BG60331B2 - 2,6-substituted piridine compounds - Google Patents

Abstract

The compounds are used in agriculture as herbicides and as intermediates used in the preparation of herbicides. New 2,6-substituted-3,5-pyridinedicarboxylic acids, as well as their esters, salts, amides, halides and cyano derivatives, their preparation and use are described. 5 claims

Description

The invention relates to a new class of broad-spectrum 2,6-substituted-3,5-pyridinedicarboxylic acid derivatives such as herbicides.

Pyridine derivatives have been studied for many years. For example

2,6-bis- (trifluoromethyl) -4-pyridinols are useful as herbicides and fungicides (1). These compounds are characterized by the substitution of 4 positions by a hydroxyl radical. In addition to the hydroxyl radical, the pyridine nucleus may also be substituted by a bromine, chlorine or iodine radical. Trifluoromethyl pyridine derivatives are also disclosed in (2 and 3), where the nucleus is further substituted by halogens, as well as many other substituents. Some of these compounds are also useful as herbicides.

Also known for their fungicidal action are 4-substituted 2,6-dichloro-3,5-dicyanopyridines, where the 4-position is substituted by alkyl, phenyl, naphthyl or pyridyl groups. Such compounds are disclosed in (4), and similar compounds are disclosed in (5), wherein the 4-position is substituted by a heterocyclic group wherein the heteroatom is oxygen or sulfur.

2,6-Dialkyl-3-phenylcarbamyl-5-pyridinecarboxylates and 5-cyan compounds useful as herbicides have been disclosed (6). No 2-haloalkyl radicals or substitution of the 4-position of the pyridine ring have been described.

Pyridine derivatives have also been addressed in the search for new herbicides (7, 8 and 9). All of these patents disclose polychaloproducts of carboxypyridines. Common to all of them is the direct replacement of the ring carbon by halogen at the 3- and 5-positions, while the 2- and 6- positions are occupied by carboxylate groups. The 4-position is open to substitution by various materials including halogens, hydroxy radicals, alkoxy and carboxyl groups. Such compounds have applications such as herbicides, bactericides and fungicides. Compounds in which the 4-position is occupied by a silver salt are used to obtain X-ray images with the intravenous administration of such compounds (7).

Brief description of the invention

It is an object of the invention to provide herbicidal compositions for the application of the new pyridines of the invention.

Another object of the invention is to find new methods for the preparation of new compounds of the invention as well as novel intermediates useful for this purpose.

The novel compounds of the invention are useful as herbicides or intermediates used for the preparation of herbicides and are represented by Formula I

of lower alkyl, lower alkenyl, lower alkynyl, lower alkenylalkyl, haloalkyl haloalkenyl, _{C} 7} cycloalkyl, C ₃₆ cycloalkanylalkyl, C _{3 6} cycloalkenyl, aryl, arylmethyl, alkoxyalkyl, benzyloxymethyl, alkylthioalkyl, dialkoxyalkyl, / 1-alkoksi1 -alkylthio / alkylaminoalkylamine alkylamino acid ring moieties, including from 1 to 3 heteroatoms selected from 0, S and N, and wherein the radical is bonded to the pyridine ring via a C-C bond and lower alkyl substituted with a saturated or unsaturated heterocyclic radical, where the heteroatom is selected from 0, S and N;

R, and R _g are independently selected from alkyl, fluorinated methyl and chlorofluorinated methyl radical, with the proviso that one of R, and R ₂ is a fluorinated methyl or chlorofluorinated methyl radical and X and Y are independently selected from the group consisting of

Z

Z is C ₂ Z ₃ R ₃ where Z is selected from 0 and NR ₇ , where R ₇ is hydrogen or lower alkyl and where Z ₂ is selected from 0 and S, wherein at each washing, R ₃ is independently selected from hydrogen, alkyl C ₁₄ , alkenylalkyl C ₃ ', cycloalkenylalkyl, cyanoalkyl, or alkynylalkyl C ₃ ';

—C \

wherein R ' is selected from hydrogen and halogen, < z > N ' ₆ where R1 and R6 are independently selected from hydrogen, lower alkyl and phenyl; -CH ₂ OH and C = N.

The compounds of the invention of particular interest, such as herbicides, include the compounds of the above Formula I, wherein X and Y are both ester groups, wherein R ₃ in each ester group is independently an alkyl group having 1-3 carbon atoms. Of these, 3,5-diester compounds are preferred, more preferred compounds are those when R 1 and R ₂ are unequally fluorinated methyl radicals; in these more preferred groups, the most preferred compounds are those wherein R is an alkyl or alkylthioalkyl substituent having 1-5 carbon atoms.

In the invention, the term "alkyl" means straight or branched chain radicals that include ethyl, methyl, propyl, 1-ethylpropyl, 1-methylpropyl, pbutyl, 2,2-dimethylpropyl, pentyl, isobutyl, isopropyl and the like. The term "cycloalkyl" is used to mean cycloalkyl radicals such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

The term " lower alkyl " means here an alkyl radical of 1 to 7 carbon atoms. The terms "lower alkenyl" and "lower alkynyl" mean here alkenyl and alkynyl groups having 2 to 7 carbon atoms. Examples of such alkenyl groups include ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl,

3-butenyl, 2-methyl, 1-propenyl, 2-methyl-2-propenyl, 1-methylethenyl, and the like. Examples of such low alkyl groups include ethynyl, 1-propynyl, 2-propynyl, etc.

The term "saturated and unsaturated heterocyclic radicals" means heterocyclic radicals having from 3 to 6 ring atoms, including from 1 to 3 heteroatoms, selected from 0, S and N, and generally include furyl, pyridyl, thienyl, tyranyl, oxiranyl and aziridinyl and aziridinyl and aziridinyl et al.

The term "cycloalkylalkyl" is used to mean alkyl radicals substituted with a C _3-6 cycloalkyl radical. The term "haloalkyl" is used to mean alkyl radicals substituted by one or more halogen atoms.

The term "fluorinated methyl" means methyl radicals having one or more fluorine atoms attached thereto, including radicals where all the hydrogen atoms are replaced by fluorine.

The term "chlorofluorinated methyl" means a methyl radical having at least one hydrogen substituted with fluorine and at least one other hydrogen substituted with chlorine.

Detailed description of the invention

Scheme I below describes a method by which symmetric pyridines (D) according to the invention can be obtained. They are conveniently obtained from the dihydropyridines (C), which are obtained from the corresponding dihydroxypyridines (B) by dehydration. Suitable dehydrating agents are sulfuric acid, toluenesulfonic acid, trifluoroacetic anhydride and the like. The dihydroxypiperidines (B) are generally obtained from the corresponding dihydroxytetrahydropyranes (A) by treatment with aqueous or gaseous ammonia. To obtain the desired dihydroxytetrahydropyran (A), a suitable aldehyde is reacted with a suitable 3-ketoester and a catalytic amount of a base such as piperidine or KF in a suitable reaction medium. This reaction yields dihydroxytetrahydropyran, which, by reaction with NH ₃ or NH ₃ OH, produces the dihydroxypiperidine, which, upon dehydration, produces the dihydropyridine. The isolation of dihydroxytetrahydropyran and dihydroxypiperidine intermediates is not necessary in this reaction scheme, even though the intermediate may be isolated as in some of the following examples. The oxidation of dihydropyridine (C) gives the symmetric pyridines (D) according to the invention. Scheme 1 illustrates the reaction scheme.

In the preparation of dihydropyridine compounds wherein the 4-position is substituted by either aryl, arylmethyl, phenylmethoxymethyl or heterocyclic radicals, where the heteroatom is oxygen or sulfur, it is preferable to use a catalytic amount of organic acid as a dehydrating substance in the place of the acid at the site of the acid. . Toluenesulfonic acid in the middle of the reaction is considered to be suitable for this purpose. The reaction usually takes place at reflux temperature and the water is removed by azeotropic distillation. For the preparation of the basic amount of 3,4-dihydropyridine isomers from the corresponding piperidine, the preferred dehydrating agent is trifluoroacetic anhydride. In this method, the reaction medium is usually hydrochloride derivatives such as hydrochloride such as methylene chloride.

Scheme I <A)

The above Scheme I provides the symmetric diesters of 2,6-bis substituted-3,5-pyridine-dicarboxylic acids represented by formula (D).

Diester compounds of formula I having the formula

where R, R _p R ₂ and R ₃ have the meanings as defined above except that R 1 and R ₂ cannot both be CF ₃ , and where each R ₃ is the same and must be different from hydrogen, may be obtained by a novel dehydrofluorination reaction in which an equimolar mixture of the corresponding dihydropyridine is reacted, wherein one of R, and R ₂ has one fluorine greater than the product and a non-aqueous organic base such as 1,8-diazabicyclo-15.4.01-undex- 5-ene (s) or 2,5-lutidine, trialkylamines and pyridine or mono-, di- and trialkyl substituted pyridine in the presence of a catalytic amount of DBU h sta or in a suitable solvent such as tetrahydrofuran or an aromatic solvent such as toluene.

Similarly, diester compounds of formula II, wherein one of R 1 and R ₂ has two fluorines less than the other (i.e. one of Rj and Rj is CF ₃ and the other is CFH ₂ /, are obtained by further reducing the compound thus obtained as follows. The compound of formula II, wherein one of R ₃ and 1% is CF ₃ and the other is CF ₂ H, is reduced to the corresponding 1,2-dihydropyridine using as a strong reducing substance alkali metal borohydride such as sodium borohydride in any suitable solution, preferably N, N-dimethylformamide. The dihydropyridine thus obtained is once again dehydrofluorinated using an anhydrous organic base such as DBU or 2,6lutidine in a suitable solvent, such as diethyl ether or tetrahydrofuran of the corresponding pyridine compound, in which one of R ₁ and R 1 is CF ₃ and the other is CFH ₂ . If necessary, this sequence of sodium borohydride reduction / dehydrofluorination can be repeated to form a pyridine compound, wherein one of R ₃ and 1% is CF ₃ and the other is CH ₃ , proceeding again with 1,2 dihydropyridine intermediate.

These novel reactions are used herein to produce particularly effective herbicides according to the invention.

Monocarboxy compounds represented by the following Formula III

(where R, R ₍ , 1% and R ₃ are each as defined in formula I above) may be obtained as derivatives of compounds of formula (D) or II by partial / or selective / hydrolysis. that when R1 in formula III is a difluoromethyl radical (-CHF ₂ ) and R is not a difluoromethyl radical, the ester group attached to the difluoromethyl radical is selectively removed by hydrolysis, leaving the ester group on the substituent side unaffected.

To obtain a compound of formula I, wherein the 3,5-ester groups are different, a compound represented by formula IV is first obtained

I 1 and .X1.

«1 N ^κ ί wherein R, R _p Rj and R ₃ have the same meaning as in formula I and Hal is a halogen selected from chlorine, bromine and fluorine.

The compounds of formula IV can be prepared by mixing a compound of formula III with excess thionyl halide or another suitable substance, the reaction being refluxed for several hours. The compounds of formula IV are refluxed with suitable alcohol for several hours. The desired product is recovered by known methods to give the desired compound of formula I, wherein X and Y are different esters.

It is possible to mix a mixture of a compound of formula III and an excess of suitable alkyl halide in a suitable solvent, such as N, N-dimethylformamide (DMF) or acetone with 4 equivalents of potassium fluoride or one equivalent of potassium carbonate as a base. After stirring constantly for about 16 hours, the precipitate was poured into water and extracted with solvent. The solvent extract was dried and concentrated to give an asymmetric dicarboxylic acid diester.

For the preparation of a pyridinedicarboxylic acid of formula V, or * 1 N * 1 where R, R _p Rj have the same meaning as in formula I above, a suitable pyridinedicarboxylic acid ester is mixed with an excess of a suitable base and a suitable solvent. The mixture was refluxed for several hours and concentrated. After concentration, the desired product is recovered and purified by known methods to obtain the desired pyridines carboxylic acid. Symmetric dicarboxylic acid can also be obtained by hydrolysis of the corresponding ester as described. Ordinary recrystallization from a suitable solvent purifies the product.

Compounds of the present invention represented by Formula VI

wherein R, R, and R ₂ are as defined above, may be prepared by reaction of a compound of formula V with excess thionyl or phosphorus halide at reflux for several hours. The product was concentrated and dried.

The symmetric diester compound of formula I can also be obtained by reaction of a compound of formula VI with a suitable alcohol at reflux for about 15-20 h. A mixture of one equivalent of a compound of formula VI, excess of a suitable, is possible Alkyl halide and two equivalents of potassium carbonate are stirred in a suitable solvent such as N, N-dimethylformamide for several hours and then poured into water. The desired product is recovered by known methods of solvent extraction and purification.

The appropriate ester is obtained from the corresponding carbonyl chloride with the addition of suitable alcohol to obtain the desired ester. This can be done for both symmetric and asymmetric compounds of the formula described.

Compounds of the invention represented by Formula VII

0 R O Rj B 1 II / XX ⁴ Ri N R2 wherein R, R, R, R, R and R are as e

as defined in formula I, are prepared by reaction of a compound of formula IV with an appropriate amount of amine or ammonia. The process is illustrated in Examples 88 and 89.

Compounds of the invention represented by Formula VIII

N / Oh -s R w about H_ / * ' N \ R · And | N Ri

where R, R _p R ₂ , R ₃ , R ₃ and R ₆ are as defined in formula I, are prepared by reaction of an excess of a suitable amine or ammonia with a compound of formula VI. The process is similar to that in Examples 88 and 89.

Compounds of the present invention represented by Formula IX

where R, Rp R ₂ and R ₃ are as defined in formula I, can be prepared by reaction of a compound of formula VII, wherein R _s and R ₆ are both hydrogen, with an excess of a dehydrating agent such as phosphorus reflux . The process is illustrated in Examples 92 and 93.

Compounds of the present invention represented by formula X? I »1 <> - c ^> x ^ cH1OH _F GC» 1 N X>

where R, Rp Rj and R ₃ are as defined in formula I, are prepared by reaction of a compound of formula III with an excess of reducing substance, such as borane in a suitable solvent. The process is illustrated in Example 96 below.

Compounds of the invention represented by formula XI 10 wherein R, Rp R ₂ and R ₃ are as defined in formula I, can be prepared by reaction of a compound of formula X with a suitable oxidant such as pyridinium chlorochromate in a suitable solvent such as methylene chloride . The procedure is illustrated in Example 97.

Compounds of the present invention represented by formula XII x

where R and R 1 are R ₂ as defined in formula I, are prepared by reaction of a compound of formula VIII, wherein R ₃ and R ₆ are hydrogen with excess reflux phosphorus oxychloride. The procedure is similar to that described in Example 92.

Compounds of the present invention represented by Formula XIII i

wherein R, Rj and R ₂ are as defined in formula I, can be prepared by reacting a compound of formula V with excess borane in a procedure similar to that described in Example 96 below.

Compounds of the present invention represented by Formula XIV

wherein R, R ₍ , R ₃ and R 1 are as defined in formula I, are prepared by reacting compounds of formula XIII with two equivalents of a suitable oxidant such as pyridinium chlorochromate in a procedure similar to that described in example 97.

Thioester compounds of the present invention of formula XV

are prepared by reaction of a suitable thiol with a compound of formula IV in the same manner as to obtain a simple ester.

Similarly, the dithioesters represented by formula XVI

are prepared by reaction of a compound of formula VI with a suitable thiol. Generally, the preparation of different thioester species is parallel to the preparation of the esters described above. Thioesters are illustrated in Examples 140-149.

Imide compounds of the invention represented by Formula XVII

are prepared from the corresponding amides of the formula by reaction of the amide with thionyl chloride to give chloroimide, followed by reaction of the chloroimide with alcohol. This method is illustrated in Example 152.

The preparation of the compounds of the present invention is illustrated by the following examples, in which, for the most part, the preparation of dihydroxytetrahydrofuran (A), dihydroxypiperidine (B) and dihydropyridine (C) precursors is illustrated in detail in steps, isolating each precursor previously start synthesis of the next. A particularly preferred synthesis of compounds preceding dihydropyridine is prepared according to Example jj ('' single-site synthesis '') without isolating dihydroxytetrahydrofuran and dihydroxypiperidine precursors. According to this preferred method of obtaining the desired dihydropyridines, a reaction is first carried out in which a mixture of two equivalents of a suitable 3-ketoester, one equivalent of a suitable aldehyde and a catalytic amount of piperidine are reacted at 40-100 ° C pure or in a suitable solvent / as for example methylene chloride or toluene / for 420 hours. After completion of the reaction, as indicated by the * 'FNMR analysis, a suitable solvent is added to the product and gaseous ammonia is passed through the mixture until the second reaction is complete. The reaction mixture was then purged with nitrogen to remove excess ammonia. The reaction mixture was then cooled with an ice water bath to 5-10 ° C. After the reaction mixture was stirred for 10 min to 2 h, the mixture was poured onto crushed ice, the methylene chloride layer was separated, dried and concentrated to obtain the desired dihydropyridines in a single vessel without isolation of the precursor, dihydroxytetrahydrofuran and dihydropyridine. The desired dihydropiperidine is obtained in a higher yield.

For the preparation of dihydroxytetrahydropyran, the precursor of structure A, the method of Day et al / 10 / can be used. According to this method, a suitable aldehyde is reacted with a suitable 3-ketoester and a catalytic amount of piperidine with or without a suitable reaction medium.

Preparation of dihydroxytetrahydropyranes

The following examples of a-m show the typical methods for preparing the precursors of structure (A) indicated in Scheme 1 above.

Example A. Preparation of diethyl 2,6bis (trifluoromethyl) -2,6-dihydroxy-4-propyl-tetrahydro-3,5-pyridicarboxylate.

Place 20 g (0.278 mol (butyraldehyde), 102 g (0.555 mol) ethyl trifluoroacetoacetate and approximately 150 ml ethanol in a 500 ml one-hole flask. 3 g / 0.0156 mol / potassium fluoride were added. The mixture was stirred at room temperature for 18 h. The material was concentrated and diluted with ethyl ether. The organic portions were washed with water, dried and concentrated to give a white powder. The crude product was recrystallized from hot methylcyclohexane to give 13 g (10.7%) of the product, m.p. 128132 ° C.

Calculated for C ₁₆ H _{J 2} O, F ₆ : C 43.63; H, 5.00 Found: C, 43.58; H, 5.04.

Example B. Preparation of dimethyl 2,6bis (trifluoromethyl) -2,6 dihydroxy-4-isobutyl-tetrahydro-3,5-pyridicarboxylate.

To a mechanically stirred mixture of 280 g (2.0 mol) of 80% pure methyl trifluoroacetoacetate and 86 g (1.0 mol) of isovaleraldehyde was added 1 ml of piperidine. An exothermic reaction was obtained and the temperature of the reaction mixture reached 105 ° C. After stirring for 5 hours, the reaction mixture was turned into a powder of 450 ml of hexane and 30 ml of ether and cooled with a dry ice bath to give 1.68 g of the first crop, m.p. 83-87 ° C and 14.51 g of a second crop, m.p. 67-73 ° C.

The first harvest is the desired product that contains a mixture of 5: 1 cis and transisomers.

For C ₁ H _{2 O} F ₆ O ₇ : Calculated C 42.26; H, 4.73 Found: C, 42.54; H, 4.77

The second crop is a mixture of 2: 1 cis and transisomers. The mother liquor was concentrated to give 344 g of a precipitate, which is a crude mixture of cis and transisomers of the desired product.

The cisisomer has structure A1 with two ester groups in the cis- position, while the transisomer has structure A2 with both ester groups 5

Additional compounds were prepared according to the method described in Example A and listed in Table 1 by reaction of a suitable aldehyde with a suitable trifluoroacetoacetate.

in the trans field, as shown below: FCF

- (A 1) (A 2)

Table

Preparation of dihydroxytetraped and CH ₃ CH _{2 -} C><

Fr.

I

C — OCHiCH2

p N. Example R mp ° C Calculated Found Clear Found

p -CH1CH3 J23-127 42.25 42.41 4.69 4.72 d —CH2CH2CH2CH3 45-61 44.93 4516 5-28 5.27 e -CH (CH3h 88-98 4363 43-72 5.00 5.05 f -CHiCHCCHjh 87-90 44.95 45.02 5.28 5.20 8 - CH (CH 2 CH 3) 2 105-111 46.15 46.23 555 5.66

98-101 43.84 43.96 4.60 4.52 fl Calc'd Found Calc'd Found 100-103 ♦ 7-60 ♦ 7.38 5.26 5.63 120-123 ♦ 9.07 ♦ 9.79 ♦ .70 ♦ ♦ 2

77. S-I

128-136

90-93

49.03 ♦ 9.45 4.7] 40.73 40.69 4.56 ♦ 8.11 47.68 4.25

71 .71

4.71

4.07

Preparation of dihydroxypiperidines

Four different methods can be used to prepare the dihydroxypiperidine precursor (B). The first method (Method I) uses a method in which a mixture of two equivalents of 3-ketoesters, one equivalent of a suitable aldehyde and 1.5 equivalents of ammonium hydroxide is refluxed in ethanol for 4-18 h and concentrated again to obtain the method similar to that described in the literature.

In method II / 11 / a mixture of one equivalent of dihydroxytetrahydropyran with structure A, 1: 5 equivalents of aqueous ammonium hydroxide and an appropriate amount of ethanol was stirred at room temperature or refluxed for 4-18 h and concentrated. The precipitate is recrystallized from a suitable solvent or otherwise purified to give (B).

In Method III, gaseous ammonia was bubbled through a solution of dihydroxytetrahydrofuran of structure (A) in a suitable solvent (such as tetrahydrofuran, toluene or methylene chloride) for several hours, until the FNMR assay was complete. The reaction mixture was concentrated and the precipitate was recrystallized from a suitable solvent to give a precursor of structure (B).

In method IV, a mixture of two equivalents of suitable 3-ketoesters, one equivalent of a suitable aldehyde and a catalytic amount of piperidine are stirred with or without a suitable solvent at 40-100 ° C for several hours to several days, until ¹⁹ F NMR analysis shows complete reaction. After completion of the above first step of method IV, a suitable solvent is added to the above reaction mixture if the first reaction step is carried out without solvent. An anhydrous ammonium gas stream was passed through the solution at 40-70 ° C until ^{, 9} F NMR showed a complete reaction, usually for a period of about six to ten hours. The reaction mixture was concentrated and the precipitate was recrystallized from a suitable solvent to give a prototype structure (B).

Method IV is the preferred method because it provides a high yield of the desired product.

The following examples n-ff are presented to further illustrate the I-V methods.

Example n. Preparation of dimethyl 2,6bis (trifluoromethyl) -2,6-dihydroxy-4-isobutyl-3,5-piperidinecarboxylate.

To a solution of 344 g (0.920 mol) of the crude product of Example B in 500 ml of THF (THF) was transferred 58 g (3.41 mol) of gaseous ammonia for 3 hours. The reaction mixture was concentrated and the precipitate (332 g) was concentrated. recrystallized from hexanether to give 53.7 g (13% yield of methyl trifluoroacetoacetate) of the desired product as a white solid, m.p. 102-106 ° C.

Calcd for C ₁₃ H ₂₁ R _& ^ _rk06: C, 42.36; H, 5.00; N, 3.29

Found: C, 42.84; H, 4.94; N, 3.29

The mother liquor was concentrated to give more crude desired product.

Example about Preparation of diethyl 2,6bis (trifluoromethyl) -2,6-dihydroxy-4- (2-furyl) -3,5-piperidinecarboxylate.

Put in a 500 ml three-necked flask 60 ml of ethanol, 29.07 g (0.3 mol) of 2-furaldehyde and 110 g (0.6 mol) of ethyltrifluoroacetoacetate. The reaction mixture was cooled in an ice bath before being slowly added with stirring 21.15 g / 0.35 mol / aqueous ammonium hydroxide. The mixture was refluxed for 2 h and cooled. The resulting precipitate was filtered off and recrystallized from hot ethanol to give 53.34 g (39%) of crystals, m.p. 129-131 ° C.

Calcd for C _{17 H] 7} P _in H, 0 _7: C, 44.06; H, 4.10; N, 3.02

Found: C, 44.04; H, 4.12; N, 3.03

Example p. Preparation of diethyl 2,6bis (trifluoromethyl) -2,6-dihydroxy-4-propyl-3,5-piperidinecarboxylate.

In a 500 ml round bottom flask was placed 150-200 ml ethanol and 40 g / 0.0909 mol / product of Example a. The mixture was stirred with a magnetic stirrer while slowly adding 8.23 g / 0.136 mol / 58% aqueous ammonium hydroxide to the flask. The mixture was stirred for 18 h under nitrogen. The precipitate was filtered to give 17.83 g (44.68%) of the desired product, m.p. 140-142 ° C.

Calculated for C _lt H 2 _J 0 ₆ N ₎ F ₇ : C 43.73; H, 5.23; N, 3.18

Found: C, 43.67; H, 5.26; N, 3.19

Example q. Preparation of trans-diethyl

2,6-bis- (difluoromethyl) -2,6-dihydroxy-4 isobutyl-3,5-piperidinecarboxylate.

To a solution of 25.0 g (0.150 mol) ethyl difluoroacetoacetate (EDFAA) and 8.04 ml (0.075 mol (isovaler) ian) aldehyde was added 2 ml piperidine. The reaction mixture becomes exothermic and the temperature of the mixture reaches 86 ° C. After the temperature of the reaction mixture had dropped to room temperature, the mixture was treated with THF (100 ml). Gaseous NH ₃ was passed through the above THF solution until ¹⁹ F NMR showed completion of the reaction. The reaction mixture was concentrated to 32.77 g (100%) of oil containing the desired product and its cisisomer. This oil was recrystallized from hexane to give a solid. Part of this solid (5.0 g) was dissolved in ether. The ether solution was washed with water, dried (MgSO ₄ ) and concentrated to an oil which crystallized on standing. Recrystallization from hexane gave 1.0 g (22.8%) of this desired product as a white solid, m.p. 98100 ° C. This material is identified as a transisomer with &lt; 1 &gt; F NMR.

Calculated for C ₁₇ H _{J 7} F ₄ NO _is : C 48.92; H, 6.52; N, 3.36

Found: 48.93; H, 6.51; N 3.31 Example D. Preparation of diethyl 2,6bis (trifluoromethyl) -2,6-dihydroxy-4-butyl-3,5-piperidinecarboxylate.

In a 500 ml three-necked flask was placed g (0.0881 mol) of the product of Example d in Table I and about 200-250 ml of THF. The flask is equipped with two dry ice fridges and an inlet for nitrogen. 5 g of ammonia (0.294 mol) were bubbled into the solution and the solution was stirred for 18 h. The organic layers were concentrated, diluted with ethyl ether, washed with water, dried over anhydrous MgSO ₄ and concentrated. The precipitate was crystallized with n-hexane and filtered to give

7.57 g / 19% / desired product, m.p. 77-80 ° C.

Calculated for C ₁₇ H _M F ₆ N ₁ 0 _6: C, 45.03; H, 5.51; N, 3.09

Found: C, 44.96; H, 5.58; N, 3.03.

Other examples of 2,6-dihydroxypiperidines of structure B are prepared according to the method described above from Examples η to d and are listed in Table 2.

Table 2 Found Calculated Found

Preparation of dihydroxypiperidines

P.

CMjCHi — p

Example R mp ° C 1 -CH ₃ 133-135 ( —CH ₂ CHi 129-131 0 —Song 83-19 V —CHiCHfCHjh 69-73 W 103-103 N.

p N. N Clear Found Removed Found 41.07 42 35 43.74 41.21 42.40 44 NE 4.15 4.94 3 7 » 4.25 5.00 $ 13 3.42 3-29 1 10 3.35 333 7 74 43.03 43.20 531 5.30 3.09 3.11 42.38 4303 196 4.06 2.92 273

1 179 * In P. N 13J-135 Z -CHtCHjCHjh 96-99 m 134-141 bb ο 99-101 se —CHjCHjSCHj 55-73 122-123 <m m —CHjCHiOCHtCH) 1.42 » ff 102-109

45.59 45.51 4.25 4.03 5.91 5.52 45.51 45.59 4.25 4.29 5.91 5.90 46.25 46.67 5.92 5.79 3.00 3.17 49.21 50.39 4.72 4.67 197 179 4121 47.96 4.27 4.25 19 « 179 40.7 « 40.91 4.92 4.94 197 3.10 40.12 40.97 4.90 4.70 3.17 3.40 43.50 43.92 5.37 5.30 191 3.14 41.75 49.74 4.97 4.17 171 171

Preparation of dihydropyridines Dihydropyridine prototypes of structure (C) are obtained by dehydration of the corresponding dihydroxypiperidines with dehydrating agents such as concentrated sulfuric acid (method V) or trifluoroacetic anhydride (method VI) or by azeotropically removing acid such as water, such as using a catalyst (method VII).

To further illustrate the above methods V-VII, the following examples gg-ff are provided.

Example dd. Preparation of a 2: 1 mixture of dimethyl.

2,6-bis (trifluoromethyl) -1,4-dihydro-

4-Isobutyl-3,5-pyridinedicarboxylate and its 3,4-dihydropyridine isomer.

To the mixture cooled to ice-cold water of 200 ml of concentrated sulfuric acid and 200 ml of methyl chloride was added 48.7 g (0.115 mol) of the product of Example η at a time.

