CN112552152A - 卤代酮类化合物及联烯基促进的环醇的碳碳键断裂制备卤代酮类化合物的方法 - Google Patents
卤代酮类化合物及联烯基促进的环醇的碳碳键断裂制备卤代酮类化合物的方法 Download PDFInfo
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Abstract
本发明公开了一种卤代酮类化合物及通过联烯基促进的环醇的碳碳键断裂制备卤代酮类化合物的方法。该方法系在催化剂,氧化剂,卤代剂,有机试剂/水的混合溶剂中,高效地将环醇转化为对应卤代酮类化合物。本发明原料简单易得,操作简单,反应条件温和,底物范围广,官能团兼容性好,有优良的区域选择性。
Description
技术领域
本发明属于化学合成技术领域,具体涉及卤代酮类化合物及通过联烯基促进的环醇的碳碳键断裂制备卤代酮类化合物的方法。
背景技术
近些年来,C-C键断裂作为一种构建各种有机分子的高效策略,开始越来越引起化学家们广泛的关注(Rybtchinski,B.;Milstein,D.Angew.Chem.,Int.Ed.1999,38,870-883;Necas,D.;Kotora,M.Curr.Org.Chem.2007,11,1566-1591;Kim,D.-S.;Park,W.-J.;Jun,C.-H.Chem.Rev.2017,117,8977-9015.)。因为小环的环张力存在,环丙烷以及环丁烷衍生物在C-C键断裂中有着举足轻重的作用(Rubin,M.,Rubina,M.;Gevorgyan,V.Chem.Rev.2007,107,3117-3179;Seiser,T.;Cramer,N.Org.Biomol.Chem.2009,7,2835-2840;C.Synthesis,2011,21,3389-3407;Seiser,T.;Saget,T.;Tran,D.N.;Cramer,N.Angew.Chem.,Int.Ed.2011,50,7740-7752;Fumagalli,G.;Stanton,S.;Bower,J.F.Chem.Rev.2017,117,9404-9432.)。同时,因为环烷醇可以轻松的通过环烷酮制备得到,所以环丙醇,环丁醇及其衍生物被认为是有机合成中最重要的C3和C4合成子之一,该类化合物的研究近些年也取得了非常显著的成果(Kulinkovich,O.Chem.Rev.2003,103,2597-2632;Cramer,N.;Seiser,T.Synlett 2011,4,449-460;Wu,X.;Zhu,C.Chem.Rec.2018,18,587-598;Liu,Y.;Wang,Q.;Chen,Z.;Zhou,C.;Xiong,B.;Zhang,P.;Yang,C.;Zhou,Q.Beilstein J.Org.Chem.2019,15,256-278.)。但是,对于非张力环体系,因为其环张力的减小,C-C键越发稳定,故而相较于张力环而言,非张力环醇体系的研究要少的多(Yayla,H.;Wang,H.;Tarantino,K.;Orbe,H.;Knowles,R.J.Am.Chem.Soc.2016,138,10794-10797;Guo,J.;Hu,A.;Chen,Y.;Sun,J.;Tang,H.;Zuo,Z.Angew.Chem.Int.Ed.2016,55,15319-15322;Wang,D.;Mao,J.;Zhu,C.Chem.Sci.2018,9,5805-5809;Zhao,K.;Yamashita,K.;Carpenter,J.;Sherwood,T.;Ewing,W.;Cheng,P.;Knowles,R.J.Am.Chem.Soc.2019,141,8752-8757)。因此,进一步发展非张力环醇的C-C键断裂方法,就显得尤为重要。
发明内容
本发明的目的在于提供一种反应条件温和、高效、底物范围广,高区域选择性的通过联烯基促进的环醇的碳碳键断裂制备卤代酮类化合物的方法。
本发明是采用以下具体技术方案来实现的:
本发明提出了一种通过联烯基促进的环醇的碳碳键断裂制备卤代酮类化合物的方法,在催化剂,氧化剂,卤代剂,有机试剂/水的混合溶剂中,将环醇转化为对应卤代酮类化合物,反应过程如反应式(1)所示:
其中,
n为-2到3的整数;
X为卤素;
R1和R2分别独立地为氢,烷基。
Y为氧,烷基。
优选地,
n为-2,-1,0,1,2,3;
X为氟,氯,溴;
R1和R2分别独立地为氢,C1-C5烷基。
Y为氧,C1-C5烷基。
作为进一步改进,本发明的具体操作步骤如下:
1)反应管连接氩气钢瓶抽换气3次,在氩气保护下依次加入催化剂、氧化剂、卤代剂、含有环醇的有机试剂和水。将反应管置于10℃冷浴中,搅拌12–14小时;
