本发明涉及化学技术领域，尤其是一种3-叔胺四取代氧化吲哚化合物及其制备方法。
背景技术：
3-叔胺基氧化吲哚广泛存在于合成药物和天然产物中，吸引了许多化学工作者及医药化学团队的广泛关注，例如，具有抗菌和抗肿瘤活性的天然产物分子psychotrimine，则是从植物psychotriarostrata中分离得到；血管加压素受体拮抗剂ssr-149415也含有3-叔胺基四取代氧化吲哚骨架结构。因此，采用方法学合成更多类型的3-叔胺基氧化吲哚，可以为吲哚类化合物的新药开发和成药性研究奠定物质基础，对药物的筛选和制药行业具有重要的应用价值。
技术实现要素：
本发明的目的是：提供一种3-叔胺四取代氧化吲哚化合物及其制备方法，它是一类重要的医药中间体类似物和药物分子类似物，对药物筛选和制药行业具有重要的应用价值，且其合成方法非常经济简便。
本发明是这样实现的：3-叔胺四取代氧化吲哚化合物，该化合物具有如下通式(ⅰ)的结构：
式(i)中，r为苄基或取代的苄基；y为c或氧或硫；n为1或2。
将各种取代的3-卤氧化吲哚，以无机碱为催化剂，直接以二级环胺作溶剂和反应底物在加温条件下发生3-叔胺基化反应，获得3-叔胺四取代氧化吲哚化合物。
合成路线如下：
其中各种取代的3-卤氧化吲哚，二级环胺2的结构式，其取代基满足r为苄基、取代的苄基；y为c或氧或硫；n为1或2；x为cl或br。
所述的无机碱为碳酸钠或碳酸钾或磷酸钠或磷酸钾。
所述的反应温度为50-100℃。
所推测的反应机理如下：
3-卤氧化吲哚1在无机碱催化下，脱去卤化氢生成中间体；中间体然后在二级环胺2亲核进攻下发生3-叔胺基化取代反应得到产物3-叔胺四取代氧化吲哚化合物3，副产物卤化氢被生成的三级胺产物中和成有机盐，促使反应进行完全。
通过采用上述技术方案，以各种取代的3-卤氧化吲哚，以无机碱为催化剂，直接以二级环胺作溶剂和反应底物在加温条件下发生3-叔胺基化反应，获得3-叔胺四取代氧化吲哚化合物，该类氧化吲哚骨架可以为生物活性筛选提供化合物源，对药物的筛选和制药行业具有重要的应用价值。本发明操作简单易行，原料合成便宜易得，可以在无溶剂中进行，也具有较好的空气稳定性，适用性广，对于各种取代基都有很好的兼容性。
附图说明
附图1及附图2为本发明的实施例的化合物3aa-1谱图数据；
附图3及附图4为本发明的实施例的化合物3aa谱图数据；
附图5及附图6为本发明的实施例的化合物3bf-1谱图数据；
附图7及附图8为本发明的实施例的化合物3bb谱图数据
具体实施方式
本发明的实施例1：3-苄基氯取代氧化吲哚(1a)128.5mg(0.5mmol)溶解于吗啉(2ml)中，加入10.6毫克na2co3(20mol％)，搅拌下于65℃反应5h(tlc检测)。冷却至室温,直接经硅胶柱层析[洗脱剂：v(乙酸乙酯)/v(石油醚)＝1/10]纯化得淡黄色油状液体3aa140.2mg,收率91％。核磁共振和高分辨质谱测试等结果如下：1hnmr(cdcl3,500mhz)δ:2.73-2.80(m,4h),3.20(d,j＝12.5hz,1h),3.37(d,j＝12.5hz,1h),3.69-3.71(m,4h),6.61(d,j＝7.5hz,1h),6.81(d,j＝7.5hz,2h),6.93-7.07(m,4h),7.13-7.16(m,1h),7.34(d,j＝7.5hz,1h),8.55(brs,1h)；13cnmr(cdcl3,125mhz)δ:40.5,47.5,67.3,72.0,109.8,122.3,125.1,126.4,127.5,128.7,128.8,130.2,134.4,140.9,178.8；hr-ms(esi-tof)m/z:calcdforc19h20n2nao2{[m+na]+}331.1417,found331.125.
