本发明属于有机合成技术领域，具体涉及一种吡唑啉酮并苯二氮杂卓类化合物的合成方法。
背景技术：
吡唑啉酮并苯二氮杂卓是一类重要的含氮稠杂环类化合物，该类化合物不仅在自然界中广泛存在，而且许多都具有抗菌、抗癌、抗病毒、抗焦虑和神经保护等独特的生物及药物活性。
目前，尽管现有文献中已经报道了合成吡唑啉酮并苯二氮杂卓类化合物的可靠方法，但这些方法仍然存在原料不易得到、合成步骤多、操作繁琐和原子经济性低等问题。
因此，研究并开发从简单易得的原料出发，经过简洁的操作来合成吡唑啉酮并苯二氮杂卓类化合物的新方法，具有十分重要的理论意义和实用前景。
技术实现要素：
本发明解决的技术问题是提供了一种吡唑啉酮并苯二氮杂卓类化合物的合成方法，该合成方法通过1-芳基吡唑烷酮类化合物和炔丙醇类化合物之间的[4+3]环化反应，高效地、区域选择性地合成了吡唑啉酮并苯二氮杂卓类化合物，该方法具有原料简单易得、操作简便、条件温和、选择性好及底物适用范围广等优点，具有潜在的工业应用前景。
本发明为解决上述技术问题采用如下技术方案，一种吡唑啉酮并苯二氮杂卓类化合物的合成方法，包括如下操作：以1-芳基吡唑烷酮类化合物1和炔丙醇类化合物2为原料，在铑或钌催化剂和添加剂存在下，有机溶剂中反应得到吡唑啉酮并苯二氮杂卓类化合物3，反应方程式为：
其中：r1为氢、卤素、三氟甲基、氰基、硝基、c1-4烷基或c1-4烷氧基；r2为氢或c1-4烷基；r3为氢或c1-4烷基；r4为c1-6链状烷基、c3-6环烷基、噻吩基、吡啶基、苯基或取代苯基，取代苯基苯环上的取代基为卤素、三氟甲基、硝基、c1-4烷基或c1-4烷氧基；r5和r6各自独立为c1-4烷基、c3-6环烷基或共同组成c4-6环烷基。
进一步地，在上述技术方案中，所述反应溶剂选自1,2-二氯乙烷(dce)、甲醇(ch3oh)、甲苯(toluene)、乙腈(ch3cn)、二氯甲烷(dcm)或丙酮(acetone)。
在实验过程中发现上述反应溶剂除起到溶解原料的作用外，对反应收率影响较大，其中甲苯、二氯乙烷、二氯甲烷和丙酮效果良好，甲苯反应结果最佳。
进一步地，在上述技术方案中，所述铑催化剂为二氯(五甲基环戊二烯基)合铑(iii)二聚体{简称[rhcp*cl2]2}、五甲基环戊二烯基醋酸铑(iii){简称rhcp*(oac)2}或[rhcl(cod)]2；所述钌催化剂为[ru(p-cymene)cl2]2。采用其它金属催化剂，例如cocp*(co)i2、mnbr(co)5或[ircp*cl2]2等催化剂时，反应几乎不发生(收率低于5％)。
进一步地，在上述技术方案中，所述添加剂为醋酸锌、醋酸、醋酸钠、醋酸铯、醋酸钾中的一种或几种混合。优选情况下，添加剂为醋酸锌与醋酸、醋酸钠、醋酸铯、醋酸钾其中之一组成。为进一步降低成本和提高收率，最优选情况下，添加剂为醋酸锌和醋酸钠组合，两者摩尔比例最佳为1:1。
进一步地，在上述技术方案中，所述1-芳基吡唑啉酮类化合物1、炔丙醇类化合物2、添加剂和催化剂的投料摩尔比为1:1-1.5:0.5-1.0:0.02-0.03。
进一步地，在上述技术方案中，所述反应温度为80-110℃。
进一步地，在上述技术方案中，所得产物3可通过不同还原剂的作用得到不同的产物。例如采用钯碳催化氢化，将双键还原得到化合物4；采用四氢铝锂还原，将吡唑啉酮的酰胺键打开得到化合物5。
发明有益效果：
本发明与现有技术相比具有以下优点：1)合成过程简单、高效，通过1-芳基吡唑烷酮类化合物和炔丙醇类化合物之间的一锅串联反应，即可高选择性地合成出吡唑啉酮并苯二氮杂卓类化合物；2)原料价廉易得，反应条件温和，操作简便，底物的适用范围广；3)反应原子经济性高，符合绿色化学的要求。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1
向15ml反应瓶中依次加入1a、2a、溶剂、催化剂和添加剂，盖上塞子密封，将其置于油浴中升温搅拌反应。待反应结束后，冷却至室温，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得白色固体产物3a。
通过改变反应的催化剂、添加剂、溶剂、反应物之间的当量比和反应温度等反应条件，得到一系列的结果，见表1。
表1不同反应条件下3a的合成a
实施例2
向15ml反应瓶中依次加入1a(48.7mg,0.3mmol)、2a(48.1mg,0.3mmol)、甲苯(2ml)、二氯(五甲基环戊二烯基)合铑(iii)二聚体([rhcp*cl2]2,4.7mg,0.0075mmol)、醋酸锌(27.5mg,0.15mmol)和醋酸钠(12.3mg,0.15mmol)，盖上塞子密封，将其置于100℃油浴中搅拌反应4h。待反应结束后，冷却至室温，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得白色固体产物3a(80.5mg,88％)。该化合物的表征数据为：1hnmr(400mhz,cdcl3)δ1.67(s,6h),2.77(t,j＝7.2hz,2h),4.10(t,j＝7.2hz,2h),5.99(s,1h),6.99-7.01(m,1h),7.03-7.07(m,1h),7.18-7.20(m,2h),7.25-7.26(m,2h),7.28-7.33(m,3h).13c{1h}nmr(100mhz,cdcl3)δ26.9,33.3,49.0,63.1,116.3,124.4,127.4,127.9,128.1,129.3,132.1,132.6,136.5,139.9,144.4,149.6,173.6.hrmscalcdforc20h21n2o:305.1648[m+h]+,found:305.1647.
实施例3
依照实施例2的方法和步骤a,b，通过改变反应物1和2，可以合成出各种吡唑啉酮并苯二氮杂卓类化合物3a-3z和3aa-3ee，具体结果如下：
a反应条件:1(0.3mmol),2(0.3mmol),[rhcp*cl2]2(0.0075mmol),zn(oac)2(0.15mmol),naoac(0.15mmol),toluene(2ml),100℃,4h；b分离收率。
---------------------------------------------------------------------
代表性产物表征数据如下：
5,5,9-trimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3b)
whitesolid(80.4mg,84％).1hnmr(400mhz,cdcl3)δ1.66(s,6h),2.20(s,3h),2.77(t,j＝7.6hz,2h),4.07(t,j＝7.6hz,2h),5.99(s,1h),6.80(s,1h),7.06(d,j＝8.0hz,1h),7.16(d,j＝8.0hz,1h),7.19-7.21(m,2h),7.30-7.33(m,3h).13c{1h}nmr(150mhz,cdcl3)δ20.8,26.9,33.3,49.0,62.7,116.2,127.3,128.1,128.5,129.2,132.4,132.5,134.0,136.7,139.8,144.3,147.2,173.2.hrmscalcdforc21h23n2o:319.1805[m+h]+,found:319.1804.
9-methoxy-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3c)
lightyellowsolid(70.2mg,70％).1hnmr(400mhz,cdcl3)δ1.65(s,6h),2.77(t,j＝7.2hz,2h),3.65(s,3h),4.06(t,j＝7.2hz,2h),6.02(s,1h),6.54(d,j＝2.4hz,1h),6.81(dd,j1＝9.2hz,j2＝2.4hz,1h),7.18-7.23(m,3h),7.30-7.33(m,3h).13c{1h}nmr(150mhz,cdcl3)δ26.8,33.4,49.1,55.4,62.6,113.1,117.2,117.3,127.5,128.2,129.2,134.0,136.7,140.1,143.1,143.9,156.2,172.9.hrmscalcdforc21h23n2o2:335.1754[m+h]+,found:335.1754.
