Saccharin derivatives

This application is a 371 of PCT/EP95/02975 filed Jul. 27, 1995, published as WO96/05198 Feb. 22, 1996.
The present application relates to saccharin derivatives of the formula I ##STR3## where the substituents have the following meanings: L and M are hydrogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylthio, chlorine, cyano, methylsulfonyl, nitro or trifluoromethyl;
Z is hydrogen, C.sub.1 -C.sub.4 -alkyl, C.sub.3 -C.sub.8 -cycloalkyl, C.sub.3 -C.sub.6 -alkenyl, C.sub.3 -C.sub.5 -alkynyl, C.sub.1 -C.sub.4 -acyl, benzyl or phenyl, the phenyl rings in each case being unsubstituted or substituted by halogen or C.sub.1 -C.sub.4 -alkyl;
Q is a radical T-J, where
T is a carbonyl radical CO or the radical --CHY,
J is a 4-linked isoxazole ring of the formula II ##STR4## where R.sup.1 is hydrogen or C.sub.1 -C.sub.4 -alkyl and
R.sup.2 is C.sub.1 -C.sub.4 -alkyl, cyclopropyl, 1-methylcyclopropyl or 1-methylthiocyclopropyl;
Y is an OH group, a hydroxyl group which may be acylated by C.sub.2 -C.sub.4 -acyl or a chlorine atom;
and agriculturally customary salts of the compounds I.
The invention further relates to herbicidal compositions, containing the compounds I, and methods of controlling undesired plant growth using the saccharin derivatives I. Moreover, the present invention also encompasses intermediates for preparing the final products I according to the invention and preparation processes for the products I, using the novel intermediates of the formulae B2 and IV ##STR5##
Saccharin derivatives having herbicidal action cannot be inferred from the prior art. However, unsubstituted saccharin (o-sulfobenzimide, ie. L, M, Q and Z in formula I=H) has been known as a synthetic sweetener for a long time. 4-Hydroxysaccharin is further known as a sweetener (German Offenlegungsschrift 3 607 343). The use of saccharin derivatives in pest control is also known, eg. JP publication 72/00419, 73/35457 (fungicides) and in pharmacy, eg. EP-A 594 257 and patents further mentioned therein.
Heterocyclic compounds having a sulfonamide-containing ring have been disclosed as herbicides, a typical representative which can be mentioned here being bentazone ##STR6##
It is an object of the present invention to make available novel herbicides having a basic structure which was hitherto unknown for this indication. We have found that this object is achieved by the compounds I and the intermediates B2 defined at the outset.
Compounds of the formula I where R.sup.1 =H are obtained by acylating .beta.-ketoesters of the formula A1 �Y. Oikawa et al., JOC 43 (1978), 2087! with an acid chloride of the formula IV to give an ester of the formula B1, converting this by reaction with p-toluenesulfonic acid in toluene to a 1,3-diketone of the formula C1, then either converting the 1,3-diketone C1 to an enol ether D1 using ethyl orthoformate or to an enamine D2 using dimethylformamide dimethyl acetal and reacting D1 or D2 with hydroxylamine to give the saccharin derivative of the formula I.1. The reaction sequence is summarized in the following reaction scheme: ##STR7##
The .beta.-ketoesters of the formula A1 used as starting materials are known and can be obtained eg. by reaction of Meldrum's acid with acid chlorides of the formula R.sup.2 --COCl and subsequent reaction with tert-butanol. ##STR8##
The reaction of .beta.-ketoesters of the formula A1 with benzoyl chlorides and the subsequent acid-catalyzed decomposition to 1,3-diketones is known, eg. from EP-A 527 037 and EP-A 560 483. Both the condensation of 1,3-diketones with triethyl orthoformate and the reaction of the enol ethers D1 formed in this case with hydroxylamine to give isoxazoles is known, eg. from EP-A 527 036 and EP-A 560 483. The reaction of 1,3-diketones with orthoamides such as dimethylformamide dimethyl acetal and the subsequent reaction of the enamines D2 formed in this case with hydroxylamine to give isoxazoles is described by Menozzi in J. Het. Chem. 20 (1983), 645.
If, however, R.sup.1 has the meaning C.sub.1 -C.sub.4 -alkyl, the compounds of the formula I are obtained by reacting saccharincarbonyl chlorides of the formula IV with alkynylstannanes of the formula A2 to give benzoylalkynes of the formula B2 and then subjecting these to a cycloaddition with nitrile oxides of the formula C2 to give the isoxazoles of the formula I.2: ##STR9##
In the formulae mentioned above, L and M have the meaning given at the outset and Z is hydrogen, C.sub.1 -C.sub.4 -alkyl, C.sub.3 -C.sub.8 -cycloalkyl, C.sub.3 -C.sub.6 -alkenyl, C.sub.3 -C.sub.5 -alkynyl, C.sub.1 -C.sub.4 -acyl, or benzyl or phenyl which is unsubstituted or substituted by halogen or C.sub.1 -C.sub.4 -alkyl.
Alkynylstannanes of the formula A2 are accessible in a known manner from trialkyltin chloride and lithium acetylides. Aroylalkynes are prepared in a manner known per se from alkynylstannanes and benzoyl chlorides in the presence of palladium catalysts such as bis(triphenylphosphine)palladium(II) chloride, as described eg. by Crisp in Synth. Comm. 19 (1989), 1745.
Nitrile oxides of the formula C2 are obtained in a manner known per se from hydroxamoyl chlorides and tertiary amines such as triethylamine. The cycloaddition of aroylalkynes and nitrile oxides to give isoxazoles is disclosed eg. in EP-A 487 357.
The starting substances of the formula IV are prepared in a manner known per se by reaction of the saccharincarboxylic acid derivatives III ##STR10## with thionyl chloride.
