AU614775B2

AU614775B2 - Substituted azoles and azines, processes for their preparation and their use as herbicides

Info

Publication number: AU614775B2
Application number: AU23568/88A
Authority: AU
Inventors: Friedrich Dr Arndt; Gabriele Dr. Dorfmeister; Wilfried Dr. Franke; Michael Dr. Ganzer; Gerhard Dr. Johann; Richard Dr. Rees
Original assignee: Schering AG
Current assignee: Bayer Pharma AG
Priority date: 1987-10-09
Filing date: 1988-10-07
Publication date: 1991-09-12
Anticipated expiration: 2008-10-07
Also published as: JPH01157977A; KR890006615A; FI884625A0; FI92585C; ES2058206T3; EP0311135B1; EP0311135A2; HUT49356A; JP2765873B2; DE3734745A1; IL87887A; PH27146A; FI884625A; EP0311135A3; CN1032479A; DK563488D0; DE3881468D1; DK563488A; SU1722204A3; FI92585B

Description

'614775 COMONWALT OFAUSTRALIA PA-MU ACT1952 NAME ADDRESS OF APPLICANT: Schering Aktiengesellschaft 170-178 Mullerstrasse 1000 Berlin Federal Republic of Germany NAME(S) OF INqVENTOR(S): Michael GANZER Wilfried FRANKE Gabriele DORFMEISTER :00 0Gerhard JOHANN Friedrich ARNDT Richard REES 0

S

ADDRESS FOR SERVICE: 'GoesDAVIES &COLLTSON Patent Attorneys *1 Little Collins Street, Melbourne, 3000.

COMPLETE SPECIFICATION FOR THE INVENTION ENTITLED: Subst ited azoles and azines, processes for their preparation and their use as herbicides The following statement is a full description of this invention, including the best method of performing it known to me/us:- -2- Description This invention relates to new substituted azoles and azines, processes for their preparation and their use as herbicides.

It is known that certain triazolopyridazine and benzothiazolylazolidines possess herbicidal activity (EP applications 0 176 101 and 0 230 874). However the herbicidal activity of these known compounds is not always sufficient or selectivity problems can occur in important crops.

The object of the present invention is to make new compounds that do not show these disadvantages and have ii* improved biological properties over the known compounds.

i It has now been found that a heterocyclic i substituted azole and azine of formula I

I

I .zin which

R

1 is cyano-C 1

-C

3 alkyl, X is one of the groups -CH(CH 3

-CH

2

-CH=N-,

-CH

2 or with the proviso that when Z Z 2

Z

4 or Z6, X is not Y is hydrogen or fluorine, Z is a heterocyclic group of formulae Z 1 to Z 8 o Cn Cl 0 97E., 910626,immdat.1OO,a:\23568sch.res 7 -3- 0

~K~M

N

z 3 'M4 3

Z

4

U

0 Z 6 *0 4 6 *0 00 @6 S 6006 66 6 *66 0 06 66 0 0 6 60 6 60 66

NH

z 7 0 N 0 @06066 0 *600 4 *6 06 6 06, 0 *6 @6 0 0406 66 6 00 6S Q is CH,

R

1 4 is hydrogen or methyl,

R

3 is hydrogen or methyl, U is oxygen or sulphur, and T is -CH 2 or 910626,immdaL 100,a: \23568sch.res,3 4- 2 .is hydrogen, C -C alkyl, haoC_,__Tk c :ja fly--_OTr -C -alkynyl. surprisingly show an outstanding selectivity to crops whilst at the same time have interesting herbicidal activity.

The expression "halogen" means fluorine, chlorine, bromine and iodiriq. The term "haloalkyl" means that one or Ii more hydrogen atoms u! the alkyl hroup are replaced by halogen.

ill Examples of heterocyclic rings are pyrrole, oxazole.

thiazole. imidazol'e, pyridine, oxazine. thiazine, pyrimidine, pyrazine, triazine, oxadiazine and thiadiazineas well as their di-, tetra- or preferably hexahydro derivatives.

15The compounds of the invention of general formula I can be prepared by a process in which A) when Z is a 3.4-dimethyl-3-pyrroline--2.5-dion-l-yl group, a compound of general formula II 20

R'

NH

2

(II)

in which Ri X and Y have the meanings given under general formula I. is treated with 2.2'-dimetiylmaleic anhydride.

B) when Z isa 4.5.

K [3,4-a]pyridin-8 general formula x 6, 7-tetrahydro-2H-l, 2. 3-triazolo- ;-ium-3--olat-2-yl group, a compound of

II

R 1 Ni II S S

S*

SS

S

S.

0 S. S

S

20 S S *5 in which R 1 X and Y have the meanings given under general formula I. is diazotised with nitrous acid.

treated with piperidine-2-carboxylic acid, and cyclised using a dehydrating agent, C) when Z is a 2,3,5,6,7,8-hexahydro-lH-imidazo~l,5-a]pyridine-1.3--dion-2-yl or a 2,3.5,6.7.8-hexahydro- 1H-1l,4-triazolo[l.2-a]pyridiflC-1,3-dion-2-y1 group.

a compound of general formula II R 0

NN

xY II in which R 1 X and Y have the meanings given under general formula I. is treated with a compound of general formula V or VI 00 U 2

U

IFV

I

U 1 -6in which Q, U 1 and U 2 have the meanings given under general formula I and R is C C -alkyl, D) when Z is a 2.3,5,6,7.,8-hexahydro-lH--imidazo~l.5-a]- Sprdn-l.3-dion-2-yl or a 2,3,5,6.7.8-hexahydrolH-1.,3 4-triazolo~l. 2-a~pyridine-l. 3-dion--2-yl group.

a compound of general formula III

R

0 N N=C=U 1 x

Y

inwih**XadYhaetemaig ie 'ude geea foml ,i*ecedwt opudo geea fomua*I

*N

too**: in whichR.U 1 X and have the meanings givene *udgeneral formula I d is reCte wit a copoundlo E) whe Z sagopo general formula

N-

-7in which R 12

R

13

R

1

R

1 and T have the meanings given under general formula I. a compound of ii general formula IIla 11 (IIa) x czzN in which R X and Y have the meanings given under general formula I. is treated with a compound of 1 general formula VIII 1

R

00 0 12 N NN 2 0in which R 12 13 R~1 R and T have the meanings given under general formtula I, and then ***cyclised to a thiadiazole ring in the presence of an oxidising agent, I F) when Z is a 4.5,6,7-tetrahydroindazol-2-yl group and L is C C ly r ao C- alkyl. a compound of general formula IV R 1 0i NH-NH 2 1

(IV)

X :rZ( in which Rl X and Y have the meanings given under general formula I. is reacted with a compound of ge~neral formula IX V 0 U C R 23 (IX) 1 in 2 1hc R s 4 Calkyl or halo-C -C -alkyl, G) when Z is a 4,5,6,7-tetrahydroindazol-2-yl and L is C 1-C 4-alkoxy, a compound of general formula X

H

in which Rl. X and Y have the meanings given under Igeneral formula I. except R 1 is not hydrogen, is treated with a dialkyl sulphate or alkyl tosylate.

H) when Z is a 4,5,6,7-tetrahydroindazol-2-yl group and L Jj is halogen or cyano. a c0ompound of general formula

X

R. 7 r O 7. -9 if I in which R1, X and Y have the meanings given under general formula I, except R 1 is not hydrogen, is converted to the corresponding compound in which L is halogen, using a phosphorus halide, a phosphorus oxyhalide, phosgene, thionyl chloride or oxalyl chloride, and if necessary converting this with sodium i cyanide to the corresponding compound in which L is cyano, I) when Z is a 2H-1,2,4-triazolin-3-on-2-yl group, a compound of general formula IV I .R I0

NH-NH

2 in which RI, X and Y have the meanings given under general formula I, is reacted with a compound of Si general formula XI .N 7 oC/R 7 S R S 25 2

(XI)

8

I

in which R 7 and R 8 have the meanings given under general formula I and R24 is C 1

-C

4 -alkyl, J) when Z is a 3H-1,3.4-oxadiazol-2-on-3-yl group, a compound of general formula XII 0 R I 0 N..NH-NHZCI

(XII)

Y

in which R 1

R

9 1 X and Y have the meanings given under general formula I. is reacted with phosgene. or a functionally reaxtive derivative, K) when Z is a 5,6,7,8-tetrahydroquinazoline-2,4(lH,3H)- *~*15dion-3-yl group or a l,2,4.5.6,7-hexahydro-2.4-dioxo- 3H-cyclopentapyrimidin-3-yl group, a compound of general formula XXII R H H 200 N NX N 0 00 0 (CH )(XXII) 002c 25 in which R. X, Y and p have the meanings given :0 under general formula I, and R is C -C 4 -alkyl, is cyclised under basic conditions and optionally treated with a compound of general formula XXIII R 7- B (XXIII) in which R 27 has the meaning given under general formula I. except hydrogen, and B is halogen or p-toluenesulphonate, optionally using an acid binding reagent.

