MXPA97004318A - Process for the manufacture of 2-aril-5-perfluoroalquilpirrol derivatives and useful intermediate products of the mis - Google Patents

Abstract

A one-step process for preparing 2-aryl-5-perfluoroalkyl pyrrole derivatives is provided directly from the perfluoroacetylated Strecker reaction product. Said pyrrole derivatives are insecticides, and also useful as precursors for other insecticidal arylpyrrole compounds. In addition amide nitrile intermediates are provided, useful in the preparation of arylpyrrole insecticide compounds

Description

PROCESS FOR THE MANUFACTURE OF 2-ARIL-5-PERFLÜOROALQOILPIRROL DERIVATIVES AND OTHED INTERMEDIATE PRODUCTS THEREOF BACKGROUND OF THE INVENTION Arylpyrrole carbonitrile compounds are highly effective insecticidal, acaricidal, and nematicidal agents with a single mode of action and a broad spectrum of activity. In particular, 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile compounds demonstrate effective control over a wide range of pests, and can control resistant pests, such as biotypes resistant to pyrethroid, organophosphate, cyclodiene, organochlorine , organotin, carbamate, and benzophenylurea, from Helicovefa / Heliothis spp., Spodoptera spp., Trichoplusia spp., Pseudoplusia spp., and Tetranychus spp. Because there is apparently no cross-resistance, the 2-aryl-5 compounds (trifluoromethyl) pyrrole-3-carbonitrile and its derivatives have potential for use in resistance management programs. In addition, these pyrroles have little effect on beneficial species, making them also excellent candidates for integrated pest management programs. These programs are essential in today's crop production. Therefore, the methods for preparing said pyrroles and the intermediates to facilitate their manufacture are of great use. Among the present methods for preparing 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile on a manufacturing scale are 1,3-dipolar cycloaddition of 3-oxazolin-5-one with 2-chloroacrylonitrile (US 5,030). .735), and the cycloaddition reaction of the appropriate oxazole amine derivatives with 2-chloroacrylonitrile or 2,3-dichloropropionitrile (US 5,446,170). It is also known the 1,3-dipolar cycloaddition of the mesionic intermediate of the acid-catalyzed cyclization of a Reissert compound with a suitable alkyne, to give an N-substituted pyrrole product, as described by WM McEwen et al., "Journal of Organic Chemistry ", 1980, 45, 1301-1308. However, these mesionic intermediates go through a reaction of 1, 4- REP: 24795 cycloaddition with ethylenic dienophiles to give an aroylpyrrole derivative, and as such, are not useful as precursors of arylpyrrole insecticides. Therefore, it is an object of this invention to provide an alternate and efficient manufacturing process for the arylpyrrole class of highly effective pesticides. It is another object of this invention to provide a source of important intermediate nitrile amide compounds, useful in the manufacture of arylpyrrole pesticidal agents. It is an advantage of this invention that the manufacturing process consists of a single effective step that produces an arylpyrrole precursor of formula I, capable of being converted to a wide variety of highly effective insecticidal, acaricidal, and nematicidal agents. It is another advantage of this invention, the fact that the total number of synthetic steps from the initial Strecker reaction product to the final insecticidal arylpyrrole product, is reduced from the number of synthetic steps required by the use of current known methods, such as described herein before. It is a feature of this invention, the fact that the process provides a region-specific product. These and other features and objects of the invention will become more apparent from the detailed description set forth herein below.