Saccharincarboxylic acids III are known in some cases (4-COOH: Zincke, Liebigs Ann. 427 (1922), 231, 5-COOH: Jacobsen, Chem. Ber. 13 (1880), 1554, 6-COOH: Weber, Chem. Ber. 25 (1892), 1740). Further, the preparation of 4-chlorosaccharin-5-carboxylic acid is described in German Offenlegungsschrift 36 07 343.
Saccharincarboxylic acids can also be obtained by reacting corresponding bromo-or iodo-substituted saccharin derivatives of the formula A3 ##STR11## where L, M and Z have the abovementioned meanings, or if Z.noteq.H, compounds of the formula A4 ##STR12## with carbon monoxide and water or a C.sub.1 -C.sub.6 -alcohol at elevated pressure in the presence of a palladium, nickel, cobalt or rhodium transition metal catalyst and a base.
If, for example, L is methyl and M and Z are hydrogen, the reaction sequence can be shown as follows: ##STR13##
The catalysts nickel, cobalt, rhodium and in particular palladium can be present in metallic form or in the form of customary salts, such as in the form of halogen compounds, eg. PdCl.sub.2, RhCl.sub.3.H.sub.2 O, acetates, eg. Pd(OAc).sub.2, cyanides etc. in the known valency states. Metal complexes with tertiary phosphines, metal alkylcarbonyls, metal carbonyls, eg. CO.sub.2 (CO).sub.8, Ni(CO).sub.4, metal carbonyl complexes with tertiary phosphines, eg. (PPh.sub.3).sub.2 Ni(CO).sub.2, or transition metal salts complexed with tertiary phosphines can further be present. The last-mentioned embodiment is particularly preferred in the case of palladium as a catalyst. The nature of the phosphine ligands here is widely variable. For example, they can be represented by the following formulae: ##STR14## where n is the numbers 1, 2, 3 or 4 and the radicals R.sup.7 to R.sup.13 are low-molecular weight alkyl, eg. C.sub.1 -C.sub.6 -alkyl, aryl or C.sub.1 -C.sub.4 -alkylaryl, eg. benzyl, phenethyl or aryloxy. Aryl is, eg. naphthyl, anthryl and preferably unsubstituted or substituted phenyl, it only being necessary with respect to the substituents to take into account their inertness to the carboxylation reaction, otherwise they can be widely varied and include all inert C-organic radicals such as C.sub.1 -C.sub.6 -alkyl radicals, eg. methyl, carboxyl radicals such as COOH, COOM (M is eg. an alkali metal, alkaline earth metal or ammonium salt), or C-organic radicals bonded via oxygen, such as C.sub.1 -C.sub.6 -alkoxy radicals.
The preparation of the phosphine complexes can be carried out in a manner known per se, eg. as described in the documents mentioned at the outset. For example, commercially available metal salts such as PdCl.sub.2 or Pd(OCOCH.sub.3).sub.2 are used as starting materials and the phosphine, eg. P(C.sub.6 H.sub.5).sub.3, P(n-C.sub.4 H.sub.9).sub.3, PCH.sub.3 (C.sub.6 H.sub.5).sub.2 or 1,2-bis(diphenylphosphino)ethane added.
The amount of phosphine, based on the transition metal, is customarily from 0 to 20, in particular from 0.1 to 10, mol equivalents, particularly preferably from 1 to 5 mol equivalents.
The amount of transition metal is not critical. For cost reasons, of course, rather a small amount, eg. from 0.1 to 10 mol %, in particular from 1 to 5 mol %, based on the starting substance A3 or A4, will be used.
Reaction with carbon monoxide and at least equimolar amounts of water, based on the starting substances A3 or A4, is carried out to prepare the saccharincarboxylic acids III. The reaction component water or C.sub.1 -C.sub.6 -alkyl-OH can simultaneously also be used as a solvent, ie. the maximum amount is not critical.
However, it can also be advantageous, depending on the nature of the starting substances and the catalysts used, to use another inert solvent or the base used for the carboxylation as a solvent instead of the reaction component.
Suitable inert solvents for carboxylation reactions are customary solvents such as hydrocarbons, eg. toluene, xylene, hexane, pentane, cyclohexane, ethers, eg. methyl tert-butyl ether, tetrahydrofuran, dioxane, dimethoxyethane, substituted amides such as dimethylformamide, persubstituted ureas such as tetra-C.sub.1 -C.sub.4 -alkylureas, or nitriles such as benzonitrile or acetonitrile.
In a preferred embodiment of the process, one of the reaction components, in particular the base, is used in an excess such that no additional solvent is necessary.
Bases suitable for the process are all inert bases which are able to bind the hydrogen iodide or hydrogen bromide liberated in the reaction. Examples which can be mentioned here are tertiary amines such as triethylamine, cyclic amines such as N-methylpiperidine or N,N'-dimethylpiperazine, pyridine, amides such as N-methyl- or N,N-dimethylformamide, alkali metal or alkaline earth metal hydroxides, carbonates or hydrogen carbonates, or tetraalkyl-substituted urea derivatives such as tetra-C.sub.1 -C.sub.4 -alkylurea, eg. tetramethylurea.
The amount of base is not critical, 1 to 10, in particular 1 to 5, mol customarily being used. When the base is simultaneously used as a solvent, as a rule the amount is proportioned such that the reaction components are dissolved, unnecessarily high excesses being avoided for reasons of practicability in order to save costs, to be able to employ small reaction vessels and to guarantee maximum contact of the reaction components.
During the reaction, the carbon monoxide pressure is adjusted such that an excess of CO, based on A3 or A4, is always present. Preferably, the carbon monoxide pressure at room temperature is from 1 to 250 bar, in particular from 5 to 150 bar, of CO.