The reaction mixture was stirred for 20 min and poured into 1 liter of ice water. The methylene chloride layer was separated and washed once with 100 ml of saturated sodium bicarbonate, dried and concentrated to give 28.0 g (64.6%) of crude product. One part (5.0 g) of this product was distilled at 0.5 fertilizer (vessel temperature 120 ° C) to give 4.8 g of the desired product, n _D 25 1.4391.

Calculated for C, 46.28; N.

4.40; N, 3.60

Found: C, 46.39; H, 4.44; N, 3.60

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

5.0 g / 0.012 mol / crude cis- and trans-mixtures of the product of Example q were stirred with 10 ml of trifluoroacetic anhydride. The temperature of the reaction mixture was raised to 36 ° C. After the temperature had dropped to room temperature, the reaction mixture was concentrated. The residue was dissolved in ether and washed with saturated NaHCO ₃ , dried (MgSO ₄ ) and concentrated to an oil /

3.76 g, 82.3% (which was chromatographed on HPLC with 10% ethyl acetate / cyclohexane as eluent to give 1.73 g (37.8%) of the desired product as an oil, n _D 25 1 , 4716.

Calculated for C ₁₇ H ₂₃ F ₄ NO ₄ : C 53.54; H, 6.08; N, 3.67

Found: C, 53.38; H, 6.40; N, 3.25

Example j. Preparation of diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4- (2-thienyl) -

3,5-pyridinedicarboxylate.

Approximately 100 ml of toluene was refluxed in a Dean-Stark tube to remove the water. To the cooled toluene was added 20 g (0.0418 mol) of the product of Example w in Table 2 and 2.0 g (0.0105 mol) of p-toluaric acid. The mixture was refluxed and refluxed for 5.5 hours. The solution was cooled and filtered. The solvent was released and the product was chromatographed using 20% ethyl acetate / cyclohexane as eluent. Product weight - 2.45 g (13.3%), n _D 25 1 4937.

Calculated for C ₁₇ H _1J 0 ₄ N ₁ F _i S _(: C 46.04; H 3,38; N 3,16; S 7,22

Found: C, 46.11; H, 3.44; N, 3.12; S, 7.16

In the preferred method of producing the desired dihydropyridines, the first is the reaction, where a mixture of two equivalents of a suitable 3 ketoester, one equivalent of a suitable aldehyde and a catalytic amount of piperidine are reacted at 40-100 ° C with or without a suitable solvent (such as methylene chloride) for 4- 20 hours. After completion of the reaction indicated by * &lt; 1 &gt; F NMR analysis, methylene chloride was added to the product and ammonia gas was bubbled through to the completion of the second reaction. The reaction mixture was then purged with nitrogen to remove excess ammonia. The reaction mixture was then cooled in an ice-cold bath to 5-10 ° C before being treated with sulfuric acid. After the reaction mixture was stirred for 10 min to 2 h, the mixture was poured onto crushed ice, the methylene chloride layer was separated, dried and concentrated to give the desired dihydropyridines. In this mode of operation, the desired dihydropyridine is obtained in a single reaction vessel without isolation of the intermediate dihydroxytetrahydrofuran and dihydroxypiperidine. Therefore, the desired dihydropyridine is obtained in better yield. The following examples are given to illustrate the procedure.

Example jj. Synthesis of a mixture of diethyl

2,6-bis (trifluoromethyl) -1,4-dihydro-4-ethyl-3,5-pyridinedicarboxylate and its

The 3,4-dihydropyridine isomer in one reaction vessel.

A mixture of 368 g / 2.0 mol / ethyl trifluoroacetoacetate, 58 g / 1.0 mol / propionaldehyde and 1 ml piperidine in 400 ml methylene chloride was stirred for 1 h at 20 ° C and then for 1 h at 30 ° C, refluxed for 1 hour and then cooled. An additional 16.8 g (0.289 mol / propionaldehyde) was added to the above mixture and reflux continued for 2 h. The heating bath was removed. 108 g / 6.35 mol / ammonia were passed through the reaction mixture for 2 hours. The reaction mixture was stirred for 40 hours at 20 ° C and then cooled in ice water. Gently add 100 ml of concentrated sulfuric acid to the reaction mixture for 20 minutes, then add an additional 300 ml of concentrated sulfuric acid for 10 minutes. Pour the reaction mixture onto 600 g of crushed ice in a 4 liter container. The methylene chloride layer was separated, dried (MgSO ₄ ) and concentrated to give 386 g of an oil containing a mixture of the desired product and its 3,4-dihydro isomer. This oil was added to a strongly stirred mixture of 300 ml of concentrated sulfuric acid and 300 ml of methylene chloride. The mixture was stirred for 30 min and poured onto 1 kg of ice. The methylene chloride layer was separated, dried (MgSO ₄ ) and concentrated to give 348 g of an oil which crystallized with 400 ml of petroleum ether to remove 9.5 g of insoluble solids. The petroleum ether was filtered off and then concentrated. The precipitate was distilled in kugelror at 0.4 fertilizer to give 290 g / 74.5% oil, which is more than 90% pure mixture of the desired product containing

1.4-dihydro (84%) and its 3,4-dihydro (16%) isomers as determined by &lt; 1 &gt; F NMR analysis.

Further examples of the dihydropyridines of structure (C) of Scheme 1 are prepared according to the methods indicated in Examples gg to jj and are listed in Table 3. In all examples of Table 3, R ₃ is ethyl.

The following examples illustrate, without limitation, the preparation of certain novel herbicides and intermediates for the preparation of herbicides according to the invention.

For the preparation of symmetric 3,5-pyridinedicarboxylates according to Scheme 1, the corresponding dihydropyridines C are treated with sodium nitrite in acetic acid. The above-described 5 method is illustrated by Examples 1 to 11.

Table 3

Ewnple R

Preparation of dihydropyridines

kk - CH)

U - CH) CH) m> - CHjCHiCH) aa - OCsN3b oo - CHiCHjCHjCHj

AND> CHjCHCCHjh

With ____ Η _____ Ν

Κι 1.4 PLN odA ⁵ Cak'd Fouad Cded Fund Cak'd Found CF, too 1.4377 44.11 44.91 4DW 406 3.73 3.41 CF) too 1.4441 4627 46.41 4J7 4 19 3.39 3.62 CF, 100 14427 47.11 * 7 « 4DZ 4.M 3.49 3.47 CF) KJ I.444O 47.64 47.4 » 471 4.75 3.4? 3.44 CF, 100 1.4414 * ».» 5 4t » 5.03 109 3.33 3.35 CFj 100 1.4420 44.92 46.71 103 ! .O4 3.35 3.31 CF, 100 1.4120 JIN 5JJ4 4.63 4L7 3.09 30 »

CF) 100 1.4720 47.77 47.13 151 3.51 3.27 125 CF, 100 (·) 49.31 40J3 165 3.73 6J9 6J9 w

KJ

CF) 100 vv y - k CF) 100 ww —CH2OCH1 CFj 92 8 CL —CHiCHiOCHzCH » CF) 85 19 CU —CHiSCHj CF) 89 II ZK —CHiCHjSCH) CF) 64 14 a * a -CHfCHiCHjh CF) IOO bbb —ChicHjCHj CF, H too ccc 0 CF) H too ddd \ __ / CF) too eee ./ —CHCH1CH) CF) 80 20 CHj

LT— “CHzC <CHi)>

1.45 (6 51.46 SO.19 9.23 5.38 3.16 3.24 1.4 (45 53.40 52.46 4.40 4.42 2.91 2.92 1.4434 44 45 44.26 4.23 4.40 3.46 3.22 1.4410 47 12 46.96 4.88 4.69 3.23 3.02 1.44 (6 42.76 42.72 4.07 4.24 3 32 3.07 ) .46 (1 44.14 44.12 4.40 4.19 3.22 3.05 1.4433 50.11 5O.1S 5.37 4.99 3-25 3.22 1.4726 52.32 51.98 9.76 5.86 3.81 3.66 <c> 56.02 56.16 «14 6.42 3.44 3.42 <d) 52.18 52.33 3.92 3.99 3-20 3.16 1,441? 48.92 49.09 5-07 5.10 3.36 3-34

1.4393

30.12

5.37

3.37

3-23

) .20

Example 1. Preparation of diethyl 2,6bis (trifluoromethyl) -4-ethyl-3,5-pyridinedicarboxylates.

35 ml of crystallized acetic acid and 13.89 g (0.0354 5 mol / diethyl 2,6-bis- (trifluoromethyl) -4-ethyl-1,4-dihydro-3,5-pyridinedicarboxylate were added to a 250 ml flask. Sodium nitrite was added in an amount of 3 g (0.0434 mol) and the mixture was stirred for 72 h under nitrogen. The solution is poured 10 on ice / water and stirred. The organic particles were extracted into ether and washed with aqueous saturated sodium bicarbonate solution. The organic particles were then dried over anhydrous magnesium sulfate, filtered and concentrated to give 4.93 g (35.67%) of product, m.p. 33-35 ° C.

Calculated for C _(J H _{1 J} 0 ₄ N ₁ F ₆ : D 46.51; H 3.87; N 3.61

Found: C, 46.54; H, 3.90; N, 3.63 20

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

In a 50 ml round bottom flask was placed 20 ml of crystallized acetic acid. 25 g (0.0133 mol) of diethyl 2,6-bis (trifluoromethyl) -4-methyl-1,4-dihydro-3,5-pyridine dicarboxylate were added, then 3 g (0.0434 mol) were added slowly. / sodium nitrite. The flask was immediately supplied with a condenser and a nitrogen line, stirring was continued for 18 hours, and the mixture was poured onto crushed ice and water. The organic portions were extracted twice with ether, washed once with saturated aqueous sodium chloride and washed twice with saturated aqueous sodium bicarbonate solution. The organic portions were dried over anhydrous magnesium sulfate and concentrated to give 2.16 g (43.5%) of the product, m.p. 5558 ° C.

Calculated for C ₁₄ H ₁₅ F ₆ NO ₄ : C, 45.05; H, 3.48; N, 3.75

Found: C, 44.95; H, 3.56; N, 3.75

In a manner similar to that described in Examples 1 and 2, but substituting the appropriate starting material and reaction conditions, other pyridinedicarboxylates are obtained. The same or equivalent solvents, bases and catalysts, as well as suitable temperatures and times, are readily used in these manifestations of the process. Typical other compounds prepared according to the above methods are shown in Table 4 together with some of their physical properties.

Table 4

Preparation of symmetric 3,5-pyridinedicarboxylates / D /

Pr Source material product of example Compound An empirical formula 3 ddd Diethyl 2,6-bis (trifluoromethyl) 4-phenyl-3,5-pyridine dicarboxyl at W.NA 4 yy Diethyl 2,6-bis (trifluoromethyl) -4- (2-furyl) -3,5-pyridinedicarboxylate Ο ,, Η ,, Ε, Ν, Ο, 5 ϋ Diethyl 2,6-bis (trifluoromethyl) -4 (2-thienyl) -3,5-pyridinedicarboxylate C ₁₇ H _l3 F ₆ N, 0 ₄ S, 6 mm Diethyl 2,6-bis (trifluoromethyl) -4-propyl-3,5-pyridinedicarboxylate C..H ₁₇ 0 ₄ N, F _t 7 RR Diethyl 2,6-bis (trifluoromethyl) -4-isobutyl-3,5-pyridinedicarboxylate CnH.AN.F. 8 tt Diethyl 2,6-bis (trifluoromethyl) -4- (3-Pyridyl) -3,5-pyridinedicarboxylate c „h _h o ₄ n ₂ f ₄ 9 ss Diethyl 2,6-bis (trifluoromethyl) -4- (4-Pyridyl) -3,5-pyridinedicarboxylate C..H.4W.

10 WW Diet 2, 6-bis / trifluoro1 methyl / -4- (methoxymethyl) -3,5-pyridinedicarboxylate ς, Η, ΛΝΟ, 11 bbb Diet 2, 6 bis / difluorine ethyl / -4-propyl- 4-propyl · -3,5-pyridine! zoxylate c ₁₆ h „f ₄ no ₄ Etc. M.P. n _D 25 Analysis No ° C Element Calculated% Found% 3 1,4696 P 52.42 52.47 N. 3.47 3.51 N 3.22 3.20 4 45-47 P 48,00 47.97 N. 3.05 3.08 N 3.29 3.29 5 48-50 P 46,25 46.13 N. 2.94 2.94 N 3.14 3.14 S 7.25 7.31 6 1,4315 P 47.88 48.15 n 4.23 3.85 N 3.49 3.47 7 1,4280 p 49.15 48.93 n 4,57 4.66 N 3,37 3.45 8 1,4710 p 49.55 49.58 n 3.23 3.26 N 6.42 6.37 9 1,4711 P 49.55 49.27 n 3.23 3.27 N 6.42 6.47 10 1,4291 P 44.67 44.79 n 3.75 3.78 N 3.47 3,44 11 22 P 52,60 52.63 n 5,24 5.61 N 3,43 3.65

The following Examples 12 to 27 show a novel process for the preparation of compounds of the present invention represented by Formula II.

Example 12 Preparation of Diethyl 2- (difluoromethyl) -4-ethyl-6- (trifluoromethyl) -

3,5-pyridinedicarboxylate.

A mixture of 1558 g (4.00 mol) of diethyl 2,6bis (trifluoromethyl) -1,4-dihydro-4-ethyl-3,5-pyridinedicarboxylate, 628 g (4.0 mol) of 1,8-diazabicyclo-15,4.01-undex- The 5-ene (DBU) and 500 ml of tetrahydrofuran were refluxed for 19 hours, cooled and poured into a mixture of 2 kg of ice and 250 ml of concentrated hydrochloric acid. The organic layer was separated and the aqueous layer was extracted twice with 500 ml of CH ₂ Cl ₂ . The combined organic materials were dried (MgSO ₄ ) and concentrated. The precipitate was distilled with kugelror at 1 fertilizer (vessel temperature of 150160 ° C) to give 1158 g (78.5%) of the desired product, n _in 25 1.4458.

Calculated for C ₁₅ H ₁₆ F ₆ NO ₄ : C 48.78; H, 4.37; N, 3.79

Found: C, 48.75; H, 4.29; N, 3.72

Example 13 Preparation of Diethyl 2- (difluoromethyl) -4-n-propyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 20.0 g / 0.05 mol / diethyl 2,6bis / trifluoromethyl / -1,4-dihydro-4-p-propyl-3,5-pyridinedicarboxylate, 7.62 g / 0.05 mol / DBU and 200 ml of THF was refluxed for 9 hours, cooled and poured into 500 ml of ice water. The mixture was extracted with ether (2 x 200 mL). The ether extract was washed with dilute hydrochloric acid, dried (MgSO ₄ ), and concentrated to give 12.4 g (64.5%) of the desired product, n ₀ 25 1.4436.

Calculated for C ₁₆ H _{17 S} F _J N ₎ O ₄ : C 50.13; H, 4.73; N, 3.65

Found: C, 49.92; H, 4.71; N, 3.58

Example 14 Preparation of dimethyl 2- (difluoromethyl) -6- (trifluoromethyl) -4-isobutyl-3,5-pyridinedicarboxylate.

a / Reaction of the product from example gg with DBU.

A mixture of 23.0 g (0.0559 mol) of the product of Example gg. 12.2 g (0.077 mol) of 96% pure DBU and 100 ml of THF were refluxed for 3 days and poured into 250 ml of 3N HCl. The oily residue was extracted with ether (2 x 100 mL). The ether extracts were dried (MgSO ₄ ) and concentrated to give 14.4 g of an oil which, according to Ή NMR, contained the desired product and acid products. This oil was dissolved in ether and extracted with 100 ml of saturated sodium bicarbonate. The ether layer was dried (MgSO ₄ ) and concentrated to give 8.9 g of an oil, which is 71% pure desired product (according to ** F NMR).

The sodium bicarbonate extract was acidified with concentrated HCl to give an oil which was extracted into ether. The ether layer was dried (MgSO ₄ ) and concentrated to give 4.8 g of a precipitate containing monocarboxylic acid and dicarboxylic acid (9: 1) extracted from the desired product. This precipitate was treated with 3.0 g / 0.0217 mol / potassium carbonate, 20 ml methyl iodide and 50 ml acetone. The mixture was refluxed for 42 h and concentrated. The precipitate was treated with water and extracted with ether (2 x 100 ml). The ether layer was dried and concentrated. The precipitate was distilled with kugelror at 1 fertilizer (vessel temperature 130 ° C) to give 5.1 g (23.4% of example gg) of the desired product as an oil n _D 25 1.4478. This product crystallizes on standing; 36-37 ° C.

Calculated for C ₁ H ₁₆ F _J N ₁ O ₄ : C 48.79; H, 4.37; N, 3.79

Found C 48.75 H 4.39 N 3.77% pure desired product described above was chromatographed on HPLC using 3% ethyl acetate / cyclohexane as eluent to give a primary fraction / 0.79 g, retention time 7-8.5 min), which was identified as methyl 6- (difluoromethyl) 4- (isobutyl) -2- (trifluoromethyl) -3-pyridine-carboxylate. The second fraction (retention time 8.5-18.5 min) was an additional 6.4 g (29.4%) of pure desired product, n _D 25 1,447.

b / Reaction of a product of Example gg with tributylamine.

A mixture of 38.9 g of 80% pure product of Example gg and 20.5 g of tributylamine was heated to 155 ° C for 30 minutes. The reaction mixture was cooled to 30 ° C and diluted with 100 ml of toluene. The toluene solution was washed sequentially with 6N hydrochloric acid, saturated sodium bicarbonate and brine, dried and concentrated to give 36.4 g of 73% pure product, corresponding to 86% yield. This reaction can also be carried out with excess tributylamine (10 equivalents), giving essentially the same results.

c / Reaction of the product of Example gg with tributylamine in toluene.

A mixture of 38.9 g of 80% pure product of Example gg, 20.4 g of tributylamine and 30 ml of toluene was heated to 115 ° C for 40 min and kept at 115 ° C for 1 h and 40 min. The reaction mixture was cooled and further performed as in point b to give 36.3 g of 76% pure product, corresponding to 90% yield.

d / Reaction of a product of Example gg with triethylamine.

A mixture of 11.8 g of 80% pure product of Example gg and 3.34 g of triethylamine was heated to 100 ° C for 10 min, then at 125 ° C for 10 min. The reaction mixture was cooled and then is treated as in point b to give 8.14 g of 76% pure product which corresponds to a 63% yield.

e / Reaction of a product from example gg with

2,6-lutidine in the presence of a catalytic amount of DBU.

A mixture of 5.0 g of the product of example gg and 2.13 g of 2,6-lutidine was heated at 143 ° C for 30 min. Two drops of DBU were added and the reaction mixture was heated for another 1 h and 30 min, cooled, and then proceeded as in point b to give 4.23 g of the desired product. The reaction may also be carried out with excess 2,6-lutidine and a catalytic amount of DBU without solvent or in the presence of toluene as solvent, obtaining similar results.

Example 15 Preparation of Diethyl 2- (difluoromethyl) -4-isopropyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 50.0 g (0.12% mol / diethyl 2,6bis) -trifluoromethyl / -1,4-dihydro-4-isopropyl-3,5-pyridinedicarboxylate, 18.87 g / 0.12% mol / DBU and 200 ml of THF were refluxed for 18 h and poured into water and extracted with ether. The ether extract was washed with dilute hydrochloric acid, dried (MgSO ₄ ) and concentrated. The precipitate was distilled at 1 fertilizer to give 17.97 g (37.8%) of the desired product, which is a liquid, n _D 25 1.4465.

Calculated for C C HH ^FjNjO /. C, 50.13; H, 4.73; N, 3.65

Found: C, 50.16; H, 4.76; N, 3.65

Example 16. Preparation of diethyl 2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

Mixture of 10.0 g / 0.0240 mol / diethyl 2,6bis / trifluoromethyl / -1,4-dihydro-4-isobutyl-3,5-pyridinedicarboxylate, 3.65 g / 0.0240 mol / DBU and 150 ml The THF was refluxed for 18 h and concentrated. The precipitate was dissolved in ether and washed with dilute hydrochloric acid, dried (MgSO ₄ ) and concentrated. The precipitate was distilled at 1 fertilizer to give 4.80 g (50%) of the desired product as an oil, n _D 25 1.4436.

Calcd for C "H _2O F _{i N)} 0 _4: C, 51.39; H, 5.07; N, 3.53

Found: C, 51.35; H, 5.08; N, 3.51

Example 17. Preparation of diethyl 2- (difluoromethyl) -4-cyclopropyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

55.5 g / 3 were bubbled to a solution of 40 g (0.0916 mol) of diethyl 2,6-bis (trifluoromethyl) -2,6-dihydroxy-4-cyclopropyl-tetrahydrofuran-3,5-dicarboxylate in 200 ml of THF. , 26 mole / ammonia. The reaction mixture was concentrated to give 38.5 g (96.7%) of a solid. A portion (28 g) of this material was stirred with 27.08 g (0.129 mol) of trifluoroacetic anhydride for another day. The reaction mixture was concentrated and diluted with ether. The ether solution was washed with saturated sodium bicarbonate, dried (MgSO ₄ ) and concentrated to give 21 g (81.3%) of oil, n _D 25 1.4460. This oil is identified as diethyl 2,6-bis (trifluoromethyl) -4-cyclopropyl-1,4-dihydro-pyridine-3,5-dicarboxylate. One part (18 g) of this oil and 150 ml of THF was treated with 6.82 g (0.0449 mol) / DBU. The reaction mixture was refluxed for 24 h and concentrated. The precipitate was stirred with water and extracted with ether. The ether extract was washed with dilute HCl, dried (MgSO ₄ ) and concentrated. The precipitate was crystallized to give 13 g (76.0%) of crude product. One part (2.0 g) of this product was recrystallized from petroleum ether at low temperature to give 1.17 g (85%) of the desired product, m.p. 30-32 ° C.

Calculated for C ₆ H ₁₆ F _J N ₁ O ₄ : C 50.40; H, 4.23; N, 3.67

Found: C, 50.48; H, 4.32; N, 3.78.

In a manner similar to Example 12, other asymmetric pyridine compounds of the present invention were prepared as indicated in Table 5.

Table 5

Preparation of asymmetric diethyl pyridinedicarboxylates

Etc. Source No. Material

Compound kk w

oo uu ahh zz ww yy yee

Diethyl 2- (difluoromethyl) -4methyl-6- (trifluoromethyl) -

Diethyl 2- (difluoromethyl) -4-phenylmethoxymethyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate Diethyl 2- (difluoromethyl) -4-pbutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate

Diethyl 2- (difluoromethyl) -4-cyclohexyl-6- (trifluoromethyl) -

3,5-pyridinedicarboxylate

Diethyl 2- (difluoromethyl) -4- (1-ethylpropyl) -6- (trifluoromethyl) -

3,5-pyridinedicarboxylate

Diethyl 2- (difluoromethyl) -4 (methylthioethyl) -6- (trifluoromethyl) -

3,5-pyridinedicarboxylate

Diethyl 2- (difluoromethyl) -4- (methoxymethyl) -6- (trifluoromethyl) -

3,5-pyridinedicarboxylate

Diethyl 2- (difluoromethyl) -4- (methylthiomethyl) -6- (trifluoromethyl) -

3,5-pyridinedicarboxylate

Diethyl 2- (difluoromethyl) -4- (1methylpropyl) -6- (trifluoromethyl) -

3,5-pyridinedicarboxylate

An empirical formula

C ₂₁ N _m P, M, 0,

s., n _m RL0 ₄ s ^ adm of ε, ΛΛΝ, ο, ε ,, Η, ΛΝ, ο, δ,

Etc. No M.P. C ° n ₀ 25 Element Analysis Calculated% Found% 18 1,4410 P 47.33 47.25 N. 3.97 4.02 N 3.94 3.87 19 48-51,5 P 54.67 54.43 N. 4.37 4,17 N 3.04 3.01 20 1,4443 P 51.39 51.43 N. 5.07 5.17 N 3.53 3.48 21 1,4614 P 53.90 54.19 N. 5,24 5.33 N 3.31 3.51

22 1,4489 P 52.55 52.29 N. 5.39 5.43 N 3,40 3,33 23 1,4709 P 46.26 46.40 N. 4.37 4,41 N 3,37 3.42 24 1,448 th most common P 46.76 46.83 n 4:19 4.21 N 3.68 3.88 25 1,4748 P 44.89 45.04 n 4.02 4.07 N 3.49 3,35 26 1,4471 P 51.39 51.32 n 5.07 5.08 N 3.53 3.50

Example 27. Preparation of diethyl 2- (difluoromethyl) -4- (2,2-dimethylpropyl) -6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

To a solution of 11.0 g (0.105 mol) of 3.3 dimethylbutanol in 20 ml of methylene chloride was added 3.11 g (0.15 mol) of pyridine chlorochromate. The mixture was stirred for 2 hours. The methylene chloride solution was decanted and filtered through a silica gel column. The silica gel column was washed with 200 ml of methylene chloride. The combined methylene chloride solution was concentrated under reduced pressure at 20 ° C to give a precipitate.

3.7 g, which is 66% pure 2,2-dimethylbutyraldehyde.

A mixture of the above aldehyde, 14 g (0.076 mol / ethyltrifluoroacetoacetate, 0.5 ml piperidine and 50 ml THF was refluxed for 3 days and cooled to room temperature. 36 g of ammonia is added to the above THF solution for one hour. The reaction mixture was stirred with 100 ml of water and 100 ml of ether. The ether layer was separated, dried and concentrated to give 14.9 g of precipitate. The precipitate was poured into a cold (10 ° C) mixture of 50 ml of concentrated sulfuric acid and 50 ml of methylene chloride. The mixture was stirred for 10 min and poured onto 300 g of crushed ice. The methylene chloride layer was separated, dried and concentrated. The precipitate was distilled at 0.4 fertilizer. The starting fraction (vessel temperature 90 ° C) was discarded. The second fraction (vessel temperature 120 C) was 5.3 g of oil which was purified by HPLC using 10% ethyl acetate / cyclohexane as eluent. The first fraction was 4.83 g of syrup identified as diethyl 2,6-bis (trifluoromethyl) -1,4-dihydro-4- (2,2-dimethylpropyl) -3,5-pyridinedicarboxylate. A mixture of 3.83 g (0.0089 mol) of the above syrup, 1.41 g (0.089 mol) of DBU and 50 ml of THF was refluxed for 24 h and concentrated. The precipitate was stirred with 100 ml of 6N HCl and 100 ml of ether and filtered. The ether filtrate was separated, washed successively with water, saturated sodium bicarbonate, saturated sodium chloride, dried and concentrated. The precipitate was distilled at 1 fertilizer (130 ° C vessel temperature) to give 1.9 g of oil which was purified by HPLC using 3% ethyl acetate / chloride as eluent. The starting fraction was discarded. The second fraction gave 1.4 g of the desired product, n ₀ 25 1.4522.

Calculated for C _lg H ₂₂ F _J N ₁ 0 _4: C, 52.55; H, 5.39; N, 3.40; Found: C, 52.54; H, 5.42; N, 3.40.

The monoacid compounds represented by Formula III are prepared by selective hydrolysis of the diester compounds of Formula I, as illustrated by the following Examples 28-37.

Example 28. Preparation of 2- (difluoromethyl) -4-ethyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-ethyl ester.

A mixture of 18.5 g (0.050 mol) of the product of Example 12, 3.3 g (0.072 mol) / 85% potassium hydroxide and 100 ml of ethanol was stirred for 18 h and poured into water. The reaction mixture was extracted with 200 ml of ether. The aqueous layer was acidified with 50 ml of concentrated hydrochloric acid. The oily residue was extracted into ether (2 x 100 mL) and the ether extracts were dried (MgSO ₄ ) and concentrated. The precipitated solid was recrystallized from ether-petroleum ether to give 5 14.4 g (84.7%) of the desired product, m.p. 117120 ° C.

Calculated for C ₁₃ H _{| 2} F _{J N)} 0 _4: C, 45.76; H, 3.54; N, 4.10; Found: C, 45.77; H, 3.42; N, 4.09. 10

Example 29. Preparation of 2- (difluoromethyl) -4-propyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-ethyl ester.

32 g (0.035 mol) of product of Example 13 and 150 ml of ethanol were placed in a 500 ml flask. 15 Combine 5.51 g / 0.0835 mol / 85% potassium hydroxide and 75 ml water in a separate flask. The aqueous KOH was poured into a 500 ml flask and the mixture heated to reflux for 18 hours. The reaction mixture was concentrated 20 and stirred in water. The aqueous solution was acidified with concentrated HCl and extracted with ethyl ether. The organic portions were dried over anhydrous MgSO ₄ , filtered and concentrated to give 23.25 g (78%) of the desired product, m.p. 98-100 ° C.

Calculated for C _{| 4} H ₁₄ 0 _{4 N]} F _J: C 47.32; N.

3.98; N, 3.94. Found: C, 47.45; H, 3.99; N, 3.95.

Example 30. Preparation of 2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -

3,5-pyridinedicarboxylic acid, 5-methyl ester.

A mixture of 6.4 g (0.0173 mol) of the product of Example 14, 1.2 g (0.0182 mol) of 85% KOH, 30 ml of methanol and 2 ml of water was stirred for 2 days and concentrated. The precipitate was stirred with 200 ml of water and extracted with ether. The aqueous layer was acidified with concentrated HCl and the oily residue was extracted into ether (2 x 100 mL). The ether extracts were dried and concentrated to give 5.9 g of a solid which was recrystallized from hexane to give 4.9 of the desired product as a solid, m.p. 100-102 ° C.

