IE44573B1 - N-(1,3,4-thiadiazol-2yl)benzamides and their use as insecticides - Google Patents

Abstract

The insecticide according to the invention contains a novel thiadiazolylbenzamide of the formula I in which the substituents are as defined in Claim 1, and an inert carrier.

Description

The present invention relates to a series of novel N-(1,3,4-thiadiazbl-2~yljbenzamides, having a phenyl, naphthyl or hetero-aryl group at the 5-position of the thiadiazole ring and 2,6-sufostitution on the benzyl ring, which are useful insecticides.. .

The control of insects was one of the first problems undertaken by agricultural chemical researchand continues to be pursued vigorously by the art. Insects of many orders assault crops of all types, and also cause unsanitary conditions and nuisance by contaminating foodstuffs. The damage caused by insects is incalculable, and the control of harmful insects necessarily is of the highest priority..

Recently, the search for new and better insec15 ticides has been spurred by the withdrawal from use of the old residual insecticides.

The compounds of Formula X are new to organic chemistry. Some, items in the prior art, however, are of interest. For example, Cebalo, U.S. Patent 3,726,892, dis20 closes herbicidal l,3,4-thiadiazol-2-ylureas.

Rao, Indian J. Chem. 8., 509-13 (1970), teaches a synthesis method for -2-amino-l,3,4-thiadiazoles, which are intermediates for the compounds of this invention.

Wellinga and Mulder, U.S. Patent 3,748,356, show 25 herbicidal and insecticidal efficacy of N-ben2oyl-N’-phenyl.. areas. . .

This invention belongs to the field of agricultural chemistry, and provides novel thiadiazolyl benzamides of the formula .,-24 4573 Η Ο I II -Ν—CΓ' wherein R represents Β'Ζ·~Λί· S./ V -3s. ο— ---ο. θ ®ι· (ΥΥ W / -S σ ©. ζ\/\ wxz R\ Λ ο-a -< χ· V wherein 0 1 2 R , R and R independently represent hydrogen, chloro or bromo, provided that at least one of R% R“ and R2 represents chloro or bromo; X represents oxygen or sulfur; 445?3 4 R and R independently represent hydroqen, chloro, bromo or methyl, provided that R^ represents hydroqen when X represents oxyqen; R represents hydroqen, chloro, bromo, fluoro or tri fluoromethyl; and either 7 8 9 1) R and R represent hydrogen, one of R and R 9 represents hydrogen, and the other of R and R represents hydrogen, chloro, methoxy, bromo, iodo, fluoro, trifluoromethyl, methyl, hydroxy, phenyl, or phenyl monosubstituted with bromo, chloro or fluoro, or 2) R6 and R7 represent hydrogen, and R8 and R8 independently represent chloro, fluoro or bromo, or 8 7 9 J) R and R represent hydrogen, and R and R independently represent chloro, fluoro, bromo or trifluoromethyl, or 4) R7 and R8 represent hydrogen, and R6 and R8 independently represent chloro, fluoro or bromo, or ) R7, R8 and R8 represent hydrogen, and R8 represents chloro, fluoro or bromo, or 7 9 8 6) R , R and R represent hydrogen, and R represents acetamido, nitro, amino or cyano; and independently represent hydrogen, chloro, fluoro, bromo, inethyl or methoxy; provided that.: 1) one of R*0 and R1^ may represent hydrogen, if and only if the other represents methoxy; 2) at least one of and R^ must represent methyl or methoxy, unless A 7 a) R does not represent hydrogen, and R , R and R represent hydrogen, or 6 8 b) R and R represent hydrogen, and one or 7 9 both of R and R represent trifluoromethyl; 8-9 1) neither R nor R represents phenyl, acetamido, methoxy, nitro, amino, cyano or substituted phenyl unless both R^8 and R^^ represent methoxy; 8 9 4) two of R , R and R represent hydrogen unless both R10 and R11 represent methyl or methoxy ,r>) both r!° and represent methoxy or methyl when R represents pyridyl, naphthyl, furyl or thienyl; 6) both R10 and R^1 represent methoxy when R represents benzothiazolyl, benzoxazolyl, benzothienyl, benzofuryl, isoxazolyl, quinolyl or thiazolyl.

The present invention also provides a process for preparing the compounds of Formula I, wherein R, and rH areas defined above, which comprises either 1) acylating a. 2-amino-5-R-substituted 1,3,4-thiadiazole of the formula R—-· nh ii i wherein K is as defined in Formula 1, except that R does not represent amino- or acetamido-phenyl, -6with a benzoyl halide ot the formula I,' 4,187 3 II i 1.1 lo-t> III wherein Halo refers to chloro or bpomo, and r!° and rH arn as defined in Formula I, or / • 2) cyclizing a compound of the formula L-.x I;?· II II ? X-NI l-C-NI l-C—·Ζ % rv io wherein R^° and are as defined in Formula I, and X represents II It-C-NH- or- If-tlUMwherein R is as defined in Formula II, with a dehydrating II agent, when X represents R-C--NH--, or with an oxidizing agent, when X represents R-CII=N-, and optionally reducing a compound of Formula I wherein R 8 If represents nitro to obtain a compound wherein R represents amino, and further optionally acylating the compound wherein R represents amino to prepare a compound wherein It represents acetamido.

Novel insecticidal methods and insecticidal compositions making use of the compounds are also provided. -7‘“V ; Throughout this document, all quantities are measured in the metric system, and temperatures are on the Celsius scale. All proportions and percentages are byweight. The term halogen refers to fluoro, chloro, bromo and iodo.

A number of specific classes and types of Compounds of Formula I constitute preferred classes. A particularly preferred class of compounds are those which are of the formula 1J wherein R represents / :© ^9—Z·^· •ii··’- - 'n*« R —e: a—;N. --y V V: •χ X • β. -844373 •χ i '· ,'l I?'· wherein R^\ ί^θ, Ri7, r^8 rind R^9 independently represent hydroqen, chloro or bromo, provided that at least one of R^J and 17 18 19 or at least one of R , R and R represents chloro or bromo; X represents oxygen or sulfur,R2R represents hydrogen, chloro, bromo or methyl; R2! represents hydrogen, chloro, bromo, fluoro or tri Eluoromethyl; and either 1) 2) 23 24 25 R and R represent hydrogen, one of R and R represents hydrogen, and the other of R and R represents hydrogen, chloro, bromo, fluoro, trif1uoromethyl, methyl, hydroxy, phenyl, or phenyl monosubstituted with bromo, chloro or fluoro, or 23 24 25 R and R represent hydrogen, and R and R independently represent chloro, fluoro or bromo, or 3) R22 and R2^ represent hydrogen, i ndi’pendontl y represent chloro, trill uoromel hy I , or and Rz and I< fluoro, bromo or -944S73 2^95 99 ο a 4) R and R represent hydrogen, and Rz and Rz1 independently represent chloro, fluoro or bromo, or ) R22, R24 and R25 represent hydrogen, and R22 repre5 sents chloro, fluoro or bromo; 14 R and R independently represent hydrogen, chloro, fluoro, bromo,'methyl or methoxy; provided that: 14 1) one of R and R may represent hydrogen, if and only if the other represents methoxy; 14 2) at least one of R and R must represent methyl or methoxy, unless 99 23 a) R does not represent hydrogen, and R~ , R and R represent hydrogen, or ·.. 22 24 b) R and R represent hydrogen, and one or both of R and R represent trifluoromethyl; 3) neither R24 nor R22 represents phenyl or substituted phenyl unless both R22 and R24 represent methoxy; 4) two of R22, R24 and R25 represent hydrogen unless 14 both R and R represent methyl or methoxy; 14 ) both R and R represent methoxy When R represents pyridyl, naphthyl, furyl or thienyl.

Withiri the above class, a more preferred class 12 includes the compounds wherein R represents iin a-?--:n 'r86 -1044 573 and a further preferred class includes the compounds wherein 13 14 both R and R represent methoxy.

Tt will be understood that the present invention also includes a number of other different types or classes ol compounds, and also includes insecticidal methods and compositions making use of the various classes of compounds, for example, the following preferred classes of compounds are contemplated. Each numbered subparagraph below describes an independent class of compounds; in each class, the variable substituents have the general meanings in Formula I, if not otherwise stated. In the subparagraphs below, each general term, such as phenyl, is intended to include the substituted forms of the group referred to.

Compounds wherein: 1) R represenls phenyl; 2) R represents phenyl, or pyridyl; i) R represents pyridyl, thienyl, furyl, benzothienyl, benzofuryl, benzothiazolyl, benzoxazolyi, isoxazolyl, quinolyl or thiazolyl; 4) R represents phenyl or naphthyl; ) R represents pyridyl, benzothiazolyl, benzoxazolyi, isoxazolyl, quinolyl or thiazolyl; ()) R represents thienyl, furyl, benzoxazolyi, benzothiazolyl, benzothienyl, benzofuryl, isoxazolyl, quinolyl or thiazolyl; (1 ') /) one ol It and R represents hydrogen, and the other represents halogen or LrifIuoromethyl; -114457 3 Ή 9 8) R and R independently represent chloro, t'luoro or bromo; 9 9) R and R independently represent chloro, fluoro, bromo or trifluoromethyl; 9 ) one of R and R represents hydrogen, and the other represents halogen, trifluoromethyl, methyl or methoxy; 11) R^° and represent methoxy; 12) R^® and R^ independently represent methyl or methoxy; 13) r!° and R·11 independently represent chloro, fluoro or bromo; Compounds of subparagraph 11 above wherein: 14) R represents phenyl; ) R represents phenyl or pyridyl; 16) R represents pyridyl, thienyl, furyl, benzothienyl, 1.5; benzofuryl, benzothiazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl; 17) R represents phenyl or naphthyl; 18) R represents pyridyl, benzothiazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl; 19) R represents thienyl, furyl, benzoxazolyl, benzothiazolyl, benzothienyl, benzofuryl, isoxazolyl, quinolyl or thiazolyl; 9 ) One of R and R represents hydrogen, and the other represents halogen or trifluoromethyl; 9 21) R and R independently represent chloro, fluoro or bromo; 9 22) R and R independently represent chloro, fluoro, bromo or trifluoromethyl; 9 23) one of R and R represents hydrogen, and the other represents halogen, trifluoromethyl, methyl or methoxy; -124 4 5 7 3 Compounds of subparagraph 12 above wherein: 24) R represents phenyl; ) R represents phenyl or pyridyl; 26) R represents pyridyl, thienyl, furyl, benzothienyl, benzofuryl, benzothiazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl; 27) R represents phenyl or naphthyl; 28) R represents pyridyl, benzothiazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl; 29) R represents thienyl, furyl, benzoxazolyl, benzothiazolyl, benzothienyl, benzofuryl, isoxazolyl, quinolyl or thiazolyl; 9 ) One of R and R represents hydrogen, and the other represents halogen or trifluoromethyl; 9 51) R and R independently represent chloro, fluoro or bromo; a 12) R and R independently represent chloro, fluoro, bromo or trifluoromethyl; 9 13) one of R and R represents hydrogen, and the other represents halogen, trifluoromethyl, methyl or methoxy; Compounds of subparagraph 13 above wherein: 14) R represents phenyl; ) R represents phenyl or pyridyl; 36) R represents pyridyl, thienyl, furyl, benzothienyl, benzofuryl, benzothiazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl; 17) R represents phenyl, or naphthyl ; 18) R represents pyridyl, benzothiazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl; -1 1; 44573 19) R represents thienyl, luryl, beitzexazoly I, ben/.ethinxolyi, benzotftionyl,-benzolury1, isexazoly 1 , quinolyl or thiazolyl; 9 0) One of R and R represents - hydrogen, and the other represents halogen or trifluoromethyl; 9 41) R and R independently represent- chloro, fluoro or bromo; - 7 9 42) R and R independently represent chloro, fluoro, bromo or tri fluoromethyl; 9 43) one of R and R represents hydrogen, and the other represents halogen, trifluoromethyl, methyl or methoxy.

