微波輻射下吡唑基化環境法的研究

含有糊精素或硫醇酸的化合物具有廣的光譜活性。在農藥的發展中，環化合物農藥是最重要的發展趨勢，環化合物農藥是一個最重要的發展趨向，以5-3-硝基-4-硝基-4-硝基磺酸為母核的衍生物。由于其高生物活性，其結構獨特、安全高效、無相互作用，因此引起了人們的廣泛注意。5-3-硝基-4-硝基溶菌酶酸乙酰胺和硝基溶菌酶酸乙酰胺的反應可以縮合反應。氯原子可以通過移除或兩者一起參與環反應形成新的配合反應。這是一種重要的合成水體，在構建雙環環體系方面顯示出其特定的應用價值[4-6]。在本文中，我們報告了在微波輻射下，由5-3-甲基-4-硝基-4-硝基磺酸乙酰胺和氯仿-5-3-甲基-4-硝基磺酸乙酰胺和硝基乙酰胺反應的實驗結果。1實驗部分1.1顯微熔點測定Bruker-600核磁共振動儀,CDCl3為溶劑,TMS為內標.Brukertensor27紅外光譜儀,檢測范圍為4000~400cm-1;Feligen液質聯用儀;XRC-1顯微熔點測定儀,熔點未校正;MB20TFC-2型微波爐(蘇州三星電子有限公司).吡啶、芳香醛、芳香酮、醋酸銨、醋酸等實驗用試劑均為化學純合成試劑.5-氯-3-甲基-1-苯基-4-吡唑甲醛按文獻合成;氯化N-苯乙酮基吡啶由吡啶和α-氯代苯乙酮在苯中回流反應制備.1.2合成方法1.2.1nmr1.3在50mL的錐形瓶中,加入5-氯-3-甲基-1-苯基-4-吡唑甲醛(1)(1.0mmol,0.221g),氯化N-苯乙酮基吡啶(2)(1.2mmol,0.280g),取代苯乙酮3a~3e(1.0mmol),醋酸銨(3.0g)和醋酸(2.0mL),混合均勻,在195W微波功率下加熱30~60s.反應完成后,取出產物冷卻,加入50mL水,過濾得粗產品,用乙醇重結晶得白色固體產品4a~4e.4a:Ar=p-ClC6H4,白色固體,收率93%;m.p.148~149℃;1HNMR(CDCl3)δ:8.17(d,J=7.8Hz,2H,ArH),8.13(d,J=7.8Hz,2H,ArH),7.80(s,1H,PyH),7.76(s,1H,PyH),7.62(d,J=7.8Hz,2H,ArH),7.54(t,J=7.2Hz,4H,ArH),7.49(t,J=7.2Hz,4H,ArH),2.50(s,3H,CH3);IR(KBr)ν:3448(m),2923(w),1605(s),1548(m),1498(s),1457(vw),1382(s),1354(w),1092(s),1011(s),824(vs),756(vs)cm-1;MSm/z:455.47.4b:Ar=C6H5,白色固體,收率91%;m.p.141~142℃;1HNMR(CDCl3)δ:8.18(d,J=7.2Hz,4H,ArH),7.80(s,2H,PyH),7.62(d,J=7.8Hz,2H,ArH),7.53(t,J=7.2Hz,6H,ArH),7.47(t,J=6.6Hz,3H,ArH),2.51(s,3H,CH3);13CNMRδ:157.23,148.13,141.42,138.90,138.06,129.34,129.14,128.78,128.55,127.31,125.74,125.23,119.03,117.28,13.72;IR(KBr)ν:3030(w),2925(w),1601(s),1549(m),1500(s),1392(m),1358(m),1073(m),998(m),870(m),816(m),762(s)cm-1;MSm/z:421.40.4c:Ar=p-CH3C6H4,白色固體,收率81%;m.p.97~98℃;1HNMR(CDCl3)δ:8.18(d,J=7.2Hz,2H,ArH),8.08(d,J=6.3Hz,2H,ArH),7.76(s,1H,PyH),7.73(s,1H,PyH),7.62(d,J=7.8Hz,2H,ArH),7.53(t,J=7.2Hz,4H,ArH),7.46(d,J=7.2Hz,2H,ArH),7.33(d,J=7.2Hz,2H,ArH),2.48(s,3H,CH3),2.44(s,3H,CH3);13CNMRδ:158.30,158.19,158.02,149.26,149.23,140.52,139.12,130.61,130.39,130.23,129.85,129.68,129.63,128.50,128.40,128.28,126.81,126.32,119.86,118.40,14.84,14.80;IR(KBr)ν:3029(w),2921(w),1602(vs),1545(s),1500(s),1387(m),1353(m),996(m),820(s),764(s)cm-1;MSm/z:435.47.4d:Ar=p-CH3OC6H4,白色固體,收率85%;m.p.173~174℃;1HNMR(CDCl3)δ:8.14~8.18(m,4H,ArH),7.72(s,2H,PyH),7.62(d,J=6.6Hz,2H,ArH)7.52(br,4H,ArH),7.45(d,J=6.0Hz,2H,ArH),7.04(dJ=7.8Hz,2H,ArH),3.87(s,3H,OCH3),2.49(s,3HCH3);13CNMRδ:160.68,160.64,157.21,157.00,148.14140.83,139.59,138.17,138.12,132.09,129