CA1157475A - Insecticidal 2,6-dihalobenzoyl derivatives - Google Patents

Abstract

ABSTRACT
Compounds of formula (I) (I) wherein R and R1 are different and each represent chloro or fluoro; R2 is chloro, bromo or trifluoromethyl;
or veterinarally-acceptable salts thereof, are effective in reducing the population of manure-breeding insects.
Methods for their production are also described.

Description

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INSECTICIDAL 2,6-DIHALO ENZOYL DERIVATIVE_ This invention relates to certain novel asymmetrical

2,6-dihalobenzoyl derivatives of value for killing manure-breediny insects and is a div,isional of Canadian Application Serial No. 368,777, filed January 19, 1981.
Insecticidal 2,6-dihalobenzoyl derivatives similar to those of the present invention are described in the Journal of A ricultural Food ChemistrY, 26, No. 1, 164 g _ _ (1978~o In a first aspect of the invention there is provided a compound of the formula tI) ~R

NH~NH ~ il (I) \R1 ~ /~R2 wherein R and Rl are different and each represent chloro or fluoro; R2 is chloro, bromo or trifluoromethyl:
or a veterinarally-acceptable salt thereof.
The novel compounds are useful for reducing a popu-lation of manure-breeding insects by causing or allowing a warm-blooded animal to ingest sufficient of the com pound that the faeces derived from that animal contain an insecticidally effective amount of said compound.

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( X~5223A -2-The use of insecticides by oral administra-tion to animals for the control of manure-breeding insects is a rather new concept in insect control.
The compounds are active against the larvae S of insects which breed in manure, especially insects of the order Diptera. Especially important manure-breeding insects, against which the method of this invention is particularly effective, include the house fly ~Musca domestica), the ~table fly (Stomoxys calcitrans), the horn fly t~aematobia irritans), and _. _ the face 1y ~Musca a umnalis).
The compounds used in the method of this invention are orally administered to the animals to be treated, and pass essentially unchanged through the alimentary tract of the animal. The compound thus is excreted in the animal's faeces, where it is effec~ive against the larvae of insects; The animals which may be treated in accordance wi~h the present method include especially poultry, such as chickens, ducks, turkeys and geese; ruminants, such as cattle~ sheep and goats; and economic monogastric animals, such as horses and swine. The compounds may also be used, if desired, in carnivorous animals, such as those of the cat and dog ramilies.
Use of the method of this invention in poultry, especially chickens, and in ruminants, especially bovines, is most highly preferred.

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The exact means by which the compounds used in the m~thod of this invention are administered to the animals is not critical~ It is easiest and most conven-ient, of course, to mix the compound in the animal's feed. When the compounds are administered as feed additives, they may be used in concentrations in the feed ranging from abo~t 1 ppm. to abou~ S0 ppm. by weight. A preferred range of concentration is from about 1 ppm. to about 10 ppm. by weight.
The formulation o~ feed additives into animal feeds is a well known art. It is usual to make a concen-trated premix as a raw material for treated feeds. The formulation of the premix is guided solely by convenience in mixing feed from the premix, and by economy. The pre-mix may contain from about 1 to about 400 g./lb. of the insec~icide, depending on convenience in ~ixing feed containing the desired concentration of the compound.
Premixes may be either liquid or solid.
The improved feed premixes which are provided by this invention, can be formulated with any of the conventionally-used physiologically-acceptable carriers.
Liquid ~arriers which are suitable for premix use include glycols such as polyethylene glycols of various molecular weights and propylene glycol, inert oils including vegetable oils and highly-rerined mineral oil, and physiologically-acceptable alcohols such as ethanol. Solid premix carriers include vermiculite, diatomaceous earth, physiologically-acceptable clays such as attapulgite and montmorillonite, and granulated or powdered feed components such as cracked corn, soybean meal, alfal~a meal, rice hulls, corn cobs, .
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( cracked wheat or oats, and waste materials of grain processing.
It ~ill further be understood by those skilled in animal husbandry that animal feeds containing from S about 1 ppm. to about 50 ppm. by weight of a compound useful in the method of this invention are novel and are important embodiments of the invention. Such feeds may preferably be in the form of cereaL-based feeds, adapted to the needs of poultry, ruminants and/or monogastric animals such as horses and swine. The usual dry or slurried animal feeds, based on grains such as wheat, oats, barley, maize and the like, may be treated with compounds used in the method of this invention, just as animal feeds are routinely treated with medicaments and parasiticides in the ordinary practice of the animal husbandry art.
The compounds may also be admlnistered as additives to the animal's drinking water, in which case they should be used in a concentration of from abollt 1 ppm. to about 30 ppm., preferably from about 1 ppm.
to about 15 ppm.
Administration of the compounds by means of sustained release boluses is particularly advantageous when ruminants, especially cattle, are to be treated.
Such boluses are made as tablets are made, except that a means ~o delay the dissolution of the compound over a period of time is provided. ~oluses may be made to release the compound steadily over long perlods of time, even 100 days or more. A number of polymeric substances have been used to prepare slow-release ~ ~5~7~