Calcd for C ₁₄ H ₄ F _J N ₁ O ₄ : C 47.33; H, 3.97; N, 3.94; Found: C, 47.40; H, 3.97; N, 3.90.

In a manner similar to Examples 28, 29 and 30, other 2- (difluoromethyl) -6- (trifluoromethyl) -3-3,5-pyridinedicarboxylic acid 5-ethyl esters according to the invention were prepared as indicated in Table 6 by hydrolysis of the starting materials listed.

Table 6

3,5-pyridinedicarboxylic acid, 5-monoesters

Etc. No Product Source material An empirical formula 31 2- (difluoromethyl) -4-isopropyl6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-ethyl ester 15 ς <Η, ΛΝ, ο ₄ 32 2- (difluoromethyl) -4-isobutyl-6 (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-ethyl ester avenue 16 33 2- (difluoromethyl) -4-n-butyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-ethyl ester avenue 20 cato 34 2- (difluoromethyl) -4-cyclopropyl6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-ethyl ester 17 c _h h ₁₂ f, n, o ₄ 35 2- (difluoromethyl) -4- (methylthioethyl) - 6- (trifluoromethyl) -3,5-pyridinedicar- avenue 23 caw,

boxylic acid, 5-ethyl ester

36 2- (difluoromethyl) -4- (methoxymethyl) - eg 24 6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-ether ester ε ,, Η, ΛΝ, ο, 37 2- (difluoromethyl) -4-cyclohexyl-6-ex 21 C ₁₇ H _ie F ₃ N, O ₄

(trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-ethyl ester

Etc. No M.P. C ° n _D 25 Element % Analysis Calculated Found 31 80-87 P 47.33 47.56 N. 3.97 4:19 N 3.94 3.62 32 1,4453 P 48.79 48.55 N. 4.37 4,51 N 3.79 3.66 33 83-85 P 48.79 48.86 N. 4.37 4.36 N 3.79 3.71 34 113-115 P 47.60 47.67 N. 3.42 3.56 N 3.97 3.92 35 121,5-122,5 P 43.41 43.51 N. 3.64 3.69 N 3.62 3.62 36 108-108,5 P 43.71 43.68 N. 3,39 3.45 N 3.92 3.88 37 88-91 P 51.65 51.45 N. 4,59 4,58 N 3.54 3.60

The pyridinedicarboxylic acids of formula V according to the present invention are prepared by complete hydrolysis of the compounds of formula (D) and II, as illustrated in the following Examples 38-43.

Example 38. Preparation of 2,6-bis (trifluoromethyl) -4-ethyl-3,5-pyridinedicarboxylic acid.

In a one-hole flask was placed South / 0.025 mol / product of Example 1 and 100 ml of 10% aqueous KOH. The mixture was refluxed for 48 h and the aqueous mixture was extracted once with ethyl ether. The aqueous layer was acidified with concentrated HCl, and the organic particles were extracted twice with ether, dried over MgSO ₄ and concentrated to give 2.73 g (32.23%) of the desired product, m.p. 263-269 ° C.

Calculated for C _H H ₇ O ₄ N _t F ₆ : C, 39.87; H, 2.11; N, 4.22; F 34.44, Found: C, 39.92; H, 2.22; N, 4.17; F 34.60.

Example 39. Preparation of 2- (difluoromethyl) -4-n-propyl-6- (trifluoromethyl) -

3,5-pyridinedicarboxylic acid.

A mixture of 20.1 g / 0.0525 mol / product of Example 13, 11.4 g of 85% KOH and 100 ml of methanol was refluxed for 19 h and concentrated. The precipitate was treated with 200 ml of water and extracted with ether. The aqueous layer was separated and acidified with 30 ml of concentrated HCl. The oily residue was extracted into ether and the ether extract was dried and concentrated. The precipitate was recrystallized from chloroform to give 4.2 g (24%) of the desired product, m.p. 235.5-236.5 ° C.

Calculated for C ₁₂ H ₁₀ P ₃ O ₄ : C 44.05; H, 3.08; N, 4.28; Found: C, 43.92; H, 2.98; N

4:19.

The combined mother liquor was concentrated and the precipitate was treated with 10 g KOH, 5 50 ml methanol and 2 ml water as described above to give an additional 2.2 g (12.8%) of the desired product.

Example 40. Preparation of 6- (difluoromethyl) -4-ethyl -2- (trifluoromethyl) -3,5-pyri-10 dindicarboxylic acid.

In a 1 liter flask was placed 60 g (0.163 mol) of the product of Example 12 and 200 ml of methyl alcohol. In another flask, 150 ml of water and 21.52 g / 0.326 mol / potassium hydroxide are combined. The water KOH was poured into a 1 liter flask and the mixture was refluxed overnight. The reaction mixture was cooled and extracted once with ethyl ether. The aqueous layer was acidified with concentrated hydrochloric acid and extracted with ethyl ether. The organic portions were dried over anhydrous magnesium sulfate, filtered and concentrated to give 26.72 g (52%) of the desired product, m.p. 237239 ° C.

Calculated for C _h H ₈ O ₄ F ₎ N _j : C 42.17; H, 2.55; N, 4.47; Found: C, 43.29; H, 2.81; N, 4.34.

In a manner similar to Examples 39 and 40, other asymmetric pyridinedicarboxylic acids were prepared as indicated in Table 7 using the starting material indicated in Table 7.

Table 7

Etc. Product Outbound Empirical No material formula

41 2- (difluoromethyl) -4-isopropyl6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid 15 c ₁₂ h ₁₀ f ₅ n, o ₄ 42 2- (difluoromethyl) -4-methoxy- avenue 24 ε ,, ΗΛΝ, ο,

methyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid

43 2- (difluoromethyl) -4-isobutyl- 6- (Trifluorobutyl) -3,5-pyridinedicarboxylic acid 14 ^C , 3 ^H n ^F 5 ^N i ° 4 Etc. M.P. n _D 25 Analysis% No ° C Element Calculated Found 41 278 (dec) P 44.05 43,99 N. 3.08 3.10 N 4.28 4.24 42 243-247 P 40.14 39.95 N. 2.45 2.66 N 4.26 4,22 43 219-219,5 P 45.76 45.66 N. 3.54 3.57 N 4.10 4.08

The monoacids and dioxide chlorides of the present invention represented by Formulas IV and VI are prepared from the corresponding monoacids and dibasic acids, as shown in the following Examples 4451.

Example 44. Preparation of ethyl 5-chlorocarbon-6- (di-fluoromethyl) -4-isopropyl2- (trifluoromethyl) -pyridine-3-carboxylate.

A mixture of 3.72 g (0.105 mol) of the product of Example 31 and 50 ml of thionyl chloride was refluxed for h and concentrated in vacuo to give 3.8 g (97%) of the desired product as an oil, n _D 25 1.4570.

Calculated for C 24 H 27 Cl 2 N 4 N 4: C 45.00;

H, 3.51; N, 3.75; Found: 45.10; H, 3.53; N, 3.68.

In a manner similar to that in Example 44, other monoacid chlorides and diacid chlorides of the present invention are more than 10 extracted from said starting material and are listed in Table 8.

Table 8

Etc. Product Output Empirical No. Material Formula

45 6- (difluoromethyl) -4-ethyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate acid chloride 40 LMS ^ Oh, 46 ethyl 5-chlorocarbon-6- (difluoromethyl) -4-ethyl-2- (trifluoromethyl) -3-pyridinedicarboxylate etc. 28 α ,, Η ,, ο, Ν, ρ, α 47 ethyl -5-chlorocarbon-6- (difluoromethyl) -4-propyl-2- (trifluoromethyl) -3-pyridinecarboxylate etc. 29 C ₁₄ H ₁₃ 0 ₃ N ₁ F _j C1 48 2,6-Bis (trifluoromethyl) -4-ethyl3,5-pyridinedicarboxylic acid, double acid chloride etc. 38 Ο ,, Η, Ο, Ν, Ρ.α 49 ethyl-5- (chlorocarbon) -4-p-butyl- etc. 33 C ^ Ci.F ^ .O.

6- (difluoromethyl) -2- (trifluoromethyl) 3-pyridinecarboxylate

50 ethyl 5- (chlorocarbon) -4-cyclopropyl-ex. 34 6- (difluoromethyl) -2- (trifluoromethyl) 3-pyridinecarboxylate c ₁₄ h ₁₁ ci ₁ f ₃ n _] o ₃ 51 2- (difluoromethyl) -4-propyl-6- (tri) 39 fluoromethyl / -3,5-pyridinedicarboxylic acid, double acid chloride c ₁₂ h ₈ o ₂ n_f ₃ ci ₂

Etc. No M.P. ° C n _D 25 % Analysis Found Element Calculated 45 1,4706 P 37.74 37,83 N. 1,73 2.12 N 4,00 3.70 46 1,4583 P 43.45 43.60 N. 3.06 3.09 N 3.89 3.91 47 33-34 P 44,99 45.02 N. 3.48 3.52

invent the compounds of the present invention. 48 1,4509 P N. N 49 46-48 P N. N 50 53-54 P N. N 51 1,4713 P

Η

N

3.74 3.71 35.90 36.05 1.37 1.43 3.81 3.73 46.47 46.33 3.90 3.78 3.61 3.58 45.24 45.24 2.98 3.01 3.77 3.78 39.58 39.61 2.21 2,34 3.85 3.50

Example 52. Preparation of 3-ethyl-5-methyl 6- (difluoromethyl) -4-propyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 5.0 g of the product of Example 47 and 100 ml of methanol was refluxed for 18 h and concentrated. The precipitate was dissolved in ether. The ether solution was washed with saturated aqueous sodium bicarbonate, dried, concentrated to give 2.37 g (48%) of the desired product as an oil, n _D 25 1.4428.

Calcd. C, 48.92; H, 4.11; N, 3.80; Found: C, 49.00; H, 4.13; N, 3.76.

Example 53 Preparation of 3-ethyl 5-methyl 6- (difluoromethyl) -4-isopropyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 2.8 g (0.0074 mol) of the product of Example 44 and 60 ml of methanol was refluxed for 3 h and concentrated to give 1.61 g / 59% of the desired product as an oil , n _D 25 1,4483.

Calcd for C ₁₃ H ₁₆ F ₃ M ₄ O ₄ C 48.79; H, 5.37; N, 3.79; Found: C, 48.69; H, 4.41; N

3.75.

Example 54 Preparation of 3-ethyl 5-ethyl 2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 10 g (0.0270 mol) of the product of Example 32 and 100 ml of thionyl chloride was refluxed overnight and concentrated to give a precipitate (9.59 g). A portion (5.03 g) of this precipitate was refluxed with 50 ml of methanol for 3 h and concentrated. The precipitate /

3.72 g (distilled) to give 2.83 g (56.3%) of the desired product as an oil, n _D 25 25 1.4453.

Calcd for C ₁ H ₁₄ P ₅ M, O ₄ : C 50.13; H, 4.73; N, 3.65; Found: C, 49.91; H, 4.87; N, 3.43.

Example 55. Preparation of 3-ethyl 5-methyl 4-cyclopropyl-6- (difluoromethyl) -2- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 3.0 g (0.008 mol) of the product of Example 50 and 30 ml of methanol was refluxed for 1.5 h and concentrated. The precipitate (2.81 g) was recrystallized from petroleum ether to give 1.85 g /

63.1% / of the desired product as a white solid, m.p. 61-63 ° C.

Calculated for: C25H25F3N3O4C 49.05; H, 3.84; N, 3.81. Found: C, 48.99; H, 3.88; N, 3.79.

A second crop was isolated from the mother liquor (0.69 g, 23.5%). 49-52 ° C.

Example 56. Preparation of dimethyl-2,6bis (trifluoromethyl) -4-ethyl-3,5-pyridinedicarboxylate.

To 70 ml of methanol in a 500 ml flask was added 5 g (0.0136 mol) of the product of Example 48. The reaction mixture was refluxed and refluxed for 9 hours. The mixture was concentrated, diluted with ethyl ether, washed. with saturated aqueous sodium bicarbonate solution, dried over anhydrous MgSO ₄ and concentrated to give 3.3 g (68%) of the desired product, m.p. 45-47 ° C.

Calculated for C _l3 H ₁₁ 0 ₄ N ₁ F _6: C, 43.45; H, 3.06; N, 3.89; Found: C, 43.57; H, 3.06; N, 3.86.

In a manner similar to the procedure of Examples 52-56, other new compounds were prepared24 as indicated in connection with Table 4, taking into account the substituted starting material and reaction conditions suitable for the reactants used, further examples were obtained as well is indicated in Table 9.

Table 9

Mixed esters of 3,5-pyridinedicarboxylic acids

Etc. No Source material Reagent Product An empirical formula 57 46 isopropanol 5-ethyl 3-isopropyl-2 (difluoromethyl) -4-ethyl-6 (trifluoromethyl) -3,5-pyridinedicarboxylate C.eH.AN.F, 58 45 butanol dibutyl 6- (difluoromethyl) - 4-ethyl-2- (trifluoromethyl) - 3,5-pyridinedicarboxylate WMj 59 45 methanol dimethyl-2- (difluoromethyl) - 4-ethyl-6- (trifluoromethyl) - 3,5-pyridinedicarboxylate CAWs 60 48 isopropanol bis (isopropyl) 2,6-bis (trifluoromethyl) -4-ethyl-3,5-pyridinedicarboxylate ε ,, Η ,, ο, ΝΛ 61 46 allyl alcohol 3-ethyl 5- (2-propenyl) 6 difluoromethyl) -4-ethyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate addnl 62 46 2-chloro- ethanol 5-ethyl 3- (2-chloroethyl) 2 (difluoromethyl) -4-ethyl-6 (trifluoromethyl) -3,5-pyridinedicarboxylate c ^ dm 63 46 methyl alcohol 3-ethyl 5-methyl 6- (difluoromethyl) -4-ethyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate CAW, 64 46 2-fluoro- ethanol 3-ethyl 5- (2-fluoroethyl) 6- (difluoromethyl) -4-ethyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate 65 49 methanol 3-ethyl 5-methyl-n-butyl-6- (difluoromethyl) -2- (trifluoromethyl) 3,5-pyridinedicarboxylate CAW < 66 49 2,2,2trifluoroethanol 3- ethyl 5- (2,2,2-trifluoroethyl) - 4- p-Butyl-6- (difluoromethyl) -3,5-pyridinedicarboxylate ς, ιν, Ν, ο, 67 51 methanol dimethyl 2- (difluoromethyl) - 4-p-propyl-6- (trifluoromethyl) - 3,5-pyridinedicarboxylate c ₁₄ h ₁₄ f ₅ n, o ₄ 68 51 p-propanol dipropyl 2- (difluoromethyl) - 4-p-propyl-6- (trifluoromethyl) - CA ^p L0 ₄

3,5-pyridinedicarboxylate

Etc. No M.P. ° C n _D 25 Element Analysis% Found Calculated 57 1,4440 P 50.13 50.21 N. 4.69 4.72 N 3.65 - 3.66 58 1,4467 P 53.65 53.05 N. 5.69 5.55 N 3.29 3,37 59 47-49 P 45.74 45.79 N. 3.51 3.57 N 4.10 4.07 60 46-49 P 49.15 49.21 n 4,57 4.63 N 3,37 3,37 61 - 1,4525 P 50.39 50.34 n 4:19 4,22 N 3.67 3.66 62 1,4570 P 44.62 44.48 n 3.71 3.76 N 3.47 3,40 63 1,4448 P 47.32 47,23 n 3.94 3.99 N 3.94 3.92 64 1,4459 p 46.52 46.76 n 3.90 4.20 N 3.62 3.64 65 1,4465 P 50.13 49.97 n 4.73 4.77 N 3.65 3.65 66 37-38 P 45.24 45.69 n 3.80 3.86 N 3.10 3.14 67 1,4435 P 52.55 52.59 n 5.39 5,28 N 3,40 3,37 68 1,4451 p 52.55 52.59 n 5.39 5,28 N 3,40 3,37

Example 69. Preparation of 3-ethyl 5-methyl 2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 2.9 g (0.00817 mol) / of the product of Example 30, 11 g (0.0705 mol / ethyl iodide),

1.3 g / 0.00942 mol / potassium carbonate and 50 ml of acetone were refluxed for 4 hours and concentrated. The precipitate was treated with 200 ml of water and extracted with 50 ml of ether twice. The ether extracts were washed once with 50 ml of sodium bicarbonate, dried (MgSO ₄ ) and concentrated to give an oil which was distilled at 2 torus (vessel temperature 130 ° C) to give 3.0 g (98%). / of the desired product, n _D 25 1,4469.

Calculated for C24H25F3N3O4: C, 50.13; H, 4.73; N, 3.65; Found: C, 50.19; H, 4.78; N

3.56.

In a manner similar to the procedure of Example 69, other pyridinedicarboxylates of the present invention are obtained. As indicated above with reference to Table 4, taking into account the substituted starting material and the reaction conditions suitable for the reagent used, further examples are given according to Table 10.

Table 10

Alternative preparation of pyridinedicarboxyl derivatives

Etc. Initial Reagent Solvent Product No Maternal Conditions

70 35 KF-CH ₃ I D MF room temperature 3-ethyl 5-methyl 6- (difluoromethyl) -4- (methylthioethyl) -2 (trifluoromethyl) -3,5- pyridinedicarboxylate 71 36 KF-CH2 DMF-room 3-ethyl-5-methyl 6- (difluoromethyl) temperature til (-4-) methoxymethyl) -2- (trifluoromethyl) -3,5-pyridinedicarboxylate 72 41 K, CO ₃ -CH I acetone-reverse dimethyl 2- (difluoromethyl) -4- refrigerator (isopropyl-6- (trifluoromethyl) - 3,5-dindicarboxylate 73 43 K ₂ co ₃ - DMF-room dipropargyl 2- (difluoromethyl) - BrCH C = CH temperature of 4-isobutyl-6- / trifluoromethyl / - 3,5-pyridinedicarboxylate 74 42 K ₂ co ₃ - acetone-reverse dimethyl 2- (difluoromethyl) -4- / CH ₃ I refrigerator methoxymethyl-6- (trifluoromethyl) -3,5-pyridinedicarboxy- Lat Etc. Empirical M.P. n _s 25 % Analysis No formula ° C Item Calculated Found 70 59-60,5 P 44,89 44,87 N. 4.02 4.02 N 3.49 3.47 71 ς <Η, ΛΝο ₅ 52-54 P 45.29 45.08 N. 3.80 3.79 N 3.77 3.69 72 s ₁₄ n ₁₄ p, md 1,4573 p 47.33 47.46 N. 3.97 4.03 N 3.94 3.88 73 unlocked 1.4696 p 54.68 54.61 N. 3.86 3.84 N 3.36 3.34 74 ς, Η ,, Ρ, Ν.Ο, 43-44 P 43.71 43.78 N. 3.39 3.40 N 3.92 3.89

Example 75. Preparation of 3-methyl 5ethyl 2- (difluoromethyl) -4- (1-ethylpropyl) -6 (trifluoromethyl) -3,5-pyridinedicarboxylate.

12.0 g / 0.0386 mol / 90% pure product of Example 22, 2.6 g / 0.0394 mol / 85% potassium 5 hydroxide, 30 ml ethanol and 2 ml water are refluxed for 24 hours h and concentrate. The precipitate was treated with 100 ml of water and extracted with 100 ml of ether. The aqueous layer was acidified with 50 ml of concentrated 10 HCl. The oily residue was extracted with 200 ml of ether. The ether solution was dried (MgSO ₄ ) and concentrated to give 10.8 g of syrup. Part (8.8 g) of this syrup was mixed with 34 g of methyl iodide, 3.16 g (0.0230 mol) of K ₂ CO ₃ 15 and 30 ml of acetone. The mixture was stirred and refluxed for 3 h and concentrated. The precipitate was stirred with 100 ml of ether and 100 ml of water. The ether solution was washed once with 50 ml of saturated NaHCO ₃ , 20 dried (MgSO ₄ ) and concentrated to give

7.6 g of brown oil distilled at

1.5 fertilizer (vessel temperature 115 ° C) to give 7.6 g of distillate. The distillate was chromatographed on silica gel by HPLC using 3% ethyl acetate cyclohexane as eluent. The first fraction (retention time 14-16 min) was 2.0 g of a mixture of the desired product and an undetermined material. The second fraction (retention time 16-22 min) was 4.3 g of oil, which after distillation at 1 fertilizer (130 ° C container temperature) gave 4.1 g of the desired product as a colorless oil, n _D 25 1.4519 .

Calculated for C ₁₇ H ₂₀ F _J NO ₄ : C 51.39; H, 5.07; N, 3.53; Found: C, 51.40; H, 5.14; N, 3.50.

Other pyridinedicarboxylic acid monoesters of this invention listed in Table 2 were prepared by a method similar to that described in Example 30.

Table 11

Pyridinedicarboxylic acid monoesters

Etc. No Compound Source material An empirical formula 76 2- (difluoromethyl) -4-p-propyl- 6- (Trifluoromethyl-) 3,5-pyridinedicarboxylic acid, 5-n- avenue 68 c, ₅ h ₁₆ f ₅ no ₄ 77 propyl ester 2- (difluoromethyl) -4-n-propyl6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-methyl- 67 c ₁₃ h ₁₂ f ₅ no ₄ 78 ester 2- (difluoromethyl) -4- (methoxymethyl) 6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-methyl- 74 c ₁₂ h ₁₀ f ₅ n, 0 ₅ 79 ester 2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid, 5-propargylester 73

Etc. M.P. % Analysis No Element Calculated Found 76 69-71 P 48.79 48.71 N. 4.37 4.40 N 3.79 3.79 77 113-115 P 45.76 45.86 N. 3.54 3.65

N 4.10 3.96 78 132-133,5 P 41.99 42.09 N. 2.94 2.95 N 4.08 4.03 79 98,5-99,5 P 50.67 50.56 N. 3.72 3.75 N 3.69 3.63

Example 80. Preparation of 3-methyl 5-propargyl 2- (difluoromethyl) -4-isobutyl-6 (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 2.1 g of the product of Example 79,

1.1 g of potassium carbonate, 25.3 g of methyl iodide and 40 ml of DMF were stirred for 24 h and poured into water. The mixture was extracted with ether. The ether extract was washed twice with 100 ml of water, dried and concentrated. The precipitate was distilled at 0.5 fertilizer to give

2.1 g (96%) of the desired product as an oil, n _D 25 1,4598.

Calcd for C "H ₁₄ F _i N _J 0 _4: C, 51.91; H, 4.10; N, 3.56; Found: C, 51.92; H, 4.14; N

3.56.

Example 81. Preparation of 3-ethyl 5-methyl 2- (difluoromethyl) -4- (methoxymethyl) -6Pr. Compound #

(trifluoromethyl) -3,5-pyridinedicarboxylate.

According to the procedure of Example 69, except that the starting material is the product of Example 78, 3-ethyl 5methyl-2- (difluoromethyl) -4- (methoxymethyl) is obtained

6- (trifluoromethyl) -3,5-pyridinedicarboxylate as an oil, n _D 25 1.4467.

Calcd for _{C] 4} H ₁₄ F _j N ₁ 0 _J: C 45.29; H, 3.80; N, 3.77; Found: C, 45.39; H, 3.84; N, 3.74.

Other 5-chlorocarbonyl-3-pyridinecarboxylates of the present invention are prepared from the corresponding 3,5-pyridinecarboxylic acid 3-monoesters according to a method similar to that described in Example 44 and are listed in Table 12.

Table 12

Source Empirical Material Formula

82 3-methyl 5-chlorocarbonyl- 6- (difluoromethyl) -4-p-propyl 2- (trifluoromethyl) -3-pyridinecarboxylate 77 83 3-propyl 5-chlorocarbonyl- 6- (difluoromethyl) -4-p-propyl 2- (Trifluoromethyl) -3-pyridinecarboxylate 76

ς, Η ,, α, ρ, Ν, ο, ^ η ,, ο, ρ, ν ^

Etc. No M.P. n _D 25 Element Analysis% Calculated Found 82 47-50 P 43.41 43.62 N. 3.08 3.05 N 3.89 3.76 83 1.4560 P 46.47 46.39 N. 3.90 3.95 N 3.61 3.60

Other asymmetric pyridinedicarboxylates of the present invention are prepared from the corresponding 5-chlorocarbonyl-3-pyridine carboxylate and suitable alcohol by a method similar to that described in Example 52 and are listed in Table 13.

Table 13

Etc. No Source material Reactant Product Empirical formula 84 82 p-propanol 3-methyl-5-n-propyl 6- C ₁₆ H _1J F _J N _| O ₄ (difluoromethyl) -4-n-propyl-2- (trifluoromethyl) - 3,5-pyridinedicarboxylate 85 83 methanol 3-methyl-5-n-propyl-2- / C ₁₆ H _lg F _J N ₁ 0 ₄

difluoromethyl / -4-p-propyl

6- (trifluoromethyl) -3,5-pyridinedicarboxylate 86 82 ethanol 3-methyl 5-ethyl 6- / difluoro-C H..F, N, O ₄ methyl (4-p-propyl-2-) tri- fluoromethyl / dicarboxylate -3,5-pyridine- Etc. n _D 25 Analysis No Element Calculated% Found% 84 1,4447 P 50.13 50.25 N. 4.73 4.73 N 3.65 3.62 85 1,4453 P 50.13 50.54 N. 4.73 4.71 N 3.65 3.60 86 1,4439 P 48.79 48.69 n 4.37 4,44 N 3.79 3.74

Example 87. Preparation of 3-ethyl 5-methyl 2,6-bis- (difluoromethyl) -4-propyl-3,5-pyridinedicarboxylate.

A mixture of 5.67 g (0.016 mol) of the product of Example 11, 1.06 g (0.016 mol) of 85% KOH, 40 ml of ethanol and 10 ml of water was stirred for 24 h and concentrated. The precipitate was treated with 50 ml of water and extracted with 50 ml of ether. The aqueous layer was acidified with 50 ml of concentrated HCl. The oily precipitate was extracted with ether, dried (MgSO ₄ ) and concentrated to give 2.64 g (49%) of monoacid. Part /

1.64 g, 0.00486 moles / of this acid was refluxed with 10 ml of thionyl chloride until the HCl release ceased. The reaction mixture was concentrated and the precipitate was dissolved in ether, dried over MgSO ₄ and concentrated to give 1.22 g of the desired product as an oil, n _p 25 1.4629.

Calcd for Ο ₁₅ Η ₁₇ Ρ ₄ ΝΟ _4: C, 51.29; H, 4.88; N, 3.99. Found: C, 50.93; H, 4.99; N, 3.87.

Example 88. Preparation of ethyl 5- (aminocarbonyl) -6- (difluoromethyl) -4-ethyl-2- (trifluoromethyl) -3-pyridinecarboxylate.

Excess ammonium gas (3 g, 0.176 mol) was condensed in a 250 ml three-necked flask using dry ice / acetone refrigerators. 7 g (0.0196 mol) of the product of Example 46 was added to 50 ml of ether. The ether solution was slowly poured into the reaction flask and the whole mixture was stirred for 18 h. The resulting solid was washed with water and dried under vacuum for 18 h to give 5.67 g (86%) of desired product, m.p. Mp 165-167 ° C.

Calculated for C ₁₃ H ₁₃ 0 ₃ 1H ₂ P ₃ : C, 45.88; H, 3.82; N, 8.23; Found: C, 45.87; H, 3.84; N, 8.23.

In a manner similar to Example 88, other pyridinedicarboxamides according to the present invention were prepared as indicated in Table 14.

Table 14

Etc. No Source material Reagent Product 89 46 butylamine ethyl 5-1 (butylamino) -carbonyl 1-6- (difluoromethyl) -4-ethyl-2- (trifluoromethyl) -3-pyridinecarboxylate 90 46 aniline ethyl 6- (difluoromethyl) -4-ethyl-5-1 (phenylamino) carbonyl 1 -2- (trifluoromethyl) 3-pyridinecarboxylate 91 47 ammonium gas ethyl 5- (aminocarbonyl) -6- (difluoro-)

methyl (-4-n-propyl-2- (trifluoromethyl) 3-pyridinecarboxylate

Etc. Empirical M.P. % Analysis No formula ° C Element Found Calculated 89 ς, Η ,, Ο, Ν, Ρ, 83-85 P 51.51 51.38 N. 5:30 5.35 N 7.07 7.02 90 ο ,, η ,, ρ, να 182-183 P 54.80 54.69 N. 4.08 4.13 N 6.73 6.68 91 with "n, grandfather 141-143 P 47.46 47.64 N. 4.27 4.32 N 7.91 7.71

Example 92. Preparation of ethyl 5-cyano-6- (difluoromethyl) -4-ethyl-2- (trifluoromethyl) -3-pyridinecarboxylate.

To 100 ml of phosphorus oxychloride in a 50 ml flask was added 3.5 g (0.0102 mol) of the product of Example 88. The mixture was heated to reflux for 18 h, concentrated, washed in water and extracted with ethyl ether. The ether extracts were dried over anhydrous MgSO ₄ , concentrated and dried in vacuo to give 1.23 g (37%) of the desired product, m.p. 38-40 ° C.

Calculated for ΰ ₁₃ Η _Η 0 ₂ Ν ₂ Ε ₅ : C, 48.44; H, 3.41; N, 8.65.

Example 93. Preparation of ethyl 5-cyano-6- (difluoromethyl) -4-n-propyl-2- (trifluoromethyl) -3-pyridinecarboxylate.