I 11 The reaction according to process variant A) is suitably carried out at 20 0 C to 200°C, optionally in the presence of a solvent, whereby 2,2'-dimethylmaleic anhydride is reacted in a molar amount of 1 to 3 equivalents to 1 equivalent of the amine of formula II.

The reaction time is between 1 to 24 hcurs. Generally, the reaction is carried out in the presence of an acid, such as for example acetic acid, where the acetic acid for example can also act as solvent. It is however also possible to react both reactants using an inert solvent, such as for example dichloromethane or dimethyl sulphoxide, and to cyclise the resulting intermediate addition product with an acid anhydride, such as for example acetic anhydride.

15 The reaction according to process variant B) is generally carried out in three stages without intermediate purification of the products, according to the following reaction scheme: -12-

R

0 NN H

(XIV)

9. 0 0* 9

HO

0 j NN-

(XV)

N\

1 0

R

0 NN

N

Nz z 1 r I 0 13 4

S

S.

9 @996 *9 9 999 9 @9 9 *8

S.

*r S

S@

The aniline of general formula II, in which R

I

X

and Y have the meanings given under general formula I, can be diazotised in conventional manner in aqueous acid suspension, at a temperature of -20 0 C to +10 0 C, with sodium nitrite, with a reaction time of 0.5 to 3 hours.

The compounds of general formula XIV, in which G is halogen, especially chlorine, or other inorganic groups.

such as hydrogen sulphate, or organic groups, such as acetate, are then treated, at a temperature of -20 0 C to +20 0 C, with piperidine-2-carboxylic acid and an acid-binding agent, such as for example a trialkylamine.

The compounds of general formula XV can by cyclised with an acid anhydride, such as for example acetic anydride, using a base, such as for example pyridine, in an inert solvent, such as for example ether, to give the compound of formula I.

The reaction according to procese variant C) is suitably carried out at a temperature above 20 0 C, for example at 100°C or at the reflux temperature of the 20 reaction mixture. When the reactant is an anydride of general formula V. the reaction is suitably carried out in the presence of an acid, such as acetic acid, in which the acetic acid for example also acts as solvent. It is however also possible that both reactants are reacted with 25 or without an inert solvent, such as for example dichloromethane or dimethyl sulphoxide, and the intermediate resulting addition product is cyclised with an acid anydride, such as for example acetic anhydride.

The reaction according to process variant D) is carried out in an inert solvent at a temperature between 200C and 150 0 C, suitably at the boiling point of the solvent. Suitable solvents are for example aliphatic and aromatic, optionally chlorinated, hydrocarbons, such as petroleum ether, benzene, toluene, xylene, dichloromethane, chloroform, tetrachloromethane, *so

S.

9

S.

-T -14 1,2-d.chloroethane and chlorobenzene, as well as ethers, such as diethyl and di-n-butyl ether, methyl tert. butyl ether, tetrahydrofuran, dioxan, and ketones, such as for example acetone, methyl ethyl ketone, methyl isopropyl ketone, as well as nitriles, such as acetonitrile and propionitrile, sulphoxides such as dimethyl sulphoxide, or sulpholane.

The isocyanates or isothiocyanates of general formula III used as starting material, can easily be prepared from the aniline of general formula II, in which R

I

X and Y have the meanings given in general formula I, by known processes using phosgene or thiophosgene or their reactive

SO

derivatives.

The reaction according to process variant E) can be 15 carried out in an inert solvent, such as for example *O ether, methylene chloride, chloroform or ethyl acetate, at a temperature of -50 0 C to +50 0 C, by reacting a compound of general formula IIIa, in which R 1 X and Y have the meanings given under general formula I, with a compound of 20 general formula VIII in which R 2

R

1

R

4

R

15 and T have S. the meanings given in general formula I. The reaction Lime is between 0.5 to 10 hours. The resulting compound of general formula XVI R1 R 13

T

H R 1 12 0 N N (XVI)

Y

is thermally unstable and therefore is preferably reacted in the next reaction without isolation.

The formation of the ring can be carried out using an oxidising agent in an organic solvent. Example of organic solvents are inert solvents, such as methylene chloride, j 15 chloroform, N,N-dimethylformamide and ethyl acetate. The condensation reaction for the ring formation can be carried out in the presence of active acid acceptors generally used with oxidising agents. Suitable acid acceptors are organic bases, such as triethylamine, pyridine and dimethylaniline, and inorganic bases such as sodium hydroxide and sodium carbonate. As oxidising agents there can be used bromine, chlorine, sodium hypochlorite and others. When a substituent R represents at least a hydroxy group, the oxidising agent can be iodine.

The reaction according to process variant F) is suitably carried out using a catalyst in a suitable solvent. The reaction temperature lies between room temperature and 150 0 C, preferably at the reflux I temperature of the reaction mixture. Suitable solvents are i for example dimethyl sulphoxide, halogenated hydrocarbons, such as for example methylene chloride and chloroform, aromatic hydrocarbons, such as for example benzene, *toluene, xylene, chlorobenzene and dichlorobenzene, as "20 well as other solvents which are inert to the reactants, such as for example diethyl ether, tetrahydrofuran or dimethylformamide.

As catalysts there can be used acids, such as acetic acid or sulphuric acid, as well as ion exchange reagents.

S The hydrazines of general formula IV used as starting materials, in which R 1 X and Y have the meanings given in general formula I, are obtained by treating compounds of general formula II in acidic aqueous suspension at a temperature of -20 0 C to +10 0 C with sodium nitrite and then by reaction with a reducing agent, such as for example tin chloride.

The reaction according to process variants G) and H) can optionally be carried out with or without a solvent.

The reaction temperatures lie between room temperature and 180 0 C, preferably at the reflux temperature of the -16 reaction mixture. Suitable solvents include methylene chloride, chloroform, benzene, toulene, chlorobenzene, dichlorobenzene and xylene, as well as other solvents inert to the reactants.

The starting materials used for processes G) and H) of general formula X, in which R

I

X and Y have the meanings given in general formula I, except R 1 is not hydrogen, can be obtained according to the following raction scheme in which, in the compound of general formula XVII. R2 is a C 1

-C

4 alkyl group.

0 /N NH-NH

S(IV)

Y

c S II *em t C

O

-20 (XVII) i R e

H

X

\K Y The reaction is suitably carried out in a solvent at a temperature range of 80 0 C to 200 0 C. over 0.5 to 20 hours.

Possible solvents include toluene. xylene and acetic acid.

Compounds of general formula X can exist in three tautomeric forms, but for simplicity these are not shown s I- 1; 7* 17 Oe 0 4 00 0 0 0 in the formula X above.

The reaction according to process variant I) is carried out using a catalyst in a suitable solvent. The reaction temperatures lie between room temperature and 150 0 C, preferably at the reflux temperature of the reaction mixture. Suitable solvents are for example dimethyl sulphoxide, halogenated hydrocarbons, such as for example methylene chloride and chloroform, aromatic hydrocarbons such as for example benzene, toluene, xylene, chlorobenzene and dichlorobenzene, as well as other solvents which are inert to the reactants, such as for example diethyl ether, tetrahydrofuran or dimethylformamide.

Catalysts which can be used are acids, such as acetic 15 acid or sulphuric acid, as well as ion exchange reagents.