boluses; particularly effective polymers are the copoly-mers of polylactic and polyglycolic acids. It is necessary to retain a slow-release bolus in the rumen of the treated ruminant, so that the bolus is not carried on out of the digestive tract. Boluses are retained in the rumen most easily by making them of a high-density material, as by mixing metal particles into the composition, or by providing wings which open in the rumen and make the bolus too large to get through the opening into the omasum of the animal. Boluses should release from about 0.01 mg./kg. of body weight/day to about 2 mg./kg~/day, preferably from about 0.01 to about 0.25 mg.,'kg./day.
i~iineral blocks provide another advantageous formulation wi~h which to administer the insecticides, particularly to ruminant animals. Such blocks are usually supplied to rumi~ants, even to those on pasture.
The usual blocks are highly compressed forms of physio-logically~desirable sal~s and nutritive substances, generally incLudin~ phosphates, carbonates, halides, calcium salts, trace elements such as zinc, cobalt, manganese and the like, vitamins, steroids, and lubri-cants and binders to assist in compression.
Mineral bLocks are, of course, old in the ~5 animal husbandry art. The addition of the inse~ticides of the present method, however, provides novel blocks which ara important embcdiments of the present invention.
The insecticides should be added to the blocks in con-centrations from about O.OL% to about 0. 5~, preferabLy ~rom about 0.05% to about 0.25%.

I ~5~5 It is necessary, of course, to administer at least an insecticidally-effective amount of compound to the animal to be treated. It is most effective to measure the amount administered, however, as a concen-tration in the medium with which i~ s combined.Effective insecticidal amounts, or concentrations, are described above.
It is not implied, of course, that adminis-tration of any amount of any compound used in the method of this invention will kill all larvae of all manure-breeding insects. It is not in the na~ure of biological methods to be invariably 100~ effective.
However, the oral administration of a compound of the present method, in an insecticidally-effective amount, will produce a worthwhile reduction in the number of insect larvae which mature in the manure of the treated animal. In many cases, of course, complete control of the larvae will result, and no adults will develop. It will be understood that partial con~xol of the manure-breeding insects is significant and beneficial, andthat the population of the insects is usefully reduced, even though not aLl of them may be killed by the insecticidal treatment.
Control of manure-breeding insects in accord-ance with 'he present invention is, clearly, moreconvenient and effective than is insect control by traditional methods of applying insecticides to the manure after it has been gathered and piled. The added operation of spraying or dusting insecticides over the manure is avoided. More importantly, the method of ii .

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this invention results in the insecticidal compounds being intimately mixed through the mass of the manure, so that any larvae in the mass are sure to come into contact with the compound.
The compounds of formula (I) are preferably prepared by the reaction of a 2,6-dihydrobenzoyl iso-cyanate of the formula R
NCO
O
~Rl with a 2-aminopyridine of the formula H2N~

The reaction is preferably carried out in an organi.c solvent, such as a ketone, such as methyl ethyl ketone, methyl isobutyl ketone or acetone, a halogen-ated solvent such as dichloroethane, dichloromethane, chlorobenzene, 1,1,2-trichloroethane and the like, an ester such as ethyl acetate, butyl acetate, methyl propionate and the like, an aromatic hydrocarbon such as benzene, toluene or a xylene, a nitrile such as acetonitrile, an aliphatic hydrocarbon such as pentane, - , ..

