MXPA98003856A - Procedure for preparing 5-methylene-xazoli - Google Patents

Abstract

This invention provides a process for the preparation of a 5-methylene-1,4-oxazoline from an alkyl ketone, by the reaction of this alkyl ketone with an acetylating agent and an acid catalyst, in an appropriate solvent, and an appropriate temperature. The resulting 5-methylene-1,3-oxazoline can be chlorinated and subsequently hydrolyzed to form an alpha-chloroketone, which is useful as a fungicide.

Description

PROCEDURE FOR PREPARING 5-METHYLENE OXAZOLINES This invention relates to a process for the preparation of the 5-methylene oxazolines from the alkyl ketones. These 5-methyleneoxazolines are useful intermediates for the preparation of the a-chloroketones, which can be used as fungicides. Currently there is no known method for the formation of 5-methylene oxazolines by ring closure of the alkyl ketones, of the type described herein. The oxazolines, of the type mentioned, can be obtained from the ring closure catalyzed with an acid or a base of the alkynyl amides. Routes, previously described, to this desired 5-methyleneoxazoline of substituted alkynyl amides, require the use of strong and, consequently, expensive bases, such as sodium hydride or sodium amide. w ** These bases require the use of scrupulously anhydrous conditions and are difficult to handle. Additionally, the yields of 5-methylenexazoline from the amide of Alkynyl are unacceptably low for economic viability. Other routes described for the desired 5-methylenexazoline from the substituted alkynyl amides involve the treatment of the amide with silver ions in the N, -dimethylformamide. This type of procedure uses a It is a costly and environmentally toxic catalyst and a solvent that requires difficult processing and produces large volumes of aqueous waste loaded with organic materials. Also, the alkyl ketone is sometimes formed as a by-product in these ring closures of the alkynyl amides, when sufficient water is present. The alkyl ketone can still become the dominant product when sufficient water is present. Therefore, a convenient method for closing the alkyl ketone to the 5-methylenexazoline useful is desired. We have discovered a simple solution to these problems. An alkyl ketone is dissolved in a solvent and an acid catalyst is added together with an acetylating agent, and the resulting mixture is reacted at a suitable temperature. While not wishing to be bound by the theory, we believe that, during the course of the reaction, an intermediate enol acetate is formed which subsequently closes off 5-methyleneoxazoline. This intermediate product is transient and only postulated, but the reaction does not proceed without the acetylation agent being present. WO 95/19351 discloses the formation of derivatives of 2-aryl-5-methylenexazoline by the cyclization of an alkynyl amide, in the presence of a base. Yih et al., in Weed Science, 18, 604-607 (1970) and in "T. Agr. Food Chem., 19 r 314-317 (1971) discloses the formation of the aryl-5-methylene oxazolines from substituted alkynyl amides, using an acid, base or silver ions in an aqueous alcoholic solution. However, the formation of the 5-methylenexazolines by cyclization of an alkyl ketone is not described, taught or suggested. This invention provides a process for the preparation of the 5-methylene-1,3-oxazolines from the alkyl ketones, by the reaction of the alkyl ketone with an acetylating agent and an acid catalyst, in a fl * appropriate solvent and at a suitable temperature. If desired, An excess of the acetylating agent can be used as the solvent. Specifically, this invention provides a process for the preparation of a 2-substituted-4,4-disubstituted-5-methylene-l, 3-oxazoline of the formula (I), by the cyclization of an alkyl ketone, of the formula (II), in the presence of an acetylating agent, a catalyst # acid, an appropriate solvent or excess acetylation agent, and an appropriate reaction temperature.

