AU602305B2 - N-(halobenzoyl)-N-(polyhaloalkoxyphenyl) urea derivatives - Google Patents

Description

GRIFFIT11 HASSEL FRAZER, P.O. BOX Z1335, u. rvu. uInLi AIJSTRALI,

IA

~44 4~~4I~L~ Form PATENTS ACT 1952 COMPLETE SPECIFICATION

(ORIGINAL)

FOR OFFICE USE Short Title: Int. Cl: Application Number: _f 7' Lodged: 00 ,,q(3rnplete Specification-Lodged: 0 0 Accepted: 0 a Lapsed: 00 Published: 0 00 a cFrority: 00') 0 4vQ23O"5 Related Art: o 00 0000 0 00 00 0 This document contains the amnendments made ndtr Section 49 and is correct tor priuiting, 00 0 0 0 Nome of Applicant: TO BE COMPLETED BY APPLICANT ISTITUTO GUIDO DONEGANI S.p.A.

00 -Wedress of Applicant: Via Caduti del Lavoro, 0 0 028100 Novara, Italy 000000 a 0 Actual Inventor: Address for Service: PIETRO MASSARDO; FRANCO RAMA; PAOLO PICCARDI and VINCENZO CAPRIOLI GRIFFITH HASSEL FRAZER 71 YORK STREET SYDNEY, N.S.W. 2000, AUSTRALIA Z' Corij te Sperifir.Rtifln for thA inVflntion antitl~ci- "flflTTjVY'.', *;:RPTihq ffAvING (HALOBENZ0YL) (POLYHALOALK0XYPHENYL)UREA DERIVATIVES".

Me ,o oingstatement is a full description of this invention, including the best method of performing it known Note: The description is to be typed In double spacing, pica type face, In an area not exceeding 250 mm in depth and 160 mm In width, on tough white paper of good quality and It is to be Inserted Inside this form.

14599/78-L 1459978- LPrinted by C. J. THOMPSON, Commonwealth Govermecnt Printer, Canberra I The present invention relates to benzoylurea derivatives having insecticide activity and more precisely it relates to l-benzoyl-3-aryl-urea derivatives, which are particularly active against eggs and larvae of insects noxious in the agrarian and civil fields and to the use of such derivatives.

Furthermore, the invention relates to the process for the synthesis of these ureas.

BACKGROUND OF THE INVENTION Several l-benzoyl-3-aryl-urea derivatives endowed o.4. with insecticide activity are known. Among them, Diflubenzuron, usual appellation of the compound o4. 1-(2,6-difluorobenzoyl)-3-(4-chlorophenyl)-urea, described °in USP No. 3,993,908 Philips Corporation), is the 15 first product to be marketed.

Diflubenzuron, however, is suspected of being a carcinogen (European Chem. News 6 29 (1978)], as it contains in the molecule the unit of 4-chloro-aniline.

THE PRESENT INVENTION -oo020 One object of this invention is to provide new l-benzoyl-3-aryl-urea derivatives which have the following formula: R R4 0R R R R 7 R-CO-NH-CO-NH-0-F R R3 wherein: R is a chlorine or fluorine atom;

SR

1 is a hydrogen, chlorine or fluorine atom;

R

2 and R 3 equal to or different from each other, are a hydrogen, halogen atom, or an alkyl group containing from 1 to 4 carbon atoms; provided that when either R 2 or R 3 is hydrogen, the other is not chlorine; -2- 1 8025S/MS 1 R4 and R 5 equal to or different from each other, are a hydrogen, halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkenyloxy, haloalkenyloxy or alkynyl group;

R

6 and R 7 equal to or different from each other, are a hydrogen atom, an alkyl group containing from 1 to 3 carbon atoms, optionally substituted by halogen atoms; Y is a hydrogen or a fluorine atom; and n is a whole number from 1 to 4, extremes included.