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( X-52~3A -8-hexane or octane, or an ether such as diethyl ether, diisopropyl ether or tetrahydrofuran. The reaction should be carried out at moderate temperatures, pre-ferably at a temperature between about 0C. and about 50C.
The acid addition saLts of the compounds of this invention can be prepared in the usual manner by reacting the compound with the desired acid, in aqueous or aqueous-organic media. Acids having a low pKa of 3 or below are preferred~ Acids which may be used to form the acid addition salts include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid~ hydriodic acid, toluenesulfonic acid and the like.
The 2,6-dihalobenzoyl isocyanates to be employed as starting materials are readily prepared from the corresponding 2,6-dihalobenzamides, which are commercially available, by the method of Speziale et al., J. Org. Chem. 27, 3742 (1962); and Wellinga et 20 al., J Aaric. Food Chem. 21, 348 and 993 ~1973). In this method, the benzamide is reacted with oxalyl chloride. An improved method o~ carrying out the reaction comprises reacting the benzamide wi~h the oxalyl chloride in toluene at about 55C. while water is carefully excluded, and tnen heating the reaction mixture to the reflux ~emperature after about 18 hours at the lower temperature. Ater about 2 hours at reflux, the reaction mixture is put under vacuum and tne product is isolated by distillation.

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The 5~bromo and 5-chloro-2-aminopyridine starting materials are commercially available. The 5-trifluoromethyl-2-aminopyridine can be prepared by the method of U.S. Patent Specification No. 3,681,369.
The compounds of this invention can also be mlde by reacting a 2,6-dihalobenzamide of the formula ~R
0~--~o - CNH
\ / 2 Rl with a 2-pyridyL isocyanate of the formula N~
:)CN~

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The reaction described above is preferably run at a tempera~ure from about 50C. to about 150C. in an inert organic solvent such as described above~ except that the higher-boiling solvents should be chosen.
The compounds of this invention may further be prepared by reacting a reactive derivative of a 2,6-dihalobenzamidocarbo~ylic acid of the formula R
NH COZH
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3 ~5~'J5 with an aminopyridine of the formula H2Nl ~
S ~./

The acid just mentioned above may be used in the form of an acid chloride or bromide, or an ester.
Typical esters for this purpose include the lower alkyl esters, such as methyl, ethyl, propyl and butyl esters, phenyl esters, and the more active esters such as those formed with agents typified by dicyclohexyl-carbodiimide, isobutyl chloroformate J 2-ethoxy N-ethoxy-carbonyl-1,2-dihydroquinoline, methyl chloroformate, ethyl chloroformate, hydroxypentachlorobenzene, N,N-diisopropylcarbodiimide, N cyclohexyl-N'-(2-morpholino-ethyl)carbodiimide and other related reagents which are now w211 known in the literature.
When the acid is in the form of an acid halide, the reaction mixture should contain a hydro-halide acceptor to improve the efficiency of the reac-tion. Simple bases such as tertiary amines and alkali metal hydroxides, carbonates and bicarbonates may be ~ used as ~he hydrohalide acceptor.
Reactions of benzamido acid derivati~Jes with aminopyridines are carried out in inert organic solvents at temperatures in the range from about -20C. to about 100C., of which temperatures from about 0C. to ~he ambient temperature are preferred. The solvent may be any of a number o inert organic solvents, includiny ~, ~

