DD231715A5 - PROCESS FOR THE PREPARATION OF 2,6-BIS-FLUOR-METHYL-DIHYDROPYRIDINE-3,5-DICARBOXYLIC ACID ESTERS - Google Patents

Abstract

The invention relates to herbicidal compositions containing 2- or 6-fluorinated methyl-dihydropyridine-3,5-dicarboxylic acid esters, which may be substituted in the 4-position, and to processes for using these compounds.

Description

Field of application of the invention

The present invention relates to a novel herbicidal composition and a method for suppressing undesired plant growth.

Characteristic of the known technical solutions

Various dihydropyridines are already known in the art and have been used for various purposes. So z. For example, US Pat. No. 3,969,359 describes 3,5-dicyano-1,4-dihydropyridines which can be used industrially for scintillation purposes as detectors for radioactive radiation.

Dihydropyridines have also been used for medicinal purposes, as illustrated by U.S. Patent No. 3,441,648, which describes a large number of 1,4-dihydropyridines. Of particular interest are the 2,6-substituted 3,5-dicarboxylate compounds. These compounds are used to reduce blood pressure when administered intravenously. The most active compounds are those which are substituted in the 4-position by aryl and heterocyclic radicals in which the heteroatom is either nitrogen, sulfur or oxygen. When lowering blood pressure in animals, the trifluoromethylphenyl residues in the 4-position also appear to be very active.

More important in this context is that of Balicki u. a. in the process described in the PO-PS 89 493 for the preparation of 4-substituted derivatives of 2,6-bis (Trif! uormethyl) -3,5-dicarbäthoxy-1,4-dihydropyridines. According to the PO-PS, these compounds have not been described in the literature and have valuable pharmacological properties such. B. cytotoxic, bacteriostatic and hypotensive. In addition, they can be used as intermediates for the synthesis of novel substituted heterocyclic compounds. According to the PO-PS, these compounds were prepared by reacting an aldehyde R-CHO, wherein R represents an alkyl group having 1 to 4 carbon atoms, an unsubstituted or substituted aryl group or a heterocyclic group, wherein the heteroatom is nitrogen, oxygen or sulfur, with ethyl fluoroacetoacetate in the presence of a concentrated aqueous ammonia solution. One molar equivalent of aldehyde is reacted with 2 molar equivalents of 3-ketoester in aqueous ammonia in the presence of an organic solvent, preferably an aliphatic alcohol. The compounds obtained in this way are identified only by their melting point.

In Journal of Heterocyclic Chemistry, Vol. 17, p. 1109 and 1110, Singh et al. However, further described that the Balicki et al. in fact, compounds rather than dihydropyridines are dihydroxypiperidines. Singh et al. indicate that by the reaction of Ethyltrifiuoracetoacetat with an aromatic aldehyde and a concentrated aqueous

Ammonia solution clearly do not have the dihydropyridine structure, but rather represent substituted piperidines.

Singh states that the oxidation of the reaction product by Balicki et al. with nitric acid and several other reagents does not lead to the conversion of the reaction product into the corresponding pyridine. Like Singh et al. Generally, oxidation is used to convert the 1,4-dihydropyridines to the corresponding pyridines, but such conversion does not occur, with Singh indicating that the process product described by Balicki does not lead to 1,4-dihydropyridines.

To further demonstrate that Balicki et al. have not prepared 2,6-bis-trifluoromethyl-4-subst-1,4-dihydropyridine-3,5-dicarboxylic acid ester, a series of compounds of structures 1 and 2 have been prepared from Table 1 below, based on their respective Melting points were tested. The melting points of compounds 1 and 2 prepared by the inventors were compared with those as described by Balicki et al. for the compounds (as indicated by them) described by them. The results are summarized in Table 1.

Table 1 , -,

ORH

Ra melting point 2 ⁰ C 1 133-135 after Balicki et al. CH ₃ 1,4394 ^a 129-131 133-134 C ₂ H ₅ 1.4441 ^a 140-141 131-132 C ₃ H ₇ 1.4427 ^a 129-130 132-133 2-furyl 1.4721 ^a 103-105 128-129 2-thienyl 1,434 ^a 179 - 4-pyridyl 171-172 99-101 177-178 phenyl • 42-45 92-93

The data in Table 1 show that the compounds described by Balicki were actually dihydroxypiperidines and not dihydropyridines. Balicki et al. corrected in a later publication (Polish Journal of Chemistry, p.2439, 1981) the information on the structure of products derived from ethyl trifluoroacetoacetate, aldehydes and aqueous ammonia as compounds 2.

The Balicki et al. prepared dihydroxypiperidines 2 consist of a mixture of cis and trans isomers of structure A (cis isomer) and B (trans isomer), as indicated below. The structures of compounds prepared according to Balicki are also identified by X-ray crystallography as Dihydroxypiperidine. The mixture of isomers prepared according to Balicki can furthermore be purified by recrystallization, giving predominantly an isomer. In general, now according to Balicki et al. produced products have a higher melting point than indicated. This is due to the more precise purification of the isomeric mixture of 2 to give the sole cis-isomer.

CF

-COOEt

CF

OH

OH

U.S. Patent 4,145,432 discloses 1,4-dihydropyridines which can be used in pharmaceutical compositions for the treatment of cardiovascular and hypertension disorders in humans. The active compounds are 3,5-dicarboxylate esters, the 4-position being occupied by an aryl or heterocyclic group. In addition, the 2- and 6-positions of the dihydropyridine ring are occupied by groups selected from a wide range of groups including lower alkyl groups and substituted lower alkyl groups. the intermediates described also include 2,6-halo (lower) alkyl substitution. DE-PS 2 659 665 describes as corona dilators 1,4-dihydropyridine derivatives which have 5-cyano, 3-carboxylate and 2,6-dialkyl substitution. The 4-position of these compounds is occupied by a nitrophenyl radical.

In EP-PS 44 262 anilides containing 1,4-dihydropyridines are described. However, none of the compounds described has a substitution at the 4-position and fluoroalkyl groups at the 2- and 6-positions.

Object of the invention

The invention is intended to provide novel herbicidal compositions.

Explanation of the essence of the invention

According to the invention, the novel compositions as active ingredient compounds of the formulas 3, 4 and 5:

3 4

R _T

wherein R is selected from the group consisting of phenyl, alkyl, C ₃ -C ₆ -cycloalkyl, haloalkyl, loweralkoxyalkyl, aralkoxyalkyl, aryloxyalkyl, loweralkylthioalkyl, loweralkylcarbonyloxyalkyl, hydroxyalkyl, cycioalkanylalkyl, and heterocyclic radicals having from 3 to 6 ring carbon atoms, wherein 1 to 3 atoms Heteroatoms are selected from the group of nitrogen, sulfur and oxygen, each R ₁ is independently selected from (VCt-alkyl radicals, and each R ₂ independently is fluorinated methyl, and R _{3 is} selected from the group consisting of alkyl and fluorinated methyl radicals the

Means at least one adjuvant.

The term "alkyl" means both straight and branched chain CrCg alkyl radicals, including, for example, ethyl, methyl, propyl, n-butyl, pentyl, hexyl, isobutylene, isopropyl, 1-methylpropyl, neopentyl and 1-ethylpropyl Expression "C ₃ -C ₆ cycloalkyl" means cycloalkyl radicals such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Typical alkoxyalkyl radicals are methoxymethyl, ethoxymethyl and ethoxyethyl. A typical aralkoxyalkyl radical is phenylmethoxymethyl. A typical aryloxyalkyl radical is phenoxyalkyl. The lower alkylthioalkyl radicals include the thio counterparts of those mentioned

Niederalkoxyalkylreste.

Typical heterocyclic radicals are furyl, pyridyl and thienyl.

The term "haloalkyl" means C-pCg-alkyl radicals substituted by one or more halogen atoms, typical examples of which are fluoromethyl, chloromethyl, difluoromethyl, difluoroethyl, bromomethyl, iodomethyl, dichloromethyl, dichloroethyl and dibromomethyl, trifluoromethyl, 2- (trifluoromethyl) propyl and chlorofluorinated alkyl radicals. The term "cycioalkanylalkyl"

represents alkyl substituted by a cycloalkyl radical.

The term "fluorinated methyl" means methyl radicals having one or more fluorine atoms attached thereto, including the substitution of all hydrogen atoms by fluorine, which also refers to methyl radicals having one or more hydrogen atoms replaced by a chlorine atom, provided that the methyl radical is one or fluorine atoms associated with this radical, typical examples of which are fluoromethyl, difluoromethyl and trifluoromethyl radicals, chlorodifluoromethyl, dichlorofluoromethyl, and the like

The term "1,2-dihydropyridine" means a dihydropyridine having hydrogen atoms attached to the ring nitrogen and an adjacent carbon atom and include dihydropyridines that are found in some chemical compounds

Nomenclature systems are referred to as 1,6-dihydropyridines.

The preparation of various active ingredients is described in a number of embodiments and also subject matter

a priority same application.

Exemplary embodiments Example 1

Preparation of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4-ethyl-3,5-piperidine dicarboxylate. A mixture of 368 g (2.0 moles) of enthyltrifluoroacetate acetate, 58 g (1.0 mole). propionaldehyde and 1 ml of piperidine in 400 ml of CH ₂ CI ₂ is stirred for one hour at 20 ° C and then one hour at 50 ⁰ C and finally heated under reflux for one hour. To this mixture is then added an additional 16.0 g (0.289 mol) of propionaldehyde, followed by heating at reflux for 2 hours. Thereafter, the heating jacket is removed. During 2 hours it will be 108g

(6.35 mol) passed through ammonia gas. 19F NMR analysis then shows that the reaction mixture contains a 77% pure mixture (1: 1) of cis isomer and trans isomer.

The cited method can also be used to prepare other 2,6-dihydroxy-3,5-piperidinedicarboxylates which are starting materials for the preparation of the dihydropyridine compounds of the present invention.

Example 2

Preparation of dimethyl-1-bis-trifluoromethyl-1-dihydro-isobutyl-S 1 -pyridine dicarboxylate and its 3,4-dihydro isomer.

(a) Preparation from the product of Example 1.

An ice-cold mixture of 200ml conc. H ₂ SO ₄ and 200 ml of methylene chloride are mixed with 48.7 g (0.115 mol) of dimethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4-isobutyl-3,5-piperidinecarboxylate all at once. Thereafter, the reaction mixture is stirred for 20 minutes and then poured into 11 of ice-water. The methylene chloride layer is separated, washed once with 100 mL of saturated sodium bicarbonate, dried and concentrated to give 28 g (64.6%) of the crude product (only 1,4-dihydro-isomer). A portion (5.0 g) of this product is subjected to Kugelrohr distillation at 0.5 torr (pot temperature 12O ⁰ C) to give 4.8 g of the desired product as an oil, n ^ ⁵ 1.1439i, which is a 2: 1 Mixture of 1,4-dihydro and 3,4-dihydro isomers.

Analysis:

Calcd for C ₁₅ H ₁₇ F ₆ N ₁ O _4: C46,28; H 4.40; N 3.60

found: C46.39; H4,44; N 3.60.