10 The term "halogen" as used in the aforesaid defini- 0 0 0 0 0 "o tions preferably means a fluorine, chlorine, or bromine atom.

oo, The compounds having formula are endowed with .o insecticide activity and are fit for use in the fight against 00 o0 insect infestations in the agrarian, forestal, civil and 000 0 veterinary fields.

o o In the description of the preparation of the compounds having formula reported hereinafter, symbols R, R 1

R

2 R .0 R 4

R

5

R

6

R

7 Y and n have the same meanings as in formula I, if not otherwise specified.

The compounds having formula are obtained by S reaction between a benzoyl-isocyanate having formula:

R

RI C O N C O

(II)

with an aromatic amine having formula:

S

R 2 R R 4

R

H

2 N O O- (CF2 (III) R R 3 The reaction does not require the presence of catalysts and is carried out.in an inert solvent and at a temperature ranging between 0 C and the boiling temperature of the mixture, -3- Aromatic hydrocarbons, chlorinated hydrocarbons, ethers, ketones and acetronitrile are suitable solvents.

The benzoyl-isocyanates having formula (II) are known compounds and in a few cases they may be found on the market.

Methods for preparing them are known.

The amines having formula (III) may require a specific preparation. In particular, the amines having formula (III) may be prepared according to known methods, for instance: reaction of a sodium or potassium salt of a suitable amino-phenol in dipolar aprotic solvents with compound I° o, Y(CF 2 )n -C-X wherein X is a halogen atom such o

R

7 0 7 ooo So° a as Cl, Br, I or a tosyl or mesyl group, at tem- .o0 0 peratures ranging between 0° and 150 0 C, according 015, to the equation: ooo 0 00 0 00

R

2

R

4 R R 4 SH- -0 Na+ +Y-(CF2) n-C-X H 2 N 0) O-C-(CF2 nY+NaX R R R R7 3 5 3 (IV) (III) reduction, according to known techniques, of nitroderivatives having formula: R2 4 R6 02N O 0- -(CF2)n-Y (VI)

R

R3 R5 7 The nitroderivatives having formula may be prepared according to usual methods, by reacting a suitable 4-halonitrobenzene (VII) with a sodium or potassium salt of i L L alcohol (VIII), in a solvent consisting of the same alcohol (VIII) or in an aprotic apolar solvent, or by carrying out the reaction with the phase transfer technique in the presence of suitable catalysts, at temperatures ranging between 100 and 150 0 C, according to the equation: R R4 R R4

R

6

R

6 I NaOH 1 0 2 N-0 X+Y(CF 2 n-C-OH NaO 0 2 N 0 O- C(CF 2 -Y NaX R3 R5 R7 R3 R5 R7 o (VII) (VIII) (VI) o &o o"o in which X is a halogen atom.

The alcohols having formula (VIII) are known and may o 0: be prepared according to equation: O R6 It I Y(CF2)nMeX R-C-R 7 Y (CF2) -C-OH 2 n 6 7 2 n 7 o R 7 .oI (IX) (VIII) wherein X is a halogen atom and Me is a metal selected among Zn, Mg and Cu.

Organometallic compound (IX) may be prepared by reacting compound X(CF 2 )nX with Zn, Mg or Cu.

The nitroderivatives having formula in which at least one of radicals R 2

R

3

R

4 and R 5 is chlorine, may be obtained, also, by direct chlorination with C12 of the corresponding non-chlorinated nitroderivatives, at temperatures ranging between 250 and 150C and in the presence of catalysts such as, for instance, FeC1 3 and SbCl 5 For a person skilled in the art, it is a matter of course.that different alternative processes may be used for the synthesis of the intermediates and of the products having formula An alternative process for the synthesis of the compounds having formula consists, for instance, in reacting a benzamide having formula: co-NH2 (XI) with an isocyanate having formula:

R

2

R

4

R

6 O=C=N 0 O-C- (CF -Y (XII) R3I 5 K7 Such reaction is carried out under conditions similar to those described hereinabove for the reaction between benzoyl-isocyanat 0 Ochaving formula (II) and amines having formula (III).

o9 0 The preparation of isocyanates having formula (XII) 0 04 00 001 foresees, however, the preparation of amines having formula (III) and their reaction with phosgene. This aspect, together with the consideration that the benzoyl-isocyanates having formula (II) are available as the amides of formula (XI) are, 1.5 lead to prefer, generally, the method of synthesis mentioned hereinbefore, namely the reaction between the compounds of 09 formula (II) and (III).