9-fluoro-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3d)
whitesolid(79.3mg,82％).1hnmr(400mhz,cdcl3)δ1.67(s,6h),2.77(t,j＝7.2hz,2h),4.08(t,j＝7.6hz,2h),6.02(s,1h),6.71(dd,j1＝9.6hz,j2＝2.8hz,1h),6.95(td,j1＝8.4hz,j2＝2.8hz,1h),7.18-7.23(m,3h),7.32-7.35(m,3h).13c{1h}nmr(100mhz,cdcl3)δ26.8,33.2,49.4,63.1,114.3(d,2jc-f＝22.4hz),117.5(d,3jc-f＝8.7hz),118.4(d,2jc-f＝23.2hz),127.6,128.3,129.2,134.6(d,3jc-f＝7.3hz),135.6(d,4jc-f＝2.1hz),141.0,143.7,145.8(d,4jc-f＝2.9hz),159.4(d,1jc-f＝242.0hz),173.5.19fnmr(376mhz,cdcl3)δ-118.14–-118.08(m).hrmscalcdforc20h20fn2o:323.1554[m+h]+,found:323.1553.
9-chloro-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3e)
whitesolid(74.1mg,73％).1hnmr(400mhz,cdcl3)δ1.67(s,6h),2.75(t,j＝7.2hz,2h),4.07(t,j＝7.2hz,2h),6.00(s,1h),6.97(d,j＝2.0hz,1h),7.17-7.23(m,4h),7.32-7.36(m,3h).13c{1h}nmr(100mhz,cdcl3)δ26.8,33.1,49.2,63.3,117.5,127.6,127.7,128.4,129.2,129.8,131.7,134.3,135.3,141.2,143.8,148.2,173.6.hrmscalcdforc20h20cln2o:339.1259[m+h]+,found:339.1242.
9-bromo-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3f)
whitesolid(90.5mg,79％).1hnmr(400mhz,cdcl3)δ1.67(s,6h),2.75(t,j＝7.2hz,2h),4.07(t,j＝7.2hz,2h),6.00(s,1h),7.11-7.14(m,2h),7.17-7.19(m,2h),7.33-7.38(m,4h).13c{1h}nmr(100mhz,cdcl3)δ26.8,33.1,49.2,63.3,117.5,117.9,127.7,128.4,129.2,130.5,134.60,134.63,135.2,141.3,143.7,148.7,173.6.hrmscalcdforc20h20brn2o:383.0754[m+h]+,found:383.0751.
5,5-dimethyl-7-phenyl-9-(trifluoromethyl)-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3g)
whitesolid(91.5mg,82％).1hnmr(400mhz,cdcl3)δ1.69(s,6h),2.77(t,j＝7.2hz,2h),4.13(t,j＝7.2hz,2h),6.03(s,1h),7.15-7.17(m,2h),7.26(s,1h),7.33-7.36(m,4h),7.51(d,j＝8.4hz,1h).13c{1h}nmr(100mhz,cdcl3)δ26.9,33.0,49.3,63.8,116.4,123.9(q,1jc-f＝270.1hz),124.5(q,3jc-f＝3.6hz),126.5(q,2jc-f＝32.5hz),127.8,128.4,129.17,129,24(q,3jc-f＝3.6hz),132.9,135.1,141.6,143.8,152.5,174.1.19fnmr(376mhz,cdcl3)δ-62.22(s).hrmscalcdforc21h20f3n2o:373.1522[m+h]+,found:373.1523.
5,5-dimethyl-3-oxo-7-phenyl-2,3-dihydro-1h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepine-9-carbonitrile(3h)
lightyellowsolid(77.4mg,78％).1hnmr(400mhz,cdcl3)δ1.69(s,6h),2.75(t,j＝7.2hz,2h),4.13(t,j＝7.2hz,2h),6.00(s,1h),7.12-7.15(m,2h),7.29(d,j＝1.2hz,1h),7.31-7.36(m,4h),7.54(dd,j1＝8.4hz,j2＝1.6hz,1h).13c{1h}nmr(100mhz,cdcl3)δ26.9,32.9,49.3,64.2,107.9,116.8,118.6,127.9,128.6,129.2,131.1,133.3,134.2,136.2,142.2,143.7,153.4,174.4.hrmscalcdforc21h20n3o:330.1601[m+h]+,found:330.1596.
11-fluoro-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3i)
lightyelowsolid(62.8mg,65％).1hnmr(400mhz,cdcl3)δ1.62(s,6h),2.85(t,j＝7.2hz,2h),4.11(t,j＝7.2hz,2h),6.11(s,1h),6.77-6.79(m,1h),7.00-7.04(m,2h),7.19-7.21(m,2h),7.30-7.33(m,3h).13c{1h}nmr(100mhz,cdcl3)δ26.7,35.0(d,5jc-f＝7.2hz),51.6(d,4jc-f＝12.3hz),62.4,116.3(d,2jc-f＝24.5hz),125.5(d,3jc-f＝9.3hz),127.1(d,3jc-f＝2.9hz),127.6,128.2,129.0,136.1(d,2jc-f＝10.1hz),137.0(d,4jc-f＝2.9hz),137.2(d,4jc-f＝2.9hz),140.4,143.9,153.9(d,1jc-f＝243.4hz),174.0.19fnmr(376mhz,cdcl3)δ-119.91(dd,j1＝10.9hz,j2＝5.6hz).hrmscalcdforc20h20fn2o:323.1554[m+h]+,found:323.1551.
5,5,10-trimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3j)
whitesolid(87.0mg,91％).1hnmr(400mhz,cdcl3)δ1.66(s,6h),2.39(s,3h),2.78(t,j＝7.6hz,2h),4.09(t,j＝7.6hz,2h),5.94(s,1h),6.88(s,2h),7.05(s,1h),7.18-7.20(m,2h),7.29-7.33(m,3h).13c{1h}nmr(100mhz,cdcl3)δ21.7,26.9,33.3,48.9,63.0,117.1,125.3,127.3,128.1,129.3,129.9,131.9,136.5,137.9,139.1,144.5,149.4,173.5.hrmscalcdforc21h23n2o:319.1805[m+h]+,found:319.1804.
10-methoxy-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3k)
brownsyrup(75.1mg,75％).1hnmr(400mhz,cdcl3)δ1.66(s,6h),2.77(t,j＝7.2hz,2h),3.82(s,3h),4.06(t,j＝7.2hz,2h),5.86(s,1h),6.60(dd,j1＝8.4hz,j2＝2.0hz,1h),6.80(d,j＝2.4hz,1h),6.92(d,j＝8.8hz,1h),7.19-7.21(m,2h),7.28-7.32(m,3h).13c{1h}nmr(100mhz,cdcl3)δ26.8,33.4,49.1,55.4,62.6,113.1,117.2,117.3,127.5,128.2,129.2,134.0,136.7,140.1,143.1,143.9,156.2,172.9.hrmscalcdforc21h23n2o2:335.1754[m+h]+,found:335.1754.
10-bromo-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3l)
lightyellowsolid(99.7mg,87％).1hnmr(400mhz,cdcl3)δ1.67(s,6h),2.77(t,j＝7.6hz,2h),4.07(t,j＝7.6hz,2h),5.97(s,1h),6.86(d,j＝8.4hz,1h),7.16-7.19(m,3h),7.31-7.33(m,3h),7.38(s,1h).13c{1h}nmr(100mhz,cdcl3)δ26.8,33.1,49.2,63.3,117.5,127.6,127.7,128.4,129.2,129.8,131.7,134.3,135.3,141.2,143.8,148.2,173.6.hrmscalcdforc20h20brn2o:383.0754[m+h]+,found:383.0748.
