CN105985263A - 一种n,n-二取代氨基-丙二腈类化合物的合成方法 - Google Patents

一种n,n-二取代氨基-丙二腈类化合物的合成方法 Download PDF

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CN105985263A
CN105985263A CN201510054946.0A CN201510054946A CN105985263A CN 105985263 A CN105985263 A CN 105985263A CN 201510054946 A CN201510054946 A CN 201510054946A CN 105985263 A CN105985263 A CN 105985263A
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disubstituted amido
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CN105985263B (zh
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王少华
牟学清
徐力
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Lanqimengda Pharmaceutical Technology Ningjin Co ltd
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Lanzhou University
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Abstract

本发明涉及一种N,N-二取代氨基-丙二腈类化合物的制备方法,其反应通式如下所示

Description

一种N,N-二取代氨基-丙二腈类化合物的合成方法
技术领域
本发明属于有机合成技术领域,具体涉及一种N,N-二取代氨基-丙二腈类化合物的的合成方法。
背景技术
N,N-二取代氨基-丙二腈类化合物是一类比较重要的合成中间体,通过氰基衍生化,可以得到许多化学合成中有用的化合物,比如α-氨基酸。也能形成亚胺中间体和碳负离子,成为合成含氮杂环的重要前体。目前针对该类化合物的合成多用亚胺盐,季胺盐,硫代亚胺盐为原料,氰化钾为氰源(Justus LiebigsAnnalen der Chemie,(4),666-9;1976;Ger.Offen.,10057055,23May 2002;Journal of Organic Chemistry,50(21),4006-14;1985;Journal of theChemical Society,Perkin Transactions 1:Organic and Bio-OrganicChemistry(1972-1999),(11),2708-10;1979),步骤繁琐,而且用了剧毒的氰化钾。我们希望用原料易得的N,N-二取代的甲酰胺、相对低毒性的三甲基氰硅烷、铜金属催化剂加热条件下一步制得N,N-二取代氨基-丙二腈。
发明内容
本发明解决的技术问题是提供一种反应过程简单且易于操作的N,N-二取代氨基-丙二腈类化合物的合成方法,以替代传统的繁琐操作方法。
本发明的技术方案为:一种N,N-二取代氨基-丙二腈类化合物的合成方法。其技术特征为:N,N-二取代的甲酰胺、三甲基氰硅烷、铜金属催化剂在加热条件下按照反应式(1)进行,得到化合物N,N-二取代氨基-丙二腈。反应通式如反应1:
其中,(1)R1、R2不在同一个环系上时,两取代基可以相同,如甲基,乙基,等烷基基团;
(2)R1、R2不在同一个环系上时,两取代基可以不同,如R1可为甲基、乙基、丙基等烷基基团;R2可为苯基、苄基等芳基基团;
(3)R1、R2在同一环系上时,R1、R2连同N原子可为二氢吲哚基、1,2,3,4-四氢异喹啉基、哌啶基、吗啡啉基、4-甲基哌啶基。
在上述方法反应中,所用的铜催化剂的选择可为三氟甲烷磺酸铜、三氟甲烷磺酸亚铜、溴化铜、溴化亚铜、氯化铜、氯化亚铜、碘化亚铜。优选三氟甲烷磺酸铜。
在上述方法反应中,所用的溶剂可为正庚烷、1.2-二氯乙烷、乙腈、正己烷、环己烷、正壬烷、甲苯、四氢呋喃、1、4-二氧六环的一种或几种。优选正庚烷。
在上述方法反应中,加热所用的温度为20-120℃。
在上述方法反应中,反应中各物质的物质的量比为:N,N-二取代的甲酰胺:三甲基氰硅烷:铜催化剂:溶剂=1:2-5:0.05-0.20:10-100。
具体实施方式
以下通过具体实施例对本发明做进一步的说明,但不应该将此理解为本发明上述主题的范围仅限于以下的实施例,凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例
以N,N-二乙基甲酰胺为原料(反应式2)
将N,N-二乙基甲酰胺(50ul,0.45mmol),加入到搅拌的正庚烷中(1mL),随后依次加入三甲基氰硅烷(126ul,0.99mmol)和三氟甲烷磺酸铜(16mg,0.045mmol)在80℃下反应五小时完成反应,在旋转蒸发仪上抽干溶剂,经柱层析得淡黄色油状液体(31.5mg,64%)。
产物检测数据如下:
1H NMR(400MHz,CDCl3):δ4.78(S,1H),4.73(q,J=7.2Hz,4H),1.17(t,7.2Hz,6H);13C NMR(75MHz,CDCl3):δ110.7,46.9,44.9,12.5;MS m/z(%):137(M+,<1),111([M-25]+,25),57(100)。
以N-甲酰吗啉为原料(反应式3)
将N-甲酰吗啉(50ul,0.50mmol),加入到搅拌的正庚烷中(1mL),随后依次加入三甲基氰硅烷(141ul,1.1mmol)和三氟甲烷磺酸铜(18mg,0.050mmol)在80℃下反应五小时完成反应,在旋转蒸发仪上抽干溶剂,经柱层析得淡黄色油状液体(64.5mg,86%)
产物检测数据如下:
1H NMR(400MHz,CDCl3):δ4.65(S,1H),3.79(t,J=3.8Hz,4H),2.72(t,4.7Hz,4H);13C NMR(400MHz,CDCl3):δ109.6,66.2,50.1,48.5;MS m/z(%):149(M+,5),85(50),71(70),57(100)。
以1,2,3,4-四氢异喹啉-2-甲醛为原料(反应式4)
将1,2,3,4-四氢异喹啉-2-甲醛(50mg,0.31mmol),加入到搅拌的正庚烷中(1mL),随后依次加入三甲基氰硅烷(87ul,0.68mmol)和三氟甲烷磺酸铜(11mg,0.031mmol)。在80℃下反应五小时完成反应,在旋转蒸发仪上抽干溶剂,经柱层析得淡黄色油状液体(39.7mg,65%)。
产物检测数据如下:
1H NMR(400MHz,CDCl3):δ7.30-7.08(m,4H),4.87(s,1H),4.06-3.78(m,2H),3.05-2.94(m,4H);13C NMR(75MHz,CDCl3):δ132.6,131.8,129.0,127.4,109.9,127.2,126.7,126.5,109.9,52.5,48.5,48.4,29.0;MS m/z(%):197(M+,25),171(5),104(100)。