SUMMARY OF THE INVENTION The present invention provides an effective one-step process for the manufacture of a 2- "aryl-5-perfluoroalkylpyrrole of formula I wherein R is hydrogen or C? -C6 alkyl optionally substituted with a CtC4 alkoxy group or phenyl; n is an integer of 1, 2, 3, 4, 5, 6, 7, or 8; W is CN, N0, COORi, or COR2; L is hydrogen or halogen; M and Q are each independently hydrogen, halogen, CN, N02, C? -C alkyl, C? -C4 haloalkyl, C? -C alkoxy, C? -C haloalkoxy, C? -C4 alkylthio, C? -C4 alkylsulfinyl. , or when M and Q are in adjacent positions, they can be taken together with the carbon atoms to which they are attached, to form a ring in which MQ represents the structure -OCH20-, -OCF20-, or -CH = CH -CH = CH-; R1 and R2 are each independently CrC4 alkyl; R3, R4, and R5 are each independently hydrogen, halogen, N02, CHO, or R4 and Rs can be taken together with the atoms to which they are attached to form a ring, in which R4R5 is represented by the structure Re, R7 , Re. And R9 are each independently hydrogen, halogen, CN, or N02; and X is O, or S, which comprises reacting a nitrile amide of formula II CN j - COC wherein A, R, and n are as described hereinbefore for formula I, with at least one molar equivalent of a dienophile of formula III Y / 2 \ w i. -. wherein W is as described hereinbefore for formula I, and Y is hydrogen, Br or Cl, with the proviso that when R is hydrogen, then Y must be Br or Cl, in the presence of an acid and a solvent, and essentially in the absence of water consequences. To the extent that water is present in the process of the invention, hydrolysis of the starting materials will take place, resulting in lower yields and decreased purity of the desired arylpyrrole final product. The term halogen as used in the specification and claims designates Cl, Br, F, or I, and the term haloalkyl encompasses any alkyl group of carbon atoms, which may contain from 1 to 2? halogen atoms that can be the same or different.

The present invention further provides a nitrile amide compound of formula lia CN - < \ R (lia) wherein n and A are as described hereinbefore for formula I, and R 'is Ci-Ce alkyl optionally substituted with a d-C4 alkoxy or phenyl group.

DETAILED DESCRIPTION OF THE INVENTION The processes, to be useful in a manufacturing scale, preferably contain key intermediate compounds that can be obtained in high to quantitative production, which are stable with isolation or in situ, which can be produced from simple or readily available initial materials, which can be easily converted to the desired final product of manufacture in a minimum of reaction steps, with optimum production and purity, and if applicable, in a regional or stereospecific manner. It has now been found that the 2-aryl-5-perfluoroalkylpyrroles of formula I can be prepared directly from the perfluoroacylated nitrile amino product of formula II, by a single step synthesis, by reacting the compound of formula II with a dienophile of formula III, in the presence of an acid and a solvent, and essentially in the absence of water. The reaction is shown in Flow Chart I, where n, A, R, and W are as defined hereinbefore.

Flowchart I The solvents contemplated for use in the process of the invention are those solvents capable of sustaining essentially anhydrous conditions and partial or complete dissolution of the nitrile amide compound of formula II. Such solvents include organic solvents such as: aromatic hydrocarbons, such as benzene, xylene, toluene, and the like, preferably toluene; chlorinated aromatic hydrocarbons, such as chlorobenzene; carboxylic acid amides, such as dimethylformamide, N-methylpyrrolidone, and the like, preferably dimethylformamide; nitriles, such as acetonitrile, propionitrile, and the like; alcohols, such as isopropanol, 1-butanol, sec-butanol, and the like, preferably f-butanol. These solvents can be used alone or in combination of two or more. Acids suitable for use in the process of the invention are any acid capable of relative dehydration, because the increased water provides decreased production or purity. Suitable acids include sulfuric acid, methanesulfonic acid, t-fluoro-methanesulfonic acid, p-toluenesulfonic acid, tetrafluoroboric acid, tetrafluoroboronic acid complexes, and the like. Also suitable are boron trifluoride complexes, such as boron trifluoride acetic acid, boron trifluoride dihydrate, and the like. Preferred arylpyrrole compounds of formula I obtained by the process of the invention are those wherein n is 1 or 2, W is CN, and A is optionally substituted phenyl. The most preferred compounds of formula I obtained by the process of the invention are those wherein n is 1 or 2, W is CN, A is optionally substituted phenyl, and R is hydrogen, methyl, or ethoxymethyl; particularly preferred are those wherein n is 1, W is CN, A is p-chlorophenyl, 2,5-dichlorophenyl, 3,4,5-trichlorophenyl, p-bromophenyl, a, a, a-trifluoro-p- tolyl, or p-trifluoromethoxyphenyl, and R is hydrogen, methyl, or ethoxymethyl. The nitrile amide compounds of formula II wherein R is hydrogen, and their preparation, are described in U.S. 5,426,225. The nitrile amide compounds of formula II, wherein R is other than hydrogen, ie, formula Ia, can be obtained by perfliorioacylation of the appropriate amino nitrile of formula VI. The aminonitriles of formula VI are correspondingly obtained easily from their available benzaldehyde, furfurylaldehyde, or thienylmethylaldehyde precursors, by the well known Strecker reaction. The reaction sequence is shown in Flow Diagram II, where n, A, and R are as described hereinbefore for formula I, m is an integer of 1 or 2, Xi is Cl, OR10, or O, and R10 is hydrogen or C? -C6 alkyl, with the proviso that when Xi is O, then m must be 2, and when Xi is Cl or OR10, then m must be 1.

