US3682944A

US3682944A - Certain 3-methylene diaxyphenyl-rhodanines

Info

Publication number: US3682944A
Application number: US874946A
Authority: US
Inventors: Joseph P Brown
Original assignee: Individual
Current assignee: Individual
Priority date: 1965-10-14
Filing date: 1969-11-07
Publication date: 1972-08-08
Anticipated expiration: 1989-08-08
Also published as: FR1500474A; GB1099798A

Abstract

Insecticidal rhodanine derivatives having a formula selected from the group consisting of

WHEREIN R is alkyl of at least two carbon atoms and not more than eight carbon atoms, R1 is alkyl of not more than eight carbon atoms, R2 is selected from the group consisting of hydrogen and alkyl of not more than eight carbon atoms, and R3 is selected from the group consisting of hydrogen, chlorine and bromine.

Description

United States Patent Brown [54] CERTAIN 3-METHYLENE DIAXYPHENYL-RHODANINES [72] Inventor: Joseph P. Brown, Bryn .Castell, Geufron, Llangollen, Denbighshire, Wales [22] Filed: Nov. 7, 1969 [21 1 Appl. No.1 874,946

Related US. Application Data [63] Continuation-impart of Ser. No. 586,053, Oct.

12, 1966, abandoned.

[30] Foreign Application Priority Data Oct. 14, 1965 Great Britain ..43,612/69 [52] US. Cl. ..260/306.7, 260/3405, 260/5135, 106/15, 424/270 [51-] Int. Cl. ..C07d 99/10 [58] Field of Search ..260/306.7

[56] References Cited UNITED STATES PATENTS 2,520,178 8/1950 Surrey et al. ..260/306.7

FOREIGN PATENTS OR APPLICATIONS OTHER PUBLICATIONS Meiji Confectionary Ltd., Chem. Abstracts, 59:11500 1/ 1968 Great Britain ..'260/306.7

[15] 3,682,944 Aug. 8, 1972 (1963). Turkevich et al., Chem. Abstracts, 48:1 1392 (1954). Raval et al., Chem. Abstracts, 57:12465- 6 (1962).

Primary Examiner-Alex Mazcl Assistant Examiner-R. J. Gallagher Attorney-Paul C. Krizov, Neal E. Willis and John J. Henschke, Jr. 9

[57] ABSTRACT Insecticidal rhodanine derivatives having a formula selected from the group consisting of wherein R isalkyl of at least two carbon atoms and not more than eight carbon atoms, R is alkyl of not 2 Claims, No Drawings C ERT-AIN 3-METHYLENE DIAXYPHENYL- RHODANINES wherein R is alkyl of at least two carbon atoms and not more than eight carbon atoms, R is alkyl of not more than eight carbon atoms, R is selected from the group consisting of hydrogen and alkyl of not more than eight carbon atoms, and R is selected from the group consisting of hydrogen, chlorine and bromine, provided that the oxygen atoms of the OCH O-- group are attached to adjacent carbon atoms of the benzene nucleus, and that not more than two of R, R and R are hydrogen.

The invention includes a process for the production of a rhodanine derivative as defined above, which comprises reacting a salt of a dithiocarbamic acid having a formula selected from the group consisting of o ofi NHC s SH with a compound of the formula R1 MOOO(IJX wherein R, R, R and R are as defined above, M is selected from the group consisting of hydrogen, alkali metal, ammonia and alkyl of not more than four carbon atoms, and X is selected from the group consisting of fluorine, chlorine, bromine and iodine.

The'insecticidal compositions of the invention comprise one or more rhodanine derivatives of the above formula in admixture with a diluent.

