CN110746342B - 一种羟基内酰胺的制备方法 - Google Patents
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Abstract
Description
技术领域
本发明涉及一种羟基内酰胺化合物的制备方法。
背景技术
羟基内酰胺是一种重要的有机化合物。一方面它作为酰亚胺阳离子前体,可以发生多种有机反应,生成具有重要作用的精细有机化工品。另一方面,该结构广泛存在于天然产物以及生物活性分子中,是一种优势的医药、农药等先导化合物的结构。甚至于该类结构已经是目前市场上一线用药的母核结构,例如目前应用广泛的安眠类药物佐匹克隆。
为了得到这类化合物,目前已经发展了一些方法,归纳起来主要有三类:一是通过金属或者金属氢化物还原环状酰亚胺化合物,代表性的试剂有锌,硼氢化钠等(Journal ofOrganic Chemistry,82(4),2193-2198;2017;Synthetic Communications,36(4),435-444;2006)。该类方法需要用到当量的还原试剂,反应对水敏感,后处理产生大量的三废,没有大规模应用潜力。二是通过硅烷、硼烷等非金属还原试剂还原(SyntheticCommunications,28(13),2507-2516;1998)。该类方法也需要当量以上的还原剂,对水敏感,反应过程中产生的酸性气体对设备有较大腐蚀,后处理过程中三废量大,也不适宜工业化生产。三是通过催化氢化的方法。该类方法原子经济性高,副产物少,后处理简单,几乎无三废,是一种理想的方法。但目前该类方法的缺点是活性低,选择性差。例如非均相的钯炭催化剂,用量超过10%(WO 2007088189,WO 2009019281,WO 2008061955)。对于均相催化剂,S.H.Bergens等人(Journal of the American Chemical Society,132(37),12832-12834;2010)利用Noyori类型钌催化剂,成功实现了羟基内酰胺的制备,最低催化剂用量为0.02%。虽然该过程较为绿色,但催化剂用量大,成本高,达不到工业应用的要求。
发明内容
一方面公开一种环状酰亚胺均相催化氢化直接制备羟基内酰胺化合物的方法,通过本方法的实施,可以高效制备羟基内酰胺化合物,完全避免使用危险性试剂硼氢化钠等。
本发明通过以下技术方案实现:
一种羟基内酰胺化式(I)的制备方法,由式(II)所示环状酰亚胺在溶剂中,在碱存在下通过均相催化氢化反应制得
其中,R1,R2,R3,分别独立为H,C1-C12的烷基,芳基或者含杂原子取代的烷基,芳基,R1,R2也可以是通过环连接起来的C1-C12的烷基,芳基或者含杂原子取代的烷基,芳基。
在一些实施例中,所述催化剂为配体和铱金属前体的原位配合物,其中配体的结构为具有(III)或(IV)结构的二茂铁配体,其中Ar为苯基,4-甲基苯基,3,5-二甲基苯基,3,5-二甲基-4-甲氧基苯基;铱金属前体为[Ir(COD)Cl]2;溶剂为异丙醇、四氢呋喃、甲苯的一种或者任意比例的混合物,碱为叔丁醇钾、叔丁醇钠、叔丁醇锂、氢氧化钾、氢氧化钠、碳酸钠、碳酸钾、碳酸铯的一种或者任意比例混合物。
在一些实施例中,所述催化剂与环状酰亚胺的比例为1∶5,000-100,000,优选1∶20,000-50,000。
在一些实施例中,所述溶剂为异丙醇、四氢呋喃、甲苯中的一种或几种组合,更优选异丙醇。
在一些实施例中,所述碱为叔丁醇钾,碱与环状酰亚胺的比例为1∶5-100,优选1∶10-50。
在一些实施例中,所述均相催化氢化反应的温度为20-80摄氏度,更优选40-60摄氏度。
在一些实施例中,所述均相催化氢化反应的氢气压力为1-10MPa,优选4-6MPa。
在一些实施例中,所述均相催化氢化反应的时间为10-30小时,优选20-25小时。
本发明采用弱给电子性的三齿配体与铱配合做催化剂,一方面通过三齿配位增强了催化剂的稳定性,不易失活,另一方面精细的调控了催化剂的活性,能够选择性活化一分子氢气对环状酰亚胺进行还原,一步反应专一生成羟基内酰胺化合物。同时与现有技术相比,本方法具有原子经济性高、选择性单一、三废少、易于工业化等特点。本发明的催化剂转化数(TON,turnovernumber)高达100,000,大幅度领先于目前该领域的所有已知催化剂,易于工业化放大。
具体实施方式
以下通过具体的实施例对本发明上述的内容作进一步的详细说明,但本发明不局限于实施例。
实施例1