Although the above general formula clearly describes the compounds of Formula I, the following typical examples are presented to assure that agricultural chemists fully understand the invention; N-[5-(6-chloro-3-pyridyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide N-[5-(4-chloro-3-pyridyl)-l,3,4-thiadiazol-2-ylJ2,6-dimethoxybenzamide N-[5-(4,5-dibromo-3-pyridyl)-l,3,4-thiadiazol-2yl1-2,6-dimethylbenzamide N-15-(5-bromo-2-pyridyl)-1.,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide N-[5-(4-chloro-2-pyridyl)-1,3,4-thiadiazol-225 yl]-2,6-dimethylbenzamide N-15-(5-bromo-3-chloro-2-pyridyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N- [5-(3,4,5-trichloro-2-pyridyl)-1,3,4-thiadiazol-2-ylJ-2,6-dimethoxybenzamide -144d573 N-(5-(3-furyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(5-chloro-2-furyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide N- [ 5- (5-bromo-3-thienyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide N-[5-(5-methyl-2-thienyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide N-[5-(3-chloro-l-naphthyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide N- [5-(2-bromo-l-naphthyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide N-[5-(4-fluoro-2-naphthyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide N—15—(J-trifluoromethyl-2-naphthyl)-1,3,4-thiadiazol-2-ylJ — 2,6-dimethoxybenzamide N- (5- (4-chlorophenyl)-1,3,4-thiadiazol-2-yl]2-bromo-6-fluorobenzamide N-[5-(3-bromophenyl)-1,3,4-thiadiazol-2-yl]-2fluoro-6-methylbenzamide N— I 5—(3-iodophenyl)-1,3,4-thiadiazol-2-yl]-2fluoro-6-methoxybenzamide N- [5- (3-methylphenyl)-1,3,4-thiadiazol-2-yl]-2chloro-6-methylbenzamide N-[5-(3-hydroxyphenyl)-1,3,4-thiadiazol-2-yl]-2bromo-6-methy1benzamide N-[5-(3-phenylphenyl)-1,3,4-thiadiazol-2-yl]-2,6dimethoxybenzamide N-[5-[3-(3-fluorophenyl)phenyl]—1,3,4-thiadiazol2-y1]-2,6-dimethoxybenzamide 1544573 N- [5-[4-(3-bromophenyl)phenyl]-1,3,4-thiadiazol-2 y11-2,6-dimethoxybenzamide N-[5-[4-(2-chlorophenyl)phenyl]-l,3,4-thiadiazol2-yl)-2,6-dimethoxybenzamide N-[5-[3-(4-chlorophenyl) phenyl1-1,3,4-thiadiazol2-yl)-2,6-dimethoxybenzamide N-[5-(3,4-dibromophenyl)-1,3,4-thiadiazol-2-yl]2.6- dimethylbenzamide N-[5-(3-bromo-4-fluorophenyl)-1,3,4-thiadiazol-2yl | -2-methOXy--6-methylbenzamide N-[5-(3,4-difluorophenyl)-1,3,4-thiadiazol-2-yl]2.6- dimethOxybenzamide N-[5-(3,5-diflUorophenyl)-1,3,4-thiadiazol-2-yl]2.6- dimethylbenzamide N- [5-(3,5-dibromophenvl)-1,3,4-thiadiazol-2-yl)2.6- dimethoxybenzamide N-[5-(3-chloro-5-tri£luoromethylphenyl)-1,3,4thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(3-bromo-5-fluorophenyl)-1,3,4-thiadiazol-2yl)-2“methoxy-6-methylbenzamide N-[5-(2,4-dibromophenyl)-1,3,4-thiadiazol-2-yl]2.6- dimethylbenzamide N-[5-(4-fluorophenyl)-l,3,4-thiadiazol-2-yl)2.6- difluorobenzamide N-[5-(2-bromo-4-flUorophenyl)-1,3,4-thiadiazol-2ylJ -2,6-dimethoxybenzamide N-[5-(4-bromo-2-chlorophenyl)-1,3,4-thiadiazol-2yl]-2-methoxybenzamide -1644573 Ν- 15- (4-tr.i fluoromethylphenyl) -1, :, i-thiadiazol-2y11-2,6-dichlorobenzamide Ν-|5-(2-bromophenyl)-1,3,4-thiadiazol-2-yl)-2methoxy-6-methy I benzamide N-[5-(6-chloro-l-naphthyl)-1,3, 4-thiadiazol-2-yl]2,6-dimethoxybenzamide N-[5-(5-fluoro-2-naphthyl)-1,3,4-thiadiazol-2-yl]2.6- dimethoxybenzamide N-|5-(7-trifluoromethyl-l-naphthyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(4,5,6-trichloro-3-pyridyl)-1,3,4-thiadiazol-2-yll-2,6-dimethoxybenzamide N-[5-bromo-4,6-dichloro-i-pyridyl)-1, i,4-thiad i azol-2-yl] -2,fi-diniethylbenzamide N-(5-(3,4,5-tribromo-2-pyridyl) -1,3,4-thiadiazol2-yl)-2-methoxy-6-methylbenzamide N-[5-(i-bromo-4,6-dichloro-2-pyridyl)-1,3,4thiadiazol-2-ylJ-2,6-dimethoxybenzamide N-[5-(4-methyl-2-thienyl)-1,3,4-thiadiazol-2-yl]2.6- dimethylbenzamide N-[5-(4-bromo-5-methyl-2-thienyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-6-methylbenzamide N-[5-(4,5-dichloro-2-thienyl)-1,3,4-thiadiazol2-y)1-2,6-dimethoxybenzamide Ν- 15- (2-benzoxazolyl.)-1 , 5,4-thiadiazol-2-yl | - 2, fill i methoxybenzitm i de Ν- I fi- (2-benzo I b | th i.eny I ) - I , i, 4-th i ad i azol - 2-yl | 2.6- d i niothoxybenzamide -17N-15- (2-b'enzo [b] furyl) -1,3>4-thiadiazol-2-yl)2,6-dimethoxybenzamide - N-t5-(5—isoxazolyl)-1,3,4—thiadiazol-2-ylj-2,6— dimethoxybenzamide N-[5-(2-thiazolyl)-1,3,4-thiadiazol-2-yl]-2,6dimethoxybonzamidn N-|5-(4-iodophenyl)-l,3,4-thiadiazol-2-yl]2-chloro-6*-methoxybenzamide N- [-5- (4-iodophenyl)-1,3,4-thiadiazoi-2-yl | 10 2, fi-dichlorobenzamide N-[5-(3-iodophenyl)-1,3,4-thiadiazol-2-yl)2-bromo-6-methylbenzamide N-[5-(5-trifluoromethyl-2-naphthyl)-1,3,4-thiadia zol-2-yl 1-2,6-dimethylbenzantide _N- [5- (4-chloro-l-naphthyl)-1,3,4-thiadiazol-2-yl] 2-niethoxy-6-methylbenzamide N-[5-(2-furyl)-1,3,4-thiadlazol-2-yll-2,6-dirtiethylbcnzanildo N-(5-(5-brOmo-3-furyl)-1,3,4-thiadiazol-2-yl!20 2-methoxy-6-methylbenzamide N-[5-(6-bromo-2-benzo[b]thienyl)-1,3,4-thiadiazol 2-yl)-2,6-dimethoxybenzamide N-[5-(4-methyl-2-benzo[b]thienyl)-1,3,4-thiadiazdl-2-yl]-2,6-dimethoxybenzamide N-[5-(5-chloro-2-benzo[b]furyl)-1,3,4-thiadiazol2-yI |-2,6-dimothoxybenzamide N- I 5- (7-niethy l-2-bonzo lb) furyl )-1 , 3,4-thiadi azol2-y1|-2,6-dimethoxybenzamide -184 4 5 7 3 The preferred compounds of Formula Γ are M-[5(4-chlorophenyl)-1,3,4-thiadiazol-2-yl1-2,6-dimethylbenzamide, N- [5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6dimethoxybenzamide, N-[5-(4-fluorophenyl)-1,3,4-thiadiazol5 2-yI|-2,fi-dimethylbenzamide, N-[5-(4-trifluoromethylphenyl)1, l,4-thiadiazol-2-yl]-2,6-dimethylbenzamide, N— 15— ¢411uoropheny1)-1,3,4-thiadiazol-2-ylJ-2,6-dimethoxybenzamide, N-I 5-(3-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]—2,6— iti met hoxybenzamide, N— [ 5— (3-chloropheny 1) -1,3,4-thiadi azol1(1 2-y 1 1 - 2 , (,-dimel hoxybenzamide, N- | 5- [ j, 5-b ί s (tr i 11 uoromethyl) phenyl 1 -1,3,4-thiadiazol-2-ylJ-2,6-dimethoxybenzamide, and N-|5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6dimethoxybenzamide.