(b) one-pot preparation from methyl trifluoroacetoacetate

To a mixture of 340 g (2.0 mol) of methyl trifluoroacetoacetate, 100 mL of toluene and 0.86 g of piperidine is added 90.5 g (1.05 mol) of isovaleraldehyde over 20 minutes. The reaction mixture is then held at 80 ° C for 3 hours and diluted with 125 ml of toluene. Thereafter, ammonia gas (47.3 g, 2.78 mol) is passed through for Vh for hours. The mixture is then diluted with 100 ml of toluene. The excess of ammonia and 200 ml of toluene are removed under reduced pressure. Thereafter, the reaction mixture is diluted with 100 ml of toluene cooled to 5 ° C. and treated with 548 g (5.59 mol) of sulfuric acid. The reaction mixture is then stirred for 1½ hours and finally poured into 21 ice-water. Thereafter, the toluene layer is separated. The aqueous layer is extracted with 500 ml of toluene. Thereafter, the combined toluene solutions are washed successively with 500 ml of water, 500 ml of saturated sodium bicarbonate and 500 ml of brine and then concentrated in vacuo to give 363.6 g of a product of 59% purity, which corresponds to an overall yield of 83%.

Example 3

Preparation of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4- (5-pyridyl) -3,5-pyridinedicarboxylate.

A 250ml one-neck flask is used with 100 to 150ml conc. H ₂ SO ₄ fed. The flask is then placed in an ice water bath, followed by cooling with stirring. To the acid are added 30g (0.0636 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dlhydroxy-4- (4-pyridyl) -3,5-piperidinedicarboxylate followed by further stirring for one hour , The acid mixture is then poured onto ice cubes and extracted twice with ether. Thereafter, the organic bases are washed with aqueous saturated sodium bicarbonate and dried over anhydrous magnesium sulfate. Then the solvent is distilled off. 5 g of the residue obtained are dissolved in 40 ml of water and washed again with aqueous saturated sodium bicarbonate solution. The organic bases are extracted with ether and dried over anhydrous magnesium sulfate. Thereafter, the solvent is distilled off. 3.04 g (60.8%) of a white powder are obtained. Sp. 171-172 ° C.

Analysis:

Calculated for C ₁₃ H ₁₆ F ₆ N ₂ O ₄ : C, 49.31; H 3.65; N 6,39

found C49,33; H 3.72; N 6,39.

Example 4

Preparation of diethyl 2,6-bis (trifluoromethyl) -4-butyl-1-dihydro-S ^ -pyridine dicarboxylate.

In a 500ml flask 100ml conc. Given sulfuric acid. Then the flask is cooled in an ice bath. 4g (0.0088 mol) of diethyl 2,6-bis (trifluoromethyl) -4-butyl-2,6-dihydroxy-3,5-piperidinedicarboxylate are added to the acid followed by further stirring for one hour. The acid mixture is then poured onto ice cubes and stirred. Thereafter, the organic phases are extracted with ethyl ether. The ether extract is then washed with aqueous saturated sodium bicarbonate solution, dried over MgSO ₄ and concentrated. This gives 2.34 g (63.9%) of the product, n§ ⁵ 1.4419.

Analysis:

Calculated for C ₁₇ H ₂₁ O ₄ N ₁ F ₆ : C, 48.92; H 5.03; N 3.35

found: C48.95; H 5.09; N 3.36.

Example 5

Preparation of Diethyl ^ e-bis-trifluoromethyl-IA dihydro ^ -isopropyl-S ^ -pyridine dicarboxylate.

In a 500 ml flask 250 ml conc. Given sulfuric acid. The flask is cooled in an ice water bath. Thereafter, 25 g (0.0569 mol) of diethyl 2,6-bis (trifluoromethyl) -2 _/ 6-dihydroxy-4-isopropyl-3,5-piperidinedicarboxylate are added followed by further stirring for 90 minutes. The mixture is then poured onto ice cubes and stirred. Thereafter, the organics are extracted twice with ethyl ether. The ether extract is then washed with aqueous saturated sodium bicarbonate solution, dried over MgSO ₄ and concentrated. The crude product is chromatographed with 10% ethyl acetate / cyclohexane. Yield 6.87 g (30%) of the product; n ^ 1,444.

Analysis:

Calculated for C ^ sAI ^ Fis: C47,64; H4,71; N 3.47

found: C48.95; H 5.09; N 3.36.

Example 5

Preparation of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4-isopropyl-3,5-pyridinedicarboxylate.

In a 500ml flask 250ml conc. Given sulfuric acid. The flask is cooled in an ice water bath. Thereafter, 25 g (0.0569 mol) of diethyl ^^ - bis-trifluoromethyl-D ^^ dihydroxy ^ isopropyl-S ^ -piperidinedicarboxylate added, followed by stirring for 90 minutes. The mixture is then poured onto ice cubes and stirred. Thereafter, the organics are extracted twice with ethyl ether. The ether extract is then washed with aqueous saturated sodium bicarbonate solution, dried over MgSO ₄ and concentrated. The crude product is chromatographed with 10% ethyl acetate / cyclohexane. Yield 6.87 g (30%) of the product; n ^ ⁵ 1,444.

Analysis:

Calculated for C ^ jAMFg: C47,64; H4,71; N 3.47

found: C47.69; H 4.75; N 3.46

Example 6

Preparation of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4-isobutyl-3,5-pyridinedicarboxylate.

(a) Preparation of the product of Example C:

In a 500ml flask 250 to 300ml conc. Given sulfuric acid. The flask is cooled in an ice water bath and stirred. Thereafter, 25 g (0.0618 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4-isobutyl-3,5-piperidinedicarboxylate are added with stirring. After stirring for one hour, the acid mixture is poured onto ice pieces and stirred. Then the organic phases are extracted three times with ethyl ether, combined and washed with aqueous saturated sodium bicarbonate solution, dried over MgSO ₄ and concentrated. Chromatography with 20% ethyl acetate and cyclohexane gives 9.28 g (36%) of the product, riQ ⁵ 1.4420.

Analysis:

Calculated for C ^ H ^ O ^ Fg: C, 48.92; H5,03; N3,35

Found: C48.94; H 5.08; N 3.30.

(b) One-pot preparation from ethyl trifluoroacetoacetate

A mixture of 368 g (2.0 mol) of ethyltrifluoroacetoacetate, 0.9 g of piperidine and 100 ml of toluene is added with 90.5 g (1.05 mol) of isovaleraidehyde for 20 minutes. Thereafter, the reaction mixture is kept at 8O ⁰ C for 1 2 hours. Then an additional 4.3 g (0.05 mol) of isovaleraidehyde are added. The reaction mixture is then held for 35 minutes at 80 ° C and then cooled to 50 ⁰ C. The mixture is then passed through 30 g (1.76 mol) of ammonia gas for one hour and then nitrogen gas for Vh hours. The reaction mixture is then diluted with 200 ml of toluene and cooled to 8 ⁰ C and then treated with 566 g (5.78 mol) of sulfuric acid. Then, the reaction mixture is stirred at 5 to 10 ⁰ C for 45 minutes and poured onto 1 ¹ / 2kg of ice. Thereafter, the toluene layer is separated, washed successively with 500 ml of brine, 500 ml of saturated aqueous sodium bicarbonate and 500 ml of water, dried with MgSO ₄ and concentrated to give 394 g of the product having a purity of 90% and an overall yield of 85%.

Example 7

Preparation of Diethyl ^^ -bis-itrifluoromethyl-1-i-dihydro ^ -propyl-SjS-pyridinedicarboxylate.

In a 500 ml flask 100 to 150ml sulfuric acid are poured. Thereafter, the flask is placed in an ice bath and stirred for about 15 minutes. To the acid is added 9g (0.0205 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4-propyl-3,5-piperidinedicarboxylate. Thereafter, stirring is continued for 40 minutes. Then, the acid solution is poured onto pieces of ice, after which the resulting aqueous layer is extracted twice with ethyl ether. The organics are washed with saturated aqueous sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered and then concentrated to give 2.63 g (31.78%) of the product, no. ⁵ 1.4427.

Analysis:

Calculated for _{C ie} H ₁₇ O ₄ N ₁ F ₆ : C 47.88; H 4,23; N 3.49

Found: C47.92; H 4,28; N 3.47.

Example 8

Preparation of Diethyl ^^ - bis-trifluoromethyl-i-dihydro-phenyl-S ^ -pyridine dicarboxylate.

A mixture of 1.0 g of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4-phenyl-3,5-piperidinedicarboxylate, 0.1 g of toluenesulfonic acid and 30 ml of toluene is refluxed for 4 hours, the water is removed azeotropically. The toluene solution is washed with saturated sodium bicarbonate, dried with MgSO ₄ and concentrated in vacuo. The residue is chromatographed on silica gel using ether-petroleum ether (1: 9 v / v) as eluent. The first fraction (500 ml eluate) gives 0.70 g of an oil. The ¹ H-NMR analysis of this substance shows that this is a mixture of 1,4- and 3,4-diethyl-2,6-bis (trifluoromethyl) dihydro-4-phenyl-pyridine-3, 5-dicarboxylate is. This material is chromatographed on a silica gel plate (2000μ, 20mm χ 20mm) to give 0.66 g (71%) of an oil (n ³ _D 1.4887) which solidifies and diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4-phenyl-3,5-pyridinedicarboxylate having a melting point of 42 ^ 5 ⁰ C. _

Analysis:

Calculated for C ₁₉ H ₁₇ F ₆ NO ₄ : C 52.18; H 3.92; N 3,20

found C 52.33; H 3.95; N 3,20.

Example 9

Preparation of the sulfuric acid salt of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4- (4-pyridyl) -3,5-pyridinedicarboxylate. A 250 ml one-necked flask is filled with 100 to 150 ml conc. Sulfuric acid and then cooled in an ice water bath. There are added 30 g (0.0636 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4- (4-pyridyl) -3,5-piperidinedicarboxylate. Stirring is continued for an hour. The acid solution is poured onto ice pieces and stirred, followed by stirring twice

Ether extracted. The crystals formed in the aqueous layer are filtered off and recrystallized from acetone. The melting point is 140-142 ° C.

Analysis:

Calculated for C ₁₈ H ₁₈ O ₈ N ₂ S ₁ F _6: C 40.29; H 3.35; N, 5.22; S 5.97

Found: C40.27; H 3.38; N 5.18; S 5.98.

Example 10

Preparation of diethyl 2,6-bis- (trifluoromethyl) -1,4-dihydro-4-methyl-3,5-pyridinedicarboxylate.

A 200 ml one-necked flask is filled with 60ml conc. Sulfuric acid is charged and placed in an ice water bath to cool. The acid is treated with 5 g (0.123 mol) of diethyl-1-bis-trifluoromethyl-D-dihydroxy-methyl-S-piperidinedicarboxylate. Stirring is continued for 15 minutes and then the acid solution is poured onto ice cubes. The solution is extracted twice with ether and then washed with aqueous saturated sodium bicarbonate solution. The organic portions are dried over anhydrous magnesium sulfate, after which the solvent is distilled off. The resulting semi-solid material is triturated with petroleum ether and filtered off. The filtrate is then concentrated to give 0.9 g of the product, no. ⁵ 1.4377.

