Note: Descriptions are shown in the official language in which they were submitted.
~S~
-- 1 --
This application is a division of Serial No. 309,182
filed ~ugust 11, 197~.
~ his invention relates to certain pyridine derivatives
having herbicidal properties, and to herbicidal processes
and compositions utilising them.
According to the present invention there are provided
herbicidal pyridine compounds of the formula (I):-
W
~ N ~ O ~ o_cRl_R2
wherein Z and Y each represent a fluorine, chlorine, bromine,
iodine, or hydrogen atom, or a trifluoromethyl, difluoromethyl,or chlorodifluoromethyl radical, provided that at least one
of Z and Y is a halogenomethyl radical; Rl represents
hydrogen or an alkyl radical of 1 to 4 carbon atoms; and R2 -
is a cyano group; a carboxyl group; a carboxamide group
-CNR3R4 wherein R3 is hydrogen or an alkyl radical containing
1 co 4 carbon atoms and R4 is hydrogen, alkyl containing 1
to 4 carbon atoms which may be optionally substituted on
the omega carbon by hydroxy or phenyl, a phenyl or chloro-
phenyl radical, an alkoxy radical of 1 to 4 carbon atoms,ol a group -NR5R~ wherein R5 is hydrogen and R6 is hydrogen,
phenyl, or chlorophenyl, or the group -NR3R4 constitutes a
pyrrolidino, piperidino, or morpholino radical; a group
-CSR7 wherein R7 is phenyl; an alkoxycarbonyl group wherein
the alkoxy group contains 1 to 8 carbon atoms and may be
straight or branched, and which optionally bears one or
more hydroxy, alkoxy containing 1 to 4 carbon ato~s, or
halogen substituents, or bears a substituen~ of Formula (I)
wherein R~ represents a -~-0- radical; a cyclohexyloxycarbon~
O
~2q~ V~i
radical optionally substituted by one or more halogen
atoms or methyl radicals; an alkenyloxycarbonyl radical
in which the alkenyl group contains from 3 to 6 car~on atoms;
a phenoxycarbonyl radical optionally bearing one or more
halogen or methyl substituents; or a benzyloxycarbonyl
radical, the phenyl group of which optionally bears one or
more halogen or methyl substitutents; and, in the case of
compounds wherein R2 is a carboxyl group, salts thereof.
When R3 is an alkyl radical it is preferably an alkyl
radical of 1 to 12 carbon atoms, for example an alkyl
radical of 1 to 4 carbon atoms.
When R7 is an alkyl radical it may be for example an
alkyl radical of 1 to 20 carbon atoms. Examples of alkyl
radicals within this range include those of 1 to 12
carbon atoms, for example methyl, ethyl, propyl, butyl,
and dodecyl.
When R2 is an alkoxycarbonyl group, the alkoxy group
may contain for example from 1 to 20 carbon atoms; it
may for example contain from 1 to 12 carbon atomsO Within
this range, the alkoxy group may for example contain from
1 to 8 carbon atoms. Particular examples of alkoxy groups
within this range include methoxy, ethoxy, propoxy, butoxy,
-
~5~0~
-- 3
Salts of compounds according to the invention
wherein R2 represents a carboxylic acid may be prepared
by conventional methods known for the preparation of
salts of carboxylic acids. T~pical salts include me~al
s salts and ammonium salts. Metal salts include salts
formed with alkali metal cations, for example sodium,
potassium and lithium, and alkaline earth metal cations,
for example calcium, strontium, and magnesium. ~mmonium
salts include salts formed with the ammonium cation or
lo with a mono-, di-, tri-, or tetra-substituted ammonium
cation in which the substituents may be, for example,
aliphatic radicals of l to 6 carbon atoms; these may
be, for example, alkyl radicals of 1 to 6 carbon atoms.
One group of compounds according to the invention
includes those in which the group Z is a CF3 radical, Y
is a hydrogen atom, Rl is a methyl group, and R2 is
as defined above. Within this group, R2 may be, for
example, a carboxyl group either as such or in the form
of a salt thereof, or may be an alkoxycarbonyl radical,
for example an alkoxycarbonyl radical in which the
alkoxy group contains from l to 6 carbon atoms.
Another group of compounds according to the
invention includes those in which the group Z is a
CF3 radical, Y is a chlorine atom, Rl is a methyl group,
and R is as defined above. Within this group, R may
be, for example, a carboxyl group either as such or in
the form of a salt thereof, or may be an alkoxycarbonyl
radical, for example an alkoxycarbonyl radical wherein
the alkoxy group contains from l to 6 carbon atoms.
A further group of compounds according to the
invention includes those in which the group Z is a
difluoromethvl or chLorodifluoromethyl radical, ~ is
hydrogen or chlorine, Rl is a methyl sroup, and R2 is
as defined above. Within this group of compounds, R2
may be, for example, a carboxyl group either as such
or in the form of a salt thereof, or may be an alkoxy~
~a2~5~305
carbonyl radical, for example an alkoxycarbonyl
radical wherein the alkoxy group contains from 1 to
6 carbon atoms.
The compounds of the invention, apart from those
5 in which the group Rl in Formula (I) is a hydroqen
atom, contain an asymmetric carbon atom, and are
therefore capable of existing in two optically
isomeric forms. The present invention includes the
dextro- and laevo- rotatory isomers of each compound
lo of the invention, and their mixtures i:n all proportions.
Particular examples of compounds according to the
invention include those listed in Table I below:-
~2~5~3~5
-- 5 --
Z O ~ h
~ o E~
u~ Z Z. . u~ In Ll
. O O O o ~ O O O O
U ~ ~ ~ ~ ~ O O . O O ~1 ~1
~ Z ZQ~ ~ o U~ O o
U H
~ ~ ~0 , R
P~ ~ m m m m
C~=O ; .
o _
~ ~ .
., H l ~ ~~ ~ ~ ~ .
1:~ ~ ~ - P~ C~ C) U-C.)
o o O O o O
E~ ~ O ____ . . ~._ I
~=<Z 1_1 ~ XC`~
.___ . _._ _ ,,_
-- X
-- - .
~ ~ ~ ~ ) ~ ~ ~ ~
-
z~
O O ~ ~ ~ ~ u~ ~ r~ OD G~
o ~-.---
~Z~580S
6 --
_
E~ ~:
~Z O O c~ a~
a~
Z Z; C~
OOO ~o a:) ~ t~
~ ~ ~ ~ ~ ~ ~ ~ ~ ~ c~ ~o ~ ~r
~-1 ~ r~ ~1 ~ r I r~ r~l
'1 ~ ~ O O O O O O O
¢ Z Z . 0
H E~ ~
~:1 0
~m
.
_ . _
~ I X ~ C~ U
n ~ ~ ~ a~ o ~ O -
~ ~ X ~ ~ ~ ~ C ~ V ~
C~; C~ ~ I O ~ ~
CO U Z o
H :r: C ) C_) t) ~ 1 C,) 5 C ) C : --
t1 ~ C,). ~ ~ ~: Q Z ~
Z ~ t ) ~ Z ~1:
O ~_)--o ~ O O O Z
C~ O
H
.
~ ~ r 7 ~ ~ ~ ~
m ~
C~ V C~ .
__
. ~ ~ ~ ~ ~ ~-
C~
_ . _
a
O O O~ ~ ~ ~ O r~ O
:~ Z ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~
o
5~5
-- 7
_
~o~
~ ~_
Z Z ~r O
C~ P~ ~ ~ ~ ~r
~1~ ~ r~ O ~ ~ ,~
C ) H H O O O O O O O O O O
H E~ ~1
?~ ~ O F
_ . __ . _ .....
~c c~ ~ ~ !
o~ ~: ~ U o
a ~. C~ ~"'
a~ ~ X ~ r
~> ~; ~ c.) c~ ~ ~ ~ ~ o
Z X -- ~ o 3~ X O C~
Z Z X O O :.
C) Z
H
~1 5~ X
~ C.) U ~) ~_) C~) C- C ) C) C-
_
X ~ X ~X C) C~ O C~ C~ .
-- ~ _
~ ~ ~ rl ~ ~ ~ ~ ~ ~ ~7
t~ C~ C~ C~ C~
_
~Z
O O ~ ~ ~ ~ Ln ~ r~ O
Z ~ ~ ~ ~`I
g
.
~zlDS~5
8 --
E~ P
Z o
rS ,~
E~
~ Z Z
Z H H
O O O
~ ~ "~
rS ~; Z O O O O O O O O O O O
~) H H
H E~ ~1
~
p, _
_I
l ~ 3
a ~ ~ ~ V ~ o r- ~
r.~ ~ ~ ~ ~ ~ :C ~ ~'r
:~ ~ ~ o~)--u c~ ~ ~ x
Z C.) G ~11^1C~ 1 ~ t~l C_) CO ~_) .
H O V C ) V 3: ~ ~ ~:
E~ O O O~ c~ :~ C~ t_) ~ O Z
Z ' 3: :~ o O O V
O o_o O
H
~ ~ ~ ~ ~7 ~ ~ r~ ~7
m ~ ~ 3 3
É~ 1~ ~ C) C.) C ) C.) O C~ ~) U 10 V .,
. ..
C~ V U C~ U
.
c~ ~ ~ ~ ~ ~ ~ ~4
o c~ )
z
O O ~ ~ U~
:~ ~
~2~5~3~S
g
Z O u-, In
~5 -- u~ O
E~ E~ ~ O ~
V~ Z Z O ~ ~ ~ ~ ~ ~ ~D
O O O ~ O ~
C~ ~ ~ ~ ~ O . . ~D -~1 ~ ~U~ ~ ~
C~ C~ ~ ~ o '~ 'o o o
~: Z Z
C ) H H Q~ Q~ Q, Q. -
H E~ ~ . . . ~ E
E E E
. . I
o 5U~ V
C: ~ ~ ~ ~ X
D C~ ~ ~ O C~
:~ ~ , ~: Z ~ ~ ~ C~ C~
Z ~' Z ~ Z o o X ~C :.
H t O O C~ : =
~-)
H ~ t~l ~~1~') ~ t~ ~ ~(`1
~1 X :~ ~C X ~ 3: ~ S
¢; U C~ U U U C~ U U C)
m
E~
.~ ~.~ .~_1 .~ .~ .~ .~ .
~ C> C~ C~ U C~ U ~ t~ _-
_ _ _ .... __
r~ ~ ~ ~ ~ ~ ~ ~ ~ h h
C~ ~ ~ ~ ~ ~ ~ ~ ~ ~) ~ C~ C~
V V ~ C~ U V C~ C~
~ U C~ U
_ ~
a
Z .
