能是因为铜催化剂会催化反应体系分解。接着发明人对比DTBP考察了一系列催化剂。使用过氧化二异丙苯(DCP,序号3)、过氧化二苯甲酰(BPO,序号4)或过苯甲酸特丁酯(TBPB,序号5)时,吲哚啉2a1的产率降低,而无水过氧化叔丁醇(TBHP,序号6)、K2S2O8(序号7)和Oxone(序号8)对该反应基本无效。升温到140℃时2a1的产率继续提高到70%(序号9),而降低DTBP用量会导致产率下降(序号10)。
参照上述实施例2,在最优反应条件下,考察底物对本发明反应的影响,具体情况见下表3。
表3底物对本发明反应的影响a
结果显示,N-芳基对位有供电子基、吸电子基或苯基取代基的N-烯丙基化酰胺都能和乙腈发生反应生成对应5-位取代吲哚啉2a-d,产率中等到高。其中,氯原子似乎是最佳取代基。R3中长链N-保护基,例如辛酰基、癸酰基、十二烷酰基和硬脂酰基,在反应中都可以被兼容,没有观察到明显的位阻效应。保护基体积很大的特戊酰基苯胺的反应以73%的产率生成吲哚啉产物2d4,叔丁氧羰基保护的吲哚啉2e的产率也类似。令人惊喜的是,烷基磺酰基保护的烯丙基化苯胺也是高活性底物,N-甲磺酰基和N-乙磺酰基吲哚啉2f和2g1以中等到高的产率生成。当使用氨磺酰基、噻吩-2磺酰基或芳基磺酰基底物时,对应3-氰烷基吲哚啉2g2,3和2h仅以很低的产率生成。3-氯苯酰基也可以被兼容,对应吲哚啉产物2i以中等产率生成。该反应中,环化步骤发生在N-芳基苯环上,虽然体系中还有痕迹量未鉴别产物生成。可能由于位阻的影响,7-氯吲哚啉2j仅以7%的产率从对应邻位取代底物合成得到。N-芳基3-位被取代的N-烯丙基化酰胺也是高活性底物,不过反应中存在区域选择性问题,4-氯吲哚啉2k和它们区域异构体6-氯吲哚啉2k'同时生成。在较大位阻位点发生反应生成的产物产率略高,可能是因为它们在反应中经历了更稳定的中间体。
根据鲍德温规则,形式6-endo-trg环合过程可能是本发明的竞争反应。不过,在以上所有环合反应中发明人都实现了exo选择性。底物的烯丙基没有甲基分支时,5-exo-trig产物2l以40%产率生成,同时还有3-氰乙基吲哚2l'生成,产率为36%。
接下来发明人考察不同腈溶剂对本发明反应的影响。丁腈与N-烯丙基乙酰苯胺反应以中等到高的产率生成对应3-氰烷基吲哚啉2m。使用异丁腈作为溶剂时,3-氰烷基吲哚啉2n以较低产率生成,可能是由于异丁腈α-C-H键周围的空间位阻太大。因此,乙腈、一级腈和二级腈都可以作为氰烷基化试剂参与到本发明中,发明人呈现的是一个合成一级、二级和三级吲哚啉-3-烷基腈的通用方法。
综上所述,本发明提供了N-烯丙基苯胺与烷基腈的氰烷基化/环合反应,该反应使用廉价烷基腈与非活化烯烃直接合成3-氰烷基吲哚啉的方法。过去,活化腈的α-C-H键需要使用过量强碱和/或过渡金属催化剂,而非活化烯烃参与的烷基腈α-C-H键官能团化反应极少被报道。本发明无需金属和强碱、成本低、操作简单、底物范围广,同时使用该方法,一级、二级和三级腈产物都可以顺利合成。
目标产物的核磁数据
2a1,3-(3-甲基-1-乙酰基吲哚啉-3-基)丙腈,1:5不可分离的旋转异构体混合物(来源于N-(CO)键旋转受阻),浅黄色固体:mp 95-96℃.1H NMR(400MHz,CDCl3)δ=1.44(s,3H),1.96-2.08(m,2H),2.10-2.21(m,2H),2.25(s,3H),3.78(d,J=10.6Hz,1H),3.98(d,J=10.7Hz,1H),7.08-7.16(m,2H),7.24-7.28(m,1H),8.21(d,J=8.1Hz,1H);13C NMR(100MHz,CDCl3)δ=168.71,142.36,135.94,128.80,124.16,122.18,119.49,117.22,60.61,43.22,37.03,26.59,24.31,12.92;HRMS(ESI-TOF)Calcd for C14H17N2O+([M+H]+)229.1335.Found 229.1344.
2a2,3-(3,5-二甲基-1-乙酰基吲哚啉-3-基)丙腈,1:4的旋转异构体混合物,浅黄色固体:mp 146-147℃.1H NMR(400MHz,CDCl3)δ=1.42(s,3H),1.94-2.06(m,2H),2.09-2.18(m,2H),2.23(s,3H),2.33(s,3H),3.76(d,J=10.6Hz,1H),3.95(d,J=10.7Hz,1H),6.87(s,1H),7.06(d,J=7.8Hz,1H),8.08(d,J=8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=168.35,140.11,136.01,133.86,129.27,122.72,119.57,116.92,60.71,43.17,37.07,26.63,24.20,21.14,12.94;HRMS(ESI-TOF)Calcd for C15H19N2O+([M+H]+)243.1492.Found243.1490.
