CA1077041A - N-(1,3,4-thiadiazol-2yl) benzamides - Google Patents

Abstract

Abstract of the Disclosure The present invention relates to a series of novel N-(1,3,4-thiadiazol-2-yl)benzamides, having a phenyl, naphthyl or hetero-aryl group at the 5-position of the thiadiazole ring and 2,6-substitution on the benzyl ring, which are useful insecticides.

Description

'7~1 The present invention relates to a series of novel N-(1,3,4-thiadiazol-2-yl)benzamides, having a phenyl, naphthyl or hetero-aryl group at the 5-position of the thiadiazole ring and 2,6-substitution on the benzyl ring, which are useful insecticides.
The control of insects was one of the first problems undertaken by agricultural chemical research, and 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 food-stuffs. 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 insec-ticides has been spurred by the withdrawal from use of the old residual insecticides.
The compounds of Formula I are new to organic chemistry. Some items in the prior art, however, are of interest. For example, Cebalo, U.S. Patent 3,726,892, dis-closes herbicidal 1,3,4-thiadiazol-2-ylureas.
Rao, Indian J. Chem. 8, 509-13 (1970), teaches a synthesis method for 2-amino-1,3,4-thiadiazoles, which are intermediates for the compounds of this invention.
Wellinga and Mulder, U.S. Patent 3,748,356, show herbicidal and insecticidal efficacy of N-benzoyl-N'-phenyl-ureas.
This invention belongs to the field of agricul-tural chemistry, and provides novel thiadiazolyl benz-amides of the formula "~a R~ -N--C--~

S R
wherein R represents N~

~N-~

1 0 =-- r R---~
R1 \R2 N~
~ Il--R3 __ .____--3 Il--R4 \"( , R4--~ it------ ( j t il ~1 ¦ ~a----S . ' ~ ' ' ~ R

-Rs o r - R6~ R7 / ~ 9 \D~ . ' r~ , wherein RO, Rl and R2 independen~ly represent hydrogen, chloro or bromo, provided that at least one of RO, Rl and R2 repre- .
sents chloro or bromo;
X represents oxygen or sulfur;

.72A -4-1&77~

R3 and R4 independently represent hydrogen, chloro, bromo or methyl, provided that R3 represents hydrogen when X
re~resents oxygen;
R5 represents hydrogen, chloro, bromo, fluoro or trifluoromethyl;
and either 1) R and R represent hydrogen, one of R8 and R9 represents hydrogen, and the other of R8 and R9 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 R9 independen.ly represent chloro, fluoro or bromo, or

3) R6 and R8 represent hydrogen, and R7 and R9 independently represent chloro, fluoro, bromo or trifluoromathyl, or

4) R7 and R9 represent hydrogen, and R6 and R8 independently represent chloro, fluoro or bromo, or

5) R7, R and R represent hydrogen, and R repre-sents chloro, fluoro or bromo, or

6) R6, R and R9 represent hydrogen, and R repre-sents acetamido, nitro, amino or cyano;
R10 and Rll independently represent hydro~en, chloro, fluoro, bromo, methyl or methoxy;
provided that.:

77~41 , l) one o~ RlO and Rll may represent hydrogen, iE and ..
only if the other represents methoxy;
2) at least one of R and R must represent methyl .
or methoxy, unless .
a) R8 does not represent hydrogen, and R6, R7 and R represent hydrogen, or b) R6 and R8 represent hydrogen, and one or .
both of R7 and R9 represent trifluoromethyl;
3) neither R8 nor R9 represents phenyl, acetamido, methoxy, nitro, amino, cyano or substituted phenyl unless both RlO and Rll represent methoxy; .
4) two of ~7, R8 and R9 represent hydrogen unless .
both Rl~ and Rll represent méthyl or methoxy; .
S~ both RlO and Rll represent methoxy or methyl when R represen_s pyridyl, naphthyl, furyl or thienyl;
6) both R10 and Rll represent methoxy when R repre-sents benzothiazolyl, benzoxazolyl, benzothienyl, benzofuryl, isoxazolyl, qui'nolyl or thiazolyl.
The present invention also provides a process ~or preparing the compounds of Formula I, wherein R, R and Rll are as defined above, which comprises either l) acylatinq a 2-amino-5-R-substituted 1,3,4-thiadiazole of the formula ~ H II ~ ¦

wherein R is as defined in ~ormula I, except that R does not represent amino- or acetamido-phenyl, .', ,.

:.. : , :., - . ; ~:
. . - ~ .

77~

. .
with a benzoyl halide oE the formula R 1 o ¦
l ! . I ~
H~ l o-C--~
' ~

wherein Halo refers to chloro or bromo, and R10 and Rll are as defined in Formula I, or 2) cyclizing a compound of the formula lQ
R10 ~, ' '' ' -I

X-NI~--C--NH C~ IV ¦ ~ ~
~l wherein R10 and R I are as defined in Formula I, and X
represents O ~.
r R-C-NH- or R-CH-N- . ¦
wherein R is as defined in Formula II, with a dehydrating O
agent, when X represents R-C-NH-, or with an oxidizing agent, when X represents R-CH=~
and optionally reducing a compound of Formula I wherein R8 represents nitro to obtain a compound wherein R8 repre-sents amino, and further optionally acylating the compound wherein R8 represents amino to prepare a compound wherein .
R represents acctamido. -Novel insecticidal methods and insecticidal com-positions makin(l use oE the compounds are also provided.

~ ~77~4~ ~

Throughout this document, all quantities are measured in the metric system, and temperatures are on the Celsius scale. All proportions and percentages are by weight. The term halogen refers to fluoro, chloro, bromo and iodo.
A number of specific classes and types of com-pounds of Formula I constitute preferred classes. A par-ticularly preferred class of compounds are those which are of the formula R~Z~ N--C---~ ~- V

`.
wherein R 2 represents N~
=_= I .
~N~

1~1 5/ "Rl 6 Rl' o~

/-===~\ . ..
;1 P R20 R~O
---~ ---R2 ~-' \`-'~

X-4472A -,-~ ` lC~7709:~ ~

f___~_____~___R2~
~ , or R22 ~R23 .--r~4 'R~5 wherein R15, R16, R 7, R13 and Rl9 independently represent hydrogen, chloro or bromo, provided that at least one of R15 and R16, or at least one of R 7,. R and R 9 represents chloro or bromo;
X represents oxygen or sulfur;
R20 represents hydrogen, chloro, bromo or methyl;
R21 represents hydrogen, chloro, bromo, fluoro or -trifluoromethyl;
and either - -1) R22 and R 3 represent hydr~gen, one of R and R25 represents hydrogen, and the other of R24 and R25 represents hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, hydroxy, phenyl, or ¦
phenyl monosubstituted with bromo, chloro or fluoro, or 2) R22 and R23 represent hydroqen, and R24 and R25 independently represent chloro, fluoro or bromo, or 3) R22 and R24 represent hydrogen, and R23 and R25 independently represent chloro, fluoro, bromo or ~ri~luoromethyl, or ~:-441.!A -9 iQ~

4) R23 and R25 represent hydrogen, and R22 and R24 inde~endently represent chloro, fluoro or bromo, or 5) R , R and R represent hydrogen, and R22 repre-sents chloro, fluoro or bromo;
R13 and R14 independently represent hydrogen, chloro, fluoro, bromo, methyl or methoxy;
provided that: ¦
- 1) one of R13 and R14 may represent hydrogen, if and only if the other represents methoxy; 1:
2) at least one of R and R must represent methyl or methoxy, unless a) R24 does not represent hydrogen, and R22, R23 and R25 represent hydrogen, or .
b) R22 and R24 represent hydrogen, and one or both of R23 and R 5 represent trifluoromethyl;
3) neither R24 nor R25 represents phenyl or substituted phenyl unless both R13 and~R14 represent methoxy;
4) two of R , R and R represent hydrogen unless both R13 and R14 represent methyl or methoxy;
5) both R13 and R14 re~resent methoxy when R repre-sents pyridyl, naphthyl, furyl or thienyl.
Within the above class, a more preferred class includes the compounds wherein R12 represents RZ2~ ~R23 .. ,.

_R24 --- \~R25 -I

,~

. . - .. ~ . ~ . ~ .

