含三氟甲基合成子的制备及其反应研究
摘要
含三氟甲基合成子是合成各种含三氟甲基化合物的基石。发展廉价、易得和用途广泛的含三氟甲基合成子一直是有机氟化学的重要研究方向。本论文从廉价易得的原料1出发合成了含三氟甲基的合成子4,并对他的转化做了相应的探讨。全文分为以下三部分:
第一部分:首先从2-溴-3,3,3-三氟丙烯1出发制备了三氟甲基炔丙胺4,含氟合成子4进行苯甲酰化时没有得到期望的产物而是得到了含三氟甲基的氮杂环丙烷。通过查阅相关文献我们合成出了一系列的含三氟甲基的氮杂环丙烷6,并对氮杂环丙烷的开环反应进行尝试得到了开环产物7。
第二部分:期望通过含三氟甲基合成子的氢碘酸加成反应制备含三氟甲基的烯基碘并进而制备共轭烯炔胺类化合物。遗憾的是分别从合成子4和5出发都无法实现产物的分离提纯,反应体系的~(19)F NMR分析可能是因为烯基碘产物不稳定。然后我们对合成子4的硼氢化反应也做了尝试,但由于产物较复杂且主点溶于水相给萃取分离带来较大的挑战,因此对这部分的工作还有待进一步的研究。
第三部分:我们对合成子4和叠氮化合物的click反应进行了尝试,期望得到一系列的含三氟甲基的1,2,3-三氮唑杂环化合物。但~(19)F NMR显示反应很难进行只有痕量的产物,我们推测可能是空间位阻的原因使得产物的产率很低无法对其进行收集。
Easily available and versatile trifluoromethylated building blocks are crucial for the synthesis of trifluoromethylated compounds, which is an active field in organic fluorine chemistry. In this dissertation, the trifluorinated building blocks 4 were prepared from cheap and easily available ftuorinated material 1. Furthermore, the application of these trifluoromethylated building blocks was accomplished. The dissertation is divided into the following three parts:
PartⅠ: Firstly, the trifluorinated building blocks 4 were prepared from 3,3,3-trifluoro-2-bromo-propene 1. Aziridines containing trifluoromethyl group were obtained when trifluorinated building blocks 4 were benzoylated, which is out of expectation. After reading relevant literatures, we synthesized a series of aziridine 6 containing trifluoromethyl group, and then the ring-opening products 7 can be obtained by the reaction of aziridine 6 with water under acidic condition.
PartⅡ: The addition reaction of trifluoromethylated building blocks 4 with hydroiodide was investigated; we plan to use the resulting product to prepare enynes. Unfortunately, pure addition products can not be isolated from the addition reaction by using 4 or 5 as starting material. ~(19)F NMR analysis of the reaction system indicated that the product is unstable. Finally, the hydroboration of building blocks 4 was also investigated but only complex products were found and the isolation of major product is a greater challenge due to its high water solubility.
PartⅢ: The click reactions of 4 with azides have also been attempted with the expectation of making a series of trifluoromethyl group substituted 1,2,3-triazoles. However, the ~(19)F NMR showed that the reaction was difficult to be accomplished and only trace of product was found. The possible reason may due to the effect of steric hindrance which makes the yield of the reaction is very low.
第一部分:首先从2-溴-3,3,3-三氟丙烯1出发制备了三氟甲基炔丙胺4,含氟合成子4进行苯甲酰化时没有得到期望的产物而是得到了含三氟甲基的氮杂环丙烷。通过查阅相关文献我们合成出了一系列的含三氟甲基的氮杂环丙烷6,并对氮杂环丙烷的开环反应进行尝试得到了开环产物7。
第二部分:期望通过含三氟甲基合成子的氢碘酸加成反应制备含三氟甲基的烯基碘并进而制备共轭烯炔胺类化合物。遗憾的是分别从合成子4和5出发都无法实现产物的分离提纯,反应体系的~(19)F NMR分析可能是因为烯基碘产物不稳定。然后我们对合成子4的硼氢化反应也做了尝试,但由于产物较复杂且主点溶于水相给萃取分离带来较大的挑战,因此对这部分的工作还有待进一步的研究。
第三部分:我们对合成子4和叠氮化合物的click反应进行了尝试,期望得到一系列的含三氟甲基的1,2,3-三氮唑杂环化合物。但~(19)F NMR显示反应很难进行只有痕量的产物,我们推测可能是空间位阻的原因使得产物的产率很低无法对其进行收集。
Easily available and versatile trifluoromethylated building blocks are crucial for the synthesis of trifluoromethylated compounds, which is an active field in organic fluorine chemistry. In this dissertation, the trifluorinated building blocks 4 were prepared from cheap and easily available ftuorinated material 1. Furthermore, the application of these trifluoromethylated building blocks was accomplished. The dissertation is divided into the following three parts:
PartⅠ: Firstly, the trifluorinated building blocks 4 were prepared from 3,3,3-trifluoro-2-bromo-propene 1. Aziridines containing trifluoromethyl group were obtained when trifluorinated building blocks 4 were benzoylated, which is out of expectation. After reading relevant literatures, we synthesized a series of aziridine 6 containing trifluoromethyl group, and then the ring-opening products 7 can be obtained by the reaction of aziridine 6 with water under acidic condition.