2)待步骤1)反应完全后,将反应管提出冷浴,所得混合液用一定量的水稀释后,用一定量的二氯甲烷萃取3次后,合并有机相,用硅胶短柱过滤,浓缩,快速柱层析得卤代酮类化合物;以式(1)所示的环醇的用量为基准,所述水和二氯甲烷的用量为5.0-10.0mL/mmol,优选地,为10mL/mmol。
本发明中,所述有机试剂为甲苯、氯苯、二氯甲烷、1,2-二氯乙烷、1,1-二氯乙烷、硝基甲烷、乙醚、乙酸乙酯、丙酮、环己烷、四氢呋喃或乙腈、乙二醇二甲醚、二氧六环等中的一种或多种混合;优选地,为二氯甲烷或甲苯。
本发明中,所述有机试剂是指以式(1)所示的环醇的用量为基准,所述有机试剂的用量为1.0-10.0mL/mmol;优选地,为2.5mL/mmol。
本发明中,所述有机试剂和水的体积比为(1.0-10.0):(1.0-10.0);优选地,为1:1。
本发明中,所述催化剂选自三氟甲烷磺酸银、亚硝酸银、碳酸银、四氟硼酸银、六氟锑酸银、对甲苯磺酸银和硝酸银、醋酸银、碘化银、氟化银、六氟磷酸银、氧化银等中的一种或多种混合;优选地,为硝酸银。
本发明中,所述催化剂是指以式(1)所示的环醇的用量为基准,所述催化剂的用量为0.1-1.0mmol/mmol;优选地,为0.24mmol/mmol。
本发明中,所述氧化剂选自过硫酸钾、过硫酸钠、过硫酸铵、空气、氧气、叔丁基过氧化氢、二氧化锰等中一种或多种混合;优选地,为过硫酸钾。
本发明中,所述氧化剂是指以式(1)所示的环醇的用量为基准,所述氧化剂的用量为1.0-3.0mmol/mmol;优选地,为1.2mmol/mmol。
本发明中,所述卤代剂选自N-氯代丁二酰亚胺(NCS)、N-溴代丁二酰亚胺(NBS)、四氯化碳、N-碘代丁二酰亚胺(NIS)、N-氟代双苯磺酰胺(NFSI)和选择性氟试剂(Selectfluor)、次氯酸叔丁酯、氯、溴、碘等中一种或多种混合;优选地,为N-氯代丁二酰亚胺(NCS)、N-溴代丁二酰亚胺(NBS)和选择性氟试剂(Selectfluor)。
本发明中,所述卤代剂是指以式(1)所示的环醇的用量为基准,所述卤代剂的用量为1.0-3.0mmol/mmol;优选地,为N-氯代丁二酰亚胺(NCS)、N-溴代丁二酰亚胺(NBS):1.5mmol/mmol;选择性氟试剂(Selectfluor):2.0mmol/mmol。
本发明中,所述反应的温度为10℃-25℃;优选地,为10℃。
本发明中,所述反应的温度为12–14小时;优选地,为12小时。
本发明所述反应优选在氩气保护下进行。
本发明还提出了一种卤代酮类化合物,其结构如式(A)所示:
其中,
n为-2到3的整数;
X为卤素;
R1和R2分别独立地为氢,烷基。
Y为氧,烷基。
优选地,
n为-2,-1,0,1,2,3;
X为氟,氯,溴;
R1和R2分别独立地为氢,C1-C5烷基。
Y为氧,C1-C5烷基。
本发明公开了在氩气保护下,在有机试剂/水的混合溶剂,催化剂、氧化剂,卤代剂中,通过联烯基促进的环醇的碳碳键断裂制备卤代酮类化合物的方法。通过本发明的方法,在常压下的氩气氛围中,可以将环戊醇,环己醇,环庚醇,环辛醇等开环,由卤代剂制备得到相应卤代酮类化合物。本发明具有原料易得,操作简单,反应条件温和,底物普适性高、范围广,区域选择性高,官能团兼容性好,分离纯化方便等优点。
具体实施方式
结合以下具体实施例和反应式,对本发明作进一步的详细说明,本发明保护不局限于以下实施例。在不背离发明构思的精神和范围下,本领域技术人员能够想到的变化和优点都被包括在本发明中,并且以所附的权利要求书为保护范围。实施本发明的过程、条件、试剂、实验方法等,除以下专门提及的内容之外,均为本领域的普遍知识和公知常识,本发明没有特别限制内容。以下实施例有助于理解本发明,但不限制本发明保护范围。
注:以下实施例反应式中的equiv表示当量;mol表示摩尔;AgNO3表示硝酸银(I);K2S2O8表示过硫酸钾;NCS表示N-氯代丁二酰亚胺;NBS表示N-溴代丁二酰亚胺;Selectfluor表示选择性氟试剂,DCM表示二氯甲烷;EA表示乙酸乙酯;Toluene表示甲苯;H2O表示水;min表示分钟;h表示小时;石油醚沸程为60-90℃;核磁产率由1H NMR确定,内标为二溴甲烷,硅胶目数为300-400。
实施例1