( ` ` 1~77~
and a further ~reEerred class includes the compounds wherein both R13 and R14 represent methoxy.
It will be understood that the present invention also includes a number of other different types or classes oE compounds, and also includes insecticidal methods and compositions makinq use of the various classes of compounds.
For example, the followlng preferred classes of compounds are contemplated. Each numbered subparagraph below des-cribes an independent class of compounds; in each class, the variable substituents have the qeneral 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 o~ the group referred to.
Compounds wherein.
1) R represents phenyl;
2) R represents phenyl, or pyridyl; ¦
3) R represents pyridyl, thienyl, furyl, benzothiènyl, benzofuryl, benzothiazolyl, benzoxazblyi, isoxazolyl, ~luinolyl or thiazolyl;
4) R represents phenyl or naphthyl;
5) R represents oyridyl,. benzothiazo]yl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl;
6) R represents thienyl, furyl, benzoxazolyl, benzothia-zolyl, benzothienyl, benzofuryl, isoxazolyl, quinolyl or thiazolyl;

7) one oF R8 and R represents hydro~en, and the other represents halogen or triEluoromethyl;

X-447~A ~11-~7~
(.

8) R arld R9 in(lcpelldently represent chloro, Eluoro or brolllo;

9) R7 and R9 independently represent chloro, ~luoro, bromo or trifluoromethyl;

10) one of R8 and R9 represents hydrogen, and the other represents halogen, triEluoromethyl, methyl or methoxy;

11) R and R represent methoxy;

12) R10 and Rll independently represent methyl or methoxy;

13) R10 and Rll independently represent chloro, fluoro or bromo;
Compounds of subparagraph 11 above wherein: :

14) R represents phenyl;

15) R represents phenyl or pyridyl;

16) R represents pyridyl, thienyl, furyl, benzothienyl, benzofuryl, benzothiazolyl, benzoxazolyl, isoxazolyl, Il.
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, benzo-thiazolyl, ber.zot.hienyl, berzcfuryl, isox~zolyl, quinolyl or thiazolyl;

20) One of R8 and R9 represents hydrogen, and the other represents halogen or trifluoromethyl; .

21) R and R independently represent chloro, fluoro or bromo;

22) R and R independently represent chloro, fluoro, bromo or trifluoromethyl;

23) one of R8 and R9 represents hydrogen, and the other represents halogen, trifluoromethyl, methyl or methoxy;

X-4472~ -12- .

Compounds of subparagraph 12 above wherein:

24~ R represents phenyl;

25) R represents phenyl or pyridyl;

26) R represents pyridyl, thienyl, furyl, benzothienyl, benzoEuryl, benzothiazolyl, benzoxazolyl, isoxazolyl, ~lUinlYl or thiazolyl;

27) R represents phenyl or naphthyl;

28) R represents pyridyl, benzothiazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl;

29) R represents thienyl, furyl, benzoxazolyl, benzothi-azolyl, benzothienyl, benzofuryl, isoxazolyl, quinolyl or thiazolyl;

30) One of R8 and R9 represents hydrogen, and the other represents halogen or trifluoromethyl;

31) R8 and R9 independently represent chloro, fluoro or bromo;

32) R7 and R9 independently represent chloro, fluoro, bromo or trifluoromethyl;

33) one of R8 and R9 represents hydrogen, and the other represents halogen, trifluoromethyl, methyl or methoxy;
Compounds of su.hpara:graph 13 above wherein:

34) R represents phenyl;

35) R represents phenyl or pyridyl;

36) R represents pyridyl, thienyl, furyl, benzothienyl, benzofuryl, benzotniazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl;

37) R represents phenyl or naphthyl;

38) R represents pyridyl, benzothiazolyl, benzoxazolyl, isoxazolyl, quinolyl or thiazolyl;

X-~47~A

(. ' l~t~7~4-~ .

39) R re~resents t~iellyl, ruryl., benzoxazolyl, berlzothi-az~lyl, ~enz~tllierlyl, benz~r-lryl, isoxaz.olyL, ~luinolyl or thiazolyl;

40) One of R8 and R9 represents hydrogen, and the other represents halogen or trifluoromethyl;

41) R and R independently represent chloro, fluoro or bromo;

42) R7 and R9 independently represent chloro, fluoro, bromo or trifluoromethyl;

43) one of R8 and R9 represents hydrogen, and the other represents halogen, trifluoromethyl, methyl or methoxy.
Although the above general formula clearly des-cribes 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)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(4,5-dibromo-3-pyridyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide - N-[5-(5-bromo-2-pyridyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(4-chloro-2-pyridyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide N-[5-(5-bromo-3-chloro-2-pyridyl)-1,3,4-thia-diazol-2-yl]-2,6-dimethoxybenzamide N-~5-(3,4,5-trichloro-2-pyridyl)-1,3,4-thia-diazol-2-yll-2,6-dimethoxybenzamide X-~7~ -14-1~'77~

N- 15- (3-furyl)-1,3,4-thiadiazol-2-yl]-2,6-di-melhoxybenzamide N- 1 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-1-naphthyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(2-bromo-1-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-[5-(3-trifluoromethyl-2-naphthyl)-1,3,4-thia-diazol-2-yl]-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]-2-fluoro-6-methylbenzamide N-[5-(3-iodophenyl)-1,3,4-thiadiazol-2-yl]-2-fluoro-6-methoxybenzamide N-[5-(3-methylphenyl)-1,3,4-thiadiazol-2-yl]-2-chloro-6-methylbenzamide N- [5- (3-hydroxyphenyl)-1,3,4-thiadiazol-2-yl]-2-bromo-6-methylbenzamide N- [5- (3-phenylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N- [ 5- [ 3-(3-fluorophenyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide -- 10'77~4~

N-15-14-(3-bromoL~henyl)phenyl]-1,3,4-thiadiazol-2-yll-2,6-dimethoxybenzamide N-[5-[4-(2-chlorophenyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-[3-(4-chlorophenyl)phenyl]-1,3,4-thiadiazol-2-yll-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-2-yll-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-dibromophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(3-chloro-5-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yll-2,6-dimethoxybenzamide N- [5-(3-bromo-5-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-6-methylbenzamide N-[5-(2,4-dibromophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-difluorobenzamide N-[5-(2-bromo-4-fluorophenyl)-1,3,4-thiadiazol-2-yll-2,6-dimethoxybenzamide N-[5-(4-bromo-2-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2-methoxybenzamide '77~

N-15-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dichlorobenzamide N- [ 5- ~ 2-bromophenyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-6-methylbenzamide N- [5- (6-chloro-1-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-1-naphthyl)-1,3,4-thiadia-zol-2-yl]-2,6-dimethoxybenzamide N- [ 5-(4,5,6-trichloro-3-pyridyl)-1,3,4-thiadia-zol-2-yl]-2,6-dimethoxybenzamide N-[5-bromo-4,6-dichloro-3-pyridyl)-1,3,4-thia-diazol-2-yl]-2,6-dimethylbenzamide N- [ 5-(3,4,5-tribromo-2-pyridyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-6-methylbenzamide N- [ 5-(3-bromo-4,6-dichloro-2-pyridyl)-1,3,4-thiadiazol-2-yl]-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-thiadia-zol-2-yl]-2-methoxy-6-methylbenzamide N-15-(4,5-dichloro-2-thienyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(2-benzoxazolyl)-1,3,4-thiadiazol-2-yl]-2,6-d i.methoxyt)enz.llTli(le N-15-(2-benzo[blthienyl)-1,3,4-thi<ldiazol-2-yl]-2,6-dimethoxybenzamide X-4472~ -17-N-[5-(2-benzo[b]~uryl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(5-isoxazolyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(2-thiazolyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(4-iodophenyl)-1,3,4-thiadiazol-2-yl]-2-chloro-6-methoxybenzamide . N-15-(4-iodophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dichlorobenzamide N-15-~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]-2,6-dimethylbenzamide N-[5-(4-chloro-1-naphthyl)-1,3,4-thiadiazol-2-yl]
2-methoxy-6-methylbenzamide N-[5-(2-furyl)-1,3,4-thiadiazol-2-yl]-2,6-di-. methylbenzamide ~ -[5-(5-bromo-3-furyl)-1,3,4-thiadiazol-2-yl]-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-thiadia-zol-2-yl]-2,6-dimethoxybenzamide - N-[5-(5-chloro-2-benzo[b]furyl)-1,1,4-thiadiazol-'-yll-~,h--limcthoxyben7.amidc N-l5-(7-methyl-~-bcnzolblfuryl)-l,3,4-thiadiazol-2-yll-2,6-dimcthoxybenzamide , 'I'he pr~erred com~oullds oE Formula I are ~-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yll-2,6-dimethylbenz-ami.de, N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N- [5-(4-fluorophenyl)-1,3,4-thiadiazol-2-ylJ-2,6-dimethylbenzamide, N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide, N- [ 5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-LS-(3-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(3-chlorophenyl)-1,3,4-thiadiazol-~-yll-2,6-dimethoxybenzamide, N-[5-[3,5-bis(trifluoromethyl)-phenyll-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, and (4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.
The compounds of Formula I are made by processes which are preserltly known or are analogous to presently-known processes. All of the compounds are readily made by the acylation of 2-amino-5-R-substituted 1,3,4-thiadiazoles of the formula - 20 R---\ --NH II