The compounds of Formula I are made by processes which are presently known or are analogous to presentlyknown processes. All of the compounds are readily marie by file acylation of 2-amino-5-R-substituted 1,3,4-thiadiazoles of the formula wherein R is as defined in Formula II above, with benzoyl halides of the formula |,t<, 0 J—. z V III T'· ,1,11 wherein Halo refers to chloro or bromo, and R^0 and are as defined in Formula f, -1944573 and optionally reducing a compound of Formula 1 wherein Κθ g represents nitro to obtain a compound wherein R represents amino, and further optionally acylating the compound wherein 8 R represents amino to prepare a compound wherein R° represents acetamido. In particular, a compound of the formula 13 14 where R , R and R are as defined above, is prepared by a process which comprises either 1) acylating a 2-amino-5-R -substituted 1,3,410 thiadiazole of the formula R NHVI .12 wherein R is as defined above, with a benzoyl halide of the formula VII 14 wherein Halo refers to chloro or bromo, and R and R are as defined above, or 2) cyclizing a compound of the formula 13 so' J 5 II II II R -C-NH-NH-C-NH-C· VIII 13 14 R wherein R , R and R are as defined above, with a dehydrating agent.

In process (1) for the preparation of the compounds of the invention, the acylation step is suitably carried out in the presence of a base in a reaction solvent such as tetra20 204-44&T3 hydrofuran, dimethylformamide, dimethylsulfoxide or diethyl ether. The preferred base is sodium hydride, although organic bases such as pyridine, triethylamine and triethnnel amine may be used, as can inorganic bases including sodium hydroxide, potassium Carbonate and lithium bicarbonate.

The tempreature range of the reaction is suitably from -10° to 50°, preferably from 0° to 25°.

The intermediate aminothiadiazoles may be prepared by reactions which are now well known. In general, they are prepared either by oxidative cyclization of a thiosemicarbazone, preferably with ferric chloride, or by dehydrative cyclization of a thiosemicarbazide with a strong acid. See for example, Rao, supra, and Cebalo, supra.

The compounds of Formula 1, wherein R, R20 and R22 are as defined above, are also prepared by cyclizing a compound of the formula wherein R20 and R22 are as defined in Formula I, and X represents θ II R-C-NH- or R-CH=Nwherein R is as defined in Formula II, with a dehydrating agent, when X represents R-C-NH-, or with an oxidizing agent, when X represents R-CH=N-, and p optionally reducing a compound of Formula 1 wherein R reQ presents nitro to obtain a compound wherein R represents amino, and further optionally acylating the compound wherein 8 R represents amino to prepare a compound wherein R re21 presents acetamido.

In particular a compound of Formula I is prepared by cyclizing a compound of the formula wherein E, R^° and are as defined in Claim 1, except that R does not represent amino- or acetamidophenyl, with an oxidizing agent, and optionally reducing a compound of Formula 1 8 wherein R represents nitro to obtain a compound wherein R represents amino, and further optionally acylating the com8 pound wherein R represents amino to prepare a compound wherein • 8- ’ R represents acetamido.

In process (2) for the preparation of compounds according to the invention, useful dehydrating agents include phosphoric acid, formic acid, phosphorus pentachloride, phos15 phorus pentoxide in the presence of a strong acid, and benzoic and alkanoic acid chlorides and acid anhydrides. The preferred dehydrating agents are the strong acids, particularly methanesulfonic acid and concentrated sulfuric acid.

Dehydrative cyclizations are suitably run at tem20 peratures from 20° to 80°, preferably at room temperature.

It is Usually preferred to carry out the reactions without solvent, although solvents including the halogenated benzenes and the halogenated alkanes, including chlorobenzene, the dichlorobenzenes, chloroform and methylene dichloride, may be used if desired.

The preferred oxidizing agent is ferric chloride. Other powerful oxidizing agents can be used, for example, calcium ferricyanide. Oxidative cyclizations are preferably run in lower alkanols, for example, ethanol or propanol, at the reflux temperature of the reaction mixture. - 22 44873 In general, however, temperatures from 50° to 100° may be used if convenient.

It in preferred t e prepute eunipi nm.ls having an amino or acetamido group on a phenyl R group by first pre5 paring tho corresponding nitro-substituted compound, and reducing the nitro group by hydrogenation, using a hydrogenation catalyst, preferably a noble metal catalyst, to form tho amino-substituted compound. The amino qroup is acylated wi th acetic anhydride or acetyl halide to prepare the acetamido-substituted compound.

As organic chemists will recognize, all of the starting compounds used in preparing the compounds of Formula I are obtainable by those of ordinary skill.

The following examples show the synthesis of 15 typical compounds, and the following preparations show the synthesis of typical starting compounds. In ail of the examples, the compounds were identified by nuclear magnetic resonance analysis, elemental microanalysis, and, in some cases, by infrared analysis and mass spectroscopy.

The first group of preparations and examples illustrate typical cyclizations with dehydrating agents. Preparation 1 1- (4-chlorobenzoyl)-4-(2,6-dimethOX.ybenzoyl)thiosemicarbazidc Λ solution of 0.76 g. of ammonium thiocyanate in ml. of chlorobenzene was heated to 70° in a 100 ml. flask. After a few minutt?s, 2.0 g. of 2,6-dimethoxybenzoyl chloride in 30 ml. of chlorobenzene was added dropwise, and 44ST3 the mixture was stirred For 15 minutes after the addition was complete. Then, 1.7 g. of 4-chlorobenzoylhydrazine suspended in 20 ml. of chlorobenzene was added, and the resulting mixture was stirred at 70° for 30 minutes. The solvent was then removed under vacuum, and 50 ml. of water was added to the residue. After the aqueous mixture had been stirred for about 3 hours, the solids were collected and dried to obtain 2.7 g. of 1-(4-chlorobenzoyl)-4-(2,6dimethoxybenzoyl)thiosemicarbazide, m.p. 206-208°.

Theoretical Found C 51.84% 52.12% H 4.09 4.35 N 10.67 10.67 Example N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl1-2,6-dimethoxybenzamide A 1 g, portion of the above intermediate was added slowly, with stirring and cooling, to 5 g. of concentrated sulfuric acid. The mixture was stirred at room temperature for 4 hours, and was then poured into 300 ml. of ice. The solids which precipitated were collected, dried and recrystallized from ethyl acetate to produce 0.45 g. of N-[5(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenz- amide, m.p. 238-240°C. Theoretical Found C 54.33% 54.01% H 3.75 3.84 N 11.18 11.22 Preparation 2 - (4-hydroxybenzoy1 )-4- (2,6-dimcthoxybenzoyl)_thiosemic.arbazιbe Λ 2.0 ij. portion of 2,6-diinothoxybenzoyl chloride 5 was dissolved in 20 ml. of tetrahydrofuran, and was added to 0.76 i). ol ammonium thiocyanate in 10 ml. of tetrahydrofuran at the reflux temperature. After the addition was complete, tiic mixture was stirred at reflux temperature for 15 minutes, and then ).5 q. of 4-hydroxybenzoylhydrazine in 20 ml. of Ltd rahydrofuran was added. The reaction mixture was rolluxed for 10 minutes more, cooled, and evaporated under vacuum to produce an oily residue which consisted larqely of I -(4-hydroxybenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemicarbazide. i;xampl_e 2 N-|5-(4-hydroxyphcnyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamido The residue produced above was stirred, and 20 q. of methanesulfonic acid was added dropwise to it. After 4 hours of stirring, at room temperature, the solution was poured into 100 m). of ice water, and the pll was adjusted with ammonium hydroxide to 7.5. Λ precipitate separated, which was collected and recrystallized from acetone to produce 2.5 q. of N-I 5-(4-hydroxyphenyl)-1,3,4-thiadiazol25 dimethoxybenzamide, m.p. above 260°. Theoretical I-’ound C 57.13 56.98'.’. 11 4.23 1.96 N 11.76 11.52 Example 1 Nt[5-(4-pyridyl) --1,3,4-thiadiazol-2-yl1-2,6-dimethoxyfaenzamide Following the process of Examples 1 and 2, 2.2 g. of 2,6-dimethoxybenzOyl chloride was reacted with 1.4 g. of 4-pyridylcarbonylhydrazine to prepare the corresponding 1-(4-pyridylcarbonyl)-4-(2,6-dimeth0xybenzoyl)thiosemicarbazide.

The thiosemicarbazide, a liquid, was stirred while 10 20 g. of methanesulfonic acid was added dropwise with cooling. After 5 hours' of stirring at room temperature, the reaction mixture was worked up as described above to prepare 2.9 g. of N-[5-(4-pyridyl)-l,3,4-thiadiazol-2-yl]-2,5- dimethoxybenzamide, nr.p. 241-243°. Found Theoretical C 56.13% 55.90! H 4.12 4.21 N 16.36 16.47 Example 4 N-[5-(5-chloro-2-banzo[b]thienyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide A 4 g. portion of 1-[(5-chloro-2-benzo[b]thienyl)carbony1 ].-4-(2,6-dimethoxybenzoyl)thiosemicarbazide, prepared as above, was added to 20 g. of methanesulfonic acid to produce about 1,1 g. of N-[5-(5-chloro-2-benzo[b]thienyl)1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide, m.p. ' 260°.

Theoretical Found C 52.84% 52.62% H . 3.27 3.48 N 9.73 9.78 «4573 Example 2 Ν-15-(2-benzothiazolyl)-1,3,4-thiadiazol-2-yl1-2,6-dimethoxybenzamide Λ 4.2 q. portion of 1-[(2-benzothiazolyl)car5 bonyl I-4-(2,6-dimethoxybenzoyl) thiosemicarbazi.de was added dropwise with stirring to 16 q. of methanesulfonic acid.

The product was 2.6 g. of N-[5-(2-benzothiazolyl)-l,3,4thiadiazol-2-yl]-2,6-dimethoxybenzamide, m.p. > 260°.

Theoretical Found c 54.26% 54.38% II 3.54 3.72 N 14.06 13.81 Example 6 N- [ 5-(2-chlorophenyl)-1, 3,4-thiadiazol -2-yl]-2,6-dimethoxy· benzamide To 10 g. of methanesulfonic acid was added 1.4 g of 1-(2-chlorobenzoyl)-4 -(2,6-dimethoxybenzoy1)thiosemi- carbazide while the temperature was held at or below 35°. The product of the reaction was 1.2 g. of N-[5-(2-chloro- phenyl)-l, 1,4-thiadiazol -2-yl)-2,6-dimethoxybenzamide, m.p. 235-237°. Theoretical Found C 54.33% 54.57% H 3.75 3.95 N 11.18 11.19 44S73 Example 7 Ν- [ 5- (2-quinolyl)-1,3,4-thladiazol-2-y 1) - 2,6-diiiiethoxybenzamide A 2.0 g. portion of 2,6-dimethoxybenzoyl chloride 5 was reacted with 1.9 g. of (2-quinolyl)carbonylhydrazine to form the corresponding 1-(2-quinolylcarbonyl)-4-(2,6-dimethoxvbenzoyl)thiosemicarbazide, which was cyclized with methanesulfonic acid to produce 1.75 g. of N-[5-(2-quinolyl)1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, m.p. - 260°.