2a3,3-(3-甲基-1-乙酰基-5-溴吲哚啉-3-基)丙腈,浅黄色油状物.1H NMR(400MHz,CDCl3)δ=1.44(s,3H),1.97-2.06(m,2H),2.19(t,J=7.6Hz,2H),2.24(s,3H),3.79(d,J=10.7Hz,1H),4.02(d,J=10.7Hz,1H),7.18(d,J=1.7Hz,1H),7.37(dd,J=2.0,8.6Hz,1H),8.11(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=168.75,141.48,138.36,131.73,125.39,119.19,118.71,116.49,60.57,43.31,36.86,26.54,24.17,12.93;HRMS(ESI-TOF)Calcd for C14H16BrN2O+([M+H]+)307.0441.Found 307.0427.
2b1,3-(3-甲基-1-丙酰基-5-溴吲哚啉-3-基)丙腈,1:10的旋转异构体混合物,微黄色固体:mp 147-148℃.1H NMR(400MHz,CDCl3)δ=1.22(t,J=7.3Hz,3H),1.43(s,3H),1.94-2.08(m,2H),2.13-2.22(m,2H),2.36-2.55(m,2H),3.77(d,J=10.9Hz,1H),4.01(d,J=10.7Hz,1H),7.18(s,1H),7.36(dd,J=2.0,8.6Hz,1H),8.14(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=172.09,141.71,138.26,131.70,125.37,119.23,118.61,116.27,59.63,43.30,36.85,29.18,26.55,12.93,8.55;HRMS(ESI-TOF)C15H18BrN2O+([M+H]+)321.0597.Found 321.0597.
2b2,3-(3-甲基-1-丙酰基-5-氯吲哚啉-3-基)丙腈,浅黄色固体:mp 62-63℃.1HNMR(400MHz,CDCl3)δ=1.21(t,J=7.3Hz,3H),1.42(s,3H),1.94-2.07(m,2H),2.12-2.23(m,2H),2.37-2.55(m,2H),3.77(d,J=10.9Hz,1H),4.01(d,J=10.7Hz,1H),7.04(d,J=1.3Hz,1H),7.21(dd,J=2.2,8.6Hz,1H),8.18(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=172.05,141.23,138.00,128.76,128.68,122.51,119.28,118.08,59.66,43.28,36.77,29.09,26.47,12.88,8.55;HRMS(ESI-TOF)C15H18ClN2O+([M+H]+)277.1102.Found277.1105.
2c1,3-(3-甲基-1-辛酰基吲哚啉-3-基)丙腈,黄色固体:mp 72-73℃.1H NMR(400MHz,CDCl3)δ=0.89(t,J=7.0Hz,3H),1.28-1.44(m,11H),1.68-1.80(m,2H),1.96-2.07(m,2H),2.09-2.23(m,2H),2.35-2.50(m,2H),3.77(d,J=10.8Hz,1H),3.96(d,J=10.6Hz,1H),7.06-7.10(m,2H),7.23-7.30(m,1H),8.25(d,J=8.1Hz,1H);13C NMR(100MHz,CDCl3)δ=171.49,142.59,135.81,128.81,124.01,122.11,119.43,117.30,59.92,43.19,37.05,36.09,31.73,29.36,29.15,26.54,24.51,22.64,14.10,12.93;HRMS(ESI-TOF)C20H29N2O+([M+H]+)313.2274.Found 313.2289.
2c2,3-(3,5-二甲基-1-辛酰基吲哚啉-3-基)丙腈,浅棕色固体:mp 137-138℃.1HNMR(400MHz,CDCl3)δ=0.89(t,J=7.1Hz,3H),1.30-1.42(m,11H),1.67-1.76(m,2H),1.94-2.05(m,2H),2.07-2.23(m,2H),2.33-2.48(m,5H),3.74(d,J=10.8Hz,1H),3.94(d,J=10.6Hz,1H),6.86(s,1H),7.04-7.06(m,1H),8.11(d,J=8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=171.14,140.33,135.88,133.69,129.28,122.66,119.51,117.00,60.01,43.14,37.09,35.98,31.73,29.37,29.16,26.57,24.54,22.64,21.11,14.10,12.94;HRMS(ESI-TOF)C21H31N2O+([M+H]+)327.2431.Found 327.2432.
2c3,3-(3-甲基-1-辛酰基-5-溴吲哚啉-3-基)丙腈,浅黄色固体:mp 73-74℃.1HNMR(400MHz,CDCl3)δ=0.89(t,J=6.9Hz,3H),1.26-1.43(m,11H),1.68-1.75(m,2H),1.95-2.07(m,2H),2.18(t,J=7.3Hz,2H),2.34-2.49(m,2H),3.78(d,J=10.8Hz,1H),4.00(d,J=10.7Hz,1H),7.17(d,J=1.4Hz,1H),7.37(dd,J=2.0,8.6Hz,1H),8.14(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=171.56,141.69,138.25,131.72,125.34,119.18,118.73,116.31,59.84,43.27,36.86,35.99,31.72,29.31,29.14,26.53,24.39,22.64,14.11,12.94;HRMS(ESI-TOF)C20H28BrN2O+([M+H]+)391.1380.Found 391.1384.