A mixture of 4.0 g (0.0112 mol) of the product of Example 91 and 100 g of phosphorus oxychloride was refluxed for 20 h and concentrated. The precipitate was poured into water and extracted with ether. The ether extract was dried (MgSO ₄ ) and concentrated. The precipitate was distilled at 0.1 fertilizer to give

2.26 g of an oil which was recrystallized from hexane at low temperature to give 1.11 g of the desired product as a solid, m.p. 4041 ° C.

Calculated for C ₁₄ H ₃ F ₃ N ₂ 0 ₂ : C 50.01; H, 3.90; N, 8.33; Found; C, 49.75; H, 3.98; N, 8.21.

Example 94. Preparation of diethyl 2,6bis (trifluoromethyl) -4- (1-3-butenyl) -3,5pyridine dicarboxylate.

Dry a 250 ml three-necked flask and purge with argon. Approximately 45 ml of dry tetrahydrofuran is injected into the syringe flask. The flask was cooled to -78 ° C and filled with 14 ml / 0.0227 mol / 1.6 M n-butyl lithium followed by 2.96 ml / 0.0227 mol / diisopropyl amine. After stirring for 5 min, 8.8 g (0.0227 mol) of the product of Example 1 was diluted with 10 ml of dry tetrahydrofuran and injected into the flask. The mixture was stirred for 1 h. 4.23 g / 0.035 mol / allyl bromide was added to this mixture and the mixture was stirred for 90 min at room temperature.

The mixture was diluted with ethyl ether and washed successively with water and 10% aqueous HCl. The organic portions were dried over MgSO ₄ and concentrated. Chromatography with 5% ethyl acetate / cyclohexane gave 1.4 g (14.4%) of the desired product, n _D 25 1.4410.

Calculated for C ₁ H ₁₉ O ₄ N ₁ F ₄ : C, 50.58; N, 3.27; H, 4.44; Found: C, 50.69; H, 4.47; N, 3.30.

Example 95. Preparation of diethyl 2,6bis (trifluoromethyl) -4- (3-butenyl) -3,5-pyridinedicarboxylate.

A 250 ml three-hole flask was heated, dried and flushed with argon. Tetrahydrofuran (50 ml) was injected with a syringe and the flask was cooled to -78 ° C. To this were added 8.33 ml (0.0133 mol) of 1.6 M n-butyl lithium with a syringe and then 2 ml (0.0133 mol) of diisopropylamine. To 10 ml of dry THF was added 5 g (0.0133 mol) of the product of Example 2 and the solution was injected into the reaction mixture. The mixture was stirred for one hour. 2.4 g / 0.02 mol / allyl bromide was injected into the flask and the mixture was stirred for 90 min at room temperature.

The mixture was diluted with ethyl ether and washed successively with water and 10% HCl. The organic portions were dried, concentrated and chromatographed with 5% ethyl acetate in cyclohexane to give 0.7 g (29.26%) of product, n _D 25 1.4365.

Calculated for C ₇ H ₁₇ O ₄ N ₁ F ₆ : C, 49.39; H, 4.11; N, 3.39. Found: C, 49.54; H, 4.14; N, 3.36.

Example 96. Preparation of ethyl 6- (difluoromethyl) 4-ethyl-5-hydroxymethyl-2- (trifluoromethyl) -3-pyridinecarboxylate.

Place 30.6 g (0.09 mol) of the product of Example 28 and 40 ml of tetrahydrofuran under nitrogen in a dry 500 ml four-necked flask. The reaction mixture was cooled to 10 ° C in an ice-water bath. To the above solution was added with a syringe 180 ml / 0.18 mol / 1 M borane in tetrahydrofuran. The reaction mixture was stirred for 160 h and poured into water. The organic portions were extracted into 300 ml of ether and the ether extract was washed with 200 ml of saturated sodium bicarbonate, dried (MgSO ₄ ) and concentrated. The precipitate was crystallized from petroleum ether to give 25 g (84.9%) of the desired product, m.p. 59.5-60.5'C.

Calculated for C ₁ H ₁₄ F _J N ₁₀ O _J : C 47.71; H, 4.31; N, 4.28; Found: C, 47.72; H, 4.31; N, 4.25.

Example 97. Preparation of ethyl 6- (difluoromethyl) -4-ethyl-5-formyl-2- (trifluoromethyl) -3-pyridinecarboxylate.

A mixture of 4.74 g / 0.0145 mole / of the product from Example 96, 8.6 g / 0.0336 mole / pyridinium chlorochromate and 70 ml of CH ₂ C1 ₂ was kept at room temperature for 18 h. The CH ₂ C1 ₂ solution was decanted and chromatographed on silica gel using CH ₂ Cl ₂ as eluent. The first 2 L eluent gave 3.93 g (83.4%) of the desired product as a white solid, m.p. 63.5-65'C.

Calculated for C25H25F3O3: C, 48.01; H, 3.72; N, 4.31; Found: C, 48.02; H, 3.74; N, 4.28.

Example 98. Preparation of Diethyl 2- (difluoromethyl) -4- (2-methylsulfonylethyl) -6trifluoromethyl-3,5-pyridinedicarboxylate.

To a solution of 12.0 g (0.0289 mol) of the product of Example 23 in 200 ml of methylene chloride was added 13.0 g (0.064 mol) of m-chlorobenzoic acid. The reaction mixture was stirred for 24 h and poured into a mixture of 25 ml of 10% sodium hydroxide and 400 ml of water. The methylene chloride layer was separated and washed successively with dilute sodium bicarbonate, sodium thiosulfate, saturated sodium chloride, dried and concentrated to give 12.9 g of a solid. Part (5.0 g) of this solid was purified by HPLC using 33% ethyl acetate / cyclohexane as eluent to give 3.6 g of the desired product, m.p. 98-101 ° C.

Calculated for C ₁₆ H _{1 |} F _J N ₁ 0 ₆ S: C, 42.96; H, 4.06; N, 3.13; Found: C, 42.80; H, 4.06; N, 3.12.

Example 99. Preparation of 3-ethyl 5-methyl 6- (difluoromethyl) -4-vinyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 17.31 g (0.0387 mol) of the product of Example 98, 2.16 g (0.054 mol) of sodium hydroxide, 125 ml of water and 60 ml of ethanol was stirred for 24 h and concentrated. The precipitate was stirred with ether and 600 ml of 1.5 N sodium hydroxide. The aqueous layer was acidified with concentrated hydrochloric acid. The organic portions were extracted with methylene chloride (2 x 400 ml). The methylene chloride extracts were dried and concentrated to give 11.67 g of precipitate. A mixture of the above precipitate, 14.70 g / 0.104 mol / methyl iodide, 14.3 / 0.104 mol / potassium carbonate and 300 ml acetone was refluxed for 18 h and concentrated. The precipitate was stirred with 500 ml of water and 500 ml of ether. The ether layer was dried and concentrated. The precipitate (11.34 g) was distilled at 0.3 fertilizer to give 7.50 g (62%) of the desired product, n _in 25 1.4567.

Calculated for C ₁₄ H ₁₂ P ₅ M ₍ O ₄ : C 47.60; H 3.42; N 3.97; Found: C 47.46; H 3.55; N 3.85.

Example 100. Preparation of diethyl 412- (methylsulfinyl) -ethyl-1 -2- (difluoromethyl) -6- (trifluoromethyl) -pyridine-3,5-dicarboxylate.

To a stirred solution of 20.09 g (0.048 mol) of the product of Example 23 in 50 ml of methylene chloride cooled in an ice bath was added a solution of 10.3 g (0.050 mol) of chloroperbenzoic acid in 100 ml of methylene chloride, maintaining the temperature of the reaction is below 10 ° C. Stirring and cooling with an ice bath continued for another hour after the addition was complete.

The resulting sludge is poured into a solution obtained from 25 ml of 10% sodium hydroxide and 600 ml of water. After mixing well, the phases are separated. The aqueous phase was extracted with 50 ml of methylene chloride. The methylene chloride phases were combined, washed sequentially with a solution of 600 ml of 0.5% sodium bicarbonate, 0.5% sodium chloride solution, dried over magnesium sulfate, filtered and separated to give 20.5 g of a pale yellow solid.

The product was purified by recrystallization twice from hexane / ether to give

12.5 g white solid, m.p. 90.5-91.5 ° C, 60% yield.

Calculated for C ₁₆ H _(J F _J N ₁₀ O _J S ₁ : C 44.58; H 4.21; N 3.25; Found: C 44.45; H 4.22; N

3.20.

Example 101. Preparation of 3-ethyl 5methyl 6- (difluoromethyl) -4-methylthiomethyl] -2- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 32.8 g (0.081 mol) of the crude product of Example 25, 37 g of 10% sodium hydroxide, 35 ml of water and 125 ml of ethanol was stirred for 1 hour and concentrated. The precipitate was stirred with 70 ml of water and 200 ml of methylene chloride. The aqueous layer was acidified and the precipitate was extracted into methylene chloride. The methylene chloride extract was dried and concentrated to give 19.9 g of acid, m.p. 81-85 ° C. Part / 10.6 g, 0.1078 mol / of this acid, 5.2 ml / 0.085 mol / methyl iodide, 11.8 g / 0.085 mol / potassium carbonate and 150 ml acetone are stirred and refluxed. 24 hours. The reaction mixture was concentrated and the precipitate was stirred with 150 ml of methylene chloride and 200 ml of water. The methylene chloride layer was dried and concentrated. The precipitate was distilled at 0.25 fertilizer (vessel temperature 135-170 ° C) to give 7.16 g of distillate. This distillate was purified by HPLC using 7% ethyl acetate / cyclohexane as eluent.

The initial fraction (retention time 4-6 minutes) yielded 4.75 g of a solid which was recrystallized twice from hexane / ether to give 2.78 g of the desired product, m.p. 67-68.5 ° C.

Calculated for C ₁₄ H _t4 F _J N ₎ 0 ₄ S _| : C, 43.41; H, 3.64; N, 3.62; Found: C, 43.13; H, 3.61; N, 3.55.

Example 102. Preparation of Diethyl 6- (difluoromethyl) -2- (trifluoromethyl) -4-vinyl-3,5-pyridinedicarboxylate.

A mixture of 3.7 g of the product of Example 99, 13.75 g of 10% sodium hydroxide and 10 ml of water was stirred for 24 hours and concentrated. The precipitate was stirred with 300 ml of water and 50 ml of methylene chloride. The material layer was acidified with concentrated hydrochloric acid and extracted with methylene chloride. The methylene chloride extract was dried and concentrated to give 2.99 g of a yellow solid 5 which was recrystallized from petroleum ether to give 2.01 g of a white solid. A mixture of this solid, 1 ml of ethyl iodide, 10 ml of DMF and 2.09 g of potassium carbonate was stirred for 24 h and poured into 300 ml of water. 10 The reaction mixture was extracted with methylene chloride and the methylene chloride extract was dried and concentrated. The precipitate was distilled off at 0.1 t to give 1.41 g of the desired product n _D 25 1.4529. 15

Calculated for C ₁₅ H ₁₄ F ₅ N _h O ₄ : C 49.05; H, 3.84; N, 3.81. Found: C, 49.09; H, 3.84; N, 3.81.

Example 103. Preparation of Diethyl 4-1 /

-Ethoxy (methoxymethyl) 2- (difluoromethyl) -6-20 (trifluoromethyl) -pyridine-3,5-dicarboxylate.

To a stirred solution of 4.0 g (0.010 mol) of the product of Example 24 in 30 ml of carbon tetrachloride was added 2.5 g (0.015 mol / 25 bromine). The solution was cooled to 10 ° C, a stream of nitrogen was blown over the reaction mixture (to blow hydrogen bromide) and the reaction was illuminated with 150 W of light in place. The reaction temperature was maintained at 10-15 ° C for 6 hours. The light was removed and nitrogen flow was stopped.

A solution of 1.41 g (0.013 mol) of 2,6-lutidine in 5 ml in absolute ethanol was added to the reaction mixture and this resulting reaction mixture was stirred for 18 h at ambient temperature.

The reaction mixture was poured into 100 ml of water with 50 ml of methylene chloride. After being mixed well, the organic phase was separated, washed with 100 ml of 0.50% hydrochloric acid solution, 100 ml of 1% sodium bicarbonate, dried over magnesium sulfate, filtered and separated to give 4.29 g of a yellow oil.

The product was purified by HPLC on silica gel using 10% ethyl acetate in cyclohexane as solvent to give

2.18 g pale yellow oil, yield 48%, n _D 25 1,4446.

Calculated for: C ₁₇ H _{2 O} F ₅ N ₁ 0 ₆ : C 47.56; H, 4.70; N, 3.26 Found: C, 47.55; H, 4.71; N, 3.26.

In a manner similar to the procedure described in Example 103, the product of Example 24 is brominated and the resulting product is reacted with a suitable alcohol or alkylthiol as indicated in the following examples in Table 15 to give the listed product.

Table 15

Etc. No Source material Reagent Product 104 71 methanol 3-ethyl 5-methyl 6- (difluoromethyl) -4 (ditoxymethyl) -2- (trifluoromethyl) -3,5-pyridinedicarboxylate 105 71 methanethiol 3-ethyl 5-methyl 6- (difluoromethyl) -4-1

methoxy (methylthio) methyl-1-2- (trifluoromethyl) -3,5-pyridinedicarboxylate

Etc. No An empirical formula n _D 25 Element Analysis% Calculated Found 104 ε ,, Η, ΛΝ.ο, 1,4428 P 44.90 44.71 N. 4.02 3.81 N 3.49 3.45 105 caws 1,4457 P 43.17 43.06 N. 3.86 3.68 N 3,36 3,34

In a manner similar to Example 39, the acids according to the invention were prepared as further pyridinedicarboxylic acid was obtained in Table 16.

Table 16

Etc. Compound Source No. Material

106 2- (difluoromethyl) -4- (1-methylpropyl) -6- (tri-trans. 26 fluoromethyl) -3,5-pyridinedicarboxylic acid

107 2- (difluoromethyl) -4- (2,2-dimethyl-propyl) -6- (tri-trans. 27 fluoromethyl) -3,5-pyridinedicarboxylic acid

108 2- (Difluoromethyl) -4-cyclopropyl-6- (trifluoro-ex. 17 methyl) -3,5-pyridinedicarboxylic acid

Etc. Empirical M.P. No formula ° C 106 c ₁₃ h ₁₂ f ₅ no ₄ 222-225,5 107 c ₁₄ h „f ₅ no ₄ 247-249 108 w, n, o ₄ 260-264 (dec)

% Analysis Element Calculated Found P 45.76 45.71 N. 3.54 3.71 N 4.10 3.88 P 47.16 47.33 N. 4.03 3.97 N 3.94 3.94 P 44,32 44,22 N. 2.48 2.52 N 4.31 4.26

In a manner similar to the procedure of Example 69, other pyridine dicarboxylates according to the present invention are prepared, except that the reactions are carried out at room temperature. As indicated above with respect to Table 10, considering the substituted starting material and the reaction conditions suitable for the reagent used, further examples can be provided, as shown in Table 17.

Table 17

Etc. No Source material Reagent Solvent Product Conditions 109 43 K ₂ CO ₃ - DMF CH ₃ CH ₂ CH ₂ 1 dipropyl 2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate 110 107 k ₂ CO ₃ - CH 1 _h DMF dimethyl 2- (difluoromethyl) -4-2,2 dimethylpropyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate 111 106 to _{2 of 3} - DMF dimethyl 2- (difluoromethyl) -4- / 1-

CH ₃ 1 methylpropyl (-6-) (trifluoromethyl) - 3,5-pyridinedicarboxylate etc. 41 K ₂ CO ₃ - H-C = C-CH ₂ Br DMF dipropargyl 2- (difluoromethyl) -4-isopropyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate etc. 39 to ₂ co ₃ - H-C = C-CH ₂ Br DMF dipropargyl 2- (difluoromethyl) -4p-propyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate etc. 108 to ₂ with ₃ - CH ₃ 1 DMF dimethyl-4-cyclopropyl-2- (difluoromethyl) -6- (trifluoromethyl) -3,5-pyridinedicarboxylate etc. 108 К ₂ СО ₃ НС-ССН ₂ Br DMF dipropargyl 4-cyclopropyl-2 (difluoromethyl) -6- (trifluoromethyl) -3,5-pyridinedicarboxylate etc. 37 to ₂ with ₃ - CH ₃ 1 DMF 3-ethyl 5-methyl 4-cyclohexyl-2 (trifluoromethyl) -6- (difluoro)

methyl / -3,5-pyridinedicarboxylate

An empirical formula n _D 25 M.P. ° C Analysis% Element Calculated Found c _{] 9} h ₂₄ FjNO ₄ 1,4473 P 53.65 53.68 N. 5.69 5.65 N 3.29 3.26 c ₁₆ n, lmo ₄ 77,5-77,8 P 50.13 50.06 N. 4.73 4,49 N 3.65 3.61 ς, Η, ΛΝο, 1,4515 P 48.79 48.90 N. 4.37 4.39 N 3.79 3.77 C 'H _I4 F, NO ₄ 1,4698 P 53.61 53.60 N. 3.50 3.52 N 3.47 3,43 ^C , »H ₁₄ F ₅ NO ₄ 1,4713 P 53.61 53.74 N. 3.50 3.54 N 3.47 3,44 77-79 P 47.60 47.64 N. 3.42 3,44 N 3.97 3.92 C _lg H ₁₂ F _jN1 O ₄ 1,4783 P 53.87 53.46 N. 3.01 3.27 N 3.49 3.45 ς, ιν, ΝΑ 1,4654 P 52.81 52.73 N. 4.92 4.93 N 3.42 3,39

Example 117. Preparation of 3-methyl 5-propargyl 2- (difluoromethyl) -4-n-propyl-6 (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 5.06 g (0.0125 mol) of the product of Example 113, 1.24 g (0.0188 mol) of 85% potassium hydroxide, 65 ml of ethanol and 50 ml of water was stirred for 48 h and then extracted with ether. The aqueous layer was acidified with 30 ml of concentrated hydrochloric acid. The oily residue was extracted into 100 ml of ether. The ether extract was dried (MgSO ₄ ) and concentrated to give 3.99 g of a solid, m.p. 91-94 ° C.

Part / 2.14 g, 0.0058 mol / of the above solid, 0.80 g / 0.0058 mol / potassium 15 carbonate, 0.99 g / 0.007 mol / methyl iodide and 60 ml DMF were stirred for 72 h and poured into 200 ml of water. The oily residue was extracted twice with 100 ml of ether.

The combined ether extracts were dried over magnesium sulfate and concentrated. The precipitate was distilled to give 1.21 g (55.3%) of the desired product as an oil, n _D 25 5 1.4556.

Calculated for C ₁₆ H ₁₄ F ₅ NO ₄ : C 50.67; H, 3.72; N, 3.67. Found: C, 50.57; H, 3.73; N, 3.67.

In a manner similar to that in Examples 10 28, 29 and 30, other 2- (difluoromethyl) -6- (trifluoromethyl) -3,5-pyridinedicarboxylic acid 5-monoesters according to the present invention are obtained.

Taking into account the substituted starting material and the reaction conditions suitable for the reagent used, further examples can be obtained, as shown in Table 18.

Table 18

Etc. Source Solvent- Product No Material Condition

118 etc. 112 ethanol-water 2- (difluoromethyl) -4-isopropyl-6- (tri) room temp- fluoromethyl / -3,5-pyridinedicarboxyl nature acid 5-propargyl ester 119 etc. 27 ethanol-water 2- (difluoromethyl) -4- (2,2-dimethylpropyl) -6- room temp- (trifluoromethyl) -3,5-pyridinedicarboxyl nature acid 5-ethyl ester 120 avenue 26 ethanol-water 2- (difluoromethyl) -4- (1-methylpropyl) -6- (tri) room temp- fluoromethyl / -3,5-pyridinedicarboxyl nature acid 5-ethyl ester 121 etc. 72 ethanol-water 2- (difluoromethyl) -4-isopropyl-6- (trifluoro)

methyl / -3,5-pyridinedicarboxylic acid

5-methyl ester

Etc. No An empirical formula M.P. ° C Element Analysis% Calculated Found 118 c ₁₅ h ₁₂ f ₅ no ₄ 89-92 P 49.32 49.03 N. 3.31 3,35 N 3.83 3.79 119 herd. 110-111,5 P 50.13 50.04 N. 4.73 4.78 N 3.65 3.60 120 with ,, n, lmo ₄ 83,5-85,5 P 48.79 48.86 N. 4.37 4.38 N 3.79 3.77

121 c ₁₃ h ₁₂ f ₃ no ₄ 114-116 C H 45.76 3.54 45.86 3.57 N 4.10 4.10

In a manner similar to the procedure of Example 69, other pyridine dicarboxylates of the present invention are obtained from mono acids. Given the substituted output material and reaction conditions suitable for the reagent used, further examples are obtained as indicated in Table 19. Table 19 10 Etc. No Source Reagent material Terms Solvent Product 122 77 K ₂ CO ₃ Ave. DMF, room HC »CCH ₂ Br 5-Methyl 3-propargyl 2- (dimethurafluoromethyl) -4-p-propyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate 123 ex 120 K ₂ CO ₃ - CH ₃ 1 DMF, room temperature 3-ethyl 5-methyl 6- (difluoromethyl) -4- (1-methylpropyl) -2- (trifluoromethyl) 3,5-pyridinedicarboxylate 124 pr. 119 K ₂ CO ₃ CH ₃ 1 DMF, room temperature 3-ethyl 5-methyl 6- (difluoromethyl) -4- (2,2-dimethylpropyl) -2- (trifluoromethyl) -3,5-pyridinedicarboxylate 125 118 K ₂ CO ₃ CH ₃ 1 DMF, room temperature 3-methyl 5-propargyl 3- (difluoromethyl) -4-isopropyl-6 (trifluoromethyl) -3,5-pyridinecarboxylate Etc. No An empirical formula n _D 25 % Analysis Item Calculated Found 122 c ₁₆ h _I4 f ₃ no ₄ 1,4582 C, 50.67; 50.54 H, 3.72; 3.79 N, 3.69 123 ε.ΛΛΝΑ 1.4500 C, 50.19, 49.90 H 4.73 4.78 N, 3.65 3.59 124 c „h ₂₀ f ₃ no ₄ 1,4538 C, 51.39; 51.34 H 5.07 5.07 N, 3.53 125 c ₁₆ h ₁₄ f ₃ no ₄ 1,4589 C, 50.67; 50.47 H 3.72 3.78 N, 3.69

Example 126. Preparation of Diethyl 2- (difluoromethyl) -4- (4-pyridyl) -6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

In a manner similar to the procedure of Example 13, the product of Example ss of Table 3 reacted with 1,8-diaza-bicyclo-15.4.01-undec-5en to give the desired product as a solid, m.p. 43-45 ° C.

Calcd for C ₁₈ H ₁₃ F ₅ M ₂ O ₄ : C 51.68; H, 3.61; N, 6.70; Found: C, 51.51; H, 3.63; N, 6.66.

Example 127. Preparation of 3-ethyl 5methyl 6- (difluoromethyl) -4- (2-oxyranyl) -2 (trifluoromethyl) -3,5-pyridinedicarboxylate.

A stirred mixture of 14.0 g (0.039 mol) of the product of Example 99, 105 ml of ethanol, 70 ml (0.60 mol) of 30% hydrogen peroxide and 2.9 g (0.033 mol) of sodium bicarbonate was heated at 70 ° C. The reaction mixture was cooled and concentrated in vacuo to approximately 30 ml for 3 hours and then extracted with 75 ml of methylene chloride. The methylene chloride solution was washed with 300 ml of water. The aqueous layer was extracted twice with 75 ml of methylene chloride. The combined methylene chloride extracts were dried over magnesium sulfate and concentrated. The precipitate was purified by HPLC using 8% ethyl / acetate / cyclohexane as eluent to give a yellow solid, which after recrystallization from hexane / ether gave 2.32 g of the desired product as a white solid, m.p. 57.5-59®C.

Calculated for C ₍₄ H ₁₂ P ₃ MO ₃ : C 45.54; H 3.28; N 3.79; Found: C 45.63; H 3.28; N 3.77.

Example 128. Preparation of 3-ethyl 5methyl 4- (1,2-dibromoethyl) -6-2- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A solution of 3.0 g (0.084 mol) of the product of Example 99. 1.49 g (0.091 mol) of bromine in 30 ml of carbon tetrachloride was stirred for 3 days and concentrated. The precipitate was distilled at 0.1 torus / vessel temperature 140-150®C to give 3.45 g (80%) of the desired product as an oil, n _D 25 1.4950.

Calcd for C ₁₄ H ₁₅ Br ₂ P ₅ IR ₄ : C 32.77; H, 2.36; N, 2.73; Found: C, 33.00; H, 2.39; N, 2.93.

Example 129. Preparation of 3-ethyl 5methyl 4- (1-bromoethyl) -6- (difluoromethyl) -2 (trifluoromethyl) -3,5-pyridinedicarboxylate.

To a stirred mixture of 0.49 g (0.012 mol) of 60% sodium hydride in an oil dispersion and 4 ml of anhydrous THF was added 10 ml of methanol under nitrogen. The reaction mixture was cooled with an ice bath to 5 ° C and then treated slowly with a solution of 3.0 g (0.0058 mol) of the product of Example-128 in 2 ml of anhydrous THF while maintaining the temperature of the reaction mixture below 15®C. The mixture was stirred at 0 ° C for 2 h and poured into 180 ml of 1% hydrochloric acid, then extracted three times with 50 ml of methylene chloride. The combined methylene chloride extracts were dried over magnesium sulfate and concentrated. The precipitate was purified by radially accelerated pre-TLC using 10% ethyl acetate / cyclohexane as eluent to give 0.85 g (33%) of the desired product as a yellow oil, n _D 25 1.4734.

Calcd for C ₁₄ H _n VgR ₃ MO _4: C, 38.91; H, 2.57; N, 3.29; Found: C, 39.00; H, 2.64; N, 3.37.

Example 130. Preparation of 3-ethyl 5methyl 6- (difluoromethyl) -4-methyl-sulfonylmethyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate.

To cold (15 ° C) stirred solution of 0.5 g (0.0012 mol) of the product of Example 101 in 20 ml of methylene chloride was added 0.55 g of m-chloroperbenzoic acid in portions. The reaction mixture was stirred at ambient temperature for 16 h, poured into 150 ml of 1% aqueous sodium hydroxide. The methylene chloride layer was separated, washed with 100 ml of water, dried over magnesium sulfate and concentrated in vacuo to give a white solid. Recrystallization from ether / hexane gave 0.46 g of the desired product as a white solid, m.p. 110.5-111.5®C.

Calculated for C ₁₄ H ₁₄ P ₃ IC _{10 6} 5: C 40.10; H, 3.37; N, 3.34. Found: C, 39.97; H, 3.37; N, 3.33.

Example 131. Preparation of dimethyl 2 (difluoromethyl) -4-methylthiomethyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

A mixture of 25.0 g (0.062 mol) of the product of Example 25, 100 ml of 10% aqueous sodium hydroxide, 40 ml of ethanol and 150 ml of water was refluxed for 48 h and concentrated to approximately 150 ml. The precipitated solution was diluted with 1 liter of water and acidified to pH 1-2 with concentrated hydrochloric acid. The aqueous mixture was extracted three times with 300 ml of ether. The combined ether extracts were dried over magnesium sulfate and concentrated to give 11.7 g (55%) of a solid, m.p. 209-210 ° C.

A mixture of 7.08 g (0.0226 mol) of the above solid, 3.0 ml / 0.0475 mol / methyl iodide, 3.45 g / 0.0256 mol / potassium carbonate and 35 ml DMF was stirred for 16 h. The reaction mixture was poured into 300 ml of 1% hydrochloric acid and extracted with 100 ml of methylene chloride. The methylene chloride solution was washed sequentially with 200 ml of water and 200 ml of 1% sodium bicarbonate, dried over magnesium sulfate and concentrated. The precipitate was distilled off at 0.15 tsp (vessel temperature 120-125 ° C) to give a white solid which was recrystallized from ether / hexane to give 3.0 g (36%) of the desired product, m .t. 50.551.5 ° C.

Calculated for C _n H _n F ₃ NO ₄ S: C, 41.83; H, 3.24; N, 3.75; Found: C, 41.84; H, 3.25; N

3.75.

Example 132. Preparation of dimethyl 2 (difluoromethyl) 4-iodomethyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

Mixture of 10.43 g (0.033 moles) of solid / mp. 209-210 ° C), described in Example 131, 8.2 ml (0.132 mol / methyl iodide, 20.2 g / 0.146 mol / potassium carbonate), and 45 ml DMF was stirred at ambient temperature for 5 days. The reaction mixture was poured into 550 ml of 1% aqueous hydrochloric acid and extracted three times with 100 ml of methylene chloride. The combined extracts were washed sequentially with 1% hydrochloric acid, 1% sodium bicarbonate and 10% sodium chloride, dried over magnesium sulfate and concentrated. The precipitate was purified by HPLC using 15% ethyl acetate / cyclohexane as eluent to give a yellow oil which crystallized on standing. Recrystallization twice from ether / hexane gave 2.27 g (15%) of the desired product as a white solid, m.p. 7879 ° C.

Calculated for C _I2 H, F _S INO _4: C, 31.81; H, 2.00; N, 3.09; Found: C, 31.95; H, 1.90; N, 3.07.