O O G U l ~ ~ ~ O ~ ~`J ~') ~ U-)
Z ~
~J .. _
~()5l~30~
-- 10 --
E~ ~
~o
r~ E~ r~
tn Z Z
Z H H
ooo ~o ~ ~a ra
.~1 ~ ~ ~ rl ~ ~ -~ ~1 ~1 ~1 -~1
) O O O O O O O O O O O O
~ Z Z 0~ U~ Ul Ul
C ) H H .
U~ H
rl o
~:
Q~
c~ I O O
~ ~ ~ ~ ~ 3~
r~ ~ c~ I ~9 o .
a ~ ~
rSl ~ z o ~) o c~ ~ z ~ o
Z ~ o o ~C I Z O :.
H O ~ O : =
Z Z
C~
H 1~ ~') ~ ~ ~ t`') t`~ ~ ~ ~ ~ ~
r~ r~ c~ ~ v c c
.
.
r~
~1 ~) ~) c~ r~ a~ r~ r~ h rS- r~ r~ r~
_ c~ c~ c~ ~ c~ c~
~ ~ r~ r~ r~
~ ~J ~ U r~ r~ ~ ~ ~ ~ ~ ~ ~
~ ~ ~ c~
c~
-
a
z~
O O ~ t~ r~ a~ O ,~ ~ r~
:~: Z
C~
_ ___
~2~5~135
~;
o
E~
Z H Z
OOC
C) ~ P~
1 ~ ~ O O O O O O O O
¢ Z Z .
C,) H H
~I El
U~ ~ H
~: m
U~
~ ~ N~J N N N N N
~ O C~
a o o o o o o o o
æ _ _
H
o ~1 u~¦
C~
H C~
m
. _ _
~ N
. . h h 14 0 C~ O C.) O
æ
O O ~ ~ O ~1 ~ ~) G Ll~
o Z ~
U .~ _
~;~QS8~5
- 12 -
The formulae of two further compounds not
conveniently listed in Table I are given below:-
3 ~
N ~ O ~ OCHCN
Compound 76
(oil)
Compound 77
(oil)
In the case of a number of .he c^~mpounds in theabove table ! a physical constant in the form of a
s boiling point or melting point is not available since
the cornpounds were often isolated by thin layer chroma-
~,ography and a high proportion are viscous oils. The
structure of the compounds was confirmed by examining
their nuclear magnetic resonance spectra, which
lo corresponded with the structure assigned in Table I.
The compounds of the invention are herbicides
which are in general substantially more effective
against grass species than against broad-leaved species
of plants. They may be used to control unwanted grass
species growing alone, or at suitable rates of appli-
cation they may be used to control grass weeds growing
among broad-leaved crop plants. The compounds may be
either applied to the soil before the emergence of the
unwanted grass species (pre-emergence application) or
~S~305
- 13 -
to the above-ground parts of growing grass plants
(post-emergence application).
In another aspect, therefore, the invention
provides a process of inhibiting the growth of unwanted
plants, particularly grass species, which comprises
applying to the plants, or to the locus thereo~, a
herbicidally effective amount of a compound of formula
(I) as hereinbefore defined.
The amount of the compound to be applied will
lo depend upon a number of factors, for example the
particular plant species whose growth is to be in-
hibited, but in general an amount of from 0.0?5 to 5
kilograms per hectare is usually suitable, and preferably
from 0.1 to l.O kilograms per hectare. The skilled
worker in the art will readily be able to determine
suitable amounts for use by means of standardised
routine tests, without undue experimentation.
The compounds of the invention are preferably : _
applied in the:form of compositions, in which the
active ingredient is mixed with a carrier comprising a
solid or liqui~ diluent. Preferably the composition
further comprises a sur~ace-active agent.
The solid ~ompositions of the invention may be for
example, in the form of dusting powders, or may take
the form of granules. Suitable solid diluents include,
for example, kaolin, bentonite, kieselguhr, dolomite,
calcium carbonate, talc, powdered magnesia, and Fuller's
earth.
Solid compositions may also be in the form of
dispersible powders or grains comprising in addition to
the active ingredi.ent, a wetting agent to facilitate
the dispersion of the powder or grains in liquids.
Such powders or grains may include fillers, suspending
agents and the like.
Liquid compositions include aqueous solutions,
dispersions and emulsions containing the active in-
gredient preferably in the presence of one or more
.
~51~3C)5i
surface active agents. Water or organic liquids may be
used to prepare solutions, disper-sions, or emulsions
of the active ingredient. The liquid compositions of
the invention may also contain one or more corrosion
s inhibitors for example lauryl isoquinolinium bromide.
Surface active agents may be of the cationic,
anionic or non-ionic type. Suitable agents of the
cationic type include for e~ample quaternary ammonium
compounds, for example cetyltrimethyl ammonium bromide.
lo Suitable agents of the anionic type include for example
soaps, salts of aliphatic mono-esters of sulphuric
acid, for example sodi~m lauryl sulphate; and salts of
sulphonated aromatic compounds, for example dodecyl-
benzenesulphonate, sodium, calcium and ammonium ligno-
sulphonate, butylnaphthalene sulp~onate, and a mi~tureor the sodium salts of diisopropyl- and triiso-propyl-
naphthalenesulphonic acid. ~uitable agents of the non- - _
ionic type include, for example, the condensation
products of ethylene oxide with fatty alcohols such as
~0 oleyl alcohol and cetyl alcohol, or with alkyl phenols
such as octyl-phenol, nonylphenol~ and octylcresol.
Other non-ionic agents are the partial esters derived
from long chain fatty acids and hexitol anhydrides, for
example sorbitol mono-laurate; the condensation
2s products of the said partial esters with ethylene oxide
and the lecithins.
The compositions which are to be used in the form
of aqueous solutions, dispersions or emulsions are
generally supplied in the form of a concentrate contain-
iny a high proportion of the active ingredient, theconcentrate being diluted with water before use. These
concentrates are usually required to withstand storage
for prolonged periods and after such storage to be
capable of dilution with water in order to form aqueous
preparations which remain homogeneous for a sufficient
time to enable them to be aDplied hy conventional spray
~s~s
- 15 -
equipment. In general concentrates may conveniently
contain from 10 to 85~ and preferably from 25 to 60~ by
weight of active ingredient. Dilute preparations ready
for use may contain varying amounts of the active
ingredient, depending upon the purpose for which they
o are to be used; however, dilute preparations suitable
for many uses contain between 0.01% and 10% and prefer~
ably between 0.1% and 1~ by weight of the active
ingredient.
The compounds of the invention may be prepared
from appropriately substituted 2-halogenopyridines of
formula (II):-
Z~ ~Y
~ X (II)
wherein X repre.sents a fluorine, chlorine, bromine, oriodine atom and Y and Z are as defined in formula (I)
above. Three general routes are available for converting
the halogenopyridines (II) into compounds of the
invention; these are described below as Routes A, B and
C.
Route A is outlined in the
~z~s~()s
- 16 -
Route A
OCH3
(II) OM
O ~ OCH3
(III)
Demethylating agent z y : =
(III) e.g, Pyridine
hydrochloride
Rl (IV)
(IV) + Hal-CH-R Base (I) _ ___
(V) ~
/
~/
~2as~0~
- 17 -
In Route A, the symbols R , R , Z and Y have the
meanings previously assigned to them, Hal stands for a
halogen, preferably chlorine or brom~ne, and M is a
cation, for example sodium.
In Route A, a suitably substituted halogeno-
pyridine (II) is reacted with a metal salt of p-methoxy-
phenol, for example the sodium salt of p-methoxyphenol.
The reaction is preferably carried out in a solvent or
diluent, for example methyl ethyl ketone, tetrahydro-
lo furan; dimethylsulphoxide or dimethylacetamide. The 2-
p-methoxy-phenoxy compound (III~ so obtained is then
demethylated by a standard procedure, for example by
heating with pyridine hydrochloride or with hydrogen
bromide in acetic acid, to obtain the corresponding p-
hydroxy compound (IV). This in turn is reacted in theform of its metal salt ~for example tne sodium or
potassium salt) with the appropriate halogeno-alkanoic
acid derivative (V) to obtain the re~uired compound
(I). Preferably this reaction is carried out in a
solvent or diluent, for example methyl ethyl ketone.
Route B is outlined in the following scheme:-
( I I ) + HO~ Base (I )
Rl
1 2 Base
(IV) + Hal-CH-R > (I )
According to Route B, an approprlately substituted
2-halogenopyridine (II) i~ reacted with hydroqllinone
in the presence of a base to give the p-hydroxyphenoxy
compound (IV) already referred to in Route A. The
reaction is preferably carried out in a solvent or
~Z~S1305
diluent for the reactants. Examples of suitable
solvents include aprotic solvents, for example dimethyl-
formamide. The reaction is preferably accelerated by
heating, for example to a temperature in the range from
50 to 150. The base used in the reaction may be, for
example, an inorganic base, for example sodium or
potassium carbonate~
The second stage of Route B is identical with the
last stage of Route A and requires no further descriptior~.
Route C
Rl
(II) + H0 ~ OCH R2 Base> (I)
(VI)
lo According to Route C, an appropriately substituted 2- : =
halogenopyridine (II) is reacted with a 2-(~-hydroxy-
phenoxy)propionic acid derivative (VI) in the presence
of a base, giving the compound of the invention (I)
directly. The derivatives (VI) are known in themselves
or may be made by conventional methods. The reaction
is preferably car~ied out in the presence of a solvent
or diluent for the reactants. Examples of solvents
include lower ketones, for exarnple methyl ethyl ketone~
The reaction may be accelerated by heating and may for
example be conveniently carried out at the reflux
tempexature of the solvent. Exarnples of bases for use
in the reaction include inorganic bases, for example
anhydrous potassium carbonate. The starting materials
(II) used in Routes A, B and C may themselves be ~repared
2~ by various methods~ ~ompounds containing a fluorinated
alkyl group, ror example, may be prepared by reacting a
corresponding chlorinated compound with a fluorinating
agent so as to exchange some or all of the chlorine
atoms for fluorine atoms. Thus, 2-chloro-5-trifluoromethvl
~vridine is obtainable by reacting 2-chloro-5 trichloro
~Z~SB(~S
- 19 -
methylpyridine with a fluorinating agent, for example
antimony trifluoride or liquid hydrogen fluoride. sy
regulating the amount of fluorinating agent used in the
reaction it is possible to obtain compounds with alkyl
groups containing both fluorine and chlorine atoms; for
example, 2-chloro-5-trichloromethylpyridine may be
reacted with a limited amount of antimony trifluoride
to obtain 2-chloro-5-chlorodifluoromethylpyridine. In
these halogen exchange reactions a proportion of the
lo halogen substituent at the 2-position of the pyridine
may also exchange, so that a proportic~n of the 2-
fluorinated compound may be obtained. This is of no
practical disadvantage since the halogen at the 2-
position is displaced in the subse~uent conver~ion of
the halogenopyridine to the compound of the invention.
