本發(fā)明屬于有機化學(xué)領(lǐng)域，涉及一種吡唑的制備方法。

背景技術(shù)：

近年來，大量研究和實踐表明吡唑類化合物具有廣泛的生物活性，無論在醫(yī)藥領(lǐng)域還是在農(nóng)藥領(lǐng)域吡唑類化合物都得到了廣泛的應(yīng)用，而且吡唑環(huán)上取代位點和取代基的多樣性變化使市場化的吡唑類化合物日益豐富。目前，吡唑的工業(yè)合成常用的方法是：通過1,3-二羰基化合物和肼在縮和反應(yīng)條件下制得。2014年，我們報道了一種在叔丁醇鉀和18-冠-6的作用下，n-烷基化苯磺酰腙和末端炔通過環(huán)化反應(yīng)制備吡唑的方法(org.lett.,2014,16,576-579.)，如式一所示。

該方法存在的不足之處是：r¹僅適用于烷基，同時由于叔丁醇鉀的強堿性影響了官能團的容忍度。

本發(fā)明在三氯化鋁的條件下實現(xiàn)了上述轉(zhuǎn)化，r¹的適用范圍包括烷基、芐基、烯丙基和炔丙基。同時底物的適用范圍得到了很好的改善。

技術(shù)實現(xiàn)要素：

本發(fā)明的目的是公開一種吡唑的制備方法，其反應(yīng)通式如式二所示。

其中r¹可為：c1-6的烷基、芐基、烯丙基和炔丙基；r²可為：氫原子、甲基、甲氧基、鹵原子、硝基；r²可處于鄰位、間位或?qū)ξ?；r³可為：氫原子、甲基、甲氧基、鹵原子；r³可處于鄰位、間位或?qū)ξ弧?/p>

反應(yīng)所用三氯化鋁為市售分析純?nèi)然X。所用溶劑可為：1,2-二氯乙烷、二氯甲烷、甲苯、苯，優(yōu)選為1,2-二氯乙烷。所用溫度為室溫。反應(yīng)中n-烷基化苯磺酰腙:末端炔:三氯化鋁的摩爾比為1:2.5:2.5。

具體實施方式

以下為本發(fā)明的實施例，但本發(fā)明的內(nèi)容并不局限于此。

實施例：吡唑化合物3的制備：

氬氣保護下，將n-取代對甲苯磺酰腙1(0.2mmol)溶于1,2-二氯乙烷(2ml)中，加末端炔2(0.5mmol)，alcl3(0.5mmol)，室溫反應(yīng)至n-取代對甲苯磺酰腙1完全消失(1-10小時)，產(chǎn)物乙酸乙酯(200ml)萃取，有機相用飽和na2co3溶液洗，食鹽水洗，無水mgso4干燥，減壓蒸除溶劑，柱層析分離得吡唑化合物3。

譜圖數(shù)據(jù)如下：

3a(85％產(chǎn)率).mp53-55℃；¹hnmr(400mhz,cdcl3)δ＝3.91(s,3h),6.60(s,1h),7.28-7.32(m,1h),7.38-7.46(m,7h),7.83(d,j＝7.6hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.5,103.2,125.5,127.6,128.48,128.56,128.65,128.67,130.6,133.4,145.0,150.4ppm.

3b(95％產(chǎn)率).mp70-73℃；¹hnmr(400mhz,cdcl3)δ＝2.42(s,3h),3.92(s,3h),6.58(s,1h),7.25-7.32(m,3h),7.35-7.42(m,4h),7.83(d,j＝7.2hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,37.5,103.0,125.5,127.5,127.7,128.6,129.4,133.5,138.5,145.1,150.4ppm.

3c(81％產(chǎn)率).mp109-110℃；¹hnmr(400mhz,cdcl3)δ＝3.85(s,3h),3.90(s,3h),6.56(s,1h),6.99(d,j＝8.8hz,2h),7.28-7.32(m,1h),7.37-7.42(m,4h),7.82(d,j＝7.2hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.4,55.3,114.1,123.0,125.4,127.5,128.6,130.0,133.4,144.8,150.3,159.8ppm；hrms(esi):calcdforc17h17n2o[m+h]⁺:265.1335,found:265.1338.

3d(87％產(chǎn)率).mp67-68℃；¹hnmr(400mhz,cdcl3)δ＝3.89(s,3h),6.58(s,1h),7.14-7.18(m,2h),7.29-7.32(m,1h),7.39-7.44(m,4h),7.81-7.83(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.5,103.3,115.7,115.9,125.5,126.70,126.74,127.7,128.6,130.5,130.6,133.3,144.0,150.5,161.6,164.0ppm；hrms(esi):calcdforc16h14fn2[m+h]⁺:253.1136,found:253.1138.

3e(56％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝1.45(t,j＝7.2hz,3h),4.20(q,j＝7.2hz,2h),6.57(s,1h),7.30-7.38(m,1h),7.40-7.49(m,7h),7.84(d,j＝7.2hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝15.9,44.6,103.3,125.6,127.5,128.5,128.6,128.7,128.8,130.9,133.6,144.5,150.5ppm.