In the above formula R, R, and R as alkyl and substituted alkyl can be for example methyl, ethyl, chloromethyl, n-propyl, isopropyl, 2-cyanopropyl, nbutyl, Z-aminobutyl, sec-butyl, isobutyl, tert-butyl, amyl, hexyl, heptyl, octyl, and the varioushomologues and isomers of alkyl having not more than 8 carbon atoms, as alkenyl and substituted alkenyl can be for exand d) the meta position.

ample, vinyl, allyl, n-butenyll n-butenyl-2, 3- bromobutenyl-2, n-pentenyl-Z, n-hexenyl-2, n-heptenyl, and the various homologues and isomers of alkenyl having not more than eight carbon atoms, as cycloalkyl and substituted cycloalkyl (three to eight carbon atoms) can be for example cyclopentyl, cyclohexyl, monoand diethylcyclohexyl, cycloheptyl, 3-chlorocycloheptyl and the like, and as aralkyl and substituted aralkyl can be for example benzyl, p-aminophenylmethyl, phenylethyl, p-chlorophenylethyl and the like.

Where R represents a halogen atom, it can be chlorine, bromine, fluorine or iodine. R is preferably chlorine or bromine.

The substituent RO is preferably in the para position relative to the position of attachment of the benzene nucleus to the nitrogen atom, and R is preferably in In the formula (b) above, both oxygen atoms of the alkylenedioxy group --OCI-I O are linked to the same carbon atom of the alkylene group. Preferably one of the oxygen atoms of the methylenedioxy group is linked to the carbon atom of the benzene ring in the para position. The other oxygen atom in such cases is necessarily linked to a carbon atom in a meta position.

Representative examples of the new rhodanine derivatives of the invention are: 3(4'-ethoxyphenyl)-5- methylrhodanine; 3(2-ethoxyphenyl)5-methylrhodanine; 3(4-ethoxy-3-chlor0phenyl)-5-methylrhodanine; 3(4-ethoxy-3'-bromophenyl)-5-methylrhodanine; 3(4'-B-chloroethoxyphenyl)-5-methylrpropylrhodanine; 3(4-B-ethylhexyloxyphenyl)-5- methylrhodanine; 1 3( 4 '-cycloheptyloxyphenyl )-5- ethylrhodanine; 3(4'-n-heptenyloxyphenyl)-5-ethylrhodanine; 3(4-,B-aminopropoxyphenyl)-5-methylrhodanine; 3(4-n-propoxyphenyl)-5-benzylrhodanine; 3(34'-dipropoxyphenyl)rhodanine.

The salt of the dithiocarbamic acid that is a starting material in the process of the invention is preferably an alkali metal or ammonium salt. Where an alkali metal salt of the dithiocarbamic acid is employed, this is usually, for economic reasons, the sodium salt, but functionally other alkali metal salts, for example the lithium or potassium salts, are quite satisfactory. The ammonium salts of the dithiocarbamic acids that can be used include the substituted ammonium salts derived from, for example, primary and secondary amines, as well as the unsubstituted ammonium salts derived from ammonia itself. The last-named are often preferred, however. I

For the other reactant in the process of the invention, it is preferred to use an ester or salt of the ahaloaliphatic monocarboxylic acid. Where an ester is employed, this is preferably an ester of an alcohol containing up to four carbon atoms, especially an ethyl ester. Preferred salts are the alkali metal salts, although ammonium and amine salts can also be used. The ahalogen atom is usually chlorine or bromine, and the number of carbon atoms and their arrangement in the ester is, of course, determined by the atoms or groups R and R required in the product.

The reaction between the salt of the dithiocarbamic acid and the a-haloaliphatic monocarboxylic acid or its ester or salt occurs readily at ordinary temperatures, for example in the range 10 to 25 C.,-although the process can be conducted at lower or higher temperatures, for example from to 50 C., if desired.

In practice, the reactants are usually brought together in a liquid medium. This can conveniently be water or a mixture of water and an inert, water miscible organic solvent, for instance a lower alkanol, a ketone, or dioxan. For example, a solution of an ester in a water miscible organic solvent, or a solution in water of a salt of the a-haloaliphatic monocarboxylic acid can be added to a solution or suspension of the salt of the dithiocarbamic acid in water.

An insecticidal composition of the invention can be liquid or solid, and a liquid composition can be a solution, suspension or emulsion. Often a surface active agent is present to stabilize the composition or to facilitate its application.

A composition can contain a new rhodanine derivative as the only active ingredient, or one or more other compounds having insecticidal properties can be present.

