磺酰胺类化合物凭借其卓越的生物活性[1]和反应活性[2-5], 在药物化学领域占据着举足轻重的地位. 作为药物分子骨架的核心组成部分, 磺酰胺是构成一系列重要抗菌药物的结构基础[6], 这些药物在临床应用中展现出显著的药用价值(图1). 此外, N-芳基磺酰胺同样在农 药[7-8]、增塑剂[9]、染料[10]以及高分子材料等领域发挥着不可替代的作用. 鉴于其广泛的应用前景, 开发高效、通用的磺酰胺合成方法日益受到合成化学家们的广泛关注. 早期, 磺酰胺的合成主要依赖于磺酰氯与胺类化合物的亲核取代反应, 然而磺酰氯类化合物的制备困难、对湿度敏感以及反应条件苛刻等缺点, 严重限制了其在实际应用中的价值[32]. 在过去的几十年中, 过渡金属钯(Pd)[11-17]、铜(Cu)[18-20]、镍(Ni)[21]催化芳基亲电试剂与磺酰胺的交叉偶联反应, 已成为合成芳基磺酰胺的有效策略[22], 并在有机合成领域取得了显著进展(Scheme 1, A). 然而, 这些基于过渡金属催化的合成策略也存在一定的局限性. 如铜催化芳基硼酸与磺酰胺的C—N偶联反应, 通常需要使用大量的铜催化剂, 反应温度高, 底物范围有限, 且难以实现低活性芳基氯代物的C—N偶联. 钯催化虽然高效, 但通常需要配合复杂结构的膦配体和低溶解度的无机强碱, 导致底物的官能团兼容性差, 而使用丰产金属镍催化剂代替贵金属体系, 实现芳基(杂环芳基)卤代烃的磺酰胺化反应, 同样也依赖于富电子膦配体. 目前, 尽管过渡金属催化的偶联反应在有机合成中获得了突破性的发展, 但是这些反应主要依赖于特定的膦配体调控金属价态, 以及烷氧基醇盐和低溶解度无机强碱的使用, 导致官能团兼容性差, 并存在由此引起的固体废物后处理难题和难于在流动化学中应用等问题. 因此, 发展高效、绿色、经济且底物适用性广的N-芳基磺酰胺合成方法仍具有重要的研究意义.
图式1 传统过渡金属催化合成N-芳基磺酰胺、光氧化还原与镍协同催化的C—N偶联合成N-芳基磺酰胺及光激发丰产金属镍催化卤代芳烃与磺酰胺的C—N偶联反应Scheme 1 Traditional transition metal-catalyzed synthesis of N-arylsulfonamides, photoredox with nickel catalyzed C—N coupling for synthesis of N-arylsulfonamides, and photoexcited earth-abundant nickel-catalyzed C—N coupling of aryl halides with sulfonamides |
可见光激发的化学反应因其能在相对温和条件下实现转化而备受合成化学界关注[23]. 近年来, 将光氧化还原与镍催化相结合, 为推进有机合成中的交叉偶联反应提供了一种新策略(Scheme 1, B)[24-25]. 传统光氧化还原催化反应通常需要使用昂贵的光催化剂, 且部分金属催化剂具有毒性, 无法适用于大规模工业生产的要求; 同时反应底物局限于芳基溴代物, 范围有限. 单金属光催化已成为构建碳-氧和碳-氮键的重要合成策略[26-29], 在该过程中, 过渡金属配合物不仅能够捕获光能, 还可通过单一催化循环促进化学键的形成与断裂, 从而有效避免传统光催化体系中因外加光催化剂而引发的副反应, 同时提高反应的官能团兼容性[30]. 我们的研究兴趣主要聚焦于无需外加光催化剂、利用单一过渡金属实现光催化C—O/N偶联反应[31-36]. 在前期研究工作中[31-36], 我们开发了通过光解Ni(II)配合物生成Ni(I)物种, 进而实现Ni(I)-Ni(III)催化循环的C—O/N偶联反应. 基于这一认识, 我们小组发展了一系列无需外加光催化剂、镍催化的芳基亲电试剂与不同N-亲核试剂的C—N偶联反应[31-36]. 其中, 对于活性较低的芳基氯化物与磺酰胺也进行了初步探索, 但是由于芳基氯化物的活性较低, 目前底物的适用性仍然有一定的局限[36]. 为了解决底物实用性的问题, 本工作发展了一种高效的光催化合成N-芳基磺酰胺的方法, 通过光直接激发Ni(II)-联吡啶络合物, 产生Ni(I)活性物种启动反应, 实现多种(杂)芳基溴/碘化物与各种类型磺酰胺的C—N偶联反应. 该催化反应无需外加光敏剂, 以可溶性三级胺作碱, 底物适用范围广泛, 也能够实现生物活性分子后期的官能团化修饰, 并且在克级反应中, 依然能够保持高效的反应产率, 为合成重要的芳基磺酰胺提供了一种可行的替代方案(Scheme 1, C).
1 结果与讨论
在初步考察中, 选择以3,5-二甲基溴苯1 (2.0 equiv.)和4-甲基苯磺酰胺(TsNH2, 2) (1.0 equiv.)为底物进行C(sp2)—N偶联反应的条件探索(表1). 镍催化剂对反应的进行起着至关重要的作用, 选择4,4'-二甲氧基- 2,2'-联吡啶(5 mol%)作为配体, 对反应所用的镍催化剂进行了筛选. 常用的二价镍盐如氯化镍(NiCl2)、溴化镍(NiBr2)、碘化镍(NiI2)以及醋酸镍(Ni(OAc)2), 催化效果不是非常理想. 当以NiBr2•glyme作为催化剂时反应效果最佳, 在紫光(390~395 nm)的照射下, C(sp2)—N偶联可以高效进行, 分离产率为88%(表1, Entries 1~7). 碱对C(sp2)—N偶联反应的效率存在显著影响, 因此本文对一系列常用有机碱与无机碱开展了筛选研究. 研究发现, 有机碱的作用明显强于无机碱, 其中1,4-二氮杂二环(DABSO)、4-二甲氨基吡啶(DMAP)作碱时, 只能得到<10%的收率; 四甲基胍(TMG)、2-叔丁基-1,1,3,3-四甲基胍(BTMG)、三乙胺(TEA)、N,N-二异丙基乙胺(DIPEA)、N-甲基二环己基胺(N,N-Dicyclohexylmethyl- amine)或1,8-二氮杂二环十一碳-7-烯(DBU)作碱时, 产率仅为25%~77%; 碳酸钾(K2CO3)、甲醇钠(MeONa)或磷酸钾(K3PO4)等无机碱只得到痕量产物. 其中当选用7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯(MTBD)时, 反应具有最显著的效果, 以92%的产率得到偶联产物(表1, Entries 8~14). 同样, 配体对该反应同样起到关键作用; 在不添加联吡啶配体时, 反应效率大幅降低. 以无取代基的2,2'-联吡啶为配体时, 能得到78%的分离收率; 相比于不带取代基的配体, 当4,4'-位的取代基为给电子取代基时, 如甲基、甲氧基、叔丁基或氨基等, 产率均有明显的提高; 而以4,4'-二氨基-2,2'-联吡啶作为配体时, 也有非常好的产率(90%). 同样, 使用4,4'-二甲氧基-2,2'-联吡啶(d-OMe- bpy)为配体时, 产率最高能达到92%. 与4,4'-二氨基- 2,2'-联吡啶配体相比, 4,4'-二甲氧基-2,2'-联吡啶在反应体系中溶解性更好. 溶剂对反应的顺利进行也有明显的影响, 因此对溶剂进行了测试. 甲苯(Toluene)作为溶剂时, 只有21%的产率. 选用四氢呋喃(THF)、1,4-二氧六环(1,4-dioxane)、乙腈(MeCN)和二甲基亚砜(DMSO)作为溶剂时, 只能得到中等收率的产物, 2-MeTHF/t-BuOH (V∶V=1∶4)混合溶剂被证明是该C(sp2)—N偶联反应的最佳选择. 进一步优化表明, 光源也发挥了重要作用. 分别将反应置于紫外(360~365 nm)、紫光(390~395 nm)、蓝光(460~465 nm)、绿光(530~535 nm)和白光的照射下进行反应. 实验结果显示, 在短波长紫外区(365~370 nm)光照下, 仅能检测到有少许产物的生成; 在蓝光(460~465 nm)照射下, 仅有16%的反应产率; 在其他波长光源条件下, 如绿光和白光, 则均未监测到目标产物的生成, 只有在紫光(390~935 nm)照射下, 能获得最高产率(表1, Entries 15~18). 值得注意的是, 温度在反应中也起着重要作用. 研究发现, 室温下很难获得C(sp2)—N偶联产物. 最后, 对照实验表明, 在没有有机碱、配体和光的情况下, 无法获得目标偶联产物(表1, Entries 19~23).
表1 反应条件优化aTable 1 Optimization of reaction conditions |
| Entry | Deviation from the standard conditions | Yield/% |
|---|---|---|
| 1 | Standard conditions | 92 (88)b |
| 2 | NiCl2 | 67 |
| 3 | NiI2 | 62 |
| 4 | Ni(OAc)2 | 38 |
| 5 | NiBr2•dme | 79 |
| 6 | NiBr2 | 83 |
| 7 | NiCl2•dme | 85 |
| 8 | DABSO | 7 |
| 9 | BTMG | 67 |
| 10 | DIPEA | 25 |
| 11 | DBU | 77 |
| 12 | DMAP | 9 |
| 13 | K2CO3 | N.R. |
| 14 | MeONa | N.R. |
| 15 | Blue LEDs (460~465 nm) | 21 |
| 16 | UV (365~370 nm) | N.R. |
| 17 | Green LEDs (530~535 nm) | N.R. |
| 18 | White LEDs | N.R. |
| 19 | Standard conditions, without ligand | 13 |
| 20 | Standard conditions, without Ni(cod)2 | N.R. |
| 21 | Standard conditions, without base | N.R. |
| 22 | Standard conditions, light, r.t. | N.R. |
| 23 | Standard conditions, without light, heat to 80 ℃ | N.R. |
a Standard reaction conditions: 5-bromo-1,3-xylene (0.2 mmol), p-toluenesulfonamide (1.5 equiv., 0.3 mmol), NiBr2•glyme (5.0 mol%), 4-methoxy-2-(4-methoxy- pyridin-2-yl)pyridine (5.0 mol%, d-OMebpy), MTBD (1.5 equiv., 0.3 mmol), 2-Me-THF/tBuOH (V∶V=1∶4, 1.5 mL), purple LEDs (390~395 nm), 70 ℃, Ar, 12 h. b Isolated yield. Yields determined by 1H NMR analysis using 1,3-benzodioxole as internal standard. |
通过以上反应条件的筛选, 确定了该C(sp2)—N偶联反应的最佳反应条件为: 以NiBr2•glyme (0.01 mmol, 5.0 mol%)为催化剂, 4,4'-二甲氧基-2,2'-联吡啶为配体(0.01 mmol, 5.0 mol%), 2-甲基四氢呋喃/叔丁醇(V∶V=1∶4, 1.5 mL)为溶剂, MTBD (0.3 mmol, 1.5 equiv)为碱, 在氩气氛围下, 在光照辐射条件下, 反应的温度约为70 ℃, 反应12 h.