3f(79％產(chǎn)率).mp59-61℃；¹hnmr(400mhz,cdcl3)δ＝1.44(t,j＝7.2hz,3h),2.42(s,3h),4.19(q,j＝7.2hz,2h),6.54(s,1h),7.24-7.34(m,5h),7.38-7.42(m,2h),7.84(d,j＝7.2hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝15.9,21.2,44.6,103.2,125.6,127.4,128.0,128.5,128.7,129.4,133.7,138.5,144.5,150.5ppm；hrms(esi):calcdforc18h19n2[m+h]⁺:263.1543,found:263.1542.

3g(81％產(chǎn)率).mp56-57℃；¹hnmr(400mhz,cdcl3)δ＝1.44(t,j＝7.2hz,3h),3.86(s,3h),4.18(q,j＝7.2hz,2h),6.52(s,1h),6.99(d,j＝8.4hz,2h),7.29-7.35(m,1h),7.37-7.42(m,4h),7.83(d,j＝7.2hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝15.9,44.5,55.3,103.1,114.1,123.3,125.5,127.4,128.5,130.1,133.7,144.2,150.4,159.8ppm；hrms(esi):calcdforc18h19n2o[m+h]⁺:279.1492,found:279.1492.

3h(86％產(chǎn)率).mp93-95℃；¹hnmr(400mhz,cdcl3)δ＝1.43(t,j＝7.2hz,3h),4.17(d,j＝7.2hz,2h),6.54(s,1h),7.14-7.18(m,2h),7.28-7.32(m,1h),7.38-7.42(m,4h),7.83(d,j＝7.6hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝15.9,44.5,103.4,115.7,115.9,125.5,126.9,127.0,127.6,128.6,130.6,130.7,133.4,143.4,150.5,161.6,164.0ppm；hrms(esi):calcdforc17h16fn2[m+h]⁺:267.1292,found:267.1293.

3i(67％產(chǎn)率).mp114-117℃；¹hnmr(400mhz,cdcl3)δ＝5.38(s,2h),6.66(s,1h),7.09(d,j＝7.2hz,2h),7.21-7.30(m,4h),7.32-7.42(m,7h),7.87(d,j＝7.2hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝53.2,103.7,125.6,126.7,127.4,127.6,128.55,128.56,128.6,128.8,130.6,133.4,137.7,145.4,150.9ppm；hrms(esi):calcdforc22h19n2[m+h]⁺:311.1543,found:311.1536.

3j(80％產(chǎn)率).mp83-85℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),5.38(s,2h),6.64(s,1h),7.11(d,j＝7.2hz,2h),7.18-7.32(m,8h),7.38-7.42(m,2h),7.86-7.88(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,53.1,103.5,125.6,126.6,127.3,127.6,128.6,128.7,129.3,133.5,137.8,138.6,145.5,150.9ppm；hrms(esi):calcdforc23h21n2[m+h]⁺:325.1699,found:325.1704.

3k(95％產(chǎn)率).mp112-114℃；¹hnmr(400mhz,cdcl3)δ＝5.36(s,2h),6.64(s,1h),7.05-7.09(m,4h),7.22-7.34(m,6h),7.40-7.46(m,2h),7.87(d,j＝7.2hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝53.5,103.8,115.6,115.8,125.6,126.6,127.5,127.7,128.62,128.63,130.6,130.7,133.3,137.5,144.3,150.9,161.6,164.1ppm；hrms(esi):calcdforc22h18fn2[m+h]⁺:329.1449,found:329.1452.

3l(72％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝4.77(dd,j＝3.2,1.6hz,2h),5.03(dd,j＝16.8,1.2hz,1h),5.20(dd,j＝10.4,1.2hz,1h),6.00-6.09(m,1h),6.61(s,1h),7.29(t,j＝7.6hz,1h),7.37-7.46(m,7h), 7.84-7.86(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝52.0,103.3,117.2,125.6,127.6,128.52,128.56,128.59,128.7,130.6,133.4,133.8,145.1,150.9ppm；hrms(esi):calcdforc18h17n2[m+h]⁺:261.1386,found:261.1385.

3m(64％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝2.41(s,3h),4.76-4.79(m,2h),5.04(dd,j＝17.2,0.8hz,1h),5.22(dd,j＝10.0,1.2hz,1h),6.01-6.11(m,1h),6.60(s,1h),7.24-7.28(m,3h),7.30-7.42(m,4h),7.85(d,j＝7.2hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,52.0,103.2,117.1,125.6,127.56,127.64,128.5,128.6,129.3,133.5,133.9,138.6,145.2,150.8ppm；hrms(esi):calcdforc19h19n2[m+h]⁺:275.1543,found:275.1550.