10-fluoro-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3m)
whitesolid(34.8mg,36％).1hnmr(400mhz,cdcl3)δ1.67(s,6h),2.77(t,j＝7.6hz,2h),4.06(t,j＝7.6hz,2h),5.93(s,1h),6.77(td,j1＝8.0hz,j2＝2.4hz,1h),6.95-6.98(m,2h),7.16-7.18(m,2h),7.30-7.33(m,3h).13c{1h}nmr(100mhz,cdcl3)δ26.9,32.9,49.2,63.4,104.1(d,2jc-f＝23.8hz),111.3(d,2jc-f＝20.9hz),127.5,128.2,128.6(d,4jc-f＝2.9hz),129.2,133.6(d,3jc-f＝8.7hz),135.5,139.5,144.3,151.2(d,3jc-f＝6.5hz),161.7(d,1jc-f＝247.0hz),173.6.19fnmr(376mhz,cdcl3)δ-112.09–-112.02(m).hrmscalcdforc20h20fn2o:323.1554[m+h]+,found:323.1555.
8-fluoro-5,5-dimethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3m')
lightyellowsolid(32.8mg,34％).1hnmr(400mhz,cdcl3)δ1.65(s,6h),2.75(brs,2h),4.07(t,j＝7.6hz,2h),6.22(s,1h),6.84-6.89(m,1h),7.11(d,j＝8.0hz,1h),7.14-7.17(m,2h),7.27-7.33(m,4h).13c{1h}nmr(150mhz,cdcl3)δ26.8,33.1,49.0,61.7,112.4(d,4jc-f＝3.3hz),113.1(d,2jc-f＝21.9hz),120.8(d,2jc-f＝12.0hz),126.7,127.3,128.2,129.1(d,3jc-f＝9.9hz),133.2,141.8,143.2(d,4jc-f＝2.3hz),151.4(d,3jc-f＝5.4hz),161.0(d,1jc-f＝250.5hz),172.1.19fnmr(376mhz,cdcl3)δ-101.96(dd,j1＝9.8hz,j2＝5.6hz).hrmscalcdforc20h20fn2o:323.1554[m+h]+,found:323.1554.
2,2,5,5-tetramethyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3n)
whitesolid(80.7mg,81％).1hnmr(600mhz,cdcl3)δ1.32(s,6h),1.68(s,6h),4.03(s,2h),5.93(s,1h),6.97-7.00(m,2h),7.16-7.18(m,2h),7.20-7.23(m,1h),7.28-7.32(m,3h),7.34(d,j＝7.8hz,1h).13c{1h}nmr(100mhz,cdcl3)δ24.7,26.8,42.4,59.8,63.8,117.2,123.5,127.0,127.2,128.1,129.4,131.9,132.4,136.4,139.8,145.0,149.7,180.4.hrmscalcdforc22h25n2o:333.1961[m+h]+,found:333.1959.
5,5-dimethyl-7-(p-tolyl)-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one
(3o)
whitesolid(83mg,87％).1hnmr(600mhz,cdcl3)δ1.66(s,6h),2.36(s,3h),2.77(t,j＝7.2hz,2h),4.09(t,j＝7.2hz,2h),5.98(s,1h),7.01-7.06(m,2h),7.08(d,j＝8.4hz,2h),7.12(d,j＝7.8hz,2h),7.24-7.25(m,2h).13c{1h}nmr(150mhz,cdcl3)δ21.2,26.9,33.3,49.0,63.0,116.3,124.4,127.8,128.8,129.2,132.1,132.8,136.4,137.1,139.4,141.6,149.5,173.5.hrmscalcdforc21h23n2o:319.1805[m+h]+,found:319.1807.
7-(4-methoxyphenyl)-5,5-dimethyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3p)
whitesolid(83.9mg,84％).1hnmr(600mhz,cdcl3)δ1.66(s,6h),2.77(t,j＝7.2hz,2h),3.81(s,3h),4.09(t,j＝7.2hz,2h),5.98(s,1h),6.83-6.85(m,2h),7.03-7.07(m,2h),7.10-7.13(m,2h),7.25-7.26(m,2h).13c{1h}nmr(150mhz,cdcl3)δ26.9,33.3,49.0,55.3,62.8,113.5,116.3,124.4,127.8,130.4,132.1,132.9,136.1,136.9,139.0,149.5,159.1,173.3.hrmscalcdforc21h23n2o2:335.1754[m+h]+,found:335.1760.
7-(4-fluorophenyl)-5,5-dimethyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3q)
whitesolid(71.5mg,74％).1hnmr(400mhz,cdcl3)δ1.67(s,6h),2.77(t,j＝7.2hz,2h),4.10(t,j＝7.2hz,2h),5.97(s,1h),6.97-7.02(m,3h),7.04-7.08(m,1h),7.14-7.17(m,2h),7.25-7.27(m,2h).13c{1h}nmr(100mhz,cdcl3)δ26.9,33.2,49.0,63.0,115.0(d,2jc-f＝20.9hz),116.3,124.5,128.0,130.8(d,3jc-f＝8.0hz),132.0,132.4,135.5,139.9,140.4(d,4jc-f＝2.8hz),149.6,162.3(d,1jc-f＝244.8hz),173.5.19fnmr(376mhz,cdcl3)δ-115.13–-115.06(m).hrmscalcdforc20h20fn2o:323.1554[m+h]+,found:323.1557.
7-(4-chlorophenyl)-5,5-dimethyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3r)
whitesolid(84.2mg,83％).1hnmr(400mhz,cdcl3)δ1.66(s,6h),2.77(t,j＝7.2hz,2h),4.10(t,j＝7.6hz,2h),5.97(s,1h),6.97(d,j＝7.6hz,1h),7.05-7.09(m,1h),7.13(d,j＝8.0hz,2h),7.27-7.29(m,4h).13c{1h}nmr(100mhz,cdcl3)δ26.8,33.2,49.0,63.1,116.3,124.5,128.1,128.3,130.6,131.9,132.2,133.3,135.4,140.2,142.8,149.6,173.6.hrmscalcdforc20h20cln2o:339.1259[m+h]+,found:339.1258.
7-(4-bromophenyl)-5,5-dimethyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3s)
whitesolid(91.7mg,80％).1hnmr(400mhz,cdcl3)δ1.66(s,6h),2.77(t,j＝7.6hz,2h),4.10(t,j＝7.6hz,2h),5.96(s,1h),6.97(d,j＝7.6hz,1h),7.04-7.08(m,3h),7.26-7.30(m,2h),7.44(d,j＝8.0hz,2h).13c{1h}nmr(100mhz,cdcl3)δ26.8,33.2,49.0,63.1,116.3,121.5,124.5,128.1,130.9,131.3,131.9,132.1,135.4,140.2,143.3,149.6,173.6.hrmscalcdforc20h20brn2o:383.0754[m+h]+,found:383.0760.
5,5-dimethyl-7-(4-(trifluoromethyl)phenyl)-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3t)
whitesolid(90.4mg,81％).1hnmr(400mhz,cdcl3)δ1.68(s,6h),2.78(t,j＝7.2hz,2h),4.12(t,j＝7.2hz,2h),5.99(s,1h),6.93(d,j＝7.6hz,1h),7.05-7.09(m,1h),7.27-7.32(m,4h),7.57(d,j＝8.0hz,2h).13c{1h}nmr(100mhz,cdcl3)δ26.8,33.2,49.1,63.3,116.4,124.2(q,1jc-f＝270.8hz),124.6,125.1(q,3jc-f＝3.6hz),128.2,129.5(q,2jc-f＝31.8hz),129.6,131.8,131.9,135.3,141.1,148.0,149.7,173.8.19fnmr(376mhz,cdcl3)δ-62.40(s).hrmscalcdforc21h20f3n2o:373.1522[m+h]+,found:373.1527.