在最佳反应条件下, 对反应的底物适用范围和官能团耐受性进行了考察(表2). 首先, 对芳基溴代物的反应活性进行考察. 结果表明, 对于不同电子、位阻效应的卤代芳烃都具有良好的适用范围. 如3,5位取代溴代芳烃, 对于甲基、叔丁基、三氟甲基、三氟甲氧基、氰基、卤素或酯基等官能团(3~10), 无论3,5位取代基官能团是否相同, 都能取得良好的产率. 同样, 4-取代溴苯, 除了含常见官能团的底物(11~21)具有高效的反应活性外, 对于大位阻官能团如N-甲基甲酰胺基、N-甲基-N-甲醛氨基、吡咯啉磺酰基和反式-4-丙基环己基取代的底物(22~25), 也分别得到78%、67%、90%和83%的产率. 此外, 3-位、2,4-二位、3,4-二位及3,4,5-三位等不同取代基取代的芳基溴代烃, 反应也具有良好的收率. 另外, 烷基甲基磺酰胺与芳基4-甲基苯磺酰胺的反应活性相似, 且烷基甲基磺酰胺的产物更易于分离纯化. 因此以甲基磺酰胺作为底物, 与含醛酮类基团的化合物反应, 也能得到高效的反应收率(38, 39), 4-溴苯甲醚、2,6-二甲基-4-溴苯甲醚及2-(1-金刚烷基)-4-溴苯甲醚这类富电子的低活性溴代芳烃(41, 49, 50), 也能以良好的收率获得C(sp2)—N偶联产物. 甲基、异丙基、甲氧基、异丙氧基、甲酸甲酯基、氟或氯邻位取代的溴代芳烃(42~48), 以中等及以上的产率实现C(sp2)—N偶联. 杂环溴代芳烃作为一类重要的化合物, 是许多重要药物分子的结构单元. 因此, 对杂环溴代芳烃的底物范围也进行了测试. 3-溴吡啶及5-氯-3-溴吡啶、5-甲基-3-溴吡啶(51~53)能与4-甲基苯磺酰胺进行高效C(sp2)—N反应. 5-三氟甲基-3-溴吡啶和6-溴-3H-异苯并呋喃-1-酮由于受到电子效应的影响, 仅得到55%和70%的收率(54, 69). 嘧啶类溴代芳烃的反应收率普遍较低, 仅有40%的分离收率(70, 71). 将4-甲基苯磺酰胺替换为更易于纯化的甲基磺酰胺, 吡啶、喹啉、吲哚、苯并呋喃及苯并噻吩等溴代杂环芳烃底物(55~68)均能高效进行偶联反应. 同样, 含三氟甲基、甲氧基、氟或氯取代基的溴代吡啶(55~59), 都能获得中等及以上的良好收率. 实验表明, 该反应对于杂环溴代底物有良好的兼容性, 将为化合物中杂原子的引入提供了新途径.
表2 芳基溴化物的底物扩展aTable 2 Scope of aryl bromides |
 |
a Reaction conditions: Aryl bromides (0.2 mmol), sulfonamide (1.5 equiv., 0.3 mmol), NiBr2•glyme (5.0 mol%), 4-methoxy-2-(4-methoxypyridin-2-yl)pyridine (5.0 mol%, d-OMebpy), MTBD (1.5 equiv., 0.3 mmol), 2-Me-THF/tBuOH (V∶V=1∶4, 1.5 mL), purple LEDs (390~395 nm), 70 ℃C, Ar, 12 h. Isolated yield. |
为了进一步拓展卤代芳烃的应用范围, 选择4-碘溴苯作为反应底物, 反应选择性地以高产率获得C(sp2)—N偶联产物, 而非所预期的与芳基溴代物的偶联产物. 实验表明, 芳基碘代物在标准条件下具有高反应活性. 因此, 以4-甲基苯磺酰胺为模板, 考察了不同取代芳基碘代物的反应活性(表3). 4-位取代的碘代芳烃能以高产率得到目标产物(11, 13, 18), 其中含富电子基团的4-碘苯甲醚, 能以75%的分离收率获得芳基磺酰胺化产物. 初步的实验结果表明, 碘代芳烃在最优反应条件下的反应活性更高. 接着, 对2-位取代的芳基碘代物反应活性进行考察, 含卤素、甲基、异丙基、酯基、三氟甲氧基和甲氧基的底物都能以中等及以上的产率得到偶联产物(47, 76~81). 对于富电子且邻位存在位阻的2,4-二甲氧基碘苯, 能以58%的分离收率得到目标化合物82. 杂环碘代物如3-碘吡啶能得到与3-溴吡啶相近收率, 同时实现溴代芳烃中未能实现的化合物83的合成. 用甲基磺酰胺替代TsNH2时, 也能合成相应的目标化合物46. 在温和条件下实现的碘代芳烃N-芳基磺酰胺化反应, 有效解决了2-取代芳基溴代物活性低的问题, 进一步扩展了2-取代N-芳基磺酰胺产物的类型, 提升了该反应方法的适用性.
表3 芳基碘化物的底物扩展aTable 3 Scope of aryl iodides |
 |
a Reaction conditions: aryl iodides (0.2 mmol), 4-methylbenzenesulfonamide (1.5 equiv., 0.3 mmol), NiBr2•glyme (5.0 mol %), d-OMebpy (5.0 mol%), MTBD (1.5 equiv., 0.3 mmol), 2-Me-THF/tBuOH (V∶V=1∶4, 1.5 mL), purple LEDs (390~395 nm), 70 ℃, Ar, 12 h. Isolated yield. |
受这些结果的鼓舞, 进一步考察了磺酰胺的底物普适性, 如表4所示. 多种官能团取代的磺酰胺均能与溴代芳烃顺利发生C(sp2)—N偶联反应, 以高产率得到目标磺酰胺化产物. 该方法兼容多种类型的磺酰胺, 包括含供电子基、中性基团、吸电子基的芳基磺酰胺以及脂肪族磺酰胺, 均能以良好收率生成相应的C(sp2)—N偶联产物(84~97). 卤素、二氟甲氧基及甲氧基取代的磺酰胺也表现出优异的反应产率(85, 86, 88, 89). 2-甲基磺酰胺与4-甲基苯磺酰胺为底物的分离收率分别为81%和90%, 表明N-亲核试剂的邻位位阻效应对反应无显著影响. 受缺电子基官能团影响, 4-三氟甲基苯磺酰胺仅有中等收率(87). 氯甲酸苄酯保护的磺酰胺, 同样能以87%的分离产率得到相应的产物(90). 环丙烷磺酰胺和叔丁基磺酰胺等脂肪族磺酰胺也能克服位阻效应, 获得良好的反应收率(95, 97). 基于这些实验结果, 不同取代基的苯基、杂芳基磺酰胺、脂肪族磺酰胺都能高效地转化为目标C(sp2)—N偶联产物, 为合成具有重要应用价值的N-芳基磺酰胺类化合物提供了有效途径, 使该方法在药物化学中具有更加重要的应用价值.
表4 磺酰胺的底物扩展aTable 4 Scope of sulfonamides |
 |
a Reaction conditions: 3-fluorobromobenzene (0.2 mmol), sulfonamides (1.5 equiv., 0.3 mmol), NiBr2•glyme (5.0 mol%), d-OMebpy (5.0 mol%), MTBD (1.5 equiv., 0.3 mmol), 2-Me-THF/tBuOH (V∶V=1∶4, 1.5 mL), purple LEDs (390~395 nm), 70 ℃, Ar, 12 h. Isolated yield. |
为了进一步验证该实验方法的应用价值, 将其应用于溴代生物活性分子的后期修饰, 如Scheme 2所示. 雌酚酮作为重要的医药中间体, 通过过渡金属催化实现后期官能团化. 为了检验该方法是否可以具有很好的应用性, 在标准条件下, 溴代雌酚酮与甲基磺酰胺进行反应, 实现了雌酚酮的N-芳基磺酰胺化反应, 获得了87%的目标化合物(98), 表明该方法在药物分子修饰中具有重要应用前景. 为了验证反应在克级规模制备中的效率, 将溴代雌酚酮的N-芳基磺酰胺化反应放大20倍. 以溴代雌酚酮(4.0 mmol, 1.30 g)和甲基磺酰胺(6 mmol, 0.57 g)为原料, 在5 mol%的NiBr2•glyme和4,4'-二甲氧基- 2,2'-联吡啶作为催化剂前体, 1.5 equiv.的MTBD为碱, 在390~395 nm光照射下反应36 h, 得到95%的分离产物. 这些实例表明, 利用光激发d-OMebpy-Ni(II)-络合物生成Ni(I)物种的方法, 能以良好产率实现芳基卤化物与多种磺酰胺的芳基磺酰胺化反应. 该策略具有前所未有的底物适用范围, 展现了其在不同芳基磺酰胺合成方面的巨大潜力, 并为制备芳基磺酰胺提供了一种高效可行的途径.
基于我们课题组前期对单原子丰产金属镍催化C(sp2)-杂原子键偶联反应的研究基础[31-36], 推测该反应遵循Ni(I)/Ni(III)催化循环路径, 并对其可能的反应机理进行了阐释(Scheme 3). d-OMebpy-NiBr2配合物I在390~395 nm紫光激发下生成Ni(I)物种II, 该物种与溴代芳烃发生氧化加成得到Ni(III)芳基中间体III. 随后, 磺酰胺与镍配位, 在有机碱MTBD的作用下去质子化, 生成Ar-Ni(III)-NSO2R物种IV. 该物种通过还原消除生成芳基磺酰胺产物, 并再生活性Ni(I)物种以进入下一催化循环. 在该C—N偶联反应中, 可能是由于Ni(III)和Ni(I)的歧化反应形成了非循环、无催化活性的Ni(II)物种, 因此需要光照才能转化为活性Ni(I)物种II.
2 结论
发展了一种无外加光催化剂, 光激发丰产金属镍催化高效合成(杂)芳基磺酰胺的方法. 该方法在温和的反应条件下, 无需外加光敏剂, 使用温和、可溶性的有机胺作为碱, 提高了底物官能团的兼容性, 反应后处理简单方便, 实现了不同类型的N-芳基(杂环芳基)磺酰胺类化合物的合成, 底物范围宽广, 解决了邻位溴代芳烃的 C—N偶联反应困难的问题. 此外, 该方法能够有效用于生物活性分子的后期官能团修饰, 进一步证明了该方法的有效性和实用性, 并且在克级规模反应中, 依然能够保持高效的反应产率, 有效降低反应成本, 为芳基磺酰胺的合成开辟了新途径.
3 实验部分
3.1 仪器与试剂
1H NMR、13C NMR、19F NMR谱图使用Bruker 400 MHz核磁共振仪测定; 高分辨质谱数据由Apex IV FTMS (ESI)型高分辨质谱仪测定; 实验中所用到的溶剂(1,4-二氧六环、四氢呋喃、正戊烷、N,N-二甲基甲酰胺等)购买于国药化学试剂有限公司, 后续均经过无水无氧处理. 实验所用药品试剂(溴代芳烃、酚、双-(1,5-环辛二烯镍、2-叔丁基四甲基胍等)均为商品试剂, 没有经过进一步处理直接使用. 实验中所使用的薄层色谱(TLC)板为F-254薄层色谱板, 快速柱层析所用薄层层析硅胶(H, 200~300目)和(H, 300~400目)购自于青岛海洋化工有限公司. 薄层色谱板用ZF-254紫外分析仪进行监测, 并配合磷钼酸、碘显色. 石油醚、乙酸乙酯和二氯甲烷等溶剂均为分析纯.