2c4,3-(3-甲基-1-辛酰基-5-氯吲哚啉-3-基)丙腈,浅黄色晶体:mp 167-168℃.1H NMR(400MHz,CDCl3)δ=0.89(t,J=7.0Hz,3H),1.26-1.43(m,11H),1.68-1.76(m,2H),1.95-2.07(m,2H),2.14-2.20(m,2H),2.34-2.49(m,2H),3.78(d,J=10.8Hz,1H),4.01(d,J=10.7Hz,1H),7.03(d,J=1.6Hz,1H),7.22(dd,J=2.2,8.6Hz,1H),8.19(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=171.49,141.21,137.87,128.88,128.78,122.44,119.16,118.28,59.91,43.28,36.83,35.94,31.71,29.31,29.13,26.48,24.41,22.63,14.09,12.92;HRMS(ESI-TOF)C20H28ClN2O+([M+H]+)347.1885.Found 347.1887.
2c5,3-(3-甲基-5-苯基-1-辛酰基吲哚啉-3-基)丙腈,白色固体:mp 103-104℃.1H NMR(400MHz,CDCl3)δ=0.89(t,J=6.9Hz,3H),1.31-1.47(m,8H),1.49(s,3H),1.71-1.78(m,2H),2.02-2.12(m,2H),2.15-2.28(m,2H),2.38-2.52(m,2H),3.82(d,J=10.8Hz,1H),4.02(d,J=10.6Hz,1H),7.28(s,1H),7.34(dd,J=7.3,7.2Hz,1H),7.44(dd,J=7.7,7.4Hz,2H),7.51(dd,J=1.7,8.4Hz,1H),7.56(d,J=7.4Hz,2H),8.30(d,J=8.4Hz,1H);13CNMR(100MHz,CDCl3)δ=171.45,141.98,140.62,137.29,136.55,128.85,127.79,127.20,126.88,120.72,119.40,117.46,60.17,43.29,37.06,36.06,31.74,29.36,29.16,26.59,24.51,22.64,14.10,13.00;HRMS(ESI-TOF)C26H33N2O+([M+H]+)389.2587.Found 389.2583.
2d1,3-(3-甲基-1-癸酰基-5-溴吲哚啉-3-基)丙腈,1:10的旋转异构体混合物,浅黄色固体:mp 60-61℃.1H NMR(400MHz,CDCl3)δ=0.88(t,J=7.0Hz,3H),1.27-1.43(m,15H),1.68-1.75(m,2H),1.95-2.07(m,2H),2.18(t,J=7.2Hz,2H),2.34-2.49(m,2H),3.77(d,J=10.8Hz,1H),4.00(d,J=10.7Hz,1H),7.18(s,1H),7.37(dd,J=1.9,8.6Hz,1H),8.14(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=171.56,141.69,138.25,131.71,125.35,119.19,118.72,116.30,59.83,43.27,36.86,35.99,31.89,29.49,29.35,29.30,26.53,24.39,22.69,14.14,12.94;HRMS(ESI-TOF)C22H32BrN2O+([M+H]+)419.1693.Found419.1692.
2d2,3-(3-甲基-1-十二酰基-5-溴吲哚啉-3-基)丙腈,浅黄色固体:mp 60-61℃.1H NMR(400MHz,CDCl3)δ=0.88(t,J=7.0Hz,3H),1.26-1.43(m,19H),1.68-1.75(m,2H),1.94-2.07(m,2H),2.12-2.27(m,2H),2.34-2.49(m,2H),3.77(d,J=10.8Hz,1H),4.00(d,J=10.7Hz,1H),7.17(d,J=1.6Hz,1H),7.36(dd,J=2.1,8.7Hz,1H),8.14(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=171.56,141.69,138.25,131.71,125.35,119.19,118.72,116.30,59.83,43.27,36.86,35.99,31.92,29.64,29.64,29.53,29.49,29.35,26.53,24.39,22.71,14.15,12.94;HRMS(ESI-TOF)C24H36BrN2O+([M+H]+)447.2006.Found447.2005.
2d3,3-(3-甲基-1-十八酰基-5-溴吲哚啉-3-基)丙腈,浅黄色固体:mp 57-58℃.1H NMR(400MHz,CDCl3)δ=0.88(t,J=7.0Hz,3H),1.25-1.43(m,31H),1.68-1.75(m,2H),1.94-2.07(m,2H),2.16-2.20(m,2H),2.34-2.49(m,2H),3.77(d,J=10.8Hz,1H),4.00(d,J=10.7Hz,1H),7.17(d,J=1.4Hz,1H),7.36(dd,J=2.0,8.6Hz,1H),8.14(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=171.56,141.69,138.25,131.71,125.35,119.19,118.72,116.30,59.83,43.27,36.86,35.99,31.94,29.72,29.68,29.65,29.54,29.50,29.39,29.36,26.53,24.39,22.72,14.16,12.94;HRMS(ESI-TOF)C30H48BrN2O+([M+H]+)531.2945.Found 531.2948.