0 0409 As stated above, the compounds having formula are endowed with high insecticide activity, which shows chiefly against the larvae and eggs of insects. Among these, the p larvae and eggs of insects belonging to, more particularly the Lepidopter a, Diptera an Coleoptera orders, may be fought by means of the compounds having formula These orders comprise a great many species, which are important because of their noxiousness in agrarian, forestal, civil and veterinary fields. Therefore, the compounds having formula are fit for different uses, namely, for instance, for defending -6- ~If2 agricultural cultivations against infestations of phytophangous insects, for protecting environments infested with mosquitoes and flies, for protecting breeding cattle against a few cattle parasites, etc. Furthermore, the compounds having formula (I) show a collateral acaricide activity.

In the practice of this invention, the compounds having general formula may be utilized either as such or, i more conveniently, in the form of compositions containing, besides one or more compounds of formula as active con- I 10 stituent, also inert solid or liquid carriers and optionally I! other additives. According to the usual formulative practice, the compositions may be in the form of wettable powders, emulsifiable concentrates, etc. The amount of active constit- J uent in the compositions varies within wide ranges (1-95% by weight), depending on the type of composition and on the ,o intended use of the composition.

If required by particular situations or in order to enlarge the action spectrum, other active substances such as, for instance, other insecticides or acaricides, may be added to the compositions.

The amount of the active substance (compound having formula I) to be distributed for the insecticide treatments depends on different factors, such as, for instance, the type and the degree of infestation, the environment wherein there is infestation (agrarian cultivation, basin and water-courses, organic substrata of different nature), the type of employed composition, climatic and environmental factors, disposable application means, and so on. Generally, amounts of active substance ranging between 0.01 and 1 Kg/ha are sufficient for a good disinfestation.

II The following examples are given in order to further illustrate the invention and are not intended to be limiting.

The following abbreviations are used in the spectra of nuclear magnetic resonance H-NMR) reported in the examples: s singlet m multiplet or unresolved complex signal b (broad) broad signal ABq quartet of AB type.

EXAMPLE 1 '1o Preparation of N-(2-chloro-benzoyl)-N'-[3,5-dichloro-4-(2,2,3,3, 4,4,5,5-octafluoropentyloxy)phenyl]urea (compound No. 1) SC1 C1 S CO-NH-CO-NH

)-O-CH

2

(F

2 4 Cl S, 1.0 g of 3,5-dichloro-4-(2,2,3,3,4,4,5,5-octafluropentyloxy)aniline (prepared according to subsequent Example 3), dissolved in 15 ml of anhydrous ether, was introduced into a two neck flask having a capacity of 50 ml, equipped with cooler, dropping funnel and magnetic stirrer.

Then 0.7 g of 2-chlorobenzoylisocyanate, dissolved in ml of anhydrous ether, were dripped in at room temperature.

The mixture was kept under stirring for 30 minutes, filtered Sunder nitrogen and the precipitate was washed with ether and finally dried under nitrogen. 0.78 g of benzoylurea were obtained, having a melting point of 173-175 0

C.

4 1 EXAMPLE 2 Starting from the anilines described in Example 3 below and by operating under conditions similar to those described in Example 1, the following compounds were prepared, using 2-chlorobenzoyl-isocyalate: compound No. 2: N-(2-chlorobenzoyl)-N'-[4- (2,2,3,3,4,4,5,5-octafluoropentyloxy)phenyllurea Cl o CO-NH-CO-NH O-CH 2 (CF 4

H

m.p. =140'-142'C.

compound No. N-(2-chlorobenzoyl)-N'-[3-chloro-4- 4 41 (2,2,3,3,4,4,5,5-octafluoropentyloxy)phenyllurea 4Cl Cl Q CO-NH-CO-NH 0 -C 2 (CF 2 )4 H1 m.p. =155'-157*C.

Whereas using 2,6-difluorobenzoylisocyanate the following compounds were prepared: compound No. 4: N-(2,6-difluorobenzoyl)-N'-[4- 2 ,2,3,3,4,4,5,5-octafluoropentyloxy)phenyllurea

F

o CO-NH-CO-NH 0O-CH (CF H

F

m.p. =168*-17Q 0

C.

compound No. 5: N-t2,6-difluorobenzoyl'-N'4[3,5dichloro-4-(2,2,3,3,4,4,5,5 octafluoropentyloxy)Phenyllurea F Cl o CO-NH-CO-NH 0 O-CH (CF )H Cl M.P. =155 0 -157 0

C.