.16,128.76128.51,128.43,127.14,125.59,125.23,118.15,118.05117.56,114.14,113.90,55.41,13.72;IR(KBr)ν:3420(w),1598(vs),1542(s),1502(s),1456(m),1399(m)1249(s),1177(m),1078(w),871(w),836(w),771(w)cm-1;MSm/z:451.40.4e:Ar=p-NO2C6H4,白色固體,收率85%;m.p190~191℃;1HNMR(CDCl3)δ:8.99(s,1H,ArH),8.54(d,J=7.2Hz,1H,ArH),8.32(d,J=7.8Hz,1H,ArH)8.17(d,J=7.2Hz,2H,ArH),7.86~7.88(d,2H,PyH)7.70~7.74(m,1H,ArH),7.62~7.63(m,2H,ArH),7.55(d,J=7.8Hz,4H,ArH),7.48~7.52(m,2H,ArH),2.53(s,3H,CH3);IR(KBr)ν:3081(w),2925(w),1660(w)1602(s),1530(s),1496(s),1345(vs),1247(w),1081(w)877(w),812(w),756(s)cm-1;MSm/z:466.33.1.2.2酶法m在50mL的錐形瓶中,加入5-氯-3-甲基-1-苯基-4-吡唑甲醛(1)(1.0mmol,0.22g),酰肼5a~5g(單酰肼1.5mmol,雙酰肼0.5mmol),醋酸(2.0mL),混合均勻,在130W微波功率下加熱32~60s.反應完成后,取出產物冷卻,加入50mL水,過濾得粗產品,用乙醇重結晶得固體產品6a~6g.6a:R=Ph,白色固體,收率86%;m.p.119~120℃1HNMR(CDCl3)δ:9.43(s,1H,NH),8.41(s,1H,CH=N)7.89(s,4H,ArH),7.50(t,J=7.2Hz,4H,ArH),7.44(t,J=7.2Hz,2H,ArH),2.65(s,3H,CH3);13CNMRδ:137.69129.17,129.10,128.83,128.79,128.76,128.50,127.20127.15,127.09,125.19,124.89,14.66;IR(KBr)ν:3423(m),3190(m),3042(m),2930(w),1626(s),1552(s),1499(m),1416(m),1348(m),1289(s),1074(m),799(m)cm-1;MSm/z:339.33.6b:R=PhCH2,白色固體,收率92%;m.p.128~129℃;1HNMR(CDCl3)δ:9.70(s,1H,NH),7.78(s,1HCH=N),7.55(d,J=7.8Hz,2H,ArH),7.50(t,J=7.2Hz2H,ArH),7.44(t,J=7.2Hz,1H,ArH),7.37(d,J=7.2Hz2H,ArH),7.31(t,J=7.2Hz,2H,ArH),7.24(t,J=8.4Hz1H,ArH),4.08(s,2H,CH2),2.54(s,3H,CH3);13CNMRδ:173.45,149.07,137.69,136.06,134.84,129.48,129.35129.29,129.12,128.76,128.53,128.49,127.92,126.82124.90,112.94,39.34,14.77;IR(KBr)ν:3340(m),3074(w),2922(w),2857(w),1627(s),1525(s),1416(m),1299(m),1075(w),812(m),751(m)cm-1;MSm/z:353.33.6c:R=Fc,黃色固體,收率75%;m.p.242~244℃;1HNMR(CDCl3)δ:8.77(s,1H,NH),8.78(s,2H,CH=N),7.70~7.30(m,5H,ArH),5.60~4.00(m,9H,FcH),2.64(s,3H,CH3),2.44(s,3H,CH3);13CNMRδ:137.77,129.22,129.08,128.48,127.86,125.20,125.15,124.96,69.96,14.74;IR(KBr)ν:3446(s),2926(w),1637(m),1499(w),1403(w),1384(s),1296(w),763(w)cm-1;MSm/z:447.33.6d:R=o-HOC6H4,白色固體,收率79%;m.p.148~149℃;1HNMR(DMSO-d6)δ:11.98(s,1H,OH),11.84(s,1H,NH),8.49(s,1H,CH=N),7.89(d,J=7.2Hz,1H,ArH),7.62~7.58(m,4H,ArH),7.54(t,J=7.2Hz,1H,ArH),7.45(t,J=7.2Hz,1H,ArH),6.98~6.95(m,2H,ArH),2.51(s,3H,CH3);13CNMRδ:165.33,160.05,149.00,141.49,137.73,134.31,129.75,129.17,128.53,128.03,125.42,119.27,117.86,115.90,113.52,14.79;IR(KBr)ν:3320(m),3198(m),3065(w),2922(w),1635(s),1554(m),1497(m),1414(w),1356(m),1229(m),1076(w),753(m)cm-1;MSm/z:355.40.6e:R=m-C6H4,白色固體,收率93%;m.p.