在氩气气氛下往4.0mL的瓶中加入催化剂前体[Ir(COD)Cl]2(6.71mg,1.0×10- 2mmol,1eq),配体(III)(2.4×10-2mmol,2.4eq)和无水异丙醇(iPrOH,2.0mL)。将混合物在在充满氩气的手套箱中25℃下搅拌12.0h,得到橙红色溶液,该催化剂溶液可以直接用来做催化反应。
实施例2
在氩气气氛下往4.0mL的瓶中加入催化剂前体[Ir(COD)C1]2(6.71mg,1.0×10- 2mmol,1eq),配体IV(2.4×10-2mmol,2.4eq)和无水异丙醇(iprOH,2.0mL)。将混合物在在充满氩的手套箱中25℃下搅拌12.0h,得到橙红色溶液,该催化剂溶液可以直接用来做催化反应。
实施例3
在带磁子的玻璃试管中加入237mg2-苄基异吲哚啉-1,3-二酮(1mmol),11.2mg叔丁醇钾,氮气保护下加入2毫升异丙醇,加入10微升0.01M的催化剂(S/C=10,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品232mg,收率97%。
白色固体,1H NMR(400MHz,d6-DMSO)δ7.71-7.69(m,1H),7.66-7.53(m,3H),7.53-7.29(m,4H),7.28-7.23(m,1H),5.67(d,J=8.0Hz,1H),4.92(d,J=16Hz,1H),4.37(d,J=12Hz,1H).13C NMR(101MHz,CDCl3)δ166.15,144.89,137.74,132.09,131.42,129.42,128.49,127.68,127.11,123.76,122.47,80.28,42.11.
实施例4
在带磁子的玻璃试管中加入257mg 2-苄基-4-氯异吲哚啉-1,3-二酮(1mmol),11.2mg叔丁醇钠,氮气保护下加入2毫升四氢呋喃,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,80℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品251mg,两种异构体比例为2.5∶1,收率97%。
白色固体。1H NMR(400MHz,d6-DMSO)δ7.69-7.53(m,3H),7.36-7.26(m,5H),7.53-7.29(m,4H),7.28-7.23(m,1H),6.92(d,J=8.0Hz,0.3H),6.82(d,J=8.0Hz,0.7H),5.72(d,J=8.0Hz,0.3H),5.66(d,J=8.0Hz,0.7H),4.93-4.85(m,1H),4.38-4.34(m,1H).13CNMR(101 MHz,d6-DMSO)δ165.01,163.85,147.71,141.33,137.51,137.37,133.62,132.66,131.71,130.78,129.44,129.08,128.60,128.56,127.78,127.27,127.22,127.10,122.88,121.56,79.64,79.31,40.15.HRMS(ESI)calcd.for C15H12C1NO2[M+H]+:274.0557,Found:274.0628.
实施例5
在带磁子的玻璃试管中加入257mg 2-苄基-5-氯异吲哚啉-1,3-二酮(1mmol),6mg氢氧化钾,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入6MPa氢气,20℃反应30小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品246mg,两种异构体比例为1∶1,收率95%。
白色固体。1H NMR(400MHz,CDCl3)δ7.54-7.39(m,3H),7.31-7.27(m,5H),5.56(d,J=8.0Hz,1H),4.94-4.89(m,1H),4.29-4.25(m,1H),4.00-3.91(m,1H).13C NMR(101MHz,CDCl3)δ166.51,166.22,145.65,142.20,139.00,136.51,136.45,136.29,133.05,132.64,130.37,129.73,128.98,128.61,128.57,127.99,127.97,124.88,124.60,124.20,123.60,80.81,80.65,42.96.HRMS(ESI)calcd.forC15H12ClNO2[M+H]+:274.0557,Found:274.0629.
