CA1301152C

CA1301152C - Optically active diazabicycloalkane derivatives and their use for protecting crops from the phytotoxic effect of herbicides

Info

Publication number: CA1301152C
Application number: CA000527355A
Authority: CA
Inventors: Herbert Scholz; Adolf Zeidler; Bruno Wuerzer; Norbert Meyer
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 1986-01-15
Filing date: 1987-01-14
Publication date: 1992-05-19
Anticipated expiration: 2009-05-19
Also published as: EP0229649A3; EP0229649A2; ZA87238B; EP0229649B1; HUT43071A; DE3600903A1; BR8700127A; GR3001324T3; ATE58138T1; HU198210B; ES2018785B3; AR244313A1; DE3765941D1

Abstract

0.Z. 0050/38193 ABSTRACT OF THE DISCLOSURE: Diazabicycloalkane derivatives of the formula where R is alkyl, R1, R2, R3, R4, R5, R6, R7 and R8 are identical or different and independently of one another are each hydrogen or methyl, X
5 is chlorine or bromine, m is O or 1, n is 1 or 2. and p and q are each 0, 1 or 2, the carbon atom functioning as bridgehead having an R
configuration, and herbicidal agents containing acetanilides as herbididally active compounds and diazabicycloalkane derivatives as antagonistic agents.

Description

- l - O.Z. 0050/38193.
Optically active diazabicycloalkane derivatives and __ __._ their use for protecting ~rops from the phytotoxic effect of herbicides ... . _ _ _ The present invention re(ates to optically a~tive dia~ab;cycloalkane derivatives, crop protection agents wh;ch contain these diazabicycloalkane derivatives, herbi-cides ~hich contain acetanilides as herbicidal active in-gredients and diazabicycloalkane derivatives as antagonis-tic agents, a method ~or protecting crops from the phyto-toxic effect of herbicides based on acetanilides, and amethod for selectively con~rolling undesirable plant growth using the stated herbicides.
- Acetanilides of the formula III

~ CHz A (Ill~

R ~

~here Q9 is hydrogen, C1-Cs-alkyl or C1-Cs-alko~y, R10 and R11 are ;d2ntical or different and are each hydro-gen, C1-Cs-alkyl, C1-Cs-alkoxy or halogen, Y is chlorine or brom;ne and A ;s C1-C4-alkoxy, C1-C4-alko~yalkyl or an azole which is bonded via a ring nitrogen atom and is unsubstituted or substituted by halog2n, phenyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-perfluoro-alkyl, cyano, carboxyl or C1-C4-alkoxy-carbonyl, and A
may furthermore be a salt of an azole containing 2 or 3 nitrogen atoms, possess excellent herbicidal activity but damage the crop plants when used for . e~ample in corn, rice, sorghum or cereals - (DE-A-2 648 008, DE-A-2 744 396, DE-A-2 305 495 and US-A-3 547 620).
EP-A-31 042 and EP-A-65 724 have disclosed herbi-cides ~hich contain acetanilides of the formula lll as the herbicidal active ingredient and racemic N-dihalo-acetyldiazab;cycloalkane derivatives as antagonists.
, ~.

~` ~a~a;~

The N-dihaloacetyldiazabicycloalkane derivatives described in the above prior art references are racemate~ or diastereomer mi~tures. Nothing is known to date concerning the biological action of each of the enan-tiomers or diastereomers of such derivatives.
The invention is based on the discovery that diazabicycloalkane derivatives of the formula I
R3 Q~
~5--CH~n~X~CR~R~)m 0 N N-C0-CHX2 (I) -C H ~ H 2 ~ q R

where R is Cl-C4-alkyl, R1 R2 R3 R4 R5 6 7 8 are identical or different and independently of one another are each hydrogen or methyl, X is chlorine or bromine, m is 0 or 1, n is 1 or 2 and p and ~ are each 0, 1 or 2, are particularly efficient for increasing the toleration of crops for herbicidal acetanilides of the formula III, when the carbon atom of said derivatives of formula I functioning as the bridgehead, has an R configuration~
The diazabicycloalkane derivatives of the formula I as defined hereinabove where the carbon atom functioning as the bridge head has an R configuration, have not been disclosed so far and therefore are new.
In accordance with the inventionj the diazabicycloalkane derivatives of the formula I in which R
is methyl or ethyl, in particular methyl, are preferred.
Examples of antagonistic optically active diazabi-cycloalkane derivatives of the formula I according to the invention are 4-dichloroacetyl-5,7-dimethyl-8-oxo-1,4-diaza-bicyclo[3.3.0~octane, 5-dichloroacetyl-6,8-dimethyl-9-oxo-1,5-diazabicyclo[4.3.0~-nonane, 5-dichloroacetyl-3,3,6,8-.

- ~ .

- 2a -tetramethyl-9-oxo-1,5-diazabicyclo¦4.3.0~nonane, 7-dichlo-roacetyl-3,6,8-trimethyl-2-oxo-1,7-diazabicycloC4.3.~
nonane, 5-dichloroacetyl-6,9-dimethyl-10-oxo-1,5-diazabicy-clo~4.4.01decane, 5-dichloroacetyl-3,3,6,9-tetramethyl-10-oxo-1,5-diazabicyclor4.4.0~decane, 4-dichloroacetyl-5-methyl-8-oxo-1,4-diazabicycloC3.3.0Joctane, 5-dichloro-acetyl-6-methyl-9-oxo-1,5-diazabicyclo¦4.3.0~nonane, 6-di-chloroacetyl-7-.. ~, . .. . .

