Note: Descriptions are shown in the official language in which they were submitted.
107~233
Background of the Invention
:
Various substituted amides particularly N-su~-
stituted amides and substituted phenoxy amide are known to be
useful as insecticides, miticides, and herbici~es. Typical in-
secticidal properties of such compounds are taught in U.S.
Patent 2,426,885 as well as U.S. 2,484,295 and U.S. 2,484,296.
Herbicidal properties of such compounds are taught in U.S.
Patents 3,272,844, 3,439,018 and 3,564,607 and Belgian
Patent 739,714.
Brief Description of the Invention
This invention relates to a class of substituted
phenoxy alkyl amides and to their use as miticides when used
in a miticidally effective amount. More specifically, this
invention relates to phenoxy alkylamides having the formula:
n ~ Rl R R C _ C~
wherein Rl is either methyl or ethyl, R2 and R3 are ir.depen-
dently either hydrogen or methyl; and when R3 is nydrogen, n
is either 1 or 2; and when R3 is methyl, n is 2 and to
phenoxy alkylamides having the formula:
m~~\ C~3
wherein R is either methyl or ethyl and X is either chlorine
or trifluoromethyl, and where X is chlorine, m is 3 with
proviso that
--2--
~' .
~07~Z33
thc 2- flnd 4-po~itlon~ arc not both occupied on thc snme phenyl
ring; and where X is trifluoromethyl, m ls 1,
The chlorine atoms whose positions on the phenyl ring
are undesignated ln formula (I) will hereinafter be referred to
as "floating chlorine atoms." In the examples cited hereinbelow
snd in the claims which follow this specification, the flonting
chlorine atoms will be assigned positions on the phenyl ring.
These positions will be identified in accordance with the
following numbering system:
4 ~ H
By "mitlcidally effective amount" is meant the amount
of the herein disclosed miticidal compounds which when npplied to
the habitst of mites in any conventional manner wlll kill or sub-
stantially in~ure a significant portion of the population thereon.
Detailed Description of the Invention
The compounds of the formula (I) are prepared by the
following general method, wherein Rl, R2, R3 and n are as defined
above:
Renction No. 1
Cl Cl
>~ R NaOH (aq ~ ~ R
Cl~ 1l + Br-C~I-C-OH C ~ -CH-C-OH
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To a mixture of a molar amount of the phenol and a
slight molar excess of the acid is added a slight molar excess of
50% aqueous NaOH. The produce acid is then washed with suitable
solvents and recovered from the organic phase.
Reaction No 2
Cl
~,~ R HC-N(CH3)2
Cl~--O-~CH-C-OH + COC12
n
Cl
Cl~ - ~ -C-Cl + HCl
A slight molar excess of phosgene is introduced into
a molar amount of the acid in a suitable solvent, to which a
small amount of d~methyl formamide has been added. The excess
phosgene and HCl are then removed and the solvent is evaporated
to le~ve the acid chloride.
Reaction No. 3
Cl
~ 13 (C2~15)3N
Cln ~l R2 R3
Cl
n Rl R2 R3
--4--
~07~Z33
The acid chloride is added to a solution containing
both the acetylenic amine and the tr~ethylamine at 10-15C.
After successive washings, the product is recovered from the
organic phase.
S The compounds of formula (2) are prepared analogously.
The examples shown herein are illustrative of the method of
preparation of the compounds of both formulas.
EXAMPLE I
N-dimethylpropynyl-~ -(2,3.5-trichlorophenoxy~butyramide.
(Compound No. 3 ~n Table I below)
44.0 g (0.55 mole) of 5~/O aqueous sodium hydroxide was
added to A mixture of 42.5 g (0.22 mole) 2,3,5-trichlorophenol
and 43 4 g (0.26 mole) 2-bromobutyric acid, with rapid stirring
at an initial temperature of 15C. The temperature rose to 45C
over the course of the addition and was held between 15C and
45C with a cold water bath At the completion of the sodium
hydroxide addition, the cold bath was removed and the mixture
WA8 heated to 110C for 15 minutes. Then 50 ml water, 53 ml
perchloroethylene, and 42 ml concentrated hydrochloric acid were
~dded to the reaction mixture ~nd the mixture was heated to 85C,
then phase-separated. The organic layer was cooled and the
product, ~-(2,3,5-trichlorophenoxy)butyric acid crystallized.