Theoretical Found C 61.21% 61.09 II 4.11 4.30 N 14.28 13.95 Example 7a ]5 N-|5-(3-guinolyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Following the process described above, 2.09 g. of 2,6-dimethoxybenzoyl chloride was reacted with (3quinolyl)carbonylhydrazine to form 1-(3-quinolylcarbonyl)20 4-(2,6-dimethoxybenzoyl)thiosemicarbazide, which was cyclized with methanesulfonic acid to produce 1.7 g. of N-[5-(3quinolyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, m.p. 242-243^. «4Β73 Theoretical Found C · 61.22% 60.97% II 4.11 4.17 N 14.28 14.01 The compounds of the above examples are also prepared by the processes of Examples 7b, or 8 and 8a.

The following example illustrates .'i -typical cyclization with an oxidizing agent.

Example 7b N-(5-(4-chlorophenyl)-i,3,4-thiadiazol-2-yl]-2,6-dimethoxy5 benzamide A 3.78 g. portion of 4-chlorobenzaldehyde, 4-(2,6dimethoxybonzoyl)thiosemicarbazone, was added to 400 ml. of ethanol and 10.8 g. of ferric chloride hexahydrate was added. The mixture was stirred at reflux temperature for one hour, and was then cooled and concentrated under vacuum. The residue was washed with hydrochloric acid, and the solids were suspended in water and neutralized. The solids were separated by filtration, and taken up in ethanol. The solvent was evaporated under vacuum and the residue was recrystallized from ethyl acetate to obtain 2.1 g. of N-15-(4-chlorophenyl)-1,3,4-thiadiazol-2-ylJ-2,6-dimethoxybenzamide, m.p. 246-248°.

Found 54.195 3.47 11.27.

Theoretical 54.33% 3.75 11.18 The following preparation illustrates a tvptcal preparation et a t hi ad tare! e starting eentpenn.i !>v tv,· cyclization with ferric chloride.

Preparation 2 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole A 9.0 g. portion of 4-pyridylaldehyde, thiosemicarbazono, was added to 450 ml. of ethanol and 54 g. of ferric chloride hexahydrate was added. The mixture was stirred at reflux temperature for one hour, and was then cooled and the solvent was removed under vacuum. The residue was mixed with 40 ml. of cold concentrated hydrochloric acid, and the mixture was stored overnight in the freezer. The mixture was then filtered, and the solids were washed with three 15-ml. portions of concentrated hydrochloric acid and were dissolved in water. The pH of the solution was adjusted to 8.0 with sodium hydroxide, and the mixture was filtered again. The solids were washed with ethanol. The wash liquid was then evaporated to dryness, and the resultinq residue was recrystallized from acetone. The combined yield was 1.3 g. of 2-amino-5-(4-pyridyl)- thiadiazole, m.p. 234-236°. Theoretical Found C 47.18% 47.027. il 3. 39 3.45 N 31.44 31.39 The following two preparations i3 l.ustrate prep- .nation of starting compounds Ijy dehydrative cyclizations with ineLhanesulIonic acid and with sulfuric acid.

Preparation £ 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazola A 50 g. portion of 1-(4-chlorobenzoyl)thiosemicarbazide was slowly added with stirring to 330 g. of 5 methanesulfonic acid, while the temperature was held below °C. The mixture was stirred for 5 hours after the addition was complete, and was then poured into a liter of ice water. The pH of the mixture was adjusted to 7.5 with ammonium hydroxide, and the precipitated solids were removed by filtration and dried. The solids were then recrystallized From ethanol. Repeated recrystallizations produced a total of 33.3 g. of 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole, which was positively identified by nuclear magnetic resonance analysis.

Theoretical Found C 45.39% 45.61% H 2.86 3.12 N 19.85 19.70 Preparation 5. 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole To 48 g. of concentrated sulfuric acid at room temperature was slowly added 4.78 g. of 1-(4-chlorobenzoyl)thiosemicarbazide. The temperature rose approximately 10° during the addition. The mixture was stirred at room tem25 perature for 6 hours after the addition was complete. The reaction mixture Was then poured into ice, made basic to pH 7.5 with ammonium hydroxide, and filtered. The dried solids were recrystallized from ethanol to produce 2.4 g. of 2amino-5-(4-chlorophenyl)-1,3,4-thiadiazole, m.p. 221°C. «4573 Theoretiea! To.uni c 45.39% 45.28% 1! 2.86 2.63 N 19.85 20.02 The following examples are typical of tion of aminothiadiazoles to produce compounds of this invention.

Example 8 N-|5- (4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dichloro10 benzamide To 4 i). of 2-amino-5-(4-chlorophenyl)-1,3,4ttiiadiazolo in 200 ml. of tctrahydrofuran at room temperature was added, with cooling and stirring, 1.85 g. of 50 percent sodium hydride in oil. The cooling mantle was then Ιθ removed, and the reaction mixture was stirred for 15 minutes, after which 4.8 g. of 2,6-dichlorobenzoyl chloride was added dropwise. The mixture was stirred for 1 hour more, and excess sodium hydride was decomposed by the addition of water. The solvent was evaporated, and the residue was suspended in water and acidified with hydrochloric acid.

The solids were removed from the acid solution by filtration, dried and recrystallized from ethyl acetate to produce 4 dichlorobenzamide, m.p. -260°C. Theoretical Found C 46.84% 46.60 H 2.10 1.90 N 10.92 10.75 -τ4 4S?S Example 8a N-[5- (3-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide To 1.9 g. of 2-amino-5-(3-hydroxyphenyl)-l,3,45 thiadiazole in 100 ml. of pyridine was added 2.2 g. of 2,6-dimethoxybenzoyl chloride. The reaction mixture was stirred for three hours, with cooling as necessary to hold the temperature below 30°. The volatile substances were then evaporated under vacuum, and the residue was diluted with water. The aqueous mixture was stirred for three hours, and the solids were collected and recrystallized from acetone to produce 1.3 g. of N-[5-(3-hydroxyphenyl)*-l,3,4thiadiazol-2-ylJ-2,6-dimethoxybenzamide, m.p. 243-245°.

Theoretical Pound C 57.13% 57.38% H 4.23 4.36 N 11.76 12.01 Synthesis of the following exemplary compounds followed, in general, the process of Examples 8 and 8a. In each example below, the substituents of the aminothiadiazole and the benzoyl halide are obvious from the name of the product. The exemplary compounds will first be named, and then the amounts of the reactants, and the amounts, melting points and elemental analyses of the products, will be tabulated. <4573 Example 9 Ν-I5-(1-naphthyl)-1,3,4-thiadiazol-2-yl)-2,6-dimet hoxybenzamide Example 10 N-(5-(2,4-dichlorophony1)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzainide Example 11 N—|5—(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimcthoxybonzami do Example 12^ N-15-(3,5-dichlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 13^ N—15—(3-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide Example 14 N- I 5- (4-pyridyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzainide Example 15 N-I 5-(4-cyanophenyl)-1,3,4-thiadia2ol-2-yl)-2,6-dimethoxybenzamide Example 1]5 N-[5-[3,5-bis(trifluoromethyl)phenyl]-1, 3,4-thiadiazol-2yl]-2,6-dimethoxybenzamide Example 17 N-[5-(2-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 1)3 N-(5-phenyl-l,3,4-thiadiazol-2-yl)-2,6-dichlorobenzamide Example 19 N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6dichlorobenzamide Example 20 . 5 N-l5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yli-2-chloro-6~ methylbenzamide Example 21 N-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-ylJ-2,6-difluorobenzamide Example 22 · ·.· .