~ 31~
- 3 - O.Z. 0050/38193 methyl-10-oxo-1,b-diazabicyclo[5.3.0]decane, 5-dichloro-acetyl-3,3,6-trimethyl-9-oxo-1,5-diazabicyclo~4.3.0]nonane, 5-dichloroacetyl-4,4,6-trimethyl-9-oxo-1,5-dia2abicyclo-~4.3.0]nonane, 5-dichloroacetyl-4,4,6-trimethyl-10-oxo-1,5-diazabicyclo~4.4.0]decane, 5-dichloroacetyl-3,3,6-trimethyl-10-oxo~1,5-diazabicyclo~4.4.0]decane and 4 di-chloroacetyl-5,8-dimethyl-9-oxo-1,4-diazdbicyclo~4.3.0]-nonane.
Preferred compounds of the formula I are 5-di-chloroacetyl-6-methyl-9-oxo-1,5-diazabicyclo~4.3.0]nonane and 4-dichloroacet~l-S-methyl-8-oxo-1,4-diazabicyclo-[3.3.0]octane and 5-dichloroacetyl-3,3,6-trimethyl-9-oxo-1,5-diazabirycloC4.3.0]nonane is particularly preferred.
In all of the compounds mentioned, the carbon atom functioning as the bridgehead has an R configuration.
The novel dia abicycloalkane derivatives of the formula I can be obtained by reacting an amine of the for-mula II

`C~
~R5--C~)n~ `(CR~R2)m O N N--H ( I I ) ~R6--CH~ tCH2)q R~

where R is C1-C4-alkyl, R1, R2, R3, R4, R5, R6, R7 and R8 are identical or different and independently of one another are each hydrogen or methyl, m is 3 or 1, n is 1 or 2 and p and q are each 0, 1 or 2, the carbon atom functioning as the bridgehead having an S configuration, with a dihaloacetyl chloride of the formula X2CH-COCl, in ~hich X is chlorine or bromine, in the presence of a hydrogen chloride-binding agent and of a solvent or dil-uent at from -10 to ~50C.
Suitable diluents or solvents are hydrocarbons and halohydrocarbons, such as toluene, xylenes, chloro-benzene, dichloromethane or ethylene chloride, ethers, t~
- ~ - O.Z. OOS0/38193 such as diethyl ether, methyl tert-butyl ether, tetra-hydrofuran or 1,4-dioxane, and nitriles, such as aceto-nitrile.
Suitable hydrogen halide-binding agents are alkali metal carbonates, alkali metal bicarbonates, aqueous solu-tions of alkali metal hydroxides, trialkylamines, N,N-dialkyLanilines, such as N,N-dimethylaniline, and pyridine ~ases. The reaction is advantageously carried ou~ using from 1 to 1.2 moles of dihaloacetyl chloride per mole of the amine of the formula II. From 1 to 1~2 moles of the hydrogen chloride-bind;ng agent are added per mole of di-haloacetyl chloride.
Where X is chlorine, the novel diazabicycloalkane derivatives may furthermore be obtained by reacting an amine of the formula II with chloral hydrate in the pres-ence of an acid acceptor and a catalytic amount o~ cyanide, which is added in the form of, for example, sodium cyan;de or acetone cyanohydrin (DE-A-Z 807 340).
Some of the racemates and diastereomer mixtures of amines of the formuLa II in which the carbon atom func-tioning as the bridgehead has either an R or an S configu-ration are disclosed in DE-A-1 802 468. They can be ob-tained by the preparation process described there, by re-acting y-oxo- or ~-oxocarboxylic acids or their esters Z5 with ~,~-alkylenediamines. For example, the racemate of 6-methyl-9-oxo-1,5-diazabicyclot4.3.0]nonane can be prepared from ethyl lavulinate and propylenediamine.
The optically active amines of the formula II
which are required for the novel process and in which the carbon atom functioning as the bridgehead has an S configu-ration in each case can be prepared by resolution of the above racemates or diastereomer mixtures by means of opti-cally active acids.
Advantageously used optically active acids are chiral sulfonic acids, eg. camphorsulfonic acid or bromo-camphorsulfonic acid, and chiral hydroxycarboxylic acids and their derivatives, eg. lactic acid, tartaric acid, a~
.,~

- 5 - 0.Z. 0050/38193 diacetyltartaric acid, dibenzoyltartaric acid, ~alic acid or mandelic acid~ Optically active hydroxycarboxylic acids are preferred, lactic acid and tartaric acid, especially 3-(-)-lactic acid, being particularly noteworthy.
To prepare the diastereomeric salts from a racemic amine or a diastereomeric amine mixture and a chiral acid, these components are combined, in a suitable inert solvent, in a molar ratio of amine to acid of from 1:1 to 1:1.2, preferably 1:1, at from -20 to ~50C. After a stirring phase of up to 5 hours, during which the temperature is advantageously maintained at from -Z0 to +30C, the di-astereomeric amine salt which has crystallized out, and in which the carbon atom functioning as the bridgehead in the amine component has an S configuration, can be isolated.
Examples of suitable inert solvents for this step are alcohols, such as methanol, ethanol or isopropanol, and ethers, such as 1,2-dimethoxyethane, tert-butyl methyl ether, tetrahydrofuran or 1,4-dioxane, as well as aqueous mixtures of these solvents.
The diastereomeric amine salt which has been iso-lated and in which the amine component has the above con-figuration is washed with the solvent, and the desired amine is then liberated from the said salt. This is usually done in aqueous solution by adding a strong base, for example an aqueous solution of potassium hydroxide or sodium hydroxide. The desired amine is particularly advantageously liberated from the aqueous solution of the diastereomeric amine salt by means of a highly baslc an-ion exchanger.
During this procedure, the amine of the formula II is usually present in aqueous solution and can be ob tained in pure form by evaporating off the water under reduced pressure. The said amine can then be reacted directly with the appropriate dihaloacetyl chloride.
This process can be particularly advantageously used for the preparation and isolation of the diastereo-meric lactate of the formula IV