Certain of the chlorinated compounds required as
starting materials are believed to be new compounds t
for example 2-chloro-5-trichloromethylpyridine and 2,3.- _
dichloro-5-trichloromethylpyridine. These compounds
form a further feature of ~he invention. In addition
to their usefulness as intermediates for preparing the
compounds of the invention, they have some biological
activity as insecticides.
The invention further provides a process of
preparing 2-chloro-S-trichloromethyl pyridine which
comprises reacting 3-methylpyridine with chlorine in
the liquid phase under the influence of ultraviolet
light.
The reaction of 3-methylpyridine (as free base or
in the form of a salt) with chlorine is generally
carried out in an inert organic solvent. Conveniently
the solvent is a halogenated hydxocarbon, e.g. carbon
tetrachloride; but other solvents may be used, e.g.
hydrocarbons or ethers, provided they do not reac~
under the conditions employed to give unacceptable
quantities of undesired by-products. Reaction is slow
Q~1~(35
- 20 -
at or below room temperature, and is therefore con
veniently speeded up by heat; convenient reaction
temperatures are for example in the range 50 to
130C. The solution may be heated under reflux. It is
preferred to use dry reactants and solve~ts. Ultra-
violet light may be supplied to the reaction from a
suitable electric lamp, which for greatest efficiency
may be immersed in the reaction mixture. The reaction
generally gives rise to a mixture of products, from
lo which the desired 2-chloro-5-trichloromethylp~ridine
may be isolated by conventional methods, e.g. distil-
lation.
In an alternative process for making 2-halogeno-3-
or -5-trifluoromethylpyridines, a 2-halogeno-3- or -5-
carboxypyridine may be reacted with sulphur tetrafluoridein the presence of hydrogen fluoride, as shown below
for 2-chloro-5-trifluoromethylp~ridine:-
Cl ~ 02H SF4 ~ CF3
Compounds containing a difluoromethyl group may beprepared by treating the corresponding pyridine aldehyde
with sulphur tetrafluoride, as shown below~
~ SF4 ~ HF2
The invention is illustrated by the following
Examples, in which all parts are by weight and all
temperatures in degrees Centigrade unless otherwise
~5 specified.
:~2~5~S
- 21 -
EXAMPLE 1
This Exampl2 illustrates the preparation of a
compound according to the invention, namely, ethyl
alpha 4(5-trifluoromethyl-2-pyridyloxy)phenoxypropion-
ate ~Compound No 3).
(a) Preparation of 2-chloro-5-trichloromethylpyridine
2-Bromo-5-methylpyridine (55 g) in dry carbon
tetrachloride (600 ml) was filtered and then treated
with dry hydrogen chloride to give the hydrochlGride
salt. The solid which separated was broken up and the
mixture heate~ to reflux. Dry chlorine was passed
lo through the boiling mixture for 6~ hours with irradia-
tion b~v an ultra-violet lamp placed inside the reaction
flask. The mixture was then cooled, filtered and
evaporated to a pale yellow liquid which solidified on : =
cooling. This was identified as the required chloro
compound by its nuclear magnetic resonance spec~rum.
(b) Preparation of 2-chloro-5-trifluoromethylpyridine
and 2-chloro-5-difluorochloromethYlpyridine
2-Chloro-5-trichloromethyl pyridine (18 g) and
antimony trifluoride ~50 g) were heated together at
140 145C for 1 hour. The mixture was cooled, mixed
with ice and concentrated hydrochloric acid, and
extracted with ether. The extracts were washed with
water, dried with magnesium sulphate, and evaporated.
The products from several such preparations were
combined and distilled at atmospheric pressure through
a short column packed with Fenske rings. The product
2; boiling at 124-154C was collected and identi~ied as 2
chloro-5-tri~luoromethylpyridine. Higher boiling
fractions were redistilled at a pressure of 20 mm
mercury to give 2-chloro-5-di~luorochloromethylpyridine,
boiling at 82 to 90C.
3 ZQS805
- 22 -
(c) Preparation of 2-p-methoxyphenoxy-5-trifluoro-
methyl Pyridine
Sodium hydride (4.2 g of 50Q dispersion in oil,
washed with petroleum) was stirred in dry dimethyl-
sulphoxide (lO0 ml) and a solution of ~-methoxy phenol
(10.4 g) in dimethylsulphoxide (lO0 ml) added over a
period of a few minutes. The mixture was stirred for
30 minutes to form the sodium salt. To the solution
was added 2-chloro-5-trifluoromethylpyridine (15.0 g)
in dimethyl sulphoxide (80 ml) over a period of a few
minutes. The mixture was then heated to 70-75 for
lo 3 hours and left to cool overnight. Thin-layer chroma-
tography showed that only one compound was present.
The mixture was diluted to 1.5 litres with water, and
then extracted with ether (3 x 600 ml). The ether
ex~racts were washed several times with water and then
with molar sodium hydroxide solution, and finallv with
water (2 x 200 ml~. The ether extract was dried and
evaporated to give the required pyridine compound as a
brown oil.
(d) Preparation of 2-p-hydroxYphenoxy~5~trifluoro-
methyl pyridine
2-~-Methoxyphenoxy-5-trifluoromethylpyridine
20 (10.5 g) in glacial acetic acid ~lO0 ml) and 48%
hydrobromic acid (50 ml) were stirred and heated under
reflux for 7~ hours. The solution was then evaporated
and the remaining oil treated with sodium bicarbonate
solution and shaken with ether (2 x 300 ml). ~he ether
extract was shaken with 2-molar sodium hydroxide
solution (200 ml) and then water (150 ml). The aqueous
layers were combined, acidified with 2-molar hydrochloric
acid and extracted with ether (2 x 300 ml)O The ether
extract was dried and evaporated to give a brown oil
'~ identified as 2-~-hydrox~phenoxy-5-trifluoromethyl-
pyridine.
51~(~5
(e) Preparation of compound no 3 of Table I
2-p-Hydroxyphenoxy-5-trifluoromethylpyridine
(0.22 g), ethyl alpha-bromopropionate (0.24 g) and
potassium carbonate (0.18 g~ in methyl ethyl ketone
(5 ml) were stirred, and heated under reflux for 2 hours.
The mixture was left to cool overnight, then filtered,
and the residue washed with methyl ethyl ketone. The
filtrate and washings were evaporated and the remaining
oil subjected to a high vacuum to remo~e traces of
solvent. The nuclear magnetic resonance spectrum or
lo the oil was consistent with the structure assigned and
the compound was identified as compound no 3.
(f) Preparation of compound no 8
The product from (e) (0.3 g) was dissolved in _-
pentanol (15 ml) containing concentrated sulphuric acid~ =
(`2 drops). The:mixture was heated to reflux ~or 3~
lS hours. The solvent was removed and the residue taken
up in ether and washed with saturated sodium bicarbonate
solution. T~e ether solution was dried and evaporated
to a colourless oil which was purified by preparative
scale thin layer chromatography on silica gel with an
20 80:20 mixture of petroleum (b.p. 60-80C) and ether as
the solvent. The nuclear magnetic resonance spectrum
of the product identified it as the required pentyl
ester~
(g) Pre~aration of com~ound no_l
The product from (e) (0.14 g) in isopropanol (2
ml) was stirred at room temperature for 13/~ hours with
an aqueous solution of sodium hydroxide (1.6 ml of a
solution containing 1 g NaOH per 100 ml water). The
mixture was evaporated in a vacuum and the residue
taken up in water, acidified, and extracted with ether
~QS~
- 24 -
(2 x 50 ml). The ether extracts yielded an oil identi-
fied as the required carboxylic acid.
(h) Preparation of compounds 2, 4 to 7, and 14
Following the procedure described in paragraph
te) above, but using in each case the appropriate
s alpha bromopropionic ester instead of ethyl alpha
bromopropionate, compounds no 2, 4 to 7 inclusive,
and no l~ were prepared.
(i) Preparation of 2~4(5-trifluoromethylpyridyl-
2-oxylphenoxy~7propionyl chloride
The carboxylic acid prepared as described in
paragraph (g) above (1.2 g) was heated under reflux
with thionyl chloride (20 ml) for l hour and the excess
of thionyl chloride then removed under reduced pressure.
The residue was mixed with toluene and the toluene - =
evaporated under reduced pressure to remove traces of
th1onyl chloride. The propionyl chloride derivative
lS was obtained as an oil.
(j) Preparation of compound no 17 to 23
The acid chloride as prepared in (i) above (0.78
g) was added to an excess of aqueous ethylamine (20 ml;
solution containing 70 g ethylamine per lO0 ml). The
excess of ethylamine solution was removed under reduced
pressure. The residue was diluted with water and
extracted with ether. The ether solution was washed
with 2-molar hydrochloric acid and water, and dried
and evaporated. The residue was recrystallised from
~etroleum (b.p. oO-80) to give the ethylamide
25 (Compound no 17) with a meltina point of 96-98.
Following this procedure, compounds 18 to 23 were
prepared, using the appropriate amine instead of ethyl-
amine in each case.
3L2~
- ~5 -
(k) Preparation_of compounds 9 to 13, 15, 16, 24 and
The acid chloride as prepared in (i) above (0.87
g) was dissolved in allyl alcohol and heated at 100
for 1 hour. The excess of alcohol was removed under
reduced pressure and the remaining oil washed with
water and 2-molar hydrochloric acid and dissolved in
ether. The ether solution was dried and evaporated
and the remaining oil purified by thin-layer chromato-
graphy on silica gel using a mixture of equal volumes
. of ether and petroleum ~b.p. 60-80) as eluent. The
lo allyl ester (compound no 24) was obtained as a colour-
less oil. Compounds 9 to 13, 15, 16 and 27 were
prepared by a similar procedure, using in each case
the appropriate alcohol in place of allyl alcohol.
~1) Preparatlon of compounds 25 and 26
The acid chloride as prepared in (i) above (0.94
g) in dry ether containing pyridine (2 ml3 was mixed
with phenol (1 molar proportion) and the solution
left overnight. The solution was evaporated and the
residue purified by thin layer chromatography to give
compound 25 as a clear oil. Compound 26 was similarly
prepared.
EXAMPLE 2
This illustrates the preparation of 2-chloro-5-
trichloromethylpyridine by chlorination of 3~methyl
pyridine under the influence of ultra-violet light.
3-~ethylpyr~dir.e (10 snl) was dissolved in dry
carbon tetrachloride (300 ml). The solution was heated
to reflux (about 80) and dry chlorine gas passed
through the boiling mixture for 3 hours while it was at
the same time irradiated internally from a 100 watt
~ZQ5~05
- 26 -
ultra-violet lamp producing light of wavelength 185 nm.