The acid was separated by filtration to give 43.1 g (69~1% yield)
of the acid, m.p. 65-70C.
0.2 ml dimethyl formamide was added to a slurry of
50.3 g (0.18 mole) of ~ -(2,3,5-trichlorophenoxy)butyric acid in
``` 1071Z33
80 ml toluene. The slurry was then heated to 60C in a 500ml
flask which was fitted with a gas~inlet tube~ a stirrer, a
thermometer, and a dry ice-isopropyl alcohol condenser. 22 g
(0.23 mole) of phosgene was passed into the mixture at a
moderate rate. The dry ice condenser was then removed and
replaced with a water-cooled condenser. Excess phosgene and
HCl were removed by an argon purge through the solution at
60C. The solution was then cooled and the solvent was re-
moved in vacuum to leave 43.4 g (80% yield) of an oil, ~-(2,
3,5-trichlorophenoxy)butyryl chloride.
8.0 g (0.03 mole) of the acid chloride was added
dropwise to a mixture of 2.9 g (0.035 mole) dimethylpropargyl-
amine and 3.6 g (0.035 mole) triethylamine in 100 ml of
dichloromethane at 10-15C. Some cooling in an ice bath was
necessary to maintain the temperature. After the addition of
the acid chloride, the mixture was allowed to come to room
temperature and the product was isolated by washing with, in
succession, 100 ml portions of water, dilute HCl, 5% Na2CO3
solution, and water. The organic phase was dried over magne-
sium sulfate and the solvent was removed in vacuum to leave
7.7 g (73.6% yield) of an oil, m.p. 118-120C., which was
identified by infrared spectroscopy as N-dimethylpropynyl-
-(2,3,5-trichlorophenoxy)butyramide.
EXAMPLE II
N-methyl-N-isobutynyl- ~ -(2,3,5-trichlorophenoxy)butyramide
(Compound No. 4 in Table I below)
~ -(2,3,5-trichlorophenoxy)butyryl chloride was
prepared in a manner identical to that described in Example I.
7.0 g
~071Z33
(0.02 mole) of the ~cid chloride was added dropwise to a mixture
of 2.3 g (0.03 mole) of N-methyl-2-amino-3-butyne and 2.9 g
(0.03 mole) of triethylamine ~n 100 ml dichloromethane at 10-15C.
From this point a procedure identical to that of Example I was
followed, to yield 7.1 g (84.8% yield) of N-methyl-N-isobutynyl~-
(2,3,5-trichlorophenoxy)butyramide, m p. 73-77C, characterized
by infrared spectroscopy.
EXAMPLE III
N-dimethylacetonitr~lo- ~ -(3,4.S-trichlorophenoxy)butyramide.
(Compound No. 8 in Table I below~
50.8 g (0.63 mole) of 5~/0 aqueous sodium hydroxide was
added to a mixture of 50 g (0.25 mole~ of 3,4,5-trichlorophenol
and 50 g (0.30 mole) of 2-bromobutyric acid,~Lth rapid stirring
at an initial temperature of 15C The temperature rose to 45C
over the course of the s~dition and was held between 15C and
45C with a cold bath. At the completion of the sodium hydroxide
addition, the cold bath was removed and the mixture was heated
to 110C for 15 minutes. Then 62 ml water, 125 ml perchloro-
ethylene, and 50 ml concentrated hydrochloric acid were added to
the reaction mixture The mixture was heated to 85C, then
phase-separated. The organic layer was cooled and the product,
c~_(3,4,S-trichlorophenoxy)butyric scid, crystallized. The acid
was separated by filtration snd amounted to 54.2 g (76% yield),
m.p, 115-118C.
0.2 ml dimethyl formamide was added to a slurry of
54,2 g (0.19 mole) of ~-(3,4,5-trichlorophenoxy)butyric acid in
75 ml toluene. The slurry was then heated to 60C in a 500 ml
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~7~233
flask fitted with a gas-inlet tube, a stirrer, a thermometer
and a dry ice-isopropyl alcohol condenser. 22 g (0 23 mole)
of phosgene was p~ssed into the mixture at a moderate rate. The
dry ice condenser was then removed and replaced with a water-
cooled condenser, ~xcess phosgene and HCl were removed as the
solution was purged with argon at 60C. The solution was then
cooled, and the solvent was removed in vacuum to leave 54.9 g
(95.6% yield) of a liquid, n30 1.5506, which was ~-(3,4,5-
trichlorophenoxy)butyryl chloride.