~. ~S/ 2 wherein R is as defined in Formula II above, with benzoyl halides of the formula R' ~
Ha i o-C~

R7 1 ~
wherein ~alo refers to chloro or bromo, and R10 and R
are as defined in Formula I, ( 1~77~
and optionally reducinq a compound of Formula I wherein R8 represents nitro to obtain a compound wherein R8 repre-sents amino, and Eurther optionally acylating the compound wherein R8 represents amino to prepare a compound wherein R represents acetamido.
The acylation step is carried out in the presence of a base in a reaction solvent such as tetrahydrofuran, dimethylEormamide, dimethylsulfoxide or diethyl ether.
The preferred base is sodium hydride, although organic bases such as pyridine, triethylamine and triethanolamine may be used, as can inorganic bases including sodium hydroxide, potassium carbona~e and lithium bicarbonate. The tempera-ture range of the re~ction is from about -10 to about 50, preferably from abou, 0 to about 25.
The intermediate aminothiadiazoles are prepared by reactions which are now well known. In general, they are prepared either by oxidative cyclization of a thiosemicar-r-bazone, 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 I, wherein R, R and R
are as defined above, are also prepared by cyclizing a compound of the formula S O
X-N~C-NH-C~ - IV

wherein R10 and Rll are as defined in Formula I, and X
3() rcpresents - . :

3 ~77~34~ .

o R-C-NI 1- ot R-CH=N-wherein R is as deEined in Formula II, with a dehydrating o agent, when X represents R-C-NH-, or with an oxidizing agent, when X represents R-CH=N-, and optionally reducing a compound oE Formula I wherein ~8 represents nitro to obtain a compound wherein R8 represents amino, and further option-ally acylating the compound wherein R8 represents amino to prepare a compound wherein R8 represents acetamido.
Useful dehydrating agents include phosphoric acid, -formic acid, phosphorus pentachloride, phosphorus pentoxide in the presence o' a strong acid, and benzoic and alkanoic acid chlorides and acid anhydrides. The preferred dehy-drating agents are the strong acids, particularly methane-sulfonic acid and concentrated sulfuric acid.
Dehydrative cyclizations are run at temperatures from about 20 to about 80, preferably ~t room temperature.
It is usually preferred to carry out the reactions without solvent, although solvents including the halogenated ben-zenes and the halogenated alkanes, including chlorobenzene, the dichloroben..eres, chl~roform afid 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. In general, X~ 7~ -21-(~
however, temperatures Erom about 50 to about 100 may be used i~ convenient.
It is preferred to prepare compounds having an amino or acetamido group on a phenyl R group by first pre-paring the corresponding nitro-substituted compound, and reducing the nitro group by hydrogenation, using a hydro-genation catalyst, preferably a noble metal catalyst, to Eorm the amino-substituted compound. The amino group is acylated with 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 typical compounds, and the following preparations show the synthesis of typical starting compounds. In all 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 l-(4-chlorobenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemicar-bazide ~ solution of 0.76 g. of ammonium thiocyanate in 20 ml. oE chlorobenzene was heated to 70 in a lO0 ml.
flask. ~fter a Eew minutes, 2.0 g. of 2,6-dimethoxybenzoyl chloride in 30 ml. of chlorobenzene was added dropwise, and X-4472~ -22-~ 7~
(. , .

the mi.Yture w~s ~tirred ~or 15 minutes art~r the addition was complet~. 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-(2,6-dimethoxybenzoyl)thiosemicarbazide, m.p. 206-208.
TheoreticalFound C51.84~ 52.12%
H 4.09 4.35 N 10.67 10.67 Exa_~
N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide 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 collectedr dried and r~crys-tallized from ethyl acetate to proauce 0.45 g. of N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenz-amide, m.p. 238-240C.
TheoreticalFound C54.33~ 54.01%
~13.75 3.84 N 11.18 11.22 X-4472A -~3-!

: ~ -' ( ~377041 ['r paration 2 L--(4-hydroxybenzoyl)-4-(2,6-~imetho~ybenzoyl)thiosemicar-ba - Lde ~ 2.0 c~. portion oE 2,6-dimethoxybenzoyl chloride was dissolved in 20 ml. oE tetrahydroEuran, and was added to 0.76 ~. oE ammonium thiocy~nate in 10 ml. oE tetrahydroEuran at the reElux temperature. AEter the addition was complete, thc mixture was stirred at reflux temperature for 15 min-utes, and then 1.5 g. of 4-hydroxybenzoylhydrazine in 20 ml. -~
of tetrahydrofuran was added. The reaction mixture wasreEluxed for 30 minutes more, cooled, and evaporated under v~cuum to produce an oily residue which consisted largely of 1-(4-hydroxybenzoyl~-4-(2,6-dimethoxybenzoyl)thiosemicar-bazide.
Example _15-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-bonzamide 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 ~ourod into 300 ml. of ice water, and the p~l was adjusted with ammonium hydroxide to 7.5. A precipitate separated, which was collected and recrystallized from acetone to produce 2.5 ~ oE N-15-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yll-2,6-dimethoxybenzamide, m.p. above 260.
TheoreticalFound C57 13~ 56.98 H 4.23 3.96 N 11.76 11.52 ~-~4l;~

~ 77{~
r.x N-[5-!4-pyridyl)-1,3,4-thiadiazol-2-yll-2~6-dimeth benzamide Following the process of E~amples 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-dimethoxybenzoyl)thiosemi-carbazide.
The thiosemicarbazide, a liquid, was stirred while 20 g. of methanesulfonic acid was added dropwise with cooling A~ter 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~-1,3,4-thiadiazol-2-yl]-2,6- ~ -dimethoxybenzamide, m.p. 241-243.
- Theoretical Found - C 56.13% 55.90%
H 4.12 4.21 -N 16.36 )16.47 Example 4 _ ., N-[5-(5-chloro-2-benzo[blthienylj-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide A 4-g. portion of 1-[(5-chloro-2-benzo[blthienyl)-carbonyll~4-(2,6-dimethoxybenzoyl)thiosemicarbazide, pre-pared 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,~-thiadiazol-2-yl~-2,6-dimethoxybenzamide, m.p. ~ 260.
Theoretical Found C52.84~ 52.62%
H 3.27 3.48 N 9.73 9.78 X-447~ -25-- . ~ . . . :