实施例6
在带磁子的玻璃试管中加入224mg 2-苯基异吲哚啉-1,3-二酮(1mmol),6mg氢氧化钠,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入10MPa氢气,30℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品220mg,收率97%。
白色固体。1H NMR(400MHz,d6-DMSO)δ7.78-7.67(m,5H),7.63-7.60(m,1H),7.46-7.42(m,2H),7.23-7.19(m,1H),6.54(s,1H).13C NMR(101MHz,CDCl3)δ165.43,144.40,137.46,132.75,131.28,129.67,128.66,124.64,123.66,122.83,122.30,81.87.
实施例7
在带磁子的玻璃试管中加入237mg 2-(对甲基苯)异吲哚啉-1,3-二酮(1mmol),6mg氢氧化锂,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品230mg,收率96%。
白色固体。1H NMR(400MHz,d6-DMSO)δ7.78-7.67(m,5H),7.63-7.60(m,1H),7.46-7.42(m,2H),7.23-7.19(m,1H),6.54(s,1H).13C NMR(101MHz,CDCl3)δ168.44,145.66,136.97,135.54,133.99,132.70,130.92,130.48,125.08,124.63,124.15,84.37,21.04.
实施例8
在带磁子的玻璃试管中加入253mg 2-(4-甲氧基苯)异吲哚啉-1,3-二酮(1mmol),10mg叔丁醇锂,氮气保护下加入2毫升异丙醇,加入20微升0.01M的催化剂(S/C=5,000),充入1MPa氢气,60℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品250mg,收率98%。
白色固体;95%收率.1H NMR(600MHz,T-MeOD)δ7.81-7.79(m,1H),7.71-7.67(m,2H),7.61-7.58(m,1H),7.54-7.52(m,2H),7.02-7.00(m,2H),6.31(s,1H),3.83(s,3H).13CNMR(150MHz,T-MeOD)δ168.61,159.61,145.77,133.94,132.72,130.92,130.79,127.32,124.65,124.14,115.26,84.82,55.93.
实施例9
在带磁子的玻璃试管中加入241mg 2-(2-氟苯)异吲哚啉-1,3-二酮(1mmol),11mg叔丁醇钾,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品237mg,收率97%。
白色固体。1H NMR(400MHz,T-MeOD)δ7.82-7.80(m,1H),7.72-7.65(m,3H),7.62-7.58(m,2H),7.46-7.40(m,1H),6.99-6.94(m,1H),6.45(s,1H).13C NMR(101MHz,CDCl3)δ168.36,165.46,163.04,145.45,140.34,140.24,135.44,134.36,132.37,131.25,131.16,131.06,130.09,126.20,124.66,124.34,123.65,119.15,119.12,112.89,112.68,110.86,110.60,84.02,71.42.
实施例10
在带磁子的玻璃试管中加入258mg 2-(5-氯吡啶)异吲哚啉-1,3-二酮(1mmol),11mg碳酸钾,氮气保护下加入2毫升四氢呋喃,加入2微升0.01M的催化剂(S/C=50,000),充入6MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品251mg,收率96%。
白色固体。1H NMR(400MHz,CDCl3)δ8.59(d,J=8.0Hz,1H),8.34(d,J=4.0Hz,1H),7.91-7.89(m,1H),7.79-7.76(m,1H),7.72-7.67(m,2H),7.60-7.56(m,1H),6.73(d,J=4.0Hz,1H),5.52(d,J=4.0Hz,1H).13C NMR(101MHz,CDCl3)δ166.48,150.39,146.06,142.20,138.77,133.68,131.73,130.33,126.99,124.30,123.81,115.12,82.30.