Preparative thin layer chromatography (silica, chloro-
form/cyclohexane) on an evaporated sample of the
solution thus obtained gave three main products in
total overall yield of 10-15~; the most abundant of
these was identified by its nuclear magnetic resonance
spectrum as the desired 2-chloro-5-trichloromethyl-
pyridine. This was confirmed by mass spectrograph
analysis of the solution obtained. The other two major
lo products were 2-chloro-3-trichloromethyl pyridine and a
di(trichloromethyl)pyridine, present in amount of about
half, and about one-tenth, respectively, of the major
product.
EXAM2LE 3
This Example illustrates the preparation of 2- c
chloro-5-trichloromethylpyridine from a salt of 3-
methylpyridine.
3-Methylpyridine (15 g) in dry carbon tetra-
chloride (200 ml) was treated with dry ~Cl gas to give
the hydrochloride. The oily mixture thus obtained was
stirred and heated to reflux. Dry chlorine gas was
bubbled into the refluxing mixture for 4 hours while
illuminating it internally from the ultraviolet lclmp
used in Example 1. The reaction mixture was then
cooled, and separated by decantation into solution and
oily solid. The latter was purified, and shown
to contain unreacted 3-methylpyridine salt. The former
was evaporated to an oily semi-solid, which was shown
by thin-layer chromatography to have the character-
istics of ~-chloro-S-trichloromethylpyridine.
~IL2e~5~05
- 27 -
EXAMPLE 4
This Example describes the preparation of 2-
chloro-5-tri~luoromethylpyridine by a method alter-
native to that of ~xample 1.
6-Chloronicotinic acid (23.6 g), sulphur tetra-
fluoride (37.4 g) and anhydrous hydrogen fluoride(18.7 g) were heated in an autoclave with stirring
for 8 hours at 120. The mixture was cooled, poured
on to ice, and neutralised with concentrated sodium
hydroxide at 0. The mixt~re was extracted with ether
~0 and the extracts washed with water, dried, and evapor-
ated. The residue was distilled and the fraction
boiling at 140-150 collected. Analysis indicated
that this consisted of 2-chloro-5-trifluoromethylpyridine
with some 2-fluoro-5-trifluoromethylpyridine.
- EXAMPLE 5
This Example describes the preparation of 2-
chloro-5-trifluoromethylpyridine by a method alternative
to that of Examples 1 and 4.
2-Chloro-5-trichloromethylpyridine (30.8 g) and
anhydrous hydrogen fluoride (80 g) were heated for
20 10 hours at 200 with stirring in an autoclave. The
mixture was cooled, poured on to ice, and neutralised
at 0. The mixture was filtered and the residue and
filtrate extracted with ether. The ether extracts
were washed with water, dried, and evaporated to give
an oil. This was distilled and the fraction boiling
at 140 154 collected. Analysis indicated that this
consisted of 2-chloro-5-trifluoromethylpyridine with
some 2-fluoro-5-trifluoromethylpyridine.
3 2~05
- 28 -
E~AMPLE 6
This Example illustrates the preparation of
compound no 30 of Table I by Route A.
~a) Preparation of 2-ami_o-3-bromo-5-methylpyridine
2-Amino-5-methylpyridine (108 g) in glacial acetic
acid (300 ml) was heated to 90 100C while bromine (160
g) in acetic acid (55 ml) was slowly added with stirring.
When addition was complete, the mixture was stirred and
heated for a further 30 minutes and then allowed to
cool overnight. The solid which separated was filtered
off and mixed with ice and the mixture neutralised with
lo concentrated ammonia, keeping the temperature at 0 to
5C~ The solid was collected, washed with water, and
dried to give the bromo-compound.
b) Preparation of 3-bromo-2-chloro-5-methylpyridlne
The product from (a) (145 g) was dissolved in
concentrated hydrochloric acid (750 ml) and water (450
ml) and the solution cooled to ~10C. Sodium nitrite
(54 g) in cold water (450 ml) was added dropwise with
stirring over a period of 90 minutes while the mixture
was kept at -5C. The solution was stirred for a
further 2 hours, and then basified with concentrated
ammonia, keeping the temperature below 20C. The solid
which separated was washed with water, dried, dissolved
in ether (1500 ml) and washed with cold sodium hydroxide
solution (lM; 1 litre). The ether solution was washed
twice with water (1 litre portions), dried, and evaporated
to give the rPquir~d 3-bromo 2-chloro-5-methylpvridine.
(c) Preparation of 2,3-dichloro-5-txichloromethylpvridine
The product from (b) (64 g) in dry carbon tetra-
chloride (650 ml) was treated with dry hydrogen chloride.
~L2~ 0~
- 29 -
The precipitate was broken up and the suspension heated
under reflux while dry chlorine was bubbled into the
mixture, with illumination ~rom an ultra-violet light
source. After 4~ hours, the mixture was cooled,
filtered, and the filtrate evaporated to give the
required 2,3-dichloro-5-trichloromethylpyridine. The
mass spectrum was consistent with the structure assigned
to this compound.
(d) Preparation of 2,3-dichloro-5-tri~-luoromethyl-
pyridine
The product from ~c) ~1.0 g) and antimony tri-
o fluoride (3.0 g) were heated together at 170-180 for
30 minutesO The mixture was then cooled, mixed with
ice and water, and extracted with ether. The ether
extracts gave a brown oil containing a mixture of 2,3-
dlchloro-5-trifluoromethylpyridine and 3-chloro-2-
1S fluoro-5-trifluoromethylpyridine with a minor amount of
2,3-dichloro-3-chlorodifluoromethylpyridine.
(e~ Preparation of 3-chloro-2-p-methoxyphenoxy-5=
trifluoromethylpyridine
~ -Methoxyphenol (1.5 g) was added to a suspension
of sodium hydride (0.6 g 50% oil dispersion, washed
with petroleum) in dry dimethyl sulphoxide (30 ml) and
the mixture stirred for 15 minutes~ A solution of the
combined products (1.5 g) from several preparations
carried out as described in paragraph (d), in dimethyl-
sulphoxide (20 ml) was added to the reaction mixture
and heated to 60C for four hours. A further amount of
sodium hydride (0.3 g of 50~ oil dispersion, washed
with petroleum), and potassium carbonate (1.38 g) was
added. Heating was continued for another 4 hours. The
mixture was poured into ice and water, and extracted
with ether (400 ml). The ether extracts were washed
~2~58~5
- 30 -
with water, dilute sodium hydroxide, and water, dried,
and evaporated to give the product.
(f) Preparation of 3-chloro-2-p-hydroxyphenoxy-5-
trifluoromethylp-~ridine
The product from (e) (2 g) was heated with pyridine
hydrochloride (20 g) at 170-180C for 6 hours. The
mixture was cooled, diluted with dilute hydrochloric
acid, and extracted with ether. The ether extracts
gave an oily solid which was purified by preparative
thin layer chromatography using silica as the adsorbent
and 6% ethanol-chloroform as the solvent.
(g) Preparation of compound no 30 of Table I
lo The product from (f) (0.16 g), ethyl alpha bromo-
propionate (0.3 g), and potassium carbonate (0.25 g)
were heated and stirred ~nder reflux in methyl ethyl - =
ketone (10 ml) ~or 2 hours. The mixture was cooled and
filtered. Evaporation of the filtrate gave an oil
which was heated in a v~cuum to remove traces of
solvent. The oil was identified as compound no 30 by
examination of its mass spectrum and its purity was
confirmed by gas-liquid chromatography.
2,3-Dichloro-S-trichloromethylpyridine was also
prepared by an alternative route, as follows:-
(h) Preparation of 2-amino-3-chloro-5-methylpyridine
2-Amino-5-methylpyridine (10.8 g) in concentrated
hydrochloric acid (100 ml) was kept at 10-15C while
hydrogen peroxide (30%, 21 ml) was added dropwise with
stirring. When addition was complete the mixture was
st~rred for 1~ hours wlthout cooling, and poured on to
ice (about 200 g). The mixture was brought to pH 8-9
by adding concentrated ammonia dropwise, keeping the
temperature at 0C by adding ice. The solution was
5805
- 31 -
extracted with chloroform (2 x 300 ml). The chloroform
extracts yielded the required chloro-compound as a
yellow solid .
(i) Preparation of 2-br_mo-3-chloro-5-meth~lp~ridine
The product from paragraph (h) ~5.7 g) in hydro-
S bromic acid ~48%; 50 ml) was cooled to -15C to -10C
and bromine (2.6 ml) was added dropwise with stirring.
The temperature was then kept at -5C to 0C while
sodium nitrite (5.53 g) in water ~12 ml) was added
dropwise over a period of 45 minutes. When addition
lo was complete, the mixture was stirred a further 30
minutes at 0C and poured on to ice. The mixture was
made slightly alkaline by dropwise addition of concen-
trated ammonia, keeping the temperature at 0C with
~dded ice. The mixture was extracted with ether (150
ml). The ether extract was washed with water, sodium
bisulphite solution, and water, and then dried and
evaporated. The residue was taken up in petroleum
(b.p. 40-60C) and the solution filtered and evaporated.
The residue was identified as 2-bromo-3-chloro-5-
methylpyridine.
(j) Preparation of 2,3-dichloro-5-trichloromethyl~
pyrimidine
The product from paragraph (i) ~2.9 g) in dry
carbon tetrachloride (250 ml) was treated with dry
hydrogen chloride to convert it to the hydrochloride.
Chlorine was passed through the suspension which was
kept at 80C and illuminated hy an ultra-violet lamp
inside the reaction flask. After three hours the
solvent was removed, leaving a residue of 2,3-dichloro-
5-trichloromethylpyridine.
~ZQ5~305
- 32 -
EXAMPLE 7
This Example illllstrates the preparation of
2,3-dichloro-5-trifluoromethylpyridine hy fluorination
of 2,3-dichloro-5-trichloromethylpyrid ne, using a
fluorinating agent alternative to that of Example 6.
s 2,3-Dichloro-5-trichloromethylpyridine (35 g)
was heated with anhydrous hydrogen fluoride (100 g)
in an autoclave at 200 for 10 hours with stirring.
The cooled reaction mixture was poured on to ice and
neutralised with sodium hydroxide at 0. The mi~xture
lo was extracted with methylene chloride (750 ml). The
extracts were washed with water (500 ml), sodium
carbonate solution (500 ml) and water (500 ml~, dried,
and evaporated. The remaining oil was distilled and
the fraction of boiling point 77-83/25 Torr was collected
and identified as the required pyridine derivative~ :
EXAMPLE 8
This Example further illustrates the preparation
of 2,3-dichloro-5-trifluoromethylpyridine.
Antimony trifluoride (61 g) was melted under a
vacuum to remove moisture. The cooled material was
broken up and heated to 65-70 while antimony penta-
chloride (6.6 g) was added dropwise with stirring.