3n(81％產(chǎn)率).mp47-49℃；¹hnmr(400mhz,cdcl3)δ＝4.76(dd,j＝3.2,1.6hz,2h),5.02(dd,j＝17.2,0.8hz,1h),5.22(dd,j＝10.4,1.2hz,1h),6.00-6.10(m,1h),6.60(s,1h),7.13-7.17(m,2h),7.29-7.33(m,1h),7.39-7.46(m,4h),7.84(d,j＝7.6hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝52.0,103.5,115.6,115.8,117.3,125.6,126.7,127.7,128.6,130.5,130.6,133.3,133.8,144.1,150.9,161.6,164.1ppm；hrms(esi):calcdforc18h16fn2[m+h]⁺:279.1292,found:279.1296.

3o(83％產(chǎn)率).mp93-95℃；¹hnmr(400mhz,cdcl3)δ＝2.42(t,j＝2.4hz,1h),4.90(d,j＝2.4hz,2h),6.62(s,1h),7.28-7.32(m,1h),7.38-7.50(m,5h),7.55-7.58(m,2h),7.84-7.86(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝39.7,73.6,78.4,103.7,125.7,127.8,128.5,128.7,128.8,130.1,133.1,145.0,151.4ppm；hrms(esi):calcdforc18h15n2[m+h]⁺:259.1230,found:259.1223.

3p(88％產(chǎn)率).mp81-83℃；¹hnmr(400mhz,cdcl3)δ＝2.42-2.44(m,4h),4.91(d,j＝2.4hz,2h),6.61(s,1h),7.29-7.33(m,3h),7.38-7.42(m,2h),7.46(d,j＝8.0hz,2h),7.84-7.86(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,39.7,73.5,78.5,103.5,125.7,127.1,127.8,128.5,128.6,129.5,133.1,138.9,145.1,151.4ppm；hrms(esi):calcdforc19h17n2[m+h]⁺:273.1386,found:273.1390.

3q(59％產(chǎn)率).mp80-85℃；¹hnmr(400mhz,cdcl3)δ＝2.43(t,j＝2.4hz,1h),4.89(d,j＝2.4hz,2h),6.61(s,1h),7.16-7.21(m,2h),7.30-7.33(m,1h),7.39-7.42(m,2h),7.54-7.57(m,2h),7.83-7.85(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝39.8,73.7,78.2,103.8,115.9,116.1,125.7,126.18,126.22,127.9,128.6,130.6,130.7,133.0,144.0,151.5,161.8,164.3ppm；hrms(esi):calcdforc18h14fn2[m+h]⁺:277.1136,found:277.1141.

3r(92％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝2.53(s,3h),3.94(s,3h),6.47(s,1h),7.22-7.26(m,3h),7.41-7.50(m,5h),7.61-7.63(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,37.5,106.2,125.8,127.5,128.4,128.66,128.73,129.1,130.7,133.2,135.9,144.0,150.7ppm.

3s(80％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝2.42(s,3h),2.52(s,3h),3.93(s,3h),6.44(s,1h),7.22-7.24(m,3h),7.28(d,j＝8.0hz,2h),7.37(d,j＝7.6hz,2h),7.61-7.63(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.18,21.25,37.4,106.0,125.8,127.5,127.8,128.6,129.1,129.4,130.7,133.3,135.9,138.4,144.1,150.6ppm；hrms(esi):calcdforc18h19n2[m+h]⁺:263.1543,found:263.1541.

3t(86％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝2.52(s,3h),3.92(s,3h),6.44(s,1h),7.15-7.19(m,2h),7.22-7.25(m,3h),7.43-7.47(m,2h),7.59-7.62(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,37.4,106.3,115.7,115.9,125.8,126.78,126.81,127.6,129.1,130.5,130.6,130.7,133.1,135.9,143.0,150.8,161.5,164.0ppm；hrms(esi):calcdforc17h16fn2[m+h]⁺:267.1292,found:267.1290.

3u(95％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝2.40(s,3h),3.93(s,3h),6.60(s,1h),7.13(d,j＝7.2hz,1h),7.24-7.32(m,1h),7.40-7.47(m,5h),7.61(d,j＝7.6hz,1h),7.68(s,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.4,37.5,103.2,122.6,126.1,128.4,128.5,128.66,128.69,130.6,133.2,138.2,145.0,150.6ppm；hrms(esi):calcdforc17h17n2[m+h]⁺:249.1386,found:249.1391.

3v(82％產(chǎn)率).mp69-71℃；¹hnmr(400mhz,cdcl3)δ＝2.40(s,3h),2.42(s,3h),3.91(s,3h),6.57(s,1h),7.12(d,j＝7.6hz,1h),7.25-7.31(m,3h),7.35(d,j＝8.0hz,2h),7.60(d,j＝7.6hz,1h),7.68(s,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,21.4,37.5,103.1,122.7,126.1,127.8,128.3,128.5,128.6,129.4,133.3,138.2,138.5,145.0,150.5ppm；hrms(esi):calcdforc18h19n2[m+h]⁺:263.1543,found:263.1542.