8.0 g (0.03 mole) of the acid chloride was added drop-
wise to a mixture of 2.5 g (0.03 mole) of c~-aminoisobutyronitrile
[made by the procesure of J.V. Dubsky and W.D. Wensink, Ber. 49,
1136 (1916)] ~nd 3.1 g (0 03 mole) of triethylamine in 100 ml
methylene chloride at 10-15C. An ice bath was used to maintain
the temperature. After the addition of the acid chloride, the
mixture was allowed to come to room temperature and the product
wa~ isolated by wsshing with, in succession, 100 ml portions
of water, dilute HCl, 5% Na2CO3 solution and water. The organic
phase w~s dried over magnesium sulfate and the solvent was removed
in vacuum to give 5.6 g(48~r/o yield~ of the product, identified
by infrared ~pectroscopy as N-dimethylacetonitrilo-c~-(3,4,5-
trichlorophenoxy)butyramide, m.p. 162-164C.
EXAMPLE IV
N-dimethylacetonitrilo-~-(2.3.5-trichlorophenoxy~butyramide,
(Compound No. 9 in Table I below)
44 0 g (0 55 mole) of 5~/ aqueous sodium hydroxide was
added to a mixture of 42 5 g (0.22 mole) of 2,3,5-trichlorophenol
and 43.4 g (0.26 mole) of 2-bromobutyric acid, with rapid stirring
--8--
-` 1071Z33
at an initial temperature of 15C. The temperature rose to
45C over the course of the addition during which time a cold
water bath was applied. At the completion of the sodium hy-
droxide addition, the cold bath was removed and the mixture
was heated to 110C for a 15-minute period. Then 50 ml of
water, 53 ml of perchloroethylene, and 42 ml of concentrated
hydrochloric acid were added and the mixture was heated to
85C, then phase-separated. The organic layer was cooled and
the product, ~-t2,3,5-trichlorophenoxy)butyric acid, crystal-
lized. The acid was isolated by filtration to give 43.1 g
(69.1~ yield) of ~-(2,3,5-trichlorophenoxy) butyric acid, m.p
106-114C.
0.2 ml of dimethyl formamide was added to a slurry
of 50.3 g (0.18 mole) of ~-(2,3,5-trichlorophenoxy)butyric
acid in 80 ml of toluene. The slurry was then heated to 60C
in a 500 ml flask fitted with a gas-inlet tube, a stirrer, a
thermometer, and a dry ice-isopropyl alcohol condenser. 22 g
(0.23 mole) of phosgene was passed into the mixture at a mod-
erate rate. The dry ice condenser was then removed and re-
placed with the water-cooled condenser. Excess phosgene and
HCl were removed by an argon purge of the solution at 60C.
The solution was then cooledj and the solvent was removed
in vacuum to leave 43.4 g (80% yield) of an oil, which was
~-(2,3,5-trichlorophenoxy)butyryl chloride.
8.0 g (0.03 mole) of the acid chloride was added
dropwise to a mixture of 2.9 g (0.04 mole) of 0~-aminoisobuty-
ronitrile and 3.7 g (0.04 mole) of triethylamine in 100 ml
methylene chloride, maintained at a temperature of 10-15C
by an ice bath. After the addition of the acid chloride, the
mixture was allowed to come to room temperature and the pro-
ductwas isolated by washing with,
1071233
in succession, 100 ml portions of water, dilute HCl, 5~/0 Na2C03
solution and water The organic phase was dried over magnesium
sulfate and the solven~ was removed in vacuum to leave 7.8 g
(74.4% yield) of N-dimethylacetonitrilo-~-(2,3,5-trichlorophenoxy)
butyramide, m.p. 137-140C, characterized by infrared spectroscopy.
Other compounds~ such as those included in the following
table, can be prepared in a manner analogous to that shown in the
examples above, starting with the appropriate materials. The
compounds in the table are representative of those embodied in
the present invention. Compound numbers have been assigned to
them for purposes of ldentification throughout the balance of
the specification
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107~233
TABLE I
m.p. C.