Analysis:

Calculated for C _u H _1s O 4 N. | F ₆ : C 44.81; H4,03; N3,73

found C44.98; H 4.06; N 3.67.

Example 11

Preparation of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4- (phenylmethyl) -3,5-pyridinedicarboxylate.

250 ml of toluene are heated with a Dean / Stark trap to remove the water under reflux conditions. To the cooled toluene is then added 15g (0.0308 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4-phenyl-methyl-3,5-piperidinedicarboxylate and 2g (0.0105 mol) of toluenesulfonic acid added. The solution is heated to reflux temperature and refluxed for 2 hours. Thereafter, a further 2 g (0.0105 mol) of p-toluenesulfonic acid are added, after which the mixture is heated at reflux temperature with removal of the water by means of a Dean / Stark trap for 18 hours.

Thereafter, the mixture is cooled, filtered and concentrated. Ethyl ether is added to the concentrate. Thereafter, the organic portions are washed with saturated aqueous sodium bicarbonate solution, separated and dried over magnesium sulfate and concentrated.

Chromatograph the residue on silica gel using 10% ethyl acetate / cyclohexane as the eluent to give 1 g (7.2%) of the desired product; nQ ⁵ 1.4820.

Analysis:

Calculated for C ₂₀ H ₂₁ O ₄ N ₁ F ₆ : C 52.98; H 4.63; N 3.09;

found: C53,24; H4,27; N 3.09.

Example 12

Preparation of diethyl 2,6-bis- (trifluoromethyl) -1,4-dihydro-4- (2-furyl) -3,5-pyridinedicarboxylate.

A 250 ml one-necked flask is charged with 150 ml of toluene. This is then heated to remove the water using a Dean / Stark trap at reflux temperature. To the cooled toluene is then added 10 g (0.0217 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4- (2-furyl) -3,5-piperidinedicarboxylate and 1 g (0.005 mol). Added p-toluenesulfonic acid. Thereafter, the reaction mixture is heated to reflux temperature and held at this temperature for 4 hours while the water is separated by means of a Dean / Stark trap. The solvent is then distilled off and the crude product is chromatographed on silica gel using 20% ethyl acetate cyclohexane to give 2.48 g (26.8%) of the product; ng ⁵ 1.4720.

Analysis:

Calculated for C ₁₇ H ₁₅ F ₆ N ₁ O ₅ : C, 47.77; H 3.51; N 3,27

Found: C47.83; H 3.51; 3.25.

Example 13

Preparation of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4- (2-thienyl) -3,5-pyridinedicarboxylate.

Approximately 100 ml of toluene are heated with a Dean / Stark trap to remove the water under reflux conditions. To the cooled toluene is then added 20g (0.0418 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4- (2-thienyl) -3,5-piperidinedicarboxylate and 2.0g (0, 0105 mol) of p-toluenesulfonic acid. The mixture is heated to reflux and held for 5 ^1/2 hours at reflux conditions. The solution is cooled and filtered. The solvent is then distilled off and the product is chromatographed using 20% ethyl acetate / cyclohexane as the eluent to give 2.45 g (13.23%) of the product; n§ ⁵ 1,4937.

Analysis:

Calculated for C ₁₇ H ₁₅ O ₄ N ₁ F ₆ S _1: C 46.04; H 3.38; N 3,16; S 7,22

Found: C46.11; H3.44; N 3,12; S7,16.

Example 14

Preparation of diethyl ^ -methylthiomethyl ^^ -bis-itrifluoromethyl-1-dihydropyridine-S-dicarboxylate and diethyl-4-methylthiomethyl-e-bis-itrifluoromethyl-S-dihydropyridine-S-dicarboxylate.

To a stirred mixture of 37.0 g (0.41 mol) of methylthioacetaldehyde and 168 g (0.90 mol) of ethyl trifluoroacetoacetate is added 1.0 mL (0.01 mol) of piperidine. The reaction mixture is then heated to 80 ⁰ C, resulting in an exothermic reaction, whereby the temperature rises to 105 ⁰ C. After cooling to 9O ⁰ C, the reaction mixture is kept at this temperature for 2 hours. The cooled intermediate product is then distilled and dissolved in 200 ml of tetrahydrofuran. The solution ammonia is excessively charged. An exothermic reaction occurs, raising the reaction temperature to 40 "C. After the exothermic reaction has reached its peak, the

Reaction temperature raised to 6O ⁰ C and held for 4 hours at this temperature. The intermediate product is then distilled to give 180.3 g of an oil.

A 20 g portion of this intermediate product in 50 ml of methylene chloride is concentrated in a cooled with ice water and stirred solution of 20 ml. H ₂ SO ₄ in 100 ml of methylene chloride at a reaction temperature of less than 1O ⁰ C was added. After completion of the addition, the two-phase reaction mixture is stirred for a further 5 minutes. It is then poured into 600ml of a mixture of ice and water. After thorough mixing, separate the phases and extract the aqueous phase with 50 ml of methylene chloride. The combined methylene chloride phases are washed successively with 600 ml of 1% NaCl solution, 600 ml of 1% sodium chloride solution and 5% sodium bicarbonate solution, dried over magnesium sulfate, filtered and distilled. Kugelrohr distillation of the liquid residue gives 11.8 g of an oil collected at 130 to 150 ° C / 0.4 torr.

Purification of the product by HPLC on silica gel using 10% ethyl acetate in cyclohexane as the eluent yields a yellow oil after removal of the solvent. Kugelrohr distillation gives 4.41 g of a

yellow oil, bp range 125 to 135 ° C / 0.08 torr, yield 23%, ng ⁵ 1.4686.

This material contains 89% 1,4-dihydropyridine isomer and 11% 3,4-dihydropyridine isomer.

Analysis:

BerechnetfürC ₁₆ H ₁₇ F ₆ NO ₄ S: C42 / 76; H4,07; 3.32

Found: C42.72; H4,24; N3,07.

Example 15

Preparation of Diethyi ^^ - bis-itrifluoromethyl-1-dihydro-phenylmethoxymethyl-S ^ -pyridine dicarboxylate A mixture of 8.6 g (0.0166 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4 -phenyl-methoxymethyl-3,5-piperidinedicarboxylate, 50 ml of toluene and 1.5 g of p-toluoisulfonic acid monohydrate are kept at reflux temperature for 19 hours while the water is separated by azeotropic distillation. The toluene solution is washed successively with 100 ml of water and 100 ml of saturated sodium bicarbonate, dried with MgSO ₄ and concentrated. The residue is subjected to Kugelrohr distillation at a pressure of 2 mm. The first fraction (pot temperature 110 to 125 ° C) is discarded. The second fraction (pot temperature 130-140 ° C) gives 3.4 g of an oil which is chromatographed using a column of Waters prep 500 A silica gel with 5% ethyl acetate cyclohexane as the eluent (flow rate 250 ml / min). The first fraction (retention time 5 to 9 minutes) is 2.01 g (25%) of the desired product, ng ⁵ 1.4845.

Analysis:

Calculated for C ₂₁ H ₂₁ F ₆ N ₁ O ₅ : C, 52.40; H 4.40; N 2.91

Found: C52.48; H 4:42; N 2.92.

Example 16

(a) Preparation of diethyl-1-bis-itrifluoromethyl-1-dihydro-ethyl-S-pyridinedicarboxylate

In a 250ml one-necked flask 100 to 120ml conc. Poured sulfuric acid. Thereafter, the acid is cooled in an ice / water bath and stirred. Then, 2.5 g (0.0058 mol) of diethyl 2,6-bis (trifluoromethyl) -4-ethyl-1,4-dihydroxy-3,5-piperidinedicarboxylate (only the cis isomer) are added and the mixture is stirred Solution for 15 minutes. The acid solution is then poured onto ice pieces and extracted with ethyl ether. All organics are washed with saturated sodium bicarbonate, dried and concentrated. The crude product is chromatographed on silica gel using 20% ethyl acetate-cyclohexane to give 1 g (44.2%) of the product based on dihydroxypiperidine, ng ⁶ 1.4441.

Analysis:

Calculated for C ^ HnFeN ^: C46,27; H4,37; N 3,59

Found: C46.41; H4,19; N3,62.

(b) (improved synthesis)

A well stirred mixture of 200ml conc. H ₂ SO ₄ and 200 ml of methylene chloride are added with 88.5 g (0.208 mol) of dihydroxypiperidine dicarboxylate (only the cis isomer) from (a). Thereafter, the reaction mixture is stirred for 45 minutes and poured slowly onto 600g pieces of ice. The methylene chloride layer is separated, dried with MgSO ₄ and concentrated to give 76.7 g (94.7%) of the product based on dihydroxypiperidine.

As mentioned above, the 1,4-dihydropyridines according to the invention can be prepared directly by reacting a corresponding 3-keto ester with an aldehyde. In this example, a similar method will now be described. A mixture of 368 g (2.0 mol) of ethyl trifluoroacetoacetate, 58 g (1.0 mol) of propionaldehyde and 1 ml of piperidine in 400 ml of methylene chloride is stirred for 1 hour at 20 ⁰ C and then for 1 hour at 30 ⁰ C and then for 1 hour under Held reflux conditions and cooled. Thereafter, another 16 g (0.289 mol) of propionaldehyde are added to the mixture, followed by heating at reflux temperature for a further 2 hours. The heating jacket is then removed. Through the reaction mixture, 108 g (6.35 mol) of ammonia gas are passed over 2 hours. Thereafter, the reaction mixture is stirred for 40 hours at 20 ⁰ C and then cooled in an ice-water bath. The cooled reaction mixture is then carefully concentrated with 100 ml. Sulfuric acid is added for 20 minutes, after which within 10 minutes, a further 300ml of conc. Sulfuric acid added. Then the reaction mixture is poured onto 600g pieces of ice in a 4I beaker. The methylene chloride layer is separated, dried with MgSO ₄ and concentrated to give 386 g of an oil containing a mixture of the desired product with its 3,4-dihydroisomer. The oil is then a strongly stirred mixture of 300ml conc. H ₂ SO ₄ and 300 ml of methylene chloride added. Thereafter, the reaction mixture is stirred for 30 minutes and poured slowly onto 1 kg of ice pieces. The methylene chloride layer is separated, dried with MgSO ₄ , and concentrated to give 348 g of an oil, which is triturated to remove 9.5 g of an insoluble solid with 400 mL of petroleum ether. Thereafter, the Petroietherfiltrat is concentrated. The residue is Kugelrohr distilled at 0.4 torr to yield 290 g (74.5%), based on ethyl trifluoroacetoacetate, of an oil which is a mixture of the desired product (84%) and its 3,4-dihydroisomer (16%) according to ¹⁹ F NMR analysis.