反应管连接上氩气钢瓶,抽换气3次,依次加入K2S2O8(324.6mg,1.2mmol),NBS(266.8mg,1.5mmol),AgNO3(40.6mg,0.24mmol),1e(124.2mg,1.0mmol)的DCM(2.5mL)溶液和H2O(2.5mL)。反应管在10℃下搅拌12小时。反应液用10mL H2O,DCM 10mL X 3萃取,合并有机相,硅胶短柱(3cm)过滤,旋蒸除去溶剂。采用硅胶柱层析进行分离纯化(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=200/4/3),得产物3eb(131.9mg,65%):油状液体;1H NMR(400MHz,CDCl3)δ=5.78(t,J=6.6Hz,1H,C=CH),5.26(d,J=6.8Hz,2H,C=CH2),3.41(t,J=6.6Hz,2H,CH2Br),2.65(t,J=7.2Hz,2H,COCH2),1.88(quintet,J=7.0Hz,2H,CH2),1.76(quintet,J=7.3Hz,2H,CH2);13C NMR(100MHz,CDCl3):δ=216.6,199.9,96.6,79.5,37.9,33.2,32.0,22.9;IR(neat):ν=2943,1959,1932,1676,1437,1409,1366,1253,1157,1070,1027cm-1;MS(ESI)m/z:205[M(81Br)+H+],203[M(79Br)+H+];HRMS:Calcd for C8H12 81BrO[M(81Br)+H+]:205.0046;Found:205.0050;C8H12 79BrO[M(79Br)+H+]:203.0066;Found:203.0070.
实施例2
操作同实施例1。K2S2O8(324.8mg,1.20mmol),NBS(267.1mg,1.50mmol),AgNO3(40.6mg,0.24mmol),1d(138.0mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3db(127.5mg,57%)(洗脱剂:石油醚/乙酸乙酯=80/1):油状液体;1H NMR(400MHz,CDCl3)δ=5.78(t,J=6.6Hz,1H,C=CH),5.25(d,J=6.4Hz,2H,C=CH2),3.41(t,J=6.8Hz,2H,CH2Br),2.63(t,J=7.4Hz,2H,COCH2),1.87(quintet,J=7.1Hz,2H,CH2),1.63(quintet,J=7.5Hz,2H,CH2),1.45(quintet,J=7.6Hz,2H,CH2);13C NMR(100MHz,CDCl3):δ=216.6,200.3,96.6,79.4,38.8,33.5,32.5,27.6,23.5;IR(neat):ν=2935,2860,1957,1931,1677,1455,1438,1409,1362,1294,1252,1157,1068cm-1;MS(70eV,EI)m/z(%):218[M(81Br)+,1.58],216[M(79Br)+,1.49],69(100);HRMS:Calcd for C9H13 79BrO(M+):216.0150;Found:216.0152.
实施例3
操作同实施例1。K2S2O8(324.0mg,1.20mmol),NBS(266.2mg,1.50mmol),AgNO3(40.6mg,0.24mmol),1f(152.0mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3fb(138.7mg,60%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=200/4/3):油状液体;1H NMR(400MHz,CDCl3)δ=5.77(t,J=6.4Hz,1H,C=CH),5.24(d,J=6.4Hz,2H,C=CH2),3.40(t,J=6.8Hz,2H,CH2Br),2.61(t,J=7.4Hz,2H,COCH2),1.86(quintet,J=7.1Hz,2H,CH2),1.62(quintet,J=7.5Hz,2H,CH2),1.45(quintet,J=7.5Hz,2H,CH2),1.33(quintet,J=7.5Hz,2H,CH2);13C NMR(100MHz,CDCl3):δ=216.6,200.6,96.6,79.3,38.9,33.7,32.5,28.2,27.8,24.1;IR(neat):ν=2935,2858,1959,1933,1679,1462,1409,1363,1241,1167,1069cm-1;MS(70eV,EI)m/z(%):232[M+(81Br),2.38],230[M+(79Br),2.45],55(100);HRMS:Calcd for C10H15 79BrO(M+):230.0301;Found:230.0301.