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halogenated hydrocarbons such as have been described above, or ketones or ethers as described above.
Another process for preparing the new com-pounds i.s the reaction of a benzamide of the formula ~R1 with an active derivative of a pyridinylaminocarboxylic acid of the fo~mula t ~_~2 ~ ./

where the active derivatives are as described above.
The above reaction is b~st carried out at temperatures from about 50C. to about 150C., in inert organic solvents as described above.
All of the synthetic reactions described above consume their reactants in equimolar amounts, and so it is unnecessary to supply excess amounts of either reac-tant, unless it is desired, in a particular instance, to use an excess of a relatively inexpensive reactant to assure that the more costly reactant is completelv used.
The following preparative examples illustrate the synthesis of compounds of Formula I ~ 5 7 .' EXAMPLE 1: 1-(2,6-DIFLUOROBENZOYL)-3-(5-TRIFLUOROMETHYL-2-PYRIDINYL)UREA
An 0.7 g. portion of 5-trifluoromethyl-2-amino-pyridine was dissolved in 20 ml. of acetonitrile~ and to the solution was added 0.85 g. of 2,6-difluorobenzoyl isocyanate under a nitrogen blanket at ambient tempera-ture. A precipitate formed i~mediately. The mixture was stirred for 3 hours, ~nd was then filtered and the solids were washed with ace~onitrile. The solids were dried under vacuum to obtain 1.0 g. of the product named above, m.p. 215-220C~ Elemental analysis gave the following results:
Calculated: C, 48.71; H, 2.34; N, 12.17.
Found: C, 48.90; H, 2.39; N, 12.37.
LE 2: 1-(2- CHLORO~6 - FLUOROBENZOYL) -3-(5-BROMO-2-PYRIDINYL)UREA
An 0.4 g. portion of 5-bromo-2-aminopyridine was dissolved in 20 ml. of acetonitrile, and was reacted with 0.5 g. of 2-chloro-6-fluorobenæoyl isoc~a-nate as described in Example 1. The yield was 0.5 g.
of the desired product, m.p. 207-213C. Elemental analysis gave the following results:
Cal~ulated: C, 41.91; H, 2.16; N, 11028u Found: C, 41.76; H, 1.90; N~ 11u12.
EXAMPLE 3: 1--( 2-CHLORO--6--FLUOROBENZOYL) -3--( 5--CHLO~O--2-PYRIDINYI.) UREA
An 0.4 g. portion of 5-chloro-2-aminopyridine was dissolved in 20 ml. of acetonitrile and reacted with 0.7 g. of 2-chloro 6-fluorobenzoyl isocyanate as 57~

described in Example 1. The yield was 0.65 g. of the product named above, m.p. 210-215C. Elemental analysis gave the following results:
Calculated: C, 47.59; H, 2.46; N, 12.81.
S Found: C, 47.34; H, 2.59; N, 12.66.
EXAMPLE 4: 1-(2-CHLORO-6-FLUOROBENzOYL)-3-(5-TRIFLUORO-~THYL-2-PYRIDINYL)UREA
A portion of 5-trlfluoromethyl-2-aminopyridine is reacted with 2-chloro-6-fluorobenzoyl isocyanate as described in Exarnple 1. The reaction mixture is evaporated under vacuum and the product is recrystal-lized to obtain the product named above.
EXAMPLE 5: 1-(2,6-DICHLOROBENZOYL)-3-(5-TRI~LUORO-METHYL-2-PYRIDINYL)UREA
lS A 1.1 g. portion of 2,6-dichlorobenzoyl isocyanate and 0.8 g. of 5-trifluoromethyl-2-aminopyridine were mixed in 50 ml. of ethyl acetate at ambient tempera-ture and stirred for 18 hours. ~he solvent was then evaporated and the product was recrystallized from ethanol to obtain 0O2 g. of the product named above, rn.p. 228-230C. Elemental analysis showed:
Calculated: C, 44.47; H, 2.13; N, 11.11.
~ound: C, 44.42; H, 2.19; N, 11.18.
EXAMPLE 6: 1-(2/6-DIFLUOROBENZOYL)-3-~5-BRoMo-2-PYRIDINYL)UREA
~ 2 g. portion of 5-bromo-2-arninopyridine was reacted with 2~5 g. of 2,6-difluorobenzoyl isocyanate under nitrogerl in 50 ml. of ethyl acetate. The reaction mixture was stirred for 3 days, and was then fil~ered.

