Editing Permethrin (section)

== History ==
In the early 1970s, it was identified that in many pyrethroids, including all natural [[pyrethrin]]s and some synthetic analogs developed by that time (such as [[resmethrin]]), the [[furan]] ring, being a probable site for photo-sensitized attack by oxygen, was responsible for their instability in air and light. Hence, a group of agricultural chemists at the [[Rothamsted Experimental Station]] led by [[Michael Elliott (chemist)|Michael Elliott]] tried to substitute the 5-benzyl-3-furylmethyl alcohol with quite a few structurally similar ones. Discovering that an ester of 3-phenoxybenzyl alcohol with a slightly modified (chlorine-substituted) analog of the [[chrysanthemic acid]] they also found earlier was both photo-stable and very toxic for insects, they filed their patent applications in 1972 and published their results in [[Nature (journal)|Nature]] in 1973.<ref name=":0">{{cite journal | vauthors = Elliott M, Farnham AW, Janes NF, Needham PH, Pulman DA, Stevenson JH | title = A photostable pyrethroid | journal = Nature | volume = 246 | issue = 5429 | pages = 169–170 | date = November 1973 | pmid = 4586114 | doi = 10.1038/246169a0 | s2cid = 4176154 | bibcode = 1973Natur.246..169E }}</ref><ref>{{Cite patent|country=GB|number=1413491|title=3-SUBSTITUTED-2,2-DIMETHYL-CYCLOPROPANE CARBOXYLIC ACID ESTERS THEIR PREPARATION AND THEIR USE IN PESTICIDAL COMPOSITIONS|pubdate=1973-04-30|gdate=1975-11-12|invent1=Elliott|invent2=James|invent3=Pulman|inventor1-first=Michael|inventor2-first=Norman Frank|inventor3-first=David Allen|assign1=National Research Development Corporation}}</ref>

Numerous synthetic routes exist for the production of the DV-acid ester precursor.<ref>DV-acid = 3-(2,2-'''D'''ichloro'''v'''inyl)-2,2-dimethylcyclopropanecarboxylic acid</ref> The pathway known as the Kuraray Process uses four steps.<ref name="Leonard A. Wasselle 1981" /> In general, the final step in the [[total synthesis]] of any of the synthetic [[pyrethroid]]s is a coupling of a DV-acid ester and an alcohol. In the case of permethrin synthesis, the DV-acid [[cyclopropanecarboxylic acid]], 3-(2,2-dichloroethenyl)-2,2-dimethyl-, ethyl ester, is coupled with the alcohol, [[m-phenoxybenzyl alcohol]], through a [[transesterification]] reaction with base. [[Tetraisopropyl titanate]] or [[sodium ethylate]] may be used as the base.<ref name="Leonard A. Wasselle 1981">{{cite web | vauthors = Wasselle LA | title = Pyrethroid Insecticides | url = https://www.spglobal.com/pdf/RP143_toc_173236110917062932.pdf | work = SRI International Report #143 | location = Menlo Park, CA | date = June 1981 | access-date = 17 September 2023 | archive-date = 16 March 2024 | archive-url = https://web.archive.org/web/20240316192334/https://www.spglobal.com/pdf/RP143_toc_173236110917062932.pdf | url-status = live }}</ref>

The alcohol precursor may be prepared in three steps. First, [[m-cresol]], [[chlorobenzene]], [[sodium hydroxide]], [[potassium hydroxide]], and [[cuprous chloride]] react to yield [[m-phenoxytoluene]].<ref>{{cite patent |inventor=Colby, Thomas H. |country=US |number=4229594A |pubdate=1980-10-21 |title=Preparation of meta-phenoxytoluene}}</ref> Second, oxidation of m-phenoxytoluene over [[selenium dioxide]] provides [[m-phenoxybenzaldehyde]]. Third, a [[Cannizzaro reaction]] of the [[benzaldehyde]] in [[formaldehyde]] and potassium hydroxide affords the m-phenoxybenzyl alcohol.<ref name="Leonard A. Wasselle 1981" />