3.2 芳基磺酰胺产物的合成
向10 mL的厚壁耐压反应管中加入NiBr2•glyme (3.1 mg)和4,4'-二甲氧基-2,2'-联吡啶(2.2 mg), 用双排管将反应管置换为氩气氛围, 加入1.5 mL混合溶剂 (2-MeTHF/t-BuOH, V∶V=1∶4), 室温搅拌30 min. 催化剂预搅伴完成后, 加入芳基卤代烃(0.2 mmol)、磺酰胺(0.3 mmol)和MTBD (0.3 mmol, 46.0 mg), 光照反应12 h. 利用TLC监测反应进程. 反应结束后, 用旋转蒸发仪直接浓缩, 除去反应液中的溶剂, 残余物通过柱层析分离纯化(石油醚/乙酸乙酯, V∶V=10∶1~5∶1).
N-(3,5-二甲基苯基)-4-甲基苯磺酰胺(3): 产率88%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.67 (d, J=8.0, 2H), 7.23 (d, J=8.0, 2H), 6.73 (s, 1H), 6.68 (s, 2H), 6.49 (br, 1H, NH), 2.38 (s, 3H), 2.22 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 143.80, 139.07, 136.59, 136.33, 129.70, 127.38, 126.89, 118.85, 21.60, 21.31; HRMS (ESI) calcd for C15H17NO2SNa [M+Na]+ 298.0872, found 298.0867.
N-(3,5-二叔丁基苯基)-4-甲基苯磺酰胺(4): 产率86%, 黄色固体. 1H NMR (400 MHz, CDCl3) δ: 7.62 (d, J=7.6 Hz, 2H), 7.21 (d, J=8.0 Hz, 2H), 7.15 (s, 1H), 6.81 (s, 2H), 6.37 (br, 1H, NH), 2.37 (s, 3H), 1.22 (s, 18H); 13C NMR (100 MHz, CDCl3) δ: 151.96, 143.64, 136.33, 136.05, 129.49, 127.64, 119.25, 116.78, 34.90, 31.34, 21.54; HRMS (ESI) calcd for C21H29NO2SNa [M+Na]+ 382.1811, found 382.1804.
N-(3,5-双(三氟甲基)苯基)-4-甲基苯磺酰胺(5): 产率82%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.72 (d, J=7.6 Hz, 2H), 7.58 (s, 1H), 7.52 (s, 2H), 7.30 (d, J=7.6 Hz, 2H), 7.06 (br, 1H, NH), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 145.28, 138.66, 135.21, 132.96 (q, J=33.5 Hz), 130.28, 127.45, 122.92 (q, J=270.8 Hz), 119.92 (q, J=3.3 Hz), 118.28 (q, J=3.9 Hz), 21.68; 19F NMR (376 MHz, CDCl3) δ: －63.22 (s, 6F); HRMS (ESI) calcd for C15H11F6NO2SNa [M+Na]+ 406.0307, found 406.0303.
N-(3,5-二甲氧基苯基)-4-甲基苯磺酰胺(6): 产率80%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.71 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.0 Hz, 2H), 6.82 (br, 1H, NH), 6.25 (s, 2H), 6.18 (s, 1H), 3.70 (s, 6H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 161.26, 144.01, 138.67, 136.11, 129.76, 127.43, 99.01, 97.19, 55.44, 21.58; HRMS (ESI) calcd for C15H17NO4SNa [M+Na]+ 330.0770, found 330.0772.
N-(3-氰基-5-甲基苯基)-4-甲基苯磺酰胺(7): 产率60%, 黄色固体. 1H NMR (400 MHz, CDCl3) δ: 7.68 (d, J=8.4 Hz, 2H), 7.28 (d, J=8.4 Hz, 2H), 7.19 (s, 1H), 7.14 (s, 2H), 6.85 (br, 1H, NH), 2.41 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.64, 140.92, 137.57, 135.51, 130.01, 129.12, 127.22, 125.74, 120.61, 118.27, 113.07, 21.61, 21.19; HRMS (ESI) calcd for C15H14N2- O2SNa [M+Na]+ 309.0668, found 309.0664.
N-(3-氟-5-甲氧基苯基)-4-甲基苯磺酰胺(8): 产率94%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.72 (d, J=8.0 Hz, 2H), 7.26 (d, J=8.0 Hz, 2H), 7.01 (br, 1H, NH), 6.44 (dt, J=10.4, 2.0 Hz, 2H), 6.33 (dt, J=10.4, 2.4 Hz, 1H), 3.72 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.89 (d, J=243.3 Hz), 161.48 (d, J=12.8 Hz), 144.41, 138.82 (d, J=13.2 Hz), 135.97, 129.95, 127.44, 102.24, 100.27 (d, J=25.8 Hz), 98.34 (d, J=25.1 Hz,), 55.75, 21.70; 19F NMR (376 MHz, CDCl3) δ: －109.91 (t, J=9.4 Hz, 1F); HRMS (ESI) calcd for C14H14FNO3SNa [M+Na]+ 318.0571, found 318.0568.
N-(3-氯-5-甲氧基苯基)-4-甲基苯磺酰胺(9): 产率86%, 灰白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.72 (d, J=8.4 Hz, 2H), 7.26 (d, J=8.0 Hz, 2H), 7.19 (br, 1H, NH), 6.67 (t, J=2.0 Hz, 1H), 6.60 (t, J=2.0 Hz, 2H), 3.72 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 160.91, 144.45, 138.71, 135.87, 135.55, 129.99, 127.43, 113.01, 111.09, 104.97, 55.72, 21.70; HRMS (ESI) calcd for C14H14ClNO3SNa [M+Na]+ 334.0275, found 334.0272.
3-((4-甲基苯基)磺酰胺基)-5-(三氟甲基)苯甲酸甲酯(10): 产率72%, 黄色固体. 1H NMR (400 MHz, CDCl3) δ: 8.00 (s, 1H), 7.89 (s, 1H), 7.71 (d, J=8.0 Hz, 2H), 7.63 (s, 1H), 7.26 (d, J=8.0 Hz, 2H), 3.94 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 165.37, 144.86, 138.20, 135.61, 132.42 (q, J=33.2 Hz), 130.13, 127.43, 124.47, 122.63 (q, J=3.8 Hz), 121.12 (q, J=3.6 Hz), 52.97, 21.70; 19F NMR (376 MHz, CDCl3) δ: －63.00 (s, 3F); HRMS (ESI) calcd for C16H14F3NO4SNa [M+Na]+ 396.0488, found 396.0482.
N-(4-溴苯基)-4-甲基苯磺酰胺(11): 产率50%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J=8.4 Hz, 2H), 7.35 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.0 Hz, 2H), 6.95 (d, J=8.4 Hz, 2H), 6.69 (br, 1H, NH), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.37, 135.81, 135.75, 132.49, 129.94, 127.39, 123.13, 118.61, 21.70; HRMS (ESI) calcd for C13H12BrNO2SNa [M+Na]+ 347.9664, found 347.9663.
N-(4-氯苯基)-4-甲基苯磺酰胺(12): 产率87%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.01 (d, J=8.8 Hz, 2H), 6.71 (br, 1H, NH), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.32, 135.91, 135.21, 131.18, 129.91, 129.58, 127.40, 123.22, 21.70; HRMS (ESI) calcd for C13H12ClNO2SNa [M+Na]+ 304.0169, found 304.0168.
N-(4-氟苯基)-4-甲基苯磺酰胺(13): 产率67%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J=8.4 Hz, 2H), 7.31 (br, 1H, NH), 7.22 (d, J=8.0 Hz, 2H), 7.06 (dd, J=8.8, 4.8 Hz, 2H), 6.90 (t, J=8.8 Hz, 2H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 160.69 (d, J=243.6 Hz), 144.14, 135.81, 132.53, 129.81, 127.42, 124.55 (d, J=8.4 Hz), 116.15 (d, J=22.6 Hz), 21.62; 19F NMR (376 MHz, CDCl3) δ: －116.46~－116.52 (m, 1F); HRMS (ESI) calcd for C13H12FNO2SNa [M+Na]+ 288.0465, found 288.0464.
N-(4-氰基苯基)-4-甲基苯磺酰胺(14): 产率67%, 浅棕色固体. 1H NMR (400 MHz, DMSO-d6) δ: 11.00 (br, 1H, NH), 7.73 (d, J=8.0 Hz, 2H), 7.67 (d, J=8.8 Hz, 2H),7.36 (d, J=8.0 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 143.96, 142.35, 136.21, 133.69, 129.98, 126.76, 118.73, 118.43, 105.34, 20.98; HRMS (ESI) calcd for C14H12N2O2SNa [M+Na]+ 295.0512, found 295.0511.
4-甲基-N-(对甲苯基)苯磺酰胺(15): 产率73%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.62 (d, J=8.0 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.03 (d, J=8.0 Hz, 2H), 6.93 (d, J=8.0 Hz, 2H), 6.44 (br, 1H, NH), 2.38 (s, 3H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 143.70, 136.14, 135.17, 133.92, 129.82, 129.60, 127.33, 122.13, 21.51, 20.82; HRMS (ESI) calcd for C14H15NO2SNa [M+Na]+ 284.0716, found 284.0712.
N-(4-乙基苯基)-4-甲基苯磺酰胺(16): 产率77%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.63 (d, J=8.4 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.06 (d, J=8.4 Hz, 2H), 6.96 (d, J=8.4 Hz, 2H), 6.52 (br, 1H, NH), 2.58 (q, J=7.6 Hz, 2H), 2.38 (s, 3H), 1.18 (t, J=7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 143.83, 141.79, 136.39, 134.09, 129.72, 128.77, 127.42, 122.39, 28.33, 21.66, 15.54; HRMS (ESI) calcd for C15H17NO2SNa [M+Na]+ 298.0872, found 298.0871.
N-(4-异丙基苯基)-4-甲基苯磺酰胺(17): 产率74%, 浅黄色固体. 1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J=8.0 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.09 (d, J=8.0 Hz, 2H), 6.97 (d, J=8.0 Hz, 2H), 6.49 (br, 1H, NH), 2.87~2.80 (m, 1H), 2.38 (s, 3H), 1.19 (d, J=6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 146.18, 143.77, 136.46, 134.23, 129.70, 127.41, 127.30, 122.09, 33.58, 24.00, 21.62; HRMS (ESI) calcd for C16H19NO2SNa [M+Na]+ 312.1029, found 312.1030.
N-(4-(叔丁基)苯基)-4-甲基苯磺酰胺(18): 产率80%, 浅黄色固体. 1H NMR (400 MHz, CDCl3) δ: 7.65 (d, J=7.6 Hz, 2H), 7.23 (d, J=8.0 Hz, 4H), 6.96 (d, J=8.0 Hz, 2H), 6.34 (br, 1H, NH), 2.39 (s, 3H), 1.26 (s, 9H); 13C NMR (100 MHz, CDCl3) δ: 148.45, 143.79, 136.58, 133.95, 129.73, 127.42, 126.26, 121.62, 34.46, 31.41, 21.65; HRMS (ESI) calcd for C17H21NO2SNa [M+Na]+ 326.1185, found 326.1184.
