CN111732516A - 一种n-芳基取代杂环化合物的制备方法 - Google Patents
一种n-芳基取代杂环化合物的制备方法 Download PDFInfo
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Abstract
本发明涉及有机化学合成技术领域,具体涉及一种N‑芳基取代杂环化合物的制备方法,是以碱为促进剂,有机溶剂条件下,胺类化合物和硝基类衍生物,以1:1~1:3的摩尔比,在常温常压下反应30‑60分钟;反应结束后加水淬灭,有机溶剂萃取,柱层析分离(V石油醚:V乙酸乙酯=40:1~20:1),得到N‑芳基取代杂环衍生物。本发明利用硝基苯作为Ar‑H来源,N‑甲基苯胺、N‑乙基苯胺、N‑甲基杂环、四氢喹啉等都可以作为胺源,在t‑BuONa/DMSO/O2体系下,实现芳环的直接芳胺化反应。这种方法有以下优点:方法简单,高的原子经济性,避免使用了昂贵的过渡金属,温和的反应条件,产生的是环境友好的副产物。
Description
技术领域
本发明属于有机化学合成技术领域,涉及一种N-芳基取代杂环化合物的制备方法。
背景技术
N-芳基取代杂环化合物是很多天然产物和药物的重要结构单元(Hili R, YudinA K. Nat. Chem. Boil.2006, 2(6): 284-287),另外,这些化合物可以用来制备配体,人工染料,电子材料和光学材料(Lawrence, S. A. Cambridge University Press,Cambridge, 2004; pp 265-305)。因此,发展了很多种合成N-芳基取代杂环化合物的方法。在这些方法中,最经典的方法是Ullmann偶联(Ullmann F. Ueber eine neueBildungsweise von Diphenylaminderivaten[J]. Ber. Deut. Chem. Ges.1903, 36(2):2382-2384) 和Buchwald-Hartwig 偶联(Guram A S, Buchwald S L. J. Am. Chem. Soc.1994, 116(17): 7901-7902; Paul F, Patt J, Hartwig J. F. J. Am. Chem. Soc.1994, 116(13): 5969-5970; Shekhar S, Ryberg P, Hartwig J F, et al. J. Am. Chem. Soc. 2006, 128(11): 3584-3591)。这些方法的缺点是需要预制备芳基卤化物或者芳基硼酸酯,同时会产生卤化氢或者硼酸副产物,不利于原子经济性。而CDC偶联胺化反应可以很好的解决这一问题,CDC偶联胺化反应是Ar-H键和N-H键直接偶联,不需要预官能团化。在过去的几十年中,直接Ar-H胺化构建N-芳基化合物的研究主要集中在铱,钯,铁,铜,钴,银,锰等过渡金属催化( Park Y, Kim Y, Chang S. Chem. Rev. 2017,117, 9247-9301; Cho S H, Kim J Y, Kwak J, Chang S. Chem. Soc. Rev. 2011,40, 5068; YuanJ, Liu C, Lei A. Chem. Commun. 2015,51, 1394-1409; Kim H, Chang S. ACS Catal. 2016,6, 2341-2351)。这种方法是过渡金属在导向基的辅助下插入Ar-H键形成稳定的环状金属络合中间体,接着和胺源反应生成含C-N键的目标产物。
尽管过渡金属催化的Ar-H直接胺基化反应广泛应用,但是也存在一系列的缺点,例如:1) 需要用到昂贵的配体和催化剂,有时需要一些添加剂;2)需要较苛刻的条件(高温或者是长时间反应);3)产生重金属污染,尤其是在合成对重金属含量要求较高的化合物时;4)反应底物中导向基团的去除是较大的难题。通过文献调研我们发现,无金属催化的Ar-H 和N-H 直接偶联的CDC反应研究较少,仍然存在很大的挑战性和研究价值。
发明内容
本发明的目的在于提供一种非金属条件下直接氧化脱氢偶联(CDC)制备N-芳基取代杂环化合物的制备方法,利用硝基苯作为Ar-H来源,N-甲基苯胺、N-乙基苯胺、N-甲基杂环、四氢喹啉等都可以作为胺源,在t-BuONa/DMSO/O2体系下,实现芳环的直接芳胺化反应。这种方法有以下优点:方法简单,高的原子经济性,避免使用了昂贵的过渡金属,温和的反应条件,产生的是环境友好的副产物。
本发明所述的N-芳基取代杂环化合物的制备方法,是以碱为促进剂,有机溶剂条件下,胺类化合物和硝基类化合物,以1:1~1:3的摩尔比,在常温常压下反应30-60分钟;反应结束后加水淬灭,有机溶剂萃取,柱层析分离(V石油醚:V乙酸乙酯 = 40:1~20:1),得到N-芳基取代杂环衍生物。
