CN115215896A - 一种1,5-二氮八元杂环烷类化合物的制备方法 - Google Patents
一种1,5-二氮八元杂环烷类化合物的制备方法 Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 229910001873 dinitrogen Inorganic materials 0.000 title claims abstract description 7
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- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- 229910052802 copper Inorganic materials 0.000 claims abstract description 16
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- 229910052799 carbon Inorganic materials 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 51
- 238000006243 chemical reaction Methods 0.000 claims description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 12
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- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 6
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- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 claims description 4
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- HWUPLUNLNUHIQZ-UHFFFAOYSA-N copper;trifluoromethanesulfonic acid Chemical compound [Cu].OS(=O)(=O)C(F)(F)F.OS(=O)(=O)C(F)(F)F HWUPLUNLNUHIQZ-UHFFFAOYSA-N 0.000 claims description 3
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- 238000000034 method Methods 0.000 abstract description 14
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- 125000002252 acyl group Chemical group 0.000 description 1
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- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
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- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
技术领域
本发明涉及有机合成技术领域,尤其是涉及一种1,5-二氮八元杂环烷类化合物的制备方法。
背景技术
1,5-二氮八元杂环烷类化合物作为一种中等环状含氮杂环化合物,是生物活性分子中重要的结构支架,并在医药领域有着重要作用。然而,由于焓和熵的原因,八元环难以制备,存在合成挑战。
因此,开发一种高效简单的方法来快速构建具有含多种碳取代的1,5-二氮八元杂环烷类化合物非常重要。
发明内容
本发明旨在至少解决现有技术中存在的技术问题之一。为此,本发明提出一种1,5-二氮八元杂环烷类化合物的制备方法,仅使用铜催化剂就可以实现,且产率高。
根据本发明的第一方面实施例的提供的1,5-二氮八元杂环烷类化合物的制备方法,包括如下步骤:
将式II所示的化合物与式III所示的化合物在铜催化剂和有机溶剂存在下进行反应得到式I所示的化合物:
式I所示的化合物、式II所示的化合物和式III所示的化合物的结构式如下:
其中,R为取代或未取代的苯基、苄基;
R1为H或C1~10的烷基;
R2为C1~10的烷基。
根据本发明实施例的1,5-二氮八元杂环烷类化合物的制备方法,至少具有如下有益效果:
本发明是通过廉价金属铜催化重氮化合物和咪唑烷化合物,[5+3]环加成反应制备得到1,5-二氮八元杂环烷类化合物。金属-烯醇卡宾表现出卡宾和乙烯基活性,而后者由于硅醚基团的供电子氧原子在乙烯基位置增强了亲电性,更具竞争力。因此,亲核加成优先发生在乙烯基位置,随后作为1,3-偶极体发生[5+3]环加成,该方法仅使用铜催化剂就可以实现,且产率高。
根据本发明的一些实施例,R1为H、C1~6的烷基;R2为C1~6的烷基。
根据本发明的一些实施例,所述式II所示的化合物、式III所示的化合物和铜催化剂的摩尔比为1:1~5:0.05~0.5。
根据本发明的一些实施例,所述铜催化剂包括溴化亚铜、溴化铜、氯化铜、三氟甲磺酸铜、三氟甲磺酸亚铜、三苯基磷溴化亚铜、双三氟甲磺酸亚胺四乙氰铜或六氟磷酸四(乙腈)铜中的至少一种。由此,铜催化剂催化式II所示的化合物和式III所示的化合物进行[5+3]环加成。
根据本发明的一些实施例,所述铜催化剂包括溴化亚铜、三苯基磷溴化亚铜、溴化铜中的至少一种。由此,进一步提高产率。
根据本发明的一些实施例,所述有机溶剂包括二氯甲烷、1,2-二氯乙烷、甲苯、乙酸乙酯、N,N-二甲基甲酰胺、乙腈或四氢呋喃中的至少一种。
根据本发明的一些实施例,所述反应的温度为0℃~80℃。由此,所述反应的温度在这个范围内能够促进反应的进行。
根据本发明的一些实施例,所述反应的温度为25℃~60℃。由此,当反应温度在25℃~60℃时,能够进一步提高产率。
根据本发明的一些实施例,所述反应的时间为2h~48h。
根据本发明的一些实施例,所述反应的时间为12h~24h。
定义和一般术语
“C1-10的烷基”表示碳原子总数为1-10的烷基,包括C1-10的直链烷基、C1-10的支链烷基和C3-10的环烷基,例如可以为碳原子总数为1、2、3、4、5、6、7、8、9或10的直链烷基、碳原子总数为1、2、3、4、5、6、7、8、9或10的支链烷基或者碳原子总数为3、4、5、6、7、8、9或10的环烷基,例如可以为甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基、环丙基、甲基环丙基、乙基环丙基、环戊基、甲基环戊基、环己基等。针对“C1-6的烷基”具有与此相似的解释,所不同的是,碳原子数不同。
“取代或未取代的苯基”表示任选苯基中有至少一个H被本文定义的相应基团所取代。
本文使用的“取代或未取代的”是指基团可以被或可以不被一个或更多个选自以下的基团进一步取代:烷基、烯基、炔基、芳基、卤素、卤代烷基、卤代烯基、卤代炔基、卤代芳基、羟基、烷氧基、烯氧基、芳氧基、苄氧基、卤代烷氧基、卤代烯氧基、卤代芳氧基、硝基、硝基烷基、硝基烯基、硝基炔基、硝基芳基、硝基杂环基、氨基、烷基氨基、二烷基氨基、烯基氨基、炔基氨基、芳基氨基、二芳基氨基、苯基氨基、二苯基氨基、苄基氨基、二苄基氨基、肼基、酰基、酰氨基、二酰氨基、酰氧基、杂环基、杂环氧基、杂环基氨基、卤代杂环基、羧基酯、羧基、羧基酰胺、巯基、烷硫基、苄硫基、酰硫基和含磷基团。进一步优选地,所述取代基选自烷基、烷氧基或卤素。
本发明的其它特征和优点将在随后的说明书中阐述,并且,部分地从说明书中变得显而易见,或者通过实施本发明而了解。
附图说明
本发明的上述和/或附加的方面和优点从结合下面附图对实施例的描述中将变得明显和容易理解,其中:
图1为本发明实施例1制得的产物1a的1H NMR谱图;
图2为本发明实施例1制得的产物1a的13C NMR谱图;
图3为本发明实施例2制得的产物1b的1H NMR谱图;
图4为本发明实施例2制得的产物1b的13C NMR谱图;
图5为本发明实施例3制得的产物1c的1H NMR谱图;
图6为本发明实施例3制得的产物1c的13C NMR谱图;
图7为本发明实施例4制得的产物1d的1H NMR谱图;
图8为本发明实施例4制得的产物1d的13C NMR谱图;
图9为本发明实施例5制得的产物1e的1H NMR谱图;
图10为本发明实施例5制得的产物1e的13C NMR谱图;
图11为本发明实施例6制得的产物1f的1H NMR谱图;
图12为本发明实施例6制得的产物1f的13C NMR谱图。
具体实施方式
以下是本发明的具体实施例,并结合实施例对本发明的技术方案作进一步的描述,但本发明并不限于这些实施例。