1~41 Example _ I
_-l5-~2-benzothiazolyl)-1,3,4-thiadiazol-2-yll-2!6-dimethoxy-benzamide A 4.2 g. portion of 1-[(2-benzothiazolyl)car-bonyll-4-(2,6-dimethoxybenzoyl)thiosemicarbazide was added dropwise with stirrinq to 16 cl. of methanesulfonic acid.
The product was 2.6 g. o~ N-[5-(2-benzothiazolyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, m.p. > 260.
TheoreticalFound C54.26% 54.38%
H 3.54 3.72 N 14.06 13.81 -Example 6 N-[5-(2-chlorophenyl)-1,3_4 thiadiazol-2-yl]-2,6-dimeth~y~
benzamide To iO g. of methanesulfonic acid was added 1.4 g.
oE 1-(2-chlorobenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemi-carbazide while the temperature was l~eld at or below 35.
The product of the reaction was 1.2 g. of N- [5-(2-chloro-20 phenyl)-1,3,4-thiadiazol-2-yl]-2,6-dirnethoxybenzamide, m.p. 235-237~
TheoreticalFound C54.33% 54.57 H 3.75 3.95 N 11.18 11.19 x-447~ -26-~$7?'~
;.....
~xam~le _ N-l5-~2-cluinolyl)-1,3,4-thiadiazol-2-yll-2,6-dimethoxy-benzamide -A 2.0 g. portion of 2,6-dimethoxybenzoyl chloride was reacted with 1.9 g. of (2-quinolyl)carbonylhydrazine to form the corresponding l-(2-quinolylcarbonyl)-4-(2,6-di-methoxybenzoyl)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 C61.21~ 61.09'~
~4.11 4.30 N14.28 13.95 Example 7a N-15-(3-quinolyl)-l,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide Following the process described above, 2.09 g.
of 2,6-dimethoxybenzoyl chloride was~reacted with (3-quinolyl)carbonylhydrazine to form l-(3-quinolylcarbonyl)-4-(2,6-dimethoxybenzoyl)thiosemicarbaz~de, which was cyclized with methanesulfonic acid to produce 1.7 g. of N-[5 (3-quinolyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, m.p. 242-243.

., .

Theoretica_ Found C 61.22% 60.97%
l~ 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.

X-447~ 8-The following example illustrates a typical cyclization with an oxidizing agent.
Example 7b N-15-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide A 3.78 q. portion of 4-chlorobenzaldehyde, 4-(2,6-dimethoxybcll~oyl)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-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy- ;
benzamide, m.p. 246-248.
Theoretical Found C54.33% 54.19%
H 3.75 3.47 N 11.18 11.27 X-447~ 9_ t 1~:377~3 ( The following preparation illustrates a typical preparation of a thiadiazole startin~ compound by oxidative cyclization with ferric chloride.
Preparation _ 2-amino-5-(4-pyridy_) 1,3,4-thiadiazole A 9.0 g. portion of 4-pyridylaldehyde, thiosemi-carbazone, 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 hydro-ch~oric 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 hydro-chloric 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 r i ethanol. The wash liquid was then eyaporated to dryness, and the resulting residue was recrystallized from acetone.
20 The combined yield was 1.3 g. of 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole, m.p. 234-236.
Theoretical Found C 47.18~ 47.02%
H 3.39 3.45 N 31.44 31.39 'I'he ~ollowing two preparations illustrate prep-aration o~ starting com~ounds by dehydrative cyclizations with methanesulfonic acid and with sulfuric acid.

107'~41 Preparation _ 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole ~ 50 g. portion of 1-(4-chlorobenzoyl)thiosemi-carbazide was slowly added with stirring to 330 g. of methanesulfonic acid, while the temperature was held below 35C. The mixture was stirred for 5 hours after the addition was complete, and was then poured into a liter of ice water.
The pll of the mixture was adjusted to 7.5 with ammonium hydroxide, and the precipitated solids were removed by [iltration and dried. The solids were then recrystallized from ethanol. Repeated recrystallizations produced a total oE 33.3 g. of 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole, which was positively identified by nuclear magnetic reson-ance analysis.
TheoreticalFound C45.39% 45.61 ~ 2.86 3.12 N 19.85 19.70 Preparation 5 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole To 48 9. 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 tem-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 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole, m.p. 221C.

X-~7 ' :: ' 1~77041 Thcorctical ~ound C 45.39% 45.28%
Il 2.86 2.63 N 19.85 20.02 The following examples are typical of the acyla-tion of aminothiadiazoles to produee eompounds of this invention.
Example 8 N-[5-(4-ehlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-diehloro-benzamide To 4 g. of 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole in 200 ml. of tetrahydrofuran at room tempera-ture was added, with cooling and stirring, 1.85 g. of 50 percent sodium hydride in oil. The cooling mantle was then removed, and the reaction mixture was stirred for 15 min-utes, 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 deeomposed by the addition of water. The solvent was evaporated, and the residue was suspended in water and aeidified with hydrochloric acid.
The solids were removed from the acid solution by filtra-tion, dried and recrystallized from ethyl acetate to produce 4 g. of N-~5-t4-chlorophenyl)-1,3,4-thiadiazol-2-yll-2,6-dichlorobenzamide, m.p. ~260C.
TheoreticalFound C 46.84% 46.60%
H 2.10 1.90 N 10.92 10.75 X-~47~ -32-1,0~70~:~

~xample 8a N-15-(3-hydroxypherlyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-_ benzamide To 1.9 g. of 2-amino-5-(3-hydroxyphenyl)-1,3,4-thiadiazo]e in lO() ml. of pyridine was added 2.2 9. of ~,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)-1,3,4-thiadiazol-2-yl~-2,6-dimethoxybenzamide, m.p. 243-245.
Theoretical Found 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.

X-447~A -33-1(~77()4 Examplc 9 N- 15-(1-naphthyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide Example 10 N- 1 5- ( 2,4-dichlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-di-methoxybenzamide ~xample 11 N-15-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-am i I:xample 12 N-15-(3,5-dichlorophenyl)-1,3,4-thiadiazol-2-ylJ-2,6-di-methoxybenzamide Example 13 N- 15-(3-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide Example 14 N- [ 5-(4-pyridyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenz-amide Example 15 20 N-l5-(4-cyanophenyl)-1,3,4-thiadiazol-2-yll-2,6-dimethoxy-benzamide Example _ N- [ 5-[3,5-bis(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example _ N- [ 5-(2-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide Example 18 N-(5-phenyl-1,3,4-thiadiazol-2-yl)-2,6-dichlorobenzamide X-447~A _34_ .
.: : : , .
~.:... .. .: .. :

l077n~l Example 19 N-~5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dichlorobenzamide ~xa_ple 20 N-l5-(4-chloropllcnyl)-1,3,4-thiadiazol-2-ylJ-2-chloro-6-methylbenzamicle Example 21 N-l5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-difluoro-benzamide Example 22 N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethyl-benzamide Example 23 N-[5-(4-bromophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dichloro-benzamide Example 24 N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dichloro-benzamide Exa_~ 25 _ _ _ 20 N-[5-(4-chlorcphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide Ex_mple 26 N-[5-(3,4-dichlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-di-methylbenzamide ~xample 27 N-~5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethyl-benzamide Example 28 . . _ .
N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-30 dimethylbenzamide X-4472~ -35-., : - .. . .
. -, . ' ~: ' 10'770~
_xample 29 N-15-(4-bromophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethyl-benzamide L~xample _ N-(5-phenyl-1,3,4-thiadiazol-2-yl)-2,6-dimethylbenzamide Example _ N-15-(4-~luorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-~enzamide l.xam~-le 32 . . _ N-~5-(2-thienyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenz-amide Example _ N-[5-(2-furyl)-1,3,4-thiadiazol-2-yl}-2,6-dimethoxybenzamide Example 34 N-[5-(4-methylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy- ;
benzamide Example _ N-[5-(4-phenylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide Fxample 36 N-15-(3-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Example _ N-l5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide Example 38 _ N-l5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide X-4~7~ -36-1(3'77t)4~L