N-[5- (4-chlorophenyl)-1,3,4—thiadiazol-2-yl]-2,6-dimethylbenzamide Example 23 W-[5-(4-bromopheny1)-1,3,4-th iadiazol-2~y11-2,6-d i chloro)5 benzamide Example 24 N-(5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dichlorobenzamide _ : Example 25 N-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 26 .N-[5-(3,4-dichlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimothylben-zaraide Example 27 N-f5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide Example 28 N-(5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-ylJ-2,630 dimothylbenzamidc - -36 <<β»3 Example Ν- 15- (4-bromophenyl) -1,3,4-thiadiazel-2-yl]-2, 6-dimethylbenzamide Example 30 ν-(5-phenyl-l,3,4-thiadiazol-2-yl)-2,6-dimethylbenzamide Example 31 N-I 5-(4-Fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxyboiizami do Example 32 N-[5-(2-thienyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 33 N-[5-(2-Furyl)-1,3,4-thiadiazol-2-ylJ-2,6-dimethoxybenzamide Example 34 n- [ 5-(4-methylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 35 N-[5-(4-phenylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide 0 li’lSS’ElS Αϋ Ν—15—(3-tri Fluoromethylphenyl)-1,3,4-thiadiazol-2-yl]—2,6— dimethoxybenzamide Example 37 N-I 5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy25 benzamide Example 38 N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide Example 39 N- (5-phcnyl-l,3,4-thiadiazoL-2-yl) -2 , 6-dimothoxybenzanude Example 40 N- [5-(4-chlorophenyl)-1,3,4-thiadiazol-2-ylj-2-methoxybenzamide Example 41 N-[5-(3-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl)-2,6dimethylbenzamide Example 42 N-[5-[4-(4-bromophenyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6dimethoxybenzamide Example 43 N-[5-(4-(4-chlorophenyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6 dimethoxybenzamide Example 44 N-[5-(4-bromophenyl)-1,3,4-thiadiazol-2-ylJ-2,6-dimethoxybenzamide Example 45 N-[5-[4-(4-fluorophenyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6 dimethoxybenzamide Example 46 N-[5-(2-naphthyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 47 N-[5-(3,4-dichlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimcthoxybenzamide «4573 Example 48 N-15-()-hydroxyphenyl)-1,3,4-thiadiazol-2-y1 I —2,6-dimethoxybenzamidc Example 4 9 N-[5-(4-methoxyphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 50_ N-I 5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 51 N- 15-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethy1benzamjde Example 52 N-15-(2-naphthyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide Example 53 N~I 5-(3,5-bis(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethylbenzamide Example 54 N-[5-(3-thienyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 55 N-I 5-(3-furyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 56 N-[5-(5-bromo-2-furyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 57 N-15-(4-iodophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example 58 N- 15- (5-bromo- J-pyridy 1 )-1, 3,4-thiadiazol-2-y 1J-i, 6-ilimethoxybenzamide Example 59 n-15- (5-chloro-2-thienyl)-1,3,4-thiadiazol-2“y13-2,6-dimethoxybenzamide Example 60 N-[5-(3-isoxazolyl)-1,3 >4-thiadiazol-2-yl]-2,6-dimethoxy benzamide - 40 44S73 z tt ·#' co o in cn in KO cn r* Γ· cn KO CO KO tt4 03 co m in o* r- o o © r- © cn in 00 © in © © »—1 © rH KO in © rH rH a\ rd rd rd «η rH i—1 (—) rd «—1 rd rH rd rH rd rd 00 r- in in r- rH in rd TT cn © rd CM cq m rd *r CM o I—i CO 00 P- in cn cn m CM rd τ cn tr ΓΠ Q· cq CM m CM rd CM CM CM tr KO 00 © o © CM rd CM CM KO rd P- CM r- CM in m 00 o 00 co O rd CM © KO © tr CM υ tr © p- © r- m co co r- rd in CM © © CM KO tr m tr in in in tr in in tr in in in tr o rd 00 m Γ © h» o © w rd in rd tr m tr m KO tr • CM CM CM CM CM CM CM CM CM CM · 1 © o © o o © • U © KO KO © KO rd KO KO 00 CM ko co ko p· KO a o O CM CM TT rd tT CM cn *T cq CM in CM tr CM CM A A CM CM CM A CM CM A CM Λ CM A ϋ Ό Jd Φ rH TJ >1·Η 0 N 0 C rd Φ £ CQ U Cp OfQinmfQinco.—IK0O U1 (M N fO I O ' a m •rd -r4 £iΛ rij -P ω ι—I 0« · e o <0 z X ω tn m in O in O CQ © CM © in CQ © O CM CM CM CM rH CM CM CQ CM CM CM © O rd CM m tr m KO r» CO © O rd rd rd rd rd rd rd rd rd rd rd CM CM © *T CM CM CM CQ CM CM Example Amino- Benzoyl M,P., No. thiadiazole Chloride Product °C. %C %H %N 3* CM »—! rd © © M* rd rd i—l rd r- o *3* · LO rd rd rd © LO CO Ο Γ* CM r-( CM © •’M’ O CO f—4 i—4 M* O' i—4 i—4 r—) rd O CO CO CO CM CO i—4 r- r- CO © i—4 rd © cn co m* r- r—4 rd CM <3\ CO CM © CM r—4 CM i—4 M1 © © •-4 i—4 r- r- -3· cn ro © rd CM cn M* cn 'O’ © r-4 CO *3* CO 03 ro i—4 i—4 CM © 3* Γ- γο © r- Γ- ΓΟ ro M4 CM © © cn CO CM i—l © co CM σι O © 00 i—I co r-4 Ή CM r- r—4 © CO © O © © © r- M* *3* CM r- CM © r- CM m* σ © CM CM o* © © © © © © © © © © © © © © © o CO CM CM o ι—1 cn © o σι © O’ O in M* ro M* © © © © ro ro ro CO r-4 CM CM CM CM CM CM CM CM CM CM CM CM i—4 CM CM 1 o 4 M· 00 © rd © O CO OO © co co © ro CO r~ © co CM CO © M· M* © ro CM CO CO rd CM CM Λ CM CM CM CM CM CM CM CM CM ι—1 CM CM CO © cn . 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N I «rl ο Ό ii Π3 © © r-l CN ,-l co K CO CN CN © Ή κ w o Ν’ rH CN Ν’ N* © Ν’ N* Ν’ © © N* N* F Ν’ oo cn Ν’ Ν’ Ο ι-H CN CO Ν’ © © © © © •κ π eiP fr? co in fr © co CM fr CM O © © CO (Ό © © I—ί © -© #> ni o cm © fr © CM © © CM • 4 © © ID © © Co © © o iiP © CM © CM : Γ- CO σι © co fr σι © fr © © © © fr fr.fr Γ* o fr © fU Γ- σι © o CM CM 1 I © η* © © CM CM CM © © © CM { I © cn co © © O © © . CM CM CM I t CM CM P O TJ •-Λ4 CU © r· . r- © © CM © CM CM © Φ © Tj >© Ο M N 0 • C-4 CM © © CM © © CM © © CM © O G) © N Π3 t © Ο Ό a © o © © © CM © .© © © fu · e o w cn - © - co © © © © cn © «4573 It will bo understood that tho compounds of Examples 8-60, above, are also made by the processes of Examples 1 and 7b.

The following examples illustrate the preparation of amino- and acetamido-substituted compounds.

Example 61 N- |j-(4-aininophenyl),—1 , 3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide Λ 3.6 g. portion of the nitrophenyl compound prepared in Example 50 was hydrogenated in tetrahydrofuran in the presence of 5% palladium on carbon catalyst. After the hydrogenation, the solvent was evaporated to dryness under vacuum, and the residue was recrystallized from ethyl acetate. The catalyst was washed with ethanol and dimethylformamide, and the solvents were evaporated to dryness. The residue was recrystallized from ethyl acetate, and the combined recrystallized products were identified as 1.8 g. of N-(4-aminophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy- benzamide, m.p. 232-234° Theoretical Found C 57.30% 56.95' H 4.49 4.67 N 15.73 15.41 Kxample 62 Ν-I 5-(4-acotamidophenyl)-1,3,4-thiadiazol-2-yl]-2,6dimethoxybenzamide An 0.5 g. portion of the product of Example 61 was dissolved in 20 ml. of pyridine, and 0.2 ml. of acetic anhydride in 5 ml- of tetrahydrofuran was added while the 0873 reaction mixture was cooled to hold the tomperaline below 35°. Alter the addition, the mixture was stilted tor lb hours at room temperature, and was evaporated to dryness under vacuum. The residue was recrystallized from ethyl acetate to give. 0.25 g. of N-[5-(4-acetamidophenyl)-1,3,4thiadiazol-2-yl]-2,6-dimethoxybenzamide, m.p. 211-213°.

Theoretical Found C 57.42% 57.70% H 4.31 4.61 N 14.10 13.80 The compounds of Formula I have been thoroughly tested against live insects to determine the range of their insecticidal efficacy. The following tests are typical of the experiments performed and the results obtained.

In many instances, repeated tests at an application rate have been performed, and the results of such tests have been averaged. Blank spaces in the data tables below indicate that no test at the named application rate has been done. Compounds are identified by their example numbers. Test 1 Mexican bean beetle and southern armyworm test Each compound to be tested was formulated by dissolving 10 mg. of the compound in 1 ml. of solvent comprising 1:1 anhydrous ethanol:acetone containing 23 g. of Toximul R and 13 g. Toximul S per liter. (Toximuls are trademarks for sulfonate/nonionic blended surfactants produced by Stepan Chemical Co., Northfield, Illinois, U.S.A.) Each sample was then dispersed in 9 ml. of water to provide 44873 a 1000 ppm. concentration of the test, compound. This dispersion was diluted with water to produce lower concentrations, when desired. The dispersion was sprayed evenly over ten-day-old bean plants and the plants were set aside until dry.

Leaves were then removed from the plants, and the cut ends of the leaves were wrapped in water-soaked cotton. Two leaves were placed in each 100-mm. plastic petri dish, and 5 second- or third-instar Mexican bean beetle larvae (Epilachna varivestis) and 5 second- or third-instar southern armyworm larvae (Spodoptera eridania) were placed in each dish. Three replicate dishes were used for each test compound. The dishes were held at about 25° and 51 percent relative humidity for 4 days, and the first evaluation of the insecticidal efficacy was made. Some of the dishes wore held in flic controlled room for three days more, and another evaluation was made.

Insecticidal efficacy was rated on the following scale, compared to solvent controls and nontreated controls. = no control 1=1-7 larvae dead = 8-14 larvae dead = 15 larvae dead The following table reports the results of testing typical compounds.