2d4,3-(3-甲基-1-新戊酰基-5-溴吲哚啉-3-基)丙腈,浅黄色固体:mp 167-168℃.1H NMR(400MHz,CDCl3)δ=1.37(s,9H),1.40(s,3H),1.95-2.07(m,2H),2.17-2.32(m,2H),3.93(d,J=10.5Hz,1H),4.16(d,J=10.5Hz,1H),7.17(d,J=2.0Hz,1H),7.36(dd,J=2.1,8.7Hz,1H),8.12(d,J=8.7Hz,1H);13C NMR(100MHz,CDCl3)δ=176.49,143.10,138.13,131.50,125.10,120.29,119.12,116.51,61.45,43.86,40.27,35.67,27.58,24.74,12.96;HRMS(ESI-TOF)C17H22BrN2O+([M+H]+)349.0910.Found 349.0911.
2e,3-甲基-3-(2-氰基乙基)-5-氯吲哚啉-1-羧酸叔丁酯,2:5的旋转异构体混合物,白色固体:mp 62-63℃.1H NMR(400MHz,CDCl3)δ=1.31(s,3H),1.49(s,9H),1.84-1.93(m,2H),1.95-2.06(m,1H),2.12-2.20(m,1H),3.59(d,J=11.6Hz,1H),3.79(d,J=11.6Hz,1H),6.94(d,J=2.1Hz,1H),7.10(dd,J=2.0,8.6Hz,1H),7.30(brs,0.26H(1H minor),不可交换),7.71(brs,0.65H(1H major),不可交换);13C NMR(100MHz,CDCl3)δ=151.00,139.98(br,major and minor),136.61(br,major and minor),127.51,126.63,121.68(br),118.18,114.94,80.42(br,major and minor),58.39,41.40(br,major and minor),36.00,27.35,25.44,11.88;HRMS(ESI-TOF)C17H22ClN2O2 +([M+H]+)321.1364.Found321.1376.
2f1,3-(3-甲基-1-甲磺酰基-5-溴吲哚啉-3-基)丙腈,黄色油状物.1H NMR(400MHz,CDCl3)δ=1.43(s,3H),1.96-2.12(m,2H),2.15-2.23(m,1H),2.34-2.42(m,1H),2.93(s,3H),3.61(d,J=10.3Hz,1H),3.90(d,J=10.3Hz,1H),7.24(d,J=1.9Hz,1H),7.28(d,J=8.6Hz,1H),7.38(dd,J=2.0,8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=140.53,138.47,132.04,126.55,119.14,116.56,114.88,61.49,43.20,36.25,34.86,25.73,12.96;HRMS(ESI-TOF)C13H16BrN2O2S+([M+H]+)343.0110.Found 343.0108.
2f2,3-(3-甲基-1-甲磺酰基-5-氯吲哚啉-3-基)丙腈,浅棕色油状物.1H NMR(400MHz,CDCl3)δ=1.44(s,3H),1.96-2.11(m,2H),2.14-2.22(m,1H),2.33-2.41(m,1H),2.93(s,3H),3.62(d,J=10.3Hz,1H),3.91(d,J=10.3Hz,1H),7.09(d,J=1.8Hz,1H),7.24(dd,J=1.9,8.6Hz,1H),7.34(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=140.01,137.94,129.33,129.20,123.64,118.98,114.46,61.62,43.21,36.32,34.83,25.75,12.96;HRMS(ESI-TOF)C13H16ClN2O2S+([M+H]+)299.0616.Found 299.0616.
2g1,3-(3-甲基-1-乙磺酰基-5-溴吲哚啉-3-基)丙腈,黄色油状物.1H NMR(400MHz,CDCl3)δ=1.40-1.43(m,6H),1.95-2.09(m,2H),2.13-2.21(m,1H),2.32-2.40(m,1H),3.14(q,J=7.4Hz,2H),3.69(d,J=10.4Hz,1H),3.93(d,J=10.4Hz,1H),7.20(d,J=1.5Hz,1H),7.25(d,J=8.6Hz,1H),7.35(dd,J=1.7,8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=140.83,138.12,131.92,126.39,119.00,116.08,114.92,61.45,44.57,43.28,36.38,25.84,12.94,7.73;HRMS(ESI-TOF)C14H18BrN2O2S+([M+H]+)357.0267.Found 357.0257.
2g2,N,N,3-三甲基-3-(2-氰基乙基)-5-溴吲哚啉-1-磺酰胺,黄色油状物.1H NMR(400MHz,CDCl3)δ=1.41(s,3H),1.95-2.07(m,2H),2.12-2.20(m,1H),2.31-2.39(m,1H),2.90(s,6H),3.67(d,J=10.2Hz,1H),3.84(d,J=10.2Hz,1H),7.17(s,1H),7.23(d,J=8.6Hz,1H),7.33(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=141.68,137.83,131.75,125.99,119.12,115.67,115.47,61.70,43.28,38.26,36.45,25.83,12.94;HRMS(ESI-TOF)C14H19BrN3O2S+([M+H]+)372.0376.Found 372.0379.
2g3,3-(3-甲基-1-(噻吩-2-基磺酰基)-5-溴吲哚啉-3-基)丙腈,浅棕色油状物.1H NMR(400MHz,CDCl3)δ=1.26(s,3H),1.77-1.92(m,2H),1.96-2.04(m,1H),2.10-2.18(m,1H),3.59(d,J=10.8Hz,1H),3.82(d,J=10.8Hz,1H),7.11-7.13(m,2H),7.40(dd,J=1.2,8.6Hz,1H),7.53(d,J=8.6Hz,1H),7.59(d,J=4.8Hz,1H),7.62(d,J=3.1Hz,1H);13CNMR(100MHz,CDCl3)δ=139.98,138.80,135.44,133.00,132.91,131.93,127.79,126.27,118.82,117.25,116.51,61.01,43.14,36.45,25.99,12.75;HRMS(ESI-TOF)C16H16BrN2O2S2 +([M+H]+)410.9831.Found 410.9846.