5,5-dimethyl-7-(4-nitrophenyl)-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3u)
lightyellowsolid(68.1mg,65％).1hnmr(400mhz,cdcl3)δ1.70(s,6h),2.79(t,j＝7.2hz,2h),4.12(t,j＝7.6hz,2h),6.03(s,1h),6.89-6.91(m,1h),7.07-7.11(m,1h),7.29-7.32(m,2h),7.34-7.31(m,2h),8.16-8.19(m,2h).13c{1h}nmr(100mhz,cdcl3)δ26.7,33.2,49.1,63.4,116.5,123.5,124.7,128.5,130.0,131.4,131.8,134.7,141.9,147.1,149.8,151.0,173.8.hrmscalcdforc20h20n3o3:350.1499[m+h]+,found:350.1497.
5,5-dimethyl-7-(o-tolyl)-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one
(3v)
whitesolid(85.9mg,90％).1hnmr(400mhz,cdcl3)δ1.69(s,6h),1.96(s,3h),2.76(brs,2h),4.11(t,j＝7.2hz,2h),5.74(s,1h),6.79(d,j＝8.0hz,1h),6.94-6.98(m,1h),7.13-7.16(m,2h),7.17-7.24(m,4h).13c{1h}nmr(100mhz,cdcl3)δ19.7,26.9,33.4,49.2,63.8,115.9,124.4,125.7,127.38,127.40,130.1,130.2,131.1,132.3,135.0,136.5,140.4,144.0,148.9,174.6.hrmscalcdforc21h23n2o:319.1805[m+h]+,found:319.1808.
7-(2-bromophenyl)-5,5-dimethyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3w)
whitesolid(99.7mg,87％).1hnmr(400mhz,cdcl3)δ1.71(s,6h),2.77(t,j＝7.2hz,2h),4.13(t,j＝7.2hz,2h),5.75(s,1h),6.77(d,j＝7.6hz,1h),6.98-7.02(m,1h),7.16-7.31(m,5h),7.59(d,j＝8.0hz,1h).13c{1h}nmr(150mhz,cdcl3)δ26.8,33.2,49.0,63.2,116.4,124.6,127.46,127.50,128.1,129.3,129.4,131.9,132.0,134.0,135.3,140.6,146.2,149.6,173.7.hrmscalcdforc20h20brn2o:383.0754[m+h]+,found:383.0757.
5,5-dimethyl-7-(m-tolyl)-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one
(3x)
whitesolid(78.3mg,82％).1hnmr(400mhz,cdcl3)δ1.67(s,6h),2.33(s,3h),2.77(t,j＝7.6hz,2h),4.10(t,j＝7.2hz,2h),5.98(s,1h),6.98-7.02(m,3h),7.04-7.08(m,1h),7.11(d,j＝7.6hz,1h),7.20(t,j＝7.2hz,1h),7.25-7.26(m,2h).13c{1h}nmr(150mhz,cdcl3)δ21.4,26.9,33.3,49.0,63.0,116.3,124.4,126.4,127.8,128.0,128.1,129.9,132.2,132.7,136.5,137.7,139.7,144.4,149.5,173.5.hrmscalcdforc21h23n2o:319.1805[m+h]+,found:319.1807.
7-(3-chlorophenyl)-5,5-dimethyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3y)
lightyellowsolid(74.1mg,73％).1hnmr(400mhz,cdcl3)δ1.69(s,6h),2.77(t,j＝7.2hz,2h),4.10(t,j＝7.2hz,2h),5.97(s,1h),6.98(d,j＝8.0hz,1h),7.06-7.10(m,2h),7.20(s,1h),7.22-7.28(m,4h).13c{1h}nmr(150mhz,cdcl3)δ26.8,33.2,49.0,63.2,116.4,124.6,127.46,127.50,128.1,129.3,129.4,131.9,132.0,134.0,135.3,140.6,146.2,149.6,173.7.hrmscalcdforc20h20cln2o:339.1259[m+h]+,found:339.1258.
5,5-dimethyl-7-(thiophen-2-yl)-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3z)
whitesolid(76.3mg,82％).1hnmr(400mhz,cdcl3)δ1.64(s,6h),2.76(t,j＝7.2hz,2h),4.07(t,j＝7.2hz,2h),6.26(s,1h),6.86(d,j＝3.6hz,1h),6.97(t,j＝4.0hz,1h),7.14(t,j＝7.6hz,1h),7.22(d,j＝5.2hz,1h),7.25-7.32(m,2h),7.37(d,j＝8.0hz,1h).13c{1h}nmr(150mhz,cdcl3)δ26.7,33.2,48.8,62.3,116.6,124.7,124.9,126.7,127.0,128.4,130.3,131.7,132.2,139.4,146.7,149.2,172.8.hrmscalcdforc18h19n2os:311.1213[m+h]+,found:311.1218.
7-cyclopropyl-5,5-dimethyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3aa)
whitesolid(70.8mg,88％).1hnmr(400mhz,cdcl3)δ0.61(q,j＝5.2hz,2h),0.82-0.87(m,2h),1.54(s,6h),1.58-1.62(m,1h),2.73(t,j＝7.2hz,2h),4.04(t,j＝7.2hz,2h),5.66(s,1h),7.18-7.26(m,3h),7.90(d,j＝7.6hz,1h).13c{1h}nmr(100mhz,cdcl3)δ7.0,19.2,27.0,33.3,49.0,62.7,116.1,124.6,127.4,128.9,133.5,134.3,135.9,148.4,173.6.hrmscalcdforc17h21n2o:269.1648[m+h]+,found:269.1649.
5-ethyl-5-methyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3bb)
whitesolid(77.3mg,81％).1hnmr(400mhz,cdcl3)δ0.86(t,j＝7.2hz,3h),1.60(s,3h),1.63-1.72(m,1h),2.53-2.62(m,1h),2.68-2.75(m,1h),2.83-2.91(m,1h),4.03-4.10(m,1h),4.14-4.21(m,1h),5.92(s,1h),7.01(d,j＝7.6hz,1h),7.04-7.08(m,1h),7.19-7.23(m,2h),7.26-7.27(m,2h),7.30-7.34(m,3h).13c{1h}nmr(100mhz,cdcl3)δ9.0,26.3,32.0,33.3,48.7,66.7,116.4,124.5,127.4,127.8,128.1,129.2,132.0,133.0,138.2,144.4,149.4,172.8.hrmscalcdforc21h23n2o:319.1805[m+h]+,found:319.1803.
5-(tert-butyl)-5-methyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3cc)
whitesolid(69.6mg,67％).1hnmr(400mhz,cdcl3)δ1.16(s,9h),1.74(s,3h),2.49(dd,j1＝16.4hz,j2＝6.4hz,1h),3.12-3.21(m,1h),4.01(td,j1＝13.6hz,j2＝6.8hz,1h),4.22(dd,j1＝12.8hz,j2＝6.8hz,1h),6.19(s,1h),6.95(d,j＝7.6hz,1h),6.97-7.01(m,1h),7.19-7.21(m,4h),7.28-7.35(m,3h).13c{1h}nmr(100mhz,cdcl3)δ23.1,27.8,33.9,42.7,47.5,72.1,115.8,124.0,127.1,127.2,128.1,129.5,131.8,132.7,135.9,137.1,145.6,150.1,174.9.hrmscalcdforc23h27n2o:347.2118[m+h]+,found:347.2114.
5-cyclohexyl-5-methyl-7-phenyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3dd)
whitesolid(79.3mg,71％).1hnmr(400mhz,cdcl3)δ0.92-1.01(m,1h),1.07-1.32(m,4h),1.50-1.53(m,1h),1.61-1.64(m,5h),1.79-1.82(m,1h),1.89-1.92(m,1h),2.62-2.73(m,2h),2.85-2.93(m,1h),4.02-4.10(m,1h),4.14-4.21(m.1h),6.05(s,1h),7.00(d,j＝7.6hz,1h),7.04-7.08(m,1h),7.19-7.22(m,2h),7.25-7.27(m,2h),7.31-7.34(m,3h).13c{1h}nmr(150mhz,cdcl3)δ24.5,26.3,26.6,26.8,28.0,28.7,33.5,45.4,48.7,69.6,116.5,124.6,127.4,127.7,128.1,129.2,131.9,133.3,135.8,138.0,144.8,149.2,172.5.hrmscalcdforc25h29n2o:373.2274[m+h]+,found:373.2275.