R1 wherein Z is alkyl or substituted alkyl, substituted aryl or aryl, heteroaryl or substituted heteroaryl, or phenylene; R is a hydrogen atom or an alkyl group; and R1 and R2 are each, independently, an alkyl or substituted alkyl group, or R1 and R2, together with the carbon atom to which they are attached, form a cyclic structure. In this invention, alkyl means a straight chain alkyl group (C 1 -C s) or a branched chain (C 3 -C 8) alkyl group, and include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl , isobutyl, secondary butyl, tertiary butyl, n-amyl, isoamyl, n-hexyl, isooctyl and the like. "Substituted alkyl" means an alkyl group substituted with one or more substituents, selected from the group consisting of alkoxy, halogen, alkylthio and cyano. "Alkoxy" means a straight chain (C 1 -C 4) alkyl group or a branched chain (C 3 -C 4) alkyl group attached to an oxygen atom, for example, methoxy, ethoxy, isobutoxy and the like. Alkylthio means a straight chain (C 1 -C 4) alkyl group or a branched chain (C 3 -C 4) alkyl group, attached to a sulfur atom, for example methylthio, n-propylthio, sec. -butylthio and the like. Halogen means bromine, chlorine, fluorine and iodine.

Aryl means phenyl, naphthyl, or phenyl or naphthyl substituted with one to three substituents, independently selected from the group consisting of halogen, alkyl, alkynyl, alkoxy, nitro or cyano. Examples include, but are not limited to, phenyl, 2-naphthyl, 4-nitrophenyl, 4-chlorophenyl, 3,5-dimethylphenyl, 2,6-difluorophenyl, 3,5-dichloro-4-methylphenyl, 3, 5- dichloroenyl, 3,5-difluorophenyl, 3,5-dibromophenyl, 3-chloro-4-ethyl-5-fluorophenyl, 3,5-dichloro-4-cyanophenyl, 3,5-dichloro-4-methoxyphenyl, 3,5- 10 difluoro-4-propargylphenyl, 3,5-dibromo-4-methylphenyl and the like. Alkynyl means an alkynyl group (C2-Cg), for example, ethynyl, propargyl, 2-hexynyl, and the like. Heteroaryl means an aromatic ring of 5 members, which may contain an oxygen atom, a sulfur atom, 1, 2 or 3 nitrogen atoms, an oxygen atom with 1 or 2 nitrogen atoms, or a sulfur atom with 1 or 2 nitrogen atoms , or a 6-membered aromatic ring, containing 1, 2 or 3 nitrogen atoms, or a Heteroaryl substituted with up to two substituents, selected from halogen, alkyl, haloalkyl or cyano. Examples include, but are not limited to 2-furyl, 2-thienyl, 4-chloro-2-thienyl, 2-oxazolyl, 2-imidazolyl, 1,2,4-triazolyl-1-yl, 2-imidazolyl, 2- pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 4-pyridazinyl, 4-pyrimidinyl, 2-pyrazinyl, 1, 3, 5-triazin-2-yl, 4-chloro-3-pyridyl and the like. Phenylene means 1,4-phenylene. In a preferred form of this embodiment, Z is a group, alkyl (C ^ -Cs), phenyl or substituted phenyl, with up to three substituents, independently selected from the group consisting of: halogen, (C1-C4) alkyl, (C 1 -C 4) alkoxy, (C 2 -Cg) alkynyl, nitro and cyano, 2-naphthyl, 3-pyridyl and 1,4-phenylene; R is a hydrogen atom or an alkyl group (C] _-C4) and R1 and R2 are each, independently, a (C1-C4) alkyl group, or R1 and R2, together with the carbon atom to which join, form a cyclopentyl or cyclohexyl ring. In a more preferred form of this invention, Z is 3-heptyl, 4-halophenyl, 2,6-dihalophenyl, 4-alkyl (C1-C4) -phenyl, 3,5-dihalophenyl, 3,5-dialkyl (C1-) C4) -phenyl, 4-alkyl (C 1 -C 4) -3,5-dihalophenyl, 4-cyano-3,5-dihalophenyl, 4-alkoxy (0 ^ -04) -3,5-dihalophenyl, 4-nitrophenyl, 2-naphthyl, 3-pyridyl or 1,4-phenylene; R is a hydrogen atom, methyl or ethyl, and R1 and R2 are each, independently, a methyl or ethyl group, or R1 and R2, together with the carbon atom to which they are attached, form a cyclohexyl ring. In an even more preferred form of this invention, Z is 4-chlorophenyl, 2,6-difluorophenyl, 3,5-dimethylphenyl, 3,5-dichloro-4-methylphenyl, 4-nitrophenyl, 1,4-phenylene, 2- Naphyl, 3-pyridyl or 3-heptyl; R is a hydrogen atom and R1 and R2 are each, independently, methyl or ethyl.