- 6 - 0.Z. 0050/381~3 r ~ ~H cor~
O ~J~H H--f--OH ( IV) CH3 CH~ CH3 _ 5 1 ~

It is surprising that the amine components, which are aminals of geminal amines, do not undergo a cleavage reaction under the reaction conditions, ie. when treated with an acid, since it is known that such aminals can usually be readily cleaved into a carbonyl compound and two amino components by acid catalysis (P.A.S. Smith, Open-Chain Nitrogen Compounds, vol. 1, page 3Z2, ~.A.
8enjamin, Inc., New York, Amsterdam 1965). For example, Troeger's base undergoes racemization in an acidic medium (E~L. Eliel, Stereochemie der Kohlenstoffverbindungen, page 466~ Verlag Chemie, Weinheim, 1965).
The a~ine salts which remain in the solution when the racemates or diastereomer mixtures are resolved, and in the amine component of which the carbon atom function-ing as the bridgehead has the undesirable configuration, can be converted, by racemizat;on, ;nto m;xtures ;n which the carbon atom functioning as the bridgehead has both an R and an S configuration. These mixtures can then be re-ZO solved again (recycling).
Surpris;ngly, the racemizat;on react;on can also becarr;ed out very advantageously using lactic acid (saving of steps). In th;s procedure, the am;ne salt in which the am;ne component has the wrong configuration is heated to 70-105C ;n aqueous solution. After about 3-9 hours, racemization is complete, and the particular mixture can be obtained in pure form by evaporating the water.
This step can be carried out equally well w;th both the D(-)-lactate and the L(+) lactate, the former being preferably usecl.
It is of course also possible to adopt the reverse - 7 - O.Z. 0050/38193 procedure and use the amines of the formula II for resol-ving racemic lactic acid. We have found that both (L)-and (D)-3,6,6-trimethyl-9-oxo-1~5-diazabicyclo[4.3.0]nonane are particularly useful for this purpose.
S The Examples which follow illustrate the inven-tion.

3,3,6-Trimethyl-9-oxo-1,5-diazabicycloC4.3.0]nonane D(-)-lactate 10 a) 20.5 9 (0.113 mole) of racemic 3,3,6-trimethyl-9-oxo-1,5-diazabicyclo~4.3.0]nonane in 100 ml of tetra-hydrofuran are initially taken. 14 9 (0.113 mole) of purified, 75% strength by weight aqueous D(-)-lactic acid are added dropwise at room temperature, the mixture is stirred for 3 hours at room temperature and at 10C, and the product is filtered off under suction and washed twice with cold tetrahydrofuran.
Yield: 28.6 9 Mp: 70-72C
(~)2DU = +3 5 (c = S; water) (The concentrat;on c is stated in each case in g per 100 ml of solvent.) b) 2740 9 (1 mole) of purified 3.3~ strength by weight aqueous D(-)-lactic acid are initially taken, and 182 9 (1 mole) of racemic 3,3,6-trimethyl-9-oxo-1,5-diazabi-cycloC4.3~0]nonane are introduced slowly at 22C. The reaction is slightly exothermic, and the temperature in-creases to 25C. Stirring is continued for 1 hour, and the mixture is evaporated down in a rotary evaporator at a maximum bath temperature of 70C and under 30 mm Hg.
277 9 of residue are obtained in the form of a reddish oil, to ~hich 300 ml of tetrahydrofuran are added while stirring. After about 1 hour, the suspension containing the precipitated colorless crystals is cooled to -5C and stirred for half an hour at this temPerature, and the pro-duct is washed with 3 x S0 m~ of tetrahydrofuran at -20C
and dried in a drying oven at 53C.

- 8 - O.Z. OOS0/38193 Yield: 252.2 9 = 92.7~.

S(-)-3,3,6-Trimethyl-9-oxo-1,5-cliazabicyclo~4~3.0~nonane D(-)-lactate Z0 9 of the lactate from ~xample 1 are dissolved in 500 ~l of tetrahydrofuran, and the gently stirred solu-tion is cooled to -20C. After 3 hours, the precipitate is filterecl off under suction.
Yield: 7.2 9 1û Mp.: 103-105C
()2D0 = _10.70 (c = 2; water) S(+)-3,3,6-Trimethyl-9-oxo-1,5-diazabicyclo~4.3.0]nonane 4.7 9 (0.017 mole) of the lactate from Example 2 are dissolved in 172 ml of water, and the solution is poured, in the course of 3 hours, over a column which has a diameter of 2 cm and a length of 36 cm and contains a strongly basic anion e~changer. After the solution has passed through, the column is washed at the same rate ~ith Z0 300 ml of water. The aqueous solutions collected are evaporated to dryness in a rotary evaporator, and the resi-due is dried overnight in a drying oven.
Yield: 3 9 = 95.5~ of theory Mp.: ~8.5-89C
(~)2~ = ~34.2 (c - 2; water) R(-)-5-Dichloroacetyl-3,3,6-trimethyl-9-oxo-1,5-diazabi-cyclo~4.3.0~nonane 3 9 (0.01648 mole) of the amine from Lxample 3 and 1.9 9 (0.0184 mole) of triethylamine in 16.5 ml of toluene are initially taken. 2.7 9 (0.0179 mole) of di-chloroacetyl chloride are added at from 30 to 35C in the course of 15 minutes, the mixture is stirred for 2 hours at 30C, 16.5 ml of water are added and stirring is con-tinued for 1 hour at 3C. The product is filtered offunder suction at room temperature and washed twi~e with 5 ml of water and t~ice with 4 ml of cold isopropano~.