3w(88％產(chǎn)率).mp69-71℃；¹hnmr(400mhz,cdcl3)δ＝2.40(s,3h),3.90(s,3h),6.57(s,1h),7.12-7.19(m,3h),7.25-7.32(m,1h),7.41-7.45(m,2h),7.59(d,j＝7.6hz,1h),7.67(s,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.4,37.4,103.3,115.7,115.9,122.6,126.1,126.70,126.73,128.45,128.51,130.5,130.6,133.1,138.2,143.9,150.6,161.5,164.0ppm；hrms(esi):calcdforc17h16fn2[m+h]⁺:267.1292,found:267.1297.

3x(83％產(chǎn)率).mp129-132℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),3.92(s,3h),6.58(s,1h),7.21(d,j＝8.0hz,2h),7.41-7.47(m,5h),7.72(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,37.5,103.0,125.4,128.5,128.7,129.3,130.6,130.7,137.3,144.9,150.6ppm.

3y(80％產(chǎn)率).mp90-94℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),2.41(s,3h),3.91(s,3h),6.55(s,1h),7.21(d,j＝8.0hz,2h),7.27(d,j＝8.0hz,2h),7.50(d,j＝8.0hz,2h),7.71(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,37.5,102.8,125.4,127.8,128.6,129.26,129.32,130.7,137.2,138.4,145.0,150.5ppm；hrms(esi):calcdforc18h19n2[m+h]⁺:263.1543,found:263.1542.

3z(90％產(chǎn)率).mp68-71℃；¹hnmr(400mhz,cdcl3)δ＝1.25(s,3h),3.86(s,3h),3.90(s,3h),6.53(s,1h),6.98-7.00(m,2h),7.21(d,j＝7.6hz,2h),7.37-7.39(m,2h),7.72(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,37.3,55.3,102.7,114.1,123.0,125.4,129.3,130.0,130.5,137.3,144.8,150.4,159.8ppm；hrms(esi):calcdforc18h19n2o[m+h]⁺:279.1492,found:279.1496.

3aa(96％產(chǎn)率).mp111-114℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),3.89(s,3h),6.54(s,1h),7.13-7.25(m,4h),7.40-7.44(m,2h),7.71(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,37.4,103.1,115.6,115.9,125.4,126.8,129.3,130.5,130.6,137.4,143.9,150.6,161.6,164.0ppm；hrms(esi):calcdforc17h16fn2[m+h]⁺:267.1292,found:267.1290.

3ab(80％產(chǎn)率).mp61-63℃；¹hnmr(400mhz,cdcl3)δ＝1.44(t,j＝7.2hz,3h),2.37(s,3h),4.20(q,j＝7.2hz,2h),6.54(s,1h),7.21(d,j＝8.0hz,2h),7.41-7.48(m,5h),7.73(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝16.0,21.2,44.6,103.1,125.5,128.4,128.7,128.8,129.3,130.8,131.0,137.2,144.4,150.6ppm；hrms(esi):calcdforc18h19n2[m+h]⁺:263.1543,found:263.1543.

3ac(71％產(chǎn)率).mp89-91℃；¹hnmr(400mhz,cdcl3)δ＝1.44(t,j＝7.2hz,3h),2.37(s,3h),2.41(s,3h),4.19(q,j＝7.2hz,2h),6.51(s,1h),7.20-7.34(m,6h),7.72(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝16.0,21.25,21.27,44.5,103.0,125.4,128.0,128.7,129.2,129.3,130.8,137.1,138.4,144.4,150.5ppm；hrms(esi):calcdforc19h21n2[m+h]⁺:277.1699,found:277.1704.

3ad(87％產(chǎn)率).mp110-112℃；¹hnmr(400mhz,cdcl3)δ＝1.43(t,j＝7.2hz,3h),2.37(s,3h),3.85(s,3h),4.17(q,j＝7.2hz,2h),6.49(s,1h),6.97-7.00(m,2h),7.20(d,j＝7.6hz,2h),7.35-7.37(m,2h),7.72(d,j＝8.4hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝16.0,21.2,44.4,55.3,102.9,114.1,123.3,125.4,129.2,130.1,130.9,137.1,144.1,150.5,159.7ppm；hrms(esi):calcdforc19h21n2o[m+h]⁺:293.1648,found:293.1647.

3ae(73％產(chǎn)率).mp71-74℃；¹hnmr(400mhz,cdcl3)δ＝1.43(t,j＝7.2hz,3h),2.37(s,3h),4.16(q,j＝7.2hz,2h),6.51(s,1h),7.14-7.25(m,4h),7.39-7.42(m,2h),7.72(d,j＝7.6hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝16.0,21.2,44.5,103.2,115.6,115.9,125.4,127.0,129.3,130.56,130.61,130.64,137.3,143.3,150.6,161.5,164.0ppm；hrms(esi):calcdforc18h18fn2[m+h]⁺:281.1449,found:281.1450.