化合物3ab至3bh的制备方法同化合物3aa，投料比与化合物3aa相同，可得到化合物3ab至3bh，反应见表1和表2，但需强调的是本发明的化合物不限于表1所表示的内容。
表1为一种3-吗啉或硫代吗啉四取代氧化吲哚的化学结构
本实施例制备化合物3ab:淡黄色油状物；产率88％；1hnmrδ:2.12(s,3h),2.70-2.79(m,4h),3.16(d,j＝12.5hz,1h),3.32(d,j＝12.5hz,1h),3.67-3.69(m,4h),6.62(d,j＝7.5hz,1h),6.69(d,j＝8.0hz,2h),6.74(d,j＝8.0hz,2h),7.02-7.05(m,1h),7.11-7.15(m,1h),7.32(d,j＝7.5hz,1h),8.91(brs,1h)；13cnmrδ:20.8,39.9,47.4,67.2,72.1,109.8,122.1,125.0,128.2,128.7,128.8,130.0,131.2,135.8,141.1,179.1；hr-ms(esi-tof)m/z:calcdforc20h22n2nao2{[m+na]+}345.1573,found345.1573。
本实施例制备化合物3ac:淡黄色油状物；产率89％；1hnmrδ:2.73-2.80(m,4h),3.18(d,j＝12.5hz,1h),3.33(d,j＝13.0hz,1h),3.62(s,3h),3.72(s,4h),6.49(d,j＝8.0hz,2h),6.67(d,j＝7.5hz,1h),6.74(d,j＝8.5hz,2h),7.06-7.09(m,1h),7.16-7.19(m,1h),7.36(d,j＝7.5hz,1h),8.90(brs,1h)；13cnmrδ:39.5,47.5,54.8,67.2,72.1,109.9,112.8,122.1,125.0,126.2,128.7,128.8,131.1,141.1,157.9,179.1；hr-ms(esi-tof)m/z:calcdforc20h22n2nao3{[m+na]+}361.1523,found361.1529。
本实施例制备化合物3ad:淡黄色油状物；产率87％；1hnmrδ:2.71-2.79(m,4h),3.14(d,j＝12.5hz,1h),3.32(d,j＝12.5hz,1h),3.68-3.71(m,4h),6.64-6.69(m,3h),7.05-7.08(m,3h),7.15-7.18(m,1h),7.33(d,j＝7.0hz,1h),8.73(brs,1h)；13cnmrδ:39.9,47.5,67.3,71.9,110.1,120.7,122.5,125.1,128.4,129.1,130.7,132.0,133.5,141.0,178.8；hr-ms(esi-tof)m/z:calcdforc19h19brn2nao2{[m+na]+}409.0522,found409.0521。
本实施例1制备化合物3ae:淡黄色油状物；产率91％；1hnmrδ:2.71-2.79(m,4h),3.17(d,j＝12.5hz,1h),3.35(d,j＝12.5hz,1h),3.69-3.71(m,4h),6.60-6.66(m,3h),6.74-6.77(m,2h),7.05-7.08(m,1h),7.15-7.18(m,1h),7.34(d,j＝7.0hz,1h),8.86(brs,1h)；13cnmrδ:39.6,47.5,67.2,72.1,109.9,114.2(d,jcf＝21.3hz),122.4,125.0,128.5,129.0,131.6,131.7,141.0,161.5(d,jcf＝243.8hz),179.0；hr-ms(esi-tof)m/z:calcdforc19h19fn2nao2{[m+na]+}349.1323,found349.1320。
本实施例制备化合物3af:淡黄色油状物；产率91％；1hnmrδ:2.76-2.86(m,4h),3.23(d,j＝12.5hz,1h),3.40(d,j＝12.5hz,1h),3.73-3.75(m,4h),6.57(d,j＝10.0hz,1h),6.65-6.69(m,2h),6.72-6.76(m,1h),6.94-6.98(m,1h),7.08-7.11(m,1h),7.17-7.20(m,1h),7.36(d,j＝6.0hz,1h),8.84(brs,1h)；13cnmrδ:40.1,47.4,67.3,71.8,110.0,113.4(d,jcf＝21.3hz),113.5,117.0(d,jcf＝21.3hz),122.4,125.0,126.0,128.3,128.8,128.9,129.0,137.1,140.9,161.9(d,jcf＝223.8hz),178.7；hr-ms(esi-tof)m/z:calcdforc19h19fn2nao2{[m+na]+}349.1323,found349.1327。