.?3L~Lr ~
9 O.Z. 0050/38193 Yield: 3.7 9 = 77.1% of theory Mp.: 170-171C
t~20 = _49 (c = 2; CHCl3) Purity: 99~ tHPLC) 3,3,6-Trimethyl-9-oxo-1,5-diazabicyclo~4.3.0]nonane L(~)-lactate The procedure is similar to that described in Example 1, except that Lti)-lactic acid is used.
Mp.: 71.5-72C
(~)2D0 = -4.2 (c = 5; water) R(+)-3,3,6-Trimethyl-9-oxo-1,5-diazabicyclo[4.3.0]nonane L(+)-lactate The procedure is similar to that described in Example 2, except that the L(+)-lactate from Example 2 is used.
Mp.: 103-105.5C
(a)2D0 = ~11.7 (c = 2; water) R(-)-3,3,6-Trimethyl-9 oxo-1,5-diazabicycloC4.3.0]nonane The procedure is similar to that described in Example 3, except that the L(+~-lactate from Example 6 is used.
Mp.: 88.5-89.5C
(a)ZD = -34.2 (c = 2; water) 5(+)-5-Dichloroacetyl-3,3,6-trimethyl-9-oxo-1,5-diazabi-cyclo~4.3.0]nonane The procedure is similar to that described in Example 4, except that the R(t)-amine from ExamPle 7 is used.

Mp.: 168-169.5C
(~)2D0 = ~50.9 (c = 2; CHCl3) Racemization of R-3r3,6-trimethyl-9-oxo-1,5-diazabicyclo-[4.3.0]nonane D(-)-lactate ~ 10 - O.Z. 0050/38193 8 9 of the sta~ed lactate, ()20 = ~12 (c ~

2; water)~ in ~00 ml of water are refluxed. The angle of rotat;on changes fro~ ~12 to ~4.5 ;n the course of 6 hours. Evaporat;on to dryness gives a residue having S a melting point of 68-72C.