As a rule, the carbonylation is carried out batchwise or continuously at from 20.degree. to 250.degree. C., in particular at from 30.degree. to 150.degree. C. In the case of batchwise operation, carbon monoxide is expediently injected into the reaction mixture continuously to maintain a constant pressure.
The products are isolated from the resulting reaction mixture in a customary manner, eg. by distillation.
The starting substances A3 and A4 required for the reaction are known or can be prepared in a manner known per se. They can be obtained either by permanganate oxidation of iodo-substituted 2-methylbenzenesulfonamides or from aminosaccharins by Sandmeyer reaction. Aminosaccharins are obtained according to known methods by reduction of nitrosaccharins which, in turn, are either known (Kastle, Amer. Chem. Journal 11 (1889), 184 or DRP 551423 (1930) or are synthesized from suitable nitrobenzene derivatives (Liebigs Ann. 669 (1963), 85) or benzenesulfonamides in a manner known from the literature.
Moreover, they can be obtained analogously to the preparation procedures of Examples 1 to 12.
The compounds I where T=--CHY can be obtained from the compounds of the formula I.2 where T=CO by reducing them with sodium borohydride to carbinols of the formula I.3, and either reacting these with methanesulfonyl chloride to give chlorides of the formula I.4 or acylating them with C.sub.2 -C.sub.4 -carboxylic anhydrides to give esters of the formula I.5. ##STR15##
With respect to the intended use, saccharin derivatives of the formula I are preferred where the radicals L and M are hydrogen, methyl, methoxy, methylthio, chlorine, cyano, methylsulfonyl, nitro or trifluoromethyl. One of the radicals L or M is further hydrogen and the other radical is one of the abovementioned radicals.
In formula I, Q is particularly preferably the radical CO-J. The radical R.sup.1 is preferably hydrogen and R.sup.5 is preferably cyclopropyl or tert-butyl.
The radical Z is particularly preferably one of the C-organic radicals mentioned, in particular methyl, ethyl, acetyl, phenyl or propargyl.
Particularly preferred active compounds can be taken from Table 1. The groups mentioned in Table 1 for a substituent are additionally considered per se, independently of the specific combinations with other substituents in which they are mentioned, to be a particularly preferred definition of the substituents concerned.
The compounds I can be present in the form of their agriculturally utilizable salts, the nature of the salt in general not mattering. Customarily, the salts of those bases which do not adversely affect the herbicidal action of I are suitable.
Suitable basic salts are particularly those of the alkali metals, preferably the sodium and potassium salts, those of the alkaline earth metals, preferably calcium, magnesium and barium salts and those of the transition metals, preferably manganese, copper, zinc and iron salts as well as the ammonium salts, which can carry one to three C.sub.1 -C.sub.4 -alkyl or hydroxy-C.sub.1 -C.sub.4 -alkyl substituents and/or a phenyl or benzyl substituent, preferably diisopropylammonium, tetramethylammonium, tetrabutylammonium, trimethylbenzylammonium and trimethyl-(2-hydroxyethyl)ammonium salts, the phosphonium salts, the sulfonium salts, preferably tri(C.sub.1 -C.sub.4)-alkylsulfonium salts, and the sulfoxonium salts, preferably tri(C.sub.1 -C.sub.4)-alkylsulfoxonium salts.
The compounds I or the herbicidal compositions containing them and their environmentally tolerable salts of, for example, alkali metals, alkaline earth metals or ammonia and amines or the herbicidal compositions containing them can control broad-leaved weeds and grass weeds highly effectively in crops such as wheat, rice, maize, soybeans and cotton without noticeably damaging the crop plants. This effect occurs especially at low application rates.
Taking into account the versatility of the application methods, the compounds I or compositions containing them can also be employed in a further number of crop plants for the elimination of undesired plants. Examples of suitable crops are the following:
Allium cepa, Ananas comosus, Arachis hypogaea, Asparagus officinalis, Beta vulgaris spp. altissima, Beta vulgaris spp. rapa, Brassica napus var. napus, Brassica napus var. napobrassica, Brassica rapa var. silvestris, Camellia sinensis, Carthamus tinctorius, Carya illinoinensis, Citrus limon, Citrus sinensis, Coffea arabica (Coffea canephora, Coffea liberica), Cucumis sativus, Cynodon dactylon, Daucus carota, Elaeis guineensis, Fragaria vesca, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hevea brasiliensis, Hordeum vulgare, Humulus lupulus, Ipomoea batatas, Juglans regia, Lens culinaris, Linum usitatissimum, Lycopersicon lycopersicum, Malus spp., Manihot esculenta, Medicago sativa, Musa spp., Nicotiana tabacum (N. rustica), Olea europaea, Oryza sativa, Phaseolus lunatus, Phaseolus vulgaris, Picea abies, Pinus spp., Pisum sativum, Prunus avium, Prunus persica, Pyrus communis, Ribes sylvestre, Ricinus communis, Saccharum officinarum, Secale cereale, Solanum tuberosum, Sorghum bicolor (S. vulgare), Theobroma cacao, Trifolium pratense, Triticum aestivum, Triticum durum, Vicia faba, Vitis vinifera, Zea mays.
Moreover, the compounds I can also be employed in crops which have been made largely resistant to the action of I or other herbicides by breeding and/or by means of genetic engineering methods.
The application of the herbicidal compositions or of the active compounds can be carried out preemergence or postemergence. If the active compounds are less tolerable for certain crop plants, application techniques can be used in which the herbicidal compositions are sprayed with the aid of the spray equipment such that the leaves of the sensitive crop plants are not affected if possible, while the active compounds reach the leaves of undesired plants growing under them or the uncovered soil surface (post-directed, lay-by).