Example 133. Preparation of 3-ethyl 5methyl 2- (difluoromethyl) -4-methylthiomethyl-6 (trifluoromethyl) -3,5-pyridinecarboxylate.

A mixture of 2.8 g (0.0077 moles) of the product of Example 131, 3.7 g (0.0092 moles) of 10% sodium hydroxide, 3 ml of water and 20 ml of ethanol was stirred at ambient temperature for an hour. 5 1/2 hours and concentrate. The precipitate was dissolved in 150 ml of water and extracted twice with 50 ml of methylene chloride. The aqueous layer was acidified to pH 1-2 with concentrated hydrochloric acid and extracted three times with methylene chloride. The combined methylene chloride extracts were dried over magnesium sulfate and concentrated to give 2.6 g of a solid.

A mixture of 2.47 g (0.0066 mol) of the above solid, 1.28 g (0.0082 mol / ethyl iodide, 0.71 g / 0.051 mol / potassium carbonate and 20 ml of DMF was stirred for 48 h. and poured into 200 ml of 1% hydrochloric acid. The mixture was extracted three times with 50 ml of methylene chloride. The combined methylene chloride extracts were washed sequentially with 150 ml of 1% sodium bicarbonate, dried over magnesium sulfate and concentrated. The precipitate was distilled at 0.3 t. The distillate (obtained at a vessel temperature of 120-130 ° C) was further purified by radially accelerated pre-TLC using 10% ethylene acetate / cyclohexane to give an oil. Distillation of this oil at 0.15 torus, carried out at a vessel temperature of 125-130 ° C, yields the desired product as a pale yellow oil, n _D 25 1.4750.

Calculated for C ₁₄ H ₁₄ F ₃ NO ₄ S: C 43.41; H, 3.64; N, 3.62; Found: C, 43.42; H, 3.65; N, 3.62.

Example 134. Preparation of 3-ethyl 5methyl 6- (difluoromethyl) -4-methyl-2 (trifluoromethyl) -3,5-pyridinedicarboxylate.

This product was isolated as a by-product in the preparation of the product of Example 101. The crude material (intermediate) was purified by HPLC as indicated in Example 101. After removal of the product of Example 101, the last fraction yielded 1.42 g of a yellow oil. which was distilled at 0.5 torus / vessel temperature 125-135 ° C to give 1.35 g of the desired product, n _D 25 1.4483.

Calculated for C ₁₃ H _{) 2} F ₅ NO ₄ : C 45.76; H, 3.54; N, 4.10; Found: C, 45.76; H, 3.52; N, 4.08.

Example 135. Preparation of 13-Carbomethoxy-5-carboethoxy-2- (difluoromethyl) -6 (trifluoromethyl) -4-pyridylmethyl-dimethylsulfonium tetrafluoroborate.

To a solution of 19.9 g (0.0513 mol) of the product of Example 101 in 150 ml of acetonitrile was added under nitrogen 10.0 g (0.051 mol) of silver tetrafluoroborate, followed immediately by

4.6 ml / 0.075 mol / methyl iodide. The reaction mixture was stirred at ambient temperature for 16 h, then kept at 45 ° C for 24 h. The gray precipitate was filtered off. The filtrate was concentrated to a pale brown oil which crystallized on standing. Recrystallization from ether tetrahydrofuran afforded 21.6 g (86% yield) of the desired product as a white solid, m.p.

119.5-121 °.

Calculated for C ₁₅ H ₁₇ BF ₉ NO ₄ S: C 36.83; H, 3.50; N, 2.86; Found: C, 36.86; H, 3.46; N

2.76.

Example 136. Preparation of 5-ethyl-methyl 2 - (difluoromethyl) -4 - [N, N-dimethylaminomethyl] -6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

To a stirred solution of 3.0 g (0.0061 moles) of the product of Example 135 in 15 ml Ν, dimethylformamide was added under nitrogen 1.4 g (0.0093 moles / sodium iodide). The reaction mixture was stirred at 25 ° C for 1/2 hour and then treated with 2.3 g (0.0091 mol) of 18% dimethylamine in ether. After stirring at ambient temperature for 1/2 hour, the reaction mixture was poured into a mixture of 500 ml of water and 100 ml of saturated sodium chloride solution. The organic portion was extracted into ether (4 x 75 mL). The ether extracts were combined and washed with 200 ml of 10% sodium chloride solution, dried over magnesium sulfate and concentrated. The precipitate was purified by HPLC using 5% ethyl acetate in cyclohexane as eluent. The desired fraction was concentrated. The precipitate was distilled at 0.1 tsp / vessel temperature 120-130 ° C to give 1.98 g / 84% yield / aqueous white oil, n _D 25 1.4518.

Calculated for Ο _{) 3} Η ₁₇ Ρ ₅ Ν ₂ Ο ₄ : C 46.88; H, 4.46; N, 7.29; Found: C, 46.70; H, 4.45; N, 7.23.

Example 137. Preparation of 5-ethyl-methyl 2 - (difluoromethyl) -4- (N-ethyl-N-methylaminomethyl) -6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

To a stirred solution of 4.0 g (0.0081 mol) of the product of Example 135 in 25 ml Ν dimethylformamide cooled to 5 ° C with an ice bath was added 1.84 g (0.012 mol) of sodium iodide. The reaction mixture was stirred at 0-5 ° C for 1 h, then allowed to warm to room / ambient / temperature. N-ethyl-N-methylamine (1.05 g, 0.017 mol) was added to the reaction mixture and the mixture was stirred for 2 h at ambient temperature, then poured into a mixture of 300 ml water and 100 ml saturated. sodium chloride solution. The organic portion was extracted into ether (4 x 100 ml) and the combined ether extracts washed with 200 ml of 10% sodium chloride solution, dried over magnesium sulfate and concentrated. The precipitated oil was purified by radially accelerated pre-TLC, followed by distillation at 0.15 t (vessel temperature 120-130 ° C) to give 2.49 g (77% yield) of the desired product as a yellow oil, n _D 25 1.4534.

Calculated for C ₁₆ H ₁₉ F ₂ N ₂ O ₄ : C 48.24; H, 4.81; N, 7.03; Found: C, 48.10; H, 4.83; N, 6.99.

Compounds of the present invention may be prepared from corresponding compounds wherein the R or R ₂ group contains one more fluorine atom than the product compound. The scheme discussed above includes one or more sodium borohydride reduction alternatives to the corresponding 1,2-dihydropyridine, followed by dehydrofluorination in the presence of anhydrous organic base such as DBU or 2,6-lutidine. This exemplary reaction can be schematically represented as follows:

Gf CFj Ry CFj CF, CFjH CFj '^ CFHj _> CF, 'CHj or K: CFj ~ CFjH CFHj CHj Ry CFj ** CFj ^ CFj ^ CFj

This method is not limited to the situation where R _t or R ₂ is CF ₃ . The reaction proceeds in the same way, for example, when R ₂ is CF ₂ H, CFH ₂ or alkyl is R, it must be dehydrofluorinated. The following Examples 138 and 139 illustrate the preparation of compounds according to the invention, in which Rj and R ₂ is at least one group CF _Jt and the other is selected from the CFH ₂ and CH _3.

Example 138. Preparation of dimethyl 2 (fluoromethyl) -4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

To a solution of 50.3 g (0.136 mol) of the product of Example 14 in 200 ml of DMF was added 21.3 g (0.568 mol) of sodium borohydride. The reaction mixture becomes exothermic and the temperature of the reaction mixture rises to 65 ° C, then drops to 40 ° C with stirring for 40 minutes. 15 ml of water are added to the reaction mixture. The mixture of the exothermic reaction was cooled to 40 ° C with an ice-water bath. The cooling bath was removed and the reaction mixture was stirred for 20 min before being poured into 1 liter of water. The organic portion was extracted into 500 ml of methylene chloride. The methylene chloride extract was dried over magnesium sulfate and concentrated. The precipitated oil (44.5 g) was purified by HPLC using 5% ethyl acetate in cyclohexane as eluent. The first

2.8 l of eluate yielded 7.6 g of oil containing 56% of the desired product, 22% of starting material and 22% of undetermined material. The second 2.5 l of the eluate afforded 24.6 g of an oil containing a mixture of dimethyl 2- (difluoromethyl) -1,2-dihydro-4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate (E) and dimethyl 6- (difluoromethyl) -1,2-dihydro-4-isobutyl-2- (trifluoromethyl) -3,5-pyridinedicarboxylate (F) and other undetermined products. This oil was crystallized from ether-hexane to give 7.4 g (15%) of a solid, m.p. 82-83 ° C, which is a 4.6: 1 mixture of the above (E) and (F). The mother liquor was concentrated to an oil (15.6 g) containing (E), (F) and other undetermined products. The above oil solution, 9.0 g / 0.0568 mol / DBU and 100 ml of ether were stirred for 18 h and washed with 100 ml of 3N hydrochloric acid. The ether solution was dried over magnesium sulfate and concentrated. The precipitated oil (14.5 g) was purified by HPLC using 5% ethyl acetate in cyclohexane as eluent. The first 2.0 l of eluate gave 8.8 g (19%) of the desired product as an oil, n _D 25 1.4567.

Calculated for C ₁₃ H ₁₇ F ₄ NO ₄ : C 51.28, H 4.88; N, 3.99. Found: C, 51.39; H, 4.76; N, 3.85.

Example 139. Preparation of dimethyl 4-isobutyl-2-methyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

To a solution of 8.8 g (0.025 mol) of the product of Example 138 in 100 ml of DMF was added 6.0 g (0.16 mol) of sodium borohydride. After stirring for 10 min, the reaction mixture was heated to 65 ° C for 20 min and maintained at 65 ° C for 1 1/2 hours before being poured into 500 ml of water. The organic portion was extracted into 500 ml of methylene chloride. The methylene chloride extract was dried over magnesium sulfate and concentrated to give 9.9 g of an oil which was purified by HPLC using 10% ethyl acetate in cyclohexane as eluent. The first 2.1 liters of eluate gave an oil that could not be further determined. The second 1.5 l of the eluate gave 2.9 g of oil, which was stirred with 2.0 g of DBU and 50 ml of ether for 4 hours. The ether solution was washed successively with 60 ml of 3N hydrochloric acid and 60 ml of water, dried on magnesium sulfate and concentrated. The precipitated 2.2 g of oil was purified by radially accelerated preparative TLC using 5% ethyl acetate in cyclohexane as eluent. The first fraction yielded oil (1.2 g), which was distilled at 1 torus (vessel temperature 140 ° C) to give 1.1 g (13% yield) of the desired product as an oil, n _by 25 1.4606 .

Calculated are C ₁₃ H _lg F ₃ NO _4: C, 54.05; H, 5.44; N, 4.20; Found: C, 54.06; H, 5.45; N

4.20.

Example 140 Ethyl 6- (difluoromethyl) -

5-11 (1-methyl ethyl) thiocarbonyl I -4-isobutyl 2- (trifluoromethyl) -3,5-pyridinedicarboxylate.

32 g (0.08 m) of the product of Example 16 and 150 ml of ethanol are placed in a one-liter flask. In a separate flask was stirred 15.84 g / 0.24 m / potassium hydroxide / 85 ° / _a / and 75 ml of water. The aqueous solution was added to the organic layer and stirring was continued for 48 h at room temperature. The reaction mixture was concentrated, diluted with water and extracted with ethyl ether. The aqueous layer was acidified with concentrated HCl, cooled and extracted with ethyl ether. The resulting layer was dried over anhydrous MgSO ₄ , filtered, concentrated and dried in vacuo to give 24.5 g (82.93%) of acid. The acid was stirred with 150-200 ml of thionyl chloride and refluxed for 24 hours. The reaction mixture was concentrated to give acid chloride in 84.97% yield.

Place in a 250 ml round bottom flask

6.25 g (0.016 m) of the acid chloride, 1.52 g (0.02 m) of propanethiol and 75-100 ml of tetrahydrofuran. 2.44 g / 0.02 m / potassium tert-butylate was added to the magnetically stirred mixture. The reaction mixture began to release heat and stirred for 30 minutes. The mixture was then poured onto ice water and extracted with methylene chloride. The organic portions were dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was distilled to give 1.95 g (28.55%), n _D 25 - 1.4704.

Calculated for C 22 H 27 N 4 S 4: C 50.58; H, 5.19; N, 5.19; Found C, 50.73; H, 5.22; N, 3.24; S, 7.42.

Example 141 B. 6-Diethyl 2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarbothioate.

70.91 g (0.1784 moles) of the product of Example 16 and 300 ml of methanol are placed in a one-liter flask. 93.73 g (1.42 moles) of 85% potassium hydroxide and 150 ml of water are combined in a separate flask. The aqueous and organic layers were combined and allowed to reflux for 48 hours. The reaction mixture was concentrated, diluted with water and extracted with ethyl ether. The ether layer is discarded. The aqueous layer was acidified with concentrated HCl and the oily residue was extracted with ether. The extract is dried over anhydrous magnesium sulfate, filtered and concentrated to give a viscous liquid (which subsequently crystallizes) in an amount of

53.7 g (88-22%). 250-300 ml of thionyl chloride are added to this acid. The reaction mixture was heated to reflux for 24 h and concentrated to give

51.7 g (86.93%) of acid chloride.

5.66 g (0.0149 moles) of acid chloride, 75-100 ml of anhydrous tetrahydrofuran and 5.57 g (0.0898 mol / ethanethiol) were placed in a 250 ml flask. 3.34 g (0.0298 mol / potassium tert-butylate) was added to the magnetically stirred mixture. The mixture recovered heat and stirred for 45 minutes. The reaction mixture was poured onto ice water and stirred. The organic portions were extracted twice with methylene chloride, washed with ice water, dried over anhydrous magnesium sulfate, concentrated and distilled. The mixture was chromatographed using 3% ethyl acetate and cyclohexane and concentrated to give 1.1 g (17.21%) of oil, n _D 25 - 1.5256.

Calculated for C ₁₇ H _2o F _J N ₁ 0 ₂ S _2: C, 47,54; H, 4.49; N, 3.26; S 14.93, Found C 47.40; H, 4.88; N, 3.21; S, 14.77.

Using procedures similar to those of Examples 140 and 141, other thioester and dithioester compounds are obtained. These compounds are shown in the following Table 20.

Table 20

Etc. Compound

142 Ethyl 6- (difluoromethyl) -4-propyl 5-1 (propylthio) carbonyl-2- (trifluoromethyl) -3-pyridinedicarboxylate

143 Ethyl 6- (difluoromethyl) -511 (1-methylethyl) thiocarbonyl14-propyl-2- (trifluoromethyl) -3-pyridinecarboxylate

144 Ethyl 6- (difluoromethyl) -5-

II (1,1-dimethylethyl) thiocarbonyl14-propyl-2- (trifluoromethyl) -3-

n _D 25 % Analysis Calculated Found 1,4754 P 49.39 48.93 N. 4.88 4,64 N 3,39 3,38 S 7.76 7.78 1,4723 P 49.39 49.48 n 4.88 4.93 N 3,39 3,34 S 7.76 7.85 1,4718 p 50.58 50.43 n 5.19 5,21 N 3.28 3.23

pyridinecarboxylate

145 Methyl-6- (difluoromethyl) -5- 1,4788 P 48,12 48.39 I (ethylthio) carbonyl I -4- (2-methyl) N. 4,54 4.77 propyl / -2- (trifluoromethyl) -3- N 3.51 3,32 pyridinecarboxylate S 8.03 7.73 146 SJS-dimethyl 2- (difluoromethyl) - 1,4788 P 44.88 45.44 4-isobutyl-6-trifluoromethyl-3,5- n -4.02 4.10 pyridinecarbothioate N 3.49 3.47 S 15.98 15,99 147 S.S-dimethyl 2,6-bis / trifluoro- mp p 42.96 43.22 methyl / -4-isobutyl-3,5- 63-66 ° n 3.60 3.79 pyridinedicarbothioate N 3,34 3.24 S 15,29 15.06 148 S, S-flHMeTmi 2,6-bis / trifluoro- mp p 41.48 41,30 methyl / -4- / propyl-3,5- 96-98 ° n 3.23 3.23 pyridinedicarbothioate N 3.46 3.46 - S 15,82 15,88 149 S.S.-diethyl 2,6-bis / trifluoro- mp p 44.34 44,29 methyl / -4-propyl-3,5- 66-69 n 3.95 3.99 pyridinedicarbothioate N 3.23 3.22 S 14,79 14,87

Example 150 3-Ethyl 5-methyl 4-methyl-2isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

An amount of 52.7 g of ethyl 3-amino-4-methyl-2-pentenoate is obtained from 98 g of ether / 2-methylpropionyl / acetate using the procedure of Aberhart u Liv, JOC 1981, 3749. The enaminester has n _p 25 = 1 , 4914, bp 92 ° / 6 mm. The above enamine (20 g) was combined with 100 ml THF with 21.6 g methyl 2,2,2-trifluoroacetoacetate and 6 g acetaldehyde. With the addition of a few drops of piperidine, spontaneous isothermia up to 60 ° C was observed. The mixture was then heated with stirring to about 70 ° C (just under reflux) for 11/2 hours. Observed by &lt; 1 &gt; F NMR, the mixture was refluxed for 5 hours and then left at room temperature overnight. The mixture was separated from THF to give 46.1 g of crude product yield, 40 g of which was dehydrated using 25 ml of trifluoroacetic anhydride and about 100 ml of CH 2 Cl 2. Exotherm was observed at 40 ° C and the material was refluxed for about one hour, then separated to give crude product which was distilled (110 ° -160 ° C (0.15 mm)).

4.5 g of this crude intermediate (0.013 mol) was added to CH ₂ Cl ₂ and 3.4 g and 2,3 dichloro-5,6-dicyanobenzquinone (DDQ) added. The reaction is exothermic. The mixture was stirred for 3 h at room temperature. The GIC shows one main peak at the same retention time as the starting material. The product was washed with NaOH / NaHSO ₃ to reduce excess DDQ. the material was separated from the solvent, then distilled to give 3.5 g of the crude product, which was further purified by HPLC with 3% ethyl acetate, 97% cyclohexane to give a purified fraction, which was then distilled / bp - 140-150 ° C at 1.5 mm / to give the desired product, n _D 25 = 1,4557, 1 g yield.

Calculated for C _{| g} H ₂₄ F ₃ NO _4: C, 54.05; H, 5.44; N, 4.20; Found: C, 53.98; H, 5.48; N, 4.20.

Example 151. 3-Ethyl 5-methyl 2-ethyl-4-isobutyl-6- (trifluoromethyl) -3,5-pyridinedicarboxylate.

Stirred mixture of 18.0 g / 0.20 mol / isovaleric aldehyde, 30.8 g / 0.20 mol / methyltrifluoroacetoacetate, 28.6 g / 0.20 mol / ethyl 3-amino-2-pentenoate, 60 ml tetra44 hydrofuran and 3 drops of piperidine were heated and refluxed for 18 h. The cooled reaction mixture was concentrated and the precipitate partially crystallized upon standing at room temperature. The solids were filtered off from an 8.0 g sample, washed with hexane and recrystallized from tetrahydrofuran / hexane to give 1.72 g (22%) of a white solid, m.p. Mp 148-150 ° C.

A stirred mixture of 72 g (0.18 mol) of crude solid obtained as indicated above, 30 ml (0.21 mol) of trifluoroacetic anhydride and 150 ml of methylene chloride was heated and refluxed for 2 hours. the mixture was concentrated to give 88.0 g of oil. To a stirred solution of 43 g / 0.09 mol / oil in 200 ml of water-cooled methylene chloride was added in portions 17.5 g / 0.077 mol / 2,3dichloro-5,6-dicyano-1,4-benzoquinone . The reaction mixture was stirred for 1 h and filtered. The filtrate was washed twice with 200 ml of 20% sodium hydroxide solution. Then, with 200 ml of 1% hydrochloric acid, it was dried over magnesium sulfate, filtered and condensed to give 28.2 g of an oil. Purification by silica gel HPLC of 10 g of sample gave, after distillation, 3.07 g (26%), pale yellow oil, bp 105-110 ° C. n _D 25 1,4582.

Calculated for C ₁₇ H ₂₂ NF ₃ O ₄ : C 56.50; H, 6.14; N, 3.88; Found: C, 56.51; H, 6.17; N, 3.84.

Example 152. Methyl 2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -5-carbethoxy-3-pyridine-N-butylimidate.

A mixture of ethyl 3-butylurea-2- (difluoromethyl) -4-isobutyl-6- (trifluoromethyl) -5-pyridinecarboxylate, obtained in the same way as the product of Example 89, was heated under reflux for one year on reflux night. Excess thionyl chloride was removed and the precipitated oil was distilled at 140 ° C (0.5 mm) to give 4.7 g of pale yellow liquid (91% yield), n _D 25 1.4668.

Place 30 ml of absolute methanol in a flame-dried 100 ml round bottom flask. Saturated with nitrogen. 0.63 g / 0.0056 mol / potassium t-butylate was added and cooled to 0 ° C. A solution of the pale yellow liquid obtained above (2.5 g, 0.0056 moles) in anhydrous ether (20 ml) was then added, all at once through a two-tip needle. The mixture immediately turns white and cloudy. Stirred at room temperature overnight. The solvent was removed and the precipitate was extracted with ether. The ether layer was washed with water, dried (MgSO ₄ ) and concentrated to give 2.49 g of a pale yellow oil. It was purified by chromatography using 30% CH ₂ Cl ₂ in gasoline as eluent to give 1.8 g of a pale yellow oil / 72% yield / n _D 25 1.4546.

Other compounds of the present invention are prepared using the various techniques described in the preceding examples, sometimes in accordance with other preparation steps well known to those skilled in the art. These compounds are listed in the following Table A, together with some of their physical properties where possible. The following abbreviations are used in Table A to indicate different functional groups substituted on the pyridine ring:

Methyl

Et - ethyl

Wr - prop

Susg - cyclopropyl

1-aziridine

1,3-dithiol

-continued s

- <J s

Ex. No. Kt X X V Rj М.П. «Β» 1 » CFj CtOXJCHjCFj Cycpr CfOXJCHjCFj CHFj 44-46 154 CFj C (O) SPr CHjCHMej CfOJSPr CHFj 1.4971 1 » CFj CfOXJMe CH ^ HMej CfOXJ—. NHfCHjh CHFj H1-1I 156 CFj CfOXJMe CH «CHj CfOXJMe CHFj bp. 100-103 / 157 CFj C (O) OEt CH ₂ S (O) Me CfOXJMe CHFj 0.1 torr 73-76 15 « CFj CfOXJEt CHjSMe C (O) OH CHFj IM9 139 CFj CfOXJEt 2GGyuk) CfOXJEt CHF ₂ 38-40 160 CFj CfOXJEt 2SP »ok) CfOXJH CHFj 129.3-131 161 CFj CfOXJEt ifThioU) CfOXJMe CHFj 1.4991 162 CFj CfOXJEt CHjSEt CfOXJMe CHFj (.4744 163 CFj CfOXJEt CHMeSMe CfOXJMe CHFj 1.473 * 16 * CFj C (OK> & 2fThiole) CfOXJEt CHj 1.5071 166 CFj CfOXJEt CHj CfOXJMe CH, 1.4591 166 CFj CfOXJEt CHjCypor CfOXJEt CHFj bp. (25-130 / 0.5 tnn 167 CFj CfOXJMe CH2CHMe2 CfOJNHMe CHFJ IB3-IU 16 « CFj CfOXJEt CHjCHMej CfOJNHMe CHFj 10 * 110 16 « CFj CfOKJEl CHEtSMe CfOXJMe CHFj 1 4731 170 CFj CfOXJEt CMejSMe CfOXJMe CHFj 1.4848 171 CFj CfOXJEt CHjCHMei CfOXJEt CHj 1.4312 172 CFj CfOXJEt CHjCHMej CfOXJMe CHj 1.4593 173 CFj CfOXJMe CHjCHMej qojoEt CHj 1.4390 17 * CFj CfOXJEt CHMeOMe CfOXJMe CHFj 1.4473 173 CFj cioyoa CHjCHjCN aoyume CHFj «3-96.3 176 CFj C (Oi) OEt CHrlAxiridiae CfOXJMe CHFj 73-1 * 177 CFj CfOXJEt CHMej CfOXJEt CHj 1.45 » (71 CFj CfOXJEt CHMej CfOXJMe CHj 1.4601 17 « CFj CfOXJEt CHMeEl CfOXJEt CHj 1.4516 ISO CFj CfOXJEt CHMeEl CfOXJMe CHj 1450Y 111 CFj CfOXJEt CH «CHNMej CfOXJEt CHFj bp. 160- 1KV0.10-0.15 torr 1 * 2 CFj CfOXJEt CMe * CHNMej CfOXJEt CHFj b.p. 130 / 0.5 torr 113 CFj adjua CHtQOJH CfOXJMe CHFj «1-12 IM CFj CfOXJMe CHjCHfOMeh CfOXJMe CHFj 44-43 185 CFj CfORJEl CHjCfOlH crajoEt CHFj 53-55 116 CFj CfOXJEt CHMeCfOJOMe CfOXJMe CHFj 56.5-51 117 CFj CfOXJEt chjqoxjh CfOXJH CHFj 176-177 IM CFj CfOXJEt CHjMe CfOXJEt CKj 1.3020 119 CFj CfOlOMe CHjCHMej C (OHX% SuOH CHFj 1 437 » l «0 CFj CfOXJMe CHjPr CfOXJMe CHFj 1.4431 191 CFj CfOXJEt CHjCHMq CfOJSPr CHFj 1,472 »2 CFj ctoxjet CHjCHMej CfOjNHBu CHFj 69-71 193 CFj CfOXJEt CHjCHMej CfOJQCHj— Crepe CHFj 1.4531 19 * CFj CfOXJEt CHjCHMcj CfOJSMe CHFj 1.4759 195 cf> CfOXJEt CHMfl CfOJSMe CHFj 14808 196 CF, CfOXJEt CHMej CfOjSEt CHFj 14783 197 CFj CfOXJEt CHjCyepr CfOXJH CHFj 96-100 19 « CFj CfOXJMe CHjCjrcpr C (O) 0M « CHFj 1 * 623 199 CFj CfOXJEt CHjCycpr CfOJOMe CHFj 1.4595 200 CFj C (O) O € HjCN CHjCHMej CtOXJCHjCN CHFj 11-90'C. 20 ( CFj CfOXJEt CKjCHMeCFj CfOXJEt CHFj 30-32 202 CFj CfOXJH CHjCHMeCFj CfOXJH CHFj 205-207 203 CFj CfOXJMe CHjCHMeCFj CfOJOMe CHFj 61-70 20 * CFj CfOXJEt CHjCHMej C (NBuXn CHFj 1.4668 203 CFj CfOXJEt CHjCHMej CfNBuXJMe CHFj 1.4546 206 CFj CN CHjCHMej CN CHFj 39-41 207 CFj CfOlSMe CHjCw CfOJSMe CHFj KMJ 208 CFj CfOXJMe CH2Cyepr CfOJSMe CHFj 1.4925 20 » CFj CfOXJMe CHMeSMe CfOXJMe CHFj 59-62 210 CFj CfOXJMe CMejSMe CfOXJMe CHFj 56-69 211 CFj CfOXJMe CHMeSMe CfOXJEt CHFj 1.4730

Ex. No. R1 X R Y Rj М.П. 212 CFj C (O) OMe CMcjSMe C (O) OEt chf ₂ 1.4847 213 CFj C (O) OMe CHjCHMei C (O) OMe CFj 80.5-82.5 214 CFj C (O) OEt CHj C (O) OEt CHj 1.4552 215 CHj C (O) OEt CHjCHMej C (O) OEt chf ₂ 1.4745 216 CHF ₂ C (O) OEt CHj C (O) OEt CHj 1.4752 217 CFj C (O) OMe CH ₂ CH — CHC (O) OET C (O) OMe chf ₂ 1.4644 218 CFj C (0) OMe (cis) CHj C (O) OMe chf ₂ 37-40 219 CFj C (O) OMe CH ₂ C (O) NH ₂ C (O) OMe chf ₂ 160-163 220 CFj C (0) OMe CH ₂ C (O) OH C (O) OMe chf ₂ 156-157 221 CFj C (O) OMe CHjCN C (O) OMc chf ₂ 137-139 222 CFj C (O) OMe CH ₂ -24l, 3-di · C (O) OMe chf ₂ 103-106 223 CFj C (O) OMe thk> lane) CHjCiOlNHCMej— C (O) OMe chf ₂ 132-133 224 CFj C (O) OMe CHjOH CH ₂ C (O) NHCMe ₂ - C (O) OMe chf ₂ 136-137 225 CFj C (O) Me CH ₂ C1 CH ₂ C (O) SCHMe ₂ C (O) OMe chf ₂ 69-70 226 CFj C (0) OMe CH ₂ C (O) OEt C (O) OMe chf ₂ 81-82 227 CFj C (O) OMe CH ₂ C (O) NMe ₂ C (O) OMe chf ₂ 137-138.5 228 CFj C (O) OMe CH ₂ CHMeg C (O) SMe chf ₂ 36-40 229 CFj C (0) OMe sngsmeg CCOJSCHMej chf ₂ 1.4752 230 CFj C (O) SMe CH ₂ Pr C (O) SMe chf ₂ 68-71 231 CFj C (O) SMe CHMeg C (O) SMe chf ₂ 96-98 232 CFj C (O) SET CHMC2 C (O) SET chf ₂ 58-62 233 CFj C (O) OMe CH2CHMEG CCOXXZHMei chf ₂ 1.4467 234 CFj C (O) SET CH ₂ Pr C (O) SET chf ₂ 32-34 1.5420 235 CFj C (OX> Me sngsmeg C (O) SPr chf ₂ 1.4780 236 CFj C (O) SET CH2CHMEG C (O) SEl CFj 34-37 237 CFj C (O) OMe USSRG C (O) SMe chf ₂ 68-71 238 CFj C (O) OMe USSRG C (O) SET chf ₂ 51-53 239 ch ₂ f C (O) OMe sngsmeg C (O) OMe CHj 1.4909 240 241 CH ₂ F CHFj C (O) OMc C (O) OMe CH ₂ Me CH ₂ CH ₂ Meg C (O) OMe C (O) OMe CHj CHj т.4795 242 CFj C (O) OEt CFj C (O) OEt chf ₂ 1.4191 243 CFj C (O) OEt chf ₂ C (O) OEt CFj 50.5-52.5 244 CFj C (O) OEt CH ₂ SMe C (O) OMe CHj 1.4904 245 CFj C (O) OMe CH ₂ SMe C (O) OMe CHj 1.4951 246 CHjF C (O) OEt CH2CHMEG C (OX> Et CHj 1.4849

As indicated, the compounds of the present invention are effective as herbicides, especially as pre-used / pre-emergent necessities for their use / herbicides. Tables 20 and 21 summarize the results of experiments conducted to determine the activity of pre-used herbicidal compounds according to the invention.