实施例4
操作同实施例1。K2S2O8(324.7mg,1.20mmol),Selectfluor(708.9mg,2.00mmol),AgNO3(40.4mg,0.24mmol),1d(138.2mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3dc(62.8mg,40%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=200/4/3):油状液体;1H NMR(400MHz,CDCl3)δ=5.78(t,J=6.4Hz,1H,C=CH),5.24(d,J=6.4Hz,2H,C=CH2),4.50(t,J=6.0Hz,1H,one proton of CH2F),4.38(t,J=6.0Hz,1H,one proton of CH2F),2.63(t,J=7.2Hz,2H,COCH2),1.79-1.60(m,4H,2XCH2),1.48-1.36(m,2H,CH2);13C NMR(100MHz,CDCl3):δ=216.6,200.5,96.6,83.8(d,J=162.7Hz),79.4,38.9,30.1(d,J=19.7Hz),24.8(d,J=5.5Hz),24.0;19F NMR(376MHz,CDCl3):δ=-218.9;IR(neat):ν=2942,2867,1959,1933,1677,1461,1411,1365,1158,1062,1040cm-1;MS(70eV,EI)m/z(%):156(M+,2.18),69(100);HRMS:Calcd for C9H13FO(M+):156.0945;Found:156.0940.
实施例5
操作同实施例1。K2S2O8(324.4mg,1.20mmol),Selectfluor(708.4mg,2.00mmol),AgNO3(40.6mg,0.24mmol),1f(152.1mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3fc(85.0mg,50%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=200/4/3):油状液体;1H NMR(400MHz,CDCl3)δ=5.77(t,J=6.6Hz,1H,C=CH),5.24(d,J=6.4Hz,2H,C=CH2),4.49(t,J=6.0Hz,1H,one proton of CH2F),4.37(t,J=6.2Hz,1H,one proton of CH2F),2.61(t,J=7.4Hz,2H,COCH2),1.79-1.57(m,4H,2XCH2),1.47-1.30(m,4H,2XCH2);13C NMR(100MHz,CDCl3):δ=216.6,200.7,96.6,84.0(d,J=162.7Hz),79.3,38.9,30.2(d,J=19.0Hz),28.7,24.9(d,J=5.5Hz),24.2;19F NMR(376MHz,CDCl3):δ=-218.7;IR(neat):ν=2937,2861,1960,1934,1678,1464,1410,1363,1158,1047cm-1;MS(70eV,EI)m/z(%):170(M+,4.72),55(100);HRMS:Calcd for C10H15FO(M+):170.1101;Found:170.1104.
实施例6
操作同实施例1。K2S2O8(676.0mg,2.50mmol),NCS(200.0mg,1.50mmol),AgNO3(85.1mg,0.50mmol),1h(151.9mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3ha(93.5mg,50%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=400/8/5):油状液体;1H NMR(400MHz,CDCl3):δ=5.78(t,J=6.6Hz,1H,C=CH),5.26(d,J=6.4Hz,2H,C=CH2),3.64-3.49(m,2H,CH2Cl),2.71-2.56(m,2H,COCH2),1.85-1.76(m,1H,one proton of CH2),1.73-1.55(m,3H,CH2+CH),1.52-1.39(m,1H,one proton of CH2),0.91(d,J=6.4Hz,3H,CH3);13CNMR(100MHz,CDCl3):δ=216.6,200.5,96.6,79.4,42.9,39.4,36.6,30.9,30.0,18.8;IR(neat):ν=2961,2930,2873,1959,1933,1678,1454,1411,1381,1289,1158,1068cm-1;MS(70eV,EI)m/z(%):188[M+(37Cl),0.52],186[M+(35Cl),1.71],55(100);HRMS:Calcd forC10H15 35ClO(M+):186.0811;Found:186.0813.