Example 17

Preparation of diethyl 2,6-bis- (trifluoromethyl) -3,4-dihydro-4-hydroxymethyl-3,5-pyridinedicarboxylate A mixture of 9 g (0.0174 mol) of cis -diethyl-1-bis-trifluoromethoxy -dihydroxy-benzyloxymethyl-S-piperidinedicarboxylate and 50 g (0.238 mol) of trifluoroacetic anhydride are stirred for 40 hours and then concentrated. The residue is then dissolved in 50 ml of ether. The ether solution is washed with saturated sodium bicarbonate solution, dried with MgSO ₄ and concentrated to give 8.7 g of a brown oil which is a mixture (2.7: 1) of diethyl 2,6-bis- (trifluoromethyl-S-dihydric). benzyloxymethyl-S ^ -pyridinedicarboxylate and diethyl-2,6-bis (trifluoromethyl) -1,4-dihydro-4-benzyloxymethyl-3,5-pyridinedicarboxylate.

The oil is dissolved in 40 ml of CH ₂ Cl ₂ and treated with 13.7 g of titanium tetrachloride. The resulting solution is stirred for one hour and then poured into 50 ml of cold 6N HCl. The mixture is then extracted twice with 50 ml of CH ₂ Cl ₂ . The combined CH ₂ Cl ₂ extracts are dried with MgSO ₄ and concentrated. Thereafter, the residue is chromatographed on silica gel with 20% ethyl acetate cyclohexane as eluent.

The first fraction is discarded. The second fraction is 3.1 g (48%) of diethyl 2,6-bis (trifluoromethyl) -3,4-dihydro-4-hydroxymethyl-3,5-pyridinedicarboxylate as an oil, ng ⁵ 1.4366.

Analysis:

CalculatedforCuH ^ Fsl ^ Os: C42.97; H, 3.86; N 3.58

Found: C42.98; H 3.90; N 3.56.

Example 18

Preparation of diethyl-1-bis-trifluoromethyl-S-dihydro-ethyl-S-pyridine dicarboxylate

A mixture of 10 g (0.0235 mol) of diethyl-1-bis-trifluoromethyl-D-dihydroxy-ethyl-S-piperidinedicarboxylate, 29.65 g (0.141 mol) of trifluoroacetic anhydride and 30 mL of CH ₂ Cl ₂ is stirred for 2 days and then concentrated. The residue is then dissolved in ether. The ether solution is washed with saturated sodium bicarbonate solution, dried with MgSO ₄ and concentrated to give 2.72 g (30%) of diethyl-bis-1-trifluoromethyl-S-dihydro-ethyl-S-pridinedicarboxylate as an oil, ⁵ g , 4186th

Analysis:

BerechnetfürC ₁₅ H ₁₇ F ₆ N, O _4: C46,28; H4,40; N 3.50

Found: C46,12; H4,42; N3,46.

Further dihydropyridines obtained from the corresponding piperidines in Table II are prepared by a similar procedure

as prepared in Example 16 (b). The preparable dihydropyridines are summarized in Table III. The radicals listed for R, R, and R ₂ refer to structures 3 and 4.

Table III

at R R ₂ = ng * C gef. H gef. N gef. 1,4- 3,4- game R ₃ R calc. calc. calc. di- di- No. hydro hydro

19 CH ₂ OCH ₃ CF ₃ CH ₂ CH ₃ 1.4436 44.45 44.26 4.23 4.40 3.46 3.22 92 8th 20 CH ₂ CH ₂ OCH ₂ CH ₃ CF ₃ 1.4419 47.12 46.96 4.88 4.69 3.23 3.02 85 15 21 CH ₂ CH ₂ SCH ₃ CF ₃ CH ₂ CH ₃ 1.4688 44.14 44.12 4.40 4.19 3.22 3.05 86 14 22 CH (CH ₂ CH ₃ J ₂ CF ₃ CH ₃ CH ₃ 1.4433 50.11 50,15 5.37 4.99 3.25 3.22 100 23 CH ₂ CH (CH ₃ ) ₂ CF ₂ H CH ₂ CH ₃ 1.4716 53.54 53.38 6.08 6.40 3.67 3.25 100

Example 24

Preparation of Diethyl ^^ - bis-difluoromethyl-i-dihydro-propyl-S ^ -pyridine dicarboxylate.

To a stirred mixture of 50.0 g (0.299 mol) of ethyldifluoroacetoacetate and 13.2 ml (0.150 mol) of butyraldehyde is added a few ml of piperidine. The temperature of the reaction mixture suddenly rises to 100 ⁰ C. After lowering the temperature, the reaction mixture is treated with 100 ml of THF and heated at reflux for Vh hours, after which it is stirred at normal temperature for 18 hours. Thereafter, the reaction mixture is concentrated to obtain 60.8 g of an oil. NH _{3 is passed} through a solution of 55.8 g (0.138 mol) of this oil in 30 mL of THF. The temperature of the reaction mixture suddenly rises to 41 ° C. After the temperature has dropped, the reaction mixture is concentrated, yielding an oil which solidifies upon settling out. Recrystallization of this solid from hexane gives 27.6 g (49.7%) of a yellow solid, the cis-isomer of diethyl 2,6-bis (difluoromethyl) -2,6-dihydroxy-4-propyl-3, 5-pipendindicarboxylat. 5.0 g (0.012 mol) of this solid are stirred with 20 ml of trifluoroacetic anhydride, the reaction temperature rises to 36 ° C. After the temperature has fallen, the reaction mixture is concentrated, the residue is dissolved in ether and washed with saturated sodium bicarbonate, dried ( MgSO ₄ ) and concentrated to give 3.48 g of an oil, which is subjected to Kugelrohr distillation twice at 0.2 torr (dropping temperature 85 ° C.) to give 2.84 g (51.5%) of diethyl-2,6- bis (difluoromethyl) -4-propyl-1,4-dihydro-3,5-pyridinedicarboxylate as a yellow oil, ng ⁵ , 1.4726.

Analysis:

Calculated for C ₁₆ H ₂₁ F ₄ NO ₄ : C, 52.32; H 5.76; N 3.81

Found: C51.98; H 5.86; N 3.66.

Example 25

Preparation of diethyl 2,6-bis (difluoromethyl) -4-cyclohexyl-1,4-dihydro-3,5-pyridinedicarboxylate. This compound is obtained from ethyl difluoroacetacetate and cyclohexanecarboxyaldehyde according to the procedure of Example 24. The crude product is purified by HPLC with 1% ethyl acetate-cyclohexane as the eluent. The first fraction is discarded. The second fraction is diethyl 2,6-bis- (difluoromethyl) -4-cyclohexyl-1 ^ -dihydro-S ^ -pyridinedicarboxylate, Sp.40 to 44 ⁰ C.

Analysis:

Calculated for C ₁₉ H ₂₅ F ₄ NO ₄ C 56.02; H 6,18; N 3.44

Found: C56,16; H 6,42; N 3.42.

Example 26

Preparation of diethyl ^^ -bis-itrifluoromethylJ ^ -cyclohexyl-S ^ -dihydro-S ^ -pyridine dicarboxylate.

This compound is obtained from Ethyltrifluoracetacetat and cyclohexanecarboxyaldehyde according to the procedure of Example 16 (c), except that the crude product is not distilled. It is isolated as an oil, n £ ⁵ 1,4586.

Analysis:

Calculated for C ₁₉ H ₂₃ F ₆ N ₁ O ₄ : C, 51.47; H 5,23; N 3,16

Found: C 50.15; H 5.38; N 3,24.

Example 27

Preparation of Diethyl ^^ - bis-itrifluoromethyl-i-dihydro-hydroxymethyl-S ^ -pyridine dicarboxylate. A solution of 198.5 g (0.385 mol) of the compound from Example E in Table II in 500 ml of CH ₂ Cl ₂ is mixed with 268 g (1.28 mol) of trifluoroacetic anhydride. Thereafter, the reaction mixture is stirred for 18 hours and concentrated in vacuo. The residue is dissolved in 500 ml of ether and stirred with saturated sodium bicarbonate solution, continuously adding 100 g of sodium bicarbonate until neutralization of the entire residual amount of trifluoroacetic acid. Thereafter, the ether layer is dried with MgSO ₄ and concentrated to give 178 g of an oil. A solution of this oil in 500 ml of CH ₂ Cl ₂ is cooled to -78 ° C and then treated with 140 g (0.740 mol) of titanium tetrachloride at once. After stirring for 30 minutes at -78 ⁰ C, the reaction mixture is allowed to warm to room temperature, after which it was concentrated in a mixture of 500ml. HCI and 500ml ice water pours. The resulting mixture is filtered through Celite. The CH ₂ Cl ₂ layer is separated, dried with magnesium sulfate and concentrated to give a mixture of oil and gum. This mixture is treated with 500 ml of ether and filtered to remove the gum. Thereafter, the ether filtrate is concentrated to give 149 g of an oil which is chromatographed on silica gel in 4 portions using 20% ethyl acetate-cyclohexane as eluent. The similar fractions are combined. The first fraction (retention time 6 to 8.5 minutes) is discarded.

The second fraction (retention time 9.5 to 23 minutes) is crystallized from petroleum ether, yielding 61 g (42%) of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4-hydroxymethyl-3,5 -pyridinedicarboxylate as a white solid having a melting point of 65 to 66 ° C.

Analysis:

Calculated for C ^ H ^ FsN ^ g: C42.97; H, 3.86; N 3.58

Found: C42.97; H, 3.87; N 3.58.

Example 28

Preparation of diethyl 2,6-bis (trifluoromethyl) -4-chloromethyl-1,4-dihydro-3,5-pyridinedicarboxylate. A mixture of 2.84 g of triphenylphosphine, 3.91 g (0.01 mol) of the product of Example 27 and 30 ml of CCI ₄ is held at reflux temperature for 18 hours, cooled and filtered. The filtrate is concentrated. The residue is heated with hot petroleum ether (100 ml), filtered and concentrated. The residue (3.0 g) is chromatographed on silica gel with CH ₂ Cl ₂ as eluent. The first fraction (1.51 eluate) gives 2.0 g of an oil which is erne-ut chromatographed on silica gel with 5% ethyl acetate-petroleum ether as eluent to give three fractions. The first fraction (retention time 6 to 8 minutes) is 0.3 g (7.3%) of diethyl ^ -e-bis-trifluoromethylM-chloromethyl-1-dihydro-S ^ -pyridine dicarboxylate as an oil, ng ⁵ 1.4592.

Analysis:

Calculated for C ₁₄ H ₁₄ Cl ₁ F ₆ N ₁ O ₄ : C41.04; H, 3.44; N, 3.42; Cl 8.35 Found: C41.02; H, 3.47; N 3.39; Cl 8,65.

Example 29

Preparation of diethyl ^ -acetoxymethyl ^^ - bis -trifluoromethyl-i ^ -dihydro-S ^ -pyridine dicarboxylate.

A solution of 3.91 g (0.01 mol) of the product of Example 27 in 20 ml of acetic anhydride and 5.0 g (0.0637 mol) of acetyl chloride are stirred for 1 hour and concentrated to an oil which crystallizes out. The resulting solid is recrystallized from 50 ml of petroleum ether (30-75 ° C), yielding 3.84 g (88.7%) of diethyl ^ -acetoxymethyl-bis-itrifluoromethyl-i-dihydro-S-pyridinedicarboxylate, m.p. 103X, results.