2h1,3-(3-甲基-1-苯磺酰基吲哚啉-3-基)丙腈,浅橙色固体:mp 154-155℃.1HNMR(400MHz,CDCl3)δ=1.22(s,3H),1.72-1.94(m,3H),2.00-2.10(m,1H),3.54(d,J=10.7Hz,1H),3.77(d,J=10.7Hz,1H),6.99(ddd,J=0.4,1.4,7.5Hz,1H),7.05(ddd,J=1.0,7.4,7.4Hz,1H),7.27(ddd,J=1.4,7.4,8.1Hz,1H),7.47-7.52(m,2H),7.60(dddd,J=1.2,1.2,6.8,8.2Hz,1H),7.69(d,J=8.2Hz,1H),7.83-7.85(m,2H);13C NMR(100MHz,CDCl3)δ=141.21,136.49,136.19,133.61,129.28,129.00,127.23,124.14,122.96,119.11,114.65,60.69,43.03,36.58,26.00,12.68;HRMS(ESI-TOF)C18H19N2O2S+([M+H]+)327.1162.Found 327.1163.
2h2,3-(3-甲基-1-(对甲苯磺酰基)吲哚啉-3-基)丙腈,黄色油状物.1H NMR(400MHz,CDCl3)δ=1.22(s,3H),1.71-1.94(m,3H),1.99-2.07(m,1H),2.39(s,3H),3.52(d,J=10.7Hz,1H),3.75(d,J=10.7Hz,1H),6.99(d,J=7.5Hz,1H),7.04(ddd,J=0.8,7.3,7.3Hz,1H),7.24-7.28(m,3H),7.67(d,J=8.2Hz,1H),7.71(d,J=8.3Hz,2H);13C NMR(100MHz,CDCl3)δ=144.70,141.29,136.29,133.43,129.91,128.93,127.28,124.06,122.97,119.22,114.67,60.68,43.00,36.61,25.89,21.59,12.68;HRMS(ESI-TOF)C19H21N2O2S+([M+H]+)341.1318.Found 341.1320.
2h3,3-(3-甲基-1-(邻甲苯磺酰基)吲哚啉-3-基)丙腈,浅黄色油状物.1H NMR(400MHz,CDCl3)δ=1.32(s,3H),1.83-1.95(m,2H),1.99-2.07(m,1H),2.14-2.22(m,1H),2.62(s,3H),3.62(d,J=10.6Hz,1H),3.79(d,J=10.6Hz,1H),7.02-7.06(m,2H),7.18-7.23(m,1H),7.31-7.34(m,2H),7.44(d,J=8.1Hz,1H),7.48(dd,J=7.5,7.5Hz,1H),7.94(d,J=7.8Hz,1H);13C NMR(100MHz,CDCl3)δ=141.90,138.11,137.02,135.93,133.36,133.08,129.31,128.84,126.44,123.77,122.95,119.20,114.61,60.54,43.20,36.53,25.77,20.88,12.80;HRMS(ESI-TOF)C19H21N2O2S+([M+H]+)341.1318.Found 341.1318.
2h4,3-(3-甲基-1-((4-溴苯基)磺酰基)吲哚啉-3-基)丙腈,黄色油状物.1H NMR(400MHz,CDCl3)δ=1.24(s,3H),1.79-2.04(m,3H),2.13-2.21(m,1H),3.49(d,J=10.5Hz,1H),3.80(d,J=10.5Hz,1H),7.02(dd,J=1.0,7.4Hz,1H),7.06(ddd,J=0.6,7.2,7.2Hz,1H),7.25-7.29(m,1H),7.62-7.64(m,3H),7.70(ddd,J=1.8,1.8,8.7Hz,2H);13C NMR(100MHz,CDCl3)δ=140.85,136.28,135.34,132.59,129.05,128.77,128.74,124.35,123.13,119.13,114.36,60.86,43.05,36.51,25.87,12.80;HRMS(ESI-TOF)C18H18BrN2O2S+([M+H]+)405.0267.Found 405.0270.
2i,3-(3-甲基-1-(3-氯苯甲酰基)吲哚啉-3-基)丙腈,白色晶体:mp 133-134℃.1H NMR(400MHz,DMSO-d6)δ=1.29(s,3H),1.89-2.01(m,2H),2.18-2.30(m,1H),2.38-2.46(m,1H),3.74(d,J=11.0Hz,1H),3.93(d,J=10.0Hz,1H),7.12(brs,1H,不可交换),7.25(brs,1H,不可交换),7.32(d,J=8.0Hz,1H),7.51-7.60(m,3H),7.69(s,1H),8.08(brs,1H,不可交换);13C NMR(100MHz,DMSO-d6)δ=166.84,142.09(br),139.24,139.06(br),133.74,131.02,130.55,128.22,127.33,126.13,124.89(br),123.65,121.09,117.30(br),61.71(br),43.54(br),35.52,25.96,12.74;HRMS(ESI-TOF)C19H18ClN2O+([M+H]+)325.1102.Found 325.1104.