Exa ple 39 N-(5-phenyl-1,3,4-thiadia7.ol-2-yl)-2,6-dimethoxybenzamidc Example 40 N-[5-(4-chiorophenyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-benzamide Example 41 N-[5-(3-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl)-2,6-dimethylbenzamide E_ample 42 10 N-[5-[4-(4-bromophenyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide 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-yl]-2,6-dimethoxy-benzamide Example 45 N-[5-[4-(4-fluorophenyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide Lxample 46 N-[5-(2-naphthyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide E_am~le 47 N-[5-(3,4-dichlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-di-methoxybenzamide X-4472~ -37-)41 Fxample 48 N- 1 5- ( 3-hydroxyphenyl)-1,3,4-thiadiazol-2-yll-2,6-dimethoxy-benzamlde Fxample 49 N-15-(4-methoxyphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide~xample _O
N-15-(4-nitrophenyl)-1,3,4-thiadiazol-2-yll-2,6-dimethoxy-benzamide F.xample 51 N- 1 5- ( 3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethyl-benzamide Example 52__ N-15-(2-naphthyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethyl-benzamide l~xample 53 N-15-(3,5-bis(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide Example 54 20 N- 1 5- ( 3-thienyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide l~xample 55 N- 15-(3-furyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide ~xample 56 N- 15-(5-bromo-2-furyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide ~x_mple 57_ N- 15-(4-iodophenyl)-1,3,4-thiadiazol-2-yl~-2,6-dimethoxy-benzamide X-4~72A -38-1077~
~xample 58 N-l5-(5-bromo-3-pyridyl)-1,3,4-thiadiazol-2-yl]-2,6-di-methoxybenzamide ~xa ~ _ N-¦5-(5-chloro-2-thienyl)-1,3,4-thiadiazol-2-yl]-2,6-di-methoxybenzamide ~xample __ N-[5-(3-isoxazolyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide X-447~A -39_ ~ o ~n ~ ~n :7; co ~ ~n ~r ~ o o o ~ n co o~ ~n o~ O O ~ O ~ ~D ~n c~

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It will be understood that the 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.
l~`xample 61 N-(4-aminophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-benzamide ~ 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 dimethyl-formamide, 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~.
TheoreticalFound C57.30% 56.95 H 4.49 4.67 N 15.73 15.41 Example 62 N-15-(4-acetamidophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzami 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 X-447~ -44-~077~

reaction mixture was cooled to hold the temperature below 35". ~fter the acldition, the mixture was stirred for 16 hours at room temL~erature, and was evaporated to ~ryness under vacuum. The residue was recrystallized from ethyl acetate to give 0.25 g. of N-[5-(4-acetamidophenyl)-1,3,4-thiadiazol-2-ylJ-2,6-dimethoxybenzamide, m.p. 211-213.
Theoretical Found C 57.42% 57.70%
l~ 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 applica-tion 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 com-prising 1:l anhydrous ethanol:acetone containing 23 g. of Toximul R an(i 13 c3. Toximul S per liter. (Toximuls are trad(?marks ~or sulfonate/nonionic blended surfactants pro-duced by Stepan Chemical Co., Northfield, Illinois, U.S.A.) Each sample was then dispersed in 9 ml. of water to provide X-4472~ -45-a 1000 ppm. concentration of the test compound. This dis-persion was diluted with water to produce lower concentra-tions, when desired. The dispersion was sprayed evenly over ten-day-old bean plants and the plants were set aside until dry.
Lcaves 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 were held in the 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.
0 = no control 1 = 1-7 larvae dead 2 = 8-14 larvae dead 3 = 15 larvae dead The following table reports the results of testing typical compounds.

X-4472~ -46-1~70~1 Table 1 .
Compound of Appln. Mexican bean Southern Example Rate beetle armyworm No.ppm. 4 day 7 day 4 day 7 day -100 1 ~ 1 1 7a 1000 2 3 0 2 X-4472~ -47_ -:
.

10'~7~

Table _ Continued Compound of Appln. Mexican bean Southern ~xampleRate beetle armyworm ::
No.ppm. 4 day 7 day 4 day 7 day 13 lO00 l 2 3 3 lO0 0 2 2 2 lO00 0 0 2 2 16 lO00 l l 3 3 lO0 0 1 3 3 l l 3 3 l l 2 2 0 1 l 2 lO0 l 2 1 0 l 2 0 0 l 2 0 0 lO0 0 0 0 1000 l 2 3 3 lO0 l 1 2 2 21 lO00 0 0 2 2 22 lO00 2 2 3 3 lO0 l 2 2 3 2 3 l 2 ~o 25 l 2 X-447~A -48-Table 1 Continued Compound of Appln. Mexican bean Southern ExampleRate beetle armyworm No.ppm. 4 day 7 day 4 day 7 day X-4472~ -49-~(~77~41 `~`

Table 1 Continued Compound of Appln. Mexican bean Southern ~xampleRate beetle armyworm No.ppm. 4 day _ day 4 day 7 day 100 0 o o o 33 1000 2 2 2 2 ~.

2.5 X-4472~ 50_ 1~77~)41 Table 1 Continued Compound o~ ~ppln. Mexican bean ~Southern L:xamplcRate beetle armyworm No.ppm. 4 day 7 day 4 day 7 day 100 0 0 1 2 :~

44 1000 0 2 1 3 X-4472~ -51-- . - : . . .. .

1~77~41 l`ab1e 1 Continued Compound of Appln. Mexican bean Southern ~xampleRate beetle armyworm No.ppm. 4 day 7 day 4 day 7 day 100 ~ O

100 0 0 3 3 ~ -5~ 1000 1 3 0 0 100 0 o o O

X-4472~ -52-107'7041 Table 1 Continued (:~om,~ouncl Or Appln. Mexican bean Southern l.xample Rate beetle armyworm No.ppm. 4 day 7 day 4 day 7 day 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.

: :, . :

Tabl~ 2 _ o u ll (l ~f ~,xample Concentration No.ppm. Control X-4472~ -54-. . : .

1C~7704~

Table 2 Continued Compound of ExampleConcentration No. ppm. Control 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 un-treated controls had emerged.
Table _ -Compound %
ofAppln. Control Control Example Rate of of _ No. ppm. LarvaeEmergence ~5 50 0 1C~7704~

Test 4 Mexican bean beetle life cycle test This test was performed according to the method ~escribed immediately above, except that the larvae were 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 Appln. Percent Control Example Rate No. ppm. 3 day 8 day 21 day 1' 1000 11 ~100 100 'I'est 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 X-4472~ -56-107~

homogeni~ed beef liver to give 100 ppm. concentration.
Iower 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-day-old blowEly 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 Appln.Control ExampleRate of No. ppm.Emergence O
~7 I()0 4~
]o O

~.07704~

Table 5 Continued Compound IL
of Appln. Control E:xampleRate of No. ppm. Emergence .

0 , 20 Test _ greater wax moth larvicide test This test was performed to evaluate certain com-pounds against the greater wax moth, ~alleria mellonella, a parasite of beehives.

Sufficient compound to give the desired concen-tration 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 X-4~7~ -58-.

`1077041 bctween three petri dishes t to each of which was added five secon(l- and third-instar larvac. The dishes were held in the controlled room for seven days, and percent control o~
the larvae was determined, compared to controls.
Table 6 Compound of Appln.
Example Rate No. ppm.Control . 1 500 0 12.5 0 12.5 0 12.5 0 12.5 0 X-4472~ -59_ 107704~

Table 6 Continued Compound of Appln. .
Example Rate No. ppm. Control 12.5 0 100 .10~

12.5 13 1 0 ' .. ;.

2.5 37 500 :-:`

12.5 0 12.5 0 2.5 0 - : , . . .

1C377~4 `~

I'est 7 Mexican bean beetle sterilization test -This test was conducted by exposing adult Mexican bean beetles to bean plants treated with dispersions con-taining lOOO 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 ~0 to 30 eggs each were collected and incubated. ~one o~
the eggs from beetles fed on plants treated with the compound of Example 36 hatched. The compound completely sterilized the ~eetles which consumed the treated foliage.
Test 8 lepidoptera on field-grown broccoli Compounds of Formula I were tested against lepi-doptera 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 th~)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 o~ about 1000 liters per hectare.
The compounds were applied three tlmes 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 com-pounds is described in the tables below as percent reduction in the number of insects, compared to the number of insects infesting untreated control plants.

.

X-447~A -61-"

~ , 1077~41 The broccoli crop was infested primarily by two species, Pieris rapae and Trichoplusia ni. Control of these two species is reported in the tables below, as is the control of all species of lepidoptera as a group.

X-447~ -62-.