2,3 Dichloro-5-trichloromethylpyridine (40 g) was then
added dropwise to the mixture and the whole heated to
160 over 45 minutes. The mixture was cooled and steam
2s distilled. The oil which distilled ovPr was extracted
with ether (2 x 100 ml). The ether extract was washed
with tartaric acid sclution ~hen water, sodi~ bic~-
bona~e, and water, and dried. The remaining oil was
distilled The fraction boiling at 71-80/18 Torr was
identified as the required pyridine derivative.
~Z~S~ 5
- 33 -
EXAMPLE 9
This Example illustrates the preparation of 3-
chloro-5-trifluoromethyl-2-p-hydroxyphenoxypyridine
by Route B.
Dry dimethylformamide (30 ml) was de-aerated by
heating under reflux under a stream of argon for 30
minutes. Hydroquinone (4.95 g) and anhydrous potassium
car~onate (6.84 g) were added and heated for 90 minutes
under reflux. 2,3-Dichloro-5-trifluoromethylpyridine
(6.48 g) in dry, de-aerated dimethyl formanlide (30 ml)
lo was added to the above mixture over a period of 4 hours.
The mixture was allowed to cool overnight and diluted
with water (500 ml~. The mixture was acidified with
dilute hydrochloric acid and extracted with ether
(2 x 400 ml). The ether extract was washed with water
(2 x 500 ml) and extracted with dilute sodium hydroxide
solution (300 ml). The ether extract was washed with
water and the aqueous fractions combined and re-acidified
with hydrochloric acid. The acidified aqueous solution
was extracted with chloroform (2 x 400 ml). ~he chloro-
form extract yielded a light brown oil which ontrituration with petroleum (b.p. 30-40) gave a
colourless solid identified as the required 3-chloro-
5~trifluoromethyl-2-p-hydroxyphenoxypyridine.
EXAMPLE 10
This Example illustrates the preparation of
2s ethyl 2~4~3-chloro-5-trifluoromethylpyridyl-2-oxy)
phenoxy~7propionate (compound no 30 of Table I).
The product from Exampie g (1.0 g) was stirred
and heated under rerlux in methyl ethyl ketone (25 ml)
with potassium carbonate (0.5 g) and ethyl 2-bromo-
propionate (1.0 g) for 4 hours. The mixture w~scooled and filtered and the filtrate evaporated to
- ~2(~ 305
- 34 -
give an oil which was purified by thin-layer chromato-
graphy on two 2 millimetre thick plates, each 20 by 20
centimetres in size, using a mixture of 20 volumes of
ether and 100 volumes of hexane as the eluent. The
product was extracted with ethanol. Evaporation of
the ethanol gave a colourless oil identified as compound
no 3~ by its nuclear magnetic resonance spectrum.
E.YAMPLE 11
Following the procedure described in Example 10,
compounds no 29, 31 to 39, 41 and 42 of Table I were
lo prepared, using the appropriate ester of 2-bromopropionic
acid in each case.
EXAMPLE 12
This Example illustrates tne preparation oî 2~-4(3-
chloro-5-trifluoromethylpyridyl~2-oxy)phenoxy~7propionic
acid (compound no 28 of Table I).
Compound no 31 of Table I (2~19 g) in isopropanol
(20 ml) was treated at room temperature dropwise with a
solution of sodium hydroxide (0.23 g) in water ~20 ml).
The mixture was stirred at room temperature for 4 hours~
then diluted to 300 ml with water. The solution was
extracted with methylene dichloride (2 x 50 ml) and
acidified with 2-molar hydrochloric acid. The acidified
solution was extracted with methylene dichloride (2 x 150
ml) and the extract dried and evaporated to give an oil.
This solidified on standing and was dried at 85 in a
vacuum to give compound no 28 with a melting point of
lQ4-107. _
.
58~5
- 35 -
EXAMPLE 13
This Example illustrates the preparation of
compounds 43 to 45 and 48 to 51 of Table I.
(a) Preparation of 2~4(3-chloro-5-trifluoromethyl-
pyridyl-2-oxy)phenoxy~7propionyl chloride.
The carboxylic acid prepared by the method of
Example 12 (16.5 g) was dissolved in an excess of
thionyl chloride (200 ml) and heated under reflux for
2 hours. The excess of thionyl chloride was removed
under reduced pressure to give the acid chloride as a
lo yellow oil. This was taken up in dry ether (220 ml)
and the solution used to prepare compounds 40, 43 to
45, 48 to 51 and 77 as follows. Since the procedures
are conventional, only brief details are given, and these
are tabulated below. :
.
.
o~
- 36 -
-- _ ~ ^ O
t_) h ~0 E~O O ~ cn E~O
O O O O O ~ ~: O ~ O O
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P. ~ ~ C ~D
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O tJI ~ ~ ~ ~ -1 ~1 .C P~ ~ ~)
~ ~ O ~ JJ ~ O ~ -
Z (~ ~ O Q t~
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H ~1 H C r~l Q~ ~1 0 h ~I C
r~l ~ O ~ O ~ O
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C~ ~ ~ ~ 0 ~
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E~ ~ O a~ u,
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za
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- 38 -
EXAMPLE 14
This Example illustrates the preparation of
compound 46 of Table I.
The solution prepared in paragraph (a) of Example
13 (20 ml) was added to a solution of phenyl hydrazine
(O.9S g) in dry ether (20 ml) at room temperature and
the mixture stirred overnight. The mixture was then
diluted with water and acidified with 2-molar hydro-
chloric acid. The ether layer was separated, washed
with water, and dried. Evaporation of the ether gave
lo the phenylhydrazide as a solid of melting point 109-
110.
EXAMPLE 15
This Example illustrates the preparation of compound
no 47 of Table -I.
The solution prepared in paragraph (a) of Example
lS 13 (20 ml) was added to a solution of propargyl alcohol
(0.25 g~ in ether (20 ml) containing potassium carbonate
(0.75 g). The mixture was stirred at room temperature
overnight. Chromatography indicated that no reaction
had taken place. The mixture was filtered and the
filtrate evaporated to an oil. Propargyl alcohol (S ml)
was added and the mixture heated for 2 hours at 100.
The mixture was cooled and the excess of propargyl
alcohol removed under reduced pressure. The residue
was purified by thin layer chromatography, using silica
gel as the solid phase and a mixture of ether (1 volume)
and petroleum (b.p. 60-80; 5 volumes) as the eluent.
The product isolated in this way was a colourless oil
which solidified on storage to give compound no 47
with a melting-point of 57.5-58.5. ___________
.... .. ~
,.
S~05
- 39 -
EXAMPLE 16
This Example illustrates the preparation of ethyl
alpha 4(5-difluorochloro-2-pyridyloxy)phenoxy propionate.
(Compound no 52) by Route A.
(a) Preparation of 5-difluorochloromethyl-2-p-methoxy-
phenoxy pyridine
The 2-chloro-5-difluorochloromethylpyridine
pr~pared in Example 1 (b) (1.0 g) in dimethylsulphoxide
(10 ml) was added to a solution of p-methoxyphenol
~0.62 g) previously reacted with sodium hydride (0.24 g
of 50~ oil dispersion, washed with petroleum) in
dimethyl sulphoxide (15 ml). The mixture was stirred
lo and heated to 60-65C for 5 hours, poured into ice, and
extracted with ether. The ether extracts were washed
with water, dilute sod~um hydroxide, and water, dried, - =
and evaporated to give arL oil identified as the required
p-methoxy compound.
(b) Preparation of S-difluorochlor .methyl-2-
~hydrox~phenoxypyridine
The product from (a) (1.0 g) was dissolved in
glacial acetic acid (12 ml) and aqueous hydrobromic
acid (48%; 5 ml) added. The reaction mixture was
stirred and heated under reflux for 3~ hours. The
mixture was cooled and evaporated under reduced
pressure. The residue was taken into ether and washed
with sodium bicarbonate solution and water. The ether
solution was dried and evaporated to yield an oil which
partially solidified. This was purified by preparative
thin layer chromatography on silica gel using a mix'ure
of 6% ethanol in chloroform as the solvent. ~
__ =
~ZQS~
- 40 -
(c) Preparation of compound no S2
The product from (b) (0.18 g) was heated under
reflux for 2~ hours in methyl ethyl ketone (10 ml) with
ethyl alpha bromopropionate (0.3 g) and potassium
carbonate (0.25 g). The mixture was cooled and the
solids filtered off and washed with methyl ethyl
ketone. The filtrate and washings were evaporated in a
vacuum to give an oil. The nuclear magnetic resonance
spectrum of this oil was consistent with its structure
assignment as compound no 52.
EXAMPLE 17
lo This Example illustrates the preparation of ethyl
2 C 4~3-chloro-5-chlorodifluoromethylpyridyl-?-o~y)-
phenoxy 7propionate (compound no 53 of Table I) using
Route C
2 t 3-Dichloro-5-chlorodifluoromethylpyridine (1.0 g) and
ethyl 2-(4-hydroxyphenoxy)propionate (1.0 g)
in methyl ethyl ketone tlO ml) containing potassium
carbonate (1.0 g) were stirred and heated under reflux
for 3 hours. The mixture was cooled and filtered.
The residue was washed with methylethyl ketone and the
filtrate and washings evaporated under reduced pressure
to give an oil. The oil was purified by thin-layer
chromatography using silica gel as the solid phase and
a mixture of ether (1 volume) and petroleum (b.p.
60-80, 4 volumes) as the eluent. The product was a
colourless oil which solidified on storage to give
compound no 53 with a melting point of 61-
z~s~os
41 -
EXAMPLE L8
This Example illustrates the preparation of
compounds 54 to 58 of Table I.
(a) Preparation of propyl 2~4(3-chloro~5-chloro-
difluoromethylpyridyl-2-oxy)phenoxy~7propionate
S 2,3-Dichloro-5-chlorodifluoropyridine was reacted
with propyl 2(4-hydroxyphenoxy)propionate in methyl
ethyl ketone as described for the corresponding ethyl
ester in Example 17. The propyl ester so obtained was
purified by dissolving it in a mixture of ether (1 vol)
lo and petroleum (b.p. 60-80, 4 volumes) and passing it
through a column of silica gel.
(b) Preparation of carboxylic acid from (a)
The propyl ester was dissolved in isopropanol and : =
treated slowly with ~odium hydroxide solution as
described in Example 12. The carboxylic acid~was
isolated as described in Example 12.
(c) Preparation of acid chloride from (b3
The 2 ~4(3-chloro-5-chlorodifluoromethylpyridyl-2-
oxy)phenoxy_7propionic acid, prepared in (b) was
heated at 100C for 2 hours with excess of thionyl
chloride and the excess of thionyl chloride then
removed under reduced pressure. The acid chloride was
then used to prepare compounds 54 to 58 as follows.
Since the procedures are conventional, only brief
details are given, and these are tabulated belo
51~05
- 42 -
.