2j,3-(3-甲基-1-乙酰基-7-氯吲哚啉-3-基)丙腈,黄色油状物.1H NMR(400MHz,CDCl3)δ=1.35(s,3H),1.95-2.00(m,2H),2.26-2.31(m,5H),3.82(d,J=11.1Hz,1H),4.12(d,J=11.2Hz,1H),7.03(dd,J=1.0,7.4Hz,1H),7.12(dd,J=8.0,7.5Hz,1H),7.29(dd,J=1.0,8.0Hz,1H);13C NMR(100MHz,CDCl3)δ=170.07,142.83,139.90,130.17,126.66,124.39,121.00,119.17,62.49,44.56,34.48,23.50,23.43,12.97;HRMS(ESI-TOF)C14H16ClN2O+([M+H]+)263.0946.Found 263.0947.
2k1,3-(3-甲基-1-乙酰基-4-氯吲哚啉-3-基)丙腈,黄色油状物.1H NMR(400MHz,CDCl3)δ=1.58(s,3H),2.00-2.08(m,1H),2.14-2.20(m,2H),2.25(s,3H),2.49-2.56(m,1H),3.78(d,J=10.8Hz,1H),4.03(d,J=10.8Hz,1H),7.00(d,J=8.0Hz,1H),7.20(dd,J=8.1,8.1Hz,1H),8.21(d,J=8.0Hz,1H);13C NMR(100MHz,CDCl3)δ=168.84,144.57,131.03,130.32,130.04,125.44,119.33,115.83,60.73,44.96,34.05,25.99,24.41,13.18;HRMS(ESI-TOF)C14H16ClN2O+([M+H]+)263.0946.Found 263.0946.
2k'1,3-(3-甲基-1-乙酰基-6-氯吲哚啉-3-基)丙腈,浅黄色固体:mp 151-152℃.1H NMR(400MHz,CDCl3)δ=1.43(s,3H),1.94-2.08(m,2H),2.16-2.19(m,2H),2.24(s,3H),3.80(d,J=10.6Hz,1H),4.01(d,J=10.6Hz,1H),6.99(d,J=8.0Hz,1H),7.06(dd,J=1.9,8.0Hz,1H),8.25(d,J=1.3Hz,1H);13C NMR(100MHz,CDCl3)δ=168.87,143.31,134.50,134.45,124.15,122.91,119.24,117.57,60.86,43.02,36.85,26.61,24.20,12.91;HRMS(ESI-TOF)C14H16ClN2O+([M+H]+)263.0946.Found 263.0957.
2k2,3-(3-甲基-1-辛酰基-4-氯吲哚啉-3-基)丙腈,白色固体:mp 121-122℃.1HNMR(400MHz,CDCl3)δ=0.89(t,J=7.0Hz,3H),1.24-1.43(m,8H),1.57(s,3H),1.69-1.76(m,2H),2.00-2.07(m,1H),2.10-2.23(m,2H),2.36-2.56(m,3H),3.77(d,J=10.8Hz,1H),4.00(d,J=10.9Hz,1H),6.99(dd,J=0.8,8.1Hz,1H),7.19(dd,J=8.1,8.1Hz,1H),8.24(d,J=7.7Hz,1H);13C NMR(100MHz,CDCl3)δ=171.61,144.80,130.93,130.29,130.02,125.28,119.31,115.85,59.98,44.93,36.18,34.09,31.72,29.29,29.14,25.97,24.39,22.63,14.10,13.19;HRMS(ESI-TOF)C20H28ClN2O+([M+H]+)347.1885.Found 347.1883.
2k'2,3-(3-甲基-1-辛酰基-6-氯吲哚啉-3-基)丙腈,浅黄色油状物.1H NMR(400MHz,CDCl3)δ=0.89(t,J=7.0Hz,3H),1.26-1.42(m,11H),1.69-1.76(m,2H),1.94-2.06(m,2H),2.10-2.28(m,2H),2.34-2.49(m,2H),3.79(d,J=10.8Hz,1H),4.00(d,J=10.6Hz,1H),6.98(d,J=8.0Hz,1H),7.05(dd,J=1.8,8.0Hz,1H),8.30(s,1H);13C NMR(100MHz,CDCl3)δ=171.68,143.52,134.44,134.37,123.98,122.87,119.25,117.63,60.12,42.98,36.85,35.99,31.73,29.30,29.16,26.59,24.37,22.65,14.12,12.93;HRMS(ESI-TOF)C20H28ClN2O+([M+H]+)347.1885.Found 347.1871.
2l,3-(1-辛酰基-5-氯吲哚啉-3-基)丙腈,浅黄色固体:mp 107-108℃.1H NMR(400MHz,CDCl3)δ=0.89(t,J=7.0Hz,3H),1.24-1.42(m,8H),1.68-1.76(m,2H),1.91-2.00(m,1H),2.07-2.16(m,1H),2.36-2.50(m,4H),3.52-3.58(m,1H),3.79(dd,J=5.0,10.6Hz,1H),4.25(dd,J=9.4,10.6Hz,1H),7.13(s,1H),7.21(dd,J=1.8,8.6Hz,1H),8.19(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=171.50,141.57,134.27,128.66,128.57,123.96,118.80,118.19,53.64,38.84,35.92,31.72,30.60,29.32,29.15,24.45,22.65,14.71,14.12;HRMS(ESI-TOF)C19H26ClN2O+([M+H]+)333.1728.Found 333.1739.