.EXAMPLE 3 Preparation of intermediate anilines.

29.6 millimoles of SnC122H20 were introduced into a two neck flask having a capacity of 50 ml, equipped with reflux cooler, dropping funnel and stirrer and dissolved in ml of 37% HC1.

Then 10 ml of a methanolic solution were dripped in, containing 5.92 millimoles of 2,6-dichloro-4-nitrophenyl- -2,2,3,3,4,4,5,5-octafluoropenthylether. The mass was heated at 60 0 C for 30 minutes.

The whole was cooled down, poured into a solution of 10% NaOH, extracted by means of ethylether and the ethereal extract was dried on Na2SO and finally concentrated. 2 g of 3,5-dichloro-4-(2,2,3,3,4,4,5,5-octafiuoropentyloxy) aniline were obtained with a yield of 86%.

*o H-NMR: 6.5 2H, arom.); 6.9-6.0-5.15 (tt, 1H, -CHF 2 o ,4.3 2H, -CH 3.5 2H, -NH 2 By operating under conditions similar to those described hereinbefore, starting from 4-nitrophenyl- 2,2,3,3,4,4,5,5-octafluoropentylether, 4-(2,2,3,3,4,4,5,5octafluoropentyloxy) aniline was obtained with a yield of H-NMR: 6.7 4H, arom.); 6.8-6.1-5.2 (tt, 1H, -CHF 4.35 2H, -CH20-); 3.5 2H, -NH2).

Starting from 2-chloro-4-nitrophenyl- 2,2,3,3,4,4,5,5-Octafluoropenthylether, 3-chloro-4- (2,2,3,3,4,4,5,5-octafluoropentyloxy) aniline was obtained with a yield of 83.6%.

1 H-NMR: 6.9-6.5 3H, arom.); 6.8-6.1-5.2 (tt, 1H, -CHF -e W 4.4 2H, -OCH 3.5 2H, NH2

I

11t- EXAMPLE 4 Determination of the insecticide activity.

TEST 1 Residual immediate activity on larvae of Spodoptera littoralis (Lepidoptera).

Tobacco leaves were treated by mechanical spraying with a water-acetone solution of the product under examination, having an acetone content of 10% by volume and containing a surfactant.

After complete evaporation of the solvents, the leaves S" were infested with second age larvae of Lepidoptera.

t The infested leaves were kept in a suitably con- ,,ditioned environment over the test.

Likewise, tobacco leaves were infested and kept, after 1 having been treated only with a water-acetone solution containing 10% of acetone and the surfactant, to be used as reference (comparison treatment).

Ten days after the infestation and after having renewed the treated substratum at least once, a computation was made of the dead larvae with respect to the comparison treat- Sment.

TEST 2 Activity on larvae of Aedes aegypti (Diptera).

Plain water (297 ml) was mixed with an acetonic solution (3 ml) of the product under examination in a suitable concentration.

Diptera larvae, being 4 days of age, which were fed suitably, were introduced into the obtained solution. Other larvae were introduced for comparison purpose into a wateracetone solution (3 ml acetone, 297 ml plain water) without any active product.

-11- Every 2-3 days, note was taken of the dead larvae and pupae and of the adults which emerged normally from the cocoon, till the emergence from the cocoon of the insects in the comparison solution was over.

The activity of the product under examination was expressed as a percent ratio of dead individuals, compared with the total number of treated individuals.

The insecticide activity in the above mentioned tests was expressed according to the following scale of values: 5 complete activity (98-100% mortality) 4 high activity (80-97% of mortality) 3 fair activity (60-79% of mortality) 2 sufficient activity (40-59% of mortality) 1 poor activity (20-39% of mortality) 0 negligible or of no value activity (0-19% of mortality).

I In the following Table i, there are reported the I insecticide activity, at the given dose, of the tested compounds.

4..