1C~77041 .
~ O ~ ~ ~ D ~ ~ O O ~ ~ ~ 1-- Cl) ~D ~ ~D ~
.~

-'1 o ~
o U~
~r co u~ ~ ~ ~ ~o <~ O ~ r~ u~ 1-- ~ ~r a~
O~ ~ ~ ~ ~ In 1-- ~ ~ 1-- u~ ~ ~ ~ In ~ In 1-- u~ 1--.~~ o o ~.~
,, c~ C~E~ .
. r a) ~` ~ 3 ~' ~ ~
a~ ~ ~ o o o o a~ D In O
~1 ~ r` ~ ~ o o o ~ ~ o ~, . a), ,, H

~. ~..............
p~ ~ ~ o o o ~ o o o ~ o o o ~ o o o ~ o o o ~

ro :
: ~
~ .
O ~ ~ O ~ ~ ~ ~D 00 -~o ~; ~ ~ ~ ~
c~ x X-4472A -63- `:

.. . . .
-:, . : ` . ; .
-:..... . '. :
` .
:.': ' ' : '- :.:
:` . ` ..... .. ` : ,~:

7704~

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 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 RatePercent No. kg./ha.Control 1 0.28 66 0.56 81 1.1 97 2.2 97 16 0.28 97 0.56 97 1. 1 100 2.2 100 22 0.28 65 0.56 81 1.1 94 2.2 97 36 0.28 75 0.56 88 1.1 97 2.2 97 38 0.28 97 0.56 100 1 . 1 100 2.2 100 The above illustrative data show the potent in-se(ticidal eEEect: ~E the compounds of Formula 1. ~nto-mologists 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, A~riotes species, Sitophilus oryzae, Nodonota ~uncticollis and Conotrachelus neruphar; Diptera such as Musca domestica, Stomoxys calcitrans, Haematobia irritans, rhormia regina, llylemya brassicae and Psila rosae; Lepi-doptera, such as Laspeyresia pomonella, Euxoa species, ~lodia interpunctella, Tartricidae species, Heliothis zea, Ostrinia nubilalis, Hellula rogatalis, Trichoplusi_ ni, Thyridopteryx ephemeraeformis, Malacosoma americanum and Spodoptera frugiperda- and Orthoptera, such as Blattella germanica and Periplaneta 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 insecticidally-effective 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 X-447~ -65-~077~4~

textiles, paper, wood products and the like are readily controlled by applying a compound tc such products. The compounds can similarly be effectiv~ly 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 neces-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 oC treated insects.
Thc cxtcnt of po~ulation reduction accomplished by a compound depends, of course, upon the application rate of ., : - .

1~77041.

the compound. At least an insecticidally-effective amount must be used in all cases. The term "insecticidally-efEective amount" is used to describe an amount which is sufficient to cause a measurable reduction in the treated insect population. Insecticidally-effective amounts are found, in general, in the range from about 1 to about 1000 ppm.
It will be understood that application rates of insecticides are usually measured in terms of the concen-tration of the insecticide in the dispersion in which it isapplied. The application rate is measured in this way becau'se it is most convenient to apply a sufficient amount ' of the dispersion to cover the foliage,'or other substance to be treated, with a thin film of the dispersion. The amount of dispersion applied is thus dependent upon the surface area of the ingestable substance to be treated, and the amount of the compound depends on its concentration in the dispersion.
The dispersions in which the compounds are applied are prepared from typical insecticidal compositions which are, however, novel because of the presence of the novel compounds of this invention. Most widely useful are aqueous dispersions prepared by mixing a small amount of a concen-trated insecticidal composition with an appropriate quantity of water to qive the desired concentration of the compound.
Such concentrated water-dispersible compositions, containing in general from about 5 to about 90 percent of the compound, are usually in the form of emulsifiable concentrates or wettable powders.

1~77041 Wettable powders comprise an intimate mixture of the active compound in an inert carrier which is a mixture of a fine inert powder and surfactants. The concentration of the active compound is usually from about 10 percent to about 90 percent by weight. The inert powder is usually chosen from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates.
Effective surfactants, comprising from about 0.5 percent to about 10 percent of the wettable powder, are found among the sulfonated lignins, the condensed naphthalenesulfonates, the naphthalenesulfonates, the alkylbenzenesulfonates, the alkyl sulfates, and nonionic surfactants such as ethylene oxide adducts of alkyl phenol.
Typical emulsifiable concentrates of the compounds comprise a convenient concentration of the compound, such as from about 50 to about 500 g. per liter of liquid, equiva-lent to from about 5 percent to about 50 percent, dissolved in an inert carrier which is a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include the aromatics, especially the xylenes, and the petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, and complex alcohols such as 2-ethoxyethanol. Suitable emul-sifiers for emulsifiable concentrates are chosen from the samc types and concentrations of surfactants used for wcttablc ~)~wdcrs.

X-4~72A -68-10770~1 It is equally practical, when desirable for any reason, to apply the compound in the form of a solution in an appropriate organic solvent, usually a bland petroleum r oil such as the spray oils which are widely used in agri-cutural chemistry.
Further, the compounds may be applied as composi-tions in the forms of dusts and aerosol preparations. Dusts comprise a compound in a finely powdered form, dispersed in a powdered inert carrier. The carrier is usually a powdered 10 clay, such as pyrophyllite, bentonite, a volcanic deposit or montmorillonite. Dusts usually contain concentrations of the compound in the range of from about 0.1 percent to about 10 percent.
Aerosol compositions comprise a compound of Formula I dissolved or dispersed in an inert carrier which is a pressure-generating propellant mixture and packaged in a container from which the mixture is dispensed through an ~`
atomizing valve. Propellant mixtures comprise either low-boiling halocarbons, which may be mixed with organic sol-20 vents, or aqueous suspensions pressurized with inert gases or gaseous hydrocarbons.

Claims (54)

The embodiments of the invention for which an exclusive property or privilege is claimed are as follows:

1. A thiadiazolylbenzamide compound of the formula I

wherein R represents , or wherein R0, R1 and R2 independently represent hydrogen, chloro or bromo, provided that at least one of R0, R1 and R2 repre-sents chloro or bromo;

X represents oxygen or sulfur;
R3 and R4 independently represent hydrogen, chloro, bromo or methyl, provided that R3 represents hydrogen when X repre-sents oxygen;
R5 represents hydrogen, chloro, bromo, fluoro or trifluoromethyl;
and either 1) R6 and R7 represent hydrogen, one of R8 and R9 represents hydrogen, and the other of R8 and R9 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 R9 independently represent chloro, fluoro or bromo, or 3) R6 and R8 represent hydrogen, and R7 and R9 independently represent chloro, fluoro, bromo or trifluoromethyl, or 4) R7 and R9 represent hydrogen, and R6 and R8 independently represent chloro, fluoro or bromo, or 5) R7, R8 and R9 represent hydrogen, and R6 repre-sents chloro, fluoro or bromo, or 6) R6, R7 and R9 represent hydrogen, and R8 repre-sents acetamido, nitro, amino or cyano;
R10 and R11 independently represent hydrogen, chloro, fluoro, bromo, methyl or methoxy;

provided that:
1) one of R10 and R11 may represent hydrogen, if and only if the other represents methoxy;
2) at least one of R10 and R11 must represent methyl or methoxy, unless a) R8 does not represent hydrogen, and R6, R7 and R9 represent hydrogen, or b) R6 and R8 represent hydrogen, and one or both of R7 and R9 represent trifluoromethyl;
3) neither R8 nor R9 represents phenyl, acetamido, methoxy, nitro, amino, cyano or substituted phenyl unless both R10 and R11 represent methoxy;
4) two of R7, R8 and R9 represent hydrogen unless both R10 and R11 represent methyl or methoxy;
5) both R10 and R11 represent methoxy or methyl when R represents pyridyl, naphthyl, furyl or thienyl;
6) both R10 and R11 represent methoxy when R repre-sents benzothiazolyl, benzoxazolyl, benzothienyl, benzofuryl, isoxazolyl, quinolyl or thiazolyl.

2. A compound of Claim 1 wherein R represents ,or

3. A compound of Claim 1 wherein R represents

4. A compound of Claim 1, 2 or 3 wherein R10 and R11 independently represent methyl or methoxy.

5. A compound of Claim 1, 2 or 3 wherein one of R8 and R9 represents hydrogen, and the other represents chloro, bromo, fluoro or trifluoromethyl.

