准备n-(2-alkoxyvinyl) 磺胺从n-tosyl-1,2,3-triazoles 和随后转换为取代 Phthalans 和 Phenethylamines
Summary
本文详细介绍了合成N-(2-alkoxyvinyl) 磺胺以及随后转换为 phthalan 和乙胺衍生物的典型实验过程。
Abstract
分解的N-tosyl-1,2,3-triazoles 与铑 (II) 乙酸二聚体在醇的存在形式综合地多才多艺的N-(2-alkoxyvinyl) 磺胺, 在各种各样的情况下起反应到负担得起有用的n和包含化合物的O。酸催化添加醇或硫到N-(2-alkoxyvinyl) 含有磺胺类的 phthalans, 分别提供了酮和 thioketals 的通道。选择性还原乙烯基在N-(2-alkoxyvinyl) 含有磺酰胺的 phthalans 通过加氢生成相应的 phthalan 在良好的产量, 而减少与钠双 (2-氧) aluminumhydride 产生环形开启的乙胺模拟。由于N-(2-alkoxyvinyl) 磺酰胺官能团是综合通用的, 但通常作用不稳定, 因此该协议强调在准备、处理和反应这些关键基板的几个有用转换.
Introduction
铑 (II)-azavinyl carbenoids 最近出现了作为一个异常地多才多艺的反应中间 en 到许多可贵的产品的路线。1,2,3,4,5,6,7,8,9,10特别地, 这些中间体的许多新颖的用途为生产杂10为化学家提供了新的和高效率的综合战略。为此, 我们集团发起了一项新的 phthalans11合成协议的开发, 这将利用最近在和 oxygen-based 核内分子内添加的进展到 Rh (II)-azavinyl carbenoids从N-sulfonyl-1,2,3-triazoles 派生的。12,13,14,15,16,17我们的方法具有一个简单的 two-step 协议, 用于将终端炔烃如1转换为N-sulfonyl-1,2,3-triazoles 2 , 并带有一个下垂的酒精 (图 1)。随后, Rh (II)-催化脱/13 OH 插入级联从2提供 phthalans 3具有反应性的N(2-alkoxyvinyl) 磺胺类官能团。
由于n-(2-alkoxyvinyl) 磺胺类基团是一种潜在的多用途, 但相对 (的n-和O-包含 synthon,16,17,18,19,20,21,22,23,24,25,26,27在各种条件下 (图 2), 我们对其熔融烯-醚/烯-磺酰胺系统的反应性感兴趣。在筛选各种还原协议后, 确定了两种方法, 它们导致了稳定的 phthalan 和/或包含乙胺的产品 (图 2, 3 → 4/5)。首先, 它被发现, 标准氢化的N-(2-alkoxyvinyl) 磺酰胺的3a与催化钯碳 (Pd/c) 有选择地减少 c = c 键屈服 phthalan 4。另外, 在乙醚/甲苯中使用钠双 (2-氧) 铝氢化物处理的3a提供了唯一替代的乙胺导数5。我们认为, 这两种转换都是有价值的, 因为它们导致具有潜在生物活性的产品类别, 包括嵌入乙胺产生的活性属性, 而在4的情况下, 金属螯合通过面向cis的N和O-原子。
在调查酸性促进的添加物以利用富含电子的 c = c 键的3a时, 发现在酒精或硫醇存在的情况下, 用催化的三甲基硅基氯化物处理此化合物, 产生了酮6 c和分别 thioketal 6e, 同时保持双 phthalan 框架的完整性。另外, 在1:1 乙酸/水溶液中搅拌3a会产生稳定的 hemiketal 6d。
Protocol
1. 合成n-磺唑 2a: (2-(1-磺-1H-12, 3-唑-4-基) 苯基) 甲醇 添加一个 3 x 10 mm 聚四氟乙烯磁性搅拌棒, 139 毫克 2 ethynylbenzyl 酒精, 和20毫克的铜 (I) 吩 (CuTC) 的烤箱干 2-5 毫升微波瓶和密封瓶安全与隔膜帽和机。由于微波的快速加热, 总是使用新的小瓶和无任何缺陷的瓶盖, 并确保瓶盖是安全和适当的安装。 真空下从瓶子中取出空气, 再用氩气充三次。 通过注射器加入4毫?…
Representative Results
本研究的所有化合物都以1H 和13C 核磁共振波谱和电喷雾质谱 (ESI) 为特征, 以确认产品结构并评估纯度。本节描述了代表性化合物的关键数据。 光谱数据与2a (图 3) 的三唑结构有很好的一致性。在2a的1H 核磁共振谱中, 三唑的特征 C5 质子出现在 8.45 ppm, 为1H …
Discussion
三2 a-b可以通过铜 (I)-催化叠氮化-炔烃 [3 + 2] 加 (CuAAC) 以 CuTC 为催化剂清洁地获得。值得注意的是, 在高温下, 三唑2a是最有效的, 通过标准氯仿回流在3h 或加热到100° c, 在微波反应器中15分钟 (注: 时间可能因微波效率的不同而变化);然而, 三唑2b通过室温下的 CuAAC 最有效地制备。因此, 在新的基板上执行本协议时, 必须努力确定此基板相关反应的最佳条件。在微?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
这项工作由汉密尔顿学院和爱德华和弗吉尼亚泰勒基金资助, 用于学生/教员的化学研究。
Materials