The reaction according to process variant J) can be carried out with or without the use of an inert solvent.

Suitable solvents are for example dimethyl sulphoxide, halogenated hydrocarbons, such as for example methylene chloride and chloroform, aromatic hydrocarbons, such as for example benzene, toluene, xylene, chlorobenzene and dichlorobenzene, as well as other solvents which are inert to the reactants, such as for example diethyl ether, tetrahydrofuran or dimethylformamide.

,25 The starting compound of general formula XII, in which

R

I

X, Y and Rg have the meanings given under general formula I, are obtained by reacting the hydrazine of general formula IV, in which R 1 X and Y have the meanings given under general formula I, with an acid derivative of formula XVIII. in which R 26 is C -C 4 -alkoxy or halo, according to the following reaction scheme: 00 00 0 00* *0000: *000 1 18

R

0 N

NH-NH

2

(IV)

Y

0

II

C

RR/

(XVIII)

26 9 0

II

R C The reaction according the process variant K) is generally carried out in a suitable solvent with the "20 addition of a base, such as for. example an alkali metal hydroxide or alcoholate, sodium hydride or triethylamine, optionally in a two phase syst-m with the addition of a i phase transfer catalyst and at temperatures between 0 0

C

according to the following reaction scheme:

L

19 OIIN NCO (III b) 5 H2 N il (CH2) p

(XXVI)

R 00C 28 1 R H H x 2p i R I

SR

1 X and Y have the meanings given under general formula I, with the enamino esters of formula XXVI, in which p is 1 or 2 and R 28 is C -C 4 -alkyl, is suitably carried out in inert solvent, such as for example dioxane. The reaction temperatures lie between room temperature and 200 0 C, preferably at the boiling point of the solvent.

SGenerally the starting materials are used in *i .25 stochiometric amounts. An excess of one or th oher eecan sometimes be advantageous.

d The compounds of the invention prepared by the 0 :0 *above-mentioned processes can be isolated from the reaction mixture by conventional means, for example by distillation of the solvent at normal or reduced pressure or by extraction.

An increased purity can as a rule be obtained by column chromatography as well as by fractional distillation.

The compounds of the invention are generally The compounds of the invention are generally crystalline or viscous substances, that are usually highly soluble in halogenated hydrocarbons, such as chloroform, sulphoxides, such as dimethyl sulphoxide, or esters, such as ethyl acetate.

The starting materials of general formula III and IV are mainly new, but can be prepared by in an analogous manner to known processes.

The active substances of the invention show a good herbicidal activity against broad leaved weeds and grasses. A selective use of the compounds of the invention in various crops is possible for example in rape, beet, soya beans, cotton, rice, barley, wheat and other cereals.

Individual active substances are particularly suitable as selective herbicides in beet, cotton, soya and cereals.

i 15 However the compounds can be used for control of weeds in i permanent crops, such as for example forestry, ornamental trees, fruit, vine, citrus, nut, banana, coffee, tea, i rubber, oil palm, cocoa, berry fruit and hop plantations and for the selective control of weeds in annual crops.

**20 The compounds of the invention can used for example I against the following plant species: Dicotyledonous weeds of the species Sinapis, Lepidium, i Galium, Stellaria, Matricaria, Anthemis, Galinsoga, Chenopodium, Brassica, Urtica, Senecio, Amaranthus, S Portulaca, Xanthium, Convolvulus, Ipomoea, Polygonum, Sesbania, Ambrosia, Cirsium, Carduus, Sonchus, Solanum, i Rorippa, Lamium, Veronica, Abutilon, Datura, Viola, Galeopsis, Papaver, Centaurea and Chrysanthemum.

Monocotyledonous weeds of the species Avena, Alopecurus. Echinochloa, Setaria, Panicum. Digitaria, Poa, Eleusine, Brachiaria, Lolium, Bromus, Cyperus, Agropyron, Sagittaria, Monocharia, Fimbristylis, Eleocharis, Ischaemum and Apera.

The rates of use vary depending on the manner of preand postemergent use between 0.05 and 5 kg/ha.

21 21 The compounds of the invention can be used either alone or in admixture with one another or with other active agents. Optionally, other plant-protective agents or pesticides can be added, depending on the purpose for the treatment. When it is desired to broaden the spectrum of activity, other herbicides can also be added.

Herbicidally active mixing partners suitable in this connection include for example, the active agents listed in Weed Abstracts, vol. 34, No.5 (1986) under the heading "Lists of common names and abbreviations employed for currently used herbicides and plant growth regulators in Weed Abstracts".

An improvement in the intensity and speed of action can be obtained, for example, by addition of suitable *15 adjuvants, such as organic solvents, wetting agents and oils. Such additives may allow a decrease in the dose.

Suitable mixture partners may include phospholipids, e.g. phosphatidylcholine, hydrogenated phosphatidylcholines phosphatidylethanolamine, N-acyl-phosphatidyl- *20 ethanolamines, phosphatidylinositol, phosphatidylserine, lysolecithin or phosphatidylglycerol.

.The designated active ingredients or their mixtures can suitable be used, for example, as powders, dusts, granules, solutions, emulsions or suspensions, with the i 25 addition of liquid and/or solid carriers and/or diluents and, optionally, binding, wetting, emulsifying and/or S* dispersing adjuvants.

Suitable liquid carriers are, for example aliphatic and aromatic hydrocarbons, such as benzene, toluene, xylene, cyclohexanone, isophorone, dimethyl sulphoxide, dimethylformamide and other mineral-oil fractions and plant oils.

Suitable solid carriers include mineral earths, e.g.

bentonite, silica gel, talcum, kaolin, attapulgite, limestone, silicic acid and plant products, e.g. flours.

I -II- 22 As surface-active agents there can be used for example calcium lignosulphonate, polyoxyethylenealkylphenyl ethers, naphthalenesulphonic acids and their salts, phenolsulphonic acids and their salts, formaldehyde condensates, fatty alcohol sulphates, as well as substituted benzenesulphonic acids and their salts.

The percentage of the active ingredient(s) in the various preparations can vary within wide limits. For example, the compositions can contain about 10 to percent by weight active ingredients, and about 90 to percent by weight liquid or solid carriers, as well as, optionally up to 20 percent by weight of surfactant.

The agents can be applied in customary fashion, for example with water as the carrier in spray mixture volumes of approximately 100 to 1,000 1/ha. The agents can be applied using low-volume or ultra-low-volume techniques or in the form of so-called microgranules.

The preparation of these formulations can be carried out in known manner, for example by milling or mixing S'020 processes. Optionally, individual components can be mixed just before use for example by the so-called commonly used tank-mixing method.

Formulations can be prepared, for example, from the Sfollowing ingredients.

A) Wettable Powder 20 percent by weight active ingredient 35 percent by weight bentonite percent by weight colloidal silicic acid 8 percent by weight calcium lignosulphonate 2 percent by weight sodium salt of N-methyl-N-oleyltaurine rI:

I;-

ji Ii iI 5 ii.

23 B) Paste percent by weight active ingredient 5 percent by weight sodium aluminium silicate percent by weight cetyl polyglycol ether with 8 mol of ethylene oxide 2 percent by weight spindle oil percent by weight polyethylene glycol 23 percent by weight water C) Emulsifiable Concentrate percent by weight active ingredient percent by weight isophorone percent by weight of a mixture of calcium dodecylbenzenesulphonate and nonylphenol- 15 polyoxyethylene.