本发明所采用的试剂、方法和设备,如无特殊说明,均为本技术领域常规试剂、方法和设备。
实施例和对比例中的原料:
溴化铜、氯化铜、三氟甲磺酸铜、三氟甲磺酸亚铜、三苯基磷溴化亚铜、六氟磷酸四(乙腈)铜、金催化剂tBuXPhosAuCl均购自安耐吉化学。
化合物2a和化合物3a~3f通过如下方法制备得到:
化合物2a
在装有40mL异丙醇的反应瓶中加入对甲苯胺Ⅰ(10mmol),转移至冰浴中,0℃下加入乙二醛(5mmol)。0℃下反应,通过TLC监测,直至反应完成。经过滤干燥得到黄色固体Ⅱ(1890mg,产率:80%)。在装有40mL四氢呋喃的反应瓶中加入Ⅱ,转移至冰浴中,0℃下缓慢加入硼氢化钠(24mmol)。30℃下反应12h,反应完后用水淬灭,用乙酸乙酯萃取三次,用水和和饱和食盐水洗涤有机相。分离有机层,用无水Na2SO4干燥,真空下旋干,得到粗产物Ⅲ(1346mg,产率:70%)。在装有20mL甲醇的反应瓶中加入Ⅲ,甲醛(5.6mmol),0.5mL乙酸。30℃下反应,通过TLC监测直至反应完成。经过滤干燥得到白色固体2a(1145mg,产率:81%)。
化合物3a~3f
在装有40mL乙腈的反应瓶中加入Ⅳ(6mmol)和对甲苯磺酰叠氮(6.6mmol),0℃下加入三乙胺(9mmol)。30℃下反应12h,加入水和二氯甲烷。用饱和食盐水洗涤,分离有机层,经无水硫酸钠干燥。真空下旋干,经柱层析法纯化得到Ⅴ。氮气保护下,在装有搅拌子的100mL两口瓶中加入20mL二氯甲烷,Ⅴ(2mmol),三乙胺(3mmol)。0℃下加入叔丁基二甲硅基三氟甲磺酸酯(2.2mmol),30℃下反应,通过TLC监测,直至反应完成。加入饱和碳酸氢钠水溶液,分离有机层,经无水硫酸钠干燥。真空下旋干,经柱层析法纯化得到3a~3f。
实施例1
本实施例提供一种1,5-二氮八元杂环烷类化合物(1a)的制备方法,步骤如下:
在25mL反应瓶中氮气保护下,化合物3a(513mg,2mmol)溶于二氯甲烷(5.0mL)中,将上述溶液利用注射泵缓慢注射入化合物2a(252mg,1.0mmol)、MS(200mg)和溴化亚铜(14mg,0.1mmol)的二氯甲烷(5.0mL)溶液中,反应体系在30℃下搅拌12小时,除去溶剂后粗产品利用硅胶柱层析分离得到无色油状产物1a(385mg,产率:80%)。
如图1和图2,所得产品1a的检测数据如下:1H NMR(500MHz,CDCl3):δ7.08(d,J=8.4Hz,2H),7.02(d,J=8.4Hz,2H),6.68(d,J=8.6Hz,2H),6.57(d,J=8.6Hz,2H),4.17(s,2H),3.79(s,2H),3.71-3.65(m,5H),3.65-3.60(m,2H),2.27(s,3H),2.24(s,3H),0.89(s,9H),-0.08(s,6H);13C NMR(125MHz,CDCl3):δ169.5,158.4,143.8,130.2,129.9,125.6,125.1,111.7,111.5,110.8,58.4,51.5,50.6,49.0,48.8,25.7,20.3,18.2,-4.3.
实施例2
本实施例提供1,5-二氮八元杂环烷类化合物(1b)的制备方法,步骤如下:
在25mL反应瓶中氮气保护下,化合物3b(597mg,2mmol)溶于二氯甲烷(5.0mL)中,将上述溶液利用注射泵缓慢注射入化合物2a(252mg,1.0mmol)、MS(200mg)和溴化亚铜(14mg,0.1mmol)的二氯甲烷(5.0mL)溶液中,反应体系在30℃下搅拌12小时,除去溶剂后粗产品利用硅胶柱层析分离得到无色油状产物1b(371mg,产率:71%)。
如图3和图4,所得产品1b的检测数据如下:1H NMR(500MHz,CDCl3):δ7.07(d,J=8.4Hz,2H),6.97(d,J=8.4Hz,2H),6.65(d,J=8.5Hz,2H),6.58(d,J=8.6Hz,2H),4.14(s,2H),3.90(s,2H),3.70-3.64(m,5H),3.62-3.58(m,2H),2.26(s,3H),2.21(s,3H),1.10-1.00(m,3H),0.99-0.94(m,18H);13C NMR(125MHz,CDCl3):δ169.5,158.2,144.1,143.8,130.2,129.9,125.7,125.0,111.6,110.87,110.85,58.3,51.4,50.3,49.5,48.7,20.31,20.29,17.8,13.6.