4-Dichloroacetyl-5,8-d;methyl-9-oxo 1,4-d;a2ab;cyclot4.3.0]-nonane ;n wh;ch ~he br;dgehead carbon atom has the R con-f;gurat;on a) 1Z4.2 9 (0.75 mole) of methyl 2-methyl-5-oxohex-anoate ;n 450 ml of n~heptane are in;t;ally taken. 52.2 9 (0~87 mole) of ethylened;amine are then added dropw;se at room temperature ;n the course of 10 m;nutes. As a result of the exotherm;c react;on, the temperature increases to 38C. 49 ml of the lower phase (aqueous methanol~ are separated off. The m;xture is cooled to 2C and st;rred for 1 hour, and the product is filtered off under suct;on, washed w;th cold n-he~tane and dr;ed. 116.3 9 of racem;c 5,8-d;methyl-9-oxo-1,4-d;azab;cycloC4.3.0~nonane are obta;ned.
Mp.: 85-87C (after recrystall;zat;on from cyclohexane).
b) 52 9 (0.31 mole) of racemic 5,8-d;methyl-9-oxo-1,4-d;azab;cycloC4.3.0~nonane are d;ssolved in 200 ml of ethanol. A solution of 46.4 g (0.31 mole) of L(+)-tar-taric acid in 520 ml of ethanol are added dropw;se at roomtemperature, and the mixture is stirred for 1 hour and cooled to 5C.
Yield: 89.1 ~ = 90.4% of theory Mp.: 152-154.5C
(~32 = +12.5 (c = 1; water) c) The diastereomeric amine salt ;s obtained by fract;onal crystall;zat;on of 5,8-dimethyl-9-oxo-1,4-di-azab;cyclo~4.3.0~nonane L~+)-tartrate from isopropanol.
()2n = -7.7 (c = 2; water) d) An aqueous solution of the tartrate from Example 10c is poured over an anion exchanger similarly to Example 3. Thereafter, 5.7 g (O.û34 mole) of the resulting amine ~ O.Z. ~050/38193 are initially taken in 50 ml of toluene together with 3.6 9 (0.036 mole) of triethylamine. 5.1 9 ~0.034 mole) of dichloroacetyl chloride are added dropwise to the cold mixture at from 30 to 35C~ and stirring is continued for 1 hour. S0 ml of water are added, the mixture is stirred for half an hour and the phases are separated.
The toluene phase is washed with twice 50 ml of water and evaporated down in a rotary evaporator to give 6 9 of a yellow oil, which is crystallized with a little tert-butyl methyl ether and washed with a small amount of the same ether.
Mp.: 113-115C
(c~)20 = -12~ (c - 1; acetone) The racemate prepared in a similar manner has a melting point of 116-117C.
Acetanilides whose toleration by crops can be im-proved by the optically active diazabicycloalkane deriva-tives of the formula I are those of the formula I~I in which R is hydrogen, C1-C5-alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl or a branched pentyl radical, or C1-C5-alkoxy, such as methoxy, ethoxy, propoxy, butoxy or pentyloxy, R10 and R11 are each hydrogen, halogen, such as fluorine, chlorine, bromine or iodine, C1-Cs-alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyL, sec-butyl, isobutyl, tert-butyl, n-pentyl or a branched pen-tyl radical, or C1-Cs-alkoxy, such as methoxy, ethoxy, propoxy, butoxy or pentyloxy, Y is chlorine or bromine and A is C1-C4-alkoxy or C1-C4-alkoxyalkyl, such as methoxy, ethoxy, methoxymethyl or 2-methoxyethyl, or an azole which is bonded via a ring nitrogen atom, eg. pyrrole, pyrazole, imidazole, 1,2,4-triazole, 1,2,3-triazole or tetrazole, which is unsubstituted or monosubstituted or polysubsti-tuted by halogen, phenyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C~-alkylthio, C1-C4-perfluoroalkyl, cyano, carboxyl or C1-C4-alkoxycarbonyl.
Examples of substituted azoles A are 2,6-dimethyl-31 3(~ .2 - 1Z - O.Z. OOS0/3~193 pyrrole, tetramethylpyrrale, 3(5)-methylpyrazole, 4-methyl-pyrazole, 3(5)-ethylpyrazole, ~-etnylpyrazole, 3(5)-iso-propylpyrazole, 4-isopropylpyrazole, 3,5-dimethylpyrazole, 3,4,5-trimethylpyr3zole, 3~5)-phenylpyrazole, 4-phenyl-pyrazole, 3,5-diphenylpyrazole, 3(5)-phenyl-St3)-methyl-pyrazole, 3tS)-chloropyrazole, 4-chloropyrazole, 4-bromo-pyrazole, 3,S-dimethyl-4-chloropyrazole, 3,5-dimethyl-4-bromopyrazole, 4-chloro-3(5)-methylpyrazole, 4-methyl-3,5-dichloropyrazole, 3(5)-methyl-4,5(3)-dichloropyrazole, 3(5)-chloro-5(3)-methylpyrazole, 4-methoxypyrazole, 3(5)-methyl-5(3)-trifluoromethylpyrazole, 3tS)-methyl-5(3)-ethoxycarbonylpyrazole, 3tS)-methyl-5t3)-methylthio-4-methoxycarbonylpyrazole, 4-cyanopyrazole, 4,5-dichloro-imidazole, 2-methyl-4,5-dichloroimidazole, 3(5)-methyl-1,2,4-triazole, 3,5-dimethyl-1,2,4-triazole, 3(5)-chloro-1,2,4-triazole, 3,5-dichloro-1,2,4-triazole, 4tS)-methyl-1,Z,3-triazole, 5-methyltetrazole and S-ch(orotetrazole.
Where the azole contains 2 or 3 nitrogen atoms, the radical A may furthermore be bonded in the form of a salt to one of the conventional strong inorganic or or-ganic acids, such as hydrochloric acid, nitric acid, sul-furic acid, trichloroacetic acid, methanesulfonic acid, perfluorohexanesulfonic acid or dodecylbenzenesulfonic acid.
Preferred acetanilides of the formula III are 25 those in which R9 is hydrogen, R10 and R11 independently of one another are each methyl or ethyl in the ortho-position, Y is chlorine and A is unsubstituted or methyl-substituted pyrazole or triazole, each of which is bonded via a ring nitrogen atom.
Examples of herbicidal chloroacetanilides are 2-chloro-2',6'-dimethyl-N-~pyrazol-1-ylmethyl)-acetanilide, 2-chloro-2',6'-dimethyl-N-(3,5-dimethylpyrazol 1-ylmethyl)-acetanilide, 2-chloro-2',6'-diethyl-N-(pyrazol-1-ylmethyl)-acetanilide, 2-chloro-6'-ethyl-N-tpyrazol-1-ylmethyl)-acet-o-toluidide, 2-chloro-6'-ethyl-N-(3,5-dimethylpyra-zol-1-ylmethyl)-acet-o-toluidide, 2-chloro-2',6'-dimethyl-N-(1,2,4-triazol-1-ylmethyl)-acetanilide, 2-chloro-6'--~`` 1.3~ L~2 - 13 - O.Z. 0050/3~193 ethyl-N-(1,2,4-triazol-1-ylmethyl)-acet-o-toluidide, 2-chloro-2',6'-diethyl-N-(2"-propyloxyethyl)-acetanilide, 2-chloro-6'-ethyl-N-(2"-methoxy-1"-methylethyl)-acet-o-toluidide, 2-chloro-2',6'-diethyl-N-(butc)xymethyl)-acet-S anilide, 2-chloro-6'-ethyl-N-(ethoxymethyl)-acet-o-tolui-dide, 2-chloro-2',6'-dimethyl-~-(2"-~ethoxyethyl)-acet-anilide, 2-chloro-6'-ethyl-~-(2"-butoxy-1"-methylethyl)-acet-o-toluidide, Z-chloro-2',6'-diethyl-N-(methoxymethyl)-acetanilide and 2-chloro-Z',6'-diethyl-N-(ethoxycarbonyl-methyl)-acetanilide.
Herbicidal active ingredients and compounds which act as antagonists (antidotes) and provide protection can be apPlied together or separately by conventional tech-niques for crop treatment agents. ~or e~ample, they can be incorporated into the soil together or separately, be-fore or after sowing. In the most common method of app-lication they are applied to the soil surface ~irectly after sowing or in the period between sow;ng and emergence of the young plants. Treatment during and after emergence of the crops is also possible. The antagonist can always be applied simuLtaneously with the herbicidal active in-gredient. Separate application, where the antagonist is first applied to the field, followed by the herbicidal actiye ingredient, or vice versa, is also possible provi-ded that the ~ime between application of the two sub-stances is not so long that the herbicidal active ingre-dient has already damaged the crops. The active ingre-dient and antagonist can be formulated, separately or together, as sprays ;n suspendable, emulsifiable or sol-uble form or as granules. It is also possible for theseeds of the crop plants to be treated with the antagonist prior to sowing. In this case, the herbicidal active ingredient is applied alone in a conventional manner.
~or a specific acetanilide, different amounts of the antagonistic compound are required, depending on the crops to be treated in each case. The ratios in Jhich the acetanilide and the diazabicycloalkane derivative can `` ~3~ 2 - 14 - O.Z. 0050/38193.
be employed may be varied within a fair~y wide range.
According to the invention, the weight ratio of the herbicidal acetanilide to the an~agonistic diazabicyclo-aLkane derivative is from 1:2 to 1:0.001, preferably from 1:0~25 to 1:0.005, in particular 1:0.01.