COMPO~ND
NO REACTION PROCEDURE PURIFICATION OF PRODUCT
54 Reflux with excess TLC using silica gel/
of 2-chloroethanol ether
for 2 hours
Reflux with excess TLC using silica gel/
of allyl alcohol ether
for 2 hours
56 Reaction with Product substantially
~-chloxophenol in pure
ether in presence
of pyridine at
room temperature
overnight
57 Reaction with TLC using silica gel/
excess of aqueous ether
methylamine
solution
58 Reaction with TLC using silica gel/
excess of ~- ether
chloLophenyl-
hydrazine
_ _
EXAMPLE 19
This Example describes the preparation of 3-
bromo-2-chloro-5-trifluoromethylpyridine.
(a) Preparation of 3-bromo-2-chloro-5-pyridine
carboxylic acid
3-Bromo-2-chloro-5-methylpyridine (30 g) in water
(650 ml) containing potassium permanganate (60 g) was
S stirred and heated under reflux for 3 hours. Further
potassium permanganate (20 g) was then added and the
mixture heated and stirred for another 2~ hoursO The
mixture was steam-distilled to remove unchanged
starting material, and then filtered while hot. The
residue was washed with hot water. The filtrate and
washings were cooled and acidified with concentrated
~Z0~05
- 43 -
hydrochloric acid. The solid which separated was
extracted with ether. The ether extract was dried
and evaporated to give 3-bromo-2-chloropyridine~5-
carboxylic acid.
(b) Preparation of 3-bromo-2-chloro-5-trifluoromethyl
pyridine
The product from (a) (12 g), sulphur tetrafluoride
(20 g) and anhydrous hydrogen fluoride (10 g) were
stirred and heated to 120 for 8 hours in an autoclave.
The product was poured on to ice and neutralised with
concentrated sodium hydroxide at 0. The mixture was
lQ extracted with ether (3 x 100 ml) and the extracts
washed with water, sodium bicarbonate solution, and
water. The extracts were dried and evaporated to give
a brown oil. This was distilled and the fraction boili~g
at 88-93 collected. This was identified as 3~bromo-
2-fluoro-5-trifluoromethylpyridine.
The product of paragraph (b3 was used as starting
material for the pxeparation of compounds 59 and 60 of
Table I, following Route C.
EXAMPLE 20
This Example describes the preparation of 2,5-
dichloro-3-trifluoromethylpyridine and 2,5-dichloro-
3-difluoromethylpyridine.
(a) Preparation of 2 5-dichloro-3-trichloromethyl-
pyridine and 2,5-dichloro-3-dichloromethylpyridine
2,5-Dichloro-3-methylpyridine (37 g) in dry
carhon tetrachloride (500 ml) was treated with
surficient dry hydrogen chloride to precipitate the
pyridine as its hydrochloride. The mixture was then
stirred and heated under reflux while dry chlorine was
12~5~30S
- 44 -
passed through and the solution irradiated by an internal
ultra-violet lamp. Chlorination was continued for 3~
hours and the solution then evaporated to give an oily
solid. This was washed with petroleum tb.p. 30-40)~
The residue was identified as consisting mainly of 2,5
dichloro-3-txichloromethyl pyridine. The filtrate was
evaporated to give an oil identified as consisting
mainly of 2,5-dichloro-3-dichlorornethylpyridine~
lo ~b) Preparation of 2 ! 5-dichloro-3-trifluoromethyl
pyridine
2,5-Dichloro-3-trichloromethylpyridine from (a)
above (30 g) in anhydrous hydrogen fluoride (90 g~ was
stirred and heated to 200 in an autocl~ve for 10 hours.
The contents wer~ cooled, poured into ice, and
neutralised with concentrated sodium hydroxide at 0.
The aqueous layer was decanted from the oily organic
layer and the latter extracted with portions of methylene
chloride (total 750 ml3. The methylene chloride
extracts were dried and evaporated to give an oil. This
was distilled and the fraction boiling at 70-76 at 20
Torr collected. Analysis indicated that this comprised
2,5-dichloro-3-trifluoromethylpyridine containing about
10 percent by weight of 5-chloro~2-fluoro-3-trifluoro-
methylpyridine.
(c) Preparation of 2,5~dichloro-3-difluoromethyl~
pyridine
2,5-Dichloro-3-dichloromethylpyridine (20 g) in
anhydrous hydrogen fluoride (60 g) was stirred and
30 heated ln an autoclave for 10 hours at 200~ The
mixture was then cooled, poured on to ice and neutralised
with concentrated sodium hydroxide solution at 0.
The aqueous layex was decanted from the organic layer
and the organic layer dissolved in rnethylene dichloride.
~o~s
- 45 -
The methylene dichloride solution was used to extract
the aqueous layer. The methylene dichloride extract
was washed with water, sodium carbonate solution, and
water, and then dried and evaporated. The remaining
oil was distilled. The fraction boiling at 85 to 98
at 22 Torr was collected and redistilled in a ~icro
spinning band apparatus. The fraction boiling at 87-
8705/25 Torr was identified as 95% pure 2,5-dichloro-
3-difluoromethylpyridine.
The 2,5-dichloro-3-trifluoromethylpyridine obtained
as described above was converted by Route C into compounds
61 and 62 of Table I, and the 2,5-dichloro-3-difluoro-
methylpyridine was converted by Route C into compound
67.
Compounds 63 to 66 were prepared by reaction of
2~4(5-chloro-3-trifluoromethylpyridyl-2-oxy)phenoxy_7
propionyl chloride with, respectively, 2-methoxyethanol,
morpholine, aniline, and benzyl alcohol, following the
procedures described in paragraphs (j) and (k) of
Example 1. The propionyl chloride required for these
preparations was made by reaction of the corresponding
acid with thionyl chloride following the procedure
described in paragraph (i) of Example 1. The required
carboxylic acid was obtained by hydrolysis of its
propyl ester with sodium hydroxide foliowing the
procedure described in paragraph (g) of Example 1.
EXAMPLE 21
This Example illustrates the preparation of ethyl
2 C4(5-difluoromethylpyridyl~2-oxy)phenoxy ~propionate
(compound no 68 of Table I.
(a) Preparation of 2-chloro~5-formyl pyridine
2-Chloro-5-cyanopyridine (15 g) in 90% formic acid
(60 ml) and water (15 ml) was stirred at 55 and
~ 5805
.
- 46 -
treated with Raney nickel/aluminium alloy (15 g). The
mixture was stirred at 55~ for 9~ hours and the warm
solution filtered. The residue was washed with warm
ethanol (ca. 25 ml) and the filtrates combined and
diluted to 600 ml with water. The solution was extracted
with ether (3 x 250 ml~. The ether extract was washed
with aqueous sodium carbonate and water/ dried, and
evaporated to give a pale yellow solid identified as 2-
chloro-5-formylpyridine.
(b~ Preparation of 2-chloro-5-difluoromethylpyridine
The product from (a) (9.9 g) and sulphur tetra-
fluoride (15.5 g) were heated in an autoclave at 153-
155 for 6 hours. The autoclave was then cooled and
vented. The mixture was basified with aqueous sodium
carbonate and extracted with methylene dichloride. The
methylene dichloride was dried and evaporated, and the
remaining oil distilled. The fraction boiling at 156-
164 was collected and identified as 2-chloro-5-difluoro-
methylpyridine containing some 2-fluoro-5-difluoromethyl-
pyridine.
(c~ Preparation of compound no 68
The product from (b) (0.44 g) and ethyl 2-(4-
hydroxyphenoxy)pxopionate (0.63 g) in methyl ethyl
ketone (10 ml) containing potassium carbonate (0.5 g)
were stirred and heated under reflux for 13% hours.
The mixture was cooled and filteredt and the filtrate
evaporated. The remaining oil was purified by thin
layer chromatography using silica gel as the solid phase
and a mixture of chloroform (75 parts by volume),
petroleum (b.p. 60-80, 25 parts) and ethyl acetate
(5 parts) as the liquid phase. The product obtained
in this way was an oil.
2~580~
- 47 -
EXAMPLE 22
This Example illustrates the preparation of ethyl
2f~4(3-bromo-5-difluoromethylpyridyl-2-oxy)phenoxy_7
propionate (compound no 70 of Table I)~
(a) Preparation of 3-bromo-2-chloro-5~formylpyridine
3-Bromo-2-chloro-5-cyanopyridine (8.6 g) in 90%
formic acid (40 ml) and water (10 ml3-were treated
with Raney nickel/aluminium alloy (8.0 g~ and the
mixture stirred and heated to 55-60 for 6 hours. The
mixture was left to stand for two days, and then filtered.
lo The filtrate was diluted to 500 ml with water and
extracted with ether (2 x 250 ml). The ether extract
was washed with aqueous sodium carbonate, dried, and
evaporated to give an oil. The oil was diluted with
toluene which was then removed under reduced pressure.
lS The residue was diluted with a little ether, the solution
filtered, and the filtrate evaporated to give an oil
identifled as the required aldehyde.
(b) Preparation of 3-bromo-2-chloro-5-difluoromethyl
pyridine
The product from (a) (5.6 g) and sulphur tetra-
fluoride (9 g) were heated in an autoclave for 6 hours
at 150. The autoclave was cooled and vented and the
contents treated with aqueous sodium carbonate. The
solution was extracted with methylene dichloride. The
methylQne dichloride extract was dried and evaporated
to give an oil which was distilled under reduced
pressure. The fraction boiling at 85-95/15 Torr
was collected and identified as 3-bromo-2-chloro-5-
difluoromethylpyridine containing a small proportion
of 2-chloro-3-fluoro-5-difluoromethylpyridine or its
2-fluoro-3-chloro isomer.
3LZ~
- ~8 -
(c) Preparation of compound no 70
The product from (b) (O.S g), ethyl 2-(4-hydroxy-
phenoxy)propionate (0.465 g), and potassium carbonate
(0.5 g) in methyl ethyl ketone (10 ml) were stirred
and heated under reflux for 5~ hours. The mixture was
filtered and evaporated to give a yellow oil. This was
purified by thin layer chromatography using silica gel
as the solid phase and as the liquid phase the mixture
described in paragraph (c) of Example ; The major
lo band was extracted with ethanol. Evaporation of the
ethanol yielded an oil which gas-liquid chromatography
showed to contain 96% of the main component. This was
identified as compound 70 by its nuclear magnetic
resonance spectrum.
EXAMPLE 23
15 This Example illustrates the preparation of ethyl
2 C 4(3-chloro-5-difluoromethylpyridyl-2-oxy~phenoxy~7
propionate ~compound no 69 of Table I~ by Route C.
(a) Preparation of 2,3-dichloro-5-difluoromethyl
A mixture of 2,3-dichloro-5-formylpyridine (3 g)
pyridine containing a minor proportion of 2,3,5~trichloro-
pyridine, was heated with sulphur tetrafluoride (4.5 g)
in an autoclave for 6 hours. The cool~d reaction
mixture was treated with aqueous sodium carbonate and
extracted with methylene dichloride~ The extract was
2s dried and evaporated and the residue distillPd in a
micro spinning band apparatus. The fraction boiling at
65~100~ was collected. Gas-liquid chromatography
indicated that this was a mixture of about 60~ of 3-
chloro-2-fluoropyridine and 40% of the required 2,3
dichloro-5-difluoromethylpyridine.