A solution of a rhodanine derivative is one in an organic solvent, for example an ester, for instance butyl acetate, a ketone, for instance methyl isobutyl ketone, a petroleum fraction, for instance white spirit, an aromatic hydrocarbon, for instance xylene or solvent naphtha, a halogenated hydrocarbon, for instance carbon tetrachloride or perchloroethylene, or some other solvent, for instance isopropyl ether or dioxan.

Such a solution can be formulated for use as an aerosol by mixing with a liquid having a boiling point below ambient temperature at atmospheric pressure for example dichlorodifluoromethane.

Where a solution contains a surface active agent, this is selected according to its solubility in the solvent but it can in general be cationic, anionic or non ionic, anionic and non-ionic materials being generally preferred. Examples of anionic surface active agents are soaps, and the alkali metal salts, particularly the sodium salts, of long-chain alkylbenzene sulfonic acids, of long-chain alkyl sulphates and of dialkylsulphosuccinates; examples of non-ionic surface active agents are ethers and esters of polyethylene glycols, for instance the polyoxyethylene derivatives of alkylphenols and of the fatty acid mono-esters of sorbitan.

Insecticidal compositions that are suspensions can be simple ones of a rhodanine derivative in finely-divided form in an aqueous medium, stabilized if necessary by the presence of a surface active agent, for instance an anionic or non-ionic agent as exemplified above.

An insecticidal composition that is an emulsion can be obtained by emulsifying a solution of a rhodanine derivative in a suitable organic solvent, generally one that is water-immiscible, with water in the presence of a surface active agent. Where the solution already contains a surface active agent as described above, an emulsion can be formed simply by mixing with water under conditions of suitable agitation. Alternatively the surface active agent can be dissolved in the water and the solution of the rhodanine derivative added subsequently.

ln compositions which are solids, the rhodanine derivative is generally present in finely divided form and the diluent is an inert powder, for instance kieselguhr, calcium carbonate, diatomaceous earth or talc. Such a solid composition may also contain a surface active agent to facilitate its application.

Therhodanine derivatives may also be incorporated in media such as paints, varnishes and polishes.

The concentration of the rhodanine derivative in a composition of the invention can vary considerably provided the required dosage (that is a lethal or toxic amount) is supplied to the pests or their environment. Where the composition is a liquid, the concentration of the active ingredient can, for example, be from 0.001 to 10 percent by weight. For a solid composition, the lower limit of concentration is generally somewhat higher, for example 0.1 by weight. Concentrates in which the concentration of the rhodanine derivative may be, for example from 10 percent to 50 percent by weight, and which are intended for dilution before use, are a convenient fonn in which the insecticides can be supplied to the user.

The invention is illustrated by the following examples.

EXAMPLE 1 This Example describes the production of the new compound 3(4-ethoxyphenyl)-5-methy1rhodanine.

Ammonium N( 4-ethoxyphenyl )dithiocarbamate,

required as a starting material for the production of the rhodanine derivative, was first obtained as follows: 6 cc. of carbon disulfide were added over a period of 15 minutes to a stirred mixture of 13.7 grams of pphenetidine, 50 cc. of ethanol and 10 cc. of concentrated ammoniumhydroxide. On cooling, ammonium N(4-ethoxyphenyl) dithiocarbamate crystallized from the reaction mixture and was filtered off, washed with ethanol and dried at room temperature.

The ammonium salt thus obtained was suspended in 35 cc. of water and to the stirred suspension was added a solution of 8.9 cc. of ethyl a-chloropropionate in 55 cc. of ethanol. Stirring was continued for 6 hours, and after standing for a further 40 hours, cc. of water were added, thereby precipitating 11.8 grams of 3(4- ethoxyphenyl)-5-methylrhodanine in a slightly impure form having a melting point of 134-142 C. The product was obtained as yellow needles having a melting point of 147-151C., by crystallization from ethanol. (Found: C, 53.8; H, 5.1; N, 5.4; S, 23.6. C I- NO S requires C, 53.4; H, 4.9; N, 5.3; S, 24.0%).

EXAMPLE 2 This example describes the production of 3(4- ethoxy-phenyl)-5-ethylrhodanine.