本实施例制备化合物3bb:淡黄色油状物；产率93％；1hnmrδ:2.14(s,3h),2.67(s,4h),3.01(s,4h),3.17(d,j＝12.5hz,1h),3.27(d,j＝12.5hz,1h),6.62-6.67(m,3h),6.74(d,j＝8.0hz,2h),7.04-7.07(m,1h),7.14-7.16(m,1h),7.31(d,j＝7.5hz,1h),8.63(brs,1h)；13cnmrδ:20.9,28.5,40.5,49.8,72.9,109.9,122.3,124.9,128.2,128.7,129.1,130.1,131.1,135.9,140.8,179.3；hr-ms(esi-tof)m/z:calcdforc20h22n2naos{[m+na]+}361.1345,found361.1352。
本实施例制备化合物3be:淡黄色油状物；产率95％；1hnmrδ:2.67-2.69(m,4h),2.98-3.05(m,4h),3.18(d,j＝12.5hz,1h),3.29(d,j＝12.5hz,1h),6.60-6.66(m,3h),6.71-6.74(m,2h),7.06-7.09(m,1h),7.16-7.19(m,1h),7.33(d,j＝7.5hz,1h),8.66(brs,1h)；13cnmrδ:28.5,40.2,49.8,72.9,109.9,114.3(d,jcf＝21.3hz),122.5,124.9,128.9(d,jcf＝20.0hz),131.6,131.7,140.7,161.5(d,jcf＝243.8hz),179.1；hr-ms(esi-tof)m/z:calcdforc19h19fn2naos{[m+na]+}365.1094,found365.1099。
本实施例制备化合物3bg:淡黄色油状物；产率90％；1hnmrδ:1.16(s,9h),2.67(s,4h),3.01-3.03(m,4h),3.20-3.27(m,2h),6.62(d,j＝7.5hz,1h),6.72(d,j＝8.0hz,2h),6.99(d,j＝8.0hz,2h),7.02-7.05(m,1h),7.12-7.15(m,1h),7.26-7.29(m,1h),8.64(brs,1h)；13cnmrδ:28.5,31.2,34.1,40.3,49.7,72.7,109.9,122.2,124.3,124.9,128.7,129.1,129.8,131.2,140.8,149.2,179.3；hr-ms(esi-tof)m/z:calcdforc23h28n2naos{[m+na]+}403.1815,found403.1815。
本实施例制备化合物3bh:淡黄色油状物；产率91％；1hnmrδ:2.68-2.70(m,4h),3.02-3.04(m,4h),3.18(d,j＝12.5hz,1h),3.27(d,j＝10.0hz,1h),6.66(d,j＝7.5hz,1h),6.74(d,j＝8.0hz,1h),6.82-6.86(m,1h),6.91(s,1h),7.06-7.09(m,1h),7.15-7.20(m,2h),7.27-7.30(m,1h),8.53(brs,1h)；13cnmrδ:28.6,40.5,49.8,72.6,110.1,121.4,122.5,124.9,128.6,128.9,129.0,129.1,129.6,133.2,136.8,140.7,178.7；hr-ms(esi-tof)m/z:calcdforc19h19brn2naos{[m+na]+}425.0294,found425.0290。
化合物3aa-1至3bi-1的制备方法同化合物3aa，投料比与化合物3aa相同，可得到化合物3aa-1至3bi-1，反应见表1和表2，但需强调的是本发明的化合物不限于表2所表示的内容。
表2表1为一种3-哌啶或吡咯烷氧化吲哚的化学结构
本实施例制备化合物3aa-1:淡黄色油状物；产率90％；1hnmr(cdcl3,500mhz)δ:1.43(d,j＝5.0hz,2h),1.55-1.60(m,4h),2.68-2.70(m,4h),3.25(d,j＝12.5hz,1h),3.35(d,j＝12.5hz,1h),6.60(d,j＝7.5hz,1h),6.79-6.81(m,2h),6.91-6.94(m,2h),6.96-7.00(m,1h),7.01-7.04(m,1h),7.10-7.14(m,1h),7.35(d,j＝7.5hz,1h),8.69(brs,1h)；13cnmr(cdcl3,125mhz)δ:24.6,26.4,41.1,48.2,72.7,109.6,121.9,125.0,126.2,127.4,128.4,129.5,130.2,134.9,140.9,179.6；hrms(esi-tof)m/z:calcd.forc20h22n2nao[m+na]+:329.1630；found:329.1639。