7-butyl-5,5-diethyl-1,2-dihydro-3h,5h-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3ee)
yellowsolid(77.7mg,83％).1hnmr(400mhz,cdcl3)δ0.78(t,j＝7.6hz,6h),0.88(t,j＝7.2hz,3h),1.26-1.33(m,2h),1.35-1.43(m,2h),1.50-1.59(m,2h),2.30-2.39(m,2h),2.52(t,j＝6.8hz,2h),2.76(t,j＝7.2hz,2h),4.05(t,j＝7.2hz,2h),5.58(s,1h),7.14-7.21(m,3h),7.42(d,j＝7.6hz,1h).13c{1h}nmr(100mhz,cdcl3)δ8.8,13.9,22.3,31.4,31.7,33.3,38.5,48.0,69.5,117.0,124.9,127.1,128.0,133.6,134.2,136.7,148.6,171.8.hrmscalcdforc20h29n2o:313.2274[m+h]+,found:313.2271.
实施例4
依照实施例2的方法和步骤a,b，通过改变反应物1和2，可以合成出各种吡唑啉酮并苯二氮杂卓类化合物3aa-3az和3ba-3bd，具体结果如下：
a反应条件:1(0.3mmol),2(0.3mmol),[rhcp*cl2]2(0.0075mmol)，zn(oac)2(0.15mmol),naoac(0.15mmol),toluene(2ml),100℃,4h；b分离收率。
---------------------------------------------------------------------
代表性产物表征数据如下：
7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3aa)
whitesolid(67.4mg,68％).1hnmr(400mhz,cdcl3)δ1.70-1.77(m,2h),1.82-1.97(m,4h),2.59-2.66(m,2h),2.78(t,j＝7.2hz,2h),4.07(t,j＝7.2hz,2h),6.15(s,1h),7.00-7.02(m,1h),7.04-7.08(m,1h),7.18-7.21(m,2h),7.24-7.27(m,2h),7.28-7.34(m,3h).13c{1h}nmr(100mhz,cdcl3)δ24.7,33.5,38.2,48.5,71.9,116.8,124.5,127.4,128.0,128.2,129.2,131.9,133.2,137.1,139.4,144.1,149.5,172.3.hrmscalcdforc22h23n2o:331.1805[m+h]+,found:331.1803.
9-methyl-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3ab)
whitesolid(64.0mg,62％).1hnmr(400mhz,cdcl3)δ1.69-1.75(m,2h),1.79-1.85(m,2h),1.89-1.94(m,2h),2.21(s,3h),2.58-2.65(m,2h),2.78(t,j＝7.2hz,2h),4.04(t,j＝7.2hz,2h),6.15(s,1h),6.82(d,j＝1.6hz,1h),7.06-7.09(m,1h),7.15(d,j＝8.4hz,1h),7.19-7.21(m,2h),7.29-7.34(m,3h).13c{1h}nmr(100mhz,cdcl3)δ20.8,24.6,33.6,38.1,48.4,71.4,116.8,127.4,128.1,128.7,129.1,132.1,133.3,134.1,137.5,139.3,144.0,147.2,171.9.hrmscalcdforc23h25n2o:345.1961[m+h]+,found:345.1962.
9-methyl-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3ac)
whitesolid(64.8mg,60％).1hnmr(400mhz,cdcl3)δ1.68-1.76(m,2h),1.79-1.84(m,2h),1.87-1.96(m,2h),2.58-2.65(m,2h),2.78(t,j＝7.2hz,2h),3.82(s,3h),4.07(t,j＝7.2hz,2h),6.14(s,1h),6.83-6.86(m,2h),7.03-7.08(m,2h),7.09-7.14(m,2h),7.24-7.29(m,2h).13c{1h}nmr(100mhz,cdcl3)δ24.6,33.5,38.1,48.4,55.3,71.5,113.5,116.9,124.6,128.0,130.2,131.8,133.6,136.5,136.9,138.4,149.5,159.1,172.0.hrmscalcdforc23h25n2o2:361.1911[m+h]+,found:361.1909.
9-chloro-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3ad)
brownsyrup(71.0mg,65％).1hnmr(400mhz,cdcl3)δ:1.68-1.75(m,2h),1.81-1.86(m,2h),1.89-1.97(m,2h),2.58-2.65(m,2h),2.78(t,j＝7.2hz,2h),4.07(t,j＝7.2hz,2h),6.12(s,1h),6.98(dd,j1＝8.0hz,j2＝1.2hz,1h),7.07(td,j1＝8.0hz,j2＝1.6hz,1h),7.11-7.14(m,2h),7.24-7.29(m,4h).13c{1h}nmr(100mhz,cdcl3)δ24.8,33.4,38.2,48.5,72.0,116.8,124.6,128.2,128.4,130.5,131.8,132.8,133.3,136.0,139.7,142.6,149.6,172.4.hrmscalcdforc22h22cln2o:365.1415[m+h]+,found:365.1411.
9-bromo-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3ae)
whitesolid(77.1mg,63％).1hnmr(400mhz,cdcl3)δ1.70-1.76(m,2h),1.82-1.95(m,4h),2.58-2.65(m,2h),2.76(t,j＝7.2hz,2h),4.03(t,j＝7.2hz,2h),6.15(s,1h),7.11-7.13(m,2h),7.17-7.19(m,2h),7.31-7.38(m,4h).13c{1h}nmr(100mhz,cdcl3)δ24.8,33.3,38.3,48.7,72.2,117.6,118.3,127.7,128.4,129.1,130.7,134.4,135.2,135.7,140.8,143.5,148.7,172.4.hrmscalcdforc22h22brn2o:409.0910[m+h]+,found:409.0906.
7-phenyl-9-(trifluoromethyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3af)
whitesolid(72.9mg,61％).1hnmr(400mhz,cdcl3)δ1.71-1.80(m,2h),1.88-1.99(m,4h),2.59-2.66(m,2h),2.77(t,j＝7.2hz,2h),4.10(t,j＝7.2hz,2h),6.17(s,1h),7.15-7.19(m,2h),7.26-7.27(m,1h),7.31-7.37(m,4h),7.51(dd,j1＝8.4hz,j2＝1.6hz,1h).13c{1h}nmr(100mhz,cdcl3)δ24.9,33.2,38.5,49.0,72.8,116.7,123.9(q,1jc-f＝270.1hz),124.6(q,3jc-f＝3.6hz),126.4(q,2jc-f＝32.5hz),127.8,128.4,129.1,129.2(q,3jc-f＝4.4hz),133.2,135.4,141.0,143.6,152.5,172.9.19fnmr(376mhz,cdcl3)δ-62.40(s).hrmscalcdforc23h22f3n2o:399.1679[m+h]+,found:399.1671.
10-methyl-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3ag)
whitesolid(74.3mg,72％).1hnmr(400mhz,cdcl3)δ1.70-1.75(m,2h),1.80-1.96(m,4h),2.39(s,3h),2.58-2.65(m,2h),2.78(t,j＝7.2hz,2h),4.06(t,j＝7.2hz,2h),6.11(s,1h),6.86-6.91(m,2h),7.04(s,1h),7.18-7.20(m,2h),7.26-7.33(m,3h).13c{1h}nmr(100mhz,cdcl3)δ20.8,24.6,33.6,38.1,48.4,71.4,116.8,127.4,128.1,128.7,129.1,132.1,133.3,134.1,137.5,139.3,144.0,147.2,171.9.hrmscalcdforc23h25n2o:345.1961[m+h]+,found:345.1958.