A suspension of ammonium N(4ethoxyphenyl)dithiocarbamate was prepared by stirring a mixture of 7 cc. of concentrated ammonium hydroxide, 13.7

grams of p-phenetidine, 9 cc. of carbon disulfide and 25 cc. of ethanol for 2 hours at C. To the suspension there was then gradually added a solution of sodium abromobutyrate obtained from 16.7 grams of ozbromobutyric acid, 4 grams of sodium hydroxide and 30 cc. of water.

After standing overnight, the reaction mixture was acidified to pH 3 by the addition of dilute hydrochloric acid, and was then warmed to 65C. for 2 hours. After cooling, 27.1 grams of slightly impure 3(4'-ethoxyphenyl)--ethylrhodanine having a melting point of 98100C. were collected by filtration. Two recrystallizations from ethanol raised the melting point of 98100C. were collected by filtration. Two recrystallizations from ethanol raised the melting point to l05l06C. (Found: C, 55.4; H, 6.4; N, 4.7; S, 20.8. C, H, -,NO S requires; C, 55.6; H, 6.1; v N, 4.5; S, 20.7%).

EXAMPLE 3 3(4'-ethoxyphenyl)-5-n-propylrhodanine was obtained from ammonium N(4-ethoxypheny1)dithiocarbamate and sodium a-bromovalerate by essentially the same procedure as that described in the previous example using one-tenth molar quantities of reactants. The yield of the initial product was 27.5 grams, and its melting point was 100-l02C. This was raised to l05l06 C. by recrystallizing twice from ethanol. (Found: C, 57.0; H, 6.1; N, 4.9; S, 21.1. C H NO S requires C, 56.9;1-l,5.8;N, 4.7; S,21.7%).

EXAMPLE 4 This Example describes the production of 3(4'ethoxy-phenyl)-5,5-dimethylrhodanine.

A solution of sodium a-bromoisobutyrate, obtained from 16.7 grams of a-bromoisobutyric acid, 4 grams of sodium hydroxide and 30 cc. of water, was added gradually to a stirred suspension of ammonium N(4- ethoxyphenyl)dithiocarbamate, itself obtained by stirring a mixture of 7 cc. of concentrated ammonium hydroxide, 13.7 grams of p-phenetidine, 9 cc. of carbon disulfide and 25 cc. of ethanol for 2 hours.

After standing overnight, the reaction mixture was acidified to pH 3 by the addition of dilute hydrochloric acid, and was then wanned at 65C. for 2 hours. The main product, which was collected by filtration after cooling, was N,N-bis(4-ethoxypheny1)thiourea. On standing, the mother liquors deposited a further crop of crystals having a melting point of 120-122C., which were identified as the required 3(4-ethoxyphenyl)-5,5- dimethylrhodanine. The melting point was raised to 122l 25C. on recrystallization from ethanol. (Found:

C, 55.1; H, 5.5; N, 5.2; S, 23.0. C, H, NO S requires C, 55.5; H, 5.4; N, 5.0; S, 22.8%).

EXAMPLE 5 This example describes the production of 3(4-n-butoxyphenyl)-5-methylrhodanine.

A solution of ammonium N(4-n-butoxyphenyl)dithiocarbamate was prepared by shaking a mixture of 16.5 grams of 4-n-butoxyaniline, 10 cc. of concentrated ammonia, 6 cc. of carbon disulfide and 30 cc. of ethanol for 2 hours and then allowing to stand at 0-5 C. overnight.

A half portion of this solution was then treated with a solution of 6.5 cc. of ethyl a-bromopropionate in 30 cc. of ethanol. Crystalline material precipitated almost immediately, and after some hours standing, the weight collected by filtration was 5.6 grams. The organic constituent of this material was identified as N,N'-bis(4-nbutoxyphenyl)thiourea. On further standing, the mother liquors from the filtration deposited a further crop of crystals weighing 1.4 grams. The melting point of these crystals was 8789C, and analysis indicated that they were the required 3(4'-n-butoxyphenyl)-5- methylrhodanine. (Found: C, 57.2; H, 5.7; N, 4.8; S, 21.4; C H NO S requires C, 56.9; H, 5.8; N, 4.7; S, 21.6%).