本实施例制备化合物3ab-1:淡黄色油状物；产率93％；1hnmr(cdcl3,500mhz)δ:1.42(s,2h),1.55-1.58(m,4h),2.13(s,3h),2.68(s,4h),3.22(d,j＝12.5hz,1h),3.31(d,j＝12.5hz,1h),6.60(d,j＝7.5hz,1h),6.68(d,j＝8.0hz,2h),6.73(d,j＝7.5hz,2h),7.01-7.04(m,1h),7.11-7.13(m,1h),7.33(d,j＝7.5hz,1h),8.59(brs,1h)；13cnmr(cdcl3,125mhz)δ:20.9,24.7,26.4,40.6,48.1,72.7,109.6,121.9,125.0,128.1,128.3,129.6,130.1,131.7,135.6,141.0,179.6；hrms(esi-tof)m/z:calcd.forc21h24n2nao[m+na]+:343.1786；found:343.1787。
本实施例制备化合物3ac-1:淡黄色油状物；产率87％；1hnmr(cdcl3,500mhz)δ:1.47(s,2h),1.60-1.62(m,4h),2.72(s,4h),3.24(d,j＝12.5hz,1h),3.33(d,j＝12.5hz,1h),3.66(s,3h),6.52(d,j＝8.5hz,2h),6.65(d,j＝7.5hz,1h),6.74(d,j＝8.5hz,2h),7.06-7.09(m,1h),7.16-7.19(m,1h),7.38(d,j＝7.5hz,1h),8.26(brs,1h)；13cnmr(cdcl3,125mhz)δ:24.7,26.5,40.2,48.2,54.9,72.8,109.6,112.8,122.0,125.1,126.8,128.4,129.7,131.2,140.9,157.9,179.5；hrms(esi-tof)m/z:calcd.forc21h24n2nao2[m+na]+:359.1735；found:359.1731。
本实施例制备化合物3ad-1:淡黄色油状物；产率85％；1hnmr(cdcl3,500mhz)δ:1.45(d,j＝5.0hz,2h),1.58-1.60(m,4h),2.09(s,3h),2.73(s,4h),3.34(s,2h),6.62(d,j＝8.0hz,1h),6.84-6.98(m,5h),7.12-7.15(m,1h),7.20(d,j＝7.5hz,1h),7.82(brs,1h)；13cnmr(cdcl3,125mhz)δ:20.2,24.7,26.5,36.4,48.1,72.2,109.4,122.0,125.0,125.4,126.4,128.4,130.0,130.3,133.7,137.4,140.7,179.5；hrms(esi-tof)m/z:calcd.forc21h24n2nao[m+na]+:343.1786；found:343.1786。
本实施例制备化合物3ae-1:淡黄色油状物；产率92％；1hnmr(cdcl3,500mhz)δ:1.43(d,j＝5.5hz,2h),1.56-1.59(m,4h),2.65-2.70(m,4h),2.22(d,j＝13.0hz,1h),3.31(d,j＝12.5hz,1h),6.59-6.65(m,3h),6.73-6.76(m,2h),7.03-7.06(m,1h),7.13-7.16(m,1h),7.35(d,j＝7.5hz,1h),8.85(brs,1h)；13cnmr(cdcl3,125mhz)δ:24.6,26.4,40.2,48.2,72.8,109.8,114.2(d,jcf＝21.3hz),122.1,125.0,128.6,129.3,131.6,140.9,161.5(d,jcf＝242.5hz),179.6；hrms(esi-tof)m/z:calcd.forc20h21fn2nao[m+na]+:347.1536；found:347.1542。
本实施例制备化合物3af-1:淡黄色油状物；产率90％；1hnmr(cdcl3,500mhz)δ:1.42-1.45(m,2h),1.56-1.61(m,4h),2.69(s,4h),3.19(d,j＝12.5hz,1h),3.31(d,j＝12.0hz,1h),6.61(d,j＝8.0hz,1h),6.68(d,j＝8.5hz,2h),7.03-7.09(m,3h),7.13-7.17(m,1h),7.33(d,j＝7.5hz,1h),7.86(brs,1h)；13cnmr(cdcl3,125mhz)δ:24.6,26.5,40.5,48.2,72.4,109.7,120.5,122.2,125.0,128.7,129.3,130.6,132.0,134.0,140.6,178.8；hrms(esi-tof)m/z:calcd.forc20h21brn2nao[m+na]+:407.0735；found:407.0746。