~;20$80~i
- 49 -
(b) Preparation of compound 69
The product from (a) ~0.65 g), and ethyl 2-(4-
hydroxyphenoxy)propionate (1.0 g) were heated under
reflux in methyl ethyl ketone (10 ml) with stirring
for 4~ hours. Th~ solution was filtered, and the
filtrate evaporated to give an oil. The oil was
purified by thin-layer chromatography/ using silica
gel as the solid phase and a mixture of chloroform
(75 parts by volume), petroleum (b.p. ~0-80, 25 parts)
lo and ethyl acetate (5 parts) as the eluent. The product
eluted was a mixture. This was chromatographed again
using a mixture of ether (1 part by volume3 and petroleum
(b.p. 60-80; 2 parts) as the eluent. Two bands
developed; the faster moving band was extracted with
ethanol and the ethanol extracts evaporated. The
remaining oil was identified as compound no 69 by its
nuclear magnetic resonance spectrum.
EXAMPLE 24
This Example describes the preparation of 2-chloro-
3,5-bistrifluoromethylpyridine.
(a) Preparation or 3,5-bis-trifluoromethylpyridine
3,5-Pyridine-dicarboxylic acid (17~5 g) containing
a proportion of pyridine 2,5-dicarboxylic acid was
heated with sulphur tetrafluoride (72 g) and hydrogen
fluoride (40 g) in an autoclave for 8 hours at 150-151.
The cooled reaction mixture was neutralised at 0 with
concentrated potassium hydroxide solution. The mixture
was extracted with methylene dichloride, and the extract
dried and evaporated. The residue was distilled and
the fraction boiling at 119-128 collected. The N~
spectrum indicated a mixture of 3,5- and 2,5-bis-
0 trifluoromethylpyridines.i
~Z~:)5~
- 50 -
(b) Preparation of 2-chloro-3,5-bis-trifluoromethyl
pyridine
The foregoing product (3.0 g) in dry carbon tetra-
chloride (250 ml) was stirred and heated under reflux
while chlorine (dried) was passed slowly through the
solution and the solution was irradia-ted by a UV lamp.
After 6~ hours the carbon tetrachloride was distilled
off and the residue distilled in a spinning band
apparatus. The fraction boiling at 75-85 was collected
lo and identified as 2-chloro-3,5-bis-trifluoromethyl-
- pyridine containing a proportion of 2,5- and 3,5-bis-
trifluoromethylpyridine.
The 2-chloro-bis-trifluoromethylpyridine so obtained
was converted into compound 71 of Table I by following
Route C.
.
ExAMæLE 25
This Example illustrates the preparation of compound
no 76.
2-(p-Hydroxyphenoxy)-5-trifluoromethylpyridine
tl. g) was heated under reflux with 2-chloropropionitrile
(1 molar equivalent) and potassium carbonate (1 g) for
three days. The mixture was filtered and the solvent
removed under reduced pressure to give an oil, which
was purified by thin-layer chromatography on silica
gel using a mixture of equal volumes of ether and
petroleum (b.p. 60-80).
EX~PLE 26
This Examples illustrates the preparation of
compound no 73.
2(p-Hydroxyphenoxy)-5-trifluoromethylpyridine
(1.25 g), potassium carbonate (0.75 g~, ethyl alpha
bromobutyrate (0.96 g) and methyl ethyl ketone ~25 ml)
LZ~53!31D5
- 51 -
were heated under reflux for 6 hours. The cooled
solution was filtered and the solution evaporated to
give an oil. This was purified by passage through a
column of silica gel using a mixture of 20% by volume
S of ether and hexane as the eluent. Compound no 73 was
obtained as a colourless oil.
Following this procedure, but using the appropriate
alpha bromo alkanoic ester in place of ethyl alpha-
bromobutyrate, compounds 72, 74 and 75 were prepared.
lo The starting esters were ethyl alpha bromovalerate,
ethyl alpha bromo isovalerate, and ethyl bromoacetate
respectively.
EXAMPLE 27
This Example illustrates the herbicidal properties
of the compounds of the invention. Each compound was .
formulated for test by mixing it with 5 ml of an
emulsion prepared by diluting 100 ml of a solution
containing 21.8 grams per litre of Span 80 and 78.2
grams per litre of Tween 20 in methyl cyclohexan~ne
to 500 ml wit~ water. Span 80 is a Trade Mark for a
surface-active agent comprising sorbitan monolaurate.
Tween 20 is a Trade Mark for a surface-active agent
comprising a condensate of twenty molar proportions of
ethylene oxide with sorbitan mono-oleate. The mixture
o~ the compound and the emulsion was shaken with glass
beads and diluted to 12 ml with water.
The spray composition so prepared was sprayed on
to young pot plants ~post-emergence test) of the species
named in Table II below, at a rate equivalent to 1000
litres per hectare. Damage to plants was assessed 14
days after spraying by comparison with untreated
plants, on a scale of 0 to 3 where 0 is no effect and 3
represents 75 to 100% kill. In ~ ~est for pre-emergence
herbicidal activity, seeds o~ the test species were
~12~5 !3~
- 52 -
placed on the surface of fibre trays of soil and wexe
sprayed with the compositions at the rate of 1000
litres per hectare. The seeds were then covered with
further soil~ Three weeks after spraying, the seedlings
in the sprayed fibre trays were compared with the
seedlings in unsprayed control trays, the damage being
assessed on the same scale of O to 3. A dash (-~ in
the table of results means that no test was made.
The resul~s are given in Table II below~ 7
/
/
/
o~
-- 53 --
_--~7 0 r~ ~ ~ ~ ~ ~ ~ ~ __
~ oo oo oo oo oo oo oo
E~ ~ ~ O ~ ~ ~ ~ ~ ~ ~ ~ ~'~ ~
~ .
E~ O ~0 ~r~ ~ ~ ~ ~ ~7~
E~ 00 00 00 00 00 00 00
~ oo oo l l ~o oo oo oo .
~ ~ _ ~
H I 1:~ C.) 1¢ m ~ m ~ m ~ m ~ m ~ a: ~: m
I E~
~ ~d U~
m P~ o ~ P~
o ...
~ ~ ~ u~ ~r ~o a:~ o~ ~0
o~ o o o o o o o
a
o o ~ U~ ~0 1_00 O~ o
~z ~ ~ _~ _l
_ ~ ~ ~ ~ ~ ~ ~ ~
~z~s~os
-- 54 --
__ _ _
~-~7 ~ ~ ~ ~
:: o oo o o o o o o o o o o o
U~ C~
Z
~: ~ ,
E~ O ~ ~ ~ ~ ~ ~ 0~
E~ 00 00 00 00 00 00 00
~ oo o o oo oo oo oo oo .
W ^ W H
:z~ ~ ~ z ~ ~ ~ ~ m ~: ~ ~ ~ .~ ~ ;~ c: a~ .
O I E ~ P~ ~
C~ ~ o w~ p~
H P~ 1:4 S'i i¢
O __
~¢ H
E-' H
~ ~ 0 o~ C~ o~
~ oo 0 o~ O O O O
~ O O O O O O O
_
Z
O O ,~ ~ ~ ~r L~ ~o ~_
C~ ~ ~ ~ ~ ~ ~
_ _ _ _ ~
~z~s~os
r ~ ~ ~ ~ ~
U~ ~ 00 00 0~ 00 00 00 00
,E¢ ~ ro~ ~ ~ ., f'~
O ~ ~ r~
00 00 00. 00 00 ,00 0~
O O O O O ~ O O 0 0 O O O O
a o I H _ . . . ____ _
H I E~ 1 ~¢ m ~ m ~ m ~ m ~: m~: m~ ~ :4
H ~ O ~ . __
H
O U~ O ~ 0 o~ o~
~X O O O O O ~::) O
Z _
O O ~ ~ _~ ~ ~r u~
oZ ~ ~7 ~ ~ ~ -- _
~2C! 5~0S
-- 56 --
~ ~7 ~ ~ ~r~ ~r~ ~ ~
U~ ~ oo oo oo oo oo oo oo
.~ ~ ~ ~o ~ o~l ~o
E~ O ~ ~ ~ ~ ~ ,1~ ~
E~ 00 00 00 00 00 00 00
~ r~O OO OO OO ~O l I OO .
a o )EZ~ _ _
o ~ ~: ~ ~ m ~ ~ ~ m ~: m ~ m ~ ~ .
~ ~ o ~: P'
~__ ~
P~ O O O O a) ~ O
o~ o o o o o o o
~ .
Z _. .
~Oz ~r oo ~ O ~ LO
U . ~
~=
OS
- 57 -
__ ~ _ o I ~ ~ ~ ~ _
u~ o 10 00 00 00 00 00 00
r~
E~ O ~ ~ 0~ 00 ~ 0
E~ 00 00 00 00 00 00 0~
~ ,~o o~ oo oo ~ oo ~ .
o æ _
z ^~ ~ ~: m ~ m ~ m ~ m ~ m ~ m ~ a:
H ~ l¢ _
H . __
~ O O O O O O O
0~ O O O O _l
~ __
Z
O O ~ O ~ ~ ~ ~r u~
O Lf ~D U~ ~ ~` I~ ~
C~ _ _ i~ _
~S805
-- 58 --
cn O 00 00
E~ ~:1 ~ ~ 7 0
E~ O ~ ~0
E~ 00 00
~ OO OO
C3 O O
~:) ,_ ~ H
E ~: ~ Z ~ ~ m ~ m
V ~;o~
'z
~ C~
~ ~ = :~
:.
51~C~5
- 59 -
The names of the test plants are as follows:-
Lt Lettuce
To Tomato
Ot/Av Cultivated oats and wild oats (Avena fatua).
Wild oats are used in the post-emergence test
and cultivated oats in the pre-emergence
test.
Ll Lolium perenne (perennial rye grass)
-
Cn Cyperus rotundus
lo St Setaria viridis
The results in Table II clearly illustrate the
selectivity of the compounds of the invention, the
grass species used in the ~est being severely damaged
or killed while the dicotyledonous plants were essentially
unharmed.