The pre-use tests are performed as follows:

A good variety of high quality soil is placed in an aluminum pan and pressed from 0.95 to 1.27 cm from the top of the pan. A predetermined number of seeds or plant propagating material for different types of plants are placed on the soil surface. The soil needed to supplement the pan after sowing the seeds or placing the planting stock is measured. A known amount of active ingredient used with acetone as solvent is mixed gently with the soil and a herbicidal / soil mixture is used to cover the pan upwards. In Table 1 below, the amount of active ingredient is equal to the ratio of 11.2 kg / ha. After processing, the pans are left in a greenhouse where they are watered from below to have the necessary moisture for swelling and growth.

Approximately 10-14 days (usually 11 days) after treatment the plants are observed and the results recorded. In some cases an additional observation is made 2428 days (usually 25 days) after processing and these observations are indicated in the asterisk tables / * / in the column after the "example". Table 1 below summarizes such results. The herbicide ratio is obtained by means of a fixed scale based on the percentage of each plant species.

The ratios are defined as follows:

% retention Ratio 0 - 24 0 24 - 49 1 50 - 74 2 75-100 3

The plant species used for one set of experiments, the data for which is given in Table 20, are identified by letters in accordance with the following legend:

A Canadian ass donkey * Cirsium '(J

With Sissampelos pareira;

E Chenopodium album;

F Polygonum hydropiper Persicaria hydropopier;

G 'Cyperus esculentus;

H Healing herbs * - Briza media;

I * Sorgum halepense;

J Bromus;

K Echinochloa crus-galli;

* - Planted by planting arvense; material

In Arctium lappa Xanthium;

D Gramophone (Ipomoea purpurea);

Example No. k | / h A B c D E F o H I ] K Example No. kg / b A 8 c D E F 0 H 1 J K 4 11.2 3 1 1 3 3 3 0 3 I 3 3 24 11.2 3 0 3 3 3 1 J 0 3 3 4 · 11.2 3 0 3 3 3 3 0 3 1 3 3 34 11.2 0 0 0 0 0 0 0 0 0 0 0 7 11.2 2 2 3 3 2 0 3 0 3 3 71 11.2 3 0 3 3 3 3 0 3 I 3 3 Μ 1U 1 0 2 2 3 3 1 3 0 3 3 103 IU 1 0 2 3 3 3 0 2 0 3 3 And 114 I • o 2 3 3 2 0 3 0 3 3 100 IU 0 0 0 0 0 0 c 0 0 0 0 12 11.2 3 2 3 3 3 3 3 3 3 3 3 49 IU 3 3 3 3 3 3 3 3 3 3 31 114 0 0 0 0 0 0 0 0 0 0 0 10 72 IU 3 2 3 3 3 3 3 3 3 3 32 11.2 3 1 3 3 3 3 3 3 3 3 3 99 11.2 3 0 J 0 3 3 0 I 0 0 1 37 114 3 0 3 3 3 3 1 3 0 3 3 41 11.2 3 0 3 3 J 3 2 J 3 3 3 η 11.2 3 1 3 3 3 3 3 3 3 3 3 42 114 0 1 0 0 3 0 1 0 0 0 3 Μ 114 0 0 0 0 0 0 0 0 0 0 0 74 IU 3 0 3 3 3 3 0 3 0 3 3 21 11.2 0 0 0 0 0 0 0 0 0 0 0 74 IU __. 0 0 0 0 0 0 0 0 0 0 Μ 114 - 0 0 1 3 - 0 0 0 3 3 15 73 IU 3 1 3 3 3 3 1 3 0 3 J 11 11.2 - 0 0 0 0 0 0 0 0 0 1 91 IU 0 0 0 0 0 0 0 0 0 0 0 t IU 0 0 0 0 I 1 0 0 0 0 3 10 IU 3 0 2 3 3 3 2 3 1 J J 4 « 11.2 0 0 0 0 3 0 0 0 0 0 3 101 IU 3 3 3 3 3 3 3 3 | J 3 41 IU 3 1 3 3 3 3 1 3 1 J 3 29 11.2 3 3 3 3 3 3 3 3 3 3 3 43 IU 0 0 0 0 0 0 0 0 0 0 0 102 IU 0 2 0 3 3 0 0 0 1 1 Μ IU 0 0 0 0 0 - 0 0 0 0 0 134 11.2 3 1 3 3 3 3 3 3 3 3 3 η 11.2 J 0 1 3 2 - 0 3 3 3 3 20 IX IU 1 0 3 0 3 3 1 0 0 1 J 99 IU 0 0 0 0 3 * 0 0 0 0 3 124 IU 0 0 0 0 3 1 0 0 0 0 1 27 IU - 0 1 3 3 - 0 3 3 3 3 104 IU 1 0 3 3 3 3 1 3 0 3 3 99 IU - 1 3 3 3 - 3 3 3 3 3 127 114 0 0 3 3 3 3 1 3 0 3 3 99 * IU - 1 3 3 3 - 3 3 3 3 3 129 IU 3 2 3 3 3 3 1 3 J J 3 40 IU - 0 0 1 3 - 0 1 1 3 3 131 IU 3 3 3 3 3 3 3 3 3 3 3 91 IU - 0 0 0 0 - 0 0 0 0 1 25 109 IU 3 0 3 3 3 3 2 3 i 3 3 η IU - 3 3 3 3 - 3 3 3 3 3 133 11.2 3 3 3 3 3 3 3 3 3 3 3 92 · IU - 3 3 3 3 - 3 3 3 3 3 40 IU 3 2 3 3 3 3 3 3 3 3 J Μ IU - 0 0 0 0 0 0 0 0 1 1 79 IU 0 0 0 0 0 0 0 0 0 0 0 42 IU - 0 2 3 3 3 0 2 0 3 3 26 IU 3 0 3 3 3 3 2 3 3 3 3 90 IU - 0 1 2 1 I 0 0 0 3 3 27 IU I 0 2 2 3 3 0 I 0 3 3 14 IU - 1 3 3 3 3 2 3 3 3 3 30 123 IU 3 2 3 3 3 3 3 3 3 3 3 40 IU - 0 0 0 0 0 0 0 0 0 0 124 114 3 0 3 3 3 3 2 3 2 3 3 29 IU -. 0 0 1 1 1 0 3 0 2 3 119 IU 0 0 0 0 0 0 0 0 0 0 0 47 IU - 0 1 2 3 2 0 0 0 2 3 109 IU 0 0 0 0 0 0 0 0 0 3 3 44 and - 0 0 0 0 0 0 0 0 0 0 43 IU 0 0 0 0 0 0 0 0 0 0 0 44 IU - 0 2 3 3 3 0 3 3 3 3 107 IU 0 0 0 0 0 0 0 0 0 0 0 19 IU 3 2 3 3 3 3 3 3 3 3 3 35 110 there 3 0 3 2 3 3 2 3 3 3 3 44 IU 3 0 2 3 3 3 0 1 0 3 3 III there 3 1 3 3 3 3 3 J 3 3 3 31 IU 3 I 2 3 3 3 0 0 0 3 3 106 IU 0 0 0 0 0 0 0 0 0 0 0 93 IU J 2 3 3 3 3 3 3 3 3 3 120 11.2 0 0 0 0 0 0 0 0 0 0 0 14 IU 3 2 3 3 3 3 2 3 3 3 3 122 IU 3 1 J 3 3 3 3 3 3 3 J 21 IU 1 0 0 2 J 3 0 0 3 3 3 117 11.2 3 3 3 3 J 3 3 3 3 3 3 44 IU 3 0 3 3 3 3 1 3 2 3 3 114 IU 0 0 0 0 0 0 0 0 0 0 0 32 IU 0 0 0 0 0 0 0 0 0 0 1 40 113 IU 3 1 2 2 3 3 1 0 0 3 3 94 IU 3 3 3 3 3 3 3 3 3 3 3 121 11.2 0 0 0 0 1 0 0 0 0 0 0 94 · IU 3 3 3 3 3 3 3 J 3 3 3 129 114 3 1 3 3 3 3 3 3 3 3 3 37 IU 0 0 0 0 0 0 0 0 0 0 0 137 there 3 0 3 3 3 3 1 3 1 3 3 η 114 3 0 3 3 3 - 0 3 3 3 3 134 IU 3 2 3 3 3 3 1 3 3 3 3 47 IU 3 0 3 3 3 - 3 3 3 3 3 121 IU 0 0 0 0 1 0 0 0 0 0 0 97 IU 0 0 I 1 I 2 0 0 1 3 3 43 129 IU 3 1 3 3 3 3 3 3 3 3 3 20 IU J 0 3 2 3 - 0 3 I 3 3 137 IU 3 0 3 3 3 3 1 3 I 3 3 41 IU 0 0 0 0 0 - 0 0 0 0 0 IX IU 3 2 3 3 3 3 1 3 3 3 3 22 IU 0 0 1 2 3 MM 0 0 0 3 3 133 IU 1 0 0 0 0 0 1 0 0 0 3 79 IU 0 0 3 3 3 - 0 3 1 3 3 134 IU 3 3 3 3 3 3 3 J 3 3 3 14 IU 3 3 3 3 3 MM 3 3 3 3 3 139 IU 3 3 3 3 3 3 3 3 3 3 3 30 IU 0 0 0 0 0 - 0 0 0 0 0 are 140 IU 2 0 0 0 3 3 0 I 0 3 1 23 IU 0 0 0 2 3 - 0 0 0 3 3 141 IU 3 0 3 2 3 3 0 3 3 3 3 33 IU 1 0 0 0 2 - 0 0 0 0 3 142 IU 3 0 3 3 3 3 0 3 0 3 J 17 IU 3 2 3 3 3 2 3 3 3 3 143 IU 0 0 1 0 2 1 0 1 0 3 J 34 IU 1 1 0 1 0 - 0 0 0 | 3 144 IU 3 0 1 0 0 0 0 0 3 0 3 90 IU 0 0 3 3 3 - 0 0 0 2 3 > 43 IU 3 3 3 J 3 3 1 3 3 3 3 99 11.2 3 2 3 3 J - 3 3 3 3 3 S3 144 IU 3 J 3 3 3 3 3 3 3 3 3 59 · there 3 3 3 3 3 - 3 3 3 3 3 147 IU 3 3 3 3 3 3 3 3 3 J 3 33 IU 0 0 0 0 0 - 0 0 0 0 0 144 IU 3 3 3 3 3 3 3 3 3 3 3 49 IU 0 0 0 - 0 - 0 0 0 0 0 149 IU 0 0 0 0 3 3 0 0 0 3 3 43 IU 0 0 3 3 3 0 3 2 3 3 190 IU 3 3 3 3 3 3 3 3 3 3 3 91 IU 0 0 0 0 0 0 0 0 0 0 0 191 there N 3 3 33 3 3 3 3 3 3 3 44 IU 0 0 0 0 1 2 0 0 0 3 3 192 114 0 N 0 1 1 3 0 2 0 3 3 47 11.2 3 2 3 3 3 3 3 3 3 3 3 60 193 114 0 0 2 2 3 3 0 0 1 3 3 74 IU 0 0 0 0 0 0 0 0 0 0 0 194 IU 0 0 0 0 0 0 0 0 0 0 0 77 IU 0 0 0 1 0 0 0 0 0 0 0 133 IU 1 0 0 0 0 0 0 0 0 0 0 13 11 2 0 0 0 0 0 0 0 0 0 0 0 154 IU 0 3 0 1 1 1 0 0 0 0 1 42 IU 1 0 0 0 0 0 0 0 0 0 J 157 11.2 3 0 1 2 3 3 0 3 1 0 3 44 11.2 3 1 3 3 3 ) 0 3 3 3 3 131 IU 1 0 0 0 2 0 1 0 0 0 3 44 IU 0 0 1 0 0 0 0 0 0 1 1 63 199 11.2 0 1 3 3 3 3 0 0 1 3 3 49 IU 3 3 3 3 3 3 3 3 3 3 3 140 11.2 0 0 0 0 0 0 0 0 0 0 1 44 IU 3 1 3 3 3 3 3 3 3 3 3 141 IU 3 0 3 3 3 3 0 3 1 3 3 112 IU 0 0 3 2 3 3 1 0 0 3 3 162 IU 3 0 3 3 3 3 0 2 0 3 3 70 IU 0 0 1 3 3 - 0 2 0 3 3 143 114 3 1 3 3 3 3 3 3 3 3 3

Table 21

Example No. kf / h A B c D E F Mr H I J K IM 11.2 1 0 1 3 3 3 0 0 0 1 3 165 11.2 0 0 2 3 2 2 0 3 3 3 3 IM 11.2 3 3 3 3 3 3 3 3 - 3 3 167 11.2 1 2 2 2 3 3 0 1 0 3 3 161 11.2 3 N 3 3 3 3 1 2 1 3 3 169 11.2 3 1 3 3 3 3 1 3 0 3 3 170 11.2 3 1 3 3 3 3 1 3 3 3 3 171 11.2 3 2 3 3 3 3 1 3 3 3 3 and 11.2 3 3 3 3 3 3 3 3 3 3 3 173 11.2 3 2 3 3 3 3 3 3 3 3 3 174 11.2 3 0 3 3 3 3 0 3 1 3 3 17J IU 3 I 3 3 3 3 1 3 0 3 3 176 11.2 0 0 1 1 1 2 0 1 - 1 3 vn 11.2 3 1 3 3 3 3 0 3 - 3 3 171 11.2 3 0 3 3 3 3 1 3 3 3 3 179 11.2 3 0 2 2 3 3 0 2 3 3 3 1J 11.2 3 0 3 3 3 3 1 3 3 3 3 »1 11.2 0 0 0 0 0 1 0 0 0 1 3 112 11.2 0 0 2 0 0 0 0 0 0 3 2 163 11.2 0 0 0 0 0 0 0 0 - 0 0 IM 11.2 1 0 2 3 1 2 0 3 - 3 3 133 11.2 0 0 0 0 0 0 0 0 - 0 0 166 11.2 3 1 3 3 3 3 0 0 - 3 3 137 11.2 N 0 0 0 3 0 0 1 N 3 0 138 IU 3 N 3 3 3 3 3 3 3 3 3 189 11.2 N 0 0 0 3 2 0 0 N 0 3 190 IU 3 1 3 3 3 3 2 3 - 3 3 191 IU 0 0 2 0 0 3 0 0 - 3 3 192 11.2 1 1 0 0 1 1 0 0 N 1 3 193 11.2 0 3 2 3 3 3 0 1 3 3 3 194 11.2 3 3 3 3 3 3 3 3 3 3 3 195 11.2 3 3 3 3 3 3 3 3 3 3 3 196 11.2 3 3 3 3 3 3 1 3 0 3 3 197 11.2 N 0 0 0 0 0 0 0 - 0 0 198 11.2 3 3 3 3 3 3 3 3 N 3 3 199 IU 3 3 3 3 3 3 3 3 N 3 3 200 11.2 1 1 3 3 3 3 0 0 - 3 3 201 11.2 3 1 3 3 3 3 0 3 3 3 3 202 11.2 1 0 0 0 0 0 0 0 N 0 0 203 11.2 3 1 3 3 3 3 2 3 3 3 3 204 11.2 0 N 0 0 0 1 0 0 0 1 3 205 IU 0 N 0 1 1 3 0 2 0 3 3 206 11.2 3 N 2 1 1 3 1 0 0 0 0 207 IU 3 N 3 3 3 3 3 3 2 3 3 203 11.2 3 3 3 3 3 3 3 J 3 3 3 209 11.2 3 3 3 3 3 3 2 3 3 3 3

210 IU 3 3 3 3 3 3 2 3 2 3 3 211 IU 3 3 3 3 3 3 3 3 J J 3 212 IU 3 N 3 3 3 3 1 3 1 3 3 213 11.2 3 3 3 3 3 3 3 3 3 3 3 215 11.2 3 1 3 3 3 3 0 3 3 3 J 216 11.2 0 3 1 1 3 1 0 0 0 0 3 217 11.2 0 0 0 0 0 0 0 0 N 0 0 219 11.2 0 0 0 0 0 0 0 0 0 0 0 220 11.2 0 1 0 0 0 0 0 0 0 0 0 221 IU 0 0 0 0 2 1 0 0 0 0 3. 222 11.2 0 0 0 0 0 0 0 0 0 0 0 223 IU 0 0 0 0 0 0 0 0 0 0 0 224 11.2 0 0 0 0 0 0 0 0 0 0 0 225 11.2 N 0 0 0 0 0 0 0 0 0 2 226 IU N 0 0 0 0 0 0 0 0 0 0 227 11.2 N 0 0 0 0 0 0 1 0 0 0 233 IU 3 2 3 3 3 3 2 3 3 3 3 234 11.2 3 1 1 3 3 3 0 0 0 2 1 235 IU 3 1 3 3 3 3 0 0 3 3 J 236 IU 3 0 3 3 3 3 0 3 1 J 3 237 IU N 1 3 3 3 3 1 3 0 3 J 238 IU N 2 3 3 3 3 0 3 J 3 3 239 IU 1 1 3 3 3 3 2 3 3 3 3 240 11.2 0 0 0 0 3 2 0 0 | 0 3 241 11.2 3 1 3 3 3 3 3 3 3 3 3 242 11.2 2 1 3 3 3 3 0 3 1 3 3 243 IU 3 1 3 3 3 3 0 3 1 3 3 244 11.2 3 3 3 3 3 3 3 3 1 3 3 245 IU N 0 3 3 3 3 3 3 3 3 3 244 11.2 N 3 3 3 3 3 2 0 0 3 3

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

L is soy;

M - sugar beet; 5

N - wheat;

O - rice;

P - sorghum;

B - Xanthium;

Q - Bilderdykia convolvulus; 10

D - Yipomea purpurea;

j t; ,

R - hemp = connabis sativa;

E - Chenopodium album F - Persicaria hydropiper;

C - Sissampelos pareira;

Y - Bromus;

S - Panicum;

K - Echinoehloa cous-gali;

T - Digitaria sanguinalis;

The results are summarized in Table 22.

Table 22

Example No. kg / h L Μ N 0 P B Q D R E F c J s K T 2 .056 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 —- .28 0 0 0 0 0 3 0 0 0 0 0 0 0 0 0 - 1.12 0 1 0 0 0 0 0 0 3 1 I 3 0 0 0 - 5.6 0 1 3 3 3 1 I 3 3 2 2 2 3 3 3 - 11.2 2 2 3 3 3 0 3 3 3 3 2 1 3 3 3 - 4 .28 - 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 1.12 - 0 0 0 0 0 1 0 3 0 - 1 0 0 0 3 5.6 - 3 3 2 3 0 2 2 0 3 - 3 3 3 3 3 5 .28 - 0 0 0 0 0 0 0 3 3 - 0 0 0 0 1 1.12 - 0 0 0 0 0 1 0 2 0 - 0 0 0 0 I 5.6 - 1 0 0 0 0 0 0 1 2 - 0 3 2 3 3 9 1.12 - 0 0 0 0 0 2 0 3 0 - 0 1 0 0 0 5.6 - 0 0 0 0 0 0 0 0 2 - 0 1 2 3 3 1 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 1 1 1 2 1 0 0 1 2 2 0 0 I 2 3 3 5.6 3 3 3 3 3 0 2 3 2 3 3 1 3 3 3 3 6 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 1 1 1 I 0 0 0 1 0 0 0 0 2 3 3 5.6 3 3 3 3 3 1 3 3 3 3 2 1 3 3 3 3 7 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .28 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 3 1.12 0 1 3 3 0 0 0 0 0 1 1 0 1 1 2 3 0 I 3 2 0 0 0 0 0 3 1 0 1 1 2 3 5.6 3 3 3 3 3 0 2 3 3 3 3 1 3 3 3 3 3 3 3 3 3 0 0 3 3 3 3 1 3 3 3 3 94 .056 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 I 1.12 0 1 0 1 0 0 0 0 0 1 - 0 0 0 1 2

And AA'VVUUUWVU

Example No. kg / b L M N o P B Q D R E F C J s K T 5.6 0 2 3 2 2 0 0 0 I 3 3 1 2 3 3 3 95 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 5.6 0 1 2 1 1 0 0 1 1 1 1 0 3 3 3 3 ) 2 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .21 0 2 0 0 3 0 3 1 0 0 0 Γ 1 3 3 3 0 3 0 0 3 0 0 0 0 1 3 0 1 3 3 3 1.12 1 3 2 2 3 0 3 3 1 3 2 2 3 3 3 3 1 3 1 2 3 0 2 3 0 3 2 2 3 3 3 3 5.6 3 3 3 3 3 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 1 3 3 3 3 3 3 3 3 3 3 43 5.6 3 3 3 3 3 1 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 1 3 3 3 3 3 3 3 3 3 3 1.12 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 0 I 2 3 3 3 3 3 3 3 3 .21 0 3 2 2 3 0 2 1 1 3 2 1 3 3 3 3 1 3 1 1 2 0 0 1 0 3 2 2 2 3 3 3 .056 0 1 0 1 0 0 0 0 0 1 1 1 1 1 3 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 1 57 5.6 I 3 3 3 3 1 3 3 2 3 2 2 3 3 3 3 1 3 3 3 3 0 2 2 1 3 2 1 3 3 3 3 1.12 0 3 0 0 0 0 2 0 1 1 1 0 1 1 3 3 - 0 2 0 0 0 0 0 0 0 1 0 0 1 0 3 3 .2 « 0 3 0 0 0 0 0 0 0 0 0 0 0 0 2 1 .056 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 13 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .21 0 2 0 1 3 0 1 0 I 0 0 0 3 3 3 3 0 0 0 0 3 0 0 0 0 0 0 0 3 3 3 3 1.12 1 3 2 2 3 0 3 3 2 2 3 0 2 3 3 3 1 3 1 1 2 0 2 2 2 3 3 1 1 3 3 3 5.6 3 3 3 3 3 1 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 94 21 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 _ 0 0 0 0 0 5.6 0 1 0 0 0 0 0 0 1 0 - 0 0 1 3 2 t 5.6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 46 5.6 2 3 1 3 3 1 3 2 I 3 1 0 3 3 3 3 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 2 61 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .21 0 1 0 1 2 0 1 0 1 1 1 0 2 2 3 3 0 1 0 0 2 0 0 0 0 2 0 0 2 3 3 3 1.12 1 2 0 2 3 0 2 2 2 3 3 0 3 3 3 3 0 3 0 2 3 0 1 2 2 3 2 1 3 3 3 3 n 5.6 1 3 3 3 3 ! 1 I 2 3 - 1 3 3 3 3 1.12 1 1 0 0 0 0 0 0 0 2 - 0 0 0 1 0 056 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 It 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 19 5.6 0 0 0 0 0 0 0 0 0 1 - 0 0 0 1 1 1.12 0 0 0 0 0 0 0 0 0 1 - 0 0 0 1 2 40 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .21 0 0 0 0 0 - 0 0 0 0 0 0 0 0 0 0 1.12 0 I 2 1 3 0 1 0 0 2 1 2 1 3 3 3 5.6 2 3 3 3 3 1 2 3 2 3 3 2 3 3 3 3 59 1.12 3 3 3 3 3 0 3 3 2 3 - 2 3 3 3 3 3 3 3 3 3 0 0 3 2 3 - 3 3 3 3 3 .24 0 2 0 2 2 0 0 0 0 0 - 0 3 3 3 3 5.6 3 3 3 3 3 1 3 3 3 3 - 3 3 3 3 3 3 3 3 3 3 1 3 3 3 3 - 3 3 3 3 3 .056 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 60 5.6 0 1 3 0 0 0 0 0 1 I - 0 1 3 3 3 1.12 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 .21 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 52 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .056 0 3 1 I 2 0 1 1 0 3 1 1 2 3 3 3 0 3 0 0 2 0 0 0 0 3 3 1 2 3 3 3 .21 2 3 3 3 3 0 3 2 3 3 3 2 3 3 3 3 | 3 3 3 3 0 1 2 3 3 3 2 3 3 3 3 1.12 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 0 3 2 3 3 3 2 3 3 3 3 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .056 0 2 1 2 1 0 1 2 1 2 2 1 2 3 2 2 5.6 3 3 3 3 2 3 3 3 3 3 3 3 3 3 3 3 1.12 2 3 3 3 3 2 3 3 2 3 3 2 3 3 3 3 .21 I 3 3 3 3 1 3 3 2 3 2 2 3 3 3 3

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Example No. kg / h L M N o P B Q D R E F c J s K T 62 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 1.12 0 0 0 0 0 0 0 0 0 3 1 0 0 0 3 3 9.6 1 3 2 2 3 1 3 2 3 3 3 2 0 3 3 3 90 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 9.6 0 0 0 0 1 0 0 0 0 2 0 I 1 2 3 3 It .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 1 2 1 2 3 0 0 2 2 3 1 0 3 3 3 3 9.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .096 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 29 9.6 0 2 2 1 3 0 1 0 1 2 1 0 1 3 3 3 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 47 9.6 1 3 3 3 3 0 2 2 2 3 3 2 3 3 3 3 1.12 0 I 0 0 0 0 1 0 0 0 0 1 0 1 1 0 .28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .096 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 93 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 9.6 1 3 3 3 3 2 1 3 2 3 3 2 3 3 3 3 1.12 0 I 0 0 0 0 0 0 0 1 1 1 0 2 1 2 .09 « 0 1 0 0 0 0 0 0 0 1 1 0 0 0 0 1 19 9.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 3 2 3 3 0 2 2 2 3 3 2 3 3 3 3 .21 0 1 0 0 0 0 0 0 1 1 1 0 0 1 3 3 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 05 « 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 44 .09 « 0 0 0 0 0 0 0 0 0 2 I 0 0 0 0 1 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1.12 0 1 0 I 3 0 1 0 2 2 2 0 1 3 3 3 9. " 1 3 3 3 3 0 2 2 3 3 3 2 3 3 3 3 31 9. " 0 2 0 1 3 0 2 2 2 3 1 0 3 3 3 3 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1.12 0 2 0 0 0 0 0 0 0 2 0 0 2 I 2 1 .09 « 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 93 1.12 3 3 3 3 3 1 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 0 2 3 3 3 3 3 3 3 3 3 9. " 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 2 3 3 3 3 3 3 3 3 3 3 .21 0 3 3 3 3 0 2 2 3 3 3 2 3 3 3 3 0 3 3 3 3 0 0 1 1 3 2 2 3 3 3 3 .09 « 2 3 3 3 I 0 1 3 3 3 3 2 0 3 3 3 1 3 2 3 0 0 0 2 2 3 3 1 0 3 3 3 .0112 0 3 0 2 1 0 2 1 2 3 2 2 0 2 2 3 0 2 0 1 0 0 0 0 0 0 0 0 0 1 2 3 16 9. " 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 1.12 2 3 3 3 3 2 3 3 3 3 3 2 3 3 3 3 .21 0 1 0 2 2 0 1 2 2 2 2 1 3 3 3 3 .09 « 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 3 .0112 0 0 0 0 0 0 0 1 0 1 0 0 0 0 1 0 21 9.6 0 2 I 1 1 0 0 1 2 3 3 2 3 3 3 3 1.12 0 0 0 0 0 0 0 0 0 2 2 0 0 0 2 2 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 64 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 9. " 2 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 1 3 0 2 3 0 3 3 3 3 3 2 3 3 3 3 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 2 2 2 94 .0112 0 0 0 0 0 0 0 0 0 0 - 0 0 0 1 1 5.6 3 3 3 3 3 3 3 3 3 3 - 3 3 3 3 3 .096 2 2 0 2 2 0 0 0 1 2 - 0 3 3 3 3 1.12 3 3 3 3 3 0 3 3 3 3 - 3 3 3 3 3 .21 2 3 3 3 3 0 3 3 2 3 - 2 3 3 3 3 11 5. " 2 3 3 3 3 0 3 3 3 3 - 3 3 3 3 3 1.12 1 3 1 3 3 0 3 3 3 3 - 3 3 3 3 3 .21 0 2 0 3 1 0 1 0 1 1 - 1 0 2 2 3 .09 « 0 0 0 0 0 0 0 0 0 0 - 0 0 0 1 0 .0112 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 17 9. " 3 3 J 3 3 0 3 3 3 3 - 3 3 3 3 3 1.12 2 3 2 3 3 0 3 3 2 3 - 2 3 3 3 3 .0112 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 - 0 0 0 I 0 .21 1 2 0 0 3 0 1 0 0 0 - 1 1 3 3 3 97 5.6 1 3 0 0 0 0 0 0 2 2 1 0 0 3 3 3 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 1 1 0 0 0 1 1 1 20 5.6 | 3 3 1 3 0 2 3 2 3 - 2 3 3 3 3 1.12 0 0 0 0 0 0 0 0 0 I - 1 0 0 1 2 .21 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 22 5.6 0 2 1 1 3 1 3 2 2 3 - 2 3 3 3 3