S

*3 S*

D

24 The following examples illustrate the preparation of compounds according to the invention.

Example 1.01 (process E) 6-(6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo[2.l-c][l.2,4]thiadiazol-3-ylidenimino)-4-(2-propynyl)-2H-1,4-benzoxazin- 3(4H)-one 2.6 g 2-Amino-4,4-dimethylpyrroline hydrochloride was suspended in 20 ml methylene dichloride. A solution of 0.75 g sodium hydroxide in 5 ml water was added dropwise with stirring at 0°C and the mixture stirred for minutes until the reaction mixture became clear. A solution of 6-isothiocyanato-4-(2-propynyl)- '15 2H-1,4-benzoxazin-3(4H)-one in 100 ml methylene dichloride was added dropwise at such a rate that the temperature did S. not rise above 5 0 C. The mixture was then stirred for 3 I hours, whereby the temperature rose to 20 0 C. With cooling i I to -20 0 C, a solution of 2.3 g bromine in 10 ml methylene S* '20 chloride was slowly added dropwise and the mixture stirred for 1 hour, whereby the temperature rose to 10 0 C. Then the i solution was washed in turn with 30 ml water, 30 ml aqueous sodium hydroxide and 30 ml water. The methylene dichloride phase was dried over anydrous magnesium O..25 sulphate, filtered and concentrated. The residue was i purified by silica gel column chromatography.

j Yield: 1.5 g 25% of theory Mp: 65 0

C

25 Preparation of the starting Material for Example 1.01 6-Isothiocyanato-4-(2-propynyl)-2H-1,4-belzoxazin-3(4H)-ofle 4 g 6-Amino-4-(2-propynyl)-2H-1,4-benzoxazin-3(4H)-one was dissolved in 100 ml metliylene chloride and treated at 5 0

C

with a suspension of 2.60 g calcium carbonate in 20 ml water. 2.9 g Thiophosgene was then added dropwise at such a rate that the temperature did not rise above 5 0 C. After 10 hours at room temperature, the phases were separated.

The organic phase was washed with 50 ml water, dried over MgSO 4 and the solvent removed under reduced pressure.

Yield: 4.1 g 84% of theory '15 Mp: 120-122 0

C.

In a similar manner the foliowing compounds were prepared according to process E.

es es 0* 4 06@

SO

0 2 000* 0 0 0 *0 0 0 0* 0 0 0 Example No Physical Constant Na me 1.02 6-(6,6-Dimethyl-3.5.6,7-tetrahydropyrrolo- (1,2,4]thiadiazol-3-ylidenimilo)- 4-methyl-2H-1, 4-benzoxazin-3 (4H) -one 1.03 6-(6.6-Dimethyl-3,5,6,7-tetrahydropyrrolo- 7-fluoro-4-(2-propynyl)-2H-1, 4-benzoxazin-3 (4H) -one mp: 133 0

C

mp: 62 0

C

26 Example No Physical Name Constant 1.04 4-(2,3-Dibromo-2-propynyl)-6-(6,6-dimethyl- 3,5,6, 7-tetrahydropyrrolo-[12,1-c] 11.2.4 Ithiadiazol-3-ylidenimino) -7-fluoro-2H-1l.4-benzoxazin-3 (4H)-one 1.05 5-(6,6-Dimethyl-5,6-dihydro--3H-thiazolo- 12, 3-c]11,2,4]thiadiazol-3-ylidenimilo)- 6-f luoro-3-(2-propynyl)-2 -benzothiazolone 1.06 5-(6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo- :15 121-c]1,2,4]thiadiazol-3-ylidenimino)- .00.6-fluoro-3-(2-propynyl)-2 (3H) -benzothiazolone *oS* 1.07 6-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo- E2,3-c][1,2.4]thiadiazol-3-ylidenimilo)- :20 4-(2-propenyl)-2H--1,4-benzoxazin-3(4H)-one 1.08 6-(6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo- 12,1-c](l,2,4]thiadiazol-3-ylidenimino)- 4-(2-propenyl)-2H-1,4-benzoxazin-3(4H)-ole *025 1.09 6-(6,,6-Dimethyl-5.6-dihydro-3H--thiazolo- 0 12,3-c][1,2,4]thiadiazol--3-ylidenimino)- 4.-(2-propynyl)-2H--1,4--benzoxazin-3(4H)-oe 1.10 6-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo-- 12,3-c] (1.2,4]thiadiazol-3-ylidenimino)- 4-propyl-2H-1.,4-benzoxazil-3 (4H) -one mp: 65 0

C

mp: 195 0

C

mp: 1900 C mp: 124-26 0

C

mp: 110 0

C

mp: 93-C mp: 53 0

C

RL

4 27 Example No Physical Constant Name 1.11 6-(6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo- 1-c] 4]thiadiazol-3-ylidenimino)- 4-propyl-2H-1, 4-benzoxazin-3 (4H) -one S@ 1.12 7-(6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo- 2, 4]thiadiazoi.-3-ylidenimino)- 1-(2-propynyl)-2(1H) -quinoxalinone 1.13 7-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo- 3-c] [1,2,4]thiadiazol-3-ylidenimino)- L- (2-propynyl) -2 (1H) -uinoxal inone 1.14 6-(6,6-Diriethyl-3,5,6,7-tetrahydropyrrolo- 12.1-c] 11,2.4 ]thiadiazol- 3-ylidenimino) 4-(2-propynyl)-2H-1.,4-benzthiazin-3(4H)-one 1.15 6-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo- (2,3-c](l,2,4]thiadiazol-3-ylidenimino)- 7-fluoro-4- (2-propynyl 4-benzoxazin- 3 (4H) -one 1.16 6-(6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo- 1-c] 2,4]thiadiazol-3-ylidenimino)- 7-f luoro-4-propyl-2H-1,4-benzoxazin-3 (4H) -one 1.17 6-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo- (1,2,4]thiadiazol-3-ylidenimino)- 7-f luoro-4-prcpyl-2Hl-1, 4-benzoxazin- 3 (4H) -one 41 16068 mp: 168 0

C

mp: 174 OC mp: 65 0

C

mp: 135-140 0

C

mp: I.L 0

OC

mp: 156-C 27 -28 Example No Physical Cons tant Name @0 0 0 00 00 0 0 0000 0* 0 0 000 0 00 00 0 0

S

00 0 1.18 4-Cyanomethyl-6-(6.6--dimethyl-3,5.6.7-tetra- mp:170-171 0

C

hydropyrrolo[2 2.4 Ithiadiazol- 3-ylidenimrino)-2H-1. 4-benzoxazin-3(4H)-oie 1.19 6-(6-Methyl--3,5,6,7-tetrahydropyrrolo- mp:171-172 0

C

.0 [1,2.4]thiadiazol-3-ylidenimino)- 4-(2-propynyl)-2H-1, 4-benzoxazin-3(4H)-one 1.20 7-Fluoro-6-(6-methyl-3,5,6,7-tetrahydro- nip:161--162 0

C

pyrrolo[2, 1-c] [1,2,4]thiadiazol-3-ylidenimino)- .5 4-(2-propynyl)-2H-1.4-benzoxazin-3(4H)-one 1.21 5-(6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo- mp:113 0

C

1-c) [1,2,4]thiadiazol-3-ylidelimilo)- 3-propyl-2 (3H) -ben~zoxazolone 1.22 5-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo- mp:113 0

C

[2,3-c)[1,2,4)thiadiazo]-3-ylidenimino)- 3-propyl-2 -benzoxazolone 0 0 00 00 00*000 @000 0 0000 **00*0 0 1.23 5-(6.6-Dimethyl-3.S.6,7-tetrahydropyrrolo- 2,4]thiadiazol-3-ylidenimino)- 6-f luoro-3-propyl-2 (3H)-benzoxazolone 1.24 5-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo- [2.3-clll.2,4)thiadiazol-3-ylidenimino)- 6-f luoro-3-propyl-2 (3H) -benzoxazolone 1.25 5-(G3.6-Direthyl-3,5,6,7-tetrahydropyrrolo- 1-c) 2,4)thiadiazol-3-ylidelimino)- 3-(2-propynyl (3H) -benzoxazolone mp: 124-127 0

C

mp: 141-142 0

C

mp: 158 0

C

29 Example No Physical Constant Name 0 to .00.

0 soS 1.26 5-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo- [1.2,4]thiadiazol-3-ylidenimino.- 3-(2-propynyl)-2 (3H)-benzoxazolone 1.27 5-C6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo- 0 1-c] 4]thiadiazol-3-ylidenimino)- 6-f luoro-3-(2-propynyl (3H)-benzoxazolone 1.28 5-(6,6-Dimethyl-5,6-dihydro-3H-thiazolo- [1,2,4]thiadiazol-3-ylidenimino)- 6-fluoro-3-(2-propynyl)-2(3H)-benzoxazolone 1.29 6-(6,6-Dimethyl-3,5,6,7-tetrahydropyrrolo.