2m1,2-((3-甲基-1-乙酰基-5-溴吲哚啉-3-基)甲基)丁腈,1:1勉强可分离的非对映异构体.非对映异构体1:黄色油状物.1H NMR(400MHz,CDCl3)δ=0.99(t,J=7.3Hz,3H),1.46(s,3H),1.49-1.57(m,2H),1.70(d,J=13.8Hz,1H),1.97-2.03(m,1H),2.10(dd,J=11.1,13.8Hz,1H),2.26(s,3H),3.77(d,J=10.8Hz,1H),4.36(d,J=10.8Hz,1H),7.15(s,1H),7.37(dd,J=1.5,8.6Hz,1H),8.14(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=169.12,141.84,138.72,131.65,125.11,122.42,118.69,116.38,59.85,44.38,43.49,28.47,28.14,27.43,24.25,11.08;HRMS(ESI-TOF)C16H20BrN2O+([M+H]+)335.0754.Found335.0755.非对映异构体2:浅黄色油状物.1H NMR(400MHz,CDCl3)δ=1.10(t,J=7.4Hz,3H),1.45(s,3H),1.60-1.68(m,2H),1.79(dd,J=3.6,14.2Hz,1H),2.00(dd,J=11.3,14.2Hz,1H),2.25(s,3H),2.55-2.62(m,1H),3.84(d,J=10.7Hz,1H),4.21(d,J=10.8Hz,1H),7.22(d,J=1.6Hz,1H),7.36(dd,J=1.9,8.6Hz,1H),8.10(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=168.91,140.85,140.55,131.47,125.42,121.96,118.76,116.27,61.57,43.16,42.77,28.87,27.07,24.69,24.14,11.36;HRMS(ESI-TOF)C16H20BrN2O+([M+H]+)335.0754.Found 335.0754.
2m2,2-((1-乙酰基-5-溴吲哚啉-3-基)甲基)丁腈,1:1勉强可分离的非对映异构体.非对映异构体1:浅黄色油状物.1H NMR(400MHz,CDCl3)δ=1.13(t,J=7.4Hz,3H),1.65-1.73(m,2H),1.92(dd,J=7.6,7.5Hz,2H),2.24(s,3H),2.59-2.68(m,1H),3.49-3.56(m,1H),3.86(dd,J=4.6,10.6Hz,1H),4.31(dd,J=9.4,10.2Hz,1H),7.30(s,1H),7.36(dd,J=1.9,8.6Hz,1H),8.11(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=168.80,141.62,135.45,131.53,127.01,121.44,118.70,116.07,55.67,38.69,38.13,31.67,26.09,24.13,11.46;HRMS(ESI-TOF)C15H18BrN2O+([M+H]+)321.0597.Found 321.0594.非对映异构体2:浅黄色油状物.1H NMR(400MHz,CDCl3)δ=1.14(t,J=7.4Hz,3H),1.66-1.81(m,3H),2.13(ddd,J=3.2,11.2,13.7Hz,1H),2.24(s,3H),2.49-2.57(m,1H),3.67-3.74(m,1H),3.79(dd,J=5.9,10.3Hz,1H),4.26(dd,J=9.8,9.8Hz,1H),7.27(s,1H),7.35(dd,J=1.8,8.7Hz,1H),8.10(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=168.70,141.73,135.41,131.42,126.68,121.11,118.55,116.22,54.19,38.01,37.47,30.98,26.18,24.18,11.55;HRMS(ESI-TOF)C15H18BrN2O+([M+H]+)321.0597.Found 321.0599.2n,2,2-二甲基-3-(3-甲基-1-乙酰基-5-溴吲哚啉-3-基)丙腈,浅黄色固体:mp 127-128℃.1H NMR(400MHz,CDCl3)δ=1.15(s,3H),1.46(s,3H),1.50(s,3H),1.87(d,J=14.9Hz,1H),2.05(d,J=14.9Hz,1H),2.25(s,3H),3.86(d,J=10.9Hz,1H),4.42(d,J=10.9Hz,1H),7.21(d,J=1.9Hz,1H),7.34(dd,J=2.0,8.6Hz,1H),8.10(d,J=8.6,1H);13C NMR(100MHz,CDCl3)δ=169.00,140.97,140.94,131.39,125.55,125.02,118.67,116.12,60.57,50.81,43.69,30.43,30.36,28.36,27.82,24.22;HRMS(ESI-TOF)Calcd for C16H20BrN2O+([M+H]+)335.0754.Found335.0756.