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( The solids were washed with dichloromethane, ethyl acetate and diethyl ether and dried under vacuum to obtain the desired product, m.p. 232-235C. The elemen~
tal analysis showed:
S Calculated: C, 43.84; H, 2~26; N, 11.80~
Found: C, 43.55; H, 2.24; N; 11.520 EXAM2LE 7: 1-(2,6-DIFLUOROBENZOYL)-3-~5-CHLORO-2-PYRIDINYL)UREA
An 0.5 g. portion of 5-chloro-2-aminopyridine was reacted with 0.6 g. of 2 t 6-difluorobenzoyl isocya nate as described in Example 1. The isola~ed product was 0.8 g. of the product named in the heading above, m~p. 226-223C. Its elemental analysis showed ~he following results:
Calculated: C, 50.10; H, 2.59; N, 13.48.
Found: C, 49.88; H, 2.51; N, 13.21.
EXAMPLE 8: 1-(2,6- DIFLUOROBE~ZOYL) -3- ( 5--TRIFLUOE~OMETHYL-2-PYRIDINYL)UREA
A portion of S-trifluoromethyl-2 pyridinyl isocyanate is reacted with a portion of 2,6-difluoro-benzamide in an inert organic solvent, and the reaction mixture is evaporated under vacuum and the residue is recrystallized to obtain the compound named in the heading, identical to the product of Example 1.
E~A~IPLE 9: 1- (2-CHLORO-6-FLUOROBENZOYL)-3-(5-BROMo-2-PYRIDINYL) UREA
A portion of 5-bromo-2-pyridinyl isocyanate is dissolved in an inert organic solvent and is reacted with 2-chloro-6-fluorobenzamide as described in ,;

~ ~5~47 ( Example 8. The product is isolated as described in that example to obtain a portion of the product named in the heading, identical to the product of Example 2.
EXAMPLE 10: 1 ( 2-CHLORO-6- FLUOROBENZOYL) -3-(5 CHLORO-2-PYRIDINYL)UREA

~ portion of 2-chloro-6-fluorobenzamide is reacted with 5-chloro-2-pyridinyl isocyanate as described in Example 8, and the product is isolated and purified as described in that example to obtain a significant yield of the product named in the heading, identical to the product of Example 3.
EXAMPLE 11: 1-( 2-CHLORO-6-FLUOROBENZOYL)-3-(S-TRI-FLUOROMETHYL-2-PYRIDINY~UREA

A portion o 2-chloro-6-fluorobenzamide is reacted with 5-trifluoromethyl-~2-pyridinyl isocyanate as described in Example 8, and the product i9 isolated as described in that example to obtain the compound named above, identical to the product of Example 4.
EXAMPLE 12: 1-(2,6-DIFLUOROBENZOYL)-3-(5-TRIFLUORO-METHYL-2-PYRIDINYL)UREA

A portion of 5-trifluoromethyl-2-aminopyrl-dine is reacted with 2,6-difluorobenzamidocarboxylic acid chloride in an inert organic solvent in the pres-ence of a hydrogen halide acceptor. The reaction mixture is washed with water and neutralized, and the organic layer is evaporated to dryness to obtain tne product named in the heading, identical to the product of Example 1.