COMPOUND or 30
NU~IB~R COMPOU~ . nD
Cl
~ O CHq
1 Cl ~ C2H5 CH3 1.5374
Cl Cl
2Cl ~ O- CH- C- ~ - C- C - CH 78-83C
C2H5 CH3
Cl Cl
O - CH - C - N~ } C - C CH 118-120C
2H5 CH3
., C
Cl 51
4~ O -C~l- C - M~- CH - C - CH 73-77C
Cl
Cl Cl
~ O CH
SCl ~ O - CH- C ~ CH- C - CH 88-98C
Cl Cl
~ o CHq
6~ O--CH--C -Nn~-C- C - CH 121-123C
Cl
Cl Cl
7~ -O- CH- C - M- CH- C CH 1.5486
Cl
~071Z33
TABT F I
(continued) '
COMPOUND
NUMBER COMPOUND MELTING POIMT
- C 1
8 Cl~O--CH--C--NH--C C----N 162-164C
C~-- C2H5 CH3
9~O--CH--C--NH--C--C=N 137-140C
~< C2H5 CH3
10~O--CH--C--N~C--C=N 72-75DC
C2H5 CH3
CF3
11Cl ~--O--CH--C--NH--C--CeN 133-136C
Cl CH3 CH3
Cl
lZ~ 1l CH3 136-140C
-12 -
~071Z33
Miticidal acti~ity of each of the ~bove compounds
on the two-spotted mite ~Tetranychus urticae (Koch~] was eval- -
uated as follo~s:
Pinto bean plants-(Phaseolus sp.), approximately
10 cm tall, are transplanted into sandy loam soil in 3-inch
clay pots and thoroughly infested with two-spotted mites of
mixed ages and sexes. Twenty-four hours later the infested
plants are inverted and dipped for 2-3 seconds in 50-50
acetone-water solutions of the test chemicals. Treated plants
are held in the greenhouse, and seven days later mortality is
determined for both the adult mites and the nymphs hatching
from eggs which were on the plants at the time of treatment.
Test concentrations range from about 0.08% down to that at
which 50% mortality occurs.
The following is a table of the results of the
above test procedure, indicating the effective concentration
at which 50% mortality was achieved.
TABLE II
Effective Concentrations on Two-Spotted Mite
[Tetranychus urticae (Koch)]
COMPOUND NUMBER PE (~) Eggs (%)
1 .03 > .05
2 .03 > .05
3 .001 .008
4 .005 .03
.08 .05
6 .005 .008
7 .05 > .05
-13-
~ 71233
T~ble II
(continued)
COMPOUND NUMBER PE (%) EGGS_(%)
8 .008 ,01
9 .0~5 >.05
.03 .05
11 .005 .03
12 >.2 .15
PE ~ Post-embryonic
> ~ Greater than
Neither the examples nor the tables hereinabove are
intended to limit the invention in any manner.
The compounds of thls invention are generally embodied
in a form suitable for convenient applic~tion. For example, the
compounts can be embodied in miticidal compositions in the form
of emulsions, suspensions, solutions, dusts, and serosol sprays.
In addition to the active compounds, such compositions generally
contain the ad3uvants which are normally found in miticide pre-
parations. One such composition can contain either a single
miticidally active compound or a combination of miticidally active
compound8. The miticide compo~itions of this invention can contain
as ad~uvants organic solvents such as sessme oil, xylene, or
heavy petroleum; water; emulsifying agents; surface active agents;
talc; pyrophyllite; diatomite; gypsum; clays; or propellants such
a8 dichlorodifluoromethane; or a combination of these. If desired,
however, the active compounds can be applied directly to feed-
stuffs, seeds, or other such matter on which the pests feed. When
-14-
1071Z33
~pplied in such a manner, it will be advantageous to use a com-
pound which is not volatile, In connecti~n with the activity
of the presently disclosed mitic~dal compounds, it should be
fully understood that the compounds need not be active as such.
' 5 The purposes of this invention will be fully served by a compound
which i5 rendered active by an external influence such as light,
or by some physiological action which the compound induces when
it is ingested into the body of the pest,
The precise manner in which the miticidal compounds of
this invention should be used in any particular instance will be
resdily apparent to a person ~killed in the art, The concentration
of the active miticide in a typical composition can vary within
rather wide limits. Ordinarily, the miticide will comprise not
more thsn about 15~/o by weight of the composition. The preferred
range of concentrstion of the miticide is about 0.1 to sbout l~/o
by weight,