4]thiadiazol-3-ylidenimino)- 3-methyl-1-propyl-1. 3-dihydro--2(2H)-.indolone 0 1.30 6-(6.6-Dimethyl-5.6-dihydro-3H-thiazolo- [1,2,4]thiadiazol-3-ylidenimino)- 3-methyl-l-prf'pyl-1. 3-dihydro-2(2H)-indolone mp: 137 0

C

mp: 169-173 0

C

mp: 138-142 0

C

0* 55 5 55 5

*S

1.31 7-(6,6-Dimethyl-3.5.6,7-tetrahydropyrrolo- [2.1-c][1,2,4]thiadiazol-3-ylidenimino)- 1- (2-propynyl (lH)-quinoxal inane 00.: So -7 -4 1. L L A 0 j a L L 0 0 30 Example 2.01 (process A) 1-C6-Fluoro-2-oxo-3--(2-propynyl)-2,3-dihydrobenzoxazol- 1-3, 4-dimethyl-3-pyrroline-2,5 (1H) -dione 2.8 g 2,3-dimethylmaleic anhydride was added to 4 g 5-amino-6-fluoro-3-(2-propynyl)-2(3H)-benzoxazolone in ml acetic acid. The mixture was stirred for 8 hours at 0 C. The cooled reaction mixture was poured into 500 ml ice/watl ,and the precipitated crystals separated and washed wit water. The product was dried in vacuo at 50 0

C.

Yield: 2.3g 38% of theory Mp: 165 0

C

In a similar manner the following compounds were prepared according to process A.

IF

II

S S

B*

S.

SO S 5.55 65 S S StS S Oh S~ S S

S

S. S 0g 5S

S*

5 3 55 0@ S *5 20 Example No Phy si cal Constant Name gig.

0 35*0

S

I

2.02 1-C6--Fluoro-2-oxo-3-(2-propynyl)-2.3-dihydrobenzthiazol-5-yl]-3,4-dimethyl-3.-pyrroline- 2,*5 (1H) -dione 2.03 1-(3-Oxo-4--(2-propynyl)-3,4-dihydro-2H-1,4benzthiazin-6-yl .4-dimethyl--3-pyrroline- 2,,5(1H)-dione 2.04 1-[2-Oxo-2.3-dihydro-1H-benzimidazol-5-yl]- 3. 4-dimethyl-3-pyrroline-2. 5(111) -dione mp 2 29 -C mp:279 0

C

mp: 2800 C I ii r .1 31 Example No Physical Constant Name 2.05 l-12-Oxo--(2-propynyl)-lH-quinoxalin-7-ylJ- 3, 4-dimethyl-3-pyrroline-2,5S(lH) -dione 2.06 1-f2-Oxo-1-(2--propynyl)-3,4-dihydrolH-quinoxalin-7-yl 1-3. 4-dirnethyl-3-pyrroline- .0 2,5(1H)-dione mp: 265 0

C

Ii 4j Ii ii ii ii Ii

S.

S S

S

SS 55 S S

S

S S 55 20 S 5* 5 *5 S

S*

S

55.5 0 5.55 S:~0

S

2.07 l-12-Oxo-3-C2-propynyl)-2. 3-dihydrobenzoxazol-S-yl 4-dimethyl-3-pyrroline- 2 SClH) -dione 2.08 1-(2-Oxo-3-propyl-2,3-dihydrobenzoxazol- 5-yl 4-dimethyl-3-pyrroline-2,5 (1H) -dione 2.09 1-(3-Methyl-2-oxo-1-propyl-1.3-dihydro- 2H-indol-6-yl)-3 ,4-dimethyl-3-pyrroline- 2, 5(lH) -dione 2.10 l-E3-Methyl-2-oxo-l-(1-methylethyl)- 1, 3-dihydro-2H-indol-6-yl)-3,.4-dimethyl- 3-pyrroline-2,5 (lH)-dione mp: 189 0

C

mp: 1100 C mp: 180 0

C

mp: l42-144*C

PT'.

V

I $1 4 32 Example 3.01 (process D) 2-17-Fluoro-3-oxo-4-(2-propynyl)-3.4-dihydro-2H-l,4benzoxazin-6-yl]perhydroimidazo(1,5-a]pyridine-1,3-dione 4.1 ml Ethyl piperidine-2--carboxylate was added to a solution of 6.4 g 7-fluoro-4-(2-propynyl)-l.4-benzoxazin- 3(4H)-on-6-yl isocyanate in 50 ml tetrahydrofuran. The mixture was heated under reflux for 10 hours. After cooling, the solvent was removed under reduced pressure and the residue purified on a silica column with ethyl acetate/hexane.

Yield: 4.8 g =52% of theory 15 Mp: 202-204 0

C

In a similar manner the following compounds were prepared according to process D.

ge 0@

S.

S

*5

S

*SS S. *S S 5 *0 .0:20 0 S 0 0 Example No Physical Constant Na me 3.02 2-(3-Oxo-4-(2-propynyl)-3,4-dihydro-2H-1.4benzoxazin-6-yl ]perhydroimidazo 11,5-a] pyridine-l. 3-dione 3.03 2-[3-Oxo-4-(2-propenyl)-3,4-dihydro-2H-1,4benzoxazin-6-yl]perhydroimidazo[l. pyridine-1, 3-dione mp: 180-185*C mp: 157-158*C 3.04 2-[7-Fluoro-3-oxo-4-(2-propynyl)-3.4-dihydro- mp:151 0

C

2H-l. 4-benzoxazin-6-yl]J-3-thioxoperhydroimidazo~l. 5-a Jpyridin-l-one t ii 33 Example No.

Name Physical Constant 3.05 2-16-Fluoro-2-oxo-3-(2-propyflyl)- 2 3 -3--thioxoperhydroimidazo pyridin-l-one mp: 189-195 0

C

4*

S

S. S 5f 3.06 2-(7-Fluoro-3-oxo-4-propyl-3, 4-dihydro-2H-1, 4-benzoxazin-6-yl) pyridine- 1, 3-dione 3.07 2-[2-Oxo-1-(2-propynyl)-H-quioxalil- mp:199-200 0

C

7-yl] perhydroimidazo pyridine 1, 2 dione 3.08 2-[2-Oxo-1-(2-propynyl)-3,4-dihydrolH-quinoxalin-7-yl] perhydroimidazopyridine-1,3--dione Se C.

S.

S.O.S.

C

OS*S

0 3.09 2-[2-Oxo-3-(2-propynyl)-2,3-dihydroperhydroimidazo pyridine-1,3-dione mp: 179*C 3.10 2-[6-Fluoro-2-oxo-3-(2-propynyl)-2, 3-dihydrobenzoxazol-5-yl] perhydroimidazo pyridine-1, 3-dione 3.11 2-(3-Methyl-2-oxo-1-propyl-1,3dihydro-2H-indol-6-yl) perhydroimidazo 5-alpyridine-1, 3-di one 3.12 2-(3-Methyl-2-oxo-l-propyl-1, 3-dihydro 2H-indol-6-yl)perhydro-1H-1, 2, 4-triazolo- 2-alpyridazine-1,3-dione 34 Example Physical No Name Constant 3.13 2-[6-Fluoro-2-oxo-3-(2-propynyl)-2,3-dihydrobenzoxazol-5-yl]perhydro-lH-1. 2,4-triazolo- [1,2-a]pyridazine-1. 3-dione 3.14 2-(2-Oxo-1--propyl-lH-quinoxalin-7-yl)perhydro-lH-1.2,4-triazolo[1,2-a]pyrid3zine- 1. 3-dione 3 0 Example 4.01 (process K) 3-(3-Oxo-4-propyl-3 ,4-dihydro-2H--l.4-benzoxazin-6-yl)- 6,*7,8-tetrahydroquinoxaline-2,. iH, 3H) -dione A solution of 4.4 g ethyl 2-[3-(3-oxo-4-propyl-3,4-dihydro- 2H-l,4-benzoxazin-6--yl)ureido]-l-cyclohexanecarboxylate in ml ethanol was added to a solution of 2.0 g sodium in 100 ml ethanol and the reaction mixture heated at boiling point for 1 hour. After the reaction had finished, the solution was concentrated and the residue taken up in 300 ml water. The precipitate was filtered off and the filtrate acidified with hydrochloric acid. The resulting precipitate was separated, washed with water and recrystallised from ethyl acetate/diisopropyl ether.