进一步地,所述胺类化合物为N-烷基或N-芳基苯胺衍生物、1,2,3,4-四氢喹啉衍生物、吲哚啉衍生物、苯胺衍生物或N-甲基吡啶衍生物,结构式为:
其中,X = C(碳)或N(氮);
R1、R2、R3、R4、R5和R6为氢、C1~C40的脂肪基团(如甲基、乙基、丙基、异丙基、丁基、苄基)、C4~C60内的芳香基团(吡啶衍生物基、苯基、取代苯基、1-萘基、2-萘基)、烷氧基、羟基、硝基、胺基或者卤素(氟、氯、溴,碘)。
进一步地,所述硝基类化合物的结构式为:
R7和R8为氢、C1~C40的脂肪基团(如甲基、乙基、丙基、异丙基、丁基、苄基)、C4~C60内的芳香基团(吡啶衍生物基、苯基、取代苯基、1-萘基、2-萘基)、烷氧基、羟基、硝基、胺基或者卤素(氟、氯、溴,碘)。
进一步地,所述的促进剂碱为t-BuONa、t-BuOK、KOH、NaOH或K2CO3,促进剂的用量为胺类衍生物摩尔量的1-3倍。
进一步地,所述的有机溶剂可采用DMF(N,N-二甲基甲酰胺)、DMA(N,N-二甲基乙酰胺)、DMSO(二甲基亚砜)、NMP(氮甲基吡咯烷酮)、CH2Cl2(二氯甲烷)、CHCl3(氯仿)、CCl4(四氯化碳)、1,2-二氯乙烷、1,4-二氧六环、乙腈、乙醚、DME(乙二醇二甲醚)或THF(四氢呋喃)等。
本发明N-芳基取代杂环化合物的合成通式为:
本发明相对于现有技术具有以下优点:
1、本发明在碱为促进剂的促进下,由胺类衍生物与硝基苯或硝基萘类衍生物进行反应,通过直接氧化脱氢偶联(CDC)的方法,一步即可高效得N-芳基取代杂环化合物,该反应原料及促进剂廉价易得,合成工艺简单。
2、反应条件温和,室温及空气条件下就能反应,产率优良(可达83%);
3、反应迅速,30-60分钟类反应完毕。
4、反应能实现克级制备。
具体实施方式
下面通过具体实施例对本发明作进一步说明。
实施例1: 3a-3h制备。
将N-甲基苯胺类化合物1a-1h (0.5 mmol)、t-BuONa(294 mg,1.5 mmol),硝基苯2a (184.5 mg, 1.5 mmol),加入2.0 mL二甲基亚砜(DMSO)中,室温下反应60 分钟后停止反应,用水淬灭,二氯甲烷萃取,柱层析分离(采用硅胶柱;洗脱剂:石油醚/乙酸乙酯 = 20/1),得到纯品N-甲基二苯基衍生物3a-3h。
其合成路线如下:
N-methyl-4-nitro-N-phenylaniline:3a
黄色固体,产率为83%; 1H NMR (400 MHz, CDCl3) δ 7.98 -7.92 (m, 2H), 7.36(t, J = 7.8 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 7.16 -7.11 (m, 2H), 6.57 (dd,J = 7.3, 5.3 Hz, 2H), 3.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.7, 146.3,138.0, 130.2, 126.7, 126.6, 125.7, 112.3, 40.5.
4-fluoro-N-methyl-N-(4-nitrophenyl) aniline: 3b
黄色固体,产率为75%;1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 9.3 Hz, 2H),7.31 - 7.10 (m,4H), 6.62 (d, J = 9.3 Hz, 2H), 3.38 (s, 1H). 13C NMR (100 MHz,CDCl3) δ 160.6 (d, J = 245.7Hz), 153.4, 142.0, 137.9, 128.22 (d, J = 8.4 Hz),125.3, 116.6(d, J = 22.6 Hz), 111.8, 40.1.
N,4-dimethyl-N-(4-nitrophenyl) aniline: 3c
黄色固体,68%;1H NMR (400 MHz, CDCl3) δ 8.14 (dd, J = 7.3, 2.1 Hz, 2H),7.40-7.32 (m, 2H), 7.25-7.17 (m, 2H), 6.73 (dd, J = 7.4, 2.0 Hz, 2H), 3.47(s, 3H), 2.49 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 154.0, 143.8, 138.0, 136.8,130.8, 126.6, 125.8, 112.2, 40.5, 21.1.
