Development of a synthetic route to the active ingredient of an agricultural herbicide
O'Donovan, Rory
(1999)
Development of a synthetic route to the active ingredient of an agricultural herbicide.
Master of Science thesis, Dublin City University.
A multistep synthesis of 4-amino-3-methyl-6-phenyl-l,2,4-triazin-5-one (Metamitron) from inexpensive phenylglyoxylonitrile and chromatographic systems to accurately monitor each step have been developed. Details of the synthetic steps are as follows:
1. Hydrolysis of phenylglyoxylonitrile to phenylglyoxylic acid amide.
2. The in situ methanolysis of this amide to phenylglyoxylic acid methyl ester.
3. The conversion of this ester to its 2-acetylhydrazone by reaction with acetylhydrazine.
4. The reaction of this 2-acetylhydrazone with hydrazine monohydrate to form phenylglyoxylic acid hydrazide 2-acetylhydrazone.
5. The cyclisation of this hydrazide derivative to 4-amino-3-methyl-6- phenyl-1,2,4-triazin-5-one (Metamitron).
During the synthetic process it was shown that
phenylglyoxylic acid methyl ester 2-acetylhydrazone and phenylglyoxylic acid hydrazide 2-acetylhydrazone were present as isomers (E- and Z-) and that isomérisation of the E-isomer of the hydrazide derivative about the carbon-nitrogen double bond must take place prior to cyclisation to Metamitron.
A series of HPLC methods was developed to accurately
monitor each stage of the synthesis. This involved the isolation and identification of the isomers of the hydrazone and hydrazide in a high state of purity. These systems enabled the identification and quantitation of each of the components and isomers present in the reaction mixtures and the identification and quantitation of impurities present in the final product (Metamitron).