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EXAMPLE 13: 1- ( 2-CHLORO-6-FLUoROBENZoYL) -3-(5-BROMO-2-PYRIDINYL) UREPL
To a portion of 2-chloro-6-fluorobenzamido-carboxylic acid chloride dissolved in an organic solvent, a hydrogen halide acceptor is added, and a portion of 5-bromo-2-aminopyridine is added. After a period of stirring, the reaction mixture is washed with water and neutralized, and the product named in the heading is isolated as described in Example 12. The product is identical to that of Example 2 above~
E~AMPLE 14: 1-(2-CHLORO-6-FLUOROBENZOYL)-3-(S-C~LORO-2-PYRIDINYL)UREA
A portion of 5-chloro-2-aminopyridine is reacted with 2-chloro-6-fluorobenzamidocarboxylic acid 1,5 chloride~in the presence of a hydrogen halide acceptor as described in Example 12. The product, named in the heading above, is isolated as described in Example 12 to obtain the desired compound, identical to the product of Example 3.
EXAMPLE 15: 1- ( 2-CHLORO-6-FLUORoBENZOYL) -3- (5-T~IFLUOROMETHYL-2-PYRIDINYL)UREA
A portion of 2-chloro-6-fluorobenzamido-carboxylic acid chloride is reacted with 5-trifluoro-methyI-2-aminopyridine in an organic solvent in the presence of a hydrogen halide acceptor as described in the examples above. The product is isolated as described in Example 12 above to obtain the compound named in the heading, identical to the product of Example 4.

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EXAMPLE 16: 1-(2,6-DIFLUOROBENZOYL)-3~(5-TRIFI,UORO-METHYL-2-PYRIDINYL)UREA
To a portion of 2,6-difluorobenzamide dissolved in an inert organic solvent i5 added a portion of S 5-trifluoromethyl-2-pyridinylaminocarboxylic acid, phenyl ester, and the reac~ion mixture is stirred at elevated temperature. After a period of stirring, the mixture is evaporated under vacuum, and the product is recrystal-lized to obtain the product named in the heading, identical to the product of Example 1.
EX~MPLE 17- 1-(2-CHLORO 6-FLUOROBENZOYL)-3-(5-BROMO~2-PYRIDINYL)UREA
A portion of 2-chloro-6-fluorobenzamide is dissolved in an organic solvent, and 5-bromo-2-pyridinyl-lS aminocarboxylic acid, phenyl ester is added. The reac-tion mixture is stirred with heating for a period of time, and is then evaporated under ~acuum. The product, identical to the product of Example 2 above, is isolated from the residue by recrystallization.
EXAMPLE 18: 1-(2-CHLORO-6-FLUOROBENZOYL)-3-(5-CHLORO-2~PYRIDINYL)UREA
A portion of 5 chloro-2-pyridinylaminocarbox-ylic acid, phenyl ester, is reac~ed with 2-chloro-6--fluorobenzamide as described in Example 16. The productnamed in the heading above, identical to the product of Example 3, is isolated by evaporating the reaction mixture, and recrystallizing the product from the residue.

1 ~ 5 ( EXA~LE 19~ 2- CHLORO--5-FLUOROBENZOYL) -3-(5-TRIFLUOROMETHYL-2-PYRIDINYL)UREA

A portion of 2-chloro-6-fiuorobenzamide is reacted with 5-trifluoromethyl-2-pyridinylaminocarbox-S ylic acid, phenyl ester, in an inert organic solvent atelevated temperature to produce the product named in the heading above~ identical to the product of Example 4, which is isolated by evaporating the reaction mixture and recrystallizing the product.
EXAMPLE 20: 1-( 2,6-DIFLUOROBENZOYL)-3-(5-TRIFLUORO-METHYL-2-PYRIDINYL)UREA
A portion of 5-trifluoromethyl-2-aminopyridine is dissolved in an inert organic solvent, and to the solution is added a portion of 2,6-difluoroben~amidocar-boxylic acid, 4-nitrophenyl ester. The reaction miX-ture is stirred at elevated temperature for a per~iod of time, after which the reaction mixture is evaporated ~o dryness under vacuum, and the product named in the heading above, identical to the product of Example 1, is isolated by recrystallization-EX~MPLE 21~ 2-CHLORO-6-FLUOROBENZOYL)-3-(5-BROMO-2-PYRIDINYL)UREA

To a solution of 2-chloro-6-fluorobenzamido-carboxylic acid, 4-nitrophenyl ester, in an inert organic solven~ is added 5-bromo-2-aminopyridine. The reaction mixture is stirred at an elevated temperature for a period of time, and is then evaporated to dryness under vacuum.
The product named in the heading above, identical to the product of Example 2, is isolated and purified by recrys~
tallization.