3af(69％產(chǎn)率).mp54-57℃；¹hnmr(400mhz,cdcl3)δ＝2.38(s,3h),4.79(d,j＝2.4hz,2h),5.04(d,j＝17.2hz,1h),5.22(d,j＝10.4hz,1h),6.06(ddd,j＝22.4,10.4,5.2hz,1h),6.60(s,1h),7.22(d,j＝8.0hz,2h),7.40-7.47(m,5h),7.74(d,j＝7.6hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,52.0,103.2,117.1,125.5,128.6,128.7,129.2,130.6,133.9,137.4,145.1,151.0ppm；hrms(esi):calcdforc19h19n2[m+h]⁺:275.1543,found:275.1549.

3ag(47％產(chǎn)率).mp77-79℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),2.41(s,3h),4.78(dt,j＝4.8,1.6hz,2h),5.01-5.07(m,1h),5.19-5.22(m,1h),6.01-6.10(m,1h),6.56(s,1h),7.21(d,j＝8.0hz,2h),7.24-7.26(m,2h),7.34-7.36(m,2h),7.74(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.26,21.29,52.0,103.0,117.1,125.6,127.7,128.6,129.25,129.32,130.6,134.0,137.3,138.6,145.1,150.9ppm；hrms(esi):calcdforc20h21n2[m+h]⁺:289.1699,found:289.1705.

3ah(87％產(chǎn)率).mp53-56℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),4.75(d,j＝4.8hz,2h),5.01(d,j＝17.2hz,1h),5.21(d,j＝10.4hz,1h),6.04(ddd,j＝22.4,10.4,4.8hz,1h),6.57(s,1h),7.14(t,j＝8.4hz,2h),7.21(d,j＝8.0hz,2h),7.43(dd,j＝8.4,5.2hz,2h),7.73(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,52.0,103.3,115.6,115.8,117.2,125.5,129.3,130.4,130.5,130.6,133.8,137.4,144.0,151.0ppm；hrms(esi):calcdforc19h18fn2[m+h]⁺:293.1449,found:293.1452.

3ai(62％產(chǎn)率).mp86-88℃；¹hnmr(400mhz,cdcl3)δ＝2.38(s,3h),5.39(s,2h),6.63(s,1h),7.09(d,j＝6.8hz,2h),7.21-7.29(m,5h),7.33-7.39(m,5h),7.76(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,53.2,103.5,125.6,126.7,127.3,128.6,128.8,129.3,130.6,137.4,137.7,145.3,151.0ppm；hrms(esi):calcdforc23h21n2[m+h]⁺:325.1699,found:325.1705.

3aj(60％產(chǎn)率).mp113-115℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,6h),5.37(s,2h),6.60(s,1h),7.10(d,j＝7.2hz,2h),7.17-7.29(m,9h),7.76(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,53.1,103.3,125.5,126.6,127.3,127.7,128.5,128.7,129.2,129.3,130.7,137.3,137.9,138.5,145.4,151.0ppm；hrms(esi):calcdforc24h23n2[m+h]⁺:339.1856,found:339.1862.

3ak(70％產(chǎn)率).mp84-89℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),5.35(s,2h),6.60(s,1h),7.04-7.09(m,4h),7.21-7.31(m,7h),7.76(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,53.2,53.4,103.7,115.6,115.8,125.5,126.6,126.7,127.4,128.6,129.3,130.5,130.6,130.7,137.5,137.6,144.3,151.0,161.6,164.1ppm；hrms(esi):calcdforc23h20fn2[m+h]⁺:343.1605,found:343.1611.

3al(78％產(chǎn)率).mp93-95℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),2.42(t,j＝2.4hz,1h),4.91(d,j＝2.4hz,2h),6.60(s,1h),7.21(d,j＝8.0hz,2h),7.42-7.50(m,3h),7.56-7.58(m,2h),7.74(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,39.8,73.5,78.5,103.5,125.7,128.75,128.8,128.83,129.3,130.2,130.3,137.6,145.0,151.6ppm；hrms(esi):calcdforc19h17n2[m+h]⁺:273.1386,found:273.1392.

3am(60％產(chǎn)率).mp117-118℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),2.42-2.43(m,4h),4.89(d,j＝2.4hz,2h),6.57(s,1h),7.21(d,j＝8.0hz,2h),7.29(d,j＝7.6hz,2h),7.46(d,j＝8.0hz,2h),7.74(d,j＝8.4hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.25,21.29,39.6,73.4,78.5,103.3,125.6,127.2,128.6,129.2,129.5,130.4,137.5,138.8,145.0,151.5ppm；hrms(esi):calcdforc20h19n2[m+h]⁺:287.1543,found:287.1548.

3an(62％產(chǎn)率).mp95-97℃；¹hnmr(400mhz,cdcl3)δ＝2.37(s,3h),2.43(t,j＝2.4hz,1h),4.88(d,j＝2.4hz,2h),6.58(s,1h),7.16-7.22(m,4h),7.53-7,57(m,2h),7.73(d,j＝8.0hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,39.7,73.7,78.3,103.7,115.8,116.1,125.6,126.2,126.3,129.3,129.37,129.41,129.6,130.2,130.6,130.7,137.7,143.9,151.6,161.7,164.2ppm；hrms(esi):calcdforc19h16fn2[m+h]⁺:291.1292,found:291.1298.