Flow Diagram II CN 'C F CO! X. r. 2 n * 1 • CHO R - NH. NaCN I NH (VI) CN I A- CH N \ - COC r. F 2"r. - -. R (I I) As an advantage, the nitrile amide of formula II can be converted directly to the desired 2-aryl-5-perfluoroalkylpyrrole of formula I, in a single step as shown hereinabove in flow diagram I. According to the process of the invention, the nitrile amide of formula II can be dispersed in a suitable solvent or mixture of solvents, and mixed with at least one molar equivalent of an appropriate dienophile of formula III, in the presence of an acid under essentially reaction conditions anhydrous The pyrrole of formula I obtained in this way can be isolated using conventional means, such as extraction, filtration, distillation, chromatographic separation, or the like. The rate of formation of the pyrrole of formula I can be increased with an increased temperature. However, it is understood that excessively high reaction temperatures can cause decomposition or unwanted side reactions, and a concomitant decrease in the production and purity of the product. Typical reaction temperatures may vary from 20 ° C to the reflux temperature of the solvent or mixture of solvents. Typically, temperatures of about 20 ° -150 ° C are used, preferably 40 ° -100 ° C. The present invention also provides nitrile amide intermediates of formula R 1 where n is an integer of 1, 2, 3, 4, 5, 6, 7, or 8; R 'is C? -C6 alkyl optionally substituted with a C? -C4 alkoxy or phenyl group; L is hydrogen or halogen; M and Q are each independently hydrogen, halogen, CN, N02, CrC alkyl, C? -C4 haloalkyl, C? -C alkoxy, C1-C4 haloalkoxy, alkylthio dC, C? -C4 alkylsulfinyl, or when M and Q are in adjacent positions, they can be taken together with the carbon atoms to which they are attached, to form a ring in which MQ represents the structure -OCH20-, -OCF20-, or -CH = CH-CH = CH-; R1 and R2 are each independently C1-C4 alkyl; R3, R4, and Rs are each independently hydrogen, halogen, N02, CHO, or R4 and R = can be taken together with the atoms to which they are attached to form a ring, in which R4R5 is represented by the structure R R I ' Re, R7, Re, and R9 are each independently hydrogen, halogen, CN, or N02; and X is O, or S. Preferred intermediate compounds of formula Ha of the invention are those wherein n is 1 or 2, R 'is methyl or ethoxymethyl, and A is optionally substituted phenyl. The most preferred compounds of formula Ha are those wherein n is 1, R 'is methyl, and A is p-chlorophenyl, p-bromophenyl, 3,5-dichlorophenyl, 3,4,5-trichlorophenyl, p- (a, a, a-trifluoro) tolyl, or p-trifluoromethoxy phenyl . While the compounds of formula I possess insecticidal activity, their greatest utility may be as precursors for certain compounds of formula IV. As an advantage, the process of the invention allows the preparation of insecticidal, acaricidal, and nematicidal agents of 2-aryl-4-halo-5- (perfluoroalkyl) pyrrole-3-carbonitrile of formula IV, in as few as four synthetic steps , from initial arylaldehyde materials that can be obtained easily. Accordingly, perfluoroacylation of the Strecker reaction product (VI), followed by the step of the process of the invention, gives the precursor of arylpyrrole (I), which can be halogenated to give the desired pesticide product (IV). The synthesis is illustrated in Flow Chart III, where n, A, R, Y, and W are as described herein above, and Hal is halogen, preferably Br or Cl. Flowchart III II) haloenation / w The halogenation methods may be any method known as those described in U.S. 5,010,098, or U.S. 5,449,789. To provide a clearer understanding of the invention, the following examples are set forth below. These examples are purely illustrative, and should not be construed as a limit to the field or fundamental principles of the invention in any way. In fact, for those skilled in the art various modifications of the invention will be apparent, in addition to those shown and described herein, of the following examples and the foregoing description. Said modifications are also intended to fall within the scope of the appended claims. The terms 1 H NMR, 13 C NMR, and 19 F NMR denote proton nuclear magnetic resonance, carbon 13, and fluorine 19, respectively. The term HPLC designates high performance liquid chromatography.