10-bromo-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3ah)
whitesolid(85.7mg,70％).1hnmr(400mhz,cdcl3)δ1.71-1.77(m,2h),1.83-1.97(m,4h),2.58-2.65(m,2h),2.78(t,j＝7.2hz,2h),4.04(t,j＝7.2hz,2h),6.12(s,1h),6.87(d,j＝8.4hz,1h),7.15-7.19(m,3h),7.29-7.34(m,3h),7.36(d,j＝2.0hz,1h).13c{1h}nmr(100mhz,cdcl3)δ24.8,33.2,38.3,48.8,72.4,120.0,121.2,127.5,127.6,128.3,129.2,132.0,133.3,135.9,140.0,143.8,150.8,172.5.hrmscalcdforc22h22brn2o:409.0910[m+h]+,found:409.0904.
7-(p-tolyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3ai)
whitesolid(77.4mg,75％).1hnmr(400mhz,cdcl3)δ1.68-1.75(m,2h),1.80-1.94(m,4h),2.36(s,3h),2.58-2.65(m,2h),2.78(t,j＝7.2hz,2h),4.07(t,j＝7.2hz,2h),6.13(s,1h),7.02-7.13(m,6h),7.23-7.27(m,2h).13c{1h}nmr(100mhz,cdcl3)δ21.2,24.7,33.5,38.2,48.5,71.8,116.8,124.5,128.0,128.9,129.0,131.9,133.4,137.0,137.1,138.9,141.2,149.5,172.2.hrmscalcdforc23h25n2o:345.1961[m+h]+,found:345.1957.
7-(4-methoxyphenyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3aj)
whitesolid(65.9mg,61％).1hnmr(400mhz,cdcl3)δ1.68-1.75(m,2h),1.79-1.84(m,2h),1.87-1.96(m,2h),2.58-2.65(m,2h),2.78(t,j＝7.2hz,2h),3.82(s,3h),4.07(t,j＝7.2hz,2h),6.14(s,1h),6.83-6.86(m,2h),7.03-7.14(m,4h),7.24-7.29(m,2h).13c{1h}nmr(100mhz,cdcl3)δ24.6,33.5,38.1,48.4,55.3,71.5,113.5,116.9,124.6,128.0,130.2,131.8,133.6,136.5,136.9,138.4,149.5,159.1,172.0.hrmscalcdforc23h25n2o2:361.1911[m+h]+,found:361.1911.
7-(4-chlorophenyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3ak)
whitesolid(71.2mg,65％).1hnmr(400mhz,cdcl3)δ1.68-1.75(m,2h),1.81-1.86(m,2h),1.89-1.97(m,2h),2.58-2.65(m,2h),2.78(t,j＝7.2hz,2h),4.07(t,j＝7.2hz,2h),6.12(s,1h),6.98(dd,j1＝8.0hz,j2＝1.2hz,1h),7.07(td,j1＝8.0hz,j2＝1.6hz,1h),7.11-7.14(m,2h),7.24-7.29(m,4h).13c{1h}nmr(100mhz,cdcl3)δ24.8,33.4,38.2,48.5,72.0,116.8,124.6,128.2,128.4,130.5,131.8,132.8,133.3,136.0,139.7,142.6,149.6,172.4.hrmscalcdforc22h22cln2o:365.1415[m+h]+,found:365.1416.
7-(4-(trifluoromethyl)phenyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3al)
whitesolid(75.3mg,63％).1hnmr(400mhz,cdcl3)δ1.71-1.78(m,2h),1.84-1.99(m,4h),2.60-2.67(m,2h),2.79(t,j＝7.2hz,2h),4.08(t,j＝7.2hz,2h),6.13(s,1h),6.93-6.95(m,1h),7.05-7.09(m,1h),7.25-7.32(m,4h),7.57(d,j＝8.0hz,2h).13c{1h}nmr(100mhz,cdcl3)δ24.8,33.4,38.3,48.7,72.3,116.8,124.2(q,1jc-f＝270.1hz),124.6,125.2(q,3jc-f＝3.7hz),128.3,129.45(q,2jc-f＝31.8hz),129.49,131.8,132.3,135.7,140.7,147.8,149.7,172.7.19fnmr(376mhz,cdcl3)δ-62.22(s).hrmscalcdforc23h22f3n2o:399.1679[m+h]+,found:399.1674.
7-cyclopropyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3am)
whitesolid(63.5mg,72％).1hnmr(400mhz,cdcl3)δ0.59-0.63(m,2h),0.82-0.87(m,2h),1.58-1.74(m,5h),1.81-1.90(m,2h),2.49-2.56(m,2h),2.73(t,j＝7.2hz,2h),4.01(t,j＝7.2hz,2h),5.79(d,j＝0.8hz,1h),7.16-7.18(m,1h),7.20-7.28(m,2h),7.88(dd,j1＝7.6hz,j2＝1.6hz,1h).13c{1h}nmr(100mhz,cdcl3)δ7.1,19.0,24.7,33.5,38.3,48.6,71.7,116.5,124.6,127.5,128.8,134.0,134.9,135.3,148.4,172.4.hrmscalcdforc19h23n2o:295.1805[m+h]+,found:295.1804.
7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3an)
whitesolid(89.8mg,87％).1hnmr(400mhz,cdcl3)δ1.31-1.40(m,1h),1.56-1.74(m,7h),2.63-2.70(m,2h),2.80(t,j＝7.2hz,2h),4.04(t,j＝7.2hz,2h),6.62(s,1h),7.04(d,j＝7.2hz,1h),7.08-7.12(m,1h),7.20-7.22(m,2h),7.28-7.34(m,5h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.8,33.5,34.1,48.6,64.8,120.6,121.4,127.8,128.0,128.3,129.0,132.8,132.9,136.1,137.6,143.7,150.7,171.3.hrmscalcdforc23h25n2o:345.1961[m+h]+,found:345.1952.
9-methyl-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3ao)
whitesolid(91.3mg,85％).1hnmr(400mhz,cdcl3)δ1.30-1.36(m,1h),1.55-1.73(m,7h),2.23(s,3h),2.62-2.68(m,2h),2.79(t,j＝7.6hz,2h),4.01(t,j＝7.6hz,2h),6.59(s,1h),6.85(d,j＝1.6hz,1h),7.09(dd,j1＝8.0hz,j2＝1.6hz,1h),7.18(d,j＝8.4hz,1h),7.21-7.24(m,2h),7.30-7.35(m,3h).13c{1h}nmr(100mhz,cdcl3)δ20.8,23.7,24.8,33.8,33.9,48.3,64.0,117.1,127.6,128.2,129.0,131.7,134.0,134.5,135.3,138.9,144.0,147.1,170.8.hrmscalcdforc24h27n2o:359.2118[m+h]+,found:359.2114.
9-methoxy-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3ap)
lightyellowsolid(86.4mg,77％).1hnmr(400mhz,cdcl3)δ1.30-1.37(m,1h),1.54-1.74(m,7h),2.65(td,j1＝12.4hz,j2＝3.6hz,2h),2.80(t,j＝7.6hz,2h),3.67(s,3h),3.99(t,j＝7.6hz,2h),6.58(d,j＝2.8hz,1h),6.61(s,1h),6.83(dd,j1＝8.4hz,j2＝2.8hz,1h),7.20-7.28(m,3h),7.29-7.34(m,3h).13c{1h}nmr(100mhz,cdcl3)δ23.7,24.8,33.8,34.0,48.4,55.5,63.9,113.7,116.2,118.3,127.7,128.2,129.0,135.4,135.6,138.8,143.0,143.5,156.6,170.7.hrmscalcdforc24h27n2o2:375.2067[m+h]+,found:375.2055.