3ao(89％產(chǎn)率).mp91-94℃；¹hnmr(400mhz,cdcl3)δ＝3.83(s,3h),3.91(s,3h),6.53(s,1h),6.94(d,j＝8.4hz,2h),7.41-7.46(m,5h),7.76(d,j＝8.4hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.4,55.2,102.7,114.0,126.3,126.7,128.4,128.7,130.7,145.0,150.3,159.3ppm.

3ap(91％產(chǎn)率).mp49-52℃；¹hnmr(400mhz,cdcl3)δ＝2.42(s,3h),3.83(s,3h),3.92(s,3h),6.51(s,1h),6.94(d,j＝8.8hz,2h),7.27(d,j＝8.0hz,2h),7.35(d,j＝8.0hz,2h),7.76(d,j＝8.8hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.2,37.4,55.2,102.5,114.0,126.8,127.6,128.6,129.3,138.6,145.2,150.1,159.4ppm.

3aq(65％產(chǎn)率).mp88-91℃；¹hnmr(400mhz,cdcl3)δ＝1.44(t,j＝7.2hz,3h),3.83(s,3h),4.18(q,j＝7.2hz,2h),6.49(s,1h),6.94(d,j＝8.4hz,2h),7.41-7.48(m,5h),7.77(d,j＝8.4hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝16.0,44.5,55.3,102.8,114.0,126.4,126.8,128.5,128.7,128.8,131.0,144.4,150.4,159.2ppm；hrms(esi):calcdforc18h19n2o[m+h]⁺:279.1492,found:279.1495.

3ar61％產(chǎn)率).mp75-77℃；¹hnmr(400mhz,cdcl3)δ＝1.43(t,j＝7.2hz,3h),2.41(s,3h),3.83(s,3h),4.18(q,j＝7.2hz,2h),6.47(s,1h),6.94(d,j＝8.8hz,2h),7.25-7.34(m,4h),7.76(d,j＝8.8hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝15.9,21.2,44.4,55.2,102.7,113.9,126.5,126.8,128.1,128.7,129.3,138.4,144.4,150.3,159.2ppm；hrms(esi):calcdforc19h21n2o[m+h]⁺:293.1648,found:293.1646.

3as(51％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝3.84(s,3h),4.77(dd,j＝3.6,1.6hz,2h),5.04(dd,j＝16.8,1.2hz,1h),5.21(dd,j＝10.4,1.2hz,1h),6.01-6.10(m,1h),6.55(s,1h),6.94(d,j＝8.8hz,2h),7.42-7.46(m,5h),7.76-7.79(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝52.0,55.3,102.9,114.0,117.2,126.3,126.9,128.56,128.62,128.7,130.8,134.0,145.1,150.8,159.3ppm；hrms(esi):calcdforc19h19n2o[m+h]⁺:291.1492,found:291.1495.

3at(45％產(chǎn)率).mp70-73℃；¹hnmr(400mhz,cdcl3)δ＝2.41(s,3h),3.84(s,3h),4.76(d,j＝4.8hz,2h),5.04(d,j＝17.2hz,1h),5.21(d,j＝10.4hz,1h),6.06(ddd,j＝22.0,10.4,4.8hz,1h),6.52(s,1h),6.94(d,j＝8.8hz,2h),7.25-7.27(m,2h),7.35(d,j＝8.0hz,2h),7.77(d,j＝8.4hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,51.9,55.3,102.7,113.9,117.1,126.3,126.9,127.8,128.6,129.3,134.0,138.5,145.1,150.7,159.2ppm；hrms(esi):calcdforc20h21n2o[m+h]⁺:305.1648,found:305.1653.

3au(63％產(chǎn)率).mp87-89℃；¹hnmr(400mhz,cdcl3)δ＝3.91(s,3h),3.92(s,3h),3.98(s,3h),6.55(s,1h),6.91(d,j＝8.4hz,1h),7.32-7,35(m,1h),7.42-7,47(m,6h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.5,55.88,55.91,102.9,108.6,111.2,118.1,126.6,128.5,128.67,128.69,130.7,145.1,148.7,149.1,150.4ppm；hrms(esi):calcdforc18h19n2o2[m+h]⁺:295.1441,found:295.1448.

3av(90％產(chǎn)率).mp56-59℃；¹hnmr(400mhz,cdcl3)δ＝3.96(s,3h),6.83(s,1h),7.16-7.20(m,1h),7.34-7.38(m,1h),7.42-7.51(m,5h),7.65-7.67(m,1h),7.75-7.77(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.6,107.1,121.9,127.4,128.5,128.7,128.8,129.0,130.5,131.0,133.5,134.4,144.0,149.4ppm；hrms(esi):calcdforc16h14brn2[m+h]⁺:313.0335,found:313.0338.

