Summary

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

Published: January 03, 2018
doi:

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cisNO-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

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).

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