9-fluoro-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3aq)
whitesolid(79.3mg,73％).1hnmr(400mhz,cdcl3)δ1.30-1.39(m,1h),1.54-1.75(m,7h),2.63-2.69(m,2h),2.80(t,j＝7.2hz,2h),4.01(t,j＝7.2hz,2h),6.65(s,1h),6.75(dd,j1＝9.6hz,j2＝2.8hz,1h),6.96-7.01(m,1h),7.20-7.26(m,3h),7.31-7.36(m,3h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.8,33.8,34.0,48.7,64.4,114.9(d,2jc-f＝22.4hz),117.7(d,2jc-f＝22.4hz),118.6(d,3jc-f＝8.7hz),127.8,128.4,129.0,136.0(d,3jc-f＝8.0hz),136.5,137.8(d,4jc-f＝2.1hz),143.3,145.7(d,4jc-f＝2.2hz),159.7(d,1jc-f＝242.7hz),171.1.19fnmr(376mhz,cdcl3)δ-117.32–-117.26(m).hrmscalcdforc23h24fn2o:363.1867[m+h]+,found:363.1861.
9-bromo-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3ar)
lightyellowsolid(95.0mg,75％).1hnmr(400mhz,cdcl3)δ1.32-1.39(m,1h),1.54-1.76(m,7h),2.62-2.69(m,2h),2.78(t,j＝7.2hz,2h),4.00(t,j＝7.2hz,2h),6.64(s,1h),7.15-7.17(m,2h),7.18-7.21(m,2h),7.32-7.36(m,3h),7.39(dd,j1＝8.4hz,j2＝2.4hz,1h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.8,33.6,34.0,48.6,64.6,118.0,118.9,127.9,128.4,129.0,131.0,134.0,136.0,136.8,137.4,143.4,148.6,171.2.hrmscalcdforc23h24brn2o:423.1067[m+h]+,found:423.1066.
7-phenyl-9-(trifluoromethyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3as)
whitesolid(103.9mg,84％).1hnmr(400mhz,cdcl3)δ1.32-1.42(m,1h),1.56-1.75(m,7h),2.64-2.72(m,2h),2.79(t,j＝7.6hz,2h),4.07(t,j＝7.6hz,2h),6.70(s,1h),7.16-7.20(m,2h),7.30-7.38(m,5h),7.54(dd,j1＝8.4hz,j2＝1.6hz,1h).13c{1h}nmr(100mhz,cdcl3)δ23.5,24.8,33.5,34.2,48.8,65.1,117.4,123.9(q,1jc-f＝270.1hz),125.0(q,3jc-f＝3.6hz),126.9(q,1jc-f＝32.5hz),128.0,128.5,128.7(q,3jc-f＝3.6hz),129.0,134.1,137.2,143.6,152.4,171.6.19fnmr(376mhz,cdcl3)δ-62.22(s).hrmscalcdforc24h24f3n2o:413.1835[m+h]+,found:413.1829.
10-methoxy-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3at)
whitesolid(79.7mg,71％).1hnmr(400mhz,cdcl3)δ1.34-1.40(m,1h),1.59-1.73(m,7h),2.65(td,j1＝13.2hz,j2＝4.0hz,2h),2.79(t,j＝7.6hz,2h),3.84(s,3h),4.01(t,j＝7.2hz,2h),6.49(s,1h),6.65(dd,j1＝8.8hz,j2＝2.4hz,1h),6.81(d,j＝2.4hz,1h),6.96(d,j＝8.4hz,1h),7.20-7.23(m,2h),7.29-7.34(m,3h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.8,33.6,33.9,48.5,55.5,64.4,104.5,109.1,126.7,127.5,128.2,129.0,132.6,133.7,138.4,144.2,150.7,159.4,171.1.hrmscalcdforc24h27n2o2:375.2067[m+h]+,found:375.2060.
10-bromo-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3au)
whitesolid(103.8mg,82％).1hnmr(400mhz,cdcl3)δ1.33-1.39(m,1h),1.54-1.75(m,7h),2.66(td,j1＝13.6hz,j2＝4.8hz,2h),2.79(t,j＝7.2hz,2h),4.01(t,j＝7.2hz,2h),6.62(s,1h),6.91(d,j＝8.4hz,1h),7.17-7.19(m,2h),7.22(dd,j1＝8.4hz,j2＝1.6hz,1h),7.31-7.34(m,3h),7.40(d,j＝1.6hz,1h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.8,33.5,34.1,48.6,64.8,120.6,121.4,127.8,128.0,128.3,129.0,132.8,132.9,136.1,137.6,143.7,150.7,171.3.hrmscalcdforc23h24brn2o:423.1067[m+h]+,found:423.1062.
2-methyl-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3av)
whitesolid(79.5mg,74％).1hnmr(400mhz,cdcl3)δ1.24(d,j＝6.8hz,3h),1.32-1.82(m,7h),1.97(d,j＝12.8hz,1h),2.51(td,j1＝13.2hz,j2＝4.8hz,1h),2.82(td,j1＝13.2hz,j2＝4.4hz,1h),3.14-3.23(m,1h),3.50(t,j＝12.8hz,1h),4.27-4.32(m,1h),6.61(s,1h),7.02-7.10(m,2h),7.20-7.22(m,2h),7.25-7.33(m,5h).13c{1h}nmr(100mhz,cdcl3)δ13.8,23.4,23.8,24.9,33.2,34.7,37.4,56.3,64.5,117.4,124.7,127.5,128.1,128.2,129.1,131,6,133.9,135.5,138.5,144.2,149.5,173.8.hrmscalcdforc24h27n2o:359.2118[m+h]+,found:359.2118.
2,2-dimethyl-7-phenyl-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3aw)
whitesolid(89.3mg,80％).1hnmr(400mhz,cdcl3)δ1.27(s,6h),1.41-1.47(m,1h),1.54-1.72(m,7h),2.65-2.71(m,2h),3.92(s,2h),6.43(s,1h),6.89-6.97(m,2h),7.17-7.19(m,2h),7.21-7.22(m,2h),7.28-7.33(m,3h).13c{1h}nmr(100mhz,cdcl3)δ23.1,24.5,25.2,33.8,42.8,62.2,63.3,118.5,122.7,127.2,127.9,128.2,129.0,131.0,132.4,136.6,139.6,144.5,150.5,176.1.hrmscalcdforc25h29n2o:373.2274[m+h]+,found:373.2269.
7-(4-ethylphenyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3ax)
whitesolid(99.4mg,89％).1hnmr(400mhz,cdcl3)δ1.25(t,j＝7.6hz,3h),1.32-1.37(m,1h),1.58-1.72(m,7h),2.62-2.69(m,4h),2.80(t,j＝7.2hz,2h),4.04(t,j＝7.6hz,2h),6.60(s,1h),7.06-7.16(m,6h),7.27-7.29(m,2h).13c{1h}nmr(100mhz,cdcl3)δ15.6,23.6,24.8,28.6,33.8,33.9,48.4,64.3,117.2,124.8,127.7,128.2,129.0,131.6,134.2,134.9,138.5,141.4,143.7,149.4,171.1.hrmscalcdforc25h29n2o:373.2274[m+h]+,found:373.2271.
7-(4-methoxyphenyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3ay)
yellowsyrup(86.6mg,77％).1hnmr(400mhz,cdcl3)δ1.32-1.38(m,1h),1.54-1.73(m,7h),2.62-2.68(m,2h),2.80(t,j＝7.6hz,2h),3.81(s,3h),4.03(t,j＝7.6hz,2h),6.57(s,1h),6.83-6.87(m,2h),7.06-7.11(m,2h),7.12-7.16(m,2h),7.26-7.28(m,2h).13c{1h}nmr(100mhz,cdcl3)δ23.7,24.8,33.8,33.9,48.3,55.3,64.2,113.6,117.2,124.9,128.3,130.1,131.5,134.2,134.3,136.5,138.3,149.4,159.3,171.0.hrmscalcdforc24h27n2o2:375.2067[m+h]+,found:375.2059.