3-chloro-N-methyl-N-(4-nitrophenyl)aniline:3d
黄色固体,白色固体,产率为73%;1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 9.3Hz, 2H), 7.38 (t, J = 8.0 Hz, 1H), 7.30-7.22 (m, 2H), 7.15 (dd, J = 8.0, 0.9Hz, 1H), 6.72 (d, J = 9.3 Hz, 2H), 3.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ153.3, 147.7, 138.8, 135.5, 131.2, 126.7, 126.6, 125.8, 124.6, 113.3, 40.5.
3-bromo-N-methyl-N-(4-nitrophenyl) aniline: 3e
黄色固体,产率为76%;1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 9.3 Hz, 2H),7.40 (m, 2H), 7.31 (t, J = 7.9 Hz, 1H), 7.18 (dd, J = 8.0, 0.8 Hz, 1H), 6.72(d, J = 9.3 Hz, 2H), 3.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 152.8, 147.3,138.5, 130.9, 129.1, 129.0, 125.3, 124.5, 122.9, 112.8, 40.0.
3-methoxy-N-methyl-N-(4-nitrophenyl) aniline: 3f
黄色固体,产率为71%;1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 9.2 Hz, 2H),7.36 (t, J = 8.1 Hz, 1H), 6.83 (m, 2H), 6.76 (s, 1H), 6.69 (d, J = 9.2 Hz,2H), 3.82 (s, 3H), 3.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 160.6, 153.2,147.1, 137.8, 130.4, 125.3, 118.2, 112.1, 111.9, 111.8, 55.0, 40.0.
3-methyl-N-(4-nitrophenyl)aniline: 3g
黄色固体, 产率为72%;1H NMR (400 MHz, CDCl3) δ 8.11- 8.00 (m, 2H), 7.35(t, J = 7.7 Hz, 1H), 7.10 (m, 3H), 6.74-6.62 (m, 2H), 3.40 (s, 3H), 2.40 (s,3H). 13C NMR (100 MHz, CDCl3) δ 154.0, 146.4, 140.4, 138.0, 130.1, 127.8,127.4, 125.9, 123.8, 112.4, 40.6, 21.5.
2-fluoro-N-methyl-N-(4-nitrophenyl) aniline: 3h
黄色固体,产率为42%;1H NMR (400 MHz, CDCl3) δ 8.04 (t, J = 6.3 Hz, 2H),7.40-7.07 (m, 4H), 6.58 (d, J = 9.3 Hz, 2H), 3.34 (s, 3H). 13C NMR (100 MHz,CDCl3) δ 158.5 (d, J = 249.5 Hz), 153.3, 138.6, 133.21 (d, J = 12.1 Hz),129.5, 128.9 (d, J = 7.8 Hz), 125.7, 125.4 (d, J = 3.4 Hz), 117.4 (d, J =19.9 Hz), 111.8, 39.8.
实施例2: 3i, 3j的制备。
将N-乙基苯胺类化合物1i、1j (0.5 mmol)、t-BuONa(294 mg,1.5 mmol),硝基苯2a (184.5 mg, 1.5 mmol),加入2.0 mL二甲基亚砜(DMSO)中,室温下反应60 分钟后停止反应,用水淬灭,二氯甲烷萃取,柱层析分离(采用硅胶柱;洗脱剂:石油醚/乙酸乙酯 = 20/1),得到纯品N-甲基二苯基衍生物3i, 3j。
其合成路线如下:
N-ethyl-4-nitro-N-phenylaniline: 3i
黄色固体,产率为71%;1H NMR (400 MHz, CDCl3) δ 8.03(d, J = 9.4 Hz, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H),7.26-7.15 (m, 2H), 6.64-6.55 (m, 2H), 3.82 (q, J = 7.1 Hz, 2H), 1.27 (t, J =7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 153.1, 144.9, 137.8, 130.3, 127.8,127.1, 126.0, 112.3, 47.2, 12.3.
N-ethyl-4-methyl-N-(4-nitrophenyl)aniline: 3j
黄色固体,产率为58%;1H NMR (400 MHz, CDCl3)) δ8.02 (d, J = 9.0 Hz, 2H), 7.29 (d, J = 7.7 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H),6.58 (d, J = 9.1 Hz, 2H), 3.88-3.74 (m, 2H), 2.42 (s, 3H), 1.28 (t, J = 6.9Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 153.3, 142.1, 137.4, 137.1, 130.9, 127.7,125.9, 111.9, 47.2, 21.1, 12.3.