PartⅡ: The addition reaction of trifluoromethylated building blocks 4 with hydroiodide was investigated; we plan to use the resulting product to prepare enynes. Unfortunately, pure addition products can not be isolated from the addition reaction by using 4 or 5 as starting material. ~(19)F NMR analysis of the reaction system indicated that the product is unstable. Finally, the hydroboration of building blocks 4 was also investigated but only complex products were found and the isolation of major product is a greater challenge due to its high water solubility.
PartⅢ: The click reactions of 4 with azides have also been attempted with the expectation of making a series of trifluoromethyl group substituted 1,2,3-triazoles. However, the ~(19)F NMR showed that the reaction was difficult to be accomplished and only trace of product was found. The possible reason may due to the effect of steric hindrance which makes the yield of the reaction is very low.
引文
[1]卿凤翎,邱小龙,有机氟化学[M],科学出版社,2007.
[2]江中兴,中国科学院上海有机化学研究所理学博士学位论文,2004.
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[2]江中兴,中国科学院上海有机化学研究所理学博士学位论文,2004.
[3]Goldman,P.;Science.1969,164,1123-1130.
[4]Wilkinson,J.A.;Chem.Rev.1992,92,505-519.
[5]Purrington,S.T.;Kagen,B.S.;Patrick,T.B.Chem.Rev.1986,86,997-1018.
[6]Yemul,S.S.;Kagan,H.B;Setton,R.Tetrahedron Lett.1980,21,277-280.
[7](a) Bumgardner,C.L.;Bunch,J.E.;Whangbo,M.H.J.Org.Chem.1986,51,4082-4083.
(b) Shimizu,M.;Fujimoto,T.;Minezaki,H.;Hata,T.;Hiyama,T.J.Am.Chem.Soc.2001,123,6947-6948.
[8]Chou,T-C.;Dong,H.;Rivkin,A.;Yoshimura,F.;Gabarda,A.E.;Cho,Y.S.;Tong,W.P.;Danishefsky,S.L.Angew.Chem.Int.Ed.2003,42,4762-4767.
[9]Chou,T-C.;Dong,H.;Rivkin,A.;Yoshimura,F.;Gabarda,A.E.;Cho,Y.S.;Tong,W.P.;Danishefsky,S.L.Angew.Chem.Int.Ed.2003,42,4762-4767.
[10]Chen,X.-Y.;Qiu,X.-L.;Qing,F.-L.Tetrahedron.2008,64,2301-2306.
[11]Tanner,D.;Angew.Chem.,Int.Ed.Engl.1994,33,599-619.
[12]Li,V.S.;Kohn,H.J.Am.Chem.Soc.1991,13,275-283.
[13]Li,A.-H.;Zhou,Y.-G.;Dai,L.-X.;Hou,X.-L.;Xia,L.-J.;Lin,L.J.Org.Chem.1998,63,4338-4348.
[14]Nakajima,K.;Okawa,K.Bull.Chem.Soc.Jpn.1978,51,1577-1578.
[15]Legters,J.;Thijs,L.;Zwanenburg,B.Tetrahedron Lett.1989,30,4881-4884.
[16]Li,Z.;Conser,K.R.;Jocobsen,E.N.J.Am.Chem.Soc.1993,115,5326-5327.
[17]Shim,J.J.;Shipman,M.;Hayes,J.F.;Alexandra M.Z.J.Am.Chem.Soc.2004,126,6868-6869.
[18]Merah,B.;Texier,F.Bulletin de la Societe Chimique de France.1980,552-558.
[19]Katagiri,T.;Uneyama,K.Tetrahedron:Asymmetry.1997,8,2933-2937.
[20]Yamauchi,Y.;Kawate,T.;Itahashi,H.;Katagiri,T.;Uneyama,K.Tetrahedron Lett.2003,44,6319-6322.
[21]Davoli,P.;Forni,A.;Moretti,L.;Prati,F.J.Fluorine Chem.1998,89,177.