The compounds I or the herbicidal compositions containing them can be applied by spraying, atomizing, dusting, scattering or watering, for example in the form of directly sprayable aqueous solutions, powders, suspensions, even high-percentage aqueous, oily or other suspensions or dispersions, emulsions, oil dispersions, pastes, dusting compositions, scattering compositions or granules. The application forms depend on the intended uses; if possible they should in each case guarantee the finest dispersion of the active compounds according to the invention.
Suitable inert auxiliaries for the preparation of directly sprayable solutions, emulsions, pastes or oil dispersions are essentially: mineral oil fractions of medium to high boiling point such as kerosene or diesel oil, further coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, eg. paraffins, tetrahydronaphthalene, alkylated naphthalene or their derivatives, alkylated benzenes and their derivatives, alcohols such as methanol, ethanol, propanol, butanol and cyclohexanol, ketones such as cyclohexanone or strongly polar solvents, eg. amines such as N-methylpyrrolidone, or water.
Aqueous application forms can be prepared from emulsion concentrates, suspensions, pastes, wettable powders or water-dispersable granules by addition of water. To prepare emulsions, pastes or oil dispersions, the substances can be homogenized in water, as such or dissolved in an oil or solvent, by means of wetting agents, adhesives, dispersants or emulsifiers. However, concentrates consisting of active substance, wetting agent, adhesive, dispersant or emulsifier and possibly solvents or oil which are suitable for dilution with water can also be prepared.
Suitable surface-active substances are the alkali metal, alkaline earth metal or ammonium salts of aromatic sulfonic acids, eg. lignosulfonic, phenolsulfonic, naphthalenesulfonic and dibutylnaphthalenesulfonic acid, as well as of fatty acids, alkyl- and alkylarylsulfonates, alkyl-, lauryl ether and fatty alcohol sulfates, and also salts of sulfated hexa-, hepta- and octadecanols as well as of fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and its derivatives with formaldehyde, condensation products of naphthalene or of the naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octyl phenol ethers, ethoxylated isooctyl-, octyl- or nonylphenol, alkylphenyl or tributylphenylpolyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol-ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers or polyoxypropylene alkyl ethers, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignin-sulfite waste liquors or methylcellulose.
Powder, scattering and dusting compositions can be prepared by mixing or joint grinding of the active substances with a solid carrier.
Granules, eg. coated, impregnated and homogeneous granules can be prepared by binding of the active compounds to solid carriers. Solid carriers are mineral earths such as silicic acids, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate and magnesium sulfate, magnesium oxide, ground synthetic materials, fertilizers, such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas and vegetable products such as cereal flour, tree bark meal, wood meal and nutshell meal, cellulose powder or other solid carriers.
In general, the formulations contain from 0.01 to 95% by weight, preferably from 0.5 to 90% by weight, of active compound. The active compounds are employed here in a purity of from 90% to 100%, preferably from 95% to 100% (according to NMR spectrum).
The compounds I according to the invention can be formulated, for example, as follows:
I. 20 parts by weight of the compound 1.05 are dissolved in a mixture which consists of 80 parts by weight of alkylated benzene, 10 parts by weight of the addition product of from 8 to 10 mol of ethylene oxide to 1 mol of oleic acid N-monoethanolamide, 5 parts by weight of calcium salt of dodecylbenzenesulfonic acid and 5 parts by weight of the addition product of 40 mol of ethylene oxide to 1 mol of castor oil. By pouring out the solution and finely dispersing it in 100,000 parts by weight of water, an aqueous dispersion is obtained which contains 0.02% by weight of the active compound.
II. 20 parts by weight of the compound 1.05 are dissolved in a mixture which consists of 40 parts by weight of cyclohexanone, 30 parts by weight of isobutanol, 20 parts by weight of the addition product of 7 mol of ethylene oxide to 1 mol of isooctylphenol and 10 parts by weight of the addition product of 40 mol of ethylene oxide to 1 mol of castor oil. By pouring the solution into and finely dispersing it in 100,000 parts by weight of water, an aqueous dispersion is obtained which contains 0.02% by weight of the active compound.
III. 20 parts by weight of the active compound 1.05 are dissolved in a mixture which consists of 25 parts by weight of cyclohexanone, 65 parts by weight of a mineral oil fraction of boiling point from 210.degree. to 280.degree. C. and 10 parts by weight of the addition product of 40 mol of ethylene oxide to 1 mol of castor oil. By pouring the solution into and finely dispersing it in 100,000 parts by weight of water, an aqueous dispersion is obtained which contains 0.02% by weight of the active compound.
IV. 20 parts by weight of the active compound 1.05 are thoroughly mixed with 3 parts by weight of the sodium salt of diisobutylnaphthalene-.alpha.-sulfonic acid, 17 parts by weight of the sodium salt of a lignosulfonic acid from a sulfite waste liquor and 60 parts by weight of powdered silica gel and ground in a hammer mill. By finely dispersing the mixture in 20,000 parts by weight of water, a spray mixture is obtained which contains 0.1% by weight of the active compound.
V. 3 parts by weight of the active compound 1.05 are mixed with 97 parts by weight of finely divided kaolin. In this way, a dusting composition is obtained which contains 3% by weight of the active compound.
VI. 20 parts by weight of the active compound 1.05 are intimately mixed with 2 parts by weight of calcium salt of dodecylbenzenesulfonic acid, 8 parts by weight of fatty alcohol polyglycol ether, 2 parts by weight of sodium salt of a phenol-urea-formaldehyde condensate and 68 parts by weight of a paraffinic mineral oil. A stable oily dispersion is obtained.