实施例3: 3k, 3l制备。
将N, N-二苯基胺类化合物1k, 1l (0.5 mmol)、t-BuONa(294 mg,1.5 mmol),硝基苯2a (184.5 mg, 1.5 mmol),加入2.0 mL二甲基亚砜(DMSO)中,室温下反应60 分钟后停止反应,用水淬灭,二氯甲烷萃取,柱层析分离(采用硅胶柱;洗脱剂:石油醚/乙酸乙酯 =20/1),得到纯品N-甲基二苯基衍生物3k, 3l.
其合成路线如下:
4-nitro-N,N-diphenylaniline: 3k
黄色固体,产率为67%;1H NMR (400 MHz, CDCl3) δ 8.05 (t, J = 6.3 Hz, 2H),7.39 (t, J = 7.8 Hz, 4H), 7.28 -7.18 (m, 6H), 6.94 (t, J = 6.3 Hz, 2H). 13CNMR (100 MHz, CDCl3) δ 153.6, 145.8, 140.3, 130.1, 126.7, 125.9, 125.6,118.3.
3-methyl-N-(4-nitrophenyl)-N-phenylaniline: 3l
黄色固体,产率为42%;1H NMR (400 MHz, CDCl3) δ 8.03 (t, J = 6.2 Hz, 2H),7.37 (t, J = 7.8 Hz, 2H), 7.29-7.16 (m, 4H), 7.01 (m, 3H), 6.91 (d, J = 9.3Hz, 2H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.1,145.2, 145.1, 139.5,129.4, 129.2, 126.7, 126.2, 126.0, 125.2, 124.9, 123.3, 117.5, 20.85.
实施例4:3o, 3p的制备。
将1,2,3,4-四氢喹啉类化合物1o, 1p (0.5 mmol)、t-BuONa(294 mg,1.5 mmol),硝基苯2a (184.5 mg, 1.5 mmol),加入2.0 mL二甲亚砜中(DMSO),室温下反应60 分钟后停止反应,用水淬灭,二氯甲烷萃取,柱层析分离(采用硅胶柱;洗脱剂:石油醚/乙酸乙酯=20/1),得到纯品N-甲基二苯基衍生物3o, 3p.
其合成路线如下:
1-(4-nitrophenyl)-1,2,3,4-tetrahydroquinoline: 3o
黄色固体,产率为63%;1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 9.2 Hz, 2H),7.23 (d, J = 8.1 Hz, 1H), 7.18 (d, J = 9.4 Hz, 3H), 7.11 (t, J = 7.6 Hz, 1H),6.99 (t, J = 7.4 Hz, 1H), 3.71 (t, J = 6.3 Hz, 2H), 2.77 (t, J = 6.3 Hz, 2H),2.05 (dd, J = 12.6, 6.3 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 153.4, 140.6,134.0, 131.0, 129.3, 126.5, 125.5, 123.0, 120.6,117.3, 48.8, 27.2, 24.1.
6-methyl-1-(4-nitrophenyl)-1,2,3,4-tetrahydroquinoline: 3p
黄色固体,产率为66%;1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 9.3 Hz, 2H),7.21-7.12 (m, 3H), 7.01 (s, 1H), 6.96 (d, J = 8.2 Hz, 1H), 3.71 (t, J = 6.3Hz, 2H), 2.74 (t, J = 6.3 Hz, 2H), 2.34 (s, 3H), 2.05 (dd, J = 12.6, 6.3 Hz,2H). 13C NMR (100 MHz, CDCl3) δ 153.5, 139.6, 137.9, 132.8, 131.3, 129.7,127.1, 125.5, 120.9, 116.7, 48.7, 27.1, 24.2, 20.8.
实施例5:3q, 3r的制备。
将N-甲基吡啶类化合物1q, 1r(0.5 mmol)、t-BuONa(294 mg,1.5 mmol),硝基苯2a (184.5 mg, 1.5 mmol),加入2.0 mL二甲基亚砜(DMSO)中,室温下反应60 分钟后停止反应,用水淬灭,二氯甲烷萃取,柱层析分离(采用硅胶柱;洗脱剂:石油醚/乙酸乙酯 = 20/1),得到纯品N-甲基二苯基衍生物3q, 3r.