Claims (5)

1.一种N,N-二取代氨基-丙二腈类化合物的合成方法,其特征为N,N-二取代的甲酰胺、三甲基氰硅烷、金属铜为催化剂在加热条件下按照反应式(1)进行,最终得到化合物N,N-二取代氨基-丙二腈。
其中:
(1)R1、R2不在同一个环系上时,两取代基可以相同,如甲基,乙基,等烷基基团;
(2)R1、R2不在同一个环系上时,两取代基可以不同,如R1可为甲基、乙基、丙基等烷基基团;R2可为苯基、苄基等芳基基团;
(3)R1、R2在同一环系上时,R1、R2连同N原子可为二氢吲哚基、1,2,3,4-四氢异喹啉基、哌啶基、吗啡啉基、4-甲基哌啶基。
2.根据权利要求书1所述的一种N,N-二取代氨基-丙二腈类化合物的制备方法,其特征是所用铜催化剂选自:三氟甲烷磺酸铜、三氟甲烷磺酸亚铜、溴化铜、溴化亚铜、氯化铜、氯化亚铜、碘化亚铜。
3.根据权利要求书1所述的一种N,N-二取代氨基-丙二腈类化合物的制备方法,其特征是所用的溶剂选自:正庚烷、1.2-二氯乙烷、乙腈、正己烷、环己烷、正壬烷、甲苯、四氢呋喃、1、4-二氧六环的一种或几种。
4.根据权利要求书1所述的一种N,N-二取代氨基-丙二腈的制备方法,其特征是所加热的温度为20-120℃。
5.根据权利要求书1所述的一种N,N-二取代氨基-丙二腈的制备方法,其特征是反应中各物质的物质的量比为:N,N-二取代的甲酰胺:三甲基氰硅烷:铜催化剂:溶剂=1:2-5:0.05-0.20:10-100。
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114249724A (zh) * 2020-09-25 2022-03-29 鲁南制药集团股份有限公司 一种唑吡坦中间体的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3019261A (en) * 1959-03-12 1962-01-30 Du Pont Nu-fluorinatedalkyl-amides of alkanoic acids and process of preparation
DE1128431B (de) * 1960-11-16 1962-04-26 Bayer Ag Verfahren zur Herstellung basisch substituierter Malonsaeuredinitrile
DE10057055A1 (de) * 2000-11-17 2002-05-23 Bayer Ag Verfahren zur Herstellung von aminosubstituierten Malonsäuredinitrilen

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3019261A (en) * 1959-03-12 1962-01-30 Du Pont Nu-fluorinatedalkyl-amides of alkanoic acids and process of preparation
DE1128431B (de) * 1960-11-16 1962-04-26 Bayer Ag Verfahren zur Herstellung basisch substituierter Malonsaeuredinitrile
DE10057055A1 (de) * 2000-11-17 2002-05-23 Bayer Ag Verfahren zur Herstellung von aminosubstituierten Malonsäuredinitrilen

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ALBERT PADWA等: "Synthetic Application of Cyanoaminosilanes as Azomethine Ylide", 《J. ORG. CHEM.》 *
P. SARAVANAN等: "Cu(OTf)2 Catalyzed Trimethylsilyl Cyanide Addition to Carbonyl Compounds", 《TETRAHEDRON LETTERS》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114249724A (zh) * 2020-09-25 2022-03-29 鲁南制药集团股份有限公司 一种唑吡坦中间体的制备方法

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