实施例11
在带磁子的玻璃试管中加入251mg 2-(2-甲基苄基)异吲哚啉-1,3-二酮(1mmol),15mg叔丁醇钠,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品249mg,收率98%。
白色固体。1H NMR(400MHz,T-MeOD)δ7.79-7.76(m,1H),7.66-7.54(m,3H),7.23-7.08(m,4H),5.66(s,1H),5.06(d,J=16Hz,1H),4.38(d,J=12Hz,1H),2.31(d,J=4Hz,3H).13C NMR(101MHz,T-MeOD)δ169.26,146.13,139.59,138.39,133.66,132.61,130.78,129.73,129.66,129.25,126.17,124.68,123.94,82.07,43.61,21.42.HRMS(ESI)calcd.for C16H15NO2[M+H]+:254.1103,Found:254.1175.
实施例12
在带磁子的玻璃试管中加入251mg 2-(3-甲基苄基)异吲哚啉-1,3-二酮(1mmol),10mg甲醇钠,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品248mg,收率98%。
白色固体。1H NMR(400MHz,CDCl3)δ7.62-7.60(m,1H),7.56-7.54(m,2H),7.46-7.43(m,1H),7.16-7.13(m,4H),5.50(s,1H),4.68(d,J=16Hz,1H),4.21(d,J=16Hz,1H),2.31(s,3H).13C NMR(101MHz,CDCl3)δ167.47,144.25,136.63,134.46,132.48,131.16,130.64,129.75,128.85,127.84,126.30,123.62,123.44,81.14,40.32,19.34.HRMS(ESI)calcd.for C16H1sNO2[M+H]+:254.1103,Found:254.1174.
实施例13
在带磁子的玻璃试管中加入251mg 2-(4-甲基苄基)异吲哚啉-1,3-二酮(1mmol),12mg甲醇钾,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品249mg,收率98%。
白色固体。1H NMR(400MHz,CDCl3)δ7.64-7.63(m,1H),7.55-7.54(m,2H),7.46-7.43(m,1H),7.20-7.18(m,2H),7.10-7.08(m,2H),5.57(s,1H),4.80(d,J=16Hz,1H),4.19(d,J=12Hz,1H),2.30(s,3H).13C NMR(101MHz,CDCl3)δ167.43,144.09,137.49,133.87,132.43,131.47,129.86,129.52,128.60,123.53,123.49,81.07,42.49,21.22.
实施例14
在带磁子的玻璃试管中加入161mg2-甲基异吲哚啉-1,3-二酮(1mmol),6mg氢氧化钠,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品158mg,收率97%。
白色固体。1H NMR(400MHz,CDCl3)δ7.60-7.58(m,1H),7.56-7.52(m,2H),7.42-7.38(m,1H),5.29(s,1H),2.91(s,3H).13CNMR(101MHz,CDCl3)δ167.70,143.92,132.27,131.55,129.83,123.35,123.19,83.71,26.23.
实施例15
在带磁子的玻璃试管中加入189mg 2-正丙基异吲哚啉-1,3-二酮(1mmol),20mg碳酸铯,氮气保护下加入2毫升四氢呋喃,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品184mg,收率96%。
白色固体。1H NMR(400MHz,CDCl3)δ7.54-7.47(m,2H),7.43-7.41(m,1H),7.36-7.32(m,1H),5.67(d,J=8.0Hz,1H),3.34-3.27(m,1H),3.17-3.10(m,1H),1.59-1.49(m,2H),0.83(t,J=8.0Hz,3H).13C NMR(101MHz,CDCl3)δ170.26,144.11,132.08,131.44,129.53,123.31,13.04,81.61,40.67,21.48,11.43.
实施例16
在带磁子的玻璃试管中加入203mg 2-异丁基异吲哚啉-1,3-二酮(1mmol),10mg叔丁醇锂,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品198mg,收率97%。
白色固体。1H NMR(400MHz,CDCl3)δ7.62-7.54(m,3H),7.46-7.42(m,1H),5.74(s,1H),3.30-3.24(m,1H),3.15-3.10(m,1H),2.07-2.00(m,1H),0.95(d,J=4.0Hz,3H),0.84(d,J=4.0Hz,3H).13C NMR(101MHz,CDCl3)δ168.17,134.45,131.49,123.07,44.77,27.44.