实施例3
本实施例提供1,5-二氮八元杂环烷类化合物(1c)的制备方法,步骤如下:
在25mL反应瓶中氮气保护下,化合物3c(597mg,2mmol)溶于二氯甲烷(5.0mL)中,将上述溶液利用注射泵缓慢注射入化合物2a(252mg,1.0mmol)、MS(200mg)和溴化亚铜(14mg,0.1mmol)的二氯甲烷(5.0mL)溶液中,反应体系在30℃下搅拌12小时,除去溶剂后粗产品利用硅胶柱层析分离得到白色固体产物1c(366mg,产率:70%)。
如图5和图6,所得产品1c的检测数据如下:1H NMR(500MHz,CDCl3):δ7.09(d,J=8.4Hz,2H),7.03(d,J=8.4Hz,2H),6.72(d,J=8.6Hz,2H),6.59(d,J=8.6Hz,2H),4.10(s,2H),3.79(s,2H),3.70-3.64(m,2H),3.63-3.57(m,2H),2.27(s,3H),2.25(s,3H),1.49(s,9H),0.90(s,9H),-0.00(s,6H);13C NMR(125MHz,CDCl3):δ167.1,155.8,144.0,143.8,130.2,129.8,125.5,125.0,113.7,111.7,111.0,80.3,58.4,50.7,49.1,48.6,28.4,26.0,20.34,20.33,18.4,-4.0.
实施例4
本实施例提供1,5-二氮八元杂环烷类化合物(1d)的制备方法,步骤如下:
在25mL反应瓶中氮气保护下,化合物3d(540mg,2mmol)溶于二氯甲烷(5.0mL)中,将上述溶液利用注射泵缓慢注射入化合物2a(252mg,1.0mmol)、MS(200mg)和溴化亚铜(14mg,0.1mmol)的二氯甲烷(5.0mL)溶液中,反应体系在30℃下搅拌12小时,除去溶剂后粗产品利用硅胶柱层析分离得到无色油状产物1d(421mg,产率:85%)。
如图7和图8,所得产品1d的检测数据如下:1H NMR(500MHz,CDCl3):δ7.09(d,J=8.4Hz,2H),7.02(d,J=8.4Hz,2H),6.69-6.59(m,4H),4.20(d,J=16.4Hz,1H),4.08(q,J=7.1Hz,1H),3.95(d,J=16.4Hz,1H),3.79-3.64(m,5H),3.61-3.49(m,2H),2.28(s,3H),2.24(s,3H),1.36(d,J=7.1Hz,3H),0.97(s,9H),0.18(s,3H),0.13(s,3H);13C NMR(125MHz,CDCl3):δ170.4,160.4,145.2,144.4,130.0,129.9,126.2,125.4,112.4,112.3,111.2,59.5,51.7,49.8,46.9,43.1,26.0,20.4,20.3,18.6,16.9,-3.3,-3.8.
实施例5
本实施例提供1,5-二氮八元杂环烷类化合物(1e)的制备方法,步骤如下:
在25mL反应瓶中氮气保护下,化合物3e(569mg,2mmol)溶于二氯甲烷(5.0mL)中,将上述溶液利用注射泵缓慢注射入化合物2a(252mg,1.0mmol)、MS(200mg)和溴化亚铜(14mg,0.1mmol)的二氯甲烷(5.0mL)溶液中,反应体系在30℃下搅拌12小时,除去溶剂后粗产品利用硅胶柱层析分离得到无色油状产物1e(387mg,产率:76%)。
如图9和图10,所得产品1e的检测数据如下:1H NMR(500MHz,CDCl3):δ7.07(d,J=8.3Hz,2H),6.99(d,J=8.3Hz,2H),6.62(dd,J=18.5,8.6Hz,4H),4.15(d,J=16.3Hz,1H),3.98(d,J=16.3Hz,1H),3.78-3.70(m,2H),3.69-3.46(m,6H),2.27(s,3H),2.22(s,3H),1.98-1.89(m,1H),1.86-1.75(m,1H),0.95(s,9H),0.81(t,J=7.3Hz,3H),0.16(s,3H),0.10(s,3H);13C NMR(125MHz,CDCl3):δ170.7,159.7,145.3,130.0,129.9,126.3,125.5,112.9,112.5,111.8,66.2,51.7,49.5,46.7,26.0,22.7,20.4,20.3,18.5,11.6,-3.4,-3.9.