4-甲基-N-(4-(三氟甲基)苯基)苯磺酰胺(19): 产率96%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.74 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 7.43 (br, 1H, NH), 7.27 (d, J=8.0 Hz, 2H), 7.19 (d, J=8.4 Hz, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.73, 140.09, 135.69, 130.10, 127.39, 126.74 (q, J=3.7 Hz), 126.50 (q, J=32.5 Hz), 124.04 (q, J=269.8 Hz), 119.66, 21.69; 19F NMR (376 MHz, CDCl3) δ: －62.26 (s, 3F); HRMS (ESI) calcd for C14H12F3NO2SNa [M+Na]+ 338.0433, found 338.0430.
4-甲基-N-(4-(三氟甲氧基)苯基)苯磺酰胺(20): 产率75%, 黄色固体. 1H NMR (400 MHz, CDCl3) δ: 7.66 (d, J=8.0 Hz, 2H), 7.25 (d, J=8.4 Hz, 2H), 7.09 (s, 4H), 6.88 (br, 1H, NH), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 146.47, 144.42, 135.84, 135.43, 129.95, 127.40, 122.74, 122.05, 120.51 (q, J=255.7 Hz), 21.62; 19F NMR (376 MHz, CDCl3) δ: －58.14 (s, 3F); HRMS (ESI) calcd for C14H12F3NO3SNa [M+Na]+ 354.0382, found 354.0381.
4-((4-甲基苯基)磺酰胺基)苯甲酸甲酯(21): 产率75%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.81 (br, 1H, NH), 7.81 (d, J=8.8 Hz, 2H), 7.70 (d, J=8.4 Hz, 2H), 7.36 (d, J=8.0 Hz, 2H), 7.21 (d, J=8.4 Hz, 2H), 3.77 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 165.67, 143.73, 142.47, 136.36, 130.63, 129.87, 126.75, 124.30, 118.09, 51.94, 20.97; HRMS (ESI) calcd for C15H15NO4SNa [M+Na]+ 328.0614, found 328.0613.
N-甲基-4-((4-甲基苯基)磺酰胺基)苯甲酰胺(22): 产率78%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.54 (br, 1H, NH), 8.25 (s, 1H), 7.68 (d, J=7.2 Hz, 4H), 7.34 (d, J=8.0 Hz, 2H), 7.14 (d, J=8.4 Hz, 2H), 2.72 (d, J=4.4 Hz, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 165.96, 143.50, 140.33, 136.49, 129.71, 129.66, 128.23, 126.71, 118.34, 26.13, 20.92; HRMS (ESI) calcd for C15H16N2O3SNa [M+Na]+ 327.0774, found 327.0777.
N-甲基-N-(4-((4-甲基苯基)磺酰胺基)苯基)甲酰胺(23): 产率67%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.30 (br, 1H, NH), 8.40 (s, 1H), 7.65 (d, J=8.0 Hz, 2H), 7.35 (d, J=8.4 Hz, 2H), 7.21 (d, J=8.8 Hz, 2H), 7.10 (d, J=8.8 Hz, 2H), 3.11 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 162.36, 143.78, 138.59, 137.12, 135.79, 130.23, 127.15, 122.87, 121.34, 31.50, 21.42; HRMS (ESI) calcd for C15H16N2O3SNa [M+Na]+ 327.0774, found 327.0774.
4-甲基-N-(4-(吡咯烷-1-基磺酰基)苯基)苯磺酰胺(24): 产率90%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.84 (br, 1H, NH), 7.70 (d, J=8.4 Hz, 2H), 7.66 (d, J=8.8 Hz, 2H), 7.36 (d, J=8.0 Hz, 2H), 7.29 (d, J=8.8 Hz, 2H), 3.05 (t, J=6.6 Hz, 4H), 2.32 (s, 3H), 1.63~1.51 (m, 4H); 13C NMR (100 MHz, DMSO-d6) δ: 143.82, 142.10, 136.23, 130.52, 129.86, 128.86, 126.75, 118.60, 47.77, 24.61, 20.9; HRMS (ESI) calcd for C17H20N2O4S2Na [M+Na]+ 403.0757, found 403.0758.
4-甲基-N-(4-((1s,4r)-4-丙基环己基)苯基)苯磺酰胺(25): 产率83%, 浅黄色固体. 1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J=8.0 Hz, 2H), 7.22 (d, J=7.6 Hz, 2H), 7.06 (d, J=7.6 Hz, 2H), 6.96 (d, J=7.6 Hz, 2H), 6.48 (br, 1H, NH), 2.38 (s, 3H), 1.83 (d, J=10.8 Hz, 4H), 1.41~1.30 (m, 3H), 1.29~1.17 (m, 1H), 1.01 (q, J=12.0 Hz, 2H), 0.89 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 145.28, 143.77, 136.42, 134.18, 129.70, 127.69, 127.40, 122.08, 44.05, 39.78, 37.07, 34.38, 33.59, 21.64, 20.12, 14.51; HRMS (ESI) calcd for C22H29NO2SNa [M+Na]+ 394.1811, found 394.1813.
N-(3-溴苯基)-4-甲基苯磺酰胺(26): 产率69%, 白色固体. NMR (400 MHz, CDCl3) δ: 7.68 (d, J=8.4 Hz, 2H), 7.26 (d, J=8.8 Hz, 2H), 7.25 (s, 1H), 7.23 (ddd, J=9.2, 2.4, 1.2 Hz, 1H), 7.10 (t, J=8.0 Hz, 1H), 7.02 (dd, J=9.2, 2.4 Hz, 1H), 6.81 (br, 1H, NH), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.45, 138.10, 135.90, 130.73, 129.98, 128.32, 127.40, 124.01, 122.95, 119.61, 21.71; HRMS (ESI) calcd for C13H12BrNO2SNa [M+Na]+ 347.9664, found 347.9670.
N-(3-氟苯基)-4-甲基苯磺酰胺(27): 产率90%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.71 (d, J=8.4 Hz, 2H), 7.25 (d, J=8.4 Hz, 2H), 7.20-7.14 (m, 1H), 7.07 (br, 1H, NH), 6.89 (dt, J=10.0, 2.0 Hz, 1H), 6.82~6.76 (m, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.04 (d, J=245.1 Hz), 144.27, 138.23 (d, J=10.2 Hz), 135.80, 130.53 (d, J=9.3 Hz), 129.82, 127.27, 116.29 (d, J=3.1 Hz), 111.90 (d, J=21.1 Hz), 108.16 (d, J=25.2 Hz), 21.55; 19F NMR (376 MHz, CDCl3) δ: －110.96 (dd, J=16.5, 9.0 Hz, 1F); HRMS (ESI) calcd for C13H12F- NO2SNa [M+Na]+ 288.0465, found 288.0466.
N-(3-氰基苯基)-4-甲基苯磺酰胺(28): 产率72%, 棕色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.72 (br, 1H, NH), 7.69 (d, J=8.4 Hz, 2H), 7.48-7.39 (m, 4H), 7.35 (d, J=8.4 Hz, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 143.80, 138.88, 136.11, 130.78, 129.92, 127.46, 126.74, 124.00, 121.99, 118.28, 112.05, 20.97; HRMS (ESI) calcd for C14H12N2O2SNa [M+Na]+ 295.0512, found 295.0515.
4-甲基-N-(间甲苯基)苯磺酰胺(29): 产率97%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.70 (d, J=8.0 Hz, 2H), 7.22 (d, J=7.6 Hz, 2H), 7.11 (s, 1H), 7.08 (d, J=8.0 Hz, 1H), 6.92~6.88 (m, 3H), 2.37 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 143.85, 139.33, 136.69, 136.25, 129.71, 129.11, 127.38, 125.98, 121.99, 118.27, 21.58, 21.39; HRMS (ESI) calcd for C14H15- NO2SNa [M+Na]+ 284.0716, found 284.0715.
N-(3-甲氧基苯基)-4-甲基苯磺酰胺(30): 产率82%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.68 (d, J=7.6 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 7.11 (t, J=8.0 Hz, 1H), 6.69 (s, 2H), 6.65~6.59 (m, 2H), 3.74 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 160.40, 144.02, 137.99, 136.19, 130.12, 129.78, 127.44, 113.35, 110.94, 106.89, 55.41, 21.63; HRMS (ESI) calcd for C14H15N- O3SNa [M+Na]+ 300.0665, found 300.0662.
4-甲基-N-(3-(三氟甲基)苯基)苯磺酰胺(31): 产率83%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.71 (d, J=8.0 Hz, 2H), 7.42 (br, 1H, NH), 7.35~7.34 (m, 3H), 7.30~7.28 (m, 1H), 7.25 (d, J=8.0 Hz, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.62, 137.48, 135.72, 131.92 (q, J=32.6 Hz), 130.08, 130.02, 127.42, 124.13, 121.85, 123.66 (q, J=270.7 Hz), 121.83 (q, J=3.7 Hz), 117.72 (q, J=3.8 Hz), 21.67; 19F NMR (376 MHz, CDCl3) δ: －62.90 (s, 1F); HRMS (ESI) calcd for C14H12F3- NO2SNa [M+Na]+ 338.0433, found 338.0435.
N-(4-氰基-2-甲基苯基)-4-甲基苯磺酰胺(32): 产率56%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.69 (d, J=7.6 Hz, 2H), 7.51 (d, J=8.8 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 7.37 (s, 1H), 7.27 (d, J=8.0 Hz, 2H), 6.65 (br, 1H, NH), 2.41 (s, 3H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.85, 139.36, 136.15, 134.51, 131.32, 130.13, 129.45, 127.25, 121.06, 118.66, 108.33, 21.74, 17.59; HRMS (ESI) calcd for C15H14N2O2SNa [M+Na]+ 309.0668, found 309.0672.
N-(4-氰基-3-氟苯基)-4-甲基苯磺酰胺(33): 产率95%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 11.31 (br, 1H, NH), 7.76 (d, J=7.6 Hz, 3H), 7.40 (d, J=8.0 Hz, 2H), 7.11~7.04 (m, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 163.03 (d, J=252.7 Hz), 144.69 (d, J=11.0 Hz), 144.30, 135.89, 134.96, 130.12, 126.80, 114.14 (d, J=33.8 Hz), 104.84 (d, J=23.8 Hz), 93.80 (d, J=15.4Hz), 21.07; 19F NMR (376 MHz, DMSO-d6) δ: －106.13 (dd, J=11.3, 7.5 Hz, 1F); HRMS (ESI) calcd for C14H11FN2O2SNa [M+Na]+ 313.0417, found 313.0420.
N-(4-氟-3-甲氧基苯基)-4-甲基苯磺酰胺(34): 产率70%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.63 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.0 Hz, 2H), 6.89 (dd, J=10.8, 8.8 Hz, 1H), 6.82 (dd, J=7.2, 2.4 Hz, 1H), 6.78 (br, 1H, NH), 6.48~6.44 (m, 1H), 3.81 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 150.32 (d, J=243.1 Hz), 147.99 (d, J=11.5 Hz), 144.22, 135.57, 132.86 (d, J=3.2 Hz), 129.80, 127.44, 116.21 (d, J=19.3 Hz), 114.38 (d, J=7.0 Hz), 108.38, 56.29, 21.63; 19F NMR (376 MHz, CDCl3) δ: －138.58 (ddd, J=11.0, 7.5, 3.8 Hz, 1F); HRMS (ESI) calcd for C14H14FNO3SNa [M+Na]+ 318.0571, found 318.0574.