实施例17
在带磁子的玻璃试管中加入203mg2-叔丁基异吲哚啉-1,3-二酮(1mmol),23mg甲醇钾,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品199mg,收率98%。
白色固体。1H NMR(400MHz,CDCl3)δ7.77-7.68(m,1H),7.53-7.44(m,3H),6.00(d,J=4.0Hz,1H),1.61(s,3H).13C NMR(101MHz,CDCl3)δ168.06,143.62,132.82,132.14,129.66,123.16,122.83,82.41,54.89,28.72.
实施例18
在带磁子的玻璃试管中加入257mg 2-(2-氟苄基)异吲哚啉-1,3-二酮(1mmol),9mg碳酸锂,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品253mg,收率98%。
白色固体。1H NMR(400MHz,d6-DMSO))δ7.63-7.55(m,1H),7.47-7.43(m,1H),7.53-7.29(m,4H),7.26-7.21(m,2H),7.06-6.99(m,2H),5.64(s,1H),4.62(d,J=16Hz,1H),4.42(d,J=16Hz,1H).13C NMR(101MHz,CDCl3)δ167.70,162.16,159.71,144.15,132.57,131.10,130.76,130.73,129.84,129.61,129.53,124.49,124.45,123.86,123.71,123.64,123.47,115.68,115.46,81.46,81.45,36.38,36.34.HRMS(ESI)calcd.for C15H12FNO2[M+H]+:258.0852,Found:258.0924.
实施例19
在带磁子的玻璃试管中加入300mg 2-(4-溴苯)异吲哚啉-1,3-二酮(1mmol),10mg叔丁醇锂,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品295mg,收率98%。
白色固体。1H NMR(600MHz,T-MeOD)δ7.83-7.81(m,1H),7.72-7.70(m,4H),7.62-7.58(m,3H),6.46(s,1H),4.60(s,3H).13C NMR(150MHz,T-MeOD)δ168.34,145.56,137.78,134.31,132.95,132.44,131.07,125.88,124.69,124.32,119.50,84.05.
实施例20
在带磁子的玻璃试管中加入241mg 2-(3-氟苯)异吲哚啉-1,3-二酮(1mmol),11mg叔丁醇钾,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品237mg,收率97%。
白色固体。1H NMR(400MHz,T-MeOD)δ7.84-7.82(m,1H),7.73-7.70(m,2H),7.69-7.67(m,1H),7.63-7.60(m,2H),7.47-7.43(m,1H),7.00-6.97(m,1H),6.49(s,1H).13C NMR(101MHz,CDCl3)δ168.39,165.10,163.49,145.54,140.38,140.31,134.38,132.43,131.26,131.20,131.08,124.70,124.36,119.21,119.19,112.88,112.74,110.87,110.70,84.07.
实施例21
在带磁子的玻璃试管中加入357mg 2-(4-氯苯)异吲哚啉-1,3-二酮(1mmol),10mg叔丁醇锂,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品251mg,收率97%。
白色固体。1H NMR(600MHz,d6-DMSO)δ7.84-7.82(m,2H),7.78-7.77(m,1H),7.74-7.72(m,1H),7.69-7.68(m,1H),7.62-7.60(m,1H),7.51-7.50(m,2H),6.92-6.91(m,1H),6.53(d,J=4.0Hz,1H).13C NMR(150MHz,d6-DMSO)δ165.56,144.29,136.48,133.01,131.05,129.82,128.65,128.57,123.72,123.54,122.98,81.95.
实施例22
在带磁子的玻璃试管中加入241mg 2-(4-氟苯)异吲哚啉-1,3-二酮(1mmol),11mg叔丁醇钾,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品238mg,收率98%。
白色固体。1H NMR(600MHz,T-MeOD)δ7.82-7.81(m,1H),7.72-7.69(m,4H),7.62-7.59(m,1H),7.21-7.18(m,2H),6.40(s,1H).13C NMR(150MHz,CDCl3)δ168.50,162.87,161.25,145.70,134.46,134.44,134.16,132.51,131.00,127.16,127.10,124.69,124.26,116.64,116.49,84.56.