Yield: 3.56 g =56% of theory Mp: >250 0

C

6.9.:20 Example 4.02 (process K) l-Methyl-3-(4-propyl-3.4-dihydro-2H-1,4-benzoxazin-6-71)- 5,6,7,8-tetrahydroquinoxaline-2,4(lH,3H)-dione 0.17 g 80% Sodium hydride suspension was added to a solution of 2.0 g 3-(4-propyl-1,4-benzoxazin-3(4H)-on- 6-yl)-5,6.7,8-tetrahydroquinoxaline-2.4(lH.3H)-dione in g~e 20 ml dimethyl formamide and the mixture stirred at 60 0

C

0 e for 1 hour. It was allowed to cool to room temperature and 0.77 g iodomethane added. It was then heated at 60 0 C for 2 hour. After cooling the crystalline precipitate was separated and recrystallised from ethyl acetate/ diisopropyl ether.

1u -36 Yield: 1.3 g 65% of theory Mp: 218 0

C

Example 5.01 (process I) 2-[6-Fluoro-2-oxo-3-(2-propynyl)-2.3-dihydrobenzthiazol- 5-yl]-2,3,5,6,7,8-hexahydro-1,2,4-triazolo[4,3-a]pyridin- 3-one 2.8 g l-Ethoxycarbonyl-2-piperidone and 1 g phosphorus pentoxide were added to a solution of 3.6 g 6-fluoro-3-(2-propynyl)benzthiazolone in 40 ml xylene and the mixture heated for 2 hours at reflux. After cooling, it was added to 100 ml water and the organic phase separated. The organic phase was washed with 40 ml aqueous S. potassium hydrogen carbonate, dried over magnesium sulphate and concentrated. The residue was chromatographed on silica gel using a mixture of ethyl acetate and hexane as eluent.

Yield: 380 mg 6.7% of theory Mp: 154-160 0

C

Preparation of the Starting Material for Example 5.01 5-Hydrazino-6-fluoro-3-(2-propynyl)benzthiazolone 4 g 5-Amino-6-fluoro-3-(2-propynyl)-2(3H)-benzthiazolone was dissolved in 50 ml concentrated hydrochloric acid and the mixture stirred for about 30 minutes at room temperature. It was cooled to -5 to +5 OC and a solution of 1.3 g sodium nitrite in 5.6 ml water added dropwise.

The mixture was then stirred for 30 minutes and cooled to 0 C. A solution of 6.8 g tin (II) chloride in 15 ml hydrochloric acid was slowly added dropwise. The mixture

P

I

I'

4 37 was then stirred for 2 hours, with the temperature held at between -10 and 0 0 C. Solid material was filtered off and the filtrate neutralised and extracted three times with ml ethyl acetate. The extracts were dried over magnesium sulphate and the solvent removed under reduced pressure.

Yield: 2.6 g 61% of theory In a similar manner the following compounds were prepared according to process I.

*d 0 ~4 q *0*0 p.

0 0 0. 0.

S

0 S 00 0* Example No.

Name Physical Constant SS S A St 0

S

*05q

A

555.

4 ,t.S 0 5.02 2-[2-Oxo-3-(2-propynyl)-2,3-dihydrobenzoxazol-5-yl] 8-hexahydro- 1,2, 4-triazolo pyridin-3-one 5.03 2-[7--Fluoro-3-oxo--4-(2-propynyl)-3-4dihydro-2H-l, 4-benzoxazin-6-yl] -2,3,5, 6,7, 8-hexahydro-l, 2, 4-triazolo [4,3-a] pyridin-3-one mp: 1900 C mp: 194-1960 C 37a 5.04 2-[6-Fluoro-2--oxo-1-(2-propynyl)-3,4dihydro-1H-quinoxalin-7-yl] -2,3,5,6,7,8hexahydro-1, 2, 4-triazolo[14, 3-a] pyridin- 3-one

S

OS

5.05 2-[6,-Fluoro-2-oxo-1-(2-propynyl)-lHquinoxalin-7y1] 8-hexahydro- 1,2, 4-triazolo pyridin-3-one 5.06 2-[6-Fluoro-2-oxo-3,4-dihydro-lHquinoxalin-7-yl] 8-hexahydro- 1,2, 4-triazolo pyridin-3-one mp: 210-211 0

C

rnp: 190-1920C '1

T

S. S

S.

S

S *SSS

S

*SSSS.

t 38 Example 6.01 (process B) U 2-[7-Fluoro-3-oxo-4-(2-propynyl)-3.4-dihydro-2H-l,4-benzoxazin-6-yl]-4,5,6,7-tetrahydro-2H-1,2,3-triazolo[3,4-a]pyridin-8-ium-3-olate g 6-Amino-7-fluoro-4-(2-propynyl)-2H-1,4-benzoxazin- 3(4H)-one was suspended in a mixture of 12.2 ml concentrated hydrochloric acid and 52 ml water and the mixture cooled to -100 to +5 0 C. A solution of 1.74 g i sodium nitrite in 6 ml water was added dropwise at such a i rate that the temperature did not rise above -5 0 C. After the addition, the mixture was stirred for 1 hour at and excess nitrous acid destroyed with urea until a test i ,*15 with iodine-starch paper was negative. The resulting solution was warmed to OOC and added dropwise to an i ice-cooled solution of 2.9 g pipecolinc acid and 10.5 ml 'i triethylamine in 38 ml water. After the addition, the mixture was stirred for 1 hour at 0°C and the mixture 20 extracted several times with methylene chloride. The combined organic phases were dried over magnesiunm i sulphate and the solvent evaporated. The residue was taken i up in 60 ml ether and treated with 5.2 ml acetic anhydride .i and 2.6 ml pyridine. The mixture was stirred overnight at 25 room temperature and poured into 150 ml ice/wate.. It was .oe extracted with ethyl acetate and the extract dried over magnesiunm sulphate and the solvent evaporated. The residue was chromatographed on silica gel using ethyl acetate/methanol (95:5) as eluent.

Yield: 1.0 g 13% of theory Mp: 202-203 0

C

9L 39 In a similar manner the following compounds were prepared according to process B.

Example No Physical Constant Name 6.02 2-L6-Fluoro--2-oxo-3-(2-propynyl)-2,3-dihydro- mp:203 0

C

-4,5.S6. 7-tetrahydro-2H-1 .2,3triazolo(3 ,4-a]pyridin-8-ium-3-olate 6.03 2-16-Fluoro-2-oxo-3-(2-propynyl)-2,3-dihydro- mp:210 0

C

7-tetrahydro-2H-1 .2,3triazolo[3 ,4-alpyridin--8-ium-3-olate U 0, p. 6SIe 0 00 00 0 *00 0 .0 00 @0 C S. 0

S.

S S 0S

S.

S 0 *0 5000 0

S

OS

0 004 Ii Example 7.01 (process J) 3-(3-Methyl-2-oxo-l-propyl-1,3- dihydro-2H-indol-6-yl]- 5-(l,l-dimethylethyl)-1,3,4-oxadiazol-2(3H)-one 2.6 g 3-Methyl-6-[N'-(2,2-dimethylpropanoyl)hydrazino]l-propyl-1H-indol-2(3H)-one was dissolved in 15 ml of a solution of phosgene in toluene and the mixture heated for 4 hours at reflux. It was stirred overnight at room temperature, 20 ml methanol carefully added and the solvent distilled under reduced pressure. The residue was chromatographed on silica gel using hexane/ethyl acetate (73) as eluent.