Analysis:

Calculated for C ₁₆ H ₁₇ F ₆ N ₁ O ₆ : C 44.35; H 3.96; N 3,23

Found: C44.19; H 3.98; N 3,18.

Example 30

Preparation of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4-neopentyl-3,5-pyridinedicarboxylate and its 3,4-dihydroisomer

A mixture of 62g (0.50 mol) of 3,3-dimethylbutyraldehyde (purity 78%), 184g (1.0 mol) of ethyl trifluoroacetoacetate, 1 ml of piperidine and 300 ml of THF is held at reflux for 32 hours and then cooled to 50 ⁰ C. , 100 g (6.47 mol) of ammonia are passed through the solution thus obtained for 10 hours. Thereafter, the reaction mixture is concentrated. The residue is dissolved in 500 ml of ether. Thereafter, the solution is washed twice with 300 ml of water, dried with MgSO ₄ and concentrated. The residue (179 g) is slowly poured for 15 minutes into an ice-cooled mixture, stirred with a mechanical stirrer, of 400 ml of conc. Sulfuric acid and 400ml CH ₂ Cl ₂ added. Then the mixture is poured on 2kg pieces of ice and stirred well. Thereafter, the CH ₂ Cl ₂ layer is separated, dried with MgSO ₄ and concentrated. The residue is then subjected to Kugelrohr distillation at 0.5 Torreiner. The first fraction is discarded. The second fraction (pot temperature 91 to 130 ⁰ C) represents 122g of a liquid which at 1 Torr fractional distillation

is subjected. The fraction with the boiling point of 121 to 130 ° C is the pure desired product, a yellow oil, ng ⁵ 1.4388, which is a mixture (3: 1) of 1,4-dihydro and 3,4-dihydro isomers.

Analysis:

Calculated for C ₁₈ H ₂₃ F ₆ N ₁ O ₄ : C 50.12; H 5.37; N 3.25

Found: C49.92; H 5.25; N 3.65.

Example 31

Preparation of diethyl ^ -bis-trifluoromethyl-i / 1-dihydro-t-methylpropylo-S ^ -pyridinecarboxylate and its 3,4-dihydroisomer

This compound is obtained from 2-methylbutyraldehyde and ethyl trifluoroacetoacetate by a procedure similar to that in Example 30 to give a colorless oil, n £ ^5, 1.4417.

Analysis:

Calculated for C ₁₇ H ₂₁ F ₆ N ₁ O ₄ : C, 48.92; H 5.07; N 3.36

Found: C49.05; H5,10; N 3.34.

With the exception of the products of Examples 17 and 27, the dihydropyridines described above can be used as intermediates in a process for the preparation of corresponding herbicidally active pyridines. The conversion of the described dihydropyridines into the corresponding pyridines is carried out by reacting the dihydropyridines with 1,8-diazobicyclo [5.4.0] undec-7-ene (DBU) in THF at reflux temperature. The process in which the dihydropyridines are used as intermediates for the preparation of herbicidally active pyridines is illustrated by the following examples.

Example 32

Preparation of Diethyl 2- (difluoromethyl) -4-propyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate A mixture of 31.0 g (0.0742 mol) of the product of Example 7,11.03g (0.0742 Mol) of DBU and 200 ml of THF is kept under reflux conditions for 18 hours and concentrated. The residue is then stirred with water and extracted with ether. Thereafter, the ether extracts are dried with MgSO ₄ and concentrated. The residue is then subjected to kugelrohr distillation at a pressure of 1 Torr. The distillate is then chromatographed on silica gel using 3% ethyl acetate-cyclohexane as the eluent to give 23.9 g (80.9%) of diethyl 2- (difluoromethyl) -4-propyl-6- (trifluoromethyl) -3, 5-pyridinedicarboxylate as an oil, ng ⁵ 1.4436.

Analysis:

Calculated for Ci ₆ H ₁₈ F ₅ NO ₄ : C 50.13; H4,74; N3,66

Found: C49.74; H4,66; N 3,55.

Example 33

Preparation of diethyl 4-cyclohexyl-2- (difluoromethyl) -6- (trifluoromethyl) -3,5-pyridinedicarboxylate A mixture of 70.0 g (0.152 mol) of the product of Example 26, 23.15 g (0.152 mol) of DBU and 250 ml of THF is kept at reflux conditions for 18 hours and concentrated. The residue is then poured into water and extracted with ether. The ether extracts are washed with dilute hydrochloric acid, dried with MgSO ₄ and concentrated. The residue is subjected to kugelrohr distillation, yielding 31.9g (49.4%) of diethyl 4-cyclohexyl-2- (difluoromethyl) -6- (trifluoromethyl) -3,5-pyridinedicarboxylate as an oil, n, ^5, 1.4614 , receives.

Analysis:

Calculated for C ₁₉ H ₂₂ F ₅ N ₁ O ₄ : C, 53.90; H 5.24; N 3.31

Found: C54,19; H 5.33; N3,51.

Example 34

Preparation of Dimethyl 2- (difluoromethyl) -6- (trifluoromethyl) -4-isobutyl-3,5-pyridinicarboxylate A mixture of 23.0 g (0.0591 mol) of the product of Example 2, 12.2 g (0.077 mol ) 96% pure DBU and 100 ml of THF are kept at reflux for 3 days and then poured into 250 ml of 3N HCl. The oily precipitate is extracted into ether (2 x 100 ml). The ether extracts are dried with MgSO ₄ and concentrated to give 14.4 g of an oil containing the desired product and acid products from the 1 H NMR data. This oil is then dissolved in ether and extracted with 100 ml of saturated sodium bicarbonate solution. The ether layer is then dried with MgSO ₄ and concentrated to give 8.9 g of an oil containing the desired product (based on the ¹⁹ F NMR data). The sodium bicarbonate extract is then treated with conc. HCI acidified to give an oil which is extracted into ether. The ether layer is then dried with MgSO ₄ and concentrated to give 4.8 g of a residue containing the monooli dicarboxylic acid (9: 1) derived from the desired product. This residue is treated with 3.0 g (0.0217 mol) of potassium carbonate, 20 ml of methyl iodide and 50 ml of acetone. Thereafter, the mixture is kept at reflux temperature for 42 hours and concentrated. The residue is treated with water and extracted with ether (2 × 100 ml). Thereafter, the ether layer is dried and concentrated. The residue is subjected to kugelrohr distillation at 1 Torr (pot temperature 130 ° C) to give 5.1 g (23.4% of Example 2) of the desired product in the form of an oil, n £ ⁵ 1.4478. This product crystallizes when allowed to stand, Sp 36 to 37 ⁰ C.

Analysis:

Calculated for _{C 15} H ₁₆ F ₅ N, O ₄ : C 48.79; H 4,37; N 3.79

Found: C48 / 75; H 4,39; N 3.77.

The desired 71% pure product described above is chromatographed by HPLC using 3% ethyl acetate / cyclohexane as the eluent to give, as the first fraction (0.79g, retention time 7 to 8.5 minutes) 6- (difluoromethyl) -4- (isobutyl) -2- (trifluoromethyl) -3-pyridinecarboxylate and additionally a second fraction (retention time 8.5 to 18.5 minutes) of 6.4 g (29.4%) of the pure desired product, n ^ ⁵ 1.4474. As stated above, the 1,2-dihydropyridines according to the invention are obtained by reduction of the correspondingly substituted

Pyridine compound with a reducing agent, such as sodium borohydride. This process is illustrated in Examples 35 to 37 below.

Example 35

Preparation of dimethyl-1 _/ 2-dihydro-2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate. A solution of 21.9 g (0.06 mol) of the product of Example 34 in 110 ml of DMF is added sequentially with 4.6 g (0.121 mol) of sodium borohydride and 30 ml of water. After stirring for 2 hours, an additional 4.6 g (0.121 mol) of sodium borohydride, 30 ml of water and 100 ml of DMF are added, after which the reaction mixture is stirred for 4 hours and concentrated. The crude product is purified by HPLC using 5% ethyl acetate in cyclohexane as eluent. The first fraction is 3.9 g of an oil containing a mixture of unidentified products. The second fraction (0.6g) was not labeled. The third fraction is 6.2 g of an oil which is recrystallized from hexane to give 2.3 g (10%) of a yellow solid. By two-fold recrystallization from hexane, 1.34 g (6%) of the desired product as a yellow solid having a melting point of 87.5 to 88.5 ⁰ C.

Analysis:

Calculated for Ci ₅ H ₁₃ F ₅ NO ₄ : C 48.52; H 4,89; N 3.77

Found: C48, 54; H, 4.68; N 3.83.

Example 36

Preparation of dimethyl 1,2-dihydro-6- (difluoromethyl) -4-isobutyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate. A solution of 53.0 g (0.144 mol) of the product of Example 34 is reduced with 25 g (0.661 mol) of sodium borohydride as described in Example. The crude product (64.4 g) is purified by HPLC using 5% ethyl acetate in cyclohexane as the eluent. The first fraction (7.9g) is an unidentified product (27%). The second fraction (1.4g) was not labeled. The third fraction is 29.9 grams of an oil containing the desired product. Recrystallization of this oil from hexane gives 26.9 g as a first crop with a melting point of 76 to 82 ° C, then 5.0 g as a second crop and 1.1 g as a third crop. The first crop is a mixture of the product of Example 35 and the desired product at a ratio of 2.7: 1. The second crop is combined with the third and six times recrystallized from cyclohexane, yielding 0.7 g of pure product in the form of a yellow solid having a melting point 79 to 81 ⁰ C.

Analysis:

Calculated for C ₁₅ H ₁₈ F ₅ NO ₄ : C 48.52; H4,89; N 3.77

Found: C48.37; H4,93; N 3.73.

Example 37

Preparation of dimethyl-t, -dihydro -isobutyl ^^ -bis-itrifluoromethyl-S.S-pyridinedicarboxylate. A 250 ml flask is charged with 35 ml of glacial acetic acid and 13.89 g (0.0354 mol) of the product of Example 6. Thereafter, sodium nitrite is added in an amount of 3 g (0.0434 mol), after which the mixture is stirred for 72 hours in a nitrogen atmosphere. Thereafter, the solution is poured onto ice / water and stirred. The organics are extracted into ether and washed with aqueous saturated sodium bicarbonate solution. The organics are then dried with anhydrous magnesium sulfate, filtered and concentrated to give 4.93 g (35.6%) of diethyl 2,6-bis (trifluoromethyl) -4-isobutyl-3,5-pyridinedicarboxylate.