[22]Akiyama,T.;Ogi,S.;Fuchibe,K.Tetrahedron Lett.2003,44,4011-4013.
[23]Aggarwal,V.K.;Vasse,J.L.Org.Lett.2003,5,3987-3990.
[24]马林鸽,许家喜.非对称氮杂环丙烷的亲核开环反应及其区域选择性.化学进展,2004,16(2),220-235.
[25]Tang,T.P.;Volkman,S.K.;Ellman,J.A.J.Org.Chem.2001,66(26),8772- 8778.
[26]Berry,M.B.;Craig,D.Synlett.1992,1,41-44.
[27]Evans,D.A.;Faul,M.M.;Bilodeau,M.T.;Anderson,B.A.;Barnes,D.M.J.Am.Chem.Soc.1993,115,5328-5329.
[28]Righi,G.;Bonini,C.Tetrahedron Lett.1996,37,6893-6896.
[29]Fiandanese,V.;Bottalico,D.;Punzi,A.Tetrahedron.2004,60,11421.
[30]Chen,L.;Li,Ch.- J.;Tetrahedron Lett.2004,45,2771-2774.
[31]Dai,W.-M.;Wu,A.Tetrahedron Lett.2001,42,81-83.
[32]Chen,Ch.-W.;Lu,T.-Y.;J.Org.Chem.2008,73,8357-8363.
[33]Qing,F.-L.;Zhang,Y.-M.;Tetrahedron Lett.1997,38,6729-6732.
[34]Qing,F.-L.;Gao,W.-Zh.;Ying,J.-W.;J.Org.Chem.2000,65,2003-2006.
[35]Legros,J.;Begue,J.P.;J Fluorine Chem.2001,107,121-125.
[36]Prie,G.;Abarbri,M.;Thibonnet,J.;Parrain,J.L.;Duchene,A.New.J.Chem.2003,27,432-441.
[37]Jeon,H.H.;Son,J.B.;Jeong,I.H.Tetrahedron Lett.2007,48,627-631.
[38]Gabriele,B.;Salerno,G.;Fazio,A.Organic Lett.2000,2,351-352.
[39]Prie,G.;Thibonnet,J.;Abarbri,M.;Parrain,J.A.Synlett.1998,8,839-840.
[40]Qing,F.-L.;Gao,W.-Z.Tetrahedron Lett.2000,41,7727-7730.
[41]Patterson,A.W.;Ellman,J.A.J.Org.Chem.2006,71,7110-7112.
[42]Brown,H.C.;Somayaji,V.;Bhat,N.G.J.Org.Chem.1989,54,6068-6075.
[43]Brown,H.C.;Gupta,S.K.J.Am.Chem.Soc.1975,97,5249-5255.
[44]Melo,Julio O.F.;Donnici,C.L.;Augusti,R.;Ferreira,V.F.;Ferreira,M.L.G.;Cunha,A.C.Quim.Nova.2006,29,569-579.
[45]张春涛,东华大学有机化学硕士学位论文,2008.
[46]Kamijo,S.;Jin,T.;Huo,Z.;Yamamoto,Y.Tetrahedron Lett.2002,43,9707-9710.
[47]Rostovtsev,V.V.;Sharpless,K.B.Angew.Chem.Int.Ed.2002,41,2596-2599.
[48]Li Z.;Xin G.-Ch.;Peng,X.;Herman H.K.;Barry S.et al.J.Am.Chem.Soc.2005,127,15998-15999.
[49]Stepanova,N.P.;Orlova,N.A.;Galishev,V.A.;Turbanova,E.S.;Petrov,A.A.Zh.Org.Khim.1985,21,979-983.
[50]Shen,Y.C.;Zheng,J.H.;Qi,M.J.Chem.Soc.Perkin Trans 1.1995,(8),997-999
[51]Zhang,C.-T.;Zhang,X.-G.;Qing,F.-L.Tetrahedron Lett.2008,49,3927-3930.
[52]Stefan,B.;Carmen,G.;Kerstin,K.;Viktor,Z.Angew.Chem.Int.Ed.2005,44, 5188-5240.
[53]Ju,Y.;Kumar,D.;Varma.,R.S.J.Org.Chem.2006,71,6697-6700.
[54]Kruper,W.J.,Rudolf,P.R.;Langhoff,C.A.J.Org.Chem.1993,58,386-3876.
[55]Alvarez,S.G.;Alvarez,M.T.Synthesis.1997,(4),413-414.
[56]Wood,Warren J.L.;Patterson,A.W.;Tsuruoka,H.;Jain,R.K.;Ellman,J.A.J.Am.Chem.Soc.2005,127,15521-15527.