Compound of Example No. 7a Table 1 Appln. Rate ppm. Mexican bean beetle 4 day 7 day 1000 2 3 100 2 2 50 2 2 25 2 _2 :10 .- ' 1 2 1000 1 2 100 1 2 1000 2 3 100 0 0 1000 0 2 1000 I 3- '100 - - 0 2 1000 .1 3 : 100 - 1 2 1000 2 1000 2 3 1000 0 1 100 0 0 1000 1 2 100 0 1 1000 1 2 100 1 1 1000 0 0 100 0 0 -25 Southern •armyworm day 7 day - 3 3 2 2 1 0 0 3 0 o ; 1 3 1 1 1 0 2 3 1 2 1 2 0 3 3 2 2 ♦4·Τ3 Table 1 Continued Compound oi Λρρΐn. Mexican bean Sent her n Example Rate beetl armyworm No. PPm· 4 day 7 day 4 day 7 day 13 1000 1 2 3 3 100 0 2 2 2 15 1000 0 0 2 2 100 0 0 0 0 16 1000 1 1 3 3 100 0 1 3 3 50 1 1 3 3 25 2 2 2 3 10 1 1 2 2 5 0 1 1 2 17 1000 2 3 3 2 100 1 2 1 0 50 1 2 0 0 25 1 2 0 0 18 1000 0 0 3 2 100 0 0 0 19 1000 0 0 3 3 100 0 0 1 1 20 1000 1 2 3 3 100 1 1 2 2 21 1000 0 0 2 2 100 0 0 0 0 22 1000 2 2 3 3 100 1 2 2 3 50 2 3 1 2 25 1 2 1 1 Table 1 Continued Compound of Appln. Mexican bean Southern Example Rate beetle armyworm No. ppm. 4 day 7 day 0 4 day • 2 7 day 23 1000 0 2 100 0 0 0 0 24 1000 0 0 3 3 100 0 0 1 1 26 1000 1 1 0 3 100 0 0 0 0 27 1000 1 2 3 3 100 2 2 2 3 50 2 3 2 2 25 2 3 1 2 20 1 3 1 2 10 1 2 1 1 28 1000 2 3 3 3 100 1 2 2 2 50 0 1 1 2 25 0 1 0 1 29 1000 2 2 3 3 100 1 2 2 2 50 1 2 1 2 25 1 1 0 0 30 1000 1 2 2 3 100 1 2 0 0 31 1000 2 3 ' 3 3 100 1 2 3 3 50 1 2 2 2 25 0 2 1 2 Table 1 Continued Compound of Example Appln. Rate Mexican bean beetle Southern armyworm No. ppm. 4 day 7 day 4 day 7_day 32 1000 1 0 3 2 100 0 0 0 0 33 1000 2 2 2 2 100 1 2 0 1 34 1000 1 3 2 2 100 0 2 0 0 35 1000 0 0 3 3 100 0 0 2 2 36 1000 2 2 3 3 100 2 2 2 3 50 2 2 2 2 25 2 2 2 3 10 1 2 2 2 5 1 2 2.5 1 1 37 1000 2 3 2 3 100 2 2 2 2 50 1 2 25 1 1 38 1000 2 3 3 3 100 2 2 i 3 50 3 3 3 3 25 3 3 10 2 3 Table 1^ Continued Compound of Example No. Appln. Rate ppm. Mexican bean beetle Knut horn armyworm 4 day 7 day 4 day - 7 day 39 1000 2 3 3 _> 100 0 I 0 0 40 1000 0 I 3 3 100 0 0 0 0 41 1000 2 2 2 2 . -- - 100 0 ,0 0 0 42 1000 0 0 2 3 100 0. 0 0 0 43 1000 0 0 3 3 10Q 0 . 0 1 2 44 1000 0 2 1 3 100 1 2 3 3-- 50 1 3 1. 2 ‘: : z 25 1 2 2 2 45 1000 0 0 3 3 100 1 1 2 2 50 0 1 2 2 25 0 1 0 1 46 1000 0 1 2 1 100 1 •1 1 0 47 1000 1 1 _ 3 3 100 0 0 1 1 48 1000 1 2 0 0 100 0 0 0 0 Tabic* Compound of Appln. Example Rate No. ppm. 1 Continued Mexican bean beetle Southern armyworm 4 day 7 day 4 day 7 day 49 1000 2 0 2 0 100 0 0 0 0 50 1000 2 0 2 0 100 0 0 0 0 51 1000 2 0 1 0 100 0 0 0 0 52 1000 1 0 1 0 100 0 0 0 0 53 1000 1 2 3 3 100 0 0 3 3 54 1000 1 3 0 0 100 0 0 0 0 55 1000 1 1 2 2 100 0 0 0 0 56 1000 3 3 2 3 100 1 2 3 3 57 1000 3 3 3 3 100 2 3 2 2 50 3 2 1 1 10 1 2 1 1 58 1000 0 1 2 2 100 0 0 0 1 59 1000 1 1 2 3 100 0 0 1 1 44373 Table 1 Continued Compound of Example Appln. Rate Mexican bean beetle Southern armyworm No. ppm. 4 day 7 day 4 day 7 day 60 1000 1 3 100 0 0 61 1000 2 0 0 0 100 0 0 0 0 62 1000 1 0 1 0 100 0 0 0 0 Test 2_ Mexican bean beetle emergence test This test was performed to determine the ability of representative compounds to prevent the emergence of adult Mexican bean beetles from pupae.

The compounds were formulated as described in Test 1 above. Bean plants were treated as described in Test 1, and leaves of the treated plants were used as hosts for third-instar Mexican bean beetle larvae in petri dishes. Three larvae were used in each dish. New leaves were added to the dishes as needed, while the larvae were maintained until they pupated, in about 3-5 days. The pupae were then placed in clean petri dishes. After 7 to 10 days, the number of adult Mexican bean beetles which had emerged were counted, and the percent control of emergence was determined compared to solvent and untreated controls. Various numbers of dishes of larvae were used in different tests; in each instance, all of the dishes were pooled for determination of the percent control. 54; Table 2 <’(jiii|> Concentration ΐ No. ppm. Control 1 100 100 50 100 25 100 10 100 22 100 100 50 100 25 100 10 100 27 100 100 50 100 25 100 10 100 28 100 100 50 48 25 3 10 11 31 100 100 50 100 25 100 10 100 36 100 100 50 100 25 100 10 100 44873 Table 2 Continued Compound of Example No. Concentration ppm. J Contn 37 100 100 50 100 25 100 10 100 38 100 93 50 50 25 65 10 50 Test 3 Mexican bean beetle life cycle test This test was performed essentially according to the method of Test 1 above, except that the larvae were in the late third-instar phase. The larvae were examined after three days to determine the larvicidal effect, and adult emergence was determined by counting the number of emerged adults after the larvae had pupated and all of the untreated controls had emerged.

Table 3 Compound of Example No.

Appln. Rate ppm. 1000 100 Control of Larvae % Control of Emergence 44873 Test 4 Mexican bean beetle life cycle test This test was performed according to the method described immediately above, except that the larvae were 5 second-instar, and they were observed three times, at 3, 8 and 21 days after treatment. The first two observations were of larvicidal effect, as the larvae had not yet begun to pupate. The 21-day observation was a count of emergence of adults from the pupae. In each case, the observations are reported below as percent control, compared to control larvae.

Table 4_ Compound of Example No. Appln. Rate ppm. Percent Control 3 day 8 day 21 day 1 1000 11 100 100 100 22 100 100 10 0 60 100 1 0 0 71 8 1000 0 20 100 18 1000 0 0 42 19 1000 0 6 100 20 1000 0 100 100 Tps_t 5 black blowfly test This test demonstrated the efficacy of typical compounds against the black blowfly, Phormia regina.

Each test compound was formulated by dissolving 4 mg. of it in 0.4 ml. of acetone and mixing it with 40 g. of homogenized beef liver to give 100 ppm. concentration, bower concentrations of the compounds were provided by using acetone solution containing other appropriate amounts of the compound.

The treated liver was divided between two 250-cc. plastic cups and each portion was infested with ten 2-dayold blowfly larvae. The liver was placed on a layer of wood chips and was covered with more chips. All the cups, including solvent-treated and untreated control cups, were held in a temperature and humidity-controlled room until the larvae pupated. All of the pupae were then removed, placed in clean plastic petri dishes, and held until adult flys emerged from control pupae.

The number of pupae per cup was recorded at the time the pupae were placed in the petri dishes. The number of emerged adults per dish was also recorded, and the percent adult control is presented in the table below.

Table 5 Compound of Example NO. Appln. Rate ppm. a Control of Emergence 1 100 100 10 15 1 0 22 LOO 0 10 0 1 0 27 100 45 10 0 1 0 44873 Table 5 Continued Compound of Λρρίη.

Example Rate No. ppm.

Control of Emergence 100 25 0 0 100 100 45 0 100 20 0 0 100 10 0 0 100 25 0 0 Test 6 greater wax moth larvicide test This test was performed to evaluate certain compounds against the greater wax moth, Calleria mellonella, a parasite of beehives.

Sufficient compound to give the desired concentration was dissolved in 5 ml. of acetone and mixed with 49 g. of a diet composed of 25 g. of oatmeal cereal for babies, 10.6 ml. of honey, 8.0 ml. of glycerin, 5.3 ml. of water and 0.5 ml. of liquid vitamin supplement. The acetone was allowed to evaporate, and the treated diet was divided between three petri dishes, .to each of which was added five second- and third-instar larvae. The dishes were held in the controlled room for seven days, and percent control of the larvae was determined, compared to controls.

Table 6 Compound of Example No. Appln, Rate ppm. Control I.. - 500 0 loo 0 50 0 25 0 12.5 0 22 500 100 100 100 50- 100 25 13 12.5 0 27 500 100 100 100 50 0 25 0 12.5 6 28 500 100 100 100 - 50 86 25 13. 12.5 0 44873 Table 6 Continued Compound of Example No. Appln. Rate ppm. % Contrc 31 500 100 100 100 50 13 25 0 12.5 0 36 500 100 100 100 50 0 25 0 20 0 12.5 13 10 0 5 0 2.5 0 37 500 0 100 0 50 0 25 0 12.5 0 38 500 100 100 13 50 0 25 0 20 7 12.5 0 10 0 5 0 2.5 0 Test 7_ Mexican bean beetle sterilization test This test was conducted by exposing adult Mexican bean beetles to bean plants treated with dispersions containing 1000.ppm. of a typical compound of Formula I. The adult beetles were maintained on the treated plants until the females had laid eggs, and egg clusters containing from 20 to 30 eggs each were collected and incubated. None of the eggs from beetles fed on plants treated with the compound of Example 36 hatched. The compound completely sterilized the beetles which consumed the treated foliage.

Test 8 lepidoptera on field-grown broccoli Compounds of Formula I were tested against lepidoptera pests infesting field-grown broccoli. The broccoli plants were transplanted into field plots, and treatment began approximately four weeks after transplanting.

The compounds named in the tables below were formulated as wettable powders, and were dispersed in water in concentrations such as to provide the application rates named below, when the dispersions were sprayed at the rate ol about 1000 liters per hectare.

The compounds were applied three times at 7-day intervals, and the insects infesting the plants were counted seven days after the third application.

The insect control obtained from use of the compounds is described in the tables below as percent reduction in the number of insects, compared to the number of insects infesting untreated control plants. 445 The broccoli crop was infested primarily by two species, Pieris rapae and Trichoj^lusia ill. Control ot tin two species is reported in the tables below, as is the control of all species of lepidoptera as a group. 44S73 rtf Μ - -Φ r4 +J rtf Di •Ρ Ο Ο Ό cd Ή β. σι q-j . . ω in co cm ot oj <-i o cn ot in- t*· © cd H tn o cm cn CO Γ OT . CM KO CM CO Γ' -CO Γi-4 - 0 P -P C O •P . cs •Φ ϋ p Φ CL . D*<« . Ο -H «1 >4 Ci r-4 QJ CX th 0 rtf Λ Λ Ο Λ ·η: rtf Ρ O.C-H Ο Φ 0) σ> rt d α Λ © Λ μ © u w •Η Ό Ρ Φ -Φ Ρ Ρ Μ CL Ο • * · rtf β Λ <-4 Φ X ; Qi Ρ · P« rtf tn < tti X 'd β 3 ΟΉ Qi.O a o g z g . t® * CM co in cm cm ι—ι co - in . j> - n σ> Γ o- h rf H co ίο CM m - r-j CT O r4 Η o σ\ o OT OT CD O CM Γ- LO > in r*r4 nf Ή 0's nf CD in cm in CM CM OJ r4 o> m r* cn ©ο o cn α o n· rP r-4 M* OT OT rd cm m CM s r—i M’ CD *1* > in h 'in p O\ CD CD cd in co σ» οοτ nf CO OT I—I r4 CM m *r co ot H H CM in nr co ot r-4 CM in r-J r-i Ο O O r-4 O O © r-4 OT CM «-4 CM OT 00 m co 44873 Test 9 imported cabbageworm on field-grown broccoli This test was carried out according to the method described in Test 8 above, except that the compounds were 5 applied only twice instead of three times. The only insect which was counted in this test was Pieris rapae.