N-(4-氯-3-甲氧基苯基)-4-甲基苯磺酰胺(35): 产率75%, 灰白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.67 (d, J=8.0 Hz, 2H), 7.24 (d, J=8.0 Hz, 2H), 7.16 (d, J=8.8 Hz, 1H), 7.10 (br, 1H, NH), 6.80 (d, J=2.4 Hz, 1H), 6.52 (dt, J=8.4, 2.0, 1H), 3.82 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 155.48, 144.38, 136.49, 135.62, 130.49, 129.89, 127.42, 119.03, 113.82, 105.82, 56.26, 21.65; HRMS (ESI) calcd for C14H14ClNO3SNa [M+Na]+ 334.0275, found 334.0276.
4-甲基-N-(3,4,5-三氟苯基)苯磺酰胺(36): 产率84%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.70 (d, J=8.4 Hz, 2H), 7.29 (d, J=8.4 Hz, 2H), 7.25 (br, 1H, NH), 6.77 (dd, J=8.4, 6.0 Hz, 2H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 151.38 (ddd, J=248.6, 10.5, 5.1 Hz), 145.02, 137.52 (dt, J=248.2, 15.1 Hz), 135.08, 132.51 (td, J=10.9, 4.1 Hz), 130.19, 127.38, 105.6 (dd, J=17.4, 7.2 Hz), 21.70; 19F NMR (376 MHz, CDCl3) δ: －132.30 (dd, J=21.1, 8.6 Hz, 2F), －164.47 (tt, J=21.1, 6.0 Hz, 1F); HRMS (ESI) calcd for C13H10F3NO2SNa [M+Na]+ 324.0277, found 324.0275.
N-(4-氟-3,5-二甲基苯基)-4-甲基苯磺酰胺(37): 产率48%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.61 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 6.69 (d, J=6.4 Hz, 2H), 6.41 (br, 1H, NH), 2.39 (s, 3H), 2.16 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 157.77 (d, J=240.8 Hz), 143.93, 135.98, 131.47 (d, J=3.5 Hz), 129.73, 127.40, 125.38 (d, J=19.3 Hz), 122.79 (d, J=5.0 Hz), 21.64, 14.72 (d, J=3.9 Hz); 19F NMR (376 MHz, CDCl3) δ: －125.08 (s, 1F); HRMS (ESI) calcd for C15H16FNO2SNa [M+Na]+ 316.0778, found 316.0776.
N-(4-甲酰基苯基)甲磺酰胺(38): 产率69%, 浅黄色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.51 (br, 1H, NH), 9.89 (s, 1H), 7.88 (d, J=8.8 Hz, 2H), 7.36 (d, J=8.4 Hz, 2H), 3.15 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 191.58, 144.26, 131.31, 131.14, 117.70, 40.04; HRMS (ESI) calcd for C8H9NO3SNa [M+Na]+ 222.0195, found 222.0191.
N-(4-乙酰基苯基)甲磺酰胺(39): 产率89%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.37 (br, 1H, NH), 7.94 (t, J=8.8 Hz, 2H), 7.29 (t, J=8.4 Hz, 2H), 3.12 (s, 3H), 2.52 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 196.55, 143.03, 131.71, 130.00, 117.55, 39.92, 26.47; HR- MS (ESI) calcd for C9H11NO3SNa [M+Na]+ 236.0352, found 236.0355.
N-甲基-N-(4-甲磺酰胺基苯基)甲酰胺(40): 产率96%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 9.78 (br, 1H, NH), 8.45 (s, 1H), 7.32 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 3.18 (s, 3H), 2.98 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 162.00, 138.19, 136.05, 122.82, 120.97, 31.24; HRMS (ESI) calcd for C9H12N2O3SNa [M+Na]+ 251.0461, found 251.0456.
N-(4-甲氧基苯基)甲磺酰胺(41): 产率86%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, J=8.8 Hz, 2H), 6.89 (d, J=8.8 Hz, 2H), 6.35 (br, 1H, NH), 3.80 (s, 3H), 2.95 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 158.12, 129.24, 124.80, 114.87, 55.61, 38.80; HRMS (ESI) calcd for C8H11NO3SNa [M+Na]+ 224.0352, found 224.0347.
N-(邻甲苯基)甲磺酰胺(42): 产率85%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.48 (d, J=8.0 Hz, 1H), 7.29~7.25 (m, 2H), 7.17 (t, J=7.2 Hz, 1H), 6.32 (br, 1H, NH), 3.05 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 134.81, 131.29, 130.94, 127.33, 126.27, 123.24, 39.87, 18.12; HRMS (ESI) calcd for C8H11NO2SNa [M+Na]+ 208.0403, found 208.0398.
N-(2-异丙基苯基)甲磺酰胺(43): 产率75%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.47 (d, J=7.2 Hz, 1H), 7.36 (d, J=7.2 Hz, 1H), 7.29~7.22 (m, 2H), 6.41 (br, 1H, NH), 3.25~3.18 (m, 1H), 3.05 (s, 3H), 1.28 (d, J=6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 142.55, 133.05, 127.16, 126.89, 126.63, 124.61, 53.57, 39.80, 27.71, 23.51; HRMS (ESI) calcd for C10H15NO2SNa [M+Na]+ 236.0716, found 236.0712.
N-(2-甲氧基苯基)甲磺酰胺(44): 产率62%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.53 (d, J=8.0 Hz, 1H), 7.14 (t, J=8.0 Hz, 1H), 6.97 (t, J=7.6 Hz, 1H), 6.92 (d, J=8.0 Hz, 1H), 6.81 (br, 1H, NH), 3.89 (s, 3H), 2.95 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 149.57, 126.14, 125.71, 121.47, 121.03, 110.83, 55.88, 39.11; HRMS (ESI) calcd for C8H11NO3SNa [M+Na]+ 224.0352, found 224.0347.
N-(2-异丙氧基苯基)甲磺酰胺(45): 产率43%, 浅黄色固体. 1H NMR (400 MHz, DMSO-d6) δ: 8.70 (br, 1H, NH), 7.26 (d, J=8.0 Hz, 1H), 7.16 (t, J=8.4 Hz, 1H), 7.06 (d, J=8.0 Hz, 1H), 6.88 (t, J=8.0 Hz, 1H), 4.70~4.64 (m, 1H), 2.93 (s, 3H), 1.29 (d, J=6.0 Hz, 6H); 13C NMR (101 MHz, DMSO-d6) δ: 150.46, 126.61, 126.43, 126.11, 120.14, 113.52, 69.85, 40.15, 21.59; HRMS (ESI) calcd for C10H15NO3SNa [M+Na]+ 252.0665, found 252.0662.
2-(甲磺酰胺基)苯甲酸甲酯(46): 产率50%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 10.47 (br, 1H, NH), 8.05 (t, J=8.0 Hz, 1H), 7.74 (t, J=8.8 Hz, 1H), 7.59~7.50 (m, 1H), 7.16~7.04 (m, 1H), 3.94 (s, 3H), 3.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 168.49, 140.92, 135.04, 131.68, 122.96, 118.15, 115.48, 52.71, 40.08; HR- MS (ESI) calcd for C9H11NO4SNa [M+Na]+ 252.0297, found 252.0297.
N-(2-氟苯基)-4-甲基苯磺酰胺(47): 产率41%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.66 (d, J=8.4 Hz, 2H), 7.59 (td, J=8.0, 2.0 Hz, 1H), 7.22 (d, J=8.0 Hz, 2H), 7.11~7.03 (m, 2H), 6.98~6.93 (m, 1H), 6.72 (br, 1H, NH), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 154.08 (d, J=243.0 Hz), 144.28, 136.02, 129.79, 127.32, 126.21 (d, J=7.4 Hz), 124.84 (d, J=4.0 Hz), 123.41, 115.53 (d, J=19.4 Hz), 100.09, 21.57; 19F NMR (376 MHz, CDCl3) δ: －129.98 (m, 1F); HRMS (ESI) calcd for C13H12FNO2SNa [M+Na]+ 288.0465, found 288.0465.
N-(2-氯-5-甲氧基苯基)甲磺酰胺(48): 产率62%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.30 (d, J=8.8 Hz, 1H), 7.22 (d, J=3.2 Hz, 1H), 6.79 (br, 1H, NH), 6.69 (dd, J=8.8, 2.8 Hz, 1H), 3.80 (s, 3H), 3.01 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 159.43, 134.28, 130.12, 116.18, 112.41, 107.75, 55.83, 39.80; HRMS (ESI) calcd for C8H10ClNO3SNa [M+Na]+ 257.9962, found 257.9960.
N-(4-甲氧基-3,5-二甲基苯基)甲磺酰胺(49): 产率81%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 6.89 (s, 2H), 6.61 (br, 1H, NH), 3.70 (s, 3H), 2.99 (s, 3H), 2.27 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 154.95, 132.37, 132.05, 122.15, 59.89, 39.01, 16.25; HRMS (ESI) calcd for C10H15NO3SNa [M+Na]+ 252.0665, found 252.0660.
N-(3-(金刚烷-1-基)-4-甲氧基苯基)甲磺酰胺(50): 产率71%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.10 (dd, J=8.8, 2.8 Hz, 1H), 7.05 (d, J=2.4 Hz, 1H), 6.83 (d, J=8.4 Hz, 1H), 6.22 (br, 1H, NH), 3.83 (s, 3H), 2.96 (s, 3H), 2.06 (s, 9H), 1.76 (s, 6H); 3C NMR (100 MHz, CDCl3) δ: 157.45, 140.09, 128.88, 122.50, 121.71, 112.35, 55.38, 40.45, 39.00, 37.17, 37.09, 29.06; HRMS (ESI) calcd for C18H25NO3SNa [M+Na]+ 358.1447, found 358.1447.
4-甲基-N-(吡啶-3-基)苯磺酰胺(51): 产率90%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.51 (br, 1H, NH), 8.28 (s, 1H), 8.24 (d, J=4.0 Hz, 1H), 7.65 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.35 (d, J=8.0 Hz, 2H), 7.27 (dd, J=8.0, 4.4 Hz, 1H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 145.24, 143.67, 141.67, 136.20, 134.51, 129.88, 127.25, 126.75, 124.01, 20.98; HRMS (ESI) calcd for C12H12N2O2SNa [M+Na]+ 271.0512, found 271.0510.
N-(5-氯吡啶-3-基)-4-甲基苯磺酰胺(52): 产率84%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.82 (br, 1H, NH), 8.29 (s, 1H), 8.24 (s, 1H), 7.69 (d, J=8.0 Hz, 2H), 7.55 (s, 1H), 7.38 (d, J=8.0 Hz, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 144.00, 143.30, 139.24, 135.88, 135.49, 130.85, 130.00, 126.69, 125.87, 20.95; HRMS (ESI) calcd for C12H11ClN2O2SNa [M+Na]+ 305.0122, found 305.0124.