实施例7
操作同实施例1。K2S2O8(676.0mg,2.50mmol),NBS(267.0mg,1.50mmol),AgNO3(85.1mg,0.50mmol),1h(152.4mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3hb(120.7mg,52%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=400/8/5):油状液体;1H NMR(400MHz,CDCl3):δ=5.78(t,J=6.4Hz,1H,C=CH),5.26(d,J=6.4Hz,2H,C=CH2),3.52-3.37(m,2H,CH2Br),2.71-2.55(m,2H,COCH2),1.93-1.82(m,1H,one proton of CH2),1.75-1.59(m,3H,CH2+CH),1.52-1.39(m,1H,one proton of CH2),0.91(d,J=5.6Hz,3H,CH3);13CNMR(100MHz,CDCl3):δ=216.6,200.5,96.7,79.5,39.6,36.6,31.7,31.3,30.8,18.7;IR(neat):ν=2961,2930,2872,1959,1932,1678,1460,1410,1380,1345,1257,1218,1168,1068cm-1;MS(70eV,EI)m/z(%):193[M+(81Br)-C3H3,45.95],191[M+(79Br)-C3H3,45.59],55(100);HRMS:Calcd for C10H15 79BrO(M+):230.0301;Found:230.0297.
实施例8
操作同实施例1。K2S2O8(65.1mg,0.24mmol),NCS(40.2mg,0.30mmol),AgNO3(17.2mg,0.10mmol),1i(33.5mg,0.20mmol),DCM(0.5mL),H2O(0.5mL),反应24小时得到3ia(20.7mg,51%)(洗脱剂:石油醚/乙酸乙酯=60/1):油状液体;1H NMR(400MHz,CDCl3):δ=5.78(t,J=6.4Hz,1H,C=CH),5.25(d,J=6.8Hz,2H,C=CH2),3.55(t,J=7.2Hz,2H,CH2Cl),2.60(t,J=7.8Hz,2H,COCH2),1.76-1.69(m,2H,CH2),1.64-1.56(m,2H,CH2),1.54-1.47(m,1H,CH),1.33(quintet,J=7.1Hz,2H,CH2),0.88(t,J=7.4Hz,3H,CH3);13C NMR(100MHz,CDCl3):δ=216.6,200.6,96.6,79.4,43.0,36.3,36.14,36.13,27.2,25.2,10.4;IR(neat):ν=2963,2932,2875,1959,1933,1678,1460,1411,1354,1292,1260,1165,1098,1068cm-1;MS(70eV,EI)m/z(%):163[M+(37Cl)-C3H3,19.13],161[M+(35Cl)-C3H3,63.6],55(100);HRMS:Calcd for C11H17 35ClO(M+):200.0962;Found:200.0963.
实施例9
操作同实施例1。K2S2O8(324.0mg,1.20mmol),NBS(266.8mg,1.50mmol),AgNO3(85.1mg,0.50mmol),1i(177.0mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3ib(128.4mg,52%)(洗脱剂:石油醚/乙酸乙酯=80/1):油状液体;1H NMR(400MHz,CDCl3):δ=5.78(t,J=6.4Hz,1H,C=CH),5.26(d,J=6.8Hz,2H,C=CH2),3.42(t,J=7.4Hz,2H,CH2Br),2.60(t,J=7.8Hz,2H,COCH2),1.87-1.76(m,2H,CH2),1.62-1.56(m,2H,CH2),1.52-1.46(m,1H,CH),1.36-1.29(m,2H,CH2),0.88(t,J=7.4Hz,3H,CH3);13C NMR(100MHz,CDCl3):δ=216.5,200.5,96.6,79.4,37.3,36.4,36.2,31.7,27.0,25.1,10.4;IR(neat):ν=3065,2962,2930,2875,1959,1932,1677,1460,1411,1381,1353,1313,1295,1254,1216,1165,1098,1068cm-1;MS(70eV,EI)m/z(%):207[M+(81Br)-C3H3,21.1],205[M+(79Br)-C3H3,21.4],55(100);HRMS:Calcd for C11H17 79BrO(M+):244.0457;Found:244.0459.