Q~
~.Z. OOS0/3~1g3 The agents according to the invention containing diazabicycloalkane d~riv-atives may be applied for instance in the ~orm of directly sprayable solutions, powders, suspensions lincluding high-percentage a~ueous, oily or other suspensions), dispersions, emulsions, oil dispersions, pastes, 5 dusts, broadcasting agents or granules by spraying, atomizing, dusting, broadcasting or watering. The forms of application depend entirely on the purpose for which the agents are being used, but they must ~nsure as fine a distribution of the active ingredients according to the invention as possible.
For the preparation of solutions, emulsions, pastes and oil dispersions to be sprayed direct, mineral oil fractions of medium to high boiling point, such as karosene or diesel oil, further coal-tar oils, and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons 5 such as benzene, toluene, xylene, and paraffin, tetrahydrocarbons such as methanol, ethanol, propanol, butanol, chloroform, carbon tetrachloride, cyclohexanol, cyclohexanone, chlorobenzene, isophorone, atc., and strongly polar solvents such as dimethylformamide, dimethyl sulfoxide, N-methyl-pyrrolidone, water, etc. are suitable.
Aqueous formulations may be prepared from emulsion concentrates, pastes, oil dispersions or wettable powders by adding water. To prepare emulsions, pastes and oil dispersions th~ ingredients as such or dissolved in an oil or solvent may be homogenized in water by means of wetting or dispersing 25 agents, adherents or emulsifiers. Concentrates which are suitable for dilution with ~ater may be prepared from active ingredient, wetting agent, adherent, emulsifying or dispersing agent and possibly solvent or oil.
Examples of surfactants are: alkali metal, alkalinfi earth metal and 30 ammonium salts of ligninsulfonic acid, naphthalenesulfonic acids, phenol-sulfonic acids, alkylaryl sulfonates, alkyl sulfates, and alkyl sulfonat~s, alkali metal and alkaline earth metal salts of dibutylnaphthalenesulfonic acid, lauryl ether sulfate, fatty alcohol sulfates, alkali metal and alkaline earth matal salts of fatty acids, 35 salts of sulfat~d hexadecanols, heptadecanols and octadecanols, salts of sulfated fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and naphthalene derivativcs with formaldehyde, condensation products of naphthalene or naphthalenasulfonic acids with phenol or formaldehyde, polyoxyethylane octylphenol ethers, ethoxylated isooctyl-40 phenol, ethoxylated octylphenol and ethoxylated nonylphenol, alkylphenolpolyglycol ethers, tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxy-16 O.Z. 0050/38193 propylene, lauryl alcohol polyglycol ether acetal, sorbitol 0sters,lignin, sulfite waste liquors and methyl cellulose.
Powders, dusts and broadcasting agents may be prapared by mixing or 5 grinding the active ingredients with a solid carrier.
Granules, e.g., coated, impregnated or homogeneous granules, may be prepared by bonding the active ingredients to solid carriers. Examples of solid carriers are mineral earths such as silicic acid, silica gels, 10 silicates, talc, kaolin, attapulgus clay, lim~stone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground plastics, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate and ureas, and vegetable products such as gr3in flours, bark meal, wood meal and nutshell meal, 5 cellulosic powders, etc.
The formulations contain from 0.1 to 95, and preferably from 0.5 to 90, Z
by weight of herbicidal active in~redient and antidote, or antidote on its `
own. The application rates for herbicidal active ingredient are from 0.1 20 to 0.5 kg/ha. This amount of active ingredient is applied either jointly or separately with such an amount of antidote that the weight ratio of active ingredient to antidote is, as stated above, fro~ 1:2 to 1:0.001, preferably from 1:0.25 to 1:0.005, and especially from 1:0.25 to 1:0.01.