EXAMPLE 1 Preparation of N-lsopropylamino (p-chlorophenyl) acetonitrile C '? Isopropyl amine (88.7 g, 1.5 mole) is added to an aqueous solution of concentrated hydrochloric acid (125 mL, 1.5 mL) in water at 25 ° -30 ° C. The resulting mixture is treated sequentially with a solution of sodium cyanide (53.9 g, 1.1 mol) in water and methylene chloride at 30 ° C, is warmed at 35 ° C, treated with a solution of p -chlorobenzaldehyde (140.6 g, 1 mol) in methylene chloride over a period of 15-25 minutes, allow to warm, keep for 3 hours at 45 ° C and cool to room temperature. The phases are. they separate and the organic phase is washed with water and concentrated in vacuo to give a residue. The residue is crystallized from heptane, to give the title product as a pale yellow crystalline solid, 190.3 g (91.2% product), mp 72.0-73.0 ° C, identified by 1H analysis and 13C NMR.

EXAMPLE 2 Preparation of N- (p-chloro-a-cyanobenzyl) -2,2,2-trifluoro-N-isopropylacetamide A watery slurry of N-isopropylamino (p-chlorophenyl) acetonitrile (25.0 g, 0.12 mol) in trifluoroacetic anhydride is heated moderately at reflux temperature for 20 hours, and is concentrated in vacuo to give an oil residue. The oil is crystallized from toluene / heptane, to give the title product as a white solid, 26.5 g (72.4% product) mp 78.5-79.5 ° C, identified by 1H, 13C analysis , and 9F NMR.

EXAMPLE 3 Preparation of N-Benzyl-N- (p-chloro-a-cyanobenzyl) -2,2,2-trifluoroacetamide Aqueous hydrochloric acid (62.5 mL of 12 N, 0.75 mol) in water (100 mL) is treated with benzylamine (80.4 g, 0.75 mol) at < 20 ° C, then treated sequentially with a solution of sodium cyanide (27.0 g, 0.55 mol) in water and methylene chloride, heated to 35 ° C, treated with a solution of p-chlorobenzaldehyde (70.3 g, 0.5 mol) in methylene chloride, allowed to warm to 50 ° C, and maintained at 45 ° C for 3.5 hours. The phases are separated and the organic phase is washed with water and concentrated to a syrup residue. The residue is dissolved in toluene and ethyl acetate, treated with trifluoroacetic anhydride (105.0 g, 0.5 mol) at 20 ° -30 ° C for a period of 30 minutes, and diluted with heptane. The resulting white fluffy solid precipitate is filtered and dried, to give the title product, 119.8 g (70.7% product), mp 131 ° -132 ° C, identified by 1 H, 13 C, and 19 F NMR analysis.

EXAMPLE 4 Preparation of 2- (p-Chlorofonyl) -5- (trifluoromethyl) -pyrrole-3-carbonitrile A mixture of N- (p-chloro-a-cyanobenzyl) -2,2,2-trifluoroacetamide (10.5 g, 0.04 mol) and toluene is cooled to 5 ° -10 ° C under a nitrogen atmosphere , it is treated with trifluoromethanesulfonic acid (12.0 g, 0.08 mol), for a period of 20 minutes, left to warm to room temperature, and kept at 25 ° C for 3 hours. The formation of the intermediate salt of 5-amino oxazole is monitored by 19 F NMR (DMSO-d6). When the formation of the intermediate salt is complete, the mixture is cooled to below 20 ° C, treated with dimethylformamide and 2-chloroacrylonitrile (5.25 g, 0.06 mol), maintained at 25 ° C for 16 hours. - 18 hours, and treated with ethyl acetate and water. The phases are separated and the organic phase is washed with water and concentrated in vacuo to give a solid residue. Flash column chromatography of the residue on silica gel, charged and eluted respectively with 15% and 20% ethyl acetate in heptane, gives the title product as pale yellow crystals, 6.14 g, (57% product), mp 237 ° -240 ° C, identified by HPLC and NMR analysis.