4-甲基-N-(5-甲基吡啶-3-基)苯磺酰胺(53): 产率91%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.43 (br, 1H, NH), 8.08 (s, 2H), 7.65 (d, J=8.4 Hz, 2H), 7.35 (d, J=8.4 Hz, 2H), 7.32 (s, 1H), 2.33 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 145.65, 143.60, 138.68, 136.27, 134.12, 133.44, 129.86, 127.46, 126.72, 20.98, 17.79; HRMS (ESI) calcd for C13H14N2O2SNa [M+Na]+ 285.0668, found 285.0665.
4-甲基-N-(5-(三氟甲基)吡啶-3-基)苯磺酰胺(54): 产率55%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.99 (br, 1H, NH), 8.64 (s, 1H), 8.56 (s, 1H), 7.75 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 2.33 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 144.62, 144.16, 141.14 (q, J=4.0 Hz), 135.74, 134.89, 130.06, 126.73, 125.33 (q, J=32.1 Hz), 123.14 (q, J=271.2 Hz), 122.66 (d, J=3.8 Hz), 20.96; 19F NMR (376 MHz, DMSO-d6) δ: －61.33 (s, 3F); HRMS (ESI) calcd for C13H11F3N2O2SNa [M+Na]+ 339.0386, found 339.0384.
N-(2-(三氟甲基)吡啶-4-基)甲磺酰胺(55): 产率74%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.98 (br, 1H, NH), 8.59 (d, J=5.2 Hz, 1H), 7.50 (s, 1H), 7.40 (d, J=5.6 Hz, 1H), 3.25 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 151.45, 147.68 (q, J=33.2 Hz), 121.53 (q, J=272.6 Hz), 114.19, 108.59 (d, J=3.0 Hz), 40.56; HRMS (ESI) calcd for C7H7F3N2O2SNa [M+Na]+ 263.0073, found 263.0069.
N-(2-甲氧基吡啶-4-基)甲磺酰胺(56): 产率77%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.46 (br, 1H, NH), 8.01 (d, J=6.0 Hz, 1H), 6.75 (d, J=6.0 Hz, 1H), 6.51 (s, 1H), 3.81 (s, 3H), 3.14 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 164.70, 148.12, 147.85, 106.94, 96.81, 53.26, 40.08; HRMS (ESI) calcd for C7H10N2O3SNa [M+Na]+ 225.0304, found 225.0302.
N-(2-氟吡啶-3-基)甲磺酰胺(57): 产率77%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 9.93 (br, 1H, NH), 8.03 (dt, J=4.8, 1.6 Hz, 1H), 7.91 (td, J=8.0, 1.6 Hz, 1H), 7.36 (ddd, J=7.6, 4.8, 1.2 Hz, 1H), 3.10 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 155.92 (d, J=234.9 Hz,), 143.13 (d, J=13.8 Hz), 135.54 (d, J=3.2 Hz), 122.69 (d, J=4.2 Hz), 120.76 (d, J=28.3 Hz), 40.63; 19F NMR (376 MHz, DMSO-d6) δ: －77.49 (d, J=10.2 Hz, 1H); HRMS (ESI) calcd for C6H7FN2O2SNa [M+Na]+ 213.0104, found 213.0106.
N-(6-氯吡啶-3-基)甲磺酰胺(58): 产率55%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.16 (br, 1H, NH), 8.23 (d, J=3.2 Hz, 1H), 7.67 (dd, J=8.4, 2.4 Hz, 1H), 7.50 (d, J=8.4 Hz, 1H), 3.08 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 144.71, 140.98, 134.73, 130.59, 124.68, 39.83; HRMS (ESI) calcd for C6H7ClN2O2SNa [M+Na]+ 228.9809, found 228.9805.
N-(6-氯-5-氟吡啶-3-基)甲磺酰胺(59): 产率55%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.48 (br, 1H, NH), 8.10 (s, 1H), 7.68 (dd, J=10.0, 1.6 Hz, 1H), 3.16 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 153.73 (d, J=257.5 Hz), 136.47 (d, J=4.4 Hz), 135.92 (d, J=4.8 Hz), 131.05 (d, J=19.4 Hz), 115.87 (d, J=22.0 Hz); HRMS (ESI) calcd for C6H6ClFN2O2SNa [M+Na]+ 246.9715, found 246.9710.
N-(喹啉-6-基)甲磺酰胺(60): 产率95%, 浅黄色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.17 (br, 1H, NH), 8.80 (s, 1H), 8.30 (d, J=7.6 Hz, 1H), 8.00 (d, J=8.8 Hz, 1H), 7.72 (s, 1H), 7.60 (dd, J=9.2, 2.0 Hz, 1H), 7.49 (dd, J=8.4, 4.0 Hz, 1H), 3.10 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 149.35, 144.85, 136.55, 135.48, 130.33, 128.47, 123.54, 122.00, 114.64, 39.48; HRMS (ESI) calcd for C10H10N2O2SNa [M+Na]+ 245.0355, found 245.0353.
N-(2-甲基喹啉-6-基)甲磺酰胺(61): 产率78%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.07 (br, 1H, NH), 8.18 (d, J=8.4 Hz, 1H), 7.89 (d, J=9.2 Hz, 1H), 7.67 (s, 1H), 7.55 (dd, J=9.2, 2.4 Hz, 1H), 7.38 (d, J=8.4 Hz, 1H), 3.07 (s, 3H), 2.62 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 157.57, 144.45, 135.69, 135.63, 129.49, 126.62, 123.54, 122.67, 115.07, 39.38, 24.70; HRMS (ESI) calcd for C11H12N2O2SNa [M+H]+ 237.0692, found 237.0693.
N-(喹啉-3-基)甲磺酰胺(62): 产率68%, 棕色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.31 (br, 1H, NH), 8.76 (s, 1H), 8.11 (s, 1H), 7.97 (t, J=8.8 Hz, 1H), 7.67 (t, J=6.8 Hz, 1H), 7.59 (t, J=7.2 Hz, 1H), 3.14 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 145.59, 144.97, 132.60, 129.08, 128.70, 128.24, 128.15, 127.74, 123.11, 40.14; HRMS (ESI) calcd for C10H10N2O2SNa [M+Na]+ 245.0355, found 245.0353.
N-(喹啉-7-基)甲磺酰胺(63): 产率68%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.28 (br, 1H, NH), 8.85 (dd, J=4.4, 1.6 Hz, 1H), 8.29 (d, J=7.6 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.80 (s, 1H), 7.47 (dd, J=8.8, 2.4 Hz, 1H), 7.43 (dd, J=8.0, 4.0 Hz, 1H), 3.11 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 151.19, 148.43, 139.55, 135.78, 129.37, 124.45, 120.33, 120.08, 115.19; HRMS (ESI) calcd for C10H10N2O2SNa [M+Na]+ 245.0355, found 245.0356.
5-(甲磺酰胺基)-1H-吲哚-1-羧酸叔丁酯(64): 产率99%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 8.12 (br, 1H, NH), 7.63 (d, J=3.6 Hz, 1H), 7.51 (d, J=2.4 Hz, 1H), 7.16 (dd, J=8.8, 2.0 Hz, 1H), 6.55~6.54 (m, 2H), 2.98 (s, 3H), 1.67 (s, 9H); 13C NMR (100 MHz, CDCl3) δ: 149.57, 133.29, 131.66, 131.46, 127.29, 119.29, 116.10, 114.71, 107.21, 84.15, 38.79, 28.22; HRMS (ESI) calcd for C14H18N2O4SNa [M+Na]+ 333.0879, found 333.0879.
N-(苯并呋喃-5-基)甲磺酰胺(65): 产率87%, 棕色固体. 1H NMR (400 MHz, DMSO-d6) δ: 9.60 (br, 1H, NH), 7.98 (d, J=2.0 Hz, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.52 (d, J=2.0 Hz, 1H), 7.19 (d, J=8.8 Hz, 1H), 6.96 (s, 1H), 2.93 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 151.72, 146.98, 133.47, 127.86, 118.95, 113.82, 111.76, 106.92, 38.68; HRMS (ESI) calcd for C9H9NO3SNa [M+Na]+ 234.0195, found 234.0192.
N-(苯并噻吩-6-基)甲磺酰胺(66): 产率89%, 浅黄色固体. 1H NMR (400 MHz, DMSO-d6) δ: 9.84 (br, 1H, s), 7.83 (d, J=8.8 Hz 2H), 7.67 (d, J=5.2 Hz, 1H), 7.40 (d, J=5.6 Hz, 1H), 7.25 (d, J=8.8 Hz, 1H), 3.00 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 140.04, 136.15, 135.11, 126.66, 124.21, 123.61, 118.41, 113.42, 39.21; HRMS (ESI) calcd for C9H9NO2S2Na [M+Na]+ 249.9967, found 249.9966.
N-(苯并噻吩-5-基)甲磺酰胺(67): 产率68%, 浅黄色固体. 1H NMR (400 MHz, DMSO-d6) δ: 9.77 (br, 1H, NH), 7.95 (d, J=8.8 Hz, 1H), 7.78 (d, J=5.6 Hz, 1H), 7.74 (s, 1H), 7.44 (d, J=5.2 Hz, 1H), 7.25 (d, J=8.8 Hz, 1H), 2.98 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 140.23, 135.24, 135.06, 128.79, 123.98, 123.32, 118.48, 114.69, 38.98; HRMS (ESI) calcd for C9H9NO2S2Na [M+Na]+ 249.9967, found 249.9966.
4-甲基-N-(5-(三氟甲基)吡啶-2-基)苯磺酰胺(68): 产率53%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 10.81 (br, 1H, NH), 8.71 (s, 1H), 7.85 (dd, J=8.8, 2.4 Hz, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.8 Hz, 1H), 7.28 (d, J=8.4 Hz, 2H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 154.24, 145.57, 144.80, 136.70, 136.43, 130.16, 127.32, 122.05 (q, J=2.3 Hz), 121.81 (q, J=17.3 Hz), 111.50, 21.74; 19F NMR (376 MHz, CDCl3) δ: －62.00 (d, J=3.4 Hz, 1H); HRMS (ESI) calcd for C13H11F3N2O2SNa [M+Na]+ 339.0386, found 339.0384.
4-甲基-N-(3-氧代-1,3-二氢异苯并呋喃-5-基)苯磺酰胺(69): 产率70%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.67 (br, 1H, NH), 7.66 (d, J=8.0 Hz, 2H), 7.55 (d, J=8.8 Hz, 1H), 7.48~7.46 (m, 2H), 7.35 (d, J=8.0 Hz, 2H), 5.30 (s, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 170.22, 143.66, 142.61, 138.73, 136.19, 129.89, 126.72, 125.99, 125.94, 124.02, 114.61, 69.79, 20.95; HRMS (ESI) calcd for C15H13NO4SNa [M+Na]+ 326.0457, found 326.0455.
4-甲基-N-(嘧啶-5-基)苯磺酰胺(70): 产率44%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.79 (br, 1H, NH), 8.88 (s, 1H), 8.50 (s, 2H), 7.68 (d, J=8.0 Hz, 2H), 7.39 (d, J=8.4 Hz, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 154.05, 148.15, 144.06, 135.78, 133.24, 130.04, 126.75, 20.99; HRMS (ESI) calcd for C11H11N3- O2SNa [M+Na]+ 272.0464, found272.0465.