25 Examples of formulations are given below.
I. 40 parts by weight of a mixture consisting of ~ parts by weight of 2-chloro-2 ,6 -dimethyl-N-lpyrazol-1-yl-methyl)-acetanilide and 1 part by weight of Rl-t-5-dichloroacetyl-3,6,6-trimethyl-9-oxo-1,5-diazabicyclot~.3.0]nonane is intimately mixed with 10 parts by weight of tho sodium salt of a phenolsulfonic acid-urea-formaldehyde condensate, 2 parts by weight of silica gel and 4a parts of water. A
stabla aqueous dispersion is obtained. Dilution with 100,000 parts by weight of water gives an aqueous dispersion containing O.O~wtX of 3~ active ingre~ient.
II. 3 parts by weight of a mixture consisting o~ 1 part by weight of Z-chloro-2 -methyl-6 -ethyl-N-Ipyrazol-1-yl-methyl)-acetanilide and 1 part by weight of Rl-~-5-dichloroacetyl-3,6,6-trimethyl-9-oxo-1.5-diazabicyclo[~.3.0]nonane is intimately mixed with 97 parts by weight of particulate kaolin. A dust is obtained containing 3X by weight of active ingredient.

~ 3~

17 O.Z.OoS0/3a193 III. 30 parts by weight of a mixture consisting of 1 part by weight of 2-chloro-2 -methyl 6 -ethyl-N-(pyrazol-1-yl-methyl~-acetanilide and 2 parts by weight of R(-1-5-dichloroacetyl-3,6,6-trimethyl-9-oxo-1,5-diazabicyclo~.3.0]nonane is intimately mi~ed with a mixture con-siqting of 92 parts by weight of powdered silica gel and ~ parts by weight of paraffin oil which has been sprayed onto the surface of this silica gel. A formulation of the active ingredient is obtained having good adherence.
?0 IV. 20 parts by weight of a mixture consisting of ~ parts by weight of 2-chloro-2 -methyl-6'-ethyl-N-ethoxymethylacetanilide and 1 part by weight of Rl-)-S-dichloroacetyl-3,6,6-trimethyl-9-oxo-1,5-diazabi-cyclo~.3.0]nonane is intimately mi~ed with 2 parts by weight of the calcium salt of dodecylbenzenesulfonic acid, 8 parts by weight of a fatty alcohol polyglycol ather, 2 parts by weight of the sodium salt of a phenolsulfonic acid-urea-formaldehyde condensate and 6~ parts by weight of a paraffinic mineral oil. A stable oily dispersion is obtained.
za v. 20 parts by weight of a mixture consisting of 10 parts by weight of 2-chloro-2 ,6 -dimethyl-N-l2-methoxymethyl)-acatanilida and 1 part by weight of Rl-)-5-dichloroacetyl-3,6,6-trimethyl-9-o~o-1,5-diaza-bicyclot~.3.0]nonane is dissolved in a mixture consisting of 40 parts by weight of cyclohexanone, 30 parts by weight of isobutanol, 20 parts by weight of the adduct of 7 moles of ethylene oxide and 1 mole of isooctylphenol, and 10 parts by weight of the adduct of ~0 moles of ethylene oxide and 1 mole of castor oil. i3y pouring the solution into 100,000 parts by weight of water and finely distribut-ing it therein, an a~ueous dispersion is obtained containing 0.02X
by weight of artive ingredient.
The novel harbicidal agents may also contain, in addition to acetanilide and diazabicycloalkane derivative, further herbicidal or growth-regulating active ingredients of di~ferent chemical structure, without the antagon-3~ istic effect being lost. They may for instance contain 2-chloro-~-ethyl-amino-6-isopropylamino-1,3,5-triazine, 2-(2-chloro-~-ethylamino-1,3,5-triazin-6-yl-amino)-2-methylpropionitrile and N-~1-ethyl-n-propyl1~2.6-dinitro-3,~-dimethylaniline.

1B O.Z. OOS0/3a193 The action of the herbicidal agents according to the .invention and the antidotes contained therein is demonstrated by the following biological experiments. For comparison purposes. a herbicidal agent disclosed in EP-A-31,~02 was ussd which contained, as herbicidal active ingredient, 2-chloro-2 ,6'-dimethyl-N-lpyrazol-1-yl-methyl)-acetanilide IA) and, as antagonistic agsnt, 5-dichlDroacetyl-3,3,6-trimethyl-9-oxo-1,5-diazabi-cyclo[S.3.0]nonane in the form of a racemic mixture.
The exp~riments show that the tolerance of the herbicidal acetanilides by 1D crop plants is decisively improved by combinQd application of the optically activ~ diazabicycloalkane d~rivatives (dihaloacetamides~ without any loss in herbicidal action.
In the greenhouse, p1astic boxes lS1 x 32 x 6 cm~ were filled with a loamy 15 sand (pH 71 containing ~.3X humus. Indian corn seeds were sown shallow in rows in this substrate, and Echinochloa crus-galli was broadcast as an unwanted grass.
Herbicide A was applied individually and in combination, and the antag-20 onists were only applied in the stated miNtures. All applications were preemergence: the agents were emulsified or suspended in water as carrier, and sprayed through finely distributing nozzles immediately after sowing.
The boxes were set up in the gr~enhouse in an average temperature range of 15 to 25C.
2~
~hese experiments were observed until the corn plants had developed 3 to 5 leaves. After this stage, no more damage by the herbicidal agents was to be expected.
30 The action of the agents was assess~d on a 0 to 100 scale, 0 denoting normal emergence and development of the plants, with reference to the untreated control, and 100 denoting nonemergence or complete destruction.
The heavy damage to the crop plant Indian corn caused by herbicide A under 35 the severe test conditions was considerably reduced by the antidotQ used for comparison purposes.
In the same mixture ratio with herbicide A, compound no. ~ eliminated the damage completely (see T~bl0 1).
The novel optically active diazabicycloalkane derivatives have an action far superior to that of the racemic mixtures.