EXAMPLE 5 Preparation of 2-Aryl-5- (trifluoromethyl) pyrrole derivatives Using essentially the same procedure described in Example 4, and substituting the appropriate starting material amino nitrile trifluoroacetylated, the following products are obtained: W mp ° C product L - -a v- 7 ¿g - 7 • ' X R. uro product CN EXAMPLE 8 Preparation of 2 - (? - Chlorophenyl) -5-trifluoromethyl-pyrrole-3-carbonitrile A mixture of p-toluenesulfonic acid (ptsa), monohydrate (19.1 g, 0.1 mol) in toluene is azeotropically dried using a Dean-Stark siphon, to obtain the anhydrous acid. The toluene is then removed in vacuo, and replaced with propionitrile. The resulting solution is treated with N- (p-chloro-a-cyanobenzyl) -2,2,2-trifluoroacetamide (13.1 g, 0.05 mol) and 2-chloroacrylonitrile (8.75 g, 0.1 mol ), is heated at 98 ° - 100 ° C for 18 hours, cooled to room temperature, and drowned with a mixture of water and ethyl acetate. The phases are separated, and the organic phase is washed with water and concentrated in vacuo, to give a residue. Flash column chromatography of the residue, using silica gel, charged and eluted with 20% ethyl acetate in heptane, gives the title product as pale yellow crystals, 4.2 g (39% product), identified by HPLC and analysis NMR.

EXAMPLE 7 Preparation of Methyl 2- (p-chloropheni0-5- (trifluoromethyl) pyrrole-3-carboxylate A watery paste of N- (p-chloro-a-cyanobenzyl) -2,2,2-trifluoroacetamide (10.5 g, 0.04 mol) in toluene, under a nitrogen atmosphere, is cooled to 10 ° C, treated with trifluoromethanesulfonic acid (12.0 g, 0.08 mol) for 10-15 minutes, allowed to warm to room temperature, and stirred for 3 hours. The reaction is monitored by 19 F NMR analysis (DMSO-d 6) to show the completion of the formation of the intermediate salt. When the formation is complete, the mixture is cooled to 10 ° C, treated with dimethylformamide, treated with methyl 2-chloroacrylate (7.2 g, 0.06 mol), allowed to warm to room temperature, stirred for 18 hours, and diluted with water and ethyl acetate. The phases are separated, and the organic phase is washed with water and concentrated, to give a solid waxy residue. Flash column chromatography of the residue on silica gel, charged and eluted with 20% ethyl acetate in heptane, gives the title product as a white crystalline solid, 7.6 g (62% product), mp 123 ° -125 ° C, identified by H analysis and 19F NMR.

EXAMPLE 8 Preparation of 2- (p-Chlorophenyl) -1-methyl-5 '(trifluoromethyl) pyrrole-3-carbonitrile A solution of N- (p-chloro-α-cyanobenzyl-2,2,2-trifluoro-N-methylacetamide (13.8 g, 0.05 mol) in toluene is treated with acrylonitrile (5.3 g, , 1 mole) and methanesulfonic acid (9.6 g, 0.1 mole), heated at 108 ° -110 ° C for 30 hours, drowned with water and extracted with ethyl acetate.The organic extracts are combined and concentrated in vacuo. to give a residue The residue is purified by flash column chromatography on silica gel, charged and eluted with 15% ethyl acetate in heptane, to give the title product as a pale yellow solid, 0.9 g, ( 63% product), mp 129 ° - 130 ° C, identified by 1H and 19F NMR analysis.

EXAMPLE 9 Preparation of 2- (p-Chlorophenyl) -1-methyl-5- (trifluoromethyl) pyrrole-3-carbonitrile A solution of N- (p-chloro-α-cyanobenzyl) -2,2,2-trifluoro-N-methylacetamide (13.8 g, 0.05 mol) in toluene is treated with tetrafluoroboric acid-diethyl etherate (10). , 5 g as is, 8.9 g real, 0.055 mol) at room temperature, heated to 60 ° C, treated with 2-chloroacrylonitrile (6.9 g, 0.075 mol) over a period of 25 minutes, maintained for 2 a 2.5 hours at 60 ° C, cooled and treated with ethyl acetate. The resulting solution is washed with water and concentrated to give a waxy residue. Flash column chromatography of the residue on silica gel, charged with 15% ethyl acetate in heptane and eluted with 20% ethyl acetate in heptane, gives the title product as pale yellow crystals, 3.1 g (22% product) , mp 129 ° - 130 ° C, identified by 1 H, 13 C, and 19 F NMR analysis.