3aw(70％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝2.42(s,3h),3.95(s,3h),6.80(s,1h),7.16-7.20(m,1h),7.25-7.30(m,2h),7.34-7.40(m,3h),7.65(d,j＝8.0hz,1h),7.75(dd,j＝8.0,1.6hz,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,37.6,106.9,121.9,127.4,127.6,128.7,128.9,129.4,131.0,133.5,134.5,138.5,144.0,149.3ppm；hrms(esi):calcdforc17h16brn2[m+h]⁺:327.0491,found:327.0498.

3ax(86％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝3.93(s,3h),6.80(s,1h),7.16-7.21(m,3h),7.35-7.38(m,1h),7.45-7.48(m,2h),7.66(d,j＝8.0hz,1h),7.74-7.76(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.5,107.2,115.7,115.9,121.9,126.6,127.4,129.0,130.6,130.7,130.9,133.5,134.3,142.9,149.4,161.5ppm；hrms(esi):calcdforc16h13brfn2[m+h]⁺:331.0241,found:331.0248.

3ay(87％產(chǎn)率).mp66-69℃；¹hnmr(400mhz,cdcl3)δ＝3.95(s,3h),6.85(s,1h),7.23-7.33(m,2h),7.41-7.49(m,6h),7.85-7.87(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.6,107.2,126.8,128.5,128.6,128.8,130.3,130.4,132.1,132.3,144.2,148.0ppm；hrms(esi):calcdforc16h14cln2[m+h]⁺:269.0840,found:269.0841.

3az(69％產(chǎn)率).mp58-60℃；¹hnmr(400mhz,cdcl3)δ＝2.42(s,3h),3.95(s,3h),6.82(s,1h),7.23-7.33(m,4h),7.38(d,j＝8.4hz,2h),7.45(d,j＝8.0hz,1h),7.85(dd,j＝7.6,1.6hz,1h)ppm；¹³c nmr(100mhz,cdcl3)δ＝21.3,37.6,107.0,126.8,127.6,128.6,128.7,129.4,130.2,130.4,132.1,132.4,138.5,144.2,147.9ppm；hrms(esi):calcdforc17h16cln2[m+h]⁺:283.0997,found:283.1004.

3ba(63％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝3.86(s,3h),3.93(s,3h),6.79(s,1h),7.00(d,j＝8.8hz,2h),7.22-7.29(m,1h),7.31-7.33(m,1h),7.40-7.45(m,3h),7.84-7.86(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.5,55.4,106.9,114.1,122.9,126.8,128.6,130.1,130.3,130.4,132.1,132.4,144.0,147.9,159.8ppm；hrms(esi):calcdforc17h16cln2o[m+h]⁺:299.0946,found:299.0950.

3bb(94％產(chǎn)率).¹hnmr(400mhz,cdcl3)δ＝3.92(s,3h),6.82(s,1h),7.15-7.19(m,2h),7.23-7.34(m,2h),7.44-7.48(m,3h),7.84-7.86(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.5,107.3,115.7,115.9,126.60,126.63,126.9,128.7,130.3,130.4,130.6,130.7,132.1,132.2,143.1,148.0,161.6,164.0ppm；hrms(esi):calcdforc16h13clfn2[m+h]⁺:287.0746,found:287.0744.

3bc(58％產(chǎn)率).mp72-75℃；¹hnmr(400mhz,cdcl3)δ＝3.92(s,3h),6.59(s,1h),7.25-7.28(m,1h),7.30-7.34(m,3h),7.43-7.48(m,5h),7.68-7.71(m,1h),7.83-7.84(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.6,103.3,123.5,125.5,127.5,128.66,128.70,128.73,129.9,130.4,134.6,135.2,145.2,149.1ppm；hrms(esi):calcdforc16h14cln2[m+h]⁺:269.0840,found:269.0840.

3bd(65％產(chǎn)率).mp72-74℃；¹hnmr(400mhz,cdcl3)δ＝2.42(s,3h),3.92(s,3h),6.57(s,1h),7.25-7.36(m,6h),7.69(d,j＝7.6hz,1h),7.83(s,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,37.6,103.1,123.5,125.5,127.4,127.5,128.6,129.4,129.8,134.5,135.3,138.7,145.3,149.0ppm；hrms(esi):calcdforc17h16cln2[m+h]⁺:283.0997,found:283.1004.

3be(87％產(chǎn)率).mp60-63℃；¹hnmr(400mhz,cdcl3)δ＝3.89(s,3h),6.56(s,1h),7.15-7.19(m,2h),7.26-7.34(m,2h),7.40-7.44(m,2h),7.67-7.70(m,1h),7.82-7.83(m,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.5,103.4,115.7,116.0,123.5,125.5,126.46,126.49,127.6,129.9,130.5,130.6,134.6,135.1,144.2,149.1,161.6,164.1ppm；hrms(esi):calcdforc16h13cln2f[m+h]⁺:287.0746,found:287.0748.