EXAMPLE 6 This example describes the production of 3(4-pentyl-oxyphenyl)-5-methylrhodanine. I

A mixture of 9 grams of 4-pentoxyani1ine, 4 cc. of carbon disulfide, 20 cc. of ethanol and 4 cc. of concentrated ammonium hydroxide was stirred at 0C. for 2 hours. Then 7 cc. of ethyl a-bromopropionate were added to the solution thus obtained, and the reaction mixture was allowed to stand overnight. On filtering, 2.6 grams of a solid mixture of ammonium bromide and N,N'-bis(4b-pentyloxyphenyl) thiourea were separated.

EXAMPLE 7 This example describes the production of 3(4'- ethoxy-3'-chlorophenyl)-5-methylrhodanine.

A solution of 1.65 cc. of ethyl a-bromopropionate in 18.6 cc. of ethanol was added to a stirred suspension of 3.1 grams of ammonium N(4-ethoxy-3-chloropheny1)dithiocarbamate in 12.4 cc. of water. (The ammonium salt was first obtained in an analogous manner to the ammonium N(4-ethoxyphenyl)dithiocarbamatedescribed in Example 1).

Next day, 31 cc. of water were added, and the residual solid, which weighed 2.5 grams, was filtered I off. 3(4'-ethoxy-3'-ch1oropheny1) rhodanine having a melting point of 171172C. was obtained by two'successive crystallizations from ethanol. (Found: C, 48.1; H, 4.1; N, 4.4; S, 20.5; C1, 11.6; 'C, H, C1 NO S requires C, 47.8; H, 4.3; N, 4.6; S, 21.2; C1, 11.8%).

EXAMPLE 8 This example describes the production of (4'-npropoxyphenyl-S-methylrhodanine.

A mixture of 15.1 grams of p-n-propoxyaniline, 9 cc. of carbon disulfide and 25 cc. of ethanol were stirred for 2 hours at 0C. A solution made from 15.3 grams of a-bromopropionic acid, 4 grams of sodium hydroxide and 30 cc. of water was added at 0C. Next day the reaction mixture was acidified to pH 3 with hydrochloric acid and heated to 60-70C. for 2 hours. After cooling, 38.1 grams of the crude product, which had a melting point of ll2-114C, were filtered off and recrystallized from 320 cc. of ethanol, yielding 21 grams of 3(4'-n-propoxyphenyl)-5-methylrhodanine in the form of pale yellow needles having a melting point of 124126C.

Analysis of the product gave C, 56.3%; H, 5.4%; N, 5.632;; C, H, NO S required C, 55.5%; H, 5.3%, N, 5.0 0.

EXAMPLE 9 This Example describes the production of 3(4'-isopropoxyphenyl)-5-methylrhodanine.

The method described in Example 8 was used. with the substitution of p-isopropoxyaniline for p-propoxyaniline.

The yield of crude product was 28.7 grams with a melting point of 9597C. This gave 24 grams of a purified product with a melting point of 103105C. upon recrystallization.

Analysis of the purified product gave C, 55.5%; H, 5.5%; N, 4.8%; C, H, NO S requires C, 55.5%; H, 5.3%; N, 5.0%.

EXAMPLE 10 EXAMPLE 1 1 This example describes the production-of 3(3',4'- methylenedioxyphenyl)-5-methylrhodanine.

The method described in Example 8 was used, with the modification that 13.7 grams of 3,4-methylenedioxy-aniline in 50 cc. of methanol were used in place of pn-propoxyaniline in ethanol.

A yield of 15.9 grams of a crude product with a melting point of 162C. was obtained. When this was slurried with hot ethanol and cooled, 13.7 grams of a purified product have a melting point of 169170C.

resulted. An analyticalsample recrystallized from ethanol had the form of irregular cream prisms with a melting point of 170-l71C.

Analysis of this sample gave C, 49.0%; H, 3.2%; N, 5.2%; C H NO S requires C, 49.4%; H, 3.3%; N, 5.2%.