~ EXAMPLE 28
This Example illustrates the herbicidal properties
of the compounds of Table I. Tests were carried out as
described in Example 27. The compound was formulated
by mixing an appropriate amount of the compound with 5
~o ml of an emulsion pxepared by diluting 160 ml of a
solution containing 21.8 grams per litre of Span 80 and
78.2 grams per litre of Tween 20 in methy~cyclohexanone
to 500 ml with water. The mixture of the compound and
emulsion was shaken with glass b~ads and diluted to 40
ml with water. Damage to plants was assessed on a
scale of O to 5 where O is O to 20% damage and S is
complete kill. In the table of results, a dash t-) means
that no test was made. The results are given in Table
III below:- ~
IDS8~5
-- 60 --
X oo ~o 'oo oo o ~ -oo oo
. O O O O O O ~ ~ O O O ~1~ O
O O o O o ~7 o o o o o o o ,~ ,~
.~ o o O O o o ~; o o o o o o o
~ o o ~1 0 O o ~ O o o ~1 o
H O O ~1 0 O O r~ 1
~ ~ 10 '~O 10 1~1 OC~l ~ 0~1
E~ ~ ~ 7 Ir')~ u~ f)tn II~r7 ul~ 11')~
E~ ~ ~ Is-) ~ u) ~ ~ ~r ~) u) ~ u7
N U') Il') Ll~ Il') Ll') 1~ U) ~ Lt~ ~ 15~ eJ~ If~ .
~ O O O O ~ O O O O O O O ~t O
H ~ O O .-~ O O ~1 .-1 ~1 O O O ~`I O ~
~1 ~:; O -~, O O O ~ O O O O 01-1 O O
~i Q ~ ~ o o o ~ O ~1 O O
O o
~ Z ~
_, ~ c) ~ m ~ m ~ m ~ m ~ m ~ m ~ m
~ o ~ ~
O _ _ _ !
H ~r n ~ ~r O O Lt~
~1 ~ O O O O O ~i ~i
æ~
~ O ~~n ~ O
oZ ~ ~ U~ In
. ~. 1, ~_
.
- ~2~S~ 5
- 61 -
_ ~ I o I o I o o , oo
o oo oo ,~ o~ I o oo
o o o ~ ~ o o ~ o o o ~ o
.~ o o o o o o o o o o ~ o
~ ~ o o o o o -o o o ~ ~ o
H O O O O O O O O . ~`I O O ~I
~:C ~ ~ O ~ O ~ O O O ~ ~1 O O
p:; L~ ) Lt)~ ~ ~ ll~ ~10
~ ~ ~r ~ ~r ~ ~ ~ ~ ~) u-)~ O O
N ~ L~') ~r L~ ~r t~') t~ L~ ~ Lr) ~I r-l
C~ ~ O O O O O O O O O O 0.0
H C_) O O O O O .-~ O O O O O O
O P~ ,_1 _1 O O O -I 0 ~1 O O O O
H R ~ O ~ O O ~1 O O ~1 0 ~1 0
H . ....
~ O O
m _ m c~ E~
~: I ~ ~ m ~ m ~ a: ~ m ~ m ~ ~q
~ o ~: ~ _
H
O ~) ~ O O O O O L
~ a .
Z a~ ~ ~1 ~ r~ ~
~Z L" D ~D ~D U~ I~
~ l
~2~i80~
-- 62 --
V oo ~10 oo oo oo oo o'o
¢ h~ ~ ~ ~ h'l ~r h'~ h~ O ~ U~ ~1
~ h') h~ ~ h~ ~ h~ h~ h~ ~ h'~ ~r U~ ~ h'~
U~ ~ h~) h'7 h--~ h~ Il') h~ ~ 11~ ~r h'~ h') h~) h~
~ v l ~r ~ ~ ~ ~ ~r 1 ') u'~ ~r h~l ~r d' In 11^)
P~ ::~ ~r o O o ~, ~1 ~t~) ~ ~, ~ o If)~r
~1 Q I ~iS~ ~ I ~ I ~ 10 1 ¦ ~r h~ U')
tl '¢
O ~~r ~ ~ ~~r u-) h') ~ ~ ~ ~ ~ Il'~
Z C~ I O I O l l l l I I 1 I
H ~ O O ~1 0 O O ~ ~--I .-( O O O O , O
V ~ Z _
H ~ W H
v ~ m ,¢ m ~ m ~: m ~: m ~ m ~ m
o ~ ~
E~ ~ _
æ a:~
O ~ ~ ~r ~ ~r ~ O O u~
H t~ O O O O O ,_1 ,_1
~C
Z ___ _
O O ~1 In CO O ~ t~ ~
~ _ r7 ~ ~ __~
. ,`~ .
s
-- 63 --
-- O O O O O O O O- - ~ O O O
~r~r ~r~ ~ ~ 0~1
~ L~ U~ I L~ ~r ~In 0
E~ ~ ~ u~ ~ u~ u~ In U7 ~n In ~ O
ut ~n L~ L~l~ Lr~u~, U)LI~ O O
P~ ~ U'l~l ~ ~1 ~ ~ O O
w a ~ ~ u~ ~ u~ ~r In ~r In I ~ o
E~ ~
a o ~r ~ ~ ~ ~r ~ ~ ~ n ~ o o
Z ~ 10 10 10 10 10 10
Z ~ o o o o o ~ o o o o ~ o .,
O ~ G Z . _ ~. ~ __
H ~ m
W _ G~ O ¢ m ~: m ~: m ~ ~ ~: m
m w U~
~: ~ri O ~ P.
~ ~ .
E~ ~
~ ~ ~ U~ Irl O O O In
H t~ O O ~1 ~1 ~1 ~i
~P~
a __ __
00 a~ O ~ ~ I~
æZ In ~O ~ ~ ~D ~`
_~
.
~ILZ~S80~
- 64 -
The names of the test plants were as follows:-
Sb Sugar beet
Rp Rape
Ct Cotton
Sy Soya bean
Mz Maize
Ww Winter wheat
Rc Rice
Sn Senecio vul~aris
lo Ip Ipomoea ~E~
Am Amaranthus retroflexus
Pi Polygonum aviculare
Ca Chenopodium alb~un
Po Portulaca oleracea
15 Xs Xanthium spinosum
Ab A~utilon theophrastii
Cv Convolvulus arvensis - -
Ot/Av Cultivated oats and wild oats (Avena atua~
Wild oats are used in the post-emergence test
and cultivated oats in the pre-emergence test
Dg Digitaria sanguinalis
Pu Poa annua
St Setaria viridis
Ec Echinochloa crus-galli
25 Sh Sorghum halepense
Ag Agropyron repens
Cn C,vperus rotundus
/
58(~5
- 65 -
EXAMPLE 29
This Example further illustrates the selective
herbicidal activity of the compounds of the invention.
Tests were carried out on a range of crop plants and
weeds, in which the compounds were applied to the
crops at ten times the rate at which they were applied
to the weeds. The test procedure was similar to that
described in Example 27. Damage was assessed 20 days
after spraying, on a scale of 0 to 10 where 0 is no
effect and 10 is complete kill. Each result given in
o the table below is the mean figure for damage to three
plants. The selective nature of the herbicidal compounds
of the invention will be readily apparent from the table
of results~ since even though the compounds were applied
to the crops at ten times the rate which caused severe
damage to the grass species in the test, there was
little or no da~age to the crop p
//
/
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-- 66 --
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U~
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~ ~ ooI~oo~ooo~oooooo~oo
p; ,c)
oo~oo~ooooooooooo~oo _
_ _ _
Z
O
E~ ~ ~ u~
~ ~ In ~ U~ ~ ~ ~ ~
H O O O ~ O O O ,--1 0 0 0 --I O O -1 0 0 0 --I O O
..~..................
14~ OOOOOOOOOOOOOOOOOOOOO
I¢ ~ Cq + + + + + + + + + + + + + + + + + t~ '
O--pO; ~ ~ I` O ~ U~ O ~ U~ O ~ ~ U~ O ~ ~
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~ --~
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-- 67 --
~ a~oa~OU~r~
~ cn a~
3 a ~ ~ ~
O ~ ~ ~
R 0 ~1 0 0 0 0 0 0 0
tq u~
O O ~ ~ ~ O ~ O O O O
~ O O O O O O O O O .,
a
E~ ~ u~ In
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V 3 ~ I ~ Lt
H OO O C) OO O O O
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-
s~
- 68 -
The meanings of the abbreviations for the names
of the test plants have been given in Example 28
excep~ for Al, which stands for Alopecurus myosuroides.
EXAMPLE 30
This Example illustrates the herbicidal activity
of compounds of the invention against a perennial yrass
species, in comparison with a previously known herbicidal
compound of a similar type~ The previously known
compound was compound A below:-
Cl ~ ~ 0l8110C4~l9
Compounds no 5 and 31 of Table I were compared with
lo compound A. In the test, pieces of the rhizome ofSorghum halepense 5 to 8 centimetres long and containing
2 to 3 nodes were buried in compost in plastic trays
in the greenhouse. The compounds were formulat*d for
test as described in Example 28. In a pre-emergence
test the compounds were sprayed on to the compost three
days after the rhizome segments had been buried. The
surface was then covered with more compost and watered~
In a post-emergence test, the rhizome segments were
left for 20 days, when shoots with two to four true
leaves had emerged, and sprayed. Assessments of
herbicidal damage were made three weeks after treatment.
ln the test, three replicates were used for each
treatment. The results are expressed as percentage
damage to the plants, and are the mean of two separate
tests. The figures for percentage damage are given
in the tables below:-
S8~5
~ 69 -
PRE-EMERGENCE RESULTS
_ RATE OF APPLICATION, kg/ha
COMPOUND
NO 0.125 0-25 ¦0-5 1.0
A 11 55 ¦69 100
58 ~8 100 9J3
31 85 . 88'. 100 100
POST-EMERGENCE RESULTS
RATE OF APPLICAT~ON, kg/ha
COMPOUND
NO 0.1250.25 1 0.5 1.0 .
A 58 85 94 100
66 88 100 100 "
31 ~ 96 100 100 100
It Can be Seen from the abOVe tab1eS that the
compounds of the inVentiOn are mOre herbiCida1 ly
effective than Compound A at lower r~te -
JEDjCmW
1~ Ju1 78
/
.
EXA.~PLE 31
This Example illustrates the herbicidal properties
of further compounds of the invention. The compounds t
were tested by the D.rocedure set forth in Example 27
and the results expressed in the same way; the results
are given in the following table, which may be regarded
as a continuation of Table II. - -
'~
- 7 1 _ 12~5~3~15
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U~ U oo oo oo oo oo oo oo oo
~ 3 ~ ~ ~ ~ ~ ~ ~o ~o .
E~ O ~ ~ ~'~ -~ ~ ~ 00 ~0
o o~ o~ oo oo oo oo oo oo
. ~ o~ o~ o~ o~ oo o~ oo oo
~Co ....... ~ ~
~ ' ~ u ~ m ~ m ~ m ~ m ~ m ~ m ~ p: ~ m
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Z ~_ _
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OJ -_ ~
;~ .
~z~s~s
-- 72 --
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o 00 00 00 00 00
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E~ O 1~ 0~1 ~ ~ ~
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~ _ _ _
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