实施例10
操作同实施例1。K2S2O8(676.0mg,2.50mmol),NCS(200.1mg,1.50mmol),AgNO3(85.1mg,0.50mmol),1j(166.0mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应17小时得到3ja(99.5mg,50%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=100/1/1):油状液体;1H NMR(400MHz,CDCl3):δ=5.78(t,J=6.4Hz,1H,C=CH),5.26(d,J=6.4Hz,2H,C=CH2),3.55-3.48(m,2H,CH2Cl),2.62-2.54(m,2H,COCH2),1.77-1.69(m,2H,CH2),1.56-1.49(m,2H,CH2),0.91(s,6H,2XCH3);13C NMR(100MHz,CDCl3):δ=216.5,200.6,96.6,79.5,44.6,41.0,36.0,34.1,33.1,26.7;IR(neat):ν=2960,2871,1959,1932,1679,1472,1412,1389,1369,1343,1292,1264,1155,1118,1071cm-1;MS(70eV,EI)m/z(%):202[M+(37Cl),0.45],200[M+(35Cl),1.36],161(100);HRMS:Calcd for C11H17 35ClO(M+):200.0968;Found:200.0971.
实施例11
操作同实施例1。K2S2O8(324.5mg,1.20mmol),NBS(267.2mg,1.50mmol),AgNO3(84.7mg,0.50mmol),1j(166.0mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3jb(143.5mg,58%,纯度:99%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=400/4/5):油状液体;1H NMR(400MHz,CDCl3):δ=5.78(t,J=6.6Hz,1H,C=CH),5.27(d,J=6.4Hz,2H,C=CH2),3.41-3.34(m,2H,CH2Br),2.61-2.53(m,2H,COCH2),1.87-1.79(m,2H,CH2),1.56-1.49(m,2H,CH2),0.90(s,6H,2XCH3);13C NMR(100MHz,CDCl3):δ=216.6,200.6,96.6,79.6,45.3,35.8,34.1,28.9,26.5;IR(neat):ν=2958,2934,2870,1959,1932,1932,1677,1471,1412,1389,1368,1307,1239,1155,1102,1071cm-1;MS(70eV,EI)m/z(%):207[M+(81Br)-C3H3,47.77],205[M+(79Br)-C3H3,51.90],55(100);HRMS:Calcd for C11H17 79BrO(M+):244.0457;Found:244.0458.
实施例12
操作同实施例1。K2S2O8(675.4mg,2.50mmol),NCS(200.3mg,1.50mmol),AgNO3(84.8mg,0.50mmol),1m(140.0mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3ma(52.4mg,30%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=200/8/5):油状液体;1H NMR(400MHz,CDCl3):δ=5.82(t,J=6.4Hz,1H,C=CH),5.28(d,J=6.4Hz,2H,C=CH2),3.79(t,J=6.4Hz,2H,CH2Cl),3.71(t,J=5.6Hz,2H,CH2),3.60(t,J=5.6Hz,2H,CH2),2.92(t,J=6.2Hz,2H,COCH2);13C NMR(100MHz,CDCl3):δ=217.0,198.2,97.0,79.8,71.1,66.2,42.6,39.1;IR(neat):ν=2985,2964,2875,1959,1932,1676,1415,1370,1299,1258,1170,1113,1044cm-1;MS(70eV,EI)m/z(%):176[M+(37Cl),2.85],174[M+(35Cl),8.76],93(100);HRMS:Calcd for C8H11 35ClO2(M+):174.0442;Found:174.0434.
实施例13
操作同实施例1。K2S2O8(676.0mg,2.50mmol),NBS(267.3mg,1.50mmol),AgNO3(85.0mg,0.50mmol),1m(140.0mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3mb(87.5mg,40%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=40/2/1):油状液体;1H NMR(400MHz,CDCl3):δ=5.82(t,J=6.4Hz,1H,C=CH),5.28(d,J=6.4Hz,2H,C=CH2),3.78(quintet,J=6.2Hz,4H,2XCH2),3.45(t,J=6.2Hz,2H,CH2),2.92(t,J=6.4Hz,2H,COCH2);13C NMR(100MHz,CDCl3):δ=217.0,198.1,97.0,79.8,70.8,66.1,39.0,30.2;IR(neat):ν=2986,2873,1958,1931,1675,1471,1417,1368,1277,1168,1106,1043,1017cm-1;MS(70eV,EI)m/z(%):220[M+(81Br),3.06],218[M+(79Br),3.14],107(100);HRMS:Calcd forC8H11 79BrO2(M+):217.9937;Found:217.9931.