Test 9 Compound of Appln.

Example Rate Percent No. kg./ha. Control 0.28 66 0.56 81 1.1 97 2.2 97 0.28 97 0.56 97 1.1 100 2.2 100 0.28 65 0.56 81 L.l 94 2.2 97 0.28 75 0.56 88 1.1 97 2.2 97 0.28 97 0.56 100 1.1 100 2.2 100 The above illustrative data show the potent insecticidal effect of the compounds of Formula T. Entomologists will understand that the compounds are broadly useful for the control of insects of the various orders which adversely affect mankind and its economic enterprises.

For example, the compounds control Coleoptera such as Anthonomus grandis, Crambus caliginosellus, Oulema melanopus, Leptinotarsa decemlineata, Hypera postica, Anthrenus scrophulariae, Tribolium confusum, Lyctidae species, Agriotes species, Sitophilus oryzae, Nodonota puncticollis and Conotrachelus neruphar; Diptera such as Musca domestica, Stomoxys calcitrans, Haematobia irritans, Phormia regina, Ilylemya brassicae and Psila rosae; Lepidoptera, such as Laspeyresia pomonella, Euxoa species, Plodia interpunctella, Tartricidae species, Heliothis zea, Ostrinia nubilalis, Hellula rogatalis, Trichoplusia ni, Thyridopteryx epKemeraeformis, Malacosoma americanum and Spodoptera frugiperda; and Orthoptera, such as Blattella germanica and Perlplaneta americana.

The compounds are useful for reducing populations of insects, and are used in a method of reducing an insect population which comprises applying an insecticidallyeffective amount of one of the compounds to a substance to be Ingested by the insects.

Insects may be caused to ingest a compound by applying the compound to any substance which they ingest.

For example, plant-infesting insects are readily controlled by applying a compound to plant parts which the insects eat, particularly the foliage. Insects which infest and consume 44*73 textiles, paper, wood products and the like are readily controlled by applying a compound tc such products. The compounds can similarly be effectively used to protect stored grain or seeds.

It is notable that the compounds interfere with the formation of successive stages of insects which ingest them. For example, when adult insects ingest the compounds, the adults are grossly unaffected, but lay sterile eggs.

When an insect larva consumes a compound, it dies without metamorphosing into the next larval stage. Last-stage larvae which consume a compound pupate, but die in the pupa form.

Entomologists will understand that it is not inferred that use of a compound of Formula I will neces15 sarily result in the extinction of an insect population. In some instances, of course, the whole population will be killed. In other instances, part of the insects will be killed and others will survive treatment with the compound. The portion of the population which will be killed depends upon the species of insect, the particular compound in use, the application rate, the vigor of the insects, the weather and other factors understood by entomologists. Thus, the term reducing a population of insects refers to a decrease in the numbers of living insects, which in some but not all instances will amount to the disappearance of the population ol Ireated insects.

Ttie extent of population reduction accomplished by

Claims (49)

What is claimed is:

1. A thiadiazolylbenzamide compound of the formula H 0 I II .·—N~CF' wherein R represents / R lZ V / / \A νΑ Λα I —I—ί— R ” vv , or A / ·; ι \=z 5t ,e~R wherein 0 1 2 . R , R and R independently represent hydrogen, chloro or bromo, provided that at least one of R°, R 1 and R 2 represents chloro or bromo; . X represents oxygen or sulfur; 3 4 R and R independently represent hydrogen, chloro, bromo or methyl, provided that R represents hydrogen when X represents oxygen; R 5 represents hydrogen, chloro, bromO, fluoro or trifluoromethyl; and either 6 7 8 9 1) R and R represent hydrogen, one of R and R 8 9 represents hydrogen, and the other of R and R represents hydrogen, chloro, methoxy, bromo, iodo, fluoro, trifluoromethyl, methyl, hydroxy, phenyl, or phenyl monosubstituted with bromo, chloro or fluoro, or 6 7 8 9

2. ) R and R represent hydrogen, and R and R independently represent chloro, fluoro or bromo, or 6 8 7 9

3. ) R and R represent hydrogen, and R and R independently represent chloro, fluoro, bromo or trifluoromethyl, or 7 9 6 8

4. ) R and R represent hydrogen, and R and R independently represent chloro, fluoro or bromo, or 7 8 9 6

5. ) R , R and R represent hydrogen, and R represents chloro, fluoro or bromo, or 6. ) R 6 , R 7 and R 9 represent hydrogen, and R® represents acetamido, nitro, amino or cyano; R 79 and R 11 independently represent hydrogen, chloro, fluoro, bromo, methyl or methoxy; provided that: 1) 2) 3) one of rIQ and may represent hydrogen, if and only if the other represents methoxy; at least one of R^° and R^ must represent methyl or methoxy, unless ,8 a) 6 7 R“ does not represent hydrogen, and R , R and R represent hydrogen, or 6 8 b) R and R represent hydrogen, and one or both 7 9 of R and R represent trifluoromethyl; 8 9 neither R nor R represents phenyl, acetamido, methoxy, nitro, amino, cyano or substituted phenyl unless both and R^ represent methoxy; 7 8 9 4) two of R , R and R represent hydrogen unless both r!0 and R^ represent methyl or methoxy; 5) both R 10 and R^ 1 represent methoxy or methyl when 6> R represents pyridyl, naphthyl, furyl or thienyl; both R^O and Z represent methoxy when R represents benzothiazolyl, benzoxazolyl, benzothienyl, benzofuryl, isoxazolyl, quinolyl or thiazolyl. 2. A compound of Claim 1 wherein R represents \ / ezzz· M-r' z V ,1/ R\ X e-- φ <==>V 3. A compound of Claim 1 or 2 wherein R represents ,R 4. A compound of any of Claims 1-3 wherein and R 11 independently represent methyl or methoxy. 5 5. A compound of any of Claims 1-4 wherein one of 8 9 R and R represents hydrogen, and the other represents halogen or trifluoromethyl.

6. A compound according to any of Claims 1-5 and which is; 10 N- [5- (4-chlorophenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethylbenzamide, N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]2.6- dimethylbenzamide, or N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol15 2-yl]-2,6-dimethylbenzamide.

, 7. A compound of any of Claims 1-5 wherein and rH represent methoxy.

8. A compound according to any of Claims 1-5 or 7 and which is: 20 ν-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]2.6- dimethoxybenzamide, N-[5- (4-fluorophenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide, N-[5-(3-trifluoromethylphenyl)-1,3,4-thiadiazol25 2-yl]-2,6-dimethoxybenzamide, 4 4 573 N-[5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide, or N-[5-(4-trifluoramethylphenyl)-l,3,4-thiadiazol2-yl]-2,6-dimethoxybenzamide.

9. A compound of any of Claims 1-4 wherein R? and R independently represent chloro, fluoro, bromo, or trifluoromethyl.

10. A compound of any of Claims 1—4 or 9 which is N-[5-(3,5-bis(trifluoromethyl)phenyl)-1,3,4-thiadiazol10 2-yl]-2,6-dimethoxybenzamide.

11. A compound according to Claim 1 of the formula wherein R represents ,30 \ / V 44873 J -f-W' \/\y >v\ J —fl----f—--R z W r 22 23 ;·—·( -/ r* •--V or wherein r 15, r 16' viD, R 1 · 3 and R 3 ^ independently represent hydrogen, i c 1 fi chloro or bromo, provided that at least one of R and R , 17 18 19 or at least one of R , R and R represents chloro or bromo; X represents oxygen or sulfur; R represents hydrogen, chloro, bromo or methyl; R represents hydrogen, chloro, bromo, fluoro or trifluoromethyl; and either 1) R 22 and R 23 represent hydrogen, one of R 24 and R 23 24 25 represents hydrogen, and the other of R and R represents hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, hydroxy, phenyl, or phenyl monosubstituted with bromo, chloro or fluoro, or 2) R 22 and R 23 represent hydrogen, and R 24 and R 23 independently represent chloro, fluoro or bromo, or 4 457S 22 24 2*3 2^ 3) R and R represent hydrogen, and R and R independently represent chloro, fluoro, bromo or 4) trifluoromethyl, or 23 25 22 24 R and R z represent hydrogen, and R z and R z independently represent chloro, fluoro or bromo, or 5) R 23 , R 2 ^ and R 23 represent hydrogen, and R 22 represents chloro, fluoro or bromo; ,14 ,13 R and R independently represent hydrogen, chloro, 10 fluoro, bromo, methyl or methoxy; provided that: 13 14 1) one of R and R may represent hydrogen, if and only if the other represents methoxy; 13 14 2) at least one of R and R must represent methyl or methoxy, unless 24 22 23 a) R does not represent hydrogen, and R , R and R represent hydrogen, or 22 24 b) R and R represent hydrogen, and one or 23 25 both of R and R represent tnfluoromethyl; 24 25 3) neither R nor R represents phenyl Or sub13 14 stituted phenyl unless both R and R represent methoxy; 4) two of R 23 , R 2 ^ and R 23 represent hydrogen unless 13 14 both R and R represent methyl or methoxy; 13 14 5) both R and R represent methoxy when R represents pyridyl, naphthyl, furyl or thienyl.