| 2-Ethynylbenzyl alcohol, 95% | Sigma Aldrich | 520039 | |
| Copper (I) thiophene-2-carboxylate | Sigma Aldrich | 682500 | |
| Chloroform, ≥99% | Sigma Aldrich | 372978 | |
| Toluenesulfonylazide, 99.24% | Chem-Impex International | 26107 | Potentially explosive |
| Dichloromethane, ≥99.5% | Sigma Aldrich | 320269 | |
| Rhodium (II) acetate dimer, 99% | Strem Chemicals | 45-1730 | |
| Silica Gel, 32-63, 60A | MP Biomedicals Inc. | 2826 | For silica gel plugs |
| Hexanes | Sigma Aldrich | 178918 | |
| Ethyl acetate | Sigma Aldrich | 439169 | |
| Chlorofom-D | Sigma Aldrich | 151823 | |
| Ethylene glycol | Sigma Aldrich | 293237 | |
| Chlorotrimethylsilane, 98% | Acros | 11012 | |
| Sodium bicarbonate | Sigma Aldrich | S6014 | Dissolved in deionized water to prepare a saturated aqueous solution |
| Sodium sulfate | Fisher Scientific | S429 | |
| Ethyl alcohol, absolute – 200 proof | Aaper Alcohol and Chemical Co. | 82304 | |
| 10 wt% Palladium on carbon | Sigma Aldrich | 520888 | Can ignite in the presence of air, hydrogen gas, and/or a flammable solvent |
| Hydrogen gas | Praxair | UN1049 | |
| Diethyl ether | Sigma Aldrich | 309966 | |
| 60 wt% sodium bis(2-methoxyethoxy)aluminum hydride solution in toluene | Sigma Aldrich | 196193 | Reacts violently with water |
| Methanol | Sigma Aldrich | 34966 | |
| Ammonium chloride | Fisher Scientific | A661 | Dissolved in deionized water to prepare a saturated aqueous solution |
| Hydrochloric acid, 37% | Sigma Aldrich | 258148 | Dissolved in deionized water to prepare a 1M solution |
| Sodium Chloride | Sigma Aldrich | S25541 | Dissolved in deionized water to prepare a saturated aqueous solution |
| 2-5 mL Microwave vials | Biotage | 355630 | |
| Microwave vial caps | Biotage | 352298 | |
| RediSep Rf Gold Normal Phase, Silica Columns, 20 – 40 micron | Teledyne Isco | 69-2203-345 | For column chromatography |
| Balloons | CTI Industries Corp. | 912100 | For hydrogenation |
| Biotage Initiator+ Microwave Reactor | Biotage | 356007 |
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Cite This Article
Bennett, J. M., Shapiro, J. D., Choinski, K. N., Mei, Y., Aulita, S. M., Dominguez, G. M., Majireck, M. M. Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines. J. Vis. Exp. (131), e56848, doi:10.3791/56848 (2018).