`` ` ~ 3~ 1Ls~Z
. 19 O.Z. 0050/3~193 Table 1 Improvement in the tolerance by Indian corn o~ the herbicide 2-chloro-2 ,6 -dimethyl-N-Ipyrazol-1-yl-methyl)-acetanilide 1A~ in admixture with S an optically active diazabicycloalkane derivative ; preemergence applic-ation in the greenhouse Harbicidal Antagonist Appl. Test plants and X damage active inqredient rate Z~a mavs Echin~ crus-qalli A - 1.0 95 100 0.25 20 100 A 5-dichloroacetyl-~5 3,3,6-trimethyl-9-oxo-1,5-diaza- 1.0~0.2515 100 bicyclot~.3.0~-nonane (racemic mixture) A Example ~ 1.0~0.25 0 100 3a

Claims

1. An optically active diazabicycloalkane derivative of the formula I

(I), where R is C1-C4-alkyl, R1, R2, R3, R4, R5, R6, R7 and R8 are identical or different and independently of one another are each hydrogen or methyl, X is chlorine or bromine, m is 0 or 1, n is 1 or

2, and p and q are each 0, 1 or 2, the carbon atom functioning as bridgehead having an R configuration.
2, A process for manufacturing optically active diazabicycloalkane derivatives of the formula I as set forth in claim 1, wherein an amine of the formula II

(II), where R is C1-C4-alkyl, R1, R2, R3, R4, R5, R6, R7 and R8 are iden-tical or different and independently of one another are each hydro-gen or methyl, X is chlorine or bromine, m is 0 or 1, n is 1 or 2, and p and q are each 0, 1 or 2, the carbon atom functioning as bridgehead having an S-configuration, is reacted with a dihaloacetyl chloride of the formula X2CH-COCl, X denoting chlorine or bromine, in the presence of 2 hydrogen chloride-binding agent and of a solvent or diluent.

3. The use of an optically active diazabicycloalkane derivative of the formula I as set forth in claim 1 for protecting crop plants against the phytotoxic action of herbicides based on acetanilides.

4. A herbicidal agent containing, as herbicidal active ingredient, at least one acetanilide of the formula III

(III), where R9 is hydrogen, C1-C5-alkyl or C1-C5-alkoxy, R10 and R11 are identical or different and are each hydrogen, C1-C5-alkyl, C1-C5-alkoxy or halogen, Y is chlorine or bromine, and A is C1-C4-alkoxy, C1-C4-alkoxyalkyl or an azole which is bonded via a ring nitrogen atom and is unsubstituted or substituted by halogen, phenyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-perfluoroalkyl, cyano, carboxyl or C1-C4-alkoxycarbonyl, and A may furthermore be a salt of an azole containing 2 or 3 nitrogen atoms, and, as antagonistic com-pound, at least one optically active diazabicycloalkane derivative of the formula I as set forth in claim 1.

5. A herbicidal agent as set forth in claim 4, containing, as herb-icidal active ingredient, an acetanilide of the formula III, where R9 is hydrogen, R10 and R11 are identical or different and are each methyl or ethyl in the o-position, Y is chlorine and A is unsub-stituted or methyl-substituted pyrazole or triazole, each of which is bonded via a ring nitrogen atom.

6. A herbicidal agent as set forth in claim 4, wherein the weight ratio of acetanilide to optically active diazabicycloalkane derivative is from 1:2 to l:0.00l.

7. A process for protecting crop plants against the phytotoxic action of herbicides based on acetanilides, wherein the crop plants, their seed or the location are treated with an effective amount of an optically active diazabicycloalkane derivative of the formula I as set forth in claim 1.

8. A process for the selective control of unwanted plant growth, wherein an acetanilide of the formula III as set forth in claim 4 and an optically active diazabicycloalkane derivative of the formula I as set forth in claim 1 are applied simultaneously or one after the other in any order either during or after sowing of the crop plant or before or during emergence of the crop plants.

9. A process for the selective control of unwanted plant growth with acetanilides of the formula III
as set forth in claim 4 wherein the seed of the crop plants is treated with an optically active diazabicycloalkane derivative of the formula I as set forth in claim 1.

10. R(-)-5-Dichloroacetyl-3,3,6-trimethyl-9-oxo-1,5-diazabicyclo[4.3.0]nonane.

11. 4-Dichloroacetyl-5,8-dimethyl-9-oxo-1,4-di-azabicyclor[4.3.0]-nonane in which the bridgehead carbon atom has the R configuration.

12. The use of a derivative as claimed in claim 10 or 11 for protecting crop plants against the phytotoxic action of herbicides based on acetanilides.

13. A process for protecting crop plants against the phytotoxic action of herbicides based on acetanilides, wherein the crop plants, their seed or the location are treated with an effective amount of a derivative as claimed in claim 10 or 11.