To widen the spectrum of action and to achieve a synergistic effect, the saccharincarboxylic acid derivatives I can be mixed with numerous representatives of other herbicidal or growth-regulating active compound groups and applied jointly. For example, suitable mixture components are diazines, 4H-3,1-benzoxazine derivatives, benzothiadiazinones, 2,6-dinitroanilines, N-phenylcarbamates, thiocarbamates, halocarboxylic acids, triazines, amides, ureas, diphenyl ethers, triazinones, uracils, benzofuran derivatives, cyclohexane-1,3-dione derivatives which carry eg. a carboxyl or carbimino group in the 2-position, quinolinecarboxylic acid derivatives, imidazolinones, sulfonamides, sulfonylureas, aryloxy- or heteroaryloxyphenoxypropionic acids and their salts, esters and amides and others.
Additionally, it may be useful to apply the compounds I on their own or together in combination with other herbicides, additionally mixed with further crop protection agents, for example with agents for controlling pests or phytopathogenic fungi and bacteria. Further of interest is the miscibility with mineral salt solutions, which are employed for the elimination of nutrition and trace element deficiencies. Nonphytotoxic oils and oil concentrates can also be added.
Depending on the aim of control, time of year, target plants and stage of growth, the application rates of active compound are from 0.01 to 3.0, preferably from 0.01 to 1.0, kg/ha of active substance (a.s.).

PREPARATION EXAMPLES
1. Acylation of Meldrum's Acid with Cyclopropanecarbonyl Chloride
22 g (0.28 mol) of pyridine are added to a solution of 20 g (0.14 mol) of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) in 100 ml of methylene chloride cooled to 5.degree. C. A solution of 16 g (0.15 mol) of cyclopropanecarbonyl chloride in 50 ml of methylene chloride is then added dropwise at 0.degree.-3.degree. C. After stirring at 25.degree. C. for 2 hours, the reaction mixture is treated with 100 ml of 5 percent HCl and briefly stirred. The organic phase is then separated off, washed with water and dried over sodium sulfate. After stripping off the solvent under reduced pressure, 27.7 g of an oil (84% of theory) are obtained, which is present according to NMR as an enol of the formula ##STR16## 2. tert-Butyl 3-oxo-3-cyclopropylpropionate ##STR17##
25 g (0.338 mol) of tert-butanol are added to a solution of 23.9 g (0.113 mol) of the compound obtained in 1. in 100 ml of toluene and the mixture is heated to boiling. After 4 hours, the reaction mixture is allowed to cool and is washed with ice-water, and the organic phase is dried over sodium sulfate. After stripping off the solvent, 20 g (82% of theory) of an oil of the above structure remain.
3. 2-Methyl-6-acetamidobenzoic Acid
90.6 g (0.6 mol) of 6-methylanthranilic acid is added to a solution of 24.8 g (0.62 mol) of NaOH in 500 ml of water and 63.4 g (0.62 mol) of acetic anhydride are then added dropwise. After stirring for one hour, the mixture is acidified to pH 3 with conc. HCl with cooling, and the precipitate which deposits is filtered off with suction, washed with water and dried under reduced pressure at 50.degree. C.
Yield: 107 g (0.55 mol)=92% of theory, m.p.: 189.degree.-190.degree. C.
4. 2-Methyl-3-nitro-6-acetamidobenzoic Acid
271 ml of 98 percent nitric acid are initially taken at -5.degree. C. and 106 g (0.55 mol) of the 2-methyl-6-acetamidobenzoic acid prepared in 1. are added in portions. After stirring at 10.degree. C. for one hour, the reaction mixture is poured into a mixture of 540 g of ice and 270 ml of water. The deposited precipitate is filtered off with suction, washed with water and dried under reduced pressure at 50.degree. C.
Yield: 75.6 g (0.317 mol)=58% of theory, m.p.: 190.degree.-191.degree. C.
The isomer nitrated in the 3-position is deposited from the filtrate after relatively long standing:
Yield: 21.3 g (0.089 mol)=16% of theory, m.p.: 180.degree.-182.degree. C.
5. 2-Methyl-3-nitro-6-aminobenzoic Acid
450 ml of 2N NaOH are initially taken and 75.6 g (0.317 mol) of 2-methyl-3-nitro-6-acetamidobenzoic acid are added. The reaction mixture is then warmed to 95.degree. C. and is stirred at this temperature for one hour. After cooling to 10.degree. C., it is acidified by addition of 425 ml of 2N HCl, and the precipitate which deposits is filtered off with suction, washed with water and dried under reduced pressure at 50.degree. C.
Yield: 50.7 g (0.258 mol)=82% of theory, m.p.: 183.degree.-184.degree. C.
6. Methyl 2-methyl-3-nitro-6-aminobenzoate
49.7 g (0.253 mol) of 2-methyl-3-nitro-6-aminobenzoic acid are dissolved in 380 ml of acetone and 43 g (0.51 mol) of sodium hydrogen carbonate are added. The mixture is then heated to boiling until evolution of CO.sub.2 is complete. 35.3 g (0.28 mol) of dimethyl sulfate are then added dropwise in the course of two hours at the boiling point of acetone to the suspension of the sodium salt of 2-methyl-3-nitro-6-aminobenzoic acid thus obtained, and the mixture is subsequently refluxed for a further 3 hours and then allowed to cool. After pouring the reaction mixture into 1.8 l of water, it is extracted with methylene chloride. After drying, the organic phase is concentrated. The solid obtained is sufficiently pure for the subsequent reaction (NMR).
Yield: 50 g (0.238 mol)=94% of theory, m.p.: 92.degree.-94.degree. C.