实施例6
本实施例提供1,5-二氮八元杂环烷类化合物(1f)的制备方法,步骤如下:
在25mL反应瓶中氮气保护下,化合物3f(597mg,2mmol)溶于二氯甲烷(5.0mL)中,将上述溶液利用注射泵缓慢注射入化合物2a(252mg,1.0mmol)、MS(200mg)和溴化亚铜(14mg,0.1mmol)的二氯甲烷(5.0mL)溶液中,反应体系在30℃下搅拌12小时,除去溶剂后粗产品利用硅胶柱层析分离得到无色油状产物1e(340mg,产率:65%)。
如图11和图12,所得产品1f的检测数据如下:1H NMR(500MHz,CDCl3):δ7.06(d,J=8.4Hz,2H),6.98(d,J=8.4Hz,2H),6.63(d,J=8.6Hz,2H),6.59(d,J=8.6Hz,2H),4.14(d,J=16.2Hz,1H),4.00(d,J=16.2Hz,1H),3.90-3.83(m,1H),3.74-3.65(m,4H),3.65-3.45(m,3H),2.26(s,3H),2.22(s,3H),1.91-1.77(m,2H),1.39-1.27(m,1H),1.16-1.05(m,1H),0.96(s,9H),0.82(t,J=7.4Hz,3H),0.14(s,3H),0.08(s,3H);13C NMR(125MHz,CDCl3):δ170.8,160.0,145.4,145.2,130.0,129.9,126.2,125.6,112.9,112.6,111.8,64.5,51.7,49.4,46.6,43.9,31.7,26.0,20.4,20.3,20.1,18.5,14.0,-3.4,-4.0.
实施例7~12
实施例7~12提供一系列的1,5-二氮八元杂环烷类化合物的制备方法,其步骤和原料与实施例1相同,其区别在于,铜催化剂不同,具体见表1。
表1
实施例14~20
实施例14~20提供一系列的1,5-二氮八元杂环烷类化合物的制备方法,其步骤和原料与实施例1相同,其区别在于,有机溶剂不同,具体见表2。
表2
溶剂 | 产率% | |
实施例14 | 甲苯 | 17 |
实施例15 | 1,2-二氯乙烷 | 78 |
实施例16 | 乙腈 | 22 |
实施例17 | 四氢呋喃 | 70 |
实施例18 | 乙酸乙酯 | 40 |
实施例19 | 甲醇 | 36 |
实施例20 | N,N-二甲基甲酰胺 | 47 |
对比例1
对比例1提供一种1,5-二氮八元杂环烷类化合物的制备方法,其制备方法和原料与实施例1相同,其区别在于,采用tBuXPhosAuCl替代实施例1中的溴化亚铜。
结果发现,在金催化剂的条件下,该方案不发生反应。
上面结合本发明实施例作了详细说明,但本发明不限于上述实施例,在所属技术领域普通技术人员所具备的知识范围内,还可以在不脱离本发明宗旨的前提下作出各种变化。
Claims (10)
2.根据权利要求1所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,R1为H、C1~6的烷基;R2为C1~6的烷基。
3.根据权利要求1所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,所述式II所示的化合物、式III所示的化合物和铜催化剂的摩尔比为1:1~5:0.05~0.5。
4.根据权利要求1所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,所述铜催化剂包括溴化亚铜、溴化铜、氯化铜、三氟甲磺酸铜、三氟甲磺酸亚铜、三苯基磷溴化亚铜、双三氟甲磺酸亚胺四乙氰铜或六氟磷酸四(乙腈)铜中的至少一种。
5.根据权利要求4所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,所述铜催化剂包括溴化亚铜、三苯基磷溴化亚铜、溴化铜中的至少一种。
6.根据权利要求1所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,所述有机溶剂包括二氯甲烷、1,2-二氯乙烷、甲苯、乙酸乙酯、N,N-二甲基甲酰胺、乙腈或四氢呋喃中的至少一种。
7.根据权利要求1所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,所述反应的温度为0℃~80℃。
8.根据权利要求7所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,所述反应的温度为25℃~60℃。
9.根据权利要求1所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,所述反应的时间为2h~48h。
10.根据权利要求9所述的1,5-二氮八元杂环烷类化合物的制备方法,其特征在于,所述反应的时间为12h~24h。
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