>270℃;1HNMR(DMSO-d6)δ:11.96(s,2H,NH),8.51(s,2H,CH=N),8.50~7.60(m,14H,ArH),2.50(s,6H,CH3);13CNMRδ:162.64,148.92,140.80,137.75,134.33,131.05,129.75,129.24,129.15,127.84,127.20,125.40,113.63,14.81;IR(KBr)ν:3452(s),3420(s),2926(w),1634(s),1496(w),1385(m),755(w)cm-1;MSm/z:600.10.6f:R=p-C6H4,白色固體,收率89%;m.p.>270℃;1HNMR(DMSO-d6)δ:11.92(s,2H,NH),8.51(s,2H,CH=N),8.10~7.50(m,14H,ArH),2.50(s,6H,CH3);13CNMRδ:148.93,137.74,129.77,129.18,128.15,125.42,14.82;IR(KBr)ν:3446(m),3207(m),3042(m),2923(w),1645(s),1552(m),1501(m),1412(m),1384(m),1282(m),760(m)cm-1;MSm/z:600.17.6g:R=2,6-C5H3N,白色固體,收率84%;m.p.>270℃;1HNMR(DMSO-d6)δ:12.28(s,2H,NH),8.78(s,2H,CH=N),8.35(d,J=7.2Hz,2H,PyH),8.32~8.29(m,1H,PyH),7.63(d,J=7.2Hz,4H,ArH),7.59(t,J=7.8Hz,4H,ArH),7.52(t,J=7.2Hz,2H,ArH),2.55(s,6H,CH3);13CNMRδ:149.36,144.64,139.93,138.15,137.53,130.15,129.27,129.20,128.77,128.56,124.88,123.53,116.46,112.77,15.01;IR(KBr)ν:3446(s),3196(m),2925(w),2856(w),1666(m),1624(m),1548(m),1412(w),1384(s),762(w)cm-1;MSm/z:601.17.1.2.3j1h,h,m在50mL的錐形瓶中,加入5-氯-3-甲基-1-苯基-4-吡唑甲醛(1)(1.0mmol,0.22g),鹽酸羥胺(1.5mmol1.04g),以DMF(2.0mL)和KOH(0.1g)混合物為反應介質,混合均勻,在130W微波功率下加熱40s.反應完成后,取出產物冷卻,加入50mL水,過濾得粗產品用乙醇重結晶得相應固體產品7a.若其它條件相同,而以醋酸(2.0mL)為反應介質,用硅膠柱層析分離得7a和7b.7a:白色固體,收率30%,m.p.138~139℃(文獻值:139~140℃);1HNMR(CDCl3)δ:8.46(s,1HCHN),8.14(s,1H,OH),7.54(d,J=7.8Hz,2H,ArH)7.49(t,J=7.2Hz,2H,ArH),7.43(t,J=7.2Hz,1HArH),2.47(s,3H,CH3);13CNMRδ:148.95,142.44142.41,137.75,137.66,129.12,129.07,128.53,128.47127.55,127.50,125.04,124.95,111.20,14.51,14.43;IR(KBr)ν:3242(s),3082(m),2977(w),1631(w),1594(w)1501(s),1442(m),1290(m),755(m)cm-1;MSm/z:236.47.7b:白色固體,收率35%,m.p.123~124℃;1HNMR(CDCl3)δ:7.60~7.40(m,5H,ArH),2.45(s,3HCH3);13CNMRδ:152.67,137.02,132.70,129.38129.319,124.92,111.79,94.17,13.08;IR(KBr)ν:3436(s),2923(m),2856(w),2226(s),1643(w),1594(m)1532(s),1491(s),1434(s),1376(s),1260(w),763(s)cm-1;MSm/z:215.33.2化合物44e的合成氯化N-苯乙酮基吡啶中的亞甲基受到羰基和吡啶氮正離子的影響,具有較強的酸性,可以發生許多活潑亞甲基的反應,如與α,β-不飽和羰基化合物在胺存在下通過共軛加成和環化形成吡啶等雜環衍生物.鑒于微波作用下的有機反應具有反應速度快、副反應少、產率高、環境友好、操作方便、產品易純化等優點,而且在微波條件下,醛和酮的縮合生成α,β-不飽和羰基化合物也可以很快速地進行,所以我們試驗了在微波條件下,5-氯-3-甲基-1-苯基-4-吡唑甲醛(1)與氯化N-苯乙酮基吡啶(2)和取代苯乙酮3a~3e在醋酸胺和醋酸混合體系中的縮合反應(Eq.1).經微波輻射1~3min、縮合、加成和環化等多個反應全部完成,生成了4-吡唑基-2,6-芳基吡啶衍生物4a~4e,產率高,反應迅速,后處理簡單方便,通過在