1i L- d 12- 1 i A TABLE 1 Insecticide Activity Compound No. Test 1 Test 2 Dose: 0.001% Dose: 0.005% Dose: 0.01 ppm 5 2 5 4 3 5 5. 4 5 3 5 5 Reference* 4 3

LII

*)The reference compound was 1-(2,6-difluorobenzoyl)3- (4-chlorophenyl) urea having formula:

F

Q0 CO-NH-CO-NH Q Cl

F

U

Claims (13)

1. Compounds having formula: R R 2 R 4 0 O-C-(CF 2 -Y (I) R1 Rg 7 R3 5 7 wherein: R is selected from the group consisting of chlorine and fluorine; oo0 o0 o R 1 is selected from the group consisting of o hydrogen, chlorine and fluorine; o o R2 and R equal to or different from each other, 15 are selected from the group consisting of o° hydrogen, halogen, a C1-C alkyl, provided that when either R 2 or R 3 is hydrogen, the other is not chlorine; o 2 R 4 and R 5 equal to or different from each other, are selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkoxy, 00 haloalkoxy, alkenyl, haloalkenyl, alkenyloxy, o haloalkenyloxy, and alkynyl groups; R 6 and R7, equal to or different from each other, are selected from the group consisting of o hydrogen and alkyl groups containing from 1 to 3 carbon atoms, optionally substituted by halogen atoms; Y is selected from the group consisting of hydrogen and fluorine; and i n is a whole number from 1 to 4, extremes included. -14- -o 8025S/MS f I F"

2. A compound according to claim 1, and which is N-(2-chlorobenzoyl)-N'-3,5-dichloro-4-(2,2,3,3,4, 4 5 octafluoropentyloxy) phenyl] urea.

3. A compound according to claim 1, and which is N-(2-chlorobenzoyl)-N'-[4-(2,2,3,3,4,4,5,5-octafluoropentyloxy) phenyl] urea.

4. A compound according to claim 1, and which is N- (2-chlorobenzoyl) I [3-chloro-4- 2, 3,3, 4,4,5, 0 0 0 0 pentyloxy) phenyl] urea. 00 7 0

5. A compound according to claim 1, and which is o N-(2,6-difluorobenzoyl)-N'-[4-(2,2,3,3,4,4,5,5-octafJluoropenty- 000 loxy) phenyl] urea. 000

6. A compound according to claim 1, and which is N-(2,6-difluorobenzoyl)-N'-113,5-dichloro-4-(2;2,3,3,4,4,5,5- 00 0 octafluoropentyloxy) phenyl] urea. 0P 0% 0 07. A process for the preparation of the compounds 0,000 0 according to claim 1, consisting in reacting, in an inert solvent and at a temperature ranging between 0 0 C and the boiling j temperature of the reaction mixture, a benzoylisocyanate having formula:f o CO-NC0 (II) wherein R and Rhave the same meanings as in formula I, with an aromatic amine having formula: XII I i ji i? j if i R 6 O-C (CF 2 -Y

7 (III) wherein R 2 R 3 R 4 R 5 R 6 R, Y and n have the o o same meanings as in formula I, and provided that when either R and R is hydrogen, the other is not chlorine. 0 0I£*I- o o QO 0414 15 0 o 20 0 0 0 00 a o o o o 0 .0 0 0

8. A method for combatting infestations of noxious insects consisting in distributing in the infestation zone an effective amount of at least one compound according to claim 1, either as such or in the form of a suitable composition.

9. An insecticide composition containing, as active ingredient, at least one compound according to claim 1, together with inert solid or liquid carriers and optionally other additives normally used in formulating such compositions.

10. Compounds having formula substantially as herein described with reference to any one of the Examples 1 to 3.

11. A process for the preparation of compounds of formula substantially as herein described with reference to any one of the Examples 1 to 3.

12. A method for combatting infestations of noxious insects substantially as herein described with reference to Example 4. -16- 8025S/MS

13. An insecticide composition substantially as herein described with reference to Example 4. DATED this 17th day of July 1990 INSTITUTO GUIDO DONEGANI SPA By their Patent Attorneys GRIFFITH HACK CO. 0 e40 04 0 on nfe 00 0 o oo 0 00 00 0 000 0084 0 40 00 0 040 0 2 04 0 0 4 0 4 044 8 4' '44' -4 -17- 8025S/MS I