The process of this invention is carried out • typically by dissolving the alkyl ketone, of the formula (II), in the desired solvent, followed by the addition of the acetylation agent and the acid catalyst. The reaction is carried out at the chosen temperature, until the reaction is complete, based on the gas chromatographic analysis. The reaction mixture is then divided between ethyl acetate and an aqueous base, typically sodium bicarbonate saturated, and the phases are separated. The aqueous phase is extracted once more, the organic phases are combined and dried over a drying agent, such as sodium sulfate. This drying agent is removed by filtration or centrifugation and the solvent is removed under reduced pressure to obtain the desired methylexaxazoline of the formula (I). The starting alkyl ketone of the formula (II), can be prepared from an alkynyl amide, by a procedure described by Yih et al., In "Agr. Food Che., 19, 314-317 (1971).

Preferred, of the formula (II), with the methyl ketones.

The solvents can be esters, for example ethyl acetate and butyl acetate; ethers, for example the tere. -butyl methyl ether, aliphatic hydrocarbons, for example heptane, chlorinated hydrocarbons, for example chloroform, aromatic hydrocarbons, for example toluene, or chlorinated aromatic compounds, for example monochlorobenzene. Preferred solvents are non-polar types, such as aliphatic hydrocarbons, hydrocarbons * and aromatics and chlorinated aromatic hydrocarbons. Any suitable acetylating agent can be used to form the postulated intermediate of "enol acetate." Preferred acetylating agents are acetic anhydride and isopropenyl acetate (1-propen-2-yl acetate). Preferred is isopropenyl acetate An excess of the acetylating agent may be employed in place of a solvent When a solvent is used, the amount of the acetylating agent used is about 1.0 to 15 equivalents per equivalent of the alkyl ketone of the formula (II) A preferred amount of the acetylating agent is about 1.25 to 10 equivalents per equivalent of the alkyl ketone, A more preferred amount of the acetylating agent is about 1.5 to 5 equivalents per equivalent of the alkyl ketone.

The acid catalyst used in the process can be a mineral acid, for example sulfuric acid, or an organic acid, for example methanesulfonic acid, p-toluenesulfonic acid, trichloroacetic acid and trifluoroacetic acid. Preferred acids are sulfuric acid, methanesulfonic acid and p-toluenesulfonic acid. The amount of the acid catalyst used is about 0.01 to 1.5 equivalents per equivalent of the alkyl ketone of the formula (II). A preferred amount of the acid catalyst is from about 0.01 to 1.0 equivalents per equivalent of the alkyl ketone. When the sulfuric acid, methanesulfonic acid or p-toluenesulfonic acid are used, a more preferred amount of the acid catalyst is about 0.05 equivalent per equivalent of the alkyl acetone. The reaction temperature is usually from about 20 ° C to the reflux temperature of the solvent system employed. A preferred temperature is about 25 to 130 ° C. A more preferred temperature is about 60 to 120 ° C. An even more preferred temperature is about 80 to 100 ° C, when isopropenyl acetate is used as the acetylating agent. The pressure is not important, but the reaction is carried out 'usually at atmospheric pressure for convenience. The reaction time will depend on the temperature employed, the substituent standard of the starting alkylet ketone, the formula (II), the solvent used, the nature of the acid catalyst, the type of the acetylating agent and the size and reactor design. However, the reaction is conveniently carried out in general in a time of about 30 minutes to about 5 days and more usually of 3 days or less. The following examples, tables and experimental procedures are provided for the practitioner's guidance and do not signify a limit of the scope of the invention, which is defined by the claims.