本实施例制备化合物3ag-1:淡黄色油状物；产率93％；1hnmr(cdcl3,500mhz)δ:1.43(d,j＝5.0hz,2h),1.55-1.60(m,4h),2.65-2.70(m,4h),3.21(d,j＝12.5hz,1h),3.31(d,j＝12.5hz,1h),6.64(d,j＝8.0hz,1h),6.72(d,j＝8.5hz,2h),6.89(d,j＝8.5hz,2h),7.02-7.06(m,1h),7.13-7.16(m,1h),7.33(d,j＝7.0hz,1h),8.76(brs,1h)；13cnmr(cdcl3,125mhz)δ:24.6,26.4,40.4,48.1,72.6,109.8,122.1,125.0,127.5,128.6,129.2,131.6,132.2,133.4,140.8,179.5；hrms(esi-tof)m/z:calcd.forc20h21cln2nao[m+na]+:363.1240；found:363.1240。
本实施例制备化合物3ah-1:淡黄色油状物；产率89％；1hnmr(cdcl3,500mhz)δ:1.44(s,2h),1.57-1.59(m,4h),2.69(d,j＝5.0hz,4h),3.25(d,j＝12.5hz,1h),3.33(d,j＝12.5hz,1h),6.50(d,j＝10.0hz,1h),6.61-6.65(m,2h),6.68-6.71(m,1h),6.87-6.92(m,1h),7.02-7.05(m,1h),7.12-7.16(m,1h),7.32(d,j＝7.0hz,1h),8.80(brs,1h)；13cnmr(cdcl3,125mhz)δ:24.7,26.5,40.8,48.2,72.5,109.9,113.2,113.4,117.0(d,jcf＝21.3hz),122.2,125.0,126.1,128.7,128.8,129.2,137.6,141.0,162.0(d,jcf＝243.8hz),179.5；hrms(esi-tof)m/z:calcd.forc20h21fn2nao[m+na]+:347.1536；found:347.1538。
本实施例制备化合物3ai-1:淡黄色油状物；产率87％；1hnmr(cdcl3,500mhz)δ:1.43-1.46(m,2h),1.58(d,j＝6.0hz,4h),2.70(s,4h),3.22(d,j＝15.5hz,1h),3.29(d,j＝15.5hz,1h),6.65(d,j＝9.5hz,1h),6.77-6.85(m,2h),6.93(s,1h),7.04-7.08(m,1h),7.13-7.18(m,2h),7.32(d,j＝9.0hz,1h),8.51(brs,1h)；13cnmr(cdcl3,125mhz)δ:24.6,26.4,40.7,48.2,72.4,109.8,121.3,122.2,125.0,128.7,128.9,129.0,129.1,129.4,133.2,137.4,140.8,179.1；hrms(esi-tof)m/z:calcd.forc20h21brn2nao[m+na]+:407.0735；found:407.0741。
本实施例制备化合物3ba-1:淡黄色油状物；产率85％；1hnmr(cdcl3,500mhz)δ:1.22-1.27(m,4h),2.74-2.78(m,2h),2.92-2.95(m,2h),3.30(d,j＝12.5hz,1h),3.50(d,j＝12.5hz,1h),6.59(d,j＝7.5hz,1h),6.74-6.81(m,1h),6.85(d,j＝7.0hz,1h),6.96-7.04(m,4h),7.10-7.12(m,1h),7.39(d,j＝7.5hz,1h),8.22(brs,1h)；13cnmr(cdcl3,125mhz)δ:23.2,42.5,47.0,70.2,109.5,122.1,125.0,126.3,127.4,127.5,128.5,129.8,130.2,130.4,134.9,140.6,179.4；hrms(esi-tof)m/z:calcd.forc19h20n2nao[m+na]+:315.1473；found:315.1477。