Claims (9)
1.一种N-烯丙基苯胺氰烷基化合成氰烷基吲哚啉(式II化合物)的方法,其特征在于,反应路线如下:
其中:
R1是氢、卤素、C1-6烷基或苯基;
R2是氢或C1-6烷基;
R3是COR6或SO2R7;
R4是氢或C1-6烷基;
R5是氢或C1-6烷基;
R6是C1-17烷基或-O-C1-6烷基;
R7是C1-6烷基、N,N-二甲基、噻吩基或
R8是氢、卤素、羟基、C1-6烷基或-O-C1-6烷基;
所述催化剂选自DTBP、DCP、BPO、TBHP、Oxone、TBPB或K2S2O8。
2.如权利要求1所述的方法,其特征在于:所述“卤素”是指氟、氯、溴或碘。
3.如权利要求2所述的方法,其特征在于:所述“卤素”是指氟、氯或溴。
4.如权利要求1所述的方法,其特征在于:所述“C1-6烷基”是指具有1-6个碳原子的饱和的直链或支链烃基;所述“C1-17烷基”是指具有1-17个碳原子的饱和的直链或支链烃基;所述“-O-C1-6烷基”,是指具有1-6个碳原子的饱和的直链或支链烷氧基。
5.如权利要求4所述的方法,其特征在于:所述具有1-6个碳原子的饱和的直链或支链烃基是指甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基或异己基;所述具有1-17个碳原子的饱和的直链或支链烃基是指甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基、异己基、n-C7H15、n-C9H19、n-C11H23、n-C17H35;所述具有1-6个碳原子的饱和的直链或支链烷氧基是指甲氧基、乙氧基或叔丁氧基。
6.如权利要求1所述的方法,其特征在于:R1选自氢、甲基、氟、氯、溴或苯基;R2选自氢或甲基;R3是COR6或SO2R7;R4是氢、甲基或乙基;R5选自氢、甲基或乙基;R6选自甲基、乙基、n-C7H15、n-C9H19、n-C11H23、n-C17H35、t-Bu或叔丁氧基;R7选自甲基、乙基、N,N-二甲基、噻吩基。
7.如权利要求1-6任一项所述的方法,其特征在于:所述催化剂为DTBP。
8.如权利要求7所述的方法,其特征在于:所述催化剂DTBP的用量为1.5-2.0当量。
9.式II化合物选自:
3-(3-甲基-1-丙酰基-5-溴吲哚啉-3-基)丙腈;
3-(3-甲基-1-丙酰基-5-氯吲哚啉-3-基)丙腈;
3-(3-甲基-1-辛酰基吲哚啉-3-基)丙腈;
3-(3,5-二甲基-1-辛酰基吲哚啉-3-基)丙腈;
3-(3-甲基-1-辛酰基-5-溴吲哚啉-3-基)丙腈;
3-(3-甲基-1-辛酰基-5-氯吲哚啉-3-基)丙腈;
3-(3-甲基-5-苯基-1-辛酰基吲哚啉-3-基)丙腈;
3-(3-甲基-1-癸酰基-5-溴吲哚啉-3-基)丙腈;
3-(3-甲基-1-十二酰基-5-溴吲哚啉-3-基)丙腈;
3-(3-甲基-1-十八酰基-5-溴吲哚啉-3-基)丙腈;
3-(3-甲基-1-新戊酰基-5-溴吲哚啉-3-基)丙腈;
3-甲基-3-(2-氰基乙基)-5-氯吲哚啉-1-羧酸叔丁酯;
3-(3-甲基-1-甲磺酰基-5-溴吲哚啉-3-基)丙腈;
3-(3-甲基-1-甲磺酰基-5-氯吲哚啉-3-基)丙腈;
3-(3-甲基-1-乙磺酰基-5-溴吲哚啉-3-基)丙腈;
N,N,3-三甲基-3-(2-氰基乙基)-5-溴吲哚啉-1-磺酰胺;
3-(3-甲基-1-(噻吩-2-基磺酰基)-5-溴吲哚啉-3-基)丙腈;
3-(3-甲基-1-苯磺酰基吲哚啉-3-基)丙腈;
3-(3-甲基-1-(对甲苯磺酰基)吲哚啉-3-基)丙腈;
3-(3-甲基-1-(邻甲苯磺酰基)吲哚啉-3-基)丙腈;
3-(3-甲基-1-((4-溴苯基)磺酰基)吲哚啉-3-基)丙腈;
3-(3-甲基-1-(3-氯苯甲酰基)吲哚啉-3-基)丙腈;
3-(3-甲基-1-乙酰基-7-氯吲哚啉-3-基)丙腈;
3-(3-甲基-1-乙酰基-4-氯吲哚啉-3-基)丙腈;
3-(3-甲基-1-乙酰基-6-氯吲哚啉-3-基)丙腈;
3-(3-甲基-1-辛酰基-4-氯吲哚啉-3-基)丙腈;
3-(3-甲基-1-辛酰基-6-氯吲哚啉-3-基)丙腈;
3-(1-辛酰基-5-氯吲哚啉-3-基)丙腈;
2-((3-甲基-1-乙酰基-5-溴吲哚啉-3-基)甲基)丁腈;
2-((1-乙酰基-5-溴吲哚啉-3-基)甲基)丁腈。
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CN112500254A (zh) * | 2019-09-16 | 2021-03-16 | 江西师范大学 | 由炔酰胺质子化引发的多烯环化反应 |
CN114874119A (zh) * | 2022-03-06 | 2022-08-09 | 昆明学院 | 光催化合成3,4-双烷基化-4-吡咯啉-2-酮衍生物的方法 |
CN114874119B (zh) * | 2022-03-06 | 2023-06-06 | 昆明学院 | 光催化合成3,4-双烷基化-4-吡咯啉-2-酮衍生物的方法 |
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