Eyalrck No. kg / h L M N o P B Q D R E F c J s K T 1.12 0 0 0 0 0 0 0 0 0 0 0 1 2 2 2 .21 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 75 .21 0 2 1 2 I 0 3 2 1 2 - 1 3 1 3 3 .056 1 2 0 2 0 0 0 0 0 0 - 0 0 0 2 2 5.6 0 3 3 3 3 1 3 3 3 3 - 1 3 3 3 3 1.12 0 2 2 2 3 0 2 1 1 3 - 1 3 2 3 3 14 .0112 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 2 1.12 3 3 3 3 3 1 3 3 3 3 - 3 3 3 3 3 5.6 3 3 3 3 3 2 3 3 3 3 - 3 3 3 3 3 .056 0 2 2 2 3 0 3 1 1 2 - 1 3 3 3 3 JI 2 3 3 3 3 1 3 3 3 3 - 3 3 3 3 3 23 5.6 1 2 0 0 1 0 1 2 0 3 - 1 2 I 2 3 1.12 0 0 0 0 0 0 0 0 0 0 - 0 1 0 0 1 .21 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 35 5.6 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 17 5.6 3 3 3 3 3 3 3 3 3 3 - 3 3 3 3 3 1.12 3 3 3 3 3 2 3 3 3 3 - 3 3 3 3 3 .0112 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 - 0 2 2 2 3 .21 0 1 0 0 2 0 0 2 0 0 - 0 2 3 3 3 34 5.6 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 2 1.12 0 0 0 0 0 0 0 0 0 0 - 0 1 0 1 0 SO 5.6 0 2 0 2 3 0 3 2 2 3 - 0 2 3 3 3 1.12 0 1 0 0 0 0 0 1 0 1 - 0 0 0 1 1 .21 0 0 0 0 0 0 0 0 0 - - 0 0 0 0 1 55 5.6 3 3 3 3 3 I 3 3 3 3 - 3 3 3 3 3 1.12 3 3 3 3 3 0 3 3 3 3 - 3 3 3 3 3 .21 2 3 2 3 3 0 3 3 3 3 - 2 3 3 3 3 .056 0 2 0 1 3 0 2 2 2 3 - 2 3 3 3 3 .0112 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 2 65 JI 0 0 0 0 1 0 0 0 0 0 - 0 2 2 2 2 .056 0 0 0 0 0 0 0 0 0 0 - 0 0 1 2 1 5.6 1 3 3 3 3 0 3 3 3 3 - 2 3 3 3 3 1.12 0 1 3 2 3 0 3 0 1 2 - 0 3 3 3 3 6 « JI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5.6 0 0 0 0 1 0 0 2 0 0 0 0 3 1 1 3 67 5.6 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 1.12 3 3 3 3 3 2 3 3 3 3 3 2 3 3 3 3 .21 1 3 3 3 3 0 3 2 2 * 3 3 1 3 3 3 3 .056 0 0 0 0 3 0 2 1 0 1 0 0 1 1 1 2 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 2 12 5.6 0 0 0 0 3 0 0 1 0 1 1 1 1 1 2 3 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 M 5.6 1 3 3 3 3 1 3 3 3 3 3 2 3 3 3 3 1.12 0 2 0 2 3 0 2 2 1 0 0 0 3 3 3 3 M 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 15 5.6 3 3 3 3 3 2 3 3 3 3 3 3 3 3 3 3 1.12 1 3 3 3 3 0 2 2 2 3 3 2 3 3 3 3 .21 0 2 0 1 1 0 1 2 0 2 t 0 2 2 2 2 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 1 t 2 16 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 2 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .21 1 2 3 3 3 0 3 1 2 2 2 I 3 3 3 3 .056 0 2 0 1 3 0 2 0 I 2 1 0 2 2 2 3 112 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1.12 0 2 1 0 3 0 2 1 1 1 I 2 2 2 2 2 5.6 0 3 3 2 3 3 3 3 3 3 3 2 3 3 3 3 70 5.6 0 2 2 2 2 0 2 2 3 3 - 1 3 3 3 3 .21 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 1.12 0 1 0 0 0 0 0 0 0 0 - 0 0 1 2 3 .056 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 24 1.12 0 3 3 2 2 0 2 2 2 3 2 2 3 3 3 3 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 11 0 0 0 0 0 0 0 0 0 0 0 0 0 0 I 2 71 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 1 2 3 2 3 0 2 2 2 3 3 2 2 3 3 3 .21 0 1 0 0 1 0 0 0 0 0 0 0 0 2 2 2 103 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5.6 1 2 3 2 3 0 3 3 I 3 2 1 3 3 3 3 69 1.12 3 3 3 3 3 0 3 3 3 3 - 3 3 3 3 3 .21 0 3 3 3 3 0 3 3 2 3 - 1 3 3 3 3 .056 0 0 0 0 2 0 3 1 0 0 - 1 2 3 3 3 .0112 0 0 0 0 0 0 0 0 0 0 0 0 1 1 2 5.6 3 3 3 3 3 2 3 3 3 3 - 3 3 3 3 3 72 5.6 3 3 3 3 3 0 3 3 3 3 - 3 3 3 3 3

Example No. kg / h L M N 0 P B Q D R E F c J s K T .0112 0 0 0 0 0 _ 0 0 0 0 0 0 0 0 0 0 1.12 0 3 3 3 3 0 3 I 2 3 3 3 3 3 3 3 .21 0 2 I 0 3 0 2 0 1 2 1 1 3 3 3 3 5.6 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 12 « .21 0 0 0 0 0 0 0 0 0 0 0 0 0 2 3 3 .036 0 0 0 0 0 - 0 0 0 0 0 0 0 0 0 1 1.12 0 1 3 2 3 0 2 2 2 2 1 1 3 3 3 3 3.6 1 2 3 3 3 0 3 2 2 3 3 3 3 3 3 3 109 1.12 0 0 0 0 0 0 3 0 0 0 0 0 0 0 0 0 3.6 0 0 0 0 0 - 1 0 0 0 0 0 1 2 2 3 110 .21 0 1 0 0 2 0 1 0 0 1 0 0 3 2 1 1.12 0 3 2 3 3 0 3 0 1 3 2 0 3 3 3 3 5.6 0 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 111 1.12 1 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .21 1 2 3 3 3 0 2 0 l 1 1 1 3 3 3 3 5.6 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 .036 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 .0112 0 0 0 0 0 - 0 0 0 0 0 0 0 0 0 0 122 3.6 3 3 3 3 3 1 3 3 3 3 3 3 3 3 3 3 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 1 3 2 2 3 0 3 2 2 3 3 3 3 3 3 3 .21 0 2 0 0 2 0 I 0 0 1 1 1 2 2 2 3 .036 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 117 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5.6 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 1.12 3 3 3 3 3 0 3 ) 3 3 3 3 3 3 3 3 JI 1 3 2 3 3 0 J 2 3 3 3 2 3 3 3 3 .036 0 2 0 0 3 0 3 0 1 1 I 0 3 3 3 3 113 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .21 0 0 0 0 0 0 0 0 0 0 0 0 0 1 I 2 1.12 0 3 2 0 3 0 3 1 2 3 3 2 3 3 3 3 5.6 0 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 123 .036 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 2 2 3 3 2 3 3 3 3 3 2 3 3 3 3 M 0 2 0 0 3 0 2 0 1 2 2 I 3 3 3 3 132 3.6 1 2 0 2 3 0 0 0 1 2 2 0 3 3 3 3 1.12 0 0 0 0 0 0 0 0 0 0 0 0 N 2 3 3 0.21 0 0 0 0 0 0 0 0 0 0 0 0 N 0 0 0 133 5.6 0 2 1 0 1 0 1 1 1 2 2 I 1 2 3 3 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 136 3.6 1 2 0 0 0 0 0 1 I 2 2 0 0 0 1 3 1.12 1 1 0 0 0 0 0 0 2 2 2 0 0 0 1 2 137 3.6 0 2 0 0 0 0 0 0 0 3 3 0 0 2 3 3 1.12 0 3 0 N 0 0 0 1 2 3 3 0 0 2 3 3 0.21 0 2 0 0 0 0 0 0 0 3 2 0 0 0 I 2 ISt 3.6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 139 3.6 0 2 3 3 3 0 3 2 2 3 3 3 3 3 3 3 1.12 0 2 0 1 3 0 2 I 0 0 0 0 2 3 3 1 0.21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 161 3.6 0 3 3 2 3 0 3 3 3 3 3 3 3 3 3 3 1.12 1 3 0 1 3 0 2 2 2 3 3 2 3 3 3 3 0.21 0 0 0 0 0 0 0 0 1 1 1 1 1 1 2 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 162 3.6 1 3 3 3 3 0 2 3 3 3 3 3 3 3 3 3 1.12 0 2 0 2 2 1 2 2 1 2 2 1 2 3 3 3 0.2 « 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .036 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 163 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 2 3 1 3 0 2 1 2 3 3 3 3 3 3 3 0.2 « 0 0 2 0 1 0 0 0 0 I 1 1 0 1 1 2 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 16 « 3.6 0 3 I 0 3 1 3 2 2 2 2 2 3 2 3 3 1.12 1 2 0 0 0 0 0 0 0 2 2 2 1 2 0 0 0.21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 163 3.6 0 0 0 0 2 0 0 1 0 0 0 1 0 3 3 3 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 2 1 2 0.21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 166 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 0.2 « 0 2 2 2 3 0 1 2 2 3 3 2 3 3 3 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 2 3 3 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 167 5.6 0 2 2 3 3 0 2 3 3 3 3 2 3 3 3 3 1.12 0 0 0 1 1 0 2 1 2 2 1 1 N 1 1 2

Example No. kg / h L M N o P B Q D R E F c 1 s K T 0.28 0 0 0 0 0 0 0 0 0 0 0 0 N 0 0 0 169 5.6 0 3 3 3 3 0 1 2 3 3 3 3 3 3 3 3 1.12 0 2 0 0 3 0 2 1 0 2 2 0 3 3 3 3 0.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 170 5.6 2 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 3 3 2 2 0 2 0 1 3 3 3 3 2 3 3 0.28 0 0 0 0 2 0 0 0 0 2 1 1 r 2 2 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 171 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 3 3 2 3 0 3 3 3 3 3 3 3 3 3 3 0.28 0 2 0 0 3 0 0 1 0 0 0 0 3 3 3 3 .056 0 1 0 0 I 0 0 0 0 0 0 0 0 1 2 0 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 172 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 0.28 0 3 3 3 3 0 1 2 1 3 3 2 3 3 3 3 .056 0 1 1 0 3 0 0 0 0 0 0 0 0 3 3 3 0.0112 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 173 3.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 2 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 0.28 0 2 1 0 3 0 2 0 0 1 1 0 3 3 3 3 .056 0 1 0 0 0 0 0 0 0 0 0 0 0 1 3 3 • 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 174 5.6 1 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 0 0 0 3 0 0 0 0 0 0 0 1 2 3 3 0.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 175 5.6 0 3 2 1 3 0 3 3 1 3 2 2 3 3 3 3 1.12 0 2 0 0 1 0 2 0 0 2 0 0 3 2 3 3 0.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 176 5.6 0 3 3 0 3 0 3 3 1 3 3 2 3 3 3 3 1.12 0 1 0 0 3 0 0 0 0 0 0 0 0 3 3 1 0.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 177 3.6 1 3 3 3 3 0 3 3 3 3 3 2 3 3 3 3 1.12 0 1 1 1 0 0 0 0 0 2 1 1 2 2 2 2 048 0 1 0 0 0 0 0 0 0 2 1 0 0 0 1 1 .03 « 0 0 0 0 0 0 0 0- 0 0 0 0 0 0 0 0 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 178 5.6 3 3 3 3 3 1 3 3 3 3 3 3 3 3 3 3 1.12 1 3 3 2 3 0 3 2 2 3 2 2 3 3 3 3 0.28 0 2 1 1 3 0 1 0 1 1 0 0 1 2 3 3 0.36 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 179 3.6 0 3 3 2 3 0 3 1 2 3 3 2 3 3 3 3 1.12 0 0 0 0 2 0 3 0 0 0 0 0 3 3 3 3 0.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ISO 3.6 2 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 3 1 2 3 0 3 0 2 2 2 J 3 3 3 3 0.28 0 1 0 0 2 0 0 0 1 2 0 1 2 1 3 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ISl 5.6 0 0 0 0 1 0 0 0 0 0 0 0 0 0 3 2 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1S2 5.6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1S4 5.6 1 3 3 1 3 I 3 2 2 3 3 3 3 3 3 3 1.12 0 0 1 0 0 0 0 0 0 2 2 1 0 1 2 3 0.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 IU 5.6 I 3 3 2 3 1 2 2 2 3 3 3 3 3 3 3 1.12 0 2 0 0 0 0 0 0 0 2 1 1 0 2 2 3 0.28 0 1 0 0 0 N 1 0 0 0 0 2 2 1 2 2 .05 « 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 117 5 « 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1.12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 189 5.4 1 2 3 1 3 0 3 I 2 3 3 2 3 3 3 3 1.12 0 0 0 0 0 0 0 0 0 1 0 0 0 I 2 3 190 5.6 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 1.12 2 2 3 1 3 0 2 2 2 3 2 1 3 3 3 3 0.28 2 3 3 1 1 0 2 2 2 2 2 1 1 3 3 3 056 0 1 0 0 0 0 0 0 0 2 2 1 1 1 0 2 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 191 3.6 0 2 1 1 2 0 1 0 2 3 3 2 2 3 3 3 1.12 1 1 0 0 0 N 0 1 2 2 2 N 1 1 2 3 0.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 192 5.6 0 1 0 0 0 N 0 0 0 0 0 0 0 1 3 3 1.12 0 0 0 0 0 N 0 0 0 0 0 0 0 0 0 0 198 5.6 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 1.12 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3

Example No. t k »/ h L m N 0 R. in Q D R Gee !? p J S K. t 0.21 3 ] 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .056 1 2 2 3 3 0 3 3 3 3 2 2 3 3 3 3 056 0 3 2 3 3 N 3 2 2 3 3 2 3 3 3 3 0.0112 0 0 0 0 1 0 0 0 1 2 1 2 1 2 2 3 0.01 p 0 0 0 0 1 N 1 0 0 0 0 1 0 0 1 2 0056 0 0 0 0 0 N 0 0 0 1 1 1 0 0 1 2 199 5.6 3 3 3 3 3 2 3 3 3 3 3 3 3 3 3 3 1.12 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 0.21 2 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 .056 1 2 1 2 3 0 2 1 2 3 2 > 1 3 3 3 3 .0% 0 3 1 2 3 N 2 2 3 3 3 1 3 3 3 3 0.0112 0 0 1 1 3 0 1 0 0 0 0 1 3 3 3 3 0.0112 0 0 0 0 2 N 2 0 0 0 0 0 1 0 2 2 .00% 0 0 0 0 0 N 0 0 0 0 0 0 0 0 1 1 200 5.6 2 3 2 1 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 2 0 0 0 N 3 1 2 3 3 1 1 2 3 3 0.21 0 2 0 0 0 0 I 0 0 1 1 0 1 2 2 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 204 5.6 0 0 0 0 0 0 0 0 0 0 0 0 3 3 3 3 1.12 0 0 0 0 0 0 0 0 0 0 0 0 N 0 0 2 20 « 5.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 1 3 3 3 3 0 3 3 2 3 3 3 3 3 3 3 & 21 0 1 0 I 3 0 0 0 0 1 1 1 3 3 3 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 N 1 2 3 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 N 0 0 0 209 3.6 3 3 3 3 3 0 3 3 3 3 3 3 3 3 3 3 1.12 0 3 3 3 3 0 3 3 3 3 3 2 3 3 3 3 0.2 » 0 1 0 1 3 0 0 0 0 0 0 0 3 3 3 3 .056 0 0 0 0 0 0 0 0 0 0 0 0 N 1 1 2 0.0112 0 0 0 0 0 0 0 0 0 0 0 0 N 0 0 0

Subsequent use, the herbicidal activity of some of the compounds of the present invention is demonstrated by the greenhouse experiment as follows. A good variety of high quality soil is placed in an aluminum pan with holes in the bottom and pressed at a distance of 0.95 25 to 1.27 cm from the top of the pan. A predetermined number of seeds from each of several bi-weekly monocotyledonous annual plant species and / or planting material for multi-annual plant visas is placed on the soil and pressed into the soil surface. The seeds and / or plant propagating material shall be covered with soil and leveled. Place the pan in a sunny place in a greenhouse and water it below as needed. After the plants reach the desired age (two to three weeks), each pan, except the control pan, is individually introduced into the spray area and sprayed at the specified ratio. At 40

Να kg / ha A in c D E 6 11.2 0 0 0 0 0 7 11.2 - 0 0 0 0 94 there - 0 0 0 0 95 11.2 - 0 0 0 0 12 11-2 0 0 1 1 0 3 » 11.2 0 0 0 0 0 32 11.2 2 0 0 0 0 37 11.2 0 0 0 1 0 13 11.2 0 1 0 2 0 39 11.2 0 0 0 0 0 2 » 11.2 0 1 0 0 0 9 « 11.2 0 0 0 0 0 19 11.2 0 0 0 0 1 11.2 0 0 0 0 0 «6 11.2 0 0 0 0 0 61 11.2 0 0 0 0 0 45 11.2 0 0 0 0 0 U 11.2 0 0 0 0 0

the spray composition has a defined amount of a mixture of emulsifying agent which gives the spray solution or suspension containing about 0.4% by weight of the emulsifier. The spray solution or suspension contains a sufficient amount of chemical to allow the applicable ratios to correspond to those given in the tables. The pans returned to the greenhouse and watered as before and the damage to the plants compared to the controls was observed approximately 10-14 days (usually 11 days) and in some cases again observed 24-28 days (usually 25 days) after spraying.

The index of herbicidal activity subsequently used in table lie is as follows:

Plant response 0-24%, 25-49%, 50-74%,

75-99%, retention 100%

Index 0 12 34 = « _u,, v Table 23 - 0 - 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0I

92 11.2 0 0 0 0 0 0 0 0 0 0 19 11.2 0 0 0 0 0 - 0 0 0 0 0 27 11.2 3 0 0 0 0 - 0 0 0 0 0 59 11.2 - 0 0 0 0 - 0 0 0 0 0 60 11.2 0 0 0 0 0 - 0 0 0 0 0 91 11.2 - 0 0 0 0 - 0 0 0 0 0 52 11.2 - 0 0 0 0 - 0 0 0 0 0 5 » 11.2 - 0 0 0 0 - 0 0 . 0 0 0 62 11.2 - 0 1 0 0 - 0 0 0 0 0 90 11.2 - 0 0 0 0 - 0 0 0 0 0 II 11-2 - 0 0 0 0 - 0 0 0 0 0 Yu 11.2 - 1 0 0 0 0 0 0 0 0 0 29 11.2 - 1 0 1 0 0 0 0 0 0 0 47 11.2 - 1 0 1 0 -. 0 0 0 0 0 41 11.2 - 0 0 0 0 0 0 0 0 0 0 46 11.2 - 0 0 0 0 0 0 0 0 0 0 15 11.2 0 1 1 1 0 0 0 0 0 0 0 44 11.2 0 0 0 1 0 0 0 0 0 0 0 31 11.2 0 0 0 0 0 0 0 0 0 0 0 53 11.2 0 1 0 1 0 0 0 0 0 0 1 16 IL 0 1 1 | 1 0 0 0 0 0 1 21 11.2 0 1 1 2 0 0 0 0 0 0 0 64 11.2 0 1 1 2 0 0 0 0 0 0 0 32 11.2 0 0 0 1 1 0 0 0 0 0 0 54 11.2 0 1 1 2 0 1 0 0 0 0 2 37 11.2 0 1 0 0 0 0 0 0 0 0 0 11 11.2 0 0 0 1 0 - 0 0 0 0 0 17 11.2 0 1 0 1 0 - 0 0 0 0 0 97 11.2 0 0 0 0 - 0 0 0 0 0 0 20 11.2 - 1 0 1 0 - 0 0 0 0 0 41 11.2 - 0 0 0 0 - 0 0 0 0 0 22 11.2 0 0 0 0 0 - 0 0 0 0 0 75 11.2 0 0 1 0 0 - 0 0 0 0 0 14 11.2 0 0 0 0 0 - 0 0 0 0 0 30 11.2 0 0 0 0 0 - 0 0 0 0 0 23 11.2 0 0 0 0 0 - 0 0 0 0 0 35 11.2 0 0 0 0 0 - 0 0 0 0 0 17 11.2 0 - 1 2 0 0 0 0 1 0 2 34 11.2 0 0 0 0 0 0 0 0 - 0 0 50 11.2 0 0 0 0 0 - 0 0 0 0 0 55 1U 0 2 1 2 2 - 2 0 0 1 2 55 · 11.2 0 2 2 2 3 - 2 1 0 2 2 33 11.2 0 1 0 1 1 - 0 0 0 0 0 49 11.2 0 0 0 1 0 - 0 0 0 0 0 65 11.2 0 0 0 0 0 - 0 0 0 0 0 51 11.2 0 0 0 0 0 0 0 0 0 0 0 61 11.2 0 0 0 0 0 0 0 0 0 0 0 67 nl 0 0 0 0 0 0 0 0 0 0 1 76 11.2 0 I 0 1 2 0 1 0 1 0 1 77 IL 0 1 1 1 1 1 0 0 0 0 0 13 11.2 0 0 1 0 0 0 0 0 0 0 0 12 11.2 0 0 1 1 0 0 0 0 0 0 0 m 11.2 0 0 0 0 0 0 0 0 0 0 0 66 11.2 0 0 0 0 0 0 0 0 0 0 0 15 11.2 1 0 0 0 0 0 2 0 0 0 2 16 11.2 0 0 0 0 0 0 0 0 0 0 0 112 11.2 2 - 1 1 0 0 0 0 0 0 0 70 11.2 0 0 0 0 0 - 0 0 0 0 0 24 11.2 0 0 0 0 0 - 0 0 0 0 0 3 « 11.2 0 0 0 0 0 0 0 0 0 0 0 71 11.2 0 0 0 0 0 0 0 0 0 0 0 103 11.2 0 0 0 0 0 0 0 0 0 0 0 100 11.2 0 0 0 0 0 0 0 0 0 0 0 69 11.2 0 1 0 0 0 - 0 0 0 0 1 72 11.2 0 0 0 0 0 - 0 0 0 0 0 99 11.2 0 - 0 0 0 0 0 0 0 0 0 11 11.2 0 0 0 1 0 0 0 0 0 0 0 42 11.2 _ 0 0 0 0 0 0 0 0 0 0 74 11.2 0 1 0 1 0 0 0 0 0 0 1 71 11.2 - 0 0 0 0 0 0 0 0 0 1 73 11.2 0 1 1 1 0 0 0 0 0 0 0 91 11.2 0 0 0 0 0 0 0 - 0 0 0 10 11.2 0 - 0 0 0 0 0 0 0 0 0 101 11.2 0 0 0 0 1 0 0 0 0 2 25 11.2 0 0 0 1 0 0 0 0 0 0 0 102 11.2 0 0 0 0 0 0 0 0 0 0 0 134 11.2 0 0 0 0 0 0 0 0 0 0 0 130 11.2 0 0 0 0 0 0 0 0 0 0 0 121 11.2 0 0 0 0 0 0 0 0 0 0 0 104 11.2 0 0 0 0 2 0 0 0 0 0 0 127 11.2 0 0 0 1 0 0 0 0 0 0 0 129 11.2 0 1 1 2 3 0 0 0 0 0 0

Table 23

111 103 11.2 11.2 0 0 1 0 0 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 2 1 111 11.2 0 1 1 1 1 1 0 0 0 0 2 ao 11.2 0 1 I 1 1 0 0 0 0 0 1 79 11.2 - 0 0 0 0 0 0 0 0 0 0 26 11.2 - 0 0 0 0 0 0 0 0 0 0 27 11.2 - 0 0 0 0 0 0 0 0 0 0 121 11.2 0 0 0 1 0 0 0 0 .0 0 0 124 11.2 0 0 0 1 0 0 0 0 0 0 0 119 11.2 0 1 0 0 0 0 0 0 0 0 0 109 11.2 0 0 0 1 0 0 0 0 0 0 0 43 11.2 0 0 0 0 0 0 0 0 0 0 0 107 112 0 - 0 0 0 0 0 0 0 0 0 no 11.2 0 0 0 1 0 0 0 0 0 0 1 Hl 112 0 - 1 2 0 0 0 0 0 0 1 106 11.2 0 - 0 0 0 0 0 0 0 0 0 120 11.2 0 - 0 1 0 0 0 0 0 0 0 122 11.2 0 1 1 1 0 0 0 0 0 0 0 117 11.2 0 1 1 2 1 0 0 0 0 0 0 lit 11.2 0 0 0 0 0 0 0 0 0 0 0 Hl 11.2 0 1 1 2 0 0 0 0 0 0 0 121 11.2 0 0 0 1 0 0 0 0 0 0 0 123 11.2 I 1 0 1 1 0 0 0 0 0 1 137 11.2 0 0 0 0 0 0 0 0 0 0 0 - 136 11.2 0 I 1 2 I 0 0 0 0 0 0 133 11.2 0 0 0 0 0 0 0 0 0 0 0 131 IU 0 0 1 1 0 0 1 0 1 1 2 131 11.2 0 1 1 1 0 0 0 0 0 0 1 139 11.2 0 1 0 1 0 0 0 0 0 0 0 140 11.2 0 0 0 0 0 0 0 0 0 0 0 141 11.2 0 0 1 I 0 1 0 0 N 0 0 142 11.2 0 0 0 0 0 0 0 0 0 0 0 143 11.2 0 0 0 0 0 0 0 0 0 0 0 144 11.2 0 0 0 0 0 0 0 0 0 0 0 146 11.2 1 0 2 1 2 1 0 0 N 0 0 147 11.2 0 1 1 1 1 0 0 0 N 0 0 I4t 11.2 1 1 1 1 2 0 0 0 0 0 1 149 11.2 N 0 1 1 0 0 0 0 0 0 0 150 112 0 0 0 0 0 0 0 0 0 0 0 132 11.2 0 0 0 0 1 0 0 0 N 0 0 133 11.2 0 1 0 0 0 0 0 0 0 0 0 IM 11.2 0 0 0 0 0 0 0 0 - 0 0 155 11.2 0 0 0 0 0 0 0 0 0 0 0 156 112 0 0 0 0 0 0 0 0 0 0 0 157 11.2 0 2 1 2 0 0 0 0 0 0 1 15t 11.2 0 0 0 0 0 0 0 0 0 0 0 159 11.2 0 0 0 1 0 0 0 0 0 0 0 160 11.2 0 0 0 0 0 0 0 0 0 0 0 161 112 0 0 0 1 0 0 0 0 0 0 0 162 11.2 0 0 0 1 0 0 0 0 0 0 0 163 11.2 0 0 0 0 0 0 0 0 0 0 0 164 11.2 0 0 0 0 0 0 0 0 0 0 0 165 11.2 0 0 0 1 1 0 0 0 0 0 0 166 11.2 0 0 0 0 0 0 0 0 0 0 0 167 11.2 0 1 0 1 0 0 0 0 0 0 0 170 11.2 0 1 I 1 0 0 1 0 0 0 0 171 11.2 1 1 1 1 0 0 0 0 0 0 0 172 11.2 0 0 0 I 0 0 0 0 0 0 0 173 11.2 0 1 0 1 0 0 0 0 0 0 0 174 11.2 0 0 0 0 0 0 0 0 0 0 0 175 11.2 0 0 1 1 0 0 0 0 0 0 0 176 11.2 0 I 0 0 0 0 0 0 0 0 0 177 11-2 0 0 0 0 0 0 0 0 0 0 0 171 11.2 0 0 0 0 0 0 0 0 0 0 0 179 11.2 0 0 0 0 0 0 0 0 0 0 0 110 11.2 0 0 0 0 0 0 0 0 0 0 0 ltl 11.2 0 0 0 0 0 0 0 0 0 0 0 112 11.2 0 0 0 0 0 0 0 0 0 0 0 1 * 3 11.2 0 0 0 0 2 0 0 0 0 0 0 IM 11.2 N 0 0 0 0 0 0 0 0 0 0 It5 11-2 N 0 0 0 0 0 0 0 0 0 0 It6 11.2 0 1 0 0 0 0 0 0 - 0 0 It7 11.2 0 0 0 0 0 0 0 0 - 0 0 1 * 9 11.2 0 1 1 0 0 0 0 0 N 0 0 190 11.2 0 0 0 0 0 0 0 0 - 0 0 191 11.2 N 0 1 1 0 0 0 0 - 0 0 192 11.2 0 0 0 0 0 0 0 0 - 0 0 193 11.2 N 0 1 0 0 0 0 0 N 0 0 194 11.2 0 I 0 1 0 0 0 0 N 0 0 195 11.2 0 1 1 1 0 0 0 0 N 0 0 196 11.2 0 1 I 1 0 0 0 0 N 0 0 197 11.2 0 0 0 0 0 0 0 0 N 0 0