实施例14
操作同实施例1。K2S2O8(324.7mg,1.20mmol),NBS(266.8mg,1.50mmol),AgNO3(40.6mg,0.24mmol),1n(152.0mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3nb(161.5mg,70%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=400/8/5):油状液体;1H NMR(400MHz,CDCl3):δ=5.78(t,J=6.4Hz,1H,C=CH),5.25(d,J=6.8Hz,2H,C=CH2),4.13(sextet,J=6.5Hz,1H,CHBr),2.63(t,J=7.2Hz,2H,COCH2),1.91-1.36(m,9H,3XCH2+CH3);13C NMR(100MHz,CDCl3):δ=216.6,200.4,96.6,79.4,51.4,40.8,38.8,27.3,26.4,23.6;IR(neat):ν=2938,2863,1959,1932,1678,1453,1409,1377,1290,1236,1158,1099,1069cm-1;MS(70eV,EI)m/z(%):232[M+(81Br),1.45],230[M+(79Br),1.47],55(100);HRMS:Calcd for C10H15 79BrO(M+):230.0301;Found:230.0302.
实施例15
操作同实施例1。K2S2O8(325.0mg,1.20mmol),Selectfluor(531.7mg,1.50mmol),AgNO3(41.0mg,0.24mmol),1n(152.1mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3nc(119.5mg,70%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=400/8/5):油状液体;1H NMR(400MHz,CDCl3):δ=5.78(t,J=6.4Hz,1H,C=CH),5.24(d,J=6.4Hz,2H,C=CH2),4.76-4.53(m,1H,CHF),2.62(t,J=7.4Hz,2H,COCH2),1.78-1.24(m,9H,3XCH2+CH3);13C NMR(100MHz,CDCl3):δ=216.6,200.5,96.7,90.7(d,J=163.5Hz),79.4,38.9,36.6(d,J=20.5Hz),24.6(d,J=4.8Hz),24.2,20.9(d,J=22.9Hz);19F NMR(376MHz,CDCl3):δ=-173.1;IR(neat):ν=2979,2937,2866,1959,1933,1678,1461,1410,1386,1234,1161,1133,1088,1069cm-1;MS(70eV,EI)m/z(%):131[(M+-C3H3),28.0],55(100);HRMS:Calcdfor C10H15FO(M+):170.1101;Found:170.1094.
实施例16
操作同实施例1。K2S2O8(675.9mg,2.50mmol),NCS(200.7mg,1.50mmol),AgNO3(84.9mg,0.50mmol),1p(165.9mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应12小时得到3pa和3pa’(100.7mg,50%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=100/1/1):油状液体;1HNMR(400MHz,CDCl3):δ=5.77(t,J1=6.6Hz,1H,C=CH),5.23(d,J1=6.4Hz,2H,C=CH2),3.33(s,2H,CH2Cl),2.60(t,J=7.4Hz,2H,COCH2),1.61-1.51(m,2H,CH2),1.34-1.27(m,2H,CH2),0.97(s,6H,2XCH3);13C NMR(100MHz,CDCl3):δ=216.7,200.5,96.7,79.4,55.4,39.6,38.6,35.2,24.9,18.9;IR(neat):ν=2960,2873,1959,1933,1680,1470,1436,1409,1387,1367,1290,1156,1115,1071cm-1;MS(70eV,EI)m/z(%):202[M+(37Cl),0.67],200[M+(35Cl),2.04],55(100);HRMS:Calcd for C11H17 35ClO(M+):200.0968;Found:200.0971.
实施例17
操作同实施例1。K2S2O8(324.7mg,1.20mmol),NBS(267.2mg,1.50mmol),AgNO3(85.1mg,0.50mmol),1p(166.3mg,1.00mmol),DCM(2.5mL),H2O(2.5mL),反应16小时得到3pb和3pb’(98.1mg,40%)(洗脱剂:石油醚/乙酸乙酯/二氯甲烷=400/3/4):油状液体;1HNMR(400MHz,CDCl3):δ=5.78(t,J=6.6Hz,1H,C=CH),5.24(d,J=6.4Hz,2H,C=CH2),3.29(s,2H,CH2Br),2.61(t,J=7.4Hz,2H,COCH2),1.62-1.51(m,2H,CH2),1.36-1.29(m,2H,CH2),1.01(s,6H,2XCH3);13C NMR(100MHz,CDCl3):δ=216.6,200.4,96.6,79.4,46.4,39.5,39.3,34.5,25.6,19.0;IR(neat):ν=2960,2903,2872,1959,1932,1678,1469,1430,1408,1386,1366,1259,1155,1101,1070cm-1;MS(70eV,EI)m/z(%):207[M+(81Br)-C3H3,12.61],205[M+(79Br)-C3H3,13.38],55(100);HRMS:Calcd for C11H17 79BrO(M+):244.0457;Found:244.0455.