Example 12 Thisexample describes the production of 3-(3'4'- methylenedioxyphenyl)-5,5dimethylrhodanine.

The method was basically that described in Example 8 using as starting materials 13.7 grams of 3,4- methylenedioxyaniline and 16.7 grams of 2-bromoisobutyric acid. A crude yield of 13 grams wasobtained which when boiled with 90 cc. of ethanol gave 4.2 grams of a purified product with a melting point of 150-153C. A further sample had a melting point of l54-l55C.

Analysis of this product gave C, 50.9%; H, 4.0%; N, 5.1%; C H NO S requires C, 51.2%; H, 3.9%; N, 5.0%.

EXAMPLE 13 This example describes the production of 3(4'npropoxyphenyl)-5-ethylrhodanine.

This method was basically that described in Example 8 using 16.7 grams of a-bromobutyric acid in place of the a-bromopropionic acid. The crude product was boiled with cc. of ethanol and cooled, giving 20.5 grams of a yellowish solid with a melting point of 1 17180C. A further recrystallized sample of this product had the same melting point.

Analysis of the compound obtained gave C, 56.8%; H, 5.7%; N, 4.9%; C H NO S requires C, 56.8%; H, 5.8 N, 4.7%.

The method used to assess the insecticidal activity of test compounds was as follows.

A 0.05 cc. portion of a 1 percent by weight solution of the compound in acetone was added to 50 cc. of distilled water contained in a clean 25 X 200 mm. rimless culture tube. The tube was then stoppered with an acetone-washed rubber stopper and shaken vigorously to ensure complete mixing. Then 25 early instar yellow fever mosquito larvae (Aedes aegypti) were introduced into the tube. After 24 hours at room temperature, mortality observations on the larvae were taken. In certain instances the test was repeated at lower concentration of the test compound. I

The results obtained on certain of the compounds described in the above Examples are shown in the following table:

%Mortality/Concentrations Compound of test compound p.p.m.

3(4'-Ethoxyphenyl )-5-methylrhodanine 100110 3(4'-Ethoxyphenyl)-5-ethylrhodanine 100/ 10 /2 3(4'-Ethoxyphenyl)-5-n-propylrhodanine /10 70/2 3(4'-Pentyloxypheny1)-5-methylrhodanine 90/10 3(4-Ethoxy-3'-chlorophenyl)-5-methyl- 100/10 rhodanine wherein R is alkyl of not more than eight carbon 2. A compound in accordance with claim 1 which is atoms and R is selected from the group consisting of 3(3a;:-methylenedioxyphenyl)-5,5-dimethylrhydrogen and alkyl of not more than eight carbon hodanine. atoms. 4: 1

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 5, 682,94 Dated August 8, 1972 Inventorts) Joseph P. Brown It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Frontpage, Item 5&7, second line, that portion of the title reading "DIAXYPHENYL" should read DIOXYPHENYL Front page, immediately following Item "1727-", there should be inserted Assignee: Monsanto Chemicals Limited, London, England Column 1, line 1, thatpart of the title reading "DIAXYPHENYL" should read DIOXYPHENYL- 7 Column line 26, immediately following "0.1" there should 'be inserted 95 r Column 5, lines 14 through 16, cancel of 98-lOOC. were collected by filtration. Iwo recrystallizations from ethanol raised the melting point". 7

Column 6, line 27, that part of the-chemical name reading l'b-pentyloxyphenyl)" should read (4-pentyloxyphenyl) Column 7, line 59, "59.9%" should be 5 9.5%

Column 10, line 2, that part'of the name of the chemical compound of Claim 2 reading "5(3'a;:methy1enediox yphenyl)" should read 3(3'4methylenedioxyphenyl) Signed and sealed this 9th day of January 1973.

(SEAL) Attest:

EDWARD M.FLETCHER, JR. ROBERT GOTTSCHALK Attesting Officer Commissioner of Patents FORM USCOMM-DC suave-bee I U75 GOVERNMENY PRINTING OFFICE: I999 0-356334

Claims

2. A compound in accordance with claim 1 which is 3(3''4''-methylenedioxyphenyl)-5,5-dimethylrhodanine.