7-(4-(trifluoromethyl)phenyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3az)
yellowsolid(101.4mg,82％).1hnmr(400mhz,cdcl3)δ1.31-1.41(m,1h),1.53-1.64(m,2h),1.69-1.76(m,5h),2.68(td,j1＝13.2hz,j2＝4.4hz,2h),2.81(t,j＝7.2hz,2h),4.05(t,j＝7.2hz,2h),6.64(s,1h),6.97-6.99(m,1h),7.09-7.13(m,1h),7.29-7.33(m,4h),7.58(d,j＝8.0hz,2h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.8,33.7,33.9,48.5,64.6,117.3,124.2(q,1jc-f＝270.2hz),125.0,125.2(q,3jc-f＝3.6hz),128.6,129.3,129.6(q,2jc-f＝32.5hz),131.3,133.2,136.9,137.4,147.7,149.5,171.4.19fnmr(376mhz,cdcl3)δ-62.42(s).hrmscalcdforc24h24f3n2o:413.1835[m+h]+,found:413.1833.
7-(m-tolyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3ba)
lightyellowsolid(92.4mg,86％).1hnmr(400mhz,cdcl3)δ1.33-1.38(m,1h),1.55-1.74(m,7h),2.33(s,3h),2.62-2.70(m,2h),2.80(t,j＝7.2hz,2h),4.04(t,j＝7.6hz,2h),6.59(s,1h),6.99-7.05(m,3h),7.08-7.12(m,2h),7.21(t,j＝7.2hz,1h),7.26-7.29(m,2h).13c{1h}nmr(100mhz,cdcl3)δ21.5,23.6,24.8,33.8,33.9,48.4,64.3,117.2,124.9,126.2,128.1,128.2,128.3,129.7,131.6,134.1,135.2,137.8,138.7,144.1,149.4,171.2.hrmscalcdforc24h27n2o:359.2118[m+h]+,found:359.2114.
7-(3-chlorophenyl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3bb)
whitesolid(99.8mg,88％).1hnmr(400mhz,cdcl3)δ1.33-1.40(m,1h),1.53-1.63(m,2h),1.68-1.75(m,5h),2.63-2.69(m,2h),2.80(t,j＝7.6hz,2h),4.04(t,j＝7.6hz,2h),6.60(s,1h),7.02(d,j＝7.2hz,1h),7.08-7.14(m,2h),7.18(d,j＝1.6hz,1h),7.23-7.32(m,4h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.8,33.7,33.9,48.5,64.4,117.3,125.0,127.3,127.7,128.6,129.0,129.5,131.4,133.3,134.1,136.3,137.4,145.9,149.5,171.3.hrmscalcdforc23h24cln2o:379.1572[m+h]+,found:379.1572.
7-(thiophen-2-yl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3bc)
whitesolid(85.4mg,81％).1hnmr(400mhz,cdcl3)δ1.26-1.38(m,1h),1.50-1.72(m,7h),2.63(td,j1＝12.4hz,j2＝4.0hz,2h),2.80(t,j＝7.6hz,2h),4.02(t,j＝7.6hz,2h),6.80(s,1h),6.86(dd,j1＝3.2hz,j2＝0.8hz,1h),6.97(dd,j1＝5.2hz,j2＝3.6hz,1h),7.16-7.20(m,1h),7.23(dd,j1＝5.2hz,j2＝1.2hz,1h),7.27-7.29(m,1h),7.31-7.35(m,1h),7.41(dd,j1＝8.0hz,j2＝1.6hz,1h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.7,33.7,33.8,48.2,64.0,117.4,125.0,125.1,126.6,127.2,128.8,131.2,132.1,133.4,134.8,146.5,149.1,170.7.hrmscalcdforc21h23n2os:351.1526[m+h]+,found:351.1523.
7-(pyridin-3-yl)-1,2-dihydro-3h-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3bd)
whitesolid(86.9mg,84％).1hnmr(400mhz,cdcl3)δ1.34-1.41(m,1h),1.54-1.65(m,2h),1.73-1.76(m,5h),2.68(td,j1＝12.8hz,j2＝4.0hz,2h),2.81(t,j＝7.6hz,2h),4.06(t,j＝7.6hz,2h),6.65(s,1h),7.00-7.01(m,1h),7.10-7.14(m,1h),7.23-7.28(m,1h),7.31-7.33(m,2h),7.47(dt,j1＝8.0hz,j2＝2.0hz,1h),8.55-8.57(m,2h).13c{1h}nmr(100mhz,cdcl3)δ23.6,24.7,33.7,34.0,48.6,64.7,117.3,123.1,125.1,128.7,131.1,133.0,135.3,136.3,136.9,139.7,148.8,149.5,149.8,171.5.hrmscalcdforc22h24n3o:346.1914[m+h]+,found:346.1908.
以1a和2a在实施例2标准条件下得到3a为例，经过对比试验验证(实验细节省略)，推测反应原理如下：
需要特别指出的是，迁移插入的区域选择性来源于oh和rh(iii)额外络合配位，生成中间体iii，接着中间体iii经历去金属化/质子化生成中间体iv,接着最可能在体系原位生成的醋酸帮助下，rh(iii)发生氧化插入到c-o键中间，生成中间体v，脱除水分子后形成中间体vi，vi发生还原消除，生成产物3a，同时释放出rh(iii)催化剂，用于下一轮催化。
实施例5
本发明所合成的产物吡唑啉酮并苯二氮杂卓类化合物3可以进行一系列反应，从而合成进一步的衍生物。例如：
向3a(60.8mg，0.2mmol)的meoh/dcm(2ml，10/3)溶液中添加pd/c(10wt％，10mg)。在室温条件下将混合物在h2(气球，1atm)下搅拌24小时。反应结束后，将反应混合物过硅藻土抽滤并在减压下浓缩。残余物过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得到白色固体产物4a(58.2mg，95％)。该化合物的表征数据如下：1hnmr(400mhz,cdcl3)δ1.53(s,3h),1.65(s,3h),1.78(dd,j1＝14.4hz,j2＝4.4hz,1h),2.42-2.49(m,1h),2.83-2.95(m,2h),3.78-3.86(m,1h),4.12(ddd,j1＝12.8hz,j2＝7.2hz,j3＝2.8hz,1h),4.42(dd,j1＝12.4hz,j2＝4.0hz,1h),6.83(d,j＝7.6hz,1h),6.89-6.92(m,1h),7.07-7.11(m,2h),7.14-7.21(m,3h),7.27-7.30(m,2h).13c{1h}nmr(100mhz,cdcl3)δ24.3,27.2,33.5,46.9,48.6,48.7,60.0,116.4,124.4,126.3,126.7,128.3,128.7,132.6,136.2,147.7,149.3,173.4.hrmscalcdforc20h23n2o:307.1805[m+h]+,found:307.1805.
在0℃下，向3a(60.8mg，0.2mmol)的thf(5ml)溶液中缓慢加入lialh4(0.4ml，1m)，然后在室温搅拌反应2h。反应结束后，加入水淬灭反应，浓缩并用etoac萃取。合并有机相，用无水硫酸钠干燥，过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得到黄色浆状物5a(33.9mg，55％)。该化合物的表征数据如下：1hnmr(400mhz,cdcl3)δ1.35(s,6h),1.95-2.01(m,2h),3.61-3.64(m,4h),3.80(t,j＝5.6hz,2h),6.08(s,1h),6.87(td,j1＝7.2hz,j2＝0.8hz,1h),6.92(dd,j1＝8.0hz,j2＝1.6hz,1h),7.04(d,j＝7.6hz,1h),7.13-7.18(m,3h),7.25-7.33(m,3h).13c{1h}nmr(100mhz,cdcl3)δ27.8,30.2,54.4,61.5,62.8,115.4,122.3,126.8,127.2,128.0,129.5,130.5,133.3,136.2,143.6,146.0,151.8.hrmscalcdforc20h25n2o:309.1961[m+h]+,found:309.1962.
以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。