EXAMPLE 10 Preparation of 2- (p-Chlorophenyl-1-methyl-5- (trifluoromethyl) pyrrole-3-carbonitrile A solution of N- (p-chloro-α-cyanobenzyl) -2,2,2-trifluoro-N-methylacetamide (13.8 g, 0.05 mol) in toluene is treated with 2-chloroacrylonitrile (4.4 g, 0.05 mol) and methanesulfonic acid (4.8 g, 0, 05 mol), heated at 110 ° C for 4 hours, treated with a second portion of 2-chloroacrylonitrile (4.4 g, 0.05 mol) and methanesulfonic acid (4.8 g, 0.05 mol), heated at 110 ° C for 12 hours, cooled and treated with ethyl acetate and water. The phases are separated, and the organic phase is washed with water and concentrated, to give a residue. The residue is chromatographed using silica gel, loaded with 15% ethyl acetate in heptane and eluted with 20% ethyl acetate in heptane, to give the title product as pale yellow crystals, 4.8 g (34% product), mp 129 ° - 130 ° C.

EXAMPLE 11 Preparation of 2- (p-Chlorophenyl) -1-isopropyl-5- (trifluoromethyl) pyrrole-3-carbonitrile A solution of N- (p-chloro-α-cyanobenzyl) -2,2,2-trifluoro-N-isopropylacetamide (6.1 g, 0.02 mol) in toluene is treated at room temperature with tetrafluoroboric acid diethyl etherate (4.2 g as is, 3.6 g real, 0.022 mol) under a nitrogen atmosphere, heated to 60 ° C, treated with 2-chloroacrylonitrile (2.62 g, 0.03 mol) for 15-20 minutes , maintained for 3 hours at 60 ° C, cooled to room temperature and treated with ethyl acetate and water. The phases are separated and the organic phase is washed with water and concentrated to give a brown residue of gum. Flash column chromatography of the residue on silica gel, charged and eluted with 15% ethyl acetate in heptane, gives the title product as a brown oil, 1.3 g (20.8% product), identified by 1H analysis , and 19F NMR and mass spectrum.

EXAMPLE 12 Preparation of -Benzyl-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile A solution of N- (p-chloro-a-cyanobenzyl) -2,2,2-trifluoro-N-benzylacetamide (10.6 g, 0.03 mol) in toluene is treated with methanesulfonic acid (3.2 g , 0.033 mol) and acrylonitrile (3.9 g, 0.045 mol), heated at 100 ° -105 ° C for 18 hours, cooled, treated with additional methanesulfonic acid (1.6 g, 0.017 mol), heated to 100 ° - 105 ° C for 22 hours, drowned with water and extracted with ethyl acetate. The organic extracts are combined, and concentrated in vacuo, to give a residue. The residue is purified by flash column chromatography, using silica gel, charged and eluted with 15% ethyl acetate in heptane, to give the title product as white crystals, 4.4 g (40.6% product), mp 103.5 ° - 105.5 ° C, identified by 1H, 3C, and 19F NMR analysis, and mass spectrum.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following:

Claims (10)

1. A process for the manufacture of a compound of formula I wherein R is hydrogen or dC 6 alkyl optionally substituted with a C 1 -C 4 alkoxy or phenyl group; n is an integer of 1, 2, 3, 4, 5, 6, 7, or 8; W is CN, N02, COOR ?, or COR2; L is hydrogen or halogen; M and Q are each independently hydrogen, halogen, CN, N02, C 1 -C 4 alkyl, C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, or when M and Q are in adjacent positions, they can be taken together with the carbon atoms to which they are attached, to form a ring in which MQ represents the structure -OCH20-, -OCF20-, or -CH = CH-CH = CH -; R1 and R2 are each independently C? -C4 alkyl; R3I R4, and Rs are each independently hydrogen, halogen, N02, CHO, or R4 and R5 can be taken together with the atoms to which they are attached to form a ring, in which R4R5 is represented by the structure t > R R? V V l "i * -c = c-c = c- Re, R7, Re, and R9 are each independently hydrogen, halogen, CN, or N02; and X is O, or S, characterized in that it is understood that a nitrile amide of formula II reacts CN N "zoc 1 wherein A, R, and n are as described hereinbefore for formula I, with at least one molar equivalent of a dienophile of formula III / = C \ wherein W is as described hereinabove for the formula I, and Y is hydrogen, Br or Cl, with the proviso that when R is hydrogen, then Y must be Br or Cl, in the presence of an acid and a solvent, and essentially in the absence of water consequences.