本实施例制备化合物3bb-1:淡黄色油状物；产率90％；1hnmr(cdcl3,500mhz)δ:1.73(s,4h),2.13(s,3h),2.73-2.76(m,2h),2.89-2.91(m,2h),3.27(d,j＝12.5hz,1h),3.44(d,j＝12.5hz,1h),6.60(d,j＝7.5hz,1h),6.71-6.76(m,4h),6.99-7.03(m,1h),7.09-7.13(m,1h),7.36(d,j＝7.0hz,1h),8.83(brs,1h)；13cnmr(cdcl3,125mhz)δ:20.9,23.2,42.0,46.9,70.2,109.7,122.0,124.9,128.2,128.4,129.8,130.0,131.7,135.6,140.8,179.8；hrms(esi-tof)m/z:calcd.forc20h22n2nao[m+na]+:329.1630；found:329.1630。
本实施例制备化合物3bc-1:淡黄色油状物；产率85％；1hnmr(cdcl3,500mhz)δ:1.78(s,4h),2.77-2.79(m,2h),2.92-2.94(m,2h),3.29(d,j＝12.5hz,1h),3.46(d,j＝13.0hz,1h),3.65(s,3h),6.52(d,j＝8.5hz,2h),6.66(d,j＝7.5hz,1h),6.78(d,j＝9.0hz,2h),7.05-7.08(m,1h),7.15-7.18(m,1h),7.41(d,j＝7.0hz,1h),8.59(brs,1h)；13cnmr(cdcl3,125mhz)δ:23.3,41.7,47.0,54.9,70.4,109.7,112.8,122.1,125.0,126.9,128.5,130.0,131.2,140.8,158.0,179.8；hrms(esi-tof)m/z:calcd.forc20h22n2nao2[m+na]+:345.1579；found:345.1579。
本实施例制备化合物3be-1:淡黄色油状物；产率87％；1hnmr(cdcl3,500mhz)δ:1.74(s,4h),2.73-2.75(m,2h),2.89-2.91(m,2h),3.27(d,j＝13.0hz,1h),3.45(d,j＝12.5hz,1h),6.60-6.65(m,3h),6.77-6.80(m,2h),7.02-7.05(m,1h),7.12-7.16(m,1h),7.37(d,j＝7.0hz,1h),8.90(brs,1h)；13cnmr(cdcl3,125mhz)δ:23.2,41.6,46.9,70.2,109.8,114.2(d,jcf＝21.3hz),122.2,124.9,128.7,129.5,131.6,140.7,161.5(d,jcf＝243.8hz),179.8；hrms(esi-tof)m/z:calcd.forc19h19fn2nao[m+na]+:333.1379；found:333.1387。
本实施例制备化合物3bf-1:淡黄色油状物；产率90％；1hnmr(cdcl3,500mhz)δ:1.75(s,4h),2.73-2.75(m,2h),2.89-2.92(m,2h),3.25(d,j＝12.5hz,1h),3.43(d,j＝12.5hz,1h),6.63(d,j＝8.0hz,1h),6.71(d,j＝8.0hz,2h),7.02-7.05(m,1h),7.08(d,j＝8.0hz,2h),7.13-7.16(m,1h),7.36(d,j＝7.5hz,1h),8.54(brs,1h)；13cnmr(cdcl3,125mhz)δ:23.3,41.9,47.0,70.1,109.9,120.6,122.3,124.9,128.8,129.5,130.6,132.0,133.9,140.6,179.4；hrms(esi-tof)m/z:calcd.forc19h19brn2nao[m+na]+:393.0578；found:393.0571。
本实施例制备化合物3bi-1:淡黄色油状物；1hnmr(cdcl3,500mhz)δ:1.76(s,4h),2.74-2.77(m,2h),2.92-2.94(m,2h),3.26(d,j＝13.0hz,1h),3.44(d,j＝12.5hz,1h),6.63(d,j＝7.5hz,1h),6.81-6.87(m,2h),6.96(s,1h),7.04-7.07(m,1h),7.14-7.17(m,2h),7.36(d,j＝7.5hz,1h),8.11(brs,1h)；13cnmr(cdcl3,125mhz)δ:23.3,42.1,47.0,69.9,109.7,121.4,122.3,125.0,128.8,129.0,129.4,129.5,133.2,137.3,140.4,179.0；hrms(esi-tof)m/z:calcd.forc19h19brn2nao[m+na]+:393.0578；found:393.0582。