3bf(88％產(chǎn)率).mp117-120℃；¹hnmr(400mhz,cdcl3)δ＝3.91(s,3h),6.57(s,1h),7.35-7.38(m,2h),7.42-7.48(m,5h),7.75-7.77(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.6,103.2,126.7,128.6,128.69,128.72,128.8,130.4,131.9,133.2,145.2,149.3ppm.

3bg(87％產(chǎn)率).mp93-96℃；¹hnmr(400mhz,cdcl3)δ＝2.42(s,3h),3.91(s,3h),6.55(s,1h),7.25-7.29(m,2h),7.33-7.38(m,4h),7.74-7.76(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,37.6,103.0,126.7,127.5,128.6,128.7,129.4,132.0,133.2,138.6,145.3,149.2ppm；hrms(esi):calcdforc17h16cln2[m+h]⁺:283.0997,found:283.1000.

3bh(92％產(chǎn)率).mp97-100℃；¹hnmr(400mhz,cdcl3)δ＝3.89(s,3h),6.54(s,1h),7.15-7.19(m,2h),7.36(d,j＝7.2hz,2h),7.40-7.44(m,2h),7.75(d,j＝8.4hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.5,103.2,115.7,116.0,126.51,126.54,126.7,128.8,130.5,130.6,131.8,133.3,144.2,149.4,161.6,164.1ppm；hrms(esi):calcdforc16h13cln2f[m+h]⁺:287.0746,found:287.0745.

3bi(47％產(chǎn)率).mp114-116℃；¹hnmr(400mhz,cdcl3)δ＝3.96(s,3h),6.70(s,1h),7.44-7.52(m,5h),7.98(d,j＝8.4hz,2h),8.26(d,j＝8.8hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.8,104.2,124.1,125.8,128.7,128.8,128.9,130.0,139.7,145.7,147.0,148.1ppm；hrms(esi):calcdforc16h14n3o2[m+h]⁺:280.1081,found:280.1086.

3bj(36％產(chǎn)率).mp106-109℃；¹hnmr(400mhz,cdcl3)δ＝4.81(dd,j＝3.6,1.6hz,2h),5.07(dd,j＝17.2,0.8hz,1h),5.26(dd,j＝10.4,0.8hz,1h),6.06(ddd,j＝22.4,10.4,5.2hz,1h),6.72(s,1h),7.44-7.52(m,5h),8.00(d,j＝8.8hz,2h),8.26(d,j＝8.8hz,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝52.4,104.3,117.7,124.1,126.0,128.76,128.79,129.0,130.0,133.4,139.8,145.8,147.0,148.6ppm；hrms(esi):calcdforc18h16n3o2[m+h]⁺:306.1237,found:306.1243.

3bk(31％產(chǎn)率).mp119-121℃；¹hnmr(400mhz,cdcl3)δ＝2.48(t,j＝2.4hz,1h),4.95(d,j＝2.4hz,2h),6.73(s,1h),7.47-7.59(m,5h),8.01-8.03(m,2h),8.26-8.28(m,2h)ppm；¹³cnmr(100mhz,cdcl3)δ＝40.1,74.0,77.9,104.5,124.1,126.1,128.8,129.0,129.3,129.5,139.4,145.7,149.1ppm；hrms(esi):calcdforc18h14n3o2[m+h]⁺:304.1081,found:304.1096.

3bl(51％產(chǎn)率).mp82-85℃；¹hnmr(400mhz,cdcl3)δ＝3.91(s,3h),6.47(dd,j＝3.2,1.6hz,1h),6.53(s,1h),6.67(d,j＝3.2hz,1h),7.40-7.49(m,6h)ppm；¹³cnmr(100mhz,cdcl3)δ＝37.6,103.0,105.5,111.2,128.68,128.72,130.3,141.7,142.9,144.8,148.8ppm；hrms(esi):calcdforc14h13n2o[m+h]⁺:225.1022,found:225.1029.

3bm(51％產(chǎn)率).mp102-104℃；¹hnmr(400mhz,cdcl3)δ＝2.42(s,3h),3.90(s,3h),6.46(dd,j＝3.2,1.6hz,1h),6.50(s,1h),6.66(d,j＝2.8hz,1h),7.26-7.30(m,2h),7.34(d,j＝8.0hz,2h),7.45(d,j＝1.2hz,1h)ppm；¹³cnmr(100mhz,cdcl3)δ＝21.3,37.5,102.8,105.4,111.2,127.4,128.6,129.4,138.7,141.7,142.9,144.8,148.9ppm；hrms(esi):calcdforc15h15n2o[m+h]⁺:239.1179,found:239.1187.

以上所述僅為本發(fā)明的優(yōu)選實施例而已，并不用于限制本發(fā)明，盡管參照前述實施例對本發(fā)明進行了詳細的說明，對于本領(lǐng)域的技術(shù)人員來說，其依然可以對前述各實施例所記載的技術(shù)方案進行修改，或者對其中部分技術(shù)特征進行等同替換。凡在本發(fā)明的精神和原則之內(nèi)，所作的任何修改、等同替換、改進等，均應(yīng)包含在本發(fā)明的保護范圍之內(nèi)。