2. The process according to claim 1, characterized in that the acid is selected from the group consisting of methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, tetrafluoroboric acid, tetrafluoroboric acid etherate, and tetrafluoroboronic acid alkanolate.

3. The process of aojecó to the r * eiviprJicaa? R? 1, cacacterizacb pacμs the dlsaLvepbe is an aromatic hydrocarbon, a halogenated aromatic hydrocarbon, an organic amide, a nitrile, an alkanol, or mixtures thereof.

4. The hydride is selected from the group selected from the group consisting of toluene, dimethylformamide, acetonitrile, propionitrile, f-butanol, and mixtures thereof.

5. The process according to claim 1, characterized in that A is wherein L is hydrogen or halogen; M and Q are each independently hydrogen, halogen, C?-C4 haloalkyl, or haloalkoxy d-C; n is 1 or 2; W is CN, and R is hydrogen or methyl.

6. A process for making a compound of formula IV IV) wherein R is hydrogen or C? -C6 alkyl optionally substituted with a C? -C4 alkoxy or phenyl group; n is an integer of 1, 2, 3, 4, 5, 6, 7, or 8; W is CN, N02, COORi, or COR2; L is hydrogen or halogen; M and Q are each independently hydrogen, halogen, CN, N02, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, or when M and Q are in adjacent positions, they can be taken together with the carbon atoms to which they are attached, to form a ring in which MQ represents the structure -OCH20-, -OCF20-, or -CH = CH-CH = CH-; R1 and R2 are each independently dC4 alkyl; R3, RA, and R5 are each independently hydrogen, halogen, NOz, CHO, or R4 and R5 can be taken together with the atoms to which they are attached to form a ring, in which R4R5 is represented by the structure - to, Re, R7, Re, and R9 are each independently hydrogen, halogen, CN, or N02; and X is O, or S; and Hal is a halogen atom; characterized in that it comprises reacting a nitrile amide of formula II CN A- CH R (II) wherein A, R, and n are as described hereinbefore for formula I, with at least one molar equivalent of a dienophile of formula III V / =. c = c w wherein W is as described hereinbefore for formula I. and Y is hydrogen, Br or Cl, with the proviso that when R is hydrogen, then Y must be Br or Cl, in the presence of an acid and a solvent, and essentially in the absence of water, to form a compound of formula I and halogenating said compound of formula I to form said compound of formula IV.

7. A compound of formula Ha CN I A- CH N I - COC n F: R. n characterized in that n is an integer of 1, 2, 3, 4, 5, 6, 7, or 8; R 'is CrC6 alkyl optionally substituted with a d-C4 alkoxy or phenyl group; L is hydrogen or halogen; M and Q are each independently hydrogen, halogen, CN, N02, C? -C alkyl, C? -C4 haloalkyl, C4 alkoxy, C? -C4 haloalkoxy, C? -C alkylthio, C? -C4 alkylsulfinyl, or when M and Q are in adjacent positions, they can be taken together with the carbon atoms to which they are attached, to form a ring in which MQ represents the structure -OCH20-, -OCF20-, or -CH = CH-CH = CH-; Ri and R2 are each independently dC4 alkyl; R3, R4, and R5 are each independently hydrogen, halogen, N02, CHO, or R4 and R5 can be taken together with the atoms to which they are attached to form a ring, in which R4R5 is represented by the structure . r * - ^ - n - > Re, 7, Re, and R9 are each independently hydrogen, halogen, CN, or N02; and X is O, or S.

8. The cxt placed according to claim 7, characterized by which 1 or 2.

9. The composition according to claim 7, c * _arac-terized, DorqueR * is methyl or ethoxymethyl.

10. The compound according to claim 7, characterized in that A is wherein L is hydrogen or halogen, and M and Q are each independently hydrogen, halogen, or haloalkyl d-C.