FLUORINE IN THE LIFE SCIENCE INDUSTRY
138
CHIMIA 2004, 58, No. 3
Chimia 58 (2004) 138–142
© Schweizerische Chemische Gesellschaft
ISSN 0009–4293
Synthesis of Some Arylsulfur
Pentafluoride Pesticides and Their
Relative Activities Compared to
the Trifluoromethyl Analogues
Patrick J. Crowley, Glynn Mitchell, Roger Salmon*, and Paul A. Worthington
Abstract: Examples of pesticides containing an arylsulfur pentafluoride group were made and their biological ac-
tivities compared to the corresponding trifluoromethyl analogues. A phenylsulfur pentafluoride analogue of the
insecticide fipronil, screened against a resistant strain of Musca domestica, showed higher activity than the cor-
responding trifluoromethyl analogue.
Keywords: Arylsulfur pentafluorides · Biological activities · Insecticide · Pesticide · Resistant strain
Introduction
Sheppard [1], who also reported on some of disulfide and silver difluoride in an inert
the properties that this substituent provides. solvent, such as nonane, then heating this
Trifluoromethyl-substituted aromatics Key observations by Sheppard’s group with further silver difluoride in a one-pot
have been found to be particularly useful were that arylsulfur pentafluorides are typ- reaction and closely monitoring the conver-
for a range of applications in the Life Sci- ically stable entities and have similar phys- sion of the easily hydrolysed trifluoride in-
ences. Incorporation of fluorine into mole- ical and electronic properties to trifluoro- to the much more stable pentafluoride. The
cules of interest often bestows unique prop- methylaromatics. Probably due to the lack reactions were typically conducted at at-
erties to these compounds. These properties of an accessible, efficient process to these mospheric pressure under an atmosphere of
can translate into improved biological per- materials incorporation of the sulfur penta- dry nitrogen in vessels fabricated from cop-
formance through interactions at the de- fluoride substituent into potentially bioac- per. Using this procedure, we produced 3-
sired target site or by increased metabolic tive molecules had been little explored for nitro and 4-nitrophenylsulfur pentafluo-
stability, uptake and distribution.
over 30 years.
In order to test the biological effect of fides, for example as shown in Scheme 1.
The nitrophenylsulfur pentafluorides
rides from the corresponding diaryl disul-
Like many companies in the late 1980s,
ICI Agrochemicals was finding interesting replacing a trifluoromethyl substituent with
activities with compounds bearing a triflu- a sulfur pentafluoride group in compounds were reduced in high yield to the corre-
oromethyl group. This led us to investigate known to possess fungicidal, herbicidal or sponding anilines, for example using hy-
other related fluorine-containing analogues insecticidal activity we wanted to prepare a drogen and Raney nickel. Further elabora-
that might, through their different physical selection of compounds that have a variety tion of these anilines gave us the building
and electronic properties, further enhance of modes of actions. Examples of the syn- blocks for the synthesis of the required tar-
the biological effects observed with the tri- theses of some of the compounds prepared get pesticides (Schemes 2 and 3).
fluoromethyl-substituted materials.
by us have been reported [2] in detail.
More recently, an alternative process to
make arylsulfur pentafluorides using ele-
mental fluorine has been reported by Bow-
den and co-workers [4], as well as some fur-
ther chemical transformations of these mol-
ecules.
Literature searches revealed some pio-
neering work on the synthesis of arylsulfur
pentafluorides carried out in the 1960s at Fluorination of Aryl Disulfides
the research laboratories of DuPont by to Arylsulfur Pentafluorides
Our initial attempts at repeating the
process described by Sheppard [1] to make
arylsulfur pentafluorides gave inconsistent Synthesis and Insecticidal Activity
results and we wanted to devise a procedure of Arylsulfur Pentafluoride Com-
that would be more amenable to scaling up. pounds
*Correspondence: Mr. R. Salmon
Tel.: + 44 1344 414829
Fax: + 44 1344 455629
E-Mail: roger.salmon@syngenta.com
Syngenta
Jealott’s Hill International Research Centre
Bracknell, Berkshire, RG42 6EY
United Kingdom
A procedure suitable to make 100 g
amounts of materials that we required was
During a research programme aimed at
developed by our process chemists, producing insecticides for the public health
Williams and Foster [3]. The key improve- market, we discovered a series of insecti-
ment was preparing the arylsulfur trifluo- cidal N-trifluoromethylphenyl pyrimidi-
ride at ambient temperature from the diaryl nones, e.g. 1 and 2. The compounds were