7. 2-Methoxycarbonyl-3-methyl-4-nitrobenzenesulfonyl Chloride
58.5 g (0.278 mol) of methyl 2-methyl-3-nitro-6-aminobenzoate are dissolved with warming in 280 ml of glacial acetic acid and this solution is poured at from 15.degree. to 20.degree. C. into 85 ml of conc. HCl. A solution of 19.3 g (0.28 mol) of sodium nitrite in 60 ml of water is then added dropwise at from 5.degree. to 10.degree. C. and the mixture is stirred at 5.degree. C. for 30 min. This diazonium salt solution is subsequently added dropwise to a solution of 374 g of SO.sub.2 in 750 ml of glacial acetic acid which contains 14 g of CuCl.sub.2 (dissolved in 30 ml of water). After completion of the evolution of nitrogen, the mixture is stirred for a further 15 min and then poured into 1.4 l of ice-water. The sulfonyl chloride is separated off by extraction with 1.2 l of methylene chloride. After drying and concentrating the organic phase, 73 g (0.25 mol) (=90% of theory) of an oil are obtained, which according to NMR (in CDCl.sub.3) is pure 2-methoxycarbonyl-3-methyl-4-nitrobenzenesulfonyl chloride.
8. 4-Methyl-5-nitrosaccharin
104 ml of 25 percent ammonia solution are initially taken, 100 ml of water are added and a solution of 48.7 g (0.166 mol) of 2-methoxycarbonyl-3-methyl-4-nitrobenzenesulfonyl chloride in 70 ml of tetrahydrofuran is then added dropwise at 10.degree. C. After stirring at 25.degree. C. for three hours, the mixture is concentrated on a rotary evaporator to remove water and THF. The residue which remains is stirred with ethyl acetate, filtered off with suction and washed with ethyl acetate. After drying under reduced pressure, 34 g (0.131 mol)=79% of theory of a white solid of m.p.: 312.degree. C. (dec.) are obtained.
9. 2,4-Dimethyl-5-nitrosaccharin
This substance can be prepared by subsequent methylation of the saccharin obtained in 8. using dimethyl sulfate in the presence of NaOH.
10. 3-Methyl-4-nitro-2-(N'-methyl)carboxamido-N-methylbenzenesulfonamide
50 ml of water are poured into 50 ml of 40 percent methylamine solution and a solution of 24.3 g (83 mmol) of 2-methoxycarbonyl-3-methyl-4-nitrobenzenesulfonyl chloride in 35 ml of THF is then added dropwise at 10.degree. C. After stirring for one hour at 25.degree. C., all volatile constituents are removed on a rotary evaporator, the residue is extracted with ethyl acetate, and the organic phase is washed with water, dried and concentrated. The residue which remains crystallizes after relatively long standing.
Yield: 10.3 g (40 mmol=48% of theory), m.p.: 125.degree.-126.degree. C., after recrystallization from ethyl acetate m.p.: 144.degree.-145.degree. C. According to NMR, the product is not a saccharin derivative but a carboxamide containing an additional sulfonamide group.
11. 4-Methyl-5-aminosaccharin
33.6 g (0.13 mol) of 4-methyl-5-nitrosaccharin are dissolved in 1.2 l of water with warming and 5 g of Pd/C (10 percent on active carbon) are added. Hydrogen gas is then passed in with vigorous stirring (pressureless hydrogenation). 9 l of H.sub.2 are absorbed in the course of 4.5 hours. After cooling to 25.degree. C., the catalyst is filtered off, and the filtrate is concentrated to a volume of 200 ml on a Rotavapor and then acidified to pH 1. The deposited precipitate is filtered off with suction, washed with water and dried under reduced pressure at 50.degree. C. 23.4 g (0.11 mol=85% of theory) of a white solid of m.p.: 272.degree.-273.degree. C. are obtained.
12. 4-Methyl-5-iodosaccharin
A mixture of 205 ml of glacial acetic acid, 160 ml of water and 40 ml of conc. HCl is initially taken and 23.4 g (0.11 mol) of 4-methyl-5-aminosaccharin are introduced with stirring at 15.degree.-20.degree. C. 7.9 g (0.115 mol) of sodium nitrite are added dropwise to the resulting suspension at 5.degree.-10.degree. C. and it is stirred at 5.degree. C. for 30 min. The diazonium salt, which is present as a suspension, is then added dropwise in portions to a solution of 19.1 g (0.115 mol) of potassium iodide in 170 ml of water which is warmed to 50.degree. C., nitrogen being formed. After cooling to room temperature, the deposited product is isolated by filtering off with suction, washed with water and dried under reduced pressure at 50.degree. C. 32.5 g (0.1 mol=91% of theory) of a solid of m.p.: 257.degree.-258.degree. C. are obtained.
A combustion analysis gives an iodine content of 38.5% (theory 39.3%).
The product is sufficiently pure for the subsequent reactions.
13. 4-Methylsaccharin-5-carboxylic Acid
6.4 g (0.002 mol) of 4-methyl-5-iodosaccharin are dissolved in 70 ml of tetramethylurea and 30 ml of water and treated with 0.7 g of bis(triphenylphosphine)palladium chloride and the mixture is heated to 100.degree. C. in a 300 ml autoclave and stirred at a pressure of 100 bar of carbon monoxide for 36 h.
For working up, the mixture is filtered, and water and tetramethylurea are removed by distillation in a high vacuum. The residue is taken up in methyl tert-butyl ether (MTBE), extracted with NaHCO.sub.3 soln. and, after acidifying with HCl, extracted again with MTBE. After concentrating, 2.8 g of 4-methylsaccharin-5-carboxylic acid (58% of theory) are obtained.
