By Nelson Bonilla

Faculty Mentor: Dr. Davis Oldham

Abstract

Synthesis Of Myclobutanil Through Appel Halogenation and Nucleophilic Addition Of Formaldehyde Using 4-Chlorobenzyl Cyanide
Nelson Bonilla, Dr. Davis Oldham

Abstract

Myclobutanil (MT) is a chiral Triazole fungicide whose main use in agriculture is the active inhibition of vital fungal enzymes, thereby inhibiting fungal growth in crops. MT has exhibited low levels of toxicity but has been observed to lead to reproductive inhibition and liver toxicity in organisms. MT is metabolized enantioselectively, in rats, into 5 chiral metabolites. The impact of MT metabolite’s stereochemistry on their toxicity has not been well explored, but MT synthesis is required to begin the investigation. In this study, reactions to add groups to 4-chlorobenzyl cyanide, for the synthesis of MT are reported. 2-phenyl-1-ethanol’s hydroxyl group was substituted with an Iodine group, thereby rendering the molecule electrophilic using appel halogenation and subsequently underwent nucleophilic bimolecular substitution using 1H-1,2,4-Triazole yielding 2-phenyl-1-1,2,4-triazole ethane. This provides precedence for the use of appel halogenation for the addition of an electrophilic group to the fungicide substrate for the addition of the 1,2,4-Triazole through SN2. 4-chlorobenzyl cyanide was alkylated using 1-bromobutane and underwent nucleophilic addition using paraformaldehyde to produce para-(1-cyano-1-hydroxymethyl) pentylchlorobenzene. Thereby providing precedence for the successful addition of an alkyl group and hydroxymethyl group through nucleophilic addition to the fungicide substrate. This also implies that nucleophilic addition could be utilized to add an allyl group as well as a 1,2,4-triazole group, through appel halogenation and SN2, to the fungicide substrate for the synthesis of MT.