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( E~AMPLE 22: 1-(2-C~LORO-6-FLUOROBENZOYL)-3-(5-CHLORO-2~PYRIDINYL)UREA

A portion of 2-chloro-6-fluorobenzamidocarbox-ylic acid, 4-nitrophenyl ester, is combined with a por-tion of 5-chloro-2-aminopyridine in an inert organic solvent. The reaction mixture is stirred at elevated temperature for a period of tlme, and is then evaporated under vacuum. The product named in the heading above, identical to the product of Example 3, is isolated by recrystallization.
EXAMPLE 23: 1-(2-CHLORO-6-FLUOROBENZOYL)-3-(5-TRIFLUOROMETHYL-2-PYRIDINYL~UREA
A solution is made in an inert organic solvent o 2-chloro-6-fluorobenzamidocarboxylic acid, 4-nitro-phenyl ester, and 5-trifluoromethyl-2-aminopyridine. The temperature of the reaction mixtuxe is raised, and tha mixture is stirred for a period of time. The mixture is then evaporated under vacuum, and the product named in the heading above, identical to the product of Example 4, is isolated and purified by recrystallization.
The ability of the method of this invention to suppress manure-breeding insects has been evaluated with the following test procedure~ A group of chickens averaging lo 6-1.8 kg. were used. The chickens were placed in wire cage pens, 2 birds per pen, and each pen was used as a treatment group. Each pen was equipped with an automatic watering trough and a feed container, and water and feed were continuously available to the birds.

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( Treated chicken feeds were made up~ contain-ing various concentrations of the test compound, as shown in the table below. The treated feed was fed for 6 weeks, and then the birds were given ~lntreated feed S for 6 weeks more.
A sample of approximately 0.5 kg. of droppings was collected from each pen once a week, and the larvi-cidal effect was determined by moistening each sample with water, and seeding 100 housefly eggs to each of the samples. The seeded samples, in l-liter plastic containers, were covered with muslin and held at room temperature until evaluated. The effect of ~he treat-ments was determined by counting the live pupae in the samples, and expressing the number of pupae in terms of percent control of the pupae, compared to the untreated control samples.
In the first test to be reported here, each concentration level of the compound was administerec to 2 pens of birds. The percent control was determined on a number of samples obtained at a number of times during the experiment, as described in the table below; it should be ~ept in mind that the administration of treated feed ended after the sixth week of the experiment, and that the birds were fed untreated feed thereafter.

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f The data above shows that the method of this invention is not only effective to suppress manure-breeding insects, but that it continues to be effective for at least a week after the administration of the com-pound is stopped.
The birds used in the above experimentgained weight normally, and showed no ill effects due to the administration of the compound.
Another test was carried out, accordihg to the method of the experiment described above, except that data was obtained at only one time, 7 days after the administration of the compound started~ The compound of Example 1 was administered at 3.8, 7.5, 15 and 30 ppm. by weight in the feed, and all treatments were 100% efective. No house flies seeded on the manure of the test birds were able to mature.

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Claims (2)

Claims:

1. A process for preparing a compound of formula (I), (I) wherein R and R1 are different and each represents chloro or fluoro and R2 is chloro, bromo or trifluoromethyl; or a veterinarally-acceptable salt thereof, which process comprises:

(a) reacting a 2,6-dihalobenzoyl iso-cyanate of the formula with a 2-aminopyridine of the formula (b) reacting a 2,6-dihalobenzamide of the formula with a 2-pyridyl isocyanate of the formula (c) reacting a reactive derivative of a 2,6-dihalobenzamidocarboxylic acid of the formula with an aminopyridine of the formula , or (d) reacting a benzamide of the formula with an active derivative of a pyridinylamino-carboxylic acid of the formula and when the salt is required, reacting the product with a corresponding acid.

2. A compound of formula (I), (I) wherein R and R1 are different and each represents chloro or fluoro and R2 is chloro, bromo or trifluoromethyl or a veterinarally-acceptable salt thereof.