This pyridine compound is hydrolyzed and transesterified to give the dimethyl ester as follows: A stirred mixture of 31.8 g (0.076 mol) of diethyl ester, 150 ml of 10% sodium hydroxide solution (0.38 mol) and 75 ml of ethanol is heated at reflux for 72 hours. Thereafter, the reaction mixture is partially concentrated, diluted with water to 250 ml and heated again at reflux temperature for 24 hours. The cooled mixture is treated with an excess of conc. Hydrochloric acid acidified and extracted with ether (1 χ 200ml, 3 χ 100ml). The combined ether extracts are dried with MgSO ₄ , filtered and concentrated to give 28.5 g residue. A portion of this residue (2.2 g) is stirred with 200 ml of dimethylformamide, 16.5 g (0.12 mol) of potassium carbonate and 25.5 g (0.18 mol) of methyl iodide for 24 hours at room temperature. This mixture is then added 11 2% hydrochloric acid. The product is extracted with methylene chloride (1 χ 200ml and 3 x 100ml). The combined extracts are washed with 300 ml of 1% hydrochloric acid and 1% sodium chloride, dried with MagS0 ₄ , filtered and concentrated. By Kugelrohr distillation to obtain 16.2 g of a light yellow oil with a boiling point of 100 to 110 ° C / 0.1 Torr, which solidifies. Recrystallization from hexane / ether to give 12.0 g (49%) of a white solid with a melting point of 80.5 to 82.5 ⁰ C.

To a stirred solution of 8.65 g (0.022 mol) of the above solid in 80 ml of dimethylformamide is added 0.83 g (0.22 mol) of sodium borohydride. Thereafter, the reaction mixture is stirred at room temperature for 1 hour and then heated to 5O ⁰ C for 15 minutes and finally cooled to room temperature again. The reaction mixture is slowly added to a stirred mixture of 600 ml of 2% hydrochloric acid and 100 ml of methylene chloride. Thereafter, the phases are separated and the aqueous phase extracted with 50 ml of methylene chloride. The combined extracts are washed with 300 ml of 1% hydrochloric acid / 1% sodium chloride, dried with MgSO ₄ , filtered and concentrated. Purification by HPLC (silica gel, 4% ethyl acetate in cyclohexane) followed by Kugelrohr distillation gives 6.79 g (79%) of a yellow oil with a boiling point of 115-125 ° C / 0.15 torr, n-1.4584.

Analysis:

BerechnetfürC _l5 H ₁₇ NO ₄ F _6: C46,28; H 4.40; N 3.60

Found: C46.40; H 4:42; N 3.36.

Example 38

S-ethyl-S-methyl-i ^ -dihydro ^ -methyl ^ -isopropyl-e-ftrifluormethyli-S ^ -pyridinedicarboxylate. 52.7 g of ethyl 3-amino-4-methyl-2-pentenoate are prepared from 98 g of ethyl (2-methylpropionyl) acetate according to Aberhart and Liv, JOC 1981, 3749. The Enaminoester has a value n ^s ₀ of 1.4914, bp 92 ° / 6mm. The cited enamine (20g) is mixed in 100ml with 21.6g of methyl 2,2,2-trifluoroacetate and 6g of acetaldehyde. After adding a few drops of piperidine it comes to a

spontaneous exothermic reaction with heating to 60 °. Thereafter, the mixture is heated at about 70 ° while stirring (slightly below the reflux temperature) for IV2 hours. The mixture is then heated at reflux temperature for 5 hours, following the process by ¹⁹ F NMR analysis, and allowing to stand overnight at room temperature. THF is then distilled off from the mixture to give 46.1 g of the crude product, of which 40 g are dehydrated with 25 ml of trifluoroacetic anhydride and about 100 ml of CH ₂ Cl ₂ . This leads to an exothermic reaction, whereby the temperature rises to 40 °. The material is then held at reflux temperature for about 1 hour and then distilled to give 4 g of crude product which is subjected to Kugelrohr distillation (100 to 16070.15 mm) no ⁵ 1.4804.

Analysis:

Calculated for C ₁₅ H ₂₀ F ₃ O ₄ : Found:

C53.75; H6.01; N4.18 C 54.20; H 6.08; N 3.95.

Example 39

3-ethyl-5-methyl-1,2-dihydro-2-ethyl-4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A stirred mixture of 18.0 g (0.20 mol) isovaleraldehyde, 30.8 g (0.20 mol) methyl trifluoroacetate, 28.6 g (0.20 mol) ethyl 3-amino-2-pentenoate, 60 mL THF and 3 drops Piperidine is heated and held at reflux temperature for 18 hours.

The cooled reaction mixture is then concentrated and the residue partially crystallized on standing at room temperature. The solids are filtered off from a 8.0 g sample, washed with hexane and recrystallized from THF / hexane to give 1.72 g (22%) of a white solid.

A stirred mixture of 72 g (0.18 mol) of the crude solid prepared above, 30 mL (0.21 mol) of trifluoroacetic anhydride and 150 mL of methylene chloride is heated and maintained at reflux temperature for 2 hours. The washed reaction mixture is then concentrated to give 88.0 g of an oil. Purification of a part thereof by HPLC gives a purified product: η ff = 1.4785.

Calcd for C ₁₆ H ₂₃ F ₃ NO _4: C 56.19, H 6.66; N 3.85

Found: C56,27; H 6,77; N 3.60.

Using similar preparative techniques as demonstrated in the previous examples, still further compounds of the invention can be prepared. These are listed together with one physical property in Table A below.

Table A

example R R ₂ R ₃ R ₁ Ri enamel boiling point No. Point 40 CH ₂ CHC ^ ³ CF ₃ et et 100 / 0.5 torr 41 CH ₂ - < ³ CF ₃ CF ₃ et et 120 / 0,5Torr 42 CF ₃ CF ₃ CF ₃ et et 60-61 43 CH ₂ CH (CH ₃ J ₂ CF ₃ CH ₃ CH ₃ CH ₃ 68-69 44 CH ₃ CF ₃ CH ₃ et et 110-120 / 0.1 torr 45 CH ₂ CH (CH ₃ J ₂ CF ₃ CH ₃ et et 140-145 / 0,15Torr 46 CH ₂ CH (CHa) ₂ CF ₂ H CH ₃ et et 140-150 / 0.1 torr

As indicated above, the compounds of the present invention are effective as herbicides, particularly as pre-emergence herbicides. Tables IV and V summarize the results of the tests carried out to determine the herbicidal pre-emergence activity of the compounds of the invention. The pre-emergence tests were conducted as follows: A good grade of soil is placed in aluminum pans and compacted to a depth of 0.95 to 1.27 cm from the top of the shell. On top of the earth is placed a number of seeds or vegetative propagules of various plant species. The soil used to evenly fill the shells after sowing or applying the vegetative propagules is weighed into a dish. The soil and a known amount of the active ingredient employed in a solvent or as a spray powder suspension are thoroughly mixed and used to cover the prepared skins. The amount of active ingredient in Table 4 corresponds to an application rate of 11.2 kg / ha. After treatment, the trays are placed on greenhouse tables, then irrigated from below as needed to ensure the necessary moisture for germination and growth.

Approximately 2 to 3 weeks after sowing and treatment, the plants are observed and the results recorded. In Table IV these are summarized. Herbicidal evaluation was based on a fixed scale based on the percent damage of each plant species. The classifications are defined as follows:

- it - vw ι uv »

% Inhibition

rating

0-24 25-49 50-74 75-100

The plant species used for a group of tests, the data of which are listed in Table IV, are identified by a letter in accordance with the following legend:

A - Creeping Thistle * B - Broadcloth C - Greater Honeygrass D - Winds E - Common Goosefoot F - Water Pepper G - Cyperngrass * H - Quercus * I - Sudan Grass * J - Dachtrespe K - Millet * Drawn from vegetative propagules

Table! V plant species A ΰ C U b I- b H I J K. preemergence A 3 2 3 3 3 - 3 3 3 3 3 connection 3 3 0 , 1 0 2 1 0 0 0 2 3 according to example no - 3 0 0 2 3 3 0 0 0 3 3 2 0 3 0 0 0 0 0 0 0 0 0 1 3 - 0 1 3 3 3 0 0 3 1 3 3 4 - 3 1 3 3 3 3 0 3 3 3 3 5 3 0 0 0 1 0 0 0 0 0 0 3 6 0 3 0 0 0 2 0 0 0 2 0 3 7 - 3 0 1 3 3 3 0 3 1 3 3 8th ' - 3 0 0 0 0 0 0 0 0 0 2 9 - 3 0 3 3 3 3 0 1 0 3 3 10 3 - 0 1 3 1 0 0 0 3 3 11 0 0 0 2 3 0 0 0 0 3 3 12 0 0 0 0 0 0 0 0 0 0 2 13 - 1 3 3 3 - 0 3 3 3 3 14 3 1 3 3 3 , 3 1 3 3 3 3 15 - 0 0 3 3 1 0 2 0 3 3 16 3 1 1 1 3 - 3 3 0 3 3 18 0 0 0 2 3 - 0 0 0 2 3 19 1 0 0 0 0 - 0 0 0 1 1 20 0 0 3 3 3 - 0 2 0 3 3 21 3 0 1 3 3 - 0 0 0 3 3 22 3 1 0 1 2 0 0 0 0 1 0 23 0 0 0 0 3 0 0 0 0 0 0 24 0 0 0 0 0 0 0 0 0 3 3 28 0 0 1 1 0 0 0 0 - 1 3 29 0 1 3 3 3 3 3 3 3 3 3 30 3 0 0 2 3 3 0 0 3 3 3 31 1 32 Table IV (continued) B C D e F G H I J K 33 Example no. 3 3 3 3 3 3 3 3 3 3 34 3 3 3 3 3 3 3 3 3 3 35 3 3 3 3 3 3 3 3 3 3 36 1 3 3 3 3 3 3 3 3 3 37 N 0 0 1 1 0 2 N 3 3 40 1 3 3 3 3 0 3 - 3 3 41 0 0 3 0 0 0 0 0 2 3 42 3 3 3 3 3 3 3 3 3 3 43 0 3 3 3 3 1 3 3 3 3 44 1 3 3 3 3 1 3 3 3 3 45 3 3 3 3 3 0 1 2 3 3 46

The compounds were further tested using the above procedure on the following plant species:

L - Soybean M - Sugar Beet N - Wheat 0 - Rice P - Millet B - Spitzklette Q - Wild Buckwheat D - Winds R - Sesbania Hemp E - Common Goosefoot F - Water Pepper C - Wooly Honeygrass J - Dachtespe S - Spleen Sprouts sp.

K - millet T - blackthorn The results are summarized in Table V.