6. Any of the following compounds of Claim 1:
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 N- [5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide

7. A compound of Claim 1 wherein R10 and R11 represent methoxy.

8. Any of the following compounds of Claim 1:
N-[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-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

9. A compound of Claim 1, 2 or 3 wherein R7 and R9 independently represent chloro, fluoro, bromo, or trifluoromethyl.

10. The compound of Claim 1, 2 or 3 which is N-[5-(3,5-bis(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

11. A compound of Claim 1 of the formula V

wherein R12 represents , , , , , , , or , wherein R15, R16, R17, R18 and R19 independently represent hydrogen, chloro or bromo, provided that at least one of R15 and R16, or at least one of R17, R 8 and R19 represents chloro or bromo;
X represents oxygen or sulfur;
R20 represents hydrogen, chloro, bromo or methyl;
R21 represents hydrogen, chloro, bromo, fluoro or trifluoromethyl;
and either 1) R22 and R23 represent hydrogen, one of R24 and R25 represents hydrogen, and the other of R24 and R25 represents hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, hydroxy, phenyl, or phenyl monosubstituted with bromo, chloro or fluoro, or 2) R22 and R23 represent hydrogen, and R24 and R25 independently represent chloro, fluoro or bromo, or 3) R22 and R24 represent hydrogen, and R23 and R25 independently represent chloro, fluoro, bromo or trifluoromethyl, or 4) R23 and R25 represent hydrogen, and R22 and R24 independently represent chloro, fluoro or bromo, or 5) R23, R24 and R25 represent hydrogen, and R22 represents chloro, fluoro or bromo;
R13 and R14 independently represent hydrogen, chloro, fluoro, bromo, methyl or methoxy;
provided that:
1) one of R13 and R14 may represent hydrogen, if and only if the other represents methoxy;
2) at least one of R13 and R14 must represent methyl or methoxy, unless a) R24 does not represent hydrogen, and R22, R23 and R25 represent hydrogen, or b) R22 and R24 represent hydrogen, and one or both of R23 and R25 represent trifluoro-methyl;
3) neither R24 nor R25 represents phenyl or sub-stituted phenyl unless both R13 and R14 represent methoxy;
4) two of R23, R24 and R25 represent hydrogen unless both R13 and R14 represent methyl or methoxy;
5) both R13 and R14 represent methoxy when R repre-sents pyridyl, naphthyl, furyl or thienyl.

12. A compound of Claim 11 wherein R12 represents

13. A compound of Claim 11 or 12 wherein both R13 and R14 represent methoxy.

14. A method of reducing an insect population which comprises applying an insecticidally-effective amount of a compound of Formula I wherein R, R10 and R11 are as defined in Claim 1 to a substance to be ingested by the insects.

15. A method of Claim 14 wherein the amount of the compound is from about 1 to about 1000 ppm.

16. A method of Claim 14 wherein the com-pound is a compound wherein R represents , , , or .

17. A method of Claim 14, 15 or 16 wherein the compound is a compound wherein R represents .

18. A method of Claim 14, 15 or 16 wherein the compound is a compound wherein R10 and R11 independently represent methyl or methoxy.

19. A method of Claim 14, 15 or 16 wherein the compound is a compound wherein one of R8 and R9 represents hydrogen, and the other represents halogen or trifluoro-methyl.

20. The method of Claim 14, 15 or 16 wherein the compound is any of the following:
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 N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide

21. A method of Claim 14, 15 or 16 wherein the compound is a compound wherein R10 and R11 represent methoxy.

22. The method of Claim 14, 15 or 16 wherein the compound is any of the following:
N-[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-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

23. A method of Claim 14, 15 or 16 wherein the compound is a compound wherein R7 and R9 independently represent chloro, fluoro, bromo, or trifluoromethyl.

24. The method of Clalm 14, 15 or 16 wherein the compound is N-[5-(3,5-bis(trifluoromethyl)-phenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

25. An insecticidal method of Claim 14 wherein the compound is of the formula V

wherein R12 represents , , , , , , , or wherein R15, R16, R17, R18 and R19 independently represent hydrogen, chloro or bromo, provided that at least one of R15 and R16, or at least one of R17, R18 and R19 represents chloro or bromo;
X represents oxygen or sulfur;
R20 represents hydrogen, chloro, bromo or methyl;
R21 represents hydrogen, chloro, bromo, fluoro or trifluoromethyl;
and either 1) R22 and R23 represent hydrogen, one of R24 and R25 represents hydrogen, and the other of R24 and R25 represents hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, hydroxy, phenyl, or phenyl monosubstituted with bromo, chloro or fluoro, or 2) R22 and R23 represent hydrogen, and R24 and R25 independently represent chloro, fluoro or bromo, or 3) R22 and R24 represent hydrogen, and R23 and R25 independently represent chloro, fluoro, bromo or trifluoromethyl, or 4) R23 and R25 represent hydrogen, and R22 and R24 independently represent chloro, fluoro or bromo, or 5) R23, R24 and R25 represent hydrogen, and R22 represents chloro, fluoro or bromo;
R13 and R14 independently represent hydrogen, chloro, fluoro, bromo, methyl or methoxy;

provided that:
1) one of R13 and R14 may represent hydrogen, if and only if the other represents methoxy;
2) at least one of R13 and R14 must represent methyl or methoxy, unless a) R24 does not represent hydrogen, and R22, R23 and R25 represent hydrogen, or b) R22 and R24 represent hydrogen, and one or both of R23 and R25 represent trifluoro-methyl;
3) neither R24 nor R25 represents phenyl or sub-stituted phenyl unless both R13 and R14 represent methoxy;
4) two of R23, R24 and R25 represent hydrogen unless both R13 and R14 represent methyl or methoxy;
5) both R13 and R14 represent methoxy when R repre-sents pyridyl, naphthyl, furyl or thienyl.

26. A method of Claim 25 wherein the compound is a compound wherein R12 represents

27. A method of Claim 25 or 26 wherein the com-pound is a compound wherein both R13 and R14 represent methoxy.

28. A process for preparing a thiadiazolyl benzamide compound of Formula I wherein R, R10 and R11 are as defined in Claim 1, which comprises either 1) acylating a 2-amino-5-R-substituted 1,3,4-thiadiazole of the formula II

wherein R is as defined in Claim 1, except that R does not represent amino- or acetamidophenyl, with a benzoyl halide of the formula III

wherein Halo refers to chloro or bromo, and R10 and R11 are as defined in Claim 1, or 2) cyclizing a compound of the formula IV

wherein R10 and R11 are as defined in Claim 1, and X repre-sents or R-CH=N-wherein R is as defined in Formula II, with a dehydrating agent, when X represents , or with an oxidizing agent, when X represents R-CH=N-, and optionally reducing a compound of Formula I wherein R8 represents nitro to obtain a compound wherein R8 represents amino, and further option-ally acylating the compound wherein R8 represents amino to prepare a compound wherein R8 represents acetamido.

29. A process of Claim 28 for preparing a compound of the formula V

wherein R12 represents , , , , , , , or wherein R15, R16, R17, R18 and R19 independently represent hydrogen, chloro or bromo, provided that at least one of R15 and R16, or at least one of R17, R18 and R19 represents chloro or bromo;
X represents oxygen or sulfur;
R20 represents hydrogen, chloro, bromo or methyl;
R21 represents hydrogen, chloro, bromo, fluoro or trifluoromethyl;
and either 1) R22 and R23 represent hydrogen, one of R24 and R25 represents hydrogen, and the other of R24 and R25 represents hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, hydroxy, phenyl, or phenyl monosubstituted with bromo, chloro or fluoro, or 2) R22 and R23 represent hydrogen, and R24 and R25 independently represent chloro, fluoro or bromo, or 3) R22 and R24 represent hydrogen, and R23 and R25 independently represent chloro, fluoro, bromo or trifluoromethyl, or 4) R23 and R25 represent hydrogen, and R22 and R24 independently represent chloro, fluoro or bromo, or 5) R23, R24 and R25 represent hydrogen, and R22 repre-sents chloro, fluoro or bromo;
R13 and R14 independently represent hydrogen, chloro, fluoro, bromo, methyl or methoxy;
provided that:
1) one of R13 and R14 may represent hydrogen, if and only if the other represents methoxy;
2) at least one of R13 and R14 must represent methyl or methoxy, unless a) R24 does not represent hydrogen, and R22, R23 and R25 represent hydrogen, or b) R22 and R24 represent hydrogen, and one or both of R23 and R25 represent trifluoromethyl;
3) neither R24 nor R25 represents phenyl or substituted phenyl unless both R13 and R14 represent methoxy;
4) two of R23, R24 and R25 represent hydrogen unless both R13 and R14 represent methyl or methoxy;
5) both R13 and R14 represent methoxy when R repre-sents pyridyl, naphthyl, furyl or thienyl;
which comprises either 1) acylating a 2-amino-5-R12-substituted 1,3,4-thiadiazole of the formula VI

wherein R12 is as defined above, with a benzoyl halide of the formula VII

wherein Halo refers to chloro or bromo, and R13 and R14 are as defined above, or 2) cyclizing a compound of the formula VIII

wherein R12, R13 and R14 are as defined above, with a dehydrating agent.

