Dissertation
Dissertation > Industrial Technology > Chemical Industry > Pesticide Industry > Rodenticide > Inorganic rodenticides

A Practical Synthesis of Flocoumafen

Author JiHongMei
Tutor CaiChun
School Nanjing University of Technology and Engineering
Course Applied Chemistry
Keywords Rodenticide Flocounmafen Reformatsky Demethylation
CLC TQ456.2
Type Master's thesis
Year 2012
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Flocoumafen is known as the second kind of anticoagulant, which has been successfully used as rodenticide. Besides having the properties of the first kind of anticoagulant, it is particularly effective against rodents resistant to the first kind.In this paper, an efficient rout to prepare flocoumafen was chosen according to the old methods. It was synthesized from phenyacetyl chloride and anisole through 9 steps, including friedel-crafts acylation, reformatsky reaction, dehydroxylation, hydrolyzation, cyclization, reduction, dehydration condensation, demethylation and dehydrohalogenation condensation. Flocomafen and the intermediates were characterized by 1H-NMR and MS.Moreover, the influence of reaction conditions was studied. In the end, we obtained a cheap simple and high-yield method, which made flocoumafen into industry practical. The first step, friedel-crafts acylation, occurred at 5℃with phenyacetyl chloride, anisole and AICl3 on ratio 1:1:1, in yield of 91.2%. The second step, reformatsky reaction, was prepared by 1-(4-methoxyphenyl)-2-phenyl-l-ethanone, Zn, BrCH2CO2Et and BF3·Et2O on ratio 1:3:3:3 through 3.5h, giving yield of 96.2%. The third step, dehydroxylation, employed ethyl 3-hydroxy-3-(4-methoxyphenyl)-4-phenyl-butanonate, TES, TFA and BF3·Et2O on ratio 1:1:3:1, providing yield of 95.3%. The forth step, hydrolyzation, refluxed ethyl 3-(4-methoxyphenyl)-4-phenyl-butanonate and NaOH(6eq) for 6h, with yield of 89.8%. The fifth step, cyclization, realized by heating 3-(4-methoxyphenyl)-4-phenyl-butanoic acid and PPA(2eq) at 100℃for 2h, with yield of 91.9%. The sixth step, reduction, worked out with 3-(4-methoxyphenyl)-1-tetralone and NaBH4 under equal ratio at 35℃for 2h, in yield of 97.6%. The seventh step, dehydration condensation, was obtained by refluxing 3-(4-methoxyphenyl)-1-tetralol,4-hydroxycoumarin and p-TsOH on ratio 1:3:2 for 2h, 1.2-ethylene dichloride as the solvent, giving yield of 90.0%. The eighth step, demethylation, treated 4-Hydroxy-3-[1.2.3,4-tetrahydro-3-(4-methoxyphenyl)-1-naphthalenyl]coumarin with HBr(6eq), affording yield of 37.2%. The ninth step, dehydrohalogenation condensation, went on with 4-Hydroxy-3-[1.2.3,4-tetrahydro-3-(4-hydroxyphenyl)-1-naphthalenyl]coumarin, 4-trifluoromethylbenzyl bromide, t-BuOK on ratio 1:1.5:1.5, in yield of 77.2%. The total yield of the route was 17.4%.

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