其合成路线如下:
N-methyl-N-(4-nitrophenyl)pyridin-2-amine: 3q
黄色固体,产率为85%;1H NMR (400 MHz, CDCl3) δ 8.41 (dd, J = 4.8, 1.1 Hz,1H), 8.19 -8.12 (m, 2H), 7.63 (td, J = 8.4, 1.9 Hz, 1H), 7.26-7.16 (m, 2H),7.11 (d, J = 8.3 Hz, 1H), 6.98 (dd, J = 7.0, 5.2 Hz, 1H), 3.59 (s, 3H). 13CNMR (100 MHz, CDCl3) δ 157.7, 152.6, 149.0, 141.4, 138.0, 125.5, 119.0,118.4, 115.0 , 38.3.
N-methyl-N-(4-nitrophenyl)pyridin-4-amine: 3r
黄色固体,产率为71%;1H NMR (400 MHz, CDCl3) δ 8.43 (m, 2H), 8.20 (d, J =9.1 Hz, 2H), 7.23 (d, J = 9.1 Hz, 2H), 6.93 (d, J = 4.8 Hz, 2H), 3.45 (s,3H). 13C NMR (100 MHz, CDCl3) δ 152.9, 152.0, 150.8, 142.7, 125.5, 121.2,113.6, 39.5.
实施例6:3s, 3s′的制备。
将苯胺1s (0.5 mmol)、t-BuONa(294 mg,1.5 mmol),硝基苯2a (184.5 mg, 1.5mmol),加入2.0 mL二甲基亚砜(DMSO)中,室温下反应60 分钟后停止反应,用水淬灭,二氯甲烷萃取,柱层析分离(采用硅胶柱;洗脱剂:石油醚/乙酸乙酯 = 20/1),得到纯品N, N二苯基衍生物3s, 3s′.
其合成路线如下:
4-nitro-N-phenylaniline: 3s
黄色固体,产率为36%;1H NMR (400 MHz, DMSO) δ 9.47 (s, 1H), 8.17 (d, J =8.6 Hz, 1H), 7.39 (t, J = 7.7 Hz, 2H), 7.33 (t, J = 7.8 Hz, 1H), 7.27-7.17(m, 4H), 6.79-6.70 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 143.1, 138.8, 135.6,129.7, 126.7, 125.7, 124.4, 117.5, 116.1.
2-nitro-N-phenylaniline: 3s′
黄色固体,产率为10%;1H NMR (400 MHz, CDCl3) δ 8.17-8.09 (m, 2H), 7.45-7.36(m, 2H), 7.22-7.16 (m, 3H), 7.00-6.91 (m, 2H), 6.35 (s, 1H). 13C NMR (100 MHz,CDCl3) δ 150.2, 139.8, 139.5, 129.8, 126.2, 124.7, 122.0, 113.7.
实施例7:3t-3v的制备。
将N-甲基苯胺1a (53.5 mg, 0.5 mmol)、t-BuONa(294 mg,1.5 mmol),硝基苯类化合物2b-2d (1.5 mmol),加入2.0 mL二甲基亚砜(DMSO)中,室温下反应60 分钟后停止反应,用水淬灭,二氯甲烷萃取,柱层析分离(采用硅胶柱;洗脱剂:石油醚/乙酸乙酯 = 20/1),得到纯品N-甲基二苯基衍生物3t-3v.
其合成路线如下:
3-chloro-N-methyl-4-nitro-N-phenylaniline: 3t
黄色固体,产率为38%;1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 9.3 Hz, 1H),7.47 (t, J = 7.7 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 7.21 (d, J = 8.1 Hz, 2H),6.71 (d, J = 2.6 Hz, 1H), 6.55 (dd, J = 9.3, 2.6 Hz, 1H), 3.38 (s, 3H). 13CNMR (100 MHz, CDCl3) δ 152.8, 145.9, 136.7, 130.4, 130.2, 128.3, 127.2,126.7, 115.1, 111.2, 40.5.
N-methyl-2,4-dinitro-N-phenylaniline: 3u
黄色固体,产率为18%;1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 8.27 (d, J =9.3 Hz, 1H), 7.36 (t, J = 7.4 Hz, 2H), 7.21 (m, 2H), 7.10 (d, J = 8.0 Hz,2H), 3.47 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.3, 146.2, 139.2, 138.8,130.1, 127.8, 126.2, 123.3, 123.1, 121.2, 42.5.