198 11.2 0 0 0 1 0 0 0 0 N 0 0 199 11.2 0 0 0 0 0 0 0 0 N 0 0 200 11.2 0 1 0 1 1 0 0 0 - 0 0 201 11.2 1 0 0 0 0 0 0 N N 0 1 202 11.2 0 0 0 0 0 0 0 0 0 0 0 203 11.2 0 0 0 0 0 0 0 0 N 0 0 204 11.2 0 0 0 0 1 0 0 0 N 0 0 209 11.2 0 0 1 0 1 0 0 0 -N 0 0 210 11.2 0 0 0 1 0 0 0 0 N 0 0 213 11.2 0 0 0 1 0 0 0 0 N 0 I 213 11.2 N 0 0 1 3 0 0 0 0 0 I 216 11.2 0 0 0 0 0 0 0 0 0 0 0 217 11.2 0 0 0 0 0 0 0 0 N 0 0 219 11.2 N 0 0 0 0 0 0 0 0 0 0 220 11.2 N 0 0 0 0 0 0 0 0 0 0 221 11.2 N 0 0 0 0 0 0 0 0 0 0 222 11.2 0 0 0 0 0 0 0 0 0 0 0 223 11.2 0 0 0 0 0 0 0 0 0 0 0 224 11.2 0 0 0 0 0 0 0 0 0 0 0 225 11.2 N 0 0 0 0 0 0 0 0 0 0 226 11.2 N 0 0. 0 0 0 0 0 0 0 0 227 11.2 N 0 1 0 0 0 0 0 0 0 0 233 '11 .2 N 0 1 0 0 0 0 0 0 0 0 234 11.2 N 0 1 1 0 0 0 0 0 0 0 235 11.2 0 0 1 1 0 0 0 0 0 0 0 236 11.2 0 0 0 1 0 0 0 0 0 0 0 237 11.2 N 0 1 1 0 0 0 0 0 0 0 238 11.2 N 1 1 1 0 1 0 0 0 0 1 240 11.2 2 0 0 0 1 0 0 0 0 0 0 241 11.2 N 0 0 0 0 0 0 0 0 0 0 242 11.2 0 0 0 0 0 0 0 0 - 0 0 243 11.2 0 0 0 0 0 0 0 0 - 0 0 244 112 0 1 1 I 0 0 0 0 - 0 0 245 11.2 0 0 1 I 1 0 0 0 0 0 1 246 11.2 N 0 1 2 1 0 0 0 0 0 0 Example Να kg / ha L Μ N ο P B Q D R E F c J s K T 5 1.12 0 0 0 0 0 0 0 0 0 3 - 0 0 0 0 0 5.6 0 1 0 0 0 0 0 0 0 0 - 0 0 0 0 0 16 11.2 2 0 3 0 I 2 0 1 1 2 1 2 1 i 1 2 .056 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .28 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.12 0 0 0 0 0 1 0 0 0 2 - 2 0 0 0 0 5.6 2 1 2 1 1 2 0 0 0 2 - 2 0 1 1 I

Table 24

Compound kg / ha Rooms Cott Rrpw Shea Sayg Ren Wipm Bygr Yem Rice Ex. 67 0.56 60 0 100 100 100 98 100 100 0 100 0.28 40 0 40 100 100 98 100 100 0 100 0.14 0 0 20 95 95 70 80 100 0 100 0.07 0 0 0 90 80 0 70 90 0 50 Ex. 72 0.56 60 0 90 100 100 98 95 100 0 100 0.28 30 0 20 98 95 70 90 95 0 95 0.14 0 0 0 90 90 0 60 90 0 60 0.07 0 0 0 80 70 0 40 50 0 40 Ex. 14 0.56 95 IS 95 100 100 100 100 100 90 100 0.28 90 0 80 100 100 100 100 100 80 100 0.14 80 0 50 too 100 98 100 100 0 too 0.07 10 0 20 100 98 80 95 100 0 98 Ex. Ill 0.56 0 0 80 98 98 30 90 95 0 98 0.28 0 0 20 95 95 30 90 95 0 90 0.14 0 0 0 80 80 0 50 80 0 30

L _t L

Compound kg / hx Rooms Cott Rrpw Shea Safe Ren Wipm Bygr Yens Rice 0.07 0 0 0 20 30 0 0 30 0 0 Ex. HO 0.56 0 0 60 91 91 40 99 98 0 90 0.28 0 0 0 90 90 0 80 15 0 50 0.14 0 0 0 10 10 0 40 70 0 30 0.07 0 0 0 40 50 0 0 20 0 0 Ex. 26 0.56 0 0 40 95 95 0 80 90 0 50 0.21 0 0 0 10 Yu 0 • 50 70 0 30 0.14 0 0 0 30 40 0 0 0 0 0 0.07 0 0 0 0 0 0 0 0 0 0 Ex. 25 0.56 40 0 90 100 100 30 100 100 0 98 0.28 0 0 20 100 91 0 98 100 0 80 0.14 0 0 0 95 95 0 90 90 0 40 0.07 0 0 0 that 70 0 80 15 0 30 Ex. 52 0.56 70 0 95 100 100 100 100 100 0 100 0.21 30 0 20 100 too 70 100 100 0 95 0.14 10 0 20 100 91 20 95 too 0 95 0.07 0 0 0 90 90 0 80 90 0 60 Ex. 53 0.56 30 0 100 100 91 80 100 100 0 100 0.21 10 0 30 100 100 60 98 100 0 98 0.14 0 0 0 15 90 0 80 10 0 50 0.07 0 0 0 10 70 0 50 70 0 30 Ex. 55 0.56 90 0 100 100 100 95 100 1001 0 100 0.21 80 0 91 100 100 70 100 100 0 95 0.14 40 0 60 91 91 40 98 100 0 95 0.07 0 0 0 90 15 0 90 15 0 70 Ex. 54 0l56 90 0 95 100 100 90 100 100 0 too 0.21 90 0 70 100 100 90 100 100 0 100 0.14 60 0 20 100 100 40 100 100 0 99 0.07 0 0 0 95 90 20 95 91 9 60 Ex. 123 0.56 0 0 0 100 98 80 95 100 0 98 L28 0 0 '0 95 95 20 95 95 0 80 0.14 0 0 0 95 85 0 60 IS 0 20 0.07 0 0 0 30 40 0 0 30 0 0 Ex. 124 0.36 0 0 0 S3 70 0 90 50 0 40 0.21 0 0 0 80 80 0 70 10 0 20 0.14 0 0 0 20 40 0 0 40 0 0 0.07 0 0 0 0 0 0 0 0 0 0 Ex. 101 056 30 0 95 100 100 20 too 100 0 20 0.21 30 0 60 100 100 0 100 100 0 10 0.14 0 0 40 too 95 0 90 too 0 IS 0.07 0 0 0 95 95 0 70 95 0 0 Ex. M 0.56 30 0 100 100 100 70 100 too 0 98 021 0 0 <0 100 98 20 100 95 0 95 014 0 0 0 95 95 0 90 95 0 80 0.07 0 0 0 80 70 0 60 80 0 30 Ex. 69 0.56 90 0 100 100 too 100 too 100 0 100 0.21 Yu 0 10 100 100 98 100 100 0 100 0.14 20 0 0 100 100 70 too 100 0 98 0.07 0 0 0 90 80 20 90 90 0 90 Ex. 80 0.56 40 0 too too 100 70 100 100 20 98 0.21 10 0 100 100 100 30 100 100 0 95 014 0 0 90 91 95 0 95 98 0 60 0.07 0 0 0 10 70 0 80 90 0 20

Table 25

Raw k / ha Rooms Coe Rooms Rape Flax Alft Sofl Pea · 2.4 91 30 100 100 100 100 90 that 1.2 90 20 100 100 100 100 20 90 A 90 0 JOO JOO (00 100 0 20 J 90 0 93 too 100 too 0 10 .13 I do 0 90 90 90 93 0 0

Compounds of the present invention have been found to be extremely effective as herbicides in various crops, including cotton, rice, sugarcane, sunflower, peanuts, wheat, barley, coffee, citrus plants. Some of the compounds of the invention are particularly useful in rice. In Table 23, the data show the effect of different compounds of the invention on different weeds in the aforementioned crops.

The plant species are labeled with: Sobe - Cotz soybean - cotton

Rrpw - Drosera rotunndifolia / chenopodium Shea - sugarcane

Sijg - Sorgum hajepense

Reri - red rice

Wipm - Panicum miliaceum Bygr - Echinochloa crus-gall Yens - Cyperus esculentus

The procedure used is the one described above in connection with Tables 20 and 21. Observations are made about 3 weeks after planting. Under each designation of the plant species, Table 23 shows the observed growth retention rate. As above, 100 means complete control, 0 means no control.

The preliminary / pre-growth / herbicidal activity of dimethyl 2- (difluoromethyl) -6- (trifluoromethyl) -4-isobutyl-

3,5-Pyridinedicarboxylate for the different crop types is listed in Table 24. Using the same procedure as described in connection with Tables 20 and 21, the herbicidal effect on the crops listed in Table 24 was observed at different application ratios. The data in Table 24 show that cotton is highly tolerable and peanuts and sunflower have some tolerance for this compound, with these crops remaining relatively unaffected by herbicides. Herbicidal activity is listed in Table 24, where 100 means complete control and 0 indicates no control. Crops with abbreviations are soybean / Sobe /, cotton / Cotz /, sugar beet / Sube /, alfalfa / Alfz /, sunflower / Sufi /, peanut / turnips /.

The tables above show one aspect of the present invention, i. the use of the compounds of the invention for the destruction or damage of undesirable plants, i. weeds.

As can be seen from the data above, some of the compounds are sufficiently safe in many crops, such as cotton, and thus can be used to selectively control weeds in such crops.

The herbicidal compounds of the invention including concentrates, which must be diluted before administration, may contain at least the active ingredient and the additive in liquid or solid form. The compounds are prepared by mixing the active ingredient with the potentiating additive, including diluents, fillers, carriers and conditioning agents, which convert the compound into finely divided multiple solids, granules, pellets, solutions, dispersions or emulsions.

Thus, the active ingredient can be used with the addition of a finely divided solid, a liquid of organic origin, water, a wetting agent, a dispersing agent, an emulsifying agent, or any suitable combination thereof.

Suitable wetting agents are thought to include alkylbenzene and alkylnaphthalene sulfonates, sulfated oily alcohols, amines or acid amides, long-chain sodium isothionate acid esters, sodium sulfosuccinate esters, sulfated or sulfonated, sulfonated, sulfonated, sulfonated, sulfonated, sulfonated, bitartarate acetylene glycols, polyoxyethylene derivatives of alkylphenols (especially isooctylphenol and nonylphenol) and polyoxyethylene derivatives of mono-high fatty acid esters of hexitol anhydrides / e.g. sorbitan (s) castor oil polyoxyethylene derivatives.

Preferred dispersants are methylcellulose, polyoxyethylene / polyoxypropylene block copolymers, polyvinyl alcohol, sodium ligninsulfonates, polymer alkylnaphthalene sulfonates, sodium naphthalenesulfonate, polymetallic bisnaphthalene sulfonate.

Moisturizing powders are water-dispersing compounds containing one or more active ingredients, an inert solid filler and one or more wetting and dispersing agents. Inert solid fillers are usually of mineral origin such as natural clays, infuser soil and synthetic materials derived from silicone and the like. Examples of such fillers include kaolin, bentonite, attapulgite clay and synthetic magnesium silicate. The wetting powder compounds of the present invention typically comprise from more than 0.5 to 60 parts / preferably from 5-20 parts / active ingredient, from about 0.25 to 25 parts / preferably 1-15 parts / wetting agent, from about 0.25 to 25 parts / preferably 1.0-15 parts / of the dispersant and 5 to about 95 parts / preferably 5-50 parts / of the inert solid filler, all parts equal in weight to the compound . Where necessary, from about 0.1 to 2.0 parts of the inert solid filler may be replaced by a corrosion inhibitor or foam agent, or both.

Other recipes include powdered concentrates consisting of 0.1 to 60% by weight of the active ingredient on a suitable excipient, these powders may be diluted for use at concentrations within about 0.1-10% by weight.

Aqueous suspensions or emulsions can be prepared by stirring an anhydrous solution of a water-insoluble active ingredient and an emulsifying agent with water to form a homogeneous mass and then homogenized to give a suitable emulsion of very finely divided particles. The resulting concentrated aqueous suspension is characterized by extremely small particle sizes, so that when diluted and sprayed, the coating is very uniform. Suitable concentrations of these recipes include from about 0.160%, preferably 5.50% by weight, of the active ingredient, the upper limit being determined by the solubility limit of the active ingredient and the solvent.

Concentrates are usually solutions of the active ingredients in water-miscible or partially water-immiscible solvents for one with surfactants. Suitable solvents for the active substances (ingredients) of the present invention include dimethylformamide, chlorinated solvents, dimethylsulfoxide, N-methylpyrrolidone, hydrocarbons and water-miscible esters or ketones. Other high concentration liquid concentrates can be prepared by dissolving the active ingredient in a solvent and then diluting it, e.g. with ketoris to obtain a sprayable concentration.

The concentrate compounds according to the invention typically contain from about 0.1 to 95 parts / preferably 5.60 parts / surfactant and when necessary about 4 to 94 parts of solvent, all parts by weight based on the total weight of the emulsifying oil .

Granules are physically stable particles containing active ingredients adhered or distributed on a basic matrix by an inert, finely divided filler. To assist in the extraction of the active ingredient from the fragment in the compound, a surfactant such as those may be present. Natural clay, pyrophyllites, illites and vermiculites are examples of possible mineral fillers. Preferred fillers are porous, absorbent, tableted particles, such as tableted and enriched fractional atapulgite or thermally expanded fractured vermiculite and finely divided clay such as kaolin clay, hydrated attapulgite or bentonite. These fillers are sprayed or mixed with the active ingredient to form the herbicide granules.

The granular compounds of the invention may contain from about 0.1 to about 30 parts by weight. of the active ingredient per 100 parts by weight clay and 0 to about 5 parts by weight surfactant per 100 parts by weight particular clay.

The compounds of the invention may also contain other additives, such as fertilizer, other herbicides, other pesticides, and the like, used as action enhancers or in combination with some of the additives described. Chemicals useful in combination with the active ingredients of the present invention include, for example, triazines, ureas, carbamates, acetanilides, uracils, acetic acid or phenolic derivatives, thiolcarbamates, triazoles, benzoic acids, nitriles, biphenyl ethers and the like like: heterocycles sulfur derivatives

2-chloro-4-ethylamino-6-isopropylamino-s-triazine

2-chloro-4,6-bis (isopropylamino) -striazine

2-chloro-4,6-bis (ethylamino) -3-triazine

3- Isopropyl-1H-2,1,3-benzothiadiazine-

4- (3H) -OH 2.2 dioxide

3-amino-1,2,4-triazole 6,7-dihydrodipyrido / 1,2-a: 2 ', 1'-c] -pyrazidinium salt

5-bromo-3-isopropyl-6-methyluracil

1,1 '-dimethyl-4,4'-bipyridinium

3-methyl-4-amino-6-phenyl-1,2,4-triazin-5- (4H) one

2- (4-chloro-6-ethylamino-1,3,5-sim-2triazinylamino) -2-methylpropionitrile

3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4 / 1 H, 3 H / dione

4- amino-6- (tertiary butyl) -3-methylthio-az-triazin-5 (4H) one

5-amino-4-chloro-2-phenyl-3 (1H) -pyridazinone

5-methylamino-4-chloro-2 - / - '- trifluoro-tolyl (-3 (2H) -pyridazinone)

5-Bromo-3- (sec-butyl) -6-methyluracil Urea

N- (4-chlorophenoxy) phenyl-N, N-dimethylcarbamide

N, N-dimethyl-N-N '- / 3-chloro-4-methylphenyl / urea

3- (3,4-dichlorophenyl) -1,1-dimethylurea

1,3-dimethyl-3- (2-benzothiazolyl) urea

3-p-chlorophenyl / -1,1-dimethylcarbamide 1-butyl-3- (3,4-dichlorophenyl) -1-methylurea

N - / 3-trifluoromethylphenyl / -Ν, Ν 'dimethyl urea

3- (3,4-dichlorophenyl) -1, methoxy-1-methylurea

2-χπορο-Ν- (1/4-methoxy-6-methyl-1,3,5triazin-2yl) aminocarbonyl / benzenesulfonamide methyl-2 /// 1 / 4,6-dimethyl-2-pyrimidinyl / amino-carbonyl / amino / sulfonyl / benzoate

Carbamates / thiocarbamates

2-chloroallyl-diethyldithiocarbamate

S- (4-chlorobenzyl) N, N -diethylthiocarbamate isopropyl N- (3-chlorophenyl) carbamate 8-2,3-dichloroallyl N, N-diisopropylthiocarbamate

8-M, M-dipropylthiocarbamate

S is propyl-N, N-dipropylthiocarbamate

8-2,3,3-trichloroallyl Ν, Ν-diisopropylthiocarbamate ethyl dipropylthiolcarbamate

Acetamides / acetanilides / anilines / amides

2-chloro- N, N-diallylacetamide

N, N-dimethyl-2,2-diphenylacetamide

N- (2,4-dimethyl-5-11) trifluoromethyl / sulfonyl amino-1-phenylacetamide

N-isopropyl-2-chloroacetamide

2'6'-diethyl-L1-methoxymethyl-2-chloroacetanilide

2'-methyl-6'-ethyl-N- (2-methoxyprop-2yl) -2-chloroacetanilide, -trifluoro-2,6-dinitro-N-dipropyl-p-toluidine

N- (1-dimethylpropynyl) -3,5-dichlorobenzamide, -trifluoro-2,6-dinitro-N-propyl-N-propyl-N- (2-chloroethyl) -p-toluidine

3,5-dinitro-4-dipropylamino-benzenesulfonamide N- (1-ethylpropyl) -3,4-dimethyl-2,6-dinitro-benzamine

Acids / esters / alcohols

2,2-dichloropropionic acid

2-methyl-4-chlorophenoxyacetic acid

2,4-Dichlorophenoxyacetic acid methyl-2-14- (2,4-dichlorophenoxy) phenoxypropionate

3-amino-2,5-dichlorobenzoic acid-methoxy-3,6-dichlorobenzoic acid

2.3.6-Trichlorophenylacetic acid N-1-naphthylphthalamic acid sodium 512-chloro-4- (trifluoromethyl / phenoxy) 1-2 nitrobenzoate

4.6-dinitro-o-sec-butylphenol

N- (phosphonomethyl) glycine and its salts potassium 4-amino-3,5,6-trichloropicolinate

2.3-Dihydro-3,3-dimethyl-2-ethoxy-5-benzofuranyl methanesulfonate

Ethers

2.4-dichlorophenyl-4-nitrophenyl ether

2-chloro-,, -trifluoro-p-tolyl-3-ethoxy-5 Ci-4-nitrodiphenyl ether

-chloro-1- (3-ethoxy-4-nitrophenoxy) -4-trifluoromethyl gasoline

Others

2,6-dichlorobenzonitrile monosodium acid methanesonate disodium methanesonate

Fertilizers useful in combination with the active ingredients include, for example, ammonium nitrate, urea, potash and superphosphate. Other useful additives include materials in which the plant roots and grows, such as compost, fertilizer, humus, sand and the like.

The herbicidal compositions of the types described above, which include compounds according to the invention are listed below:

Weight percent

I. Emulsifying concentrates

A. Compound of Example 1445,6

Monochlorobenzene26,6

C, fragrances 17,8

Calcium sulfonyl gasoline sulfonate 5.0

Castor oil, ethylated with 54 mol

100,0

B. Compound of Example Ne 10133,7

Monochlorobenzene56,3

Calcium sulfonyl gasoline sulfonate 4.3

Castor oil, ethylated with 54 mol 5.7

100,0

C. Compound of Example 511.0

Free acid of complex organic phosphate on an aromatic or aliphatic hydrophobic base / e.g. GAFAC RE-610, a registered trademark of GAF Corp./ 5.59

Polyoxyethylene / polyoxypropylene block copolymer with butanol / e.g. Tergitol XH, a registered trademark of Union Carbide Corp./1,11

C, aromas5,34

Monochlorobenzene76.96

100.00

D. Compound of Example No. 1625.00

Free acid from complex organic phosphate on an 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

Monochlorobenzene63,65

100.00

II. Liquid

A. Compound of Example No. 625.00

Methylcellulose 0.3

Silica gel 1.5

Sodium lignosulfonate 3.5

Sodium N-methyl-N-oleyl taurate -2.0

Water67.7

100,0

B. Compound of Example No. 1745.0

Methylcellulose3,3

Silica gel 1.5

Sodium lignosulfonate 3.5

Sodium L1-methyl-1H-oleyl taurate 2.0

Water47.7

100.00

III. Moisturizing powders / powder /

A. Compound of Example 525.0

Sodium lignosulfonate 3.0

Sodium N-methyl-N-oleyl-taurate 1.0

Amorphous silicone / synthetic / 71.0

100.00

B. Compound of Example No. 2180.00

Sodium dioctyl sulfosuccinate 1.25

Calcium lignosulfonate 2.75

Amorphous silicone / synthetic / 16.66

100.00

B. Compound of Example No. 610.00

Sodium lignosulfonate 3.0

Sodium N-methyl-N-oleyl-taurate 1.0

Kaolin clay86.0

100,0

V. Powdery

A. Compound of Example 22.0

Atapulgit98.00

100.00

B. Compound of Example No. 960.00

Montmorillonite 40,00 tao

B. Compound of Example No. 1530.00

Ethylene glycol 1.0

Bentonite69,00

100.00

d. Compound of Example # 16 1.0 Infuser finger 99.00 100.00 VI. Granules

A. Compound of Example No. 8

Granular attapulgite / 20/40 mesh /

15,00

85.00

100.00

B. Compound of Example No. 9 Infusion Finger / 20/40 / 30,00 70,00 100.00 IN. Compound of Example No. 18 1.0 Ethylene glycol 5.0 Methylene blue 0.1 - Pyrophyllitis 93.9 100.00 G. Compound of Example No. 19 5.0 Pyrophyllitis 95,0 100,00

According to the invention, effective amounts of the compounds of the invention are applied to the soil containing the seeds or seedlings, or can be applied to the plant medium in any convenient manner. The application of liquid and particulate solids to the soil can be accomplished in conventional ways, e.g. with powder spray, with sprays, including powder spray. The compounds may also be applied by airplane powder or sprayed due to their low dose efficacy.

The exact amount of active substance to be administered depends on various factors - the plant species, the stage of development, the type and conditions of the soil, the amount of rainfall and the specific compounds applied. In selected pre-application (pre-emergence) or soil, a dose of 0.02 to about 11.2 kg / ha is usually used, preferably 0.1 to about 5.60 kg / ha. In some cases, higher or lower doses may be required. From the description, including the examples above, one skilled in the art can readily determine the optimum ratio to be used in each case.

The term "soil" is used in the broadest sense to include all conventional "soils" as defined in Webster's New International Aictionary, Second Edition, Unabridged (1961). This term refers to any substance or medium in which a plant can root and grow and includes, in addition to soil, also compost, fertilizer, rock masses, humus, sand and the like that can promote plant growth.

Although the present invention has been described with reference to specific embodiments, the details should not be construed as limiting.

Claims (5)

Claims 1. 2,6-Substituted Pyridine Compounds of Structural Formula R wherein R is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower alkenylalkyl, haloalkyl, haloalkenyl, C ₃ _, cycloalkyl, C _{3 6} cycloalkanylalkyl, phenyl, phenylmethyl, alkoxyalkyl, benzyloxymethyl, alkylthioalkyl, dialkoxyalkyl Alkyloxyalkylalkylalkylalkylalkylalkylalkylalkylalkyloxycarbonyl a group consisting of furyl, pyridyl, thienyl, thienyl, oxiranyl and aziridinyl, wherein the radical is bonded to the pyridine ring via a C-C bond and lower alkyl substituted with a saturated or unsaturated heterocyclic radical selected from the group consisting of furyl, pyridyl, thienyl, tyranyl, oxiranyl and aziridinyl; R ₍ and R ₂ are independently selected from alkyl, fluorinated methyl and chlorofluorinated methyl radicals, provided that R ₁ and R 1 are fluorinated methyl or chlorofluorinated methyl radical and X and Y are independently selected from the group consisting of -C 22 * 3 in which Z 1 is NR ₇ , where R ₇ is selected from hydrogen and lower, alkyl and where Z ₂ is selected from O and S, and where R ₃ at each occurrence is independently selected from hydrogen, alkyl C ₁₄₆ , alkenylalkyl C _{3 4} , haloalkyl C, ₄ , cyanoalkyl, cycloalkanylalkyl, alkynylalkyl C _{3 4} provided that when Z ₂ is S in both manifestations, R ₃ is lower alkyl C ₁₂ -C 14 where R ₄ is from hydrogen and halogen bran -w _{h /} , NXR ₆ where R 1 and R ₆ are independently selected from hydrogen, lower alkyl and phenyl, -CH ₂ OH and C = N. The compound of claim 1, wherein one of R ₍ and R 1 is trifluoromethyl and the other is a fluorinated methyl radical. The compound of claim 1, wherein one of R 1 and R ₂ is trifluoromethyl and the other is alkyl radical. A herbicidal composition comprising a herbicidally effective amount of a compound represented by the structural formula wherein R is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower alkenylalkyl, haloalkyl, haloalkenyl, C _{3 7} cycloalkyl, C _{3 6} cycloalkylalkyl, phenyl, phenylmethyl, alkoxyalkyl, benzyloxymethyl, alkylthioalkyl, dialkoxyalkyl, / 1-alkoxy-1-alkylthio / alkyl, aminoalkyl, alkylaminoalkyl, dialkylamino-alkyl, alkylsulfonylalkyl, alkylsulfinylalkyl, alkyl substituted with dialkilsulfonieva salt , u ianoalkyl, carbalkoxyalkyl, carbalkoxyalkenyl, dialkylaminoalkenyl, saturated or unsaturated heterocyclic radicals selected from the group consisting of furyl, pyridyl, thienyl, thiaryl, oxiranyl and aziridinyl, where the radical C is substituted with alkynidylalkyl, alkylcarbonyl with a saturated or unsaturated heterocyclic radical selected from the group consisting of furyl, pyridyl, thienyl, thianyl, oxiranyl and aziridinyl; R ₍ and Rj are independently selected from alkyl, fluorinated methyl, and chlorofluorinated methyl radicals, provided that one of R) or Rj is fluorinated methyl or chlorofluorinated methyl radical and X and Y are independently selected from the group consisting of -C \ z ₂ R ₃ where Z is NR _? , where R _? is selected from hydrogen and lower alkyl, and where Z ₂ is selected from 0 and S, and wherein R ₃ in each occurrence is independently selected from hydrogen, alkyl C _{2 4} , alkenyl C _{3 4} , haloalkyl C _{2 4} , cyanoalkyl, cycloalkanylalkyl, and alkynylalkyl C ₃ , provided that when Z ₂ is S in both manifestations, R ₃ must be lower alkyl C, ₂ , -C \ «4 pyridylthiyl, thianyl, oxiranyl and aziridinyl; R! and R ₂ are independently selected from alkyl, fluorinated methyl and chlorofluorinated methyl radicals, provided that one of Rj and R ₂ is fluorinated methyl or chlorofluorinated methyl radical and X and Y are independently selected from the group consisting of where R ₄ is selected from the group selected from hydrogen and halogen. But with ^Ri N 1 R 1 where R ₅ and R ₆ are independently selected from hydrogen, lower alkyl and-phenyl, -CH ₂ OH and -C = N. 5. A method of combating unwanted vegetation, characterized in that it comprises administering to the place of distribution a herbicidally effective amount of a compound represented by the structural formula -C 1 Z ₂ R ₃ where Z is NR 1, where R is selected from hydrogen and lower alkyl, and wherein Z ₂ is selected from O and S, and wherein R ₃ at each occurrence is independently selected from hydrogen, alkyl C ₁₄ , alkenylalkyl C ₃₄ , haloalkyl C _{2 4} , cyanoalkyl, cycloalkanylalkyl and alkynylalkyl C _{3 4} , provided that when Z ₂ is S at both values, 1% is lower alkyl C ₁₂ where R ₄ is selected from aq. and halogen wherein R is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower alkenylalkyl, haloalkyl, haloalkenyl, C ₃₇ cycloalkyl, C ₃₆ cycloalkylalkyl, phenyl, phenylmethylalkylalkylalkylalkylalkylalkylalkylalkyl Alkoxyalkyl, amino, alkyl, alkylamino, alkylcarbamide, alkyl m group consisting of furyl, pyridyl, thienyl, thienyl, oxiranyl and aziridinyl, wherein the radical is bonded to the pyridine ring by a C-C bond and lower alkyl substituted by a saturated or unsaturated heterocyclic radical selected from the group consisting of furyl where R 1 and R ₆ are independently selected from hydrogen, lower alkyl and phenyl, -CH ₂ OH and -C = N.