.sup.13 H NMR (DMSO, 400.1 MHz): 2.85 (3H, s); 8.05 (1H, d); 8.2 (1H, d);
.sup.13 C NMR (DMSO, 100.6 MHz): 167.4 (CO); 161.3 (CO); 141.6 (quart. C); 139.7 (quart. C); 138.7 (quart. C); 135.6 (CH); 125.4 (quart. C); 118.5 (CH); 15.4 (CH.sub.3).
14. 4,N-Dimethylsaccharin-5-carboxylic Acid
7.3 g (0.02 mol) of 3-methyl-4-iodo-2-(N'-methyl)carboxamido-N-methylbenzenesulfonamide are initially taken in a 300 ml autoclave, together with 0.69 g of bis(triphenylphosphine)palladium chloride, 30 ml of water and 70 ml of tetramethylurea, and the mixture is heated to 100.degree. C. and stirred at a pressure of 100 bar of carbon monoxide for 36 h.
After working up as described in Example 12, 4.1 g of the title compound are obtained (0.014 mol=72% of theory).
.sup.1 H NMR (DMSO, 400.1 MHz): 2.9 (3H, s); 3.15 (3H, s); 8.2 (2H, 2d); 14.0 (1H, s)
.sup.13 C NMR (DMSO, 100.6 MHz): 167.3 (CO); 158.6 (CO); 139.7 (quart. C); 139.1 (quart. C); 138.9 (quart. C); 135.5 (CH); 124.6 (quart. C); 119.0 (CH); 22.9 (CH.sub.3); 15.6 (CH.sub.3).
15. 4-Amino-3-methyl-2-(N'-methyl)carboxamido-N-methylbenzenesulfonamide
In a similar manner to the procedure described in section 11, the 3-methyl-4-nitro-2-(N'-methyl)carboxamido-N-methylbenzenesulfonamide obtained in section 10 was hydrogenated without pressure. The aniline derivative of accompanying structure was obtained in 93% yield with m.p.: 217.degree.-218.degree. C. ##STR18## 16. 3-Methyl-4-iodo-2-(N'-methyl)carboxamido-N-methylbenzenesulfonamide
The above compound was diazotized according to the procedure described in section 12 and converted by reaction with KI to give the iodobenzene derivative of accompanying structure.
Yield: 95%, m.p.: 60.degree.-62.degree. C. ##STR19## 17. 2,4-Dimethylsaccharin-5-carbonyl Chloride
3.8 g (14.9 mmol) of 2,4-dimethylsaccharin-5-carboxylic acid are suspended in 100 ml of toluene, and the mixture is heated to 80.degree. C. and 3.5 g (29.8 mmol) of thionyl chloride are added dropwise. After refluxing for two hours, the solution is decanted hot and the reaction mixture is concentrated. The product obtained (3 g, 74% of theory) is of m.p.: 149.degree.-150.degree. C.
18. General Procedure for Preparing the Compounds of the Formula I.1
18.1 Acylation to Give the Intermediate of the Formula B1
60 g (0.33 mol) of tert-butyl 3-oxo-3-cyclopropylpropionate are added to a suspension of 8.4 g (0.345 mol) of magnesium turnings in 700 ml of methanol and 8 ml of carbon tetrachloride are added at 20.degree.-28.degree. C. with cooling. After stirring for 4 hours, 700 ml of acetonitrile are poured into the magnesium enolate formed and a solution of 0.32 mol of the respective saccharincarbonyl chloride IV in 100 ml of acetonitrile is then added dropwise at 20.degree.-26.degree. C. The mixture is subsequently stirred at 25.degree. C. for 16 hours and then warmed to 40.degree. C. for a further hour, and the acetonitrile and methanol are then removed by evaporation in a rotary evaporator under reduced pressure. The residue is taken up in ethyl acetate, washed with 2N HCl, and the organic phase is then washed with water, dried over sodium sulfate and concentrated. The viscous material which remains (yield: 80-90%) is used further as the crude product B1 without further purification.
18.2 Removal of the Tert-butoxycarbonyl Radical to Give the .beta.-diketone C1
0.274 mol of the product obtained in 18.1 is suspended in 900 ml of toluene, 11 g of p-toluenesulfonic acid are added and the mixture is heated to boiling for seven hours. After cooling, the reaction mixture is neutralized with 5% NaOH, and the aqueous phase is separated off, acidified to pH 1 with conc. HCl and extracted by shaking with methylene chloride. A part of the diketone C1 is isolated from this solution after washing with water and drying the organic phase. The remaining amount of C1 is obtained from the toluene solution separated off initially by washing this with water, and drying and concentrating it under reduced pressure. The yield is 77% of theory and the crude product is directly processed further in step 18.3.
18.3 Reaction of the Diketones C1 to Give the Enol Ether D1
36 mmol of the respective diketone C1 are mixed with 6.3 g (42 mmol) of acetic anhydride and 5.5 g (54 mmol) of triethyl orthoformate and the mixture is heated to boiling for three hours (110.degree. C.). All volatile constituents are then removed under reduced pressure, a crystalline residue remaining. The yield is over 95% of theory. The crude product is reacted with hydroxylamine in step 18.4 without further purification.
18.4 Ring Closure to the Isoxazole Derivative
10 mmol of the respective enol ether D1 are initially taken in 50 ml of methylene chloride, 11 mmol of hydroxylamine hydrochloride are added and a solution of 5.5 mmol of sodium carbonate in 2.5 ml of water is added dropwise at 10.degree.-15.degree. C. After stirring at 25.degree. C. for four hours, the organic phase is washed with water and separated off. After drying and stripping off the solvent, the saccharin derivative of the formula I.1 remains as a viscous oil which is purified by chromatography on silica gel (eluent: toluene/ethyl acetate=9:1). The isolated yield is from 50 to 60% of theory.