30. A process of Claim 28 for preparing a com-pound of Formula I wherein R, R10 and R11 are as defined in Claim 1, which comprises cyclizing a compound of the formula IX

wherein R, R10 and R11 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 I wherein R8 represents nitro to obtain a compound wherein R8 represents amino, and further optionally acylating the compound wherein R8 represents amino to prepare a com-pound wherein R8 represents acetamido.

31. A process of Claim 28 or 29 for preparing a compound of Formula I wherein R10 and R11 are as defined in Claim 1, and R represents , , , or , wherein R0, R1, R2, R6, R7, R8 and R9 are as defined in Claim 1, which comprises acylating a compound of the formula II

wherein R is as defined above, except that R8 does not represent amino or acetamido, with a benzoyl halide of the formula III

wherein Halo, R10 and R11 are as defined in Claim 28 and optionally reducing a compound of Formula I wherein R8 represents nitro to obtain a compound wherein R8 repre-sents amino, and further optionally acylating the compound wherein R8 represents amino to prepare a compound wherein R8 represents acetamido.

32. A process of Claim 28 for preparing a compound of Formula I wherein R10 and R11 are as defined in Claim 1, and R represents wherein R6, R7, R8 and R9 are as defined in Claim 1, which comprises acylating a compound of the formula wherein R6, R7, R8 and R9 are as defined above, except that R8 does not represent amino or acetamido, with a benzoyl halide of the formula wherein Halo, R10 and R11 are as defined in Claim 28, and optionally reducing a compound of Formula I wherein R8 represents nitro to obtain a compound wherein R8 repre-sents amino, and further optionally acylating the compound wherein R8 represents amino to prepare a compound wherein R8 represents acetamido.

33. A process of Claim 28 for preparing a compound of Formula I wherein R is as defined in Claim 41 and R10 and R11 are methyl or methoxy, which comprises acylating a compound of the formula wherein R6, R7, R8 and R9 are as defined in Claim 32, with a benzoyl halide of the formula wherein Halo, R10 and R11 are as defined in Claim 28, and optionally reducing a compound of Formula I wherein R8 represents nitro to obtain a compound wherein R8 represents amino, and further optionally acylating the compound wherein R8 represents amino to prepare a compound wherein R8 repre-sents acetamido.

34. The process of Claim 28 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.

35. The process of Claim 28 for preparing N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide which comprises acylating 2-amino-5-(4-fluorophenyl)-1,3,4-thiadiazole with 2,6-dimethyl-benzoyl chloride.

36. The process of Claim 28 for preparing N-[5-(4-trifluoromethylphenyl)-1,3,4-thia-diazol-2-yl]-2,6-dimethylbenzamide which comprises acylating 2-amino-5-(4-trifluoromethylphenyl)-1,3,4-thiadiazole with 2,6-dimethylbenzoyl chloride.

37. The process of Claim 28 for preparing N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises acylating 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole with 2,6-dimethoxybenzoyl chloride.

38. The process of Claim 28 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.

39. The process of Claim 28 for preparing N-[5-(3-trifluoromethylphenyl)-1,3,4-thia-diazol-2-yl]-2,6-dimethoxybenzamide which comprises acyl-ating 2-amino-5-(3-trifluoromethylphenyl)-1,3,4-thiadiazole with 2,6-dimethoxybenzoyl chloride.

40. The process of Claim 28 for preparing N-[5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises acylating 2-amino-5-(3-chlorophenyl)-1,3,4-thiadiazole with 2,6-dimethoxy-benzoyl chloride.

41. The process of Claim 28 for preparing N-[5-(4-trifluoromethylphenyl)-1,3,4-thia-diazol-2-yl]-2,6-dimethoxybenzamide which comprises acyl-ating 2-amino-5-(4-trifluoromethylphenyl)-1,3,4-thiadiazole with 2,6-dimethoxybenzoyl chloride.

42. The process of Claim 28 for preparing N-[5-(3,5-bis(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises acylating 2-amino-5-[3,5-bis(trifluoromethyl)phenyl]-1,3,4-thiadiazole with 2,6-dimethoxybenzoyl chloride.

43. A process of Claim 28 for preparing a compound of Formula I wherein R10 and R11 are as defined in Claim 1, and R represents , , , or , wherein R0, R1, R2, R6, R7, R8 and R9 are as defined in Claim 1, which comprises cyclizing a compound of the formula wherein R is as defined above, except that R8 does not represent amino or acetamido, and R10 and R11 are as defined in Claim 1, with a dehydrating agent, and optionally reducing a compound of Formula I wherein R8 represents nitro to obtain a compound wherein R8 represents amino, and further optionally acylating the compound wherein R8 represents amino to prepare a compound wherein R8 represents acetamido.

44. A process of Claim 28 or 43 for preparing a compound of Formula I wherein R10 and R11 are as defined in Claim 1, and R represents , wherein R6, R7, R8 and R9 are as defined in Claim 1, which comprises cyclizing a compound of the formula wherein R is as defined above, except that R8 does not represent amino or acetamido, and R10 and R11 are as defined in Claim 1, with a dehydrating agent, and optionally reducing a compound of Formula I wherein R8 represents nitro to obtain a compound wherein R8 represents amino, and further optionally acylating the compound wherein R8 repre-sents amino to prepare a compound wherein R8 represents acetamido.

45. A process of Claim 28 for preparing a compound of Formula I wherein R is as defined in Claim 44 and R10 and R11 represent methyl or methoxy, which comprises cyclizing a compound of the formula wherein R, R10 and R11 are as defined above, except that R8 does not represent amino or acetamido, with a dehydrating agent, and optionally reducing a compound of Formula I
wherein R8 represents nitro to obtain a compound wherein R8 represents amino, and further optionally acylating the compound wherein R8 represents amino to prepare a compound wherein R8 represents acetamido.

46. The process of Claim 28 for preparing N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide which comprises cyclizing 1-(4-chloro-benzoyl)-4-(2,6-dimethylbenzoyl)thiosemicarbazide with a dehydrating agent.

47. The process of Claim 28 for preparing N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide which comprises cyclizing 1-(4-fluorobenzoyl)-4-(2,6-dimethylbenzoyl)thiosemicarbazide with a dehydrating agent.

48. The process of Claim 28 for preparing N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide which comprises cyclizing 1-(4-trifluoromethylbenzoyl)-4-(2,6-dimethylbenzoyl)thio-semicarbazide with a dehydrating agent.

49. The process of Claim 28 for preparing N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-(4-chlorobenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemicarbazide with a dehydrating agent.

50. The process of Claim 28 for preparing N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-(4-fluorobenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemicarbazide with a dehydrating agent.

51. The process of Claim 28 for preparing N-[5-(3-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-(3-trifluoromethylbenzoyl)-4-(2,6-dimethoxybenzoyl)thio-semicarbazide with a dehydrating agent.

52. The process of Claim 28 for preparing N-[5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-(3-chlorobenzoyl)-4-(2,6-dimethoxybenzoyl)thiosemicarbazide with a dehydrating agent.

53. The process of Claim 28 for preparing N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-(4-trifluoromethylbenzoyl)-4-(2,6-dimethoxybenzoyl)thio-semicarbazide with a dehydrating agent.

54. The process of Claim 28 for preparing N-[5-(3,5-bis(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide which comprises cyclizing 1-[3,5-bis(trifluoromethyl)benzoyl]-4-(2,6-dimethoxybenzoyl)thiosemicarbazide with a dehydrating agent.