N,2-dimethyl-4-nitro-N-phenylaniline: 3v
黄色固体,产率为25%;1H NMR (400 MHz, CDCl3) δ 8.14-8.06 (m, 2H), 7.29-7.21(m, 3H), 6.90 (t, J = 7.3 Hz, 1H), 6.72 (d, J = 8.2 Hz, 2H), 3.33 (s, 3H),2.12 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.6, 148.3, 144.1, 135.8, 129.3,126.9, 125.7, 122.9, 120.3, 116.8, 40.4, 19.0.
实施例8:克级反应制备3a
将N-甲基苯胺1a (1.07 g, 10 mmol)、t-BuONa(5.88 g,30 mmol),硝基苯2a (3.69g, 30 mmol),加入40 mL二甲基亚砜(DMSO)中,室温下反应60 分钟后停止反应,用水淬灭,二氯甲烷萃取,柱层析分离(采用硅胶柱;洗脱剂:石油醚/乙酸乙酯 = 20/1),得到纯品N-甲基二苯基衍生物3a,白色固体,产率78%。
其合成路线如下:
尽管已经对本发明的技术方案做了较为详细的阐述和列举,应当理解,对于本领域技术人员来说,对上述实施例做出修改或者采用等同的替代方案,这对本领域的技术人员而言是显而易见,在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
Claims (7)
1.一种N-芳基取代杂环化合物的制备方法,其特征在于,以碱为促进剂,在有机溶剂条件下,胺类化合物和硝基类化合物,以1:1~1:3的摩尔比,在常温常压下反应30-60分钟;反应结束后加水淬灭,有机溶剂萃取,柱层析分离,得到N-芳基取代杂环衍生物。
3.根据权利要求2所述的一种N-芳基取代杂环化合物的制备方法,其特征在于,所述C1~C40的脂肪基团为甲基、乙基、丙基、异丙基、丁基或苄基,C4~C60内的芳香基团为吡啶衍生物基、苯基、取代苯基、1-萘基或2-萘基,卤素为氟、氯、溴或碘。
5.根据权利要求4所述的一种N-芳基取代杂环化合物的制备方法,其特征在于,所述C1~C40的脂肪基团为甲基、乙基、丙基、异丙基、丁基或苄基,C4~C60内的芳香基团为吡啶衍生物基、苯基、取代苯基、1-萘基或2-萘基,卤素为氟、氯、溴或碘。
6.根据权利要求1所述的一种N-芳基取代杂环化合物的制备方法,其特征在于,所述的促进剂碱为t-BuONa、t-BuOK、KOH、NaOH或K2CO3,促进剂的用量为胺类衍生物摩尔量的1-3倍。
7.根据权利要求1所述的一种N-芳基取代杂环化合物的制备方法,其特征在于,所述的有机溶剂采用N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、氮甲基吡咯烷酮、二氯甲烷、氯仿、四氯化碳、1,2-二氯乙烷、1,4-二氧六环、乙腈、乙醚、乙二醇二甲醚或四氢呋喃。
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5612483A (en) * | 1994-09-13 | 1997-03-18 | Bayer Aktiengesellschaft | Process for the preparation of nitro-substituted arylamines |
CN103180294A (zh) * | 2010-08-31 | 2013-06-26 | 日产化学工业株式会社 | 二胺、聚酰亚胺前体、聚酰亚胺、液晶取向剂、液晶取向膜及液晶显示元件 |
-
2020
- 2020-07-31 CN CN202010757079.8A patent/CN111732516B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5612483A (en) * | 1994-09-13 | 1997-03-18 | Bayer Aktiengesellschaft | Process for the preparation of nitro-substituted arylamines |
CN103180294A (zh) * | 2010-08-31 | 2013-06-26 | 日产化学工业株式会社 | 二胺、聚酰亚胺前体、聚酰亚胺、液晶取向剂、液晶取向膜及液晶显示元件 |
Non-Patent Citations (2)
Title |
---|
HIROFUMI UEDA ET AL.: "Acetic Acid Promoted Metal-Free Aerobic Carbon−Carbon Bond Forming Reactions at α‑Position of Tertiary Amines", 《ORGANIC LETTERS》 * |
SHAILESH KUMAR ET AL: "KOtBu-Mediated Aerobic Transition-Metal-Free Regioselective β-Arylation of Indoles: Synthesis of β‑(2-/4-Nitroaryl)-indoles", 《ORGANIC LETTERS》 * |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115521193A (zh) * | 2022-09-30 | 2022-12-27 | 陕西蒲城海泰新材料产业有限责任公司 | 一种3,3′,6,6′-四甲氧基-2,2′-联萘的工业化制备方法 |
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