*15 Yield: 1.7 g 61% of theory nD 1.5366 Preparation of the Starting Material for Example 7.01 '20 3-Methyl-6-[N'-(2,2-dimethylpropanoyl)hydrazino]-l-propyl- 1H-indol-2(3H)-one 2.5 g Triethylamine was added to a solution of 5.9 g 6-hydrazino-3-methyl-l-propyl-1H-indol-2(3H)-one in a mixture of 50 ml toluene and 20 ml acetonitrile. 3.1 g Pivaloyl chloride was added dropwise whereby thre temperature rose to about 40 0 C. The mixture was then stirred for 1.5 hours, agitated with 100 ml each of water and aqueous potassium hydrogen carbonate, dried over magnesium sulphate and the solvent removed. The residue was chromatographed on silica gel using hexane/ethyl acetate as eluent.

Yield: 2.7 g 33% of theory -41 In a similar manner t-he following compounds were prepared according to process J.

Example Name Physical No. Constant C C

C.

C C C S 0*C C CC CC C C CC C C

C*

CC..

C C CC C

CC

S C

C.

CC..

C

7.02 3-12-Oxo-3-(2-propynyl)-2,3-dihydrobenzoxazol 5-yl] 1-dimethylethyl) 1, 3,4-oxadiazol-2(3H)-one 7.03 3-[7-Fluoro-3-oxo-4-(2--propynyl)-3,4dihydro-1,4-benzoxazin-6-yl]-5-(1, 1dimethylethyl) 4-oxadiazol-2 (3H) one 7.04 3-[6-Fluoro-2-oxo-1-(2-propynyl)-3,4dihydro-1H-quinoxalin-7-yl] 1dimethylethyl) 4-oxadiazol-2 (3H) one 7.05 3-4,6-Fluoro-2-oxo-1-(2-propynyl)-lHquinoxalin-7-yl] 1-dimethylethyl) 4-oxadiazol-2 (3H) -one 7.06 3-17-Fluoro-3-oxo-3,4-dihydro-2H-1,4benzoxazin-6-ylI-5-(1, 1-dimethylethyl)- 1,3, 4-oxadiazol-2 (3H)-one mp: 127-130 0

C

mp: 143-144 0

C

mp: 66-680C mp:152-153 0

C

mp: 171-172 0

C

7.07 3-[6-Fluoro-2-oxo-3,4-dihydro-lH-quin- nip:248 0

C

oxalin-7-yl]-5-(1, 1-dimethylethyl)-1,3, 4-oxadiazol-2 (3H) -one -42 Example 8.01. (process H) 3-Chloro-2-[2-oxo-3-(2-propynyl)-2,3-dihydrobenzoxazol- 5-yl]-4,5,6,7-tetrahydro-2H-indazole A mixture of 4.5 g 2-(2-oxo-3-(2-propynyl)-2,3-dihydrobenzoxazol-5-yl]-1,3,4,5,6,7-hexahydro-2H-indazol-3-one and ml oxalyl chloride was heated for 4 hours at reflux.

After cooling, the mixture was poured into 100 ml ice/water and extracted with methylene chloride. The combined organic phases were agitated with saturated aqueous potassium hydrogen carbonate and water and dried over magnesium sulphatei The solvent removed under reduced pressure. The residue was chromatographed on silica gel 15 using a mixture of hexane and ethyl acetate as eluent.

Yield: 3.9 g =82% of theory Mp: 143-146 0

C

Preparation of the Starting Material for Example 8.01 2-(2-Oxo-3-(2-propynyl)-2, 1,3,4.5,6, 7-hexahydro-2H-indazol-3-one 2 A mixture of 4.9 g ethyl 2-cyclohexanecarboxylate and a solution of 5.8 g 5-hydrazino-3-(2-propynyl)-2(3H)-benzoxazolone in 24 ml acetic acid was heated for 1 hour under reflux. Excess acetic acid was removed under red'aced pressure. The residue was recrystallised from isopropyl ether.

Yield: 5.8 g =65% of theory Mp: 177-180 0

C

r

L

t Iii 43 In a similar manner the following compounds were prepared according to process H.

Example No 8.02 3.

3 8.03 3.

3 Physical Constant Name -Chloro-2-17-fluoro--3-oxo-4- (2-propynyl)- ,4-dihydro-2H-1,4-benzoxazin-6-yl]-4.5. 6.7etrahydro-2H-indazole -Chloro-2-[6-fluoro-3-oxo-l-(2-propynyl) ,4-dihydro-lH-quinoxalin-7-yl]-4,5.6.7etrahydro-2H-indazole mp: 150 0

C

mp: 195 0

C

SO

S

@5 6

S.

6 66 S S S 555 It 44 The following examples illustrate the possibilties for use of the compounds of the invention.

Example A In a greenhouse, the noted plant species were treated post-emergently with the noted compounds of the invention, at a rate of 0.1 kg active ingredient/ha. The compounds of the invention were sprayed evenly over the plants as emulsions or suspensions in 500 litres water/ha. Three weeks after the treatment, the compounds of the invention showed a high crop selectivity with excellent activity against the weeds.

S..

*fee 00, .0 0 00 0O 0 0 In the following table: 0 no damage 4 total destruction

S

0*S

TRZAX

BRSSS

SOLSS

HELAN

ABUTH

MATCH

VIOSS

IPOSS

VERPE

GALAP

Triticum aestivum Brassica sp.

Solanum sp.

Helianthus annuus Abutilon theophrasti Matricaria chamomilla Viola sp Ipomoea purpurea Veronica persica Galium aparine t 45 T B S H A M V I V G R R 0 E B A I P E A Z S L L U T 0 0 R L A S S A T C S S P A X S S N H H S S E P Compounds of invention S S *5 5,

S

09 5 S. Se S S

S

*5 S S C 5e

S.

S S

SS

CO

S S

S.

S

C.

C

S.

S Example 1.01 Example 1.02 Example 1.03 Example 1.04 Example 1.05 Example 1.06 Example 1.08 15 Example 1.09 Example 1.10 Example 1.1i Example 1.12 Example 1.15 Example 1.16 Example 1.17 Example 1.18 Example 1.19 Example 1.20 25 Example 1.23 Example 1.27 Example 1.28 0 4 4 4 4 4 4 4 4 4 0 3 4 4 4 4 4 4 4 4 0 4 4 4 4 4 4 4 4 4 0 4 4 4 4 2 2 4 4 4 1 1 4 3 4 4 4 4 4 3 0 1 4 3 4 4 3 4 3 2 0 2 3 4 3 2 4 4 0 3 4 4 4 4 4 4 3 1 1 3 4 4 3 4 4 3 0 3 3 4 4 4 4 3 0 3 4 4 4 4 4 2 1 3 4 4 4 4 4 3 3 1 4 4 .4 3 3 3 3 2 0 2 4 4 3 3 3 2 2 1 3 3 4 3 2 3 4 1 1 3 4 4 3 3 3 4 2 1 4 4 4 4 3 4 4 4 0 3 4 4 3 2 3 3 3 0 2 4 4 3 3 4 3 1 0 1 4 4 3 3 4 2 2 0 0 0 0 0 0 0 0 0 0 Untreated 11~_ I_ ~I 46 Example B In a greenhouse, the compounds of the invention shown in the table were applied at the rates given. For this the compounds were applied in vessels containing 1500 ml water. As test plants there were used Echinochloa crus-galli (ECHCG) in the 2 to 5 leaved stage. Three weeks after the treatment, the compounds of the invention showed strong activity against Echinochloa crus-galli.

i i I I

I

f

I

i i i i i t i i n iiI i i i i i Ii j i 1 *a.

a ea 15 as a a..

06 a 0 lose *eas see a: a, a In the following Table: 0 no damage 1 slight damage 2 medium damage 3 heavy damage 4 total destruction Compound of the invention Water application ppm Example 1.01 Example 1.02 Untreated 47- Example C i In a greenhouse, the noted plant species were treated post-emergently with the noted compounds of the invention, at a rate of 0.01 kg active ingredient/ha. The compounds of the invention were sprayed evenly over the plants as emulsions or suspensions in 500 litres water/ha. Three weeks after the treatment, the compounds of the invention showed a high crop selectivity with excellent activity against the weeds. The comparison material did not show the high efficacy.

In the following table: 0 no damage 4 total damage 0 00 S 0 06 *9

S.