Table V kg / ha plant species M N O P B Q D R e F C J S K T preemergence 1 0 0 2 0 0 0 0 3 1 0 3 2 3 3 connection 5.6 L 3 3 3 3 1 2 2 2 3 3 2 3 3 3 3 to 5.6 0 2 3 2 0 0 0 0 1 3 1 1 3 3 3 3 example 1.12 3 1 0 0 0 0 0 0 0 2 0 0 1 1 1 2 4 0.27 1 3 3 3 3 0 3 3 2 3 1 1 3 3 3 3 6 5.6 0 1 1 0 0 0 0 1 1 0 0 0 0 1 3 3 1.12 3 1 0 0 0 0 1 0 0 0 0 0 0 0 1 1 0.27 0 3 3 3 3 0 2 3 3 3 3 2 3 3 3 3 7 5.6 1 2 3 0 2 0 1 1 2 1 0 0 2 3 3 3 1.12 3 3 3 3 3 1 3 2 3 3 3 1 3 3 3 3 5.6 0 1 0 0 0 3 0 0 0 0 0 0 0 0 3 3 16a 1.12 1 1 1 0 0 0 1 0 0 0 1 0 0 1 3 - 5.6 0 2 1 1 1 0 3 0 2 3 3 0 3 1 3 3 12 5.6 0 1 0 0 0 0 1 0 0 0 0 0 0 0 1 0 1.12 0 1 0 0 0 0 1 0 0 1 1 0 0 0 0 0 9 0.27 0 3 3 3 3 3 2 3 3 2 2 1 3 3 3 - 13 11.2 0 3 3 3 3 0 1 3 3 2 2 1 3 3 3 - 5.6 3 1 0 2 0 0 1 1 3 2 1 0 0 0 2 - 1.12 1 1 0 0 0 3 1 0 3 0 3 0 0 0 0 - 10 0.27 1 0 0 0 0 0 0 0 1 0 1 0 0 0 3 - 5.6 0 0 1 0 0 0 0 0 3 0 0 0 0 0 0 - 1.12 1 0 2 2 3 0 2 3 2 3 3 1 3 3 3 3 5.6 2 3 3 3 3 0 3 3 3 3 3 1 3 3 3 3 3 5.6 2 0 0 2 0 0 0 0 0 0 0 0 0 2 2 3 1.12 3 3 1 3 3 1 3 2 3 3 - 2 3 3 3 3 14 5.6 0 1 0 3 3 0 1 0 1 2 - 0 2 3 3 3 18 1.12 1 2 0 1 1 0 0 1 1 2 2 1 1 2 3 0.27 1 23 0

Table V (continued)

Compound plant species

after example kg / ha L M N O P B Q D R e F C J S K T 0 2 1 2 3 0 3 1 2 3 2 3 3 3 3 24 5.6 0 1 0 2 0 0 0 0 0 2 - 1 0 1 3 3 1.12 3 3 3 3 3 0 3 3 3 3 - 3 3 3 3 3 2 5.6 2 2 3 3 3 0 3 2 2 3 - 1 3 3 3 3 1.12 0 1 1 1 3 0 3 1 1 1 - 0 3 3 3 3 0.27 0 2 0 0 1 0 2 0 0 1 - 0 2 2 3 2 0.056 0 2 1 2 1 0 0 0 0 2 - 0 1 1 2 2 0.011 0 0 0 0 0 0 0 0 0 0 - 0 2 1 3 3 21 5.6 0 3 0 0 0 0 0 1 0 0 - 0 0 0 1 2 20 5.6 0 0 0 0 0 0 0 0 0 1 1 0 0 0 2 2 30 5.6

The herbicidal compositions of the present invention, including concentrates which must be diluted before application, contain at least one active ingredient and adjuvant in liquid or solid form. The compositions are blended by mixing the active ingredient with an additive comprising diluents, diluents, carriers and conditioning agents to yield compositions in the form of finely divided solids, granules, pellets, solutions, dispersions or emulsions. Thus, the active ingredient can be used with an additive such as a finely divided solid, an organic-based fluid, water, a wetting agent, a dispersing agent, an emulsifier, or any suitable combination thereof.

The compositions of the present invention, especially liquids and wettable powders, contain as conditioning agents one or more surfactants in amounts which are such that a particular composition can be readily dispersed in water or oil. The incorporation of a surfactant in the composition significantly increases their efficiency. By the term "surfactant" is meant wetting agents, dispersing agents, suspending agents and emulsifying agents Anionic, cationic and nonionic agents can be used with equal success.

Preferred wetting agents are alkylbenzene and alkylnaphthalenesulfonates, sulfated fatty alcohols, amines or acid amides, long-chain acid esters of sodium isothionate, esters of sodium sulfosuccinate, sulfated or sulfonated fatty acid esters, petroleum derivatives, sulfonated vegetable oils, ditertiary acetylene glycols, polyoxyethylene derivatives of alkylphenols, especially isooctylphenol and nonylphenol, and polyoxyethylene derivatives of monoester fatty acid esters of hexitol anhydrides (eg sorbitan). Preferred dispersants are methylcellulose, polyvinyl alcohol, sodium lignosulfonates, polymeric alkylnaphthalenesulfonates, sodium naphthalenesulfonate and polymethylenebisaphthalenesulfonate.

Injectable powders are water-dispersible compositions containing one or more active agents, an inert solid insertion agent and one or more wetting and dispersing agents. The inert solid diluents are usually of mineral origin, such as the natural clays, diatomaceous earth, and synthetic silica-derived minerals, and the like. Examples of such extenders are kaolinites, attapulgite clay and synthetic magnesium silicate. The spray powder compositions according to the invention usually contain from 0.5 to 60 parts (preferably 5 to 20 parts) of active ingredient, about 0.25 to 25 parts (preferably 1 to 15 parts) of wetting agent, about 0.25 to 25 parts (preferably 1.0 to 15 Parts) dispersant and 5 to about 95 parts (preferably 5 to 50 parts) of inert solid diluent, all parts being based on the weight of the total composition. If necessary, about 0.1 to 2.0 parts of the solid inert diluent may be replaced with a corrosion inhibitor or antifoam, or both.

Other compositions contain dust concentrates containing 0.1 to 60% by weight of active ingredient at a suitable draw center! contain; these dusts may be diluted for application at concentrations in the range of about 0.1 to 10% by weight.

Aqueous suspensions or emulsions may be prepared by stirring an aqueous mixture of a water-insoluble active agent and an emulsifier until uniform and then homogenizing to obtain a stable emulsion of very finely divided particles. The resulting concentrated aqueous suspension is characterized by its extremely small particle size, so that after dilution and spraying a very uniform coating is achieved. Suitable concentrations of these compositions contain about 0.1 to 60, preferably 5 to 50,% by weight of active ingredient, the upper limit being determined by the solubility limit of the active ingredient in the solvent. In another form of aqueous suspensions, a water-immiscible herbicide is encapsulated to form a microencapsulated phase dispersed in an aqueous phase. In one embodiment, minute capsules are formed by bringing together a lignosulfonate emulsifier-containing aqueous phase and a water-immiscible chemical agent and polymethylene polyphenyl isocyanate, which disperses water-immiscible phase in the aqueous phase, followed by the addition of a polyfunctional amine he follows. The isocyanate and amine compounds react to form a solid urea envelope around the particles of the water-immiscible chemical agent thereby forming microcapsules. In general, the concentration of the microencapsulated material is about 480 to 700 g / l of the total composition, preferably 480 to 600 g / l. Concentrates are usually solutions of active ingredient in water immiscible or partially miscible solvents in combination with a surfactant. Suitable solvents for the active ingredient according to the invention are dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, hydrocarbons and water-immiscible ethers, esters or ketones. However, other highly concentrated liquid concentrates can be prepared by dissolving the active ingredient in a solvent and then adding e.g. As with kerosene to the spray concentration

is diluted. --- · -

The concentrate compositions contemplated herein generally contain from about 0.1 to 95 parts (preferably 5 to 60 parts) of active ingredient, about 0.25 to 50 parts (preferably 1 to 25 parts) of surfactant and, if desired, about 4 to 94 parts of solvent , wherein all parts are given in mass, based on the total mass of the emulsifiable oil. Granules are physically stable finely divided compositions having an active agent adhered to or distributed throughout a base matrix of an inert finely divided extender. To aid in leaching the active agent from the finely divided material, one of the above surfactants may be present in the composition. Natural clays, pyrophyllites, lllites and vermiculites are examples of useful classes of finely divided mineral extenders. The preferred extenders are porous, absorbent preformed particles such as preformed and sieved finely divided attapulgite and heat expanded finely divided vermiculite and the finely divided clays such as kaolin clays, hydrated attapulgite or bentonite clays. These extenders are sprayed or mixed with the active ingredient to form the herbicide granules. The granule compositions of the invention may contain from about 0.1 to about 30 parts by weight of active ingredient per 100 parts by weight of clay and from about 0 to about 5 parts by weight of surfactant per 100 parts by weight of finely divided clay.

The compositions of the invention may also contain other additives, for. Fertilizers, other herbicides, other pesticides, preservatives and the like which are used as adjuvants or in combination with one of the above-mentioned adjuvants. In combination with the active compounds of the invention useful chemicals are, for. For example, triazines, ureas, carbamates, acetamides, acetanilides, uracils, acetic acid or phenol derivatives, thiocarbamates, triazoles, benzoic acids, nitriles, biphenyl ethers and the like, such as:

Heterocyclic N- / S-derivatives

2-Chloro-4-ethylamino-6-isopropylamino-s-triazine 2-Chloro-4,6-bisT (isopropylamino) -s-triazine 2-Chloro-4,6-bis (ethylamino) -s-triazine 3 isopropyl-1H-2,1,3-benzothiadiazine-4- (3H) -one-2,2-dioxide 3-amino-1,2,4-triazole 6,7-dihydro-dipyrido (1,2-a: 2 ', 1'-c) -pyrazidinium salt B-bromo-S-isopropyl-S-methyluracil 1,1'-dimethyl-4,4'-bipyridinium

ureas

N '- (4-chlorophenoxy) phenyl-N, N-dimethylurea N, N'-dimethyl-N'-O-chloro-methylphenyD urea 3- (3,4-dichlorophenyl) -1,1-dimethylurea, 1,3-dimethyl 3- (2-benzothiazolyl) -substance 3- (p-Chlorophenyl) -1,1-dimethylurea 1-Butyl-3- (3,4-dichlorophenyl) -1-methylurea

Carbamates / thiolcarbamates

2-Chloroallyl diethyldithiocarbamate S- (4-chlorobenzyl) -N, N-diethylthiolcarbamate isopropyl-N- (3-chlorophenyl) carbamate S ^^ - Dichloroallyl-N, N-diisopropylthiolcarbamate Ethyl N, N-dipropylthiolcarbamate S-Propyldipropylthiolcarbamate

Acetamide / acetanilides / Aniline / amides

2-chloro-N, N-diallylacetamide N, N-dimethyl-2,2-diphenylacetamide N- (2,4-dimethyl-5 - (trifluoromethyl) sulfonyl / amino / -phenyl! Acetamide N-isopropyl-2- chloroacetanilide 2 ', 6'-diethyl-N-methoxymethyl-2-chloroacetan! id 2'-methyl-6'-ethyl-N- (2-methoxyprop-2-yl) -2-chloroacetanilide a, a :, o: trifluoro-2 _r 6-dinitro-N, N-dipropyl-p-toluidine N- (1,1-dimethylpropynyl) -3,5-dichlorobenzamide

Acids / esters / alcohols

2,2-dichloropropionic acid 2-methyl-4-chlorophenoxyacetic acid 2,4-dichlorophenoxyacetic acid methyl-2- / 4- (2,4-dichlorophenoxy) phenoxy / propionate 3-amino-2,5-dichlorobenzoic acid 2-methoxy-3,6 dichlorobenzoic acid 2,3,6-trichlorophenylacetic acid N, Naphthylphthalamic acid 5- / 2-chloro-4- (trifluoromethyl) phenoxy / 2-nitrobenzoate-Na 4,6-oinitro-o-sec-butylphenol N- (phosphonomethyl) glycine and its C 1-6 monoalkylamine and alkali metal salts and combinations thereof.