19. General preparation procedure for the cycloaddition of aroylalkynes and nitrile oxides to give saccharin derivatives of the formula I.2
19.1 Aroylalkynes from Tributyltin Alkynes
0.39 g (0.56 mmol) of bis(triphenylphosphine)palladium(II) chloride is added to a solution of 11.1 mmol of the respective saccharin acid chloride of the formula IV in 100 ml of methylene chloride and a solution of 4.9 g (14 mmol) of tributyltin propyne in 20 ml of methylene chloride is added at 20.degree.-25.degree. C. After stirring at 25.degree. C. for 16 hours, the methylene chloride is stripped off under reduced pressure and the residue obtained is purified by chromatography on silica gel (eluent: toluene/ethyl acetate=9:1). The isolated yield is from 50 to 65% of theory. Intermediates of the formula B2 prepared in this manner are compiled in Table 2.
19.2 Cycloaddition
0.6 g (7 mmol) of isobutyraldoxime is added to a solution of 6.6 mmol of the respective aroylalkyne from step 19.1 in 30 ml of methylene chloride and the mixture is then treated dropwise with 9.6 g (16 mmol) of a 12 percent NaOCl solution. After stirring at 25.degree. C. for 16 hours, the reaction mixture is extracted by shaking with water, and the organic phase is dried and concentrated. After chromatography (silica gel, toluene/hexane=8:2), the saccharin derivative of the formula I.2 is obtained in a yield of from 20 to 40%.
The compounds compiled in Table 1 are obtained in a similar manner:
TABLE 1______________________________________Saccharin derivatives I where Q = COJ ##STR20##No. R.sup.1 R.sup.2 Q pos L M Z m.p. (.degree.C.)______________________________________1.01 H C.sub.3 H.sub.5 4 H H H1.02 H C.sub.3 H.sub.5 4 H H CH.sub.31.03 H C.sub.3 H.sub.5 5 4-CH.sub.3 H H1.04 H C.sub.3 H.sub.5 5 4-Cl H CH.sub.31.05 H C.sub.3 H.sub.5 6 H H CH.sub.3 154-1561.06 H t.C.sub.4 H.sub.9 6 H H CH.sub.31.07 H t.C.sub.4 H.sub.9 4 H H H1.08 CH.sub.3 t.C.sub.4 H.sub.9 5 4-CH.sub.3 H CH.sub.31.09 i-C.sub.3 H.sub.7 t.C.sub.4 H.sub.9 5 4-Cl H Ethyl1.10 i-C.sub.3 H.sub.7 t.C.sub.4 H.sub.9 6 H H Propargyl______________________________________
TABLE 2______________________________________Saccharin derivatives of the formula B2 ##STR21##No. R2 Q pos L M Z m.p. (.degree.C.)______________________________________2.01 Cyclopropyl 4 6-CH.sub.3 H CH.sub.32.02 Cyclopropyl 5 4-CH.sub.3 H C.sub.2 H.sub.52.03 Cyclopropyl 6 5-Cl H Propargyl2.04 Cyclopropyl 5 4-Cl 7-Cl Phenyl2.05 Cyclopropyl 5 7-CH.sub.3 6-CH.sub.3 Benzyl2.06 1-Methylcyclo- 4 6-CH.sub.3 H CH.sub.3 propyl2.07 1-Methylcyclo- 5 4-CH.sub.3 7-Cl C.sub.2 H.sub.5 propyl2.08 1-Methylcyclo- 6 5-Cl H Propargyl propyl2.09 1-Methylthio- 5 4-CH.sub.3 7-CH.sub.3 Propargyl cyclopropyl2.10 1-Methylthio- 5 4-CH.sub.3 H Phenyl cyclopropyl2.11 1-Methylthio- 5 4-CH.sub.3 7-Cl Benzyl cyclopropyl2.12 tert-Butyl 4 6-CH.sub.3 7-CH.sub.3 CH.sub.32.13 tert-Butyl 5 4-Cl H C.sub.2 H.sub.52.14 tert-Butyl 6 4-Cl H Propargyl______________________________________
Use Examples
It was possible to show the herbicidal action of the saccharin derivatives of the formula I by greenhouse tests:
The cultivation vessels used were plastic flowerpots containing loamy sand with about 3.0% humus as a substrate. The seeds of the test plants were sown separately according to species.
In the case of preemergence treatment, the active compounds suspended or emulsified in water were applied directly after sowing by means of finely dispersing nozzles. The vessels were lightly watered in order to promote germination and growth, and then covered with transparent plastic hoods until the plants had taken root. This covering causes a uniform germination of the test plants if this is not adversely affected by the active compounds.
For the purpose of postemergence treatment, the test plants were first raised, according to growth form, to a height of growth of from 3 to 15 cm and only then treated with the active compounds suspended or emulsified in water. For this purpose, the test plants were either sown directly and raised in the same vessels or they were first raised separately as seedlings and transplanted into the test vessels a few days before the treatment.
The plants were kept species-specifically at 10.degree.-25.degree. C. or 20.degree.-35.degree. C. The test period extended over 2 to 4 weeks. During this time, the plants were tended and their reaction to the individual treatments was assessed.
Rating was carried out on a scale of from 0 to 100. 100 in this case means no emergence of the plants or complete destruction of at least the above-ground parts and 0 means no damage or normal course of growth.

Number	Name	Date	Kind
1937521	Limburg	Dec 1933
5457106	Takatani et al.	Oct 1995

Number	Date	Country
487 357	May 1992	EPX
527 037	Feb 1993	EPX
527 036	Feb 1993	EPX
560 483	Sep 1993	EPX
588 357	Mar 1994	EPX
594 257	Apr 1994	EPX
636 622	Feb 1995	EPX
551 423	Jun 1932	DEX
36 07 343	Sep 1986	DEX

Saccharin derivatives

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