N-glycolylhydroxamic acids: An improved synthetic method and the in situ generation and intramolecular rearrangement of N-acetoxy-N-glycolyl-2-aminofluorene

Journal Article · · Chemical Research in Toxicology; (USA)

DOI:https://doi.org/10.1021/tx00004a006· OSTI ID:5116657

Corbett, M D; Corbett, B R ^[1]

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1. Univ. of Florida, Gainesville (USA)

A new and improved method for the synthesis of glycolylhydroxamic acids is described. The two-step method involves acylation of arylhydroxylamines with acetoxyacetyl chloride, followed by saponification of the ester bond to give the desired products. The conversion of hydroxamic acids to their thallous salts followed by subsequent acetylation with acetyl chloride to give N-acyloxy esters is described. During the course of this investigation, it was observed that the N-acetoxy ester of an N-glycolylhydroxamic acid was highly unstable and underwent a novel O{yields}O acyl migration. This facile rearrangement reaction was studied for the case of N-acetoxy-N-glycolyl-2-aminofluorene (N-OAc-GAF), which gave N-hydroxy-N-(acetoxyacetyl)-2-aminofluorene (N-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 N-OAc-GAF. A competition study employed the amide N-glycolyl-2-aminofluorene (GAF) and demonstrated the absence of intermolecular transfer of the N,O-acyl (acetyl) group of N-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.

• OSTI ID: 5116657
• Journal Information: Chemical Research in Toxicology; (USA), Journal Name: Chemical Research in Toxicology; (USA) Vol. 1:4; ISSN CRTOE; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400201* -- Chemical & Physicochemical Properties
550200 -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ACETYLATION
ACYLATION
AMINES
BIOCHEMICAL REACTION KINETICS
CHEMICAL REACTIONS
CHROMATOGRAPHY
ENZYMES
HYDROXAMIC ACIDS
HYDROXY COMPOUNDS
KINETICS
LIQUID COLUMN CHROMATOGRAPHY
NITROSAMINES
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
REACTION KINETICS
SEPARATION PROCESSES
STRUCTURE-ACTIVITY RELATIONSHIPS
SYNTHESIS
TRANSFERASES