4-甲基-N-(2-甲基嘧啶-5-基)苯磺酰胺(71): 产率41%, 浅黄色固体. 1H NMR (400 MHz, CDCl3) δ: 10.53 (br, 1H, NH), 8.36 (s, 2H), 7.63 (d, J=8.0 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 2.50 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.27, 149.17, 143.88, 135.81, 130.40, 129.97, 126.74, 24.84, 20.98; HRMS (ESI) calcd for C12H13N3O2SNa [M+Na]+ 286.0621, found 286.0618.
N-(4-甲氧基苯基)-4-甲基苯磺酰胺(72): 产率75%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.58 (d, J=8.4 Hz, 2H), 7.21 (d, J=8.4 Hz, 2H), 6.98~6.95 (m, 2H), 6.78~6.73 (m, 2H), 6.43 (br, 1H, NH), 3.75 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 157.99, 143.77, 136.10, 129.67, 129.08, 127.45, 125.43, 114.52, 55.52, 21.65; HRMS (ESI) calcd for C14H15NO3SNa [M+Na]+ 300.0665, found 300.0665.
N-(3-乙酰基苯基)-4-甲基苯磺酰胺(73): 产率98%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.49 (br, 1H, NH), 7.69~7.62 (m, 4H), 7.42~7.40 (m, 2H), 7.34 (d, J=8.0 Hz, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 197.29, 143.48, 138.35, 137.61, 136.44, 129.78, 129.67, 126.72, 124.15, 124.04, 118.46, 26.66, 20.93; HRMS (ESI) calcd for C15H15NO3SNa [M+Na]+ 312.0665, found 312.0669.
N-(3-甲酰基苯基)-4-甲基苯磺酰胺(74): 产率78%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.60 (br, 1H, NH), 9.89 (s, 1H), 7.67 (d, J=8.0 Hz, 2H), 7.61 (s, 1H), 7.57 (d, J=7.2 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 2H), 2.30 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 192.75, 143.57, 138.79, 137.02, 136.36, 130.19, 129.83, 126.71, 125.86, 125.29, 118.76, 20.95; HRMS (ESI) calcd for C14H13NO3SNa [M+Na]+ 298.0508, found 298.0511.
2-((4-甲基苯基)磺酰胺基)苯甲酸甲酯(75): 产率58%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.77 (dt, J=8.0, 1.6 Hz, 1H), 7.69 (t, J=2.0 Hz, 1H), 7.67 (d, J=8.4 Hz, 2H), 7.41~7.38 (m, 1H), 7.33 (t, J=7.6 Hz, 1H), 7.22 (d, J=8.0 Hz, 2H), 7.02 (br, 1H, NH), 3.90 (s, 3H), 2.37 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 166.56, 144.27, 137.22, 136.08, 131.46, 129.90, 129.61, 127.40, 126.33, 125.57, 122.26, 52.52, 21.67; HRMS (ESI) calcd for C15H15NO4SNa [M+Na]+ 328.0614, found 328.0614.
N-(2-氯苯基)-4-甲基苯磺酰胺(76): 产率59%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.65 (d, J=8.4 Hz, 3H), 7.25~7.20 (m, 4H), 7.03 (td, J=8.0, 1.6 Hz, 1H), 6.98 (br, 1H, NH), 2.37 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 144.35, 136.03, 133.62, 129.79, 129.49, 128.00, 127.39, 125.96, 125.19, 122.48, 21.68; HRMS (ESI) calcd for C13H12ClNO2SNa [M+Na]+ 304.0169, found 304.0169.
N-(2-氯苯基)-4-甲基苯磺酰胺(77): 产率80%, 灰白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.61 (d, J=8.0 Hz, 2H), 7.31 (d, J=8.0 Hz, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.15~7.11 (m, 1H), 7.08~7.05 (m, 2H), 6.42 (br, 1H, NH), 2.39 (s, 3H), 2.00 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 143.89, 136.87, 134.64, 131.55, 130.89, 129.71, 127.27, 127.02, 126.29, 124.47, 21.65, 17.69; HRMS (ESI) calcd for C14H15NO2SNa [M+Na]+ 284.0716, found 284.0716.
N-(2-异丙基苯基)-4-甲基苯磺酰胺(78): 产率76%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.59 (d, J=8.4 Hz, 2H), 7.28 (d, J=7.6 Hz, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.18 (d, J=4.0 Hz, 2H), 7.15~7.10 (m, 1H), 6.37 (br, 1H, NH), 2.85~2.79 (m, 1H), 2.38 (s, 3H), 0.99 (d, J=6.8 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ: 143.64, 143.29, 136.63, 132.76, 129.53, 127.30, 127.00, 126.31, 126.11, 125.87, 27.27, 23.31, 21.47; HRMS (ESI) calcd for C16H19NO2SNa [M+Na]+ 312.1029, found 312.1029.
2-((4-甲基苯基)磺酰胺基)苯甲酸甲酯(79): 产率54%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 10.61 (br, 1H, NH), 7.90 (dd, J=8.0, 1.6 Hz, 1H), 7.73 (d, J=8.0 Hz, 2H), 7.68 (dd, J=8.4, 0.9 Hz, 1H), 7.47~7.41 (m, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.06~6.99 (m, 1H), 3.87 (s, 3H), 2.35 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 168.40, 144.01, 140.64, 136.57, 134.59, 131.27, 129.73, 127.39, 122.92, 119.10, 115.94, 52.56, 21.63; HRMS (ESI) calcd for C15H15NO4SNa [M+Na]+ 328.0614, found 328.0614.
4-甲基-N-(2-(三氟甲氧基)苯基)苯磺酰胺(80): 产率77%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.70~7.66 (m, 3H), 7.24~7.20 (m, 3H), 7.14~7.06 (m, 2H), 6.88 (br, 1H, NH), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.47, 139.55, 135.90, 129.83, 129.13, 127.50, 127.35, 125.47, 122.24, 120.37 (q, J=258.3 Hz), 120.21, 21.64; 19F NMR (376 MHz, CDCl3) δ: －57.60 (d, J=1.5 Hz, 3H); HRMS (ESI) calcd for C14H12F3NO3SNa [M+Na]+ 354.0382, found 354.0382.
N-(2-甲氧基苯基)-4-甲基苯磺酰胺(81): 产率83%, 浅黄色固体. 1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J=8.4 Hz, 2H), 7.51 (dd, J=8.0, 1.6 Hz, 1H), 7.19 (d, J=8.4 Hz, 2H), 7.02 (td, J=8.0, 1.6 Hz, 1H), 6.99 (br, 1H, NH), 6.89 (t, J=7.6 Hz, 1H), 6.73 (d, J=8.0 Hz, 1H), 3.64 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 149.60, 143.73, 136.45, 129.45, 127.37, 126.17, 125.37, 121.20, 121.14, 110.72, 55.73, 21.59; HRMS (ESI) calcd for C14H15NO3SNa [M+Na]+ 300.0665, found 300.0665.
N-(2,4-二甲氧基苯基)-4-甲基苯磺酰胺(82): 产率58%, 棕色固体. 1H NMR (400 MHz, CDCl3) δ: 7.55 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.8 Hz, 1H), 7.16 (d, J=8.4 Hz, 2H), 6.60 (br, 1H, NH), 6.43 (dd, J=8.8, 2.4 Hz, 1H), 6.27 (d, J=2.8 Hz, 1H), 3.76 (s, 3H), 3.48 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 158.50, 151.96, 143.47, 136.43, 129.25, 127.46, 124.61, 118.95, 104.44, 98.92, 55.61, 55.56, 21.59; HRMS (ESI) calcd for C15H17- NO4SNa [M+Na]+ 330.0770, found 330.0774.
4-甲基-N-(噻吩-3-基)苯磺酰胺(83): 产率54%, 棕色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.34 (br, 1H, NH), 7.63 (d, J=8.4 Hz, 2H), 7.38 (dd, J=5.0, 3.2 Hz, 1H), 7.33 (d, J=8.0 Hz, 2H), 6.88~6.83 (m, 1H), 6.81 (dd, J=4.8, 1.2 Hz, 1H), 2.33 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 143.22, 136.62, 135.60, 129.64, 126.71, 126.05, 122.20, 110.32, 20.99; HRMS (ESI) calcd for C11H11NO2S2Na [M+Na]+ 276.0123, found 276.0122.
N-(3-氟苯基)苯磺酰胺(84): 产率96%, 灰白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.82 (d, J=7.6 Hz, 2H), 7.57 (t, J=7.6 Hz, 1H), 7.47 (t, J=7.6 Hz, 2H), 7.21~7.16 (m, 1H), 6.93 (br, 1H, NH), 6.90 (dt, J=10.4, 2.0 Hz, 1H), 6.84~6.76 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 163.10 (d, J=245.1 Hz), 138.67, 138.21 (d, J=14.3 Hz), 133.48, 130.68 (d, J=9.2 Hz), 129.35, 127.33, 116.42 (d, J=3.0 Hz), 112.07 (d, J=21.1 Hz), 108.25 (d, J=25.2 Hz); 19F NMR (376 MHz, CDCl3) δ: －110.71~－110.78 (m, 1F); HRMS (ESI) calcd for C12H10FNO2SNa [M+Na]+ 274.0308, found 274.0307.
4-氟-N-(3-氟苯基)苯磺酰胺(85): 产率93%, 灰白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.81 (dd, J=8.8, 5.2 Hz, 2H), 7.24~7.20 (m, 1H), 7.14 (t, J=8.4 Hz, 2H), 6.91~6.78 (m, 3H), 6.69 (br, 1H, NH); 13C NMR (100 MHz, CDCl3) δ: 166.83, 164.34 (d, J=9.3 Hz), 161.93, 137.95 (d, J=10.2 Hz), 134.69 (d, J=3.1 Hz), 130.83 (d, J=9.3 Hz), 130.18 (d, J=9.4 Hz,), 116.69 (d, J=22.6 Hz), 112.39 (d, J=21.1 Hz), 108.45 (d, J=25.2 Hz); 19F NMR (376 MHz, CDCl3) δ: －103.73~－103.80 (m, 1F), －110.42~－110.49 (m, 1F); HRMS (ESI) calcd for C12H9F2NO2SNa [M+Na]+ 292.0214, found; 292.0212.
4-氯-N-(3-氟苯基)苯磺酰胺(86): 产率74%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.75 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.24 (br, 1H, NH), 7.23~7.17 (m, 1H), 6.91 (dt, J=10.0, 2.4 Hz, 1H), 6.85~6.81 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 163.13 (d, J=245.69 Hz, 1H), 140.13, 137.81 (d, J=10.2 Hz), 137.06, 130.85 (d, J=9.2 Hz), 129.69, 128.79, 116.58 (d, J=3.0 Hz), 112.48 (d, J=21.1 Hz), 108.48 (d, J=25.2 Hz); 19F NMR (376 MHz, CDCl3) δ: －110.39 (dd, J=16.17, 8.65 Hz, 1F); HRMS (ESI) calcd for C12H9ClFNO2SNa [M+Na]+ 307.9919, found 307.9919.