12. A compound of Claim 11 wherein represent» and

13. A compound of Claim 11 or 12 wherein both R 14 R represent methoxy. os’®

14. An. insecticidal composition which comprises a compound as claimed in any one of claims 1 to 13 and an inert carrier. _

15. A composition of Claim 14 wherein the 5 concentration of the compound is from 1 ppm. to 90 percent.

16. A method of reducing an insect population Which comprises applying an insecticidally-effective amount of a compound as claimed in any one of claims 1 to 13 to a substance to be ingested by the insects. 10

17. A method of Claim 16 wherein the amount of the compound is from 1 to 1000 ppm. 80 44573

18. A process for preparing a thiadiazolyl benzamide compound as claimed in Claim 1, which comprises either 1) acylating a 2-amino-5-R-substituted 1,3,4-thiadiazole 5 of the formula wherein R is as defined in Claim 1, except that R does not represent amino- or acetamidophenyl, with a benzoyl halide of the formula 1u Hal III wherein Halo refers to chloro or bromo, and R 10 and R 11 are as defined in Claim 1, or 2) cyclizing a compound of the formula II X-NH-C-NH- IV wherein R 10 and R 11 are as defined in Claim 1, and X represents II R-C-NH- or R-CH=N81 wherein R is as defined in Formula II, with a dehydrating agent, when X represents II R-C-NH-, or with an oxidizing agent, when X represents R-CH=N-, and g 5 optionally reducing a compound of Formula 1 wherein R g represents nitro to obtain a compound wherein R represents amino, and further optionally acylating the compound wherein 8 8 R represents amino to prepare a compound wherein R represents acetamido. 10

19. A process according to Claim 18 for preparing a compound of the formula as defined in claim 11 which comprises either . 1) acylating a 2-amino-5-R -substituted 1,3,415 thiadiazole of the formula 44*73 VI wherein R is as defined in claim 11, with a benzoyl halide of the formula r 13 Halo-C—J)· VII 13 14 wherein Halo refers to chloro or bromo, and R and R are as defined in claim 11, or 2) cyclizing a compound of the formula Η II II Λ A R 1 Z -C~NH-NH~C-NH-C—< VIII wherein R^ 2 , R^ 3 and R^ are as defined in claim 11, with a 10 dehydrating agent.

20. A process of Claim 18 which comprises cyclizing a compound of the formula T S 0 1—» 11 11 / \ R-CH=N-NH-C-MH-C—< * IX A wherein R, R^° and R^ 3 are as defined in Claim 1, except 15 that R does not represent amino- or acetamidophenyl, with 44373 : an oxidizing agent, and optionally reducing a compound of 8 Formula I wherein R represents nitro to obtain a compound 8 ' · wherein R represents amino, and further optionally acylating 8 the compound wherein R represents amino to prepare a compound 8 wherein R represents acetamido.

21. A process according to Claim 18 or 19 for preparing a compound of claim 2 which comprises acylating a compound of the formula —NH„ II wherein R repiesent formula is as defined above, except that R does not amino or acetamido, with a benzoyl halide of the wherein Halo, R 10 and R 11 are as defined in Claim 18, and ft optionally reducing a compound of Formula I wherein R 8 represents nitro to obtain a compound wherein R represents amino,, and further optionally acylating the compound wherein 8 _ Q R represents amino to prepare a compound wherein R represents acetamido.

22. A process for preparing a compound of acylating a compound of the according to Claims 18 or 19 claim 3 which comprises formula R does not represent amino or acetamido, Of the formula „10 above, except that with a benzoyl halide Halo-C —< - 84 44873 wherein Halo, R^ and are as defined in Claim 18, and optionally reducing a compound of Formula I wherein 8 8 R represents nitro to obtain a compound wherein R represents amino, and further optionally acylating the compound Q E wherein R represents amino to prepare a compound wherein g R represents acetamido.

23. A process according to Claims 18 or 19 for preparing a compound of claim 4 which comprises acylating a compound of the formula , / S >=·' S' „9/ wherein R f) , R?, R® and R^ are as defined in Claim 22, with a benzoyl halide of the formula “ Λ-\ Ha I o-C—·' > wherein Halo, R^ and R 1 1 · are as defined in Claim 18, and θ optionally reducing a compound of Formula I wherein R Q represents nitro to obtain a compound wherein R represents amino, and further optionally acylating the compound wherein 8 . 8 R represents amino to prepare a compound wherein R represents acetamido. 4 457 3

24. The process of any of Claims 18, 19, or 21-23 for preparing N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]2.6- dimethylbenzamide which comprises acylating 2-amino-5(4-chlorophenyl)-1,3,4-thiadiazole with 2,6-dimethylbenzoyl chloride.

25. The process of any of Claims 18, 19, or 21-23 for preparing N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2yl]-2,6-dimethylbenzamide which comprises acylating 2-amino5-(4-fluorophenyl)-1,3,4-thiadiazole with 2,6-dimethylbenzoyl chloride.

26. The process of any of Claims 18, 19, or 21-23 for preparing N-[5-(4-trifluoromethylphenyl)-l,3,4-thiadiazol- 2-yl] -2, 6-dimethylbenzamide which comprises acylating 2-amino-5-(4-trifluoromethylphenyl)-1,3,4-thiadiazole with 2.6- dimethylbenzoyl chloride.

27. The process of any of Claims 18, 19, or 21-23 for preparing N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]2.6- dimethoxybenzamide which comprises acylating 2-amino-5(4-chlorophenyl)-l,3,4-thiadiazole with 2,6-diinothoxybenzoyl chloride.

28. The process of any of Claims 18, 19, or 21-23 for preparing N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide which comprises acylating 2-amino-5(4-fluorophenyl)-1,3,4-thiadiazole with 2,6-dimethoxybenzoyl chloride.

29. The process of any of Claims 18, 19, or 21-23 for preparing N-[5-(3-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises acylating 2-amino-5-(3-trifluoromethylphenyl)-1,3,4-thiadiazole with 2,6-dimethoxybenzoyl chloride. <*4573

30. The process of any of Claims 18, 19 or 21-23 for preparing N-£5-(3-chlorophenyl)-1,3,4-thiadiazol-2ylJ-2,6-dimethoxybenzamide which comprises acylating 2amino-5-(3-chlorophenyl)-1,3,4-thiadiazole with 2,6- dim5 ethoxybenzoyl chloride.

31. The process of any of Claims 18, 19, or 21-23 for preparing N-f5-(4-trifluoromethylphenyl)-1,3,4,-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises acylating 2-amino-5-(4-trifluoromethylphenyl)-1,3,4-thiadiazole with 10 2,6-dimethoxybenzoyl chloride.

32. The process of any of Claims 18, 19 or 21-23 for preparing N-^5-(3,5-bis(trifluoromethyl)phenyl)-1,3,4thiadiazol-2-ylJ-2,6-dimethoxybenzamide which comprises acylating 2-amino- 5-D, 5-bis(trifluoromethyl)phenyl]-l,3,415 thiadiazole with 2,6-dimethoxybenzoyl chloride.

33. A process according to Claim 18 for preparing a compound of claim 2, which comprises cyclizing a compound R 8 * 10 of the formula. R' .11 IX θ wherein R is as defined above, except that R does not represent amino or acetamido, and and R^^ are as defined in Claim 1, with a dehydrating agent, and optionally Q reducing a compound of Formula I wherein R° represents θ nitro to obtain a compound wherein R represents amino, and Q further optionally acylating the compound wherein R re8 presents amino to prepare a compound wherein R represents acetamido.

34. A process of Claim 18 for preparing a compound of >ound of the formula IX 4dS73 wherein R is as defined above, except that R does not represent amino or acetamido, and R^ and R^ are as defined in Claim 1, with a dehydrating agent, and optionally 8 reducing a compound of Formula I wherein R represents nitro 8 ' to obtain a compound wherein R. represents amino, and 8 5 further optionally acylating the compound wherein R repre8 sents amino to prepare a compound wherein R represents acetamido.

35. A process of any of Claims 18, for preparing a compound of Formula I wherein R is as defined in 10 Claim 34 and ar.c represent methyl or methoxy, which comprises cyclizing a compound of the formula R’° 0 SO ii ii ii R-C-NI l-NH-C-NH-C— wherein R, R^ 9 and R^ are as defined above, except that 8 R does not represent amino or acetamido, with a dehydrating agent, and optionally reducing a compound of Formula I o . - g wherein R represents nitro to obtain a compound wherein R represents amino, and further optionally acylating the 8 compound wiierein R represents amino to prepare a compound 8 wherein R represents acetamido.

36. The process of any of Claims 18 or 33-35 for preparing N- [5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethylbenzamide which comprisescyclizingl-(4-chlorobenzoyl)-4-(2,6-dimethylbenzoyl)thiosemicarbazide with a dehydrating agent.

37. The process of- any of Claims 18 or 33-35 for preparing N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethylbenzamide which comprises cyclizing 1-(4fluorobenzoyl)-4-(2,6-dimethylbenzoyl)thiosemicarbazide with a dehydrating agent. J 4573

38. The process of any of Claims 18 or 33-35 for preparing N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol2-yl]-2,6-dimethylbenzamide which comprises cyclizing 1- (4-trifluoromethylbenzoyl)-4-(2,6-dimethylbenzoyl)thioa semicarbazide with a dehydrating agent.

39. The process of any of Claims 18 or 33-35 for preparing N-[5-(4-chlorophenyl)-l,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide which comprises cyclizing 1-(4chlorobenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemicarbazide 10 with a dehydrating agent.

40. The process of any of Claims 18 or 33-35 for preparing N-[5-(4~fluorophenyl)-l,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide which comprises cyclizing 1-(4fluorobenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemicarbazide 15 with a dehydrating agent.

41. The process of any of Claims 18 or 33-35 for preparing N-[5-(3-trifluoromethylphenyl)-1,3,4-thiadiazol2- yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-(3-trifluoromethylbenzoyl)-4-(2,6-dimethoxybenzoyl)thio20 semicarbazide with a dehydrating agent. a«s?3

42. The process of any of Claim;; Lt> or 3 *-> 1 ' lor preparing N-[5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]2,6-dimethoxybenzamide which comprises cyclizing 1-(3chlorobenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemicarbazide 5 with a dehydrating agent.

43. The process of any of Claims 18 or 33-35 for preparing N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol2-yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-(4-trifluoromethylbenzoyl)-4-(2,6-dimethoxybenzoyl)thio10 semicarbazide with a dehydrating agent.

44. The process of any of Claims 18 or 33-35 for preparing N-[5-(3,5-bis(trifluoromethyl)phenyl)-1,3,4thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-[3,5-bis(trifluoromethyl)benzoyl)-4-(2,615 dimethoxybenzoyl)thiosemicarbazide with a dehydrating agent.

45. A thiadiazolyl benzamide compound as claimed in Claim 1, substantially as hereinbefore described with particular reference to any one of the Examples.

46. An insecticidal composition as claimed in Claim 14 20 substantially as hereinbefore described with particular reference to any one of the Examples.

47. An insecticidal method as claimed in Claim 16 substantially as hereinbefore described with particular reference to any one of the Examples. 25

48. A process for preparing a thiadiazolyl benzamide compound as claimed in Claim 18 substantially as hereinbefore described with particular reference to any one of the Examples.

49. A thiadiazolyl benzamide as claimed in any one of claims 1 to 13 whenever prepared by a process according to claim 30 18 or 48.