N-glycolylhydroxamic acids: an improved synthetic method and the in situ generation and intramolecular rearrangement of N-acetoxy-N-glycolyl-2-aminofluorene.
N-glycolylhydroxamic acids: an improved synthetic method and the in situ generation and intramolecular rearrangement of N-acetoxy-N-glycolyl-2-aminofluorene.
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N-羟肟酸：一种改进的合成方法以及N-乙酰氧基-N-羟肟酸的原位生成和分子内重排。
DOI：
10.1021/tx00004a006
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发表时间：
1988
影响因子：
4.1
通讯作者：
Corbett,BR
中科院分区：
文献类型：
--
作者：
Corbett,MD;Corbett,BR
介绍了一种新的合成羟乙酰异羟肟酸的改进方法。两步法包括芳基羟胺与乙酰氧基乙酰氯的酰化反应，然后酯键皂化得到所需的产品。异羟肟酸转化为亚铊盐，然后与乙酰氯乙酰化，得到N-酰氧基酯。在此研究过程中，观察到N-羟乙酰氧肟酸的N-乙酰氧基酯高度不稳定，并经历了新的O-”O酰基迁移。以N-乙酰氧基-N-羟乙酰基-2-氨基芴（TV-OAc-GAF）为例，研究了这种简单的重排反应，得到N-羟基-N-（乙酰氧基乙酰基）-2-氨基芴（TV-OH-AcAAF）作为重排反应的唯一产物。使用HPLC研究该反应，并包括归因于TV-OAc-GAF的HPLC峰的归属。竞争研究采用酰胺N-羟乙酰基-2-氨基芴（GAF），并证明了不存在TV-OAc-GAF的N，0-酰基（乙酰基）基团的分子间转移。可能的分子内重排反应的机制，沿着考虑它可能具有的毒性的羟乙酰氧肟酸。
A new and improved method for the synthesis of glycolylhydroxamic acids is described. The two-step method involves acylation of arylhydroxylamineswith acetoxyacetyl chloride, followed by saponification of the ester bond to give the desired products. The conversion of hydroxamic acids to their thallous salts followedby subsequent acetylation with acetyl chloride to give TV-acyloxy esters is described. During the course of this investigation, it was observed that the N-acetoxy ester of an TV-glycolylhydroxamic acid was highly unstableand underwent a novel O—" O acyl migration. This facile rearrangement reaction was studied for the case of TV-acet-oxy-TV-glycolyl-2-aminofluorene (TV-OAc-GAF), which gave TV-hydroxy-7V-(acetoxyacetyl)-2-aminofluorene (TV-OH-AcAAF) as the sole product of this rearrangement. HPLC was used to investigate this reaction and included the assignment of an HPLC peak to be due to TV-OAc-GAF. A competition study employed the amide TV-glycolyl-2-aminofluorene (GAF) and demonstrated the absence of intermolecular transfer of the TV, O-acyl (acetyl) group of TV-OAc-GAF. The mechanism for the probable intramolecular rearrangement reaction is presented, along with a consideration of the possible significance it might have for the toxicity of glycolylhydroxamic acids.