Facile synthesis of 14C-nitrofurazone from 14C-urea

Abstract

The veterinary drug nitrofurazone (5-nitro-2-furaldehyde semicarbazone) exhibits excellent antimicrobial properties but its application in food-producing animals is prohibited. The illegal use of nitrofurazone is regularly monitored by food regulatory agencies. Currently, semicarbazide (SEM) is used as a marker of nitrofurazone exposure. However, the use of SEM as a marker of nitrofurazone is under scrutiny after evidence of a high incidence of false positive tests. To overcome the current dilemma, it is necessary to identify a nitrofurazone-specific marker analyte which requires conducting nitrofurazone metabolism studies in food-producing animals. The use of carbon-14 labeled nitrofurazone would facilitate metabolism studies and structural elucidation of nitrofurazone metabolites of possible utility as a marker compound. In the present work, a synthetic method is described to procure radiolabeled nitrofurazone that incorporates ¹⁴C- carbon at the semicarbazide moiety. The method incorporates ¹⁴C-carbon via employing readily available and more economically affordable [¹⁴C]-urea compared with [¹⁴C]-semicarbazide. To the best of our knowledge, there is no report on the synthesis of 5-nitro-2-furaldehyde [¹⁴C]-semicarbazone from ¹⁴C-urea. The developed method involves monoamination of [¹⁴C]-urea followed by a condensation reaction with 5-nitro-2-furaldehyde to produce 5-nitro-2-furaldehyde [¹⁴C]-semicarbazone in 85% yield with greater than 98% radiochemical purity.