Benzotrifluoride: A useful alternative solvent for organic reactions currently conducted in dichloromethane and related solvents
Benzotrifluoride: A useful alternative solvent for organic reactions currently conducted in dichloromethane and related solvents
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DOI：
10.1021/jo9620324
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发表时间：
1997-02-07
影响因子：
3.6
通讯作者：
Curran, DP
中科院分区：
文献类型：
--
作者：
Ogawa, A;Curran, DP
二氯甲烷是有机合成中最常用的溶剂之一，因为它对有机分子具有良好的溶解能力，具有良好的物理性质，并且对许多类型的试剂和反应条件具有惰性。2它的弱刘易斯碱性使其对有机金属和刘易斯酸反应特别有吸引力，3它也常用于氧化4和官能团相互转化。5然而，二氯甲烷的毒性加上其低沸点（40 ℃）可能会造成问题。6因此，开发可以替代二氯甲烷的其他溶剂是一个有用的目标。在本文中，我们报告的三氟甲苯7（C6 H5 CF 3，BTF，1）是一个潜在的有价值的替代溶剂二氯甲烷。BTF是一种透明的自由流动液体，沸点为102 ℃，熔点为-29 ℃，密度为1.2 g/mL（25 ℃）。它是一种稳定的化合物，毒性和价格相对较低。8从溶剂极性的经验测量判断，2b，c BTF的极性比氟苯、THF和乙酸乙酯略强，与五氟苯非常相似，比氯仿、吡啶和二氯甲烷略弱。尽管有这些有利的性质，BTF在有机合成中不用作溶剂。我们最近成功地使用BTF作为混合有机/氟溶剂9，表明它能够溶解各种有机化合物。这表明BTF作为标准有机合成溶剂的潜力未得到重视。为了评估这种潜力，我们从文献中选择了一系列有代表性的转化，并进行了仅在三氟甲苯取代二氯甲烷方面不同的反应对。结果表明，三氟甲苯作为溶剂对许多类型的有机反应显示出良好的潜力。我们首先研究了一些常见的醇类衍生反应。标准酰化、10、11甲苯磺酰化、12和甲硅烷基化13反应都发生在BTF中，其产率和反应时间与CH 2Cl 2中的对应物相当。这些实验的结果在辅助资料中有描述。我们接下来检查了醇类氧化的一些代表性程序。Swern氧化是将醇转化为醛或酮的公知方法，并且通常在低于-60 ℃下进行以避免不稳定中间体的分解。14然而，Swern和同事报告说，使用过量的试剂能够在更高的温度下氧化。因此，我们研究了仲醇在BTF中在-27 ℃下的Swern氧化.当在-27 ° C下将二甲基亚砜（DMSO）添加到草酰氯（1.3当量于醇）的BTF溶液中时，发生剧烈的气体逸出（推测为CO和CO2）。立即在-27 ℃下向混合物中加入2-辛醇.随后加入Et 3 N并进行后处理，得到76%产率的2-辛酮（当量1）。2-辛醇在二氯甲烷中在类似条件下氧化生成2-辛酮，产率为71%。
Dichloromethane is one of the most popular solvents in organic synthesis1 because of its good dissolving power for organic molecules, its favorable physical properties, and its inertness toward many types of reagents and reaction conditions. 2 Its weak Lewis basicity makes it especially attractive for organometallic and Lewis acid reactions, 3 and it is also commonly used in oxidations4 and functional group interconversions. 5 However, the toxicity of dichloromethane coupled with its low boiling point (40 C) can pose problems. 6 Thus, the development of other solvents that can substitute for dichloromethane is a useful goal. In this paper, we report that benzotrifluoride7 (C6H5CF3, BTF, 1) is a potentially valuable alternative solvent to CH2Cl2. BTF is a clear, free-flowing liquid with a boiling point of 102 C, a melting point of-29 C, and a density of 1.2 g/mL (25 C). It is a robust compound with a relatively low toxicity and price. 8 Judging from empirical measures of solvent polarity, 2b, c BTF is slightly more polar than fluorobenzene, THF, and ethyl acetate, very similar to pentafluorobenzene, and slightly less polar than chloroform, pyridine, and dichloromethane. 7b Despite these favorable properties, BTF is not used as a solvent in organic synthesis. Our recent success in using BTF as a hybrid organic/fluorous solvent9 showed that it is capable of dissolving a wide variety of organic compounds. This suggested that the potential of BTF as a solvent for standard organic synthesis was unappreciated. To evaluate this potential, we selected a series of representative transformations from the literature and conducted pairs of reactions differing only in the substitution of benzotrifluoride for dichloromethane. The results suggest that benzotrifluoride shows good potential as a solvent for many types of organic reactions. 8c We first examined some common derivatization reactions of alcohols. Standard acylation, 10, 11 tosylation, 12 and silylation13 reactions all occur in BTF in comparable yields and reaction times to their counterparts in CH2Cl2. The results of these experiments are described in the Supporting Information.We next checked some representative procedures for the oxidation of alcohols. The Swern oxidation is a wellknown method for the conversion of alcohols to aldehydes or ketones, and it is typically performed below-60 C in order to avoid the decomposition of unstable intermediates. 14 However, Swern and co-workers reported that the use of excess amounts of reagents enables the oxidation at higher temperatures. Thus, we examined the Swern oxidation of a secondary alcohol in BTF at-27 C. Vigorous gas evolution (presumably CO and CO2) occurred when dimethyl sulfoxide (DMSO) was added to the BTF solution of oxalyl chloride (1.3 equiv to the alcohol) at-27 C. Immediately, 2-octanol was added to the mixture at-27 C. Subsequent addition of Et3N and workup provided a 76% yield of 2-octanone (eq 1). The oxidation of 2-octanol in CH2Cl2 under similar conditions gave rise to 2-octanone in 71% yield.