本发明并不局限于上面揭示和描述的具体实施方式。在不背离发明构思的精神和范围下,对本发明的一些修改和变更也应当落入本发明的权利要求的保护范围内,并且以所附的权利要求书为保护范围。此外,尽管本说明书中使用了一些特定的术语,但这些术语只是为了方便说明,并不对本发明构成任何限制。
Claims (10)
2.如权利要求1所述的方法,其特征在于,n为-2,-1,0,1,2,3;X为氟,氯,溴;R1和R2分别独立地为氢,C1-C5烷基;Y为氧,C1-C5烷基。
3.如权利要求1所述的方法,其特征在于,所述有机试剂为甲苯、氯苯、二氯甲烷、1,2-二氯乙烷、1,1-二氯乙烷、硝基甲烷、乙醚、乙酸乙酯、丙酮、环己烷、四氢呋喃、乙腈、乙二醇二甲醚、二氧六环中的一种或多种混合;和/或,以环醇的用量为基准,所述有机试剂的用量为1.0-10.0mL/mmol;和/或,所述有机试剂和水的体积比为(1.0-10.0):(1.0-10.0)。
4.如权利要求1所述的方法,其特征在于,所述催化剂选自三氟甲烷磺酸银、亚硝酸银、碳酸银、四氟硼酸银、六氟锑酸银、对甲苯磺酸银、硝酸银、醋酸银、碘化银、氟化银、六氟磷酸银、氧化银中的一种或多种混合;和/或,以环醇的用量为基准,所述催化剂的用量为0.1-1.0mmol/mmol。
5.如权利要求1所述的方法,其特征在于,所述氧化剂选自过硫酸钾、过硫酸钠、过硫酸铵、空气、氧气、叔丁基过氧化氢、二氧化锰中一种或多种混合;和/或,以环醇的用量为基准,所述氧化剂的用量为1.0-3.0mmol/mmol。
6.如权利要求1所述的方法,其特征在于,所述卤代剂选自N-氯代丁二酰亚胺NCS、N-溴代丁二酰亚胺NBS、四氯化碳、N-碘代丁二酰亚胺NIS、N-氟代双苯磺酰胺NFSI、选择性氟试剂Selectfluor、次氯酸叔丁酯、氯、溴、碘中一种或多种混合;和/或,以环醇的用量为基准,所述卤代剂的用量为1.0-3.0mmol/mmol。
7.如权利要求1所述的方法,其特征在于,所述反应的温度为10℃-25℃;所述反应的时间为12-14小时。
8.如权利要求1所述的方法,其特征在于,所述方法具体包括以下步骤:
1)反应管连接氩气钢瓶抽换气3次,在氩气保护下依次加入催化剂、氧化剂、卤代剂、含有环醇的有机试剂和水;将反应管置于10℃冷浴中,搅拌12-14小时;其中,以环醇的用量为基准,所述有机试剂的用量为1.0-10.0mL/mmol,所述有机试剂和水的体积比为(1.0-10.0):(1.0-10.0);
2)待步骤1)反应完全后,将反应管提出冷浴,所得混合液用一定量的水稀释后,用一定量的有机溶剂萃取3次后,合并有机相,用硅胶短柱过滤,浓缩,快速柱层析得醛或酮类化合物;以环醇的用量为基准,所述水的用量为5.0-10.0mL/mmol;以环醇的用量为基准,所述有机溶剂的用量为5.0-10.0mL/mmol。
10.如权利要求9所述的卤代酮类化合物,其特征在于,n为-2,-1,0,1,2,3;X为氟,氯,溴;R1和R2分别独立地为氢,C1-C5烷基;Y为氧,C1-C5烷基。
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HASHMI ASK等: "Switch from palladium-catalyzed cycloisomerization/dimerization of terminal allenyl ketones to preferential formation of monomers by a 5-palladatricyclo[4.1.0.0(2,4)]heptane catalyst: Synthesis of furans from substrates incompatible with the commonly used", 《CHEMISCHE BERICHTE》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114790141A (zh) * | 2022-05-25 | 2022-07-26 | 大连理工大学 | 一种无过渡金属催化的氯代烯丙基酯的合成方法 |
CN114790141B (zh) * | 2022-05-25 | 2023-03-07 | 大连理工大学 | 一种无过渡金属催化的氯代烯丙基酯的合成方法 |
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