S

0O 9 S 00

TRZAX

ZEAMX

VIOSS

VERPE

SOLSS

SEBEX

IPOSS

Triticum aestivum Zea mays Viola sp Veronica persica =Solanum sp.

Sesbania exaltata Ipomoea purpurea see 25 *sees: a ABUTH Abutilon theophrasti 9.

s ~~1 48 T Z V V S S I A R E I E 0 E P B Z A 0 R L B 0 U A M S P S E S T X X S E S X S H Compounds of invention Example i.oi Example 2.01 Example 2.02 Example 3.01 Example 3 .02 Example 6.01 Untreated a 0 00 S* 00 0 0 3 3 4 4 4 4 0 0 3 4 4 2 4 4 1 a 3 3 4 4 1 2 4 4 4 4 4 0 0 3 3 4 2 0 3 4 4 4 4 4 0 0 0 0 0 0 0 0 Comparison Oxadiazon 520 0 0 0 0 0 1 1 2 I 49 SExample D In a greenhouse, the noted plant species were treated pre-emergently with the noted compounds of the invention, at a rate of 0.1 kg active ingredient/ha. The compounds of the invention were sprayed evenly over the plants as I emulsions or suspensions in 500 litres water/ha. Three weeks after the treatment, the compounds of the invention showed a high crop selectivity in sugar-beet, wheat and maize, with excellent activity against the weeds. The comparison material did not show the same high selectivity.

In the following table: i 15 0 no damage 1 1 24% damage 2 25 74% damage 3 75 89% damage S 4 90 100% damage i i BEAVX Beta vulgaris altissima TRZAX Triticum aestivum ZEAMX Zea mays S 25 GALAP Galium aparine MATCH Matricaria chamomilla 74 50 Compounds of invention Example 3.04 Example 4.01 Untreated Comparison Oxadiazon U 0 0 0 0 0 a 0 00 C CC 0 1 1 1 0 4 51 Example E In a greenhouse, the noted plant species were treated post-emergently with the noted compounds of the invention, at a rate of 0.1 kg active ingredient/ha. The compounds of the invention were sprayed evenly over the plants as emulsions or suspensions in 500 litres water/ha. Two weeks after the treatment, the compounds of the invention showed a high crop selectivity in maize with excellent activity against the weeds. The comparison material did not show i the same high selectivity.

0 SIn the following table: 0* 00 15 0 no damage 1 1 24% damage 2 25 74% damage S3 75 89% damage 4 90 100% damage *0 i ZEAMX Zea mays i ABUTH Abutilon theophrasti MATCH Matricaria chamomilla POLSS Polyganum sp.

SOLSS Solanum sp.

VERPE Veronica persica 52 Z A M P S v E B A 0 0 E A U T L L R M T C S S P X H H S S ~E Compounds of invention Example 3.04 Example 3.05 Untreated comparison 15 Oxadiazon 0 3 3 4 3 0 4 4 3 4 0 0 0 0 0 0

*W

1 0 4 3 4 4 rr__

I

i L1 53 Example F In a greenhouse, the noted plant species were treated pre-emergently with the noted compounds of the invention, at a rate of 1.0 kg active ingredient/ha. The compounds of the invention were sprayed evenly over the plants as emulsions or suspensions in 500 litres water/ha. One week after the treatment, the compounds of the invention showed excellent activity against the weeds.

In the following table: 15 0* 0 =no 1 1 2 =25 3 =75 4 =90 Sdamage S- 24% damage 74% damage 89% damage S- 100% damage Aopecurus myosuroides Avena fatua Setaris viridis Cyperus esculentus Abutilon thee >hrasti Ipomea purpurea Matricaria chamomilla 20 ALOMY

AVEFA

S SETVI S CYPES

ABUTH

25 IPOSS

MATCH

r.

r 54 A A S C A I H L V E Y 8 P A 0 E T P U 0 T M F V E T S C Compbunds of invention y A I s H s H Example 6.01 Example 6.02 Example 6.03 4 4 4 4 4 4 4 4 4 4 3 4 4 4 4 4 4 4 4 4 4 0 a 0 0 0 0 0 *a 0 0 00 be 3 a 0 Untreated T- _I 55 Example G In a greenhouse, the noted plant species were treated post-emergently with the noted compounds of the invention.

at a rate of 0.1 kg active ingredient/ha. The compounds of the invention were sprayed evenly over the plants as emulsions or suspensions in 500 litres water/ha. One week after the treatment, the compounds of the invention showed a high crop selectivity in wheat with excellent activity against the weeds.

0@ j In the following table: 0 no damage 3, 1 24% damage 2 25 74% damage 3 75 89% damage 4 90 100% damage 020 TRZAX Triticum aestivum ABUTH Abutilon theophrasti GALAP Galium aparine IPOSS Ipomea purpurea 25 MATCH Matricaria chamomilla

-J

0

-Y

56 T A G I M R B A P A Z U L. 0 T A T A S C X H P S H Compounds of invention Example 6.01 Example 6.02 Untreated 1 4 3 4 4 1 4 3 3 3 0 0 0 0 0 *0 00 0 *0 00 0.

0000 *0 0 0 000 0 0. 00 0 0 0 00 0 00 @0 0 4.

200 o6 Go

[I

ii I- -I 57 Example H In a greenhouse, the noted plant species were treated post-emergently with the noted compounds of the invention, at a rate of 0.3 kg active ingredient/ha. The compounds of the invention were sprayed evenly over the plants as emulsions or suspensions in 500 litres water/ha. Two weeks after the treatment, the compounds of the invention showed a high crop selectivity in wheat and maize with excellent activity against the weeds.

a 0 a 0* S 15 0.

SS

S B

S

In the following table: 0 no 1 1 2 25 3 75 4 90 damage 24% damage 74% damage 89% damage 100% damage

TRZAX

ZEAMX

S ABUTH

IPOSS

25 MATCH

SOLSS

VIOSS

Triticum aestivum Zea mays Abutilon theophrasti Ipomea purpurea Matricaria chamomilla Solanum sp.

Viola sp.

4. .f Compounds of invention Example 1. 13 Example 1.14 Example 1.21 Example 1.22 Example 1.24 *Example 1.25 Example 1.26 Example 2.05 Untreated 300 58 T Z A I M S V R E 0 P A 0 1 Z A U 0 T L 0 A M T S C S S X X H S H S S 0 0 3 o 0 4 o 0 4 0 0 4 0 0 4 0 0 4 0 0 3 2 1 4 4 2 4 1 4 2 4 3 4 3 4 3 4 3 4 1 0 0 0 0 0 0 0

Claims

1. A heterocyclic substituted azole and azine of formula I mm k 0 mm mm mm 6 40mm em S 0 000 4 mm em S 0 0 0* S mm *0 in which R, is cyano-Cl-C 3 alkyl, X is one of the groups -CH(CH 3 -CH 2 -CH=N-, -CH 2 or with the proviso that when Z Z 2 Z 4 OrZ6 X is not Y is hydrogen or fluorine, Z is a heterocyclic group of formulae Zj to Z C mmmccc 4 6 .0*5 m em me 9* 0e C 0500 O 00 m Omem em e 06 C CS 0 N N a UN Z 6

11-1 1 AL. U Z. 0 910626,ihnmdaL 100,a:\23568schlres,59 i ii V S 0 a n a.. 1 a i a 1 T- I 1 III~-~PY-iP~I-I i. I1 Cn 1 H3 7 T 111N O S Q is CH, R 14 is hydrogen or methyl, R 3 is hydrogen or methyl, U is oxygen or sulphur, and T is -CH 2 or 2. A herbicidal composition which comprises a compound according to claim 1, in admixture with a carrier or diluent. 3. A method of combating weeds which comprises applying to the weeds or their locus a compound according to claim 1. 4. A compound according to claim 1, a composition according to claim 2, or a method according to claim 3, substantially as hereinbefore described with reference to the Examples. DATED this 26th day of June, 1991. SCHERING AKTIENGESELLSCHAFT By Its Patent Attorneys DAVIES COLLISON 910626,imnda~t.00,aA23568schres,60