Example 1; General Procedure Used for the Preparation of the 5-methylene-1,3-oxazolines from the Alkyl Ketones To 1.0 g of the starting alkyl ketone of the formula (II) in 10 ml of solvent was added the acid catalyst and the acetylating agent, as shown in Table 1. The reaction was heated to the indicated temperature until completion, according to GC analysis. It was then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate, and the layers separated. The organic layer was washed with an aqueous base (1 x 25 ml), then dried over sodium sulfate, filtered and the solvent was removed under reduced pressure, to obtain the 5-methyleneoxaline of the formula (I).

The physical properties of the 5-methylene oxazolines, obtained by this procedure, are listed in the following Table 1. TABLE 1; Preparation of the 5-ethylene-oxazolines (I) from the alkylene ketones (II) _ \ ~ TABLE 1 (Continued) go to. IPA is isopropenyl acetate b. The number in parentheses represents the equivalents based on the starting material of the ketone c. TsOH represents p-toluenesulfonic acid d. The yield was determined by gas chromatography. and. SM represents the ketone starting material. * > 2- (3,5-dichloro-4-methylphenyl) -4-ethyl-4-methyl-5-methylene-1, 3-oxazoline: boiling point (128 ° C, 1.0 mm Hg); 13 C NMR (100 MHz, DMSO-dg) d 165.1, 156.5, 137.6, 135.0, 126.5, 126.0, 83.9, 72.7, 34.0, 28.0, 17.4, 8.1 2- (3-heptyl) -4,4-dimethyl-5-methylene-1,3-oxazoline: light brown liquid, »H NMR (400 MHz, CDCl 3) d 0.9 (t, 6H), 1.3 (m 4H ), 1.35 (s, 6H), 1.6 (m, 4H), 2.4 (m, 1H), 4.1 (d, 1H), 4.6 Jr (d, 1H). 2- (4-nitrophenyl) -4,4-dimethyl-5-methylene-l, 3-oxazoline: pale yellow solid 10, melting point = 84.5-86 ° C, XH-NMR (400 MHz, CDCl3) d 1.5 (s, 6H), 4.3 (d, 1H), 4.75 (d, 1H), 8.17 (d, 2H), 8.25 (d, 2H).

In a further aspect of this invention, the 5-methylenexazoline of the formula (°) can be further reacted with a chlorinating agent, preferably trichloroisocyanuric acid (TCIA), to form a 5- (chloromethylene) oxazoline, which is then hydrolyzed using an aqueous acid, to produce an a-chloroketone. This resultant chloroketone is useful as a fungicide. Therefore, this invention further comprises the chlorination of 5-methylenexazoline, of the formula (I), using the TCIA as the chlorinating agent, to produce a 5- (chloromethylene) oxazoline of the formula (III): by the hydrolysis of 5- (chloromethylene) oxazoline, of the formula (III), using an aqueous acid, to produce the chloroketone of the formula (IV): wherein: Z is alkyl or substituted alkyl, substituted aryl or aryl, heteroaryl or substituted heteroaryl, or phenylene; R is a hydrogen atom or an alkyl group; and R1 and R2 are each, independently, an alkyl or substituted alkyl group, or R1 and R2, together with the carbon atom to which they are attached, form a cyclic structure. In this further aspect of the present invention, The alkyl, substituted alkyl, alkoxy, alkylthio, aryl, alkynyl, heteroaryl and phenylene have the same meanings previously indicated.