实施例23
在带磁子的玻璃试管中加入175mg 1-苯基吡咯烷-2,5-二酮(1mmol),5.6mg氢氧化钾,氮气保护下加入2毫升四氢呋喃,加入5微升0.01M的催化剂(S/C=20,000),充入2MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品170mg,收率96%。
白色固体。1H NMR(600MHz,CDCl3)δ7.13-7.31(m,5H),5.82-5.89(m,1H),2.12-7.49(m,4H).13C NMR(150MHz,CDCl3)δ174.91,137.32,128.95,128.08,127.54,81.87,27.78,25.90.
实施例24
在带磁子的玻璃试管中加入323mg 1-萘基-苯并异吲哚啉-1,3-二酮(1mmol),4.0mg氢氧化钠,氮气保护下加入2毫升四氢呋喃,加入2微升0.01M的催化剂(S/C=50,000),充入2MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品315mg,收率97%。
白色固体。1HNMR(400MHz,d6-DMSO)δ8.38-8.01(m,4H),7.73-7.55(m,4H),7.46-6.99(m,2H),7.23-7.19(m,3H),6.84(s,1H).13CNMR(101MHz,CDCl3)δ167.01,142.74,136.21,134.32,132.42,133.63,133.05,129.04,128.67,128.31,127.83,127.63,127.12,126.16,125.89,125.34,124.75,121.02,119.07,104.09,91.8.
Claims (8)
1.一种环状酰亚胺均相催化氢化直接制备羟基内酰胺化合物的方法。羟基内酰胺化合物的化学结构式通式(I)表示,其由式(II)所示的环状酰亚胺通过铱-三齿配体均相催化剂,碱存在下,均相催化氢化反应制得,
(I) (II)
其中,R1,R2,R3,分别独立为H,C1-C12的烷基,芳基或者含杂原子取代的烷基,芳基;R1,R2也可以是通过环连接起来的C1-C12的烷基,芳基或者含杂原子取代的烷基,芳基;
所述的催化剂为配体和铱金属前体原位络合得到,配体的结构为具有(III)或(IV)结构的二茂铁配体,其中Ar为苯基,4-甲基苯基,3,5-二甲基苯基,3,5-二甲基-4-甲氧基苯基;铱金属前体为[Ir(COD)Cl]2,配体与金属的比例为2.0-2.4:1
,
所述的碱为叔丁醇钾、叔丁醇钠、叔丁醇锂、氢氧化钾、氢氧化钠、碳酸钠、碳酸钾、碳酸铯的一种或者任意比例混合物。
2.根据权利要求1所述的方法,反应的溶剂为异丙醇、四氢呋喃、甲苯的一种或者任意比例的混合物。
3.根据权利要求1所述的方法,催化剂与环状酰亚胺的比例为1:5,000-100,000。
4.根据权利要求2所述的方法,反应的溶剂为异丙醇、四氢呋喃、甲苯。
5.根据权利要求1或权利要求4所述的方法,碱与环状酰亚胺的比例为1:5-10。
6.根据权利要求1所述的方法,反应温度为20-80摄氏度。
7.根据权利要求1所述的方法,反应氢气压力为1-10 MPa。
8.根据权利要求1所述的方法,反应的时间为10-30小时。
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Asymmetric hydrogenation of aromatic ketones using an iridium(I) catalyst containing ferrocene-based P–N–N tridentate ligands;Huifang Nie et al.;《Tetrahedron: Asymmetry》;20131206;全文 * |
Desymmetrization of meso-Cyclic Imides via Enantioselective Monohydrogenation;Satoshi Takebayashi et al.;《J. AM. CHEM. SOC.》;20100824;表1,Scheme 1 * |
Enantioselective Iridium-Catalyzed Hydrogenation of α-Keto Amides to α-Hydroxy Amides;Guoxian Gu et al.;《Org. Lett.》;20171026;全文 * |
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