2,4-dichlorophenyl-4-nitrophenyl ether 2-chloro-a, a, a-trifluoro-p-tolyl-3-ethoxy-4-nitrodiphenyl ether

Various

2,6-Dichlorobenzonitrile Monosodium methanesulfonate Disodium methanarsonate Fertilizers suitable in combination with the active compounds are, for example, ammonium nitrate, urea, potassium carbonate and superphosphate. Other useful additives include substances in which the plant organism roots and grows, such as compost, fertilizer, humus, sand and the like. Herbicidal formulations of the types described above are illustrated in various following embodiments.

I. Emulsifiable concentrates

Wt .-%

A. Compound of Example 5 1.0

Free acid of the complex organic phosphate of an aromatic or aliphatic hydrophobic base (eg GAFAC RE-610, registered trademark of GAF Corp.) 5,59

Polyoxyethylene / polyoxypropylene block copolymer with butanol (eg Tergitol XH, registered trademark of Union Carbide Corp.) 1,11

Phenol 5.34

Monochlorobenzene 86,96

100.00

Compound according to Example 16 25.00 Free acid of complex organic phosphate or aromatic or aliphatic hydrophobic

Base (e.g., GAFAC RE-610) 5.00 polyoxyethylene / polyoxypropylene block copolymer

with butanol (e.g., Tergitol XH) 1.60

Phenol 4.75

Monochlorobenzene 63,65

100.00

II. Liquid concentrates

Wt .-%

A. Compound according to Example 6 25.00

Methylcellulose "0.3

Silica airgel, 1.5

Na lignosulfonate 3,5

Na-N-methyl-N-oleyl taurate. 2.0

Water 67.7

100.0

B. Compound of Example 17 45.0

Methylcellulose 0.3

Silica aerogel 1.5

Na lignosulfonate 3,5

Na-N-methyl-N-oleyl taurate 2.0

Water 47.3

100.0

III. wettable powder

Wt .-%

A. Compound of Example 5 25.0

Na lignosulfonate 3.0

Na-N-methyl-N-ollytaurate 1.0

Amorphous silica (synthetic) 71.0

100.0

B. Compound of Example 3 80.0

Na dioctylsulfosuccinate 1,25

Calcium lignosulfonate 2.75

Amorphous silica (synthetic) 16.00

100.00

C. Compound of Example 6 10.0

Na lignosulfonate · 3.0

Na-N-methyl-N-oleyl taurate 1.0

Kaolinite clay 86.0

100.0

IV. Water-soluble powders

Wt .-%.

A. Compound to Example 10.0

Na dioctylsulfosuccinate. 2.0

Silica aerogel 5.0

Methyl violet 0.1

Na bicarbonate "82.9

100.0

B. Compound according to Example 17 90.0

Ammonium phosphate 10.0

100.0

V. Dust

Wt .-%

A. Compound according to Example 2 2.0

Attapulgite 98.0

100.0

B. Compound of Example 9 60.0

Montmorillonite 40.0

100.0

C. Compound of Example 7 30.0

Ethylene glycol 1.0

Bentonite 69.0

100.0

C. Compound of Example 16 1.0

Diatomaceous earth 99.0

100.0 Vl. granules

Wt .-%

A. Compound according to example 8 15.0

Granular attapulgite (sieve fineness20 / 40) 85.0-

100.0

B. Compound of Example 9 30.0

Diatomaceous earth (20/40) 70.0

100.0

C. Compound of Example 6 1.0 Ethylene glycol 5.0 Methylene blue 0.1 Pyrophyllite 93.9

100.0

D. Compound of Example 13 5.0 Pyrophyllite (20/40) 95.0

100.0

When working according to the invention effective amounts of the compounds of the invention are applied to the soil containing the plants in a suitable manner. The application of liquid or finely divided solid compositions to the soil may be carried out by conventional methods, e.g. B. Pulversprühgeräten, field spray pipes and hand sprayers and Spritznebelgeräten. The compositions can also be applied from aircraft as dust or spray because of their effectiveness even in small quantities.

The application of an effective amount of the compounds of the invention to the location of undesired weeds is important and critical to the practice of the invention. The exact amount of active ingredient to be used depends on several factors, such as the plant species and its stage of development, the nature and condition of the soil, the amount of precipitation and the specific compounds used. Selective pre-emergence application to the soil usually uses an amount of from 0.1 to about 11.2 kg / ha, preferably from about 1.12 to about 5.60 kg / ha. Smaller or larger quantities may be required in some cases. One skilled in the art, given the description and examples above, can easily determine the optimum amount to be used in a particular case.

The term "soil" is used in its best sense and is intended to include all conventional "soils" as defined in Webster's New International Dictionry, Second Edition, unabridged (1961). Thus, the term applies to any substance or medium in which plants can root or grow, and includes not only soil, but also compost, fertilizer, manure, humus, sand, and the like, which are useful for promoting plant growth. While the invention has been described with reference to certain modifications, the details thereof are not to be construed as limitations except as set forth in the following claims.

Claims (49)

Invention claim: A herbicidal composition, characterized in that it contains an adjuvant and a herbicidally effective amount of a compound of the formula H OR ₁ or wherein R is selected from the group consisting of phenyl, alkyl, lower haloalkyl, lower alkoxyalkyl, lower alkylthioalkyl, lower alkylcarbonyloxyalkyl, cycloalkanylalkyl and heterocyclic radicals wherein the heteroatom is selected from the group consisting of nitrogen, sulfur and oxygen, each R _{1 being} independently selected from C ₁ -C ₄ lower-alkyl radicals and R ₂ and R _{3 are} independently selected from alkyl and fluorinated methyl radicals, with the proviso that one of R ₂ and R ₃ must be fluorinated methyl. 2. Composition according to claim 1, characterized in that R C is - ^ - alkyl. 3. Composition according to claim 2, characterized in that R _{1 is} C 1-5 alkyl. 4. The composition according to claim 3, characterized in that one of the radicals R ₂ and R _{3 is} a trifluoromethyl radical. 5. The composition according to claim 3, characterized in that one of the radicals R ₂ and R _{3 is} a difluoromethyl radical. 6. The composition according to claim 1, characterized in that R is selected from the group C ₂ -C ₄ alkyl and cyclopropylmethyl. 7. A composition according to claim 6, characterized in that R _{1 is} C ₂ -C ₄ alkyl. 8. The composition according to claim 7, characterized in that one of the radicals R ₂ and R _{3 is} a trifluoromethyl radical. 9. The composition according to claim 7, characterized in that one of the radicals R ₂ and R _{3 is} a difluoromethyl radical. 10. The composition according to claim 7, characterized in that R _{2 is} fluoroalkyl and R _{3 is} alkyl. 11. The composition according to claim 1, characterized in that R is isobutyl. 12. The composition according to claim 11, characterized in that R _{1 is} methyl. 13. The composition according to claim 12, characterized in that one of the radicals R ₂ and R _{3 is} a trifluoromethyl radical. 14. The composition according to claim 12, characterized in that one of the radicals R ₂ and R _{3 is} a difluoromethyl radical. 15. A composition according to claim 1, characterized in that R is a heterocyclic radical, wherein the heteroatom is oxygen - _; 16. The composition according to claim 1, characterized in that R is furyl. 17. The composition according to claim 1, characterized in that the heteroatom is nitrogen. 18. The composition according to claim 17, characterized in that R is pyridyl. 19. A composition according to claim 1, characterized in that the heteroatom is sulfur. 20. The composition according to claim 19, characterized in that R is thienyl. 21. A composition according to claim 1, characterized in that R is methylthiomethyl. 22. A composition according to claim 1, characterized in that R is methoxymethyl. characterized in that R is methylthioethyl. characterized in that R is ethoxyethyl. characterized in that R is ethyl. 26. A method for the suppression of undesired plant growth, characterized in that on the location of the plants, a herbicidally effective amount of a compound of the formula selected from 23. The composition according to claim 1, 24. The composition according to claim 1, 25. The composition according to claim 1, H ^ O C and wherein R is selected from the group consisting of phenyl, alkyl, lower haloalkyl, lower alkoxyalkyl, lower alkylthioalkyl, lower alkylcarbonyloxyalkyl, cycloalkanylalkyl and heterocyclic radicals wherein the heteroatom is selected from the group consisting of nitrogen, sulfur and oxygen, each R _{1 being} independently selected is selected from C ₁ -C ₄ lower alkyl radicals and each R _{2 is} independently selected from fluorinated methyl radicals. 27. The method according to claim 26, characterized in that RC _r C ₆ alkyl. 28. The method according to claim 27, characterized in that R _{1 is} C ₁ -C ₄ -AlkYl. 29. The method according to claim 28, characterized in that one of the radicals R ₂ and R _{3 is} a trifluoromethyl radical. 30. The method according to claim 28, characterized in that one of the radicals R ₂ and R _{3 is} a difluoromethyl radical. 31. The method according to claim 26, characterized in that R is selected from the group C ₂ -C ₄ alkyl and cyclopropyl methyl. 32. The method according to claim 31, characterized in that R _{1 is} C ₂ -C ₄ alkyl. 33. The method according to claim 32, characterized in that one of the radicals R ₂ and R _{3 is} a trifluoromethyl radical. 34. The method according to claim 32, characterized in that one of the radicals R ₂ and R _{3 is} a difluoromethyl radical. 35. The method according to claim 32, characterized in that R _{2 is} fluorinated methyl and R _{3 is} alkyl. 36. The method according to claim 26, characterized in that R is isobutyl. 37. The method according to claim 36, characterized in that R _{1 is} methyl. 38. The method according to claim 37, characterized in that one of the radicals R ₂ and R _{3 is} a trifluoromethyl radical. 39. The method according to claim 37, characterized in that one of the radicals R ₂ and R _{3 is} a difluoromethyl radical. 40. The method according to claim 26, characterized in that pure is heterocyclic radical, wherein the heteroatom is oxygen. 41. The method according to claim 26, characterized in that R is furyl. 42. The method according to claim 26, characterized in that the heteroatom is nitrogen. 43. The method according to claim 42, characterized in that R is pyridyl. 44. The method according to claim 26, characterized in that the heteroatom is sulfur. 45. The method according to claim 44, characterized in that R is thienyl. 46. The method according to claim 26, characterized in that R is methylthiomethyl. 47. The method according to claim 26, characterized in that R is methoxymethyl. 48. The method according to claim 26, characterized in that R is methylthioethyl. 49. The method according to claim 26, characterized in that R is ethoxyethyl. 50. The method according to claim 26, characterized in that R is ethyl.