N-(3-氟苯基)-4-(三氟甲基)苯磺酰胺(87): 产率56%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.92 (d, J=8.4 Hz, 2H), 7.74 (d, J=8.4 Hz, 2H), 7.24~7.20 (m, 1H), 6.93~6.84 (m, 2H), 6.80 (d, J=8.0 Hz, 1H), 6.64 (br, 1H, NH); 13C NMR (101 MHz, CDCl3) δ: 163.21 (d, J=246.0 Hz), 142.33, 137.48 (d, J=10.2 Hz), 135.17 (q, J=32.9 Hz), 130.99 (d, J=9.2 Hz), 127.89, 126.57 (q, J=3.6 Hz), 123.17 (q, J=271.3 Hz), 116.82 (d, J=3.1 Hz), 112.89 (d, J=21.1 Hz), 108.81 (d, J=25.2 Hz); 19F NMR (376 MHz, CDCl3) δ: －63.22 (s, 3F), －110.18 (s, 1F); HRMS (ESI) calcd for C13H9F4NO2SNa [M+Na]+ 342.0182, found 342.0183.
4-(二氟甲氧基)-N-(3-氟苯基)苯磺酰胺(88): 产率96%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.81 (d, J=8.8 Hz, 2H), 7.24~7.17 (m, 3H), 6.90 (d, J=10.0 Hz, 1H), 6.86~6.79 (m, 2H), 6.71 (br, 1H, NH), 6.57 (s, 1H); 13C NMR (101 MHz, CDCl3) δ: 163.17 (d, J=245.5 Hz), 154.75, 137.94 (d, J=10.2 Hz), 135.27, 130.85 (d, J=9.3 Hz), 129.62, 119.51, 116.55 (d, J=3.0 Hz), 115.21 (t, J=261.2 Hz), 112.42 (d, J=21.1 Hz), 108.44 (d, J=25.2 Hz); 19F NMR (376 MHz, CDCl3) δ: －82.23 (d, J=72.19 Hz, 2F), －110.44 (dd, J=17.7, 9.4 Hz, 1F); HRMS (ESI) calcd for C13H10F3NO3SNa [M+Na]+ 340.0226, found 340.0221.
N-(3-氟苯基)-4-甲氧基苯磺酰胺(89): 产率83%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.75 (d, J=8.8 Hz, 2H), 7.20~7.15 (m, 1H), 7.00 (br, 1H, NH), 6.91 (d, J=8.8 Hz, 2H), 6.89~6.88 (m, 1H), 6.82~6.76 (m, 2H), 3.83 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 163.44, 163.11 (d, J=244.9 Hz), 138.55 (d, J=10.3 Hz), 130.64 (d, J=9.3 Hz), 130.19, 129.58, 116.22 (d, J=2.9 Hz), 114.47, 111.76 (d, J=21.0 Hz), 108.15 (d, J=25.2 Hz), 55.69; 19F NMR (376 MHz, CDCl3) δ: －110.98 (dd, J=16.3, 8.7 Hz, 1F); HRMS (ESI) calcd for C13H13FNO3S [M+H]+ 304.0414, found 304.0415.
苯甲酰基(4-(N-(3-氟苯基)氨磺酰基)苯基)氨基甲酸酯(90): 产率87%, 白色固体. 1H NMR (400 MHz, DMSO-d6) δ: 10.46 (br, 1H, NH), 10.24 (br, 1H, NH), 7.71 (d, J=8.8 Hz, 2H), 7.61 (d, J=8.8 Hz, 2H), 7.38~7.35 (m, 5H), 7.22~7.16 (m, 1H), 6.91~6.81 (m, 3H), 5.16 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 162.25 (d, J=241.6 Hz), 153.17, 143.42, 139.81 (d, J=10.6 Hz), 136.22, 132.20, 130.89 (d, J=9.5 Hz), 128.47, 128.21, 128.17, 128.11, 117.83, 115.24, 110.28 (d, J=20.9 Hz), 106.15 (d, J=25.2 Hz), 66.20; 19F NMR (376 MHz, DMSO-d6) δ: －111.66 (dd, J=16.2, 7.5 Hz, 1H); HRMS (ESI) calcd for C20H17FN2O4SNa [M+Na]+ 423.0785, found 423.0787.
N-(3-氟苯基)-2-甲基苯磺酰胺(91): 产率81%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 8.00 (d, J=8.0 Hz, 1H), 7.47~7.43 (m, 1H), 7.32~7.28 (m, 2H), 7.18~7.13 (m, 1H), 6.85~6.71 (m, 3H), 2.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.19 (d, J=245.2 Hz), 138.27 (d, J=10.6 Hz), 137.27 (d, J=16.5 Hz), 133.56, 132.90, 130.73 (d, J=9.4 Hz), 130.14, 126.57, 115.47, 111.65 (d, J=20.9 Hz), 107.50 (d, J=3.3 Hz), 107.23, 20.49; 19F NMR (376 MHz, CDCl3) δ: －110.77~－110.83 (m, 1F); HRMS (ESI) calcd for C13H12FNO2SNa [M+Na]+ 288.0465, found 288.0662.
N-(3-氟苯基)萘-2-磺酰胺(92): 产率57%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 8.41 (s, 1H), 7.94~7.87 (m, 3H), 7.76 (d, J=8.4 Hz, 1H), 7.66~7.58 (m, 2H), 7.19~7.13 (m, 1H), 6.93 (d, J=10.0 Hz, 1H), 6.82~6.76 (m, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.14 (d, J=245.3 Hz), 138.21 (d, J=10.3 Hz), 135.67, 135.16, 132.14, 130.70 (d, J=9.3 Hz), 129.80, 129.48, 129.28, 129.19, 128.04, 127.82, 122.14, 116.42 (d, J=2.9 Hz), 112.12 (d, J=21.0 Hz), 108.32 (d, J=25.3 Hz); 19F NMR (376 MHz, CDCl3) δ: －110.76~－110.82 (m, 1F); HRMS (ESI) calcd for C16H12FNO2SNa [M+Na]+ 324.0465, found 324.0466.
N-(3-氟苯基)噻吩-2-磺酰胺(93): 产率82%, 浅黄色固体. 1H NMR (400 MHz, CDCl3) δ: 7.58~7.55 (m, 2H), 7.24~7.20 (m, 1H), 7.03 (dd, J=4.8, 3.6 Hz, 1H), 6.97~6.93 (m, 2H), 6.88~6.83 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 163.17 (d, J=245.5 Hz), 139.17, 137.94 (d, J=10.3 Hz), 133.35, 132.97, 130.75 (d, J=9.2 Hz), 127.59, 116.81 (d, J=3.1 Hz), 112.56 (d, J=21.0 Hz), 108.70 (d, J=25.1 Hz); 19F NMR (376 MHz, CDCl3) δ: －110.66~－110.69 (m, 1F); HRMS (ESI) calcd for C10H8FNO2S2Na [M+Na]+ 279.9873, found 279.9871.
N-(3-氟苯基)-1-苯基甲磺酰胺(94): 产率60%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.37~7.31 (m, 3H), 7.29~7.23 (m, 3H), 6.92 (dt, J=10.4, 2.0 Hz, 1H), 6.87~6.83 (m, 2H), 6.66 (br, 1H, NH), 4.34 (s, 2H); 13C NMR (100 MHz, CDCl3) δ: 163.42 (d, J=245.3 Hz), 138.82 (d, J=10.5 Hz), 131.02, 130.95, 129.26, 129.06, 128.32, 114.96 (d, J=3.0 Hz), 111.58 (d, J=21.4 Hz), 106.87 (d, J=25.8 Hz), 57.90; 19F NMR (376 MHz, CDCl3) δ: －110.20~－110.26 (m, 1F); HRMS (ESI) calcd for C13H12FNO2SNa [M+Na]+ 288.0465, found 288.0462.
N-(3-氟苯基)环丙烷磺酰胺(95): 产率96%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.32~7.26 (m, 1H), 7.05 (dt, J=10.0, 2.4 Hz), 7.01~7.00 (m, 1H), 6.88 (td, J=8.4, 2.4 Hz, 1H), 6.72 (br, 1H, NH), 2.55~2.49 (m, 1H), 1.23~1.19 (m, 2H), 1.02~0.97 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 163.27 (d, J=245.2 Hz), 138.68 (d, J=10.3 Hz), 130.80 (d, J=9.3 Hz), 116.62 (d, J=3.1 Hz), 112.08 (d, J=21.1 Hz), 108.48 (d, J=25.1 Hz), 30.16, 5.79; HRMS (ESI) calcd for C9H10FNO2SNa [M+Na]+ 238.0308, found 238.0305.
N-(3-氟苯基)甲磺酰胺(96): 产率66%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.34~7.26 (m, 1H), 7.02 (dt, J=10.0, 2.4 Hz, 1H), 6.96 (dd, J=8.0, 1.6 Hz, 1H), 6.88 (td, J=8.4, 2.4, 1H), 6.84 (br, 1H, NH), 3.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.45 (d, J=245.7 Hz), 138.53 (d, J=10.2 Hz), 131.12 (d, J=9.3 Hz), 115.69 (d, J=3.1 Hz), 112.16 (d, J=21.1 Hz), 107.65 (d, J=25.4 Hz), 39.68; 19F NMR (376 MHz, CDCl3) δ: －110.20~ －110.26 (m, 1F); HRMS (ESI) calcd for C7H8FNO2SNa [M+Na]+ 212.0152, found 212.0149.
N-(3-氟苯基)-2-甲基丙烷-2-磺酰胺(97): 产率78%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.27~7.21 (m, 1H), 7.11 (dt, J=10.4, 2.4 Hz, 1H), 6.99 (dd, J=8.4, 2.0 Hz, 1H), 6.88 (br, 1H, NH), 6.80 (td, J=8.4, 2.4 Hz, 1H), 1.42 (s, 9H); 13C NMR (100 MHz, CDCl3) δ: 163.30 (d, J=244.6 Hz), 140.47 (d, J=10.5 Hz), 130.63 (d, J=9.4 Hz), 115.30, 111.23 (d, J=21.2 Hz), 107.26 (d, J=25.7 Hz), 62.45, 24.83; 19F NMR (376 MHz, CDCl3) δ: －110.82~－110.89 (m, 1F); HRMS (ESI) calcd for C10H14FNO2SNa [M+Na]+ 254.0621, found 254.0620.
N-((8R,9S,13S,14S)-13-甲基-17-氧代-7,8,9,11,12,13, 14,15,16,17-十氢-6H-环戊二烯并[a]菲-3-基)甲磺酰胺(98): 产率87%, 白色固体. 1H NMR (400 MHz, CDCl3) δ: 7.25 (d, J=6.4 Hz, 1H), 7.02~6.98 (m, 2H), 6.68 (br, 1H, NH), 3.00 (s, 3H), 2.90 (dd, J=9.2, 4.4 Hz, 2H), 2.55~1.95 (m, 7H), 1.68~1.41 (m, 7H), 0.91 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 221.00, 138.34, 137.42, 134.47, 126.74, 121.56, 118.71, 50.53, 48.08, 44.22, 39.35, 38.17, 35.97, 31.64, 29.55, 26.44, 25.84, 21.70, 13.96; HRMS (ESI) calcd for C19H25NO3SNa [M+Na]+ 370.1447, found 370.0145.
辅助材料(Supporting Information) 所有目标化合物的1H NMR, 13C NMR和19F NMR谱图. 这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.
(Zhao, C.)