In a preferred form of this further aspect of the present invention, Z is an alkyl group (C ^ -Cs), phenyl or substituted phenyl, with up to three substituents, independently selected from the group consisting of: halogen, alkyl ( C1-C4), (C1-C4) alkoxy, (C2-Cg) alkynyl, nitro and cyano, 2-naphthyl, 3-pyridyl and 1,4-phenylene; R is a hydrogen atom or an alkyl group (C_-C4), and R1 and R2 are each, independently, a (C1-C4) alkyl group, or R1 and R2, together with the carbon atom to which join, form a cyclopentyl or cyclohexyl ring. In a more preferred form of this aspect of the present invention, 15 Z is 3-heptyl, 4-halophenyl, 2,6-dihalophenyl, 4- "Tfc? Alkyl (C.-C4) -phenyl, 3,5-dihalophenyl , 3, 5-dialkyl (C2.-C4) -phenyl, 4-alkyl (C1-C4) -3,5-dihalophenyl, 4-cyano-3,5-dihalo-phenyl, 4-alkoxy (C1-C4) 3,5-dihalophenyl, 4-nitrophenyl, 2-naphthyl, 3-pyridyl or 1,4-phenylene, R is a hydrogen atom, a methyl or ethyl group, and R 1 and R 2 are each, independently, a methyl or ethyl group, or R1 and R2, together with the carbon atom to which they are attached, form a cyclohexyl ring.

In an even more preferred form of this aspect of the present invention, Z is 4-chlorophenyl, 2,6-difluorophenyl, 3,5-dimethylphenyl, 3,5-dichloro-4-methylphenyl, 4-nitrofyl, 1,4 - phenylene, 2-naphyl, 3-pyridyl or 3-heptyl; R is a hydrogen atom and R1 and R2 are each, independently, methyl or ethyl.

The chlorination step of 1-methyloxazoline of the formula (I), with the use of TCIA, can be carried out at a temperature of about -30 to 100 ° C. A preferred chlorination temperature is around 0 to 70 ° C. More preferred, in order to obtain the best chlorination selectivity, is a temperature of about 50 ° C or lower. An even more preferred temperature is from 0 to 30 ° C. The reaction is not dependent on pressure, but a pressure of 1 atmosphere is generally preferred for convenience. The stoichiometry of the reagents is extremely important. If less than 0.333 TCI equivalent per equivalent of 5-methyleneoxazoline is used, some of the 5-methylenexazoline starting material will remain unreacted. If more than 0.333 equivalent is used, an overcoated intermediate is formed, which leads to a dichloro ketone after hydrolysis. The reaction time of the chlorination can vary from about 5 minutes to 1 hour, and is dependent on both the size and type of the reactor equipment employed and the solvent used. The chlorinating solvent is usually a polar solvent, such as, but not limited to, an ether, an ester or a ketone, for example ethyl acetate, butyl acetate and methyl t-butyl ether. Preferred solvents are ethyl acetate or butyl acetate. Non-polar solvents, such as an aromatic hydrocarbon, for example toluene, or an aliphatic hydrocarbon, for example heptane and isooctane, can also be employed when mixed with a polar-type miscible solvent or when heated to a temperature of one 40 ° C. After the chlorination reaction is carried out to the desired step, the by-product of cyanuric acid can be removed by filtration and / or by washing with a common base, such as sodium carbonate, sodium hydroxide and the like. The resulting solution, which contains the 5-chloromethylenexazoline, is then subjected to the hydrolysis step. In the hydrolysis stage, a temperature of about 50 ° C or higher is required. Preferably, the hydrolysis is carried out at about 50 to 100 ° C. More preferably, the temperature employed is about 50 to 80 ° C. An aqueous acid or a non-aqueous acid may be used in admixture with some water. A common acid, such as, but not limited to, hydrochloric acid, sulfuric acid, trifluoroacetic acid, methanesulfonic acid or toluene sulfonic acid is convenient in its use. Hydrochloric acid or sulfuric acid are preferred. An acid ion exchange resin can also be used. When hydrochloric acid or sulfuric acid is used, additional water is usually added to facilitate hydrolysis. It is preferred that about 0.05 to 0.5 equivalents of an aqueous acid be used per equivalent of 5-chloromethylenexazoline. More preferred is the use of about 0.1 to 0.25 equivalents of aqueous hydrochloric acid per equivalent of 5-chloromethylenexazoline. The hydrolysis step usually takes about 3 to 24 hours, over time depending on the nature of the Z group, the temperature and the size and nature of the equipment employed. The pressure used is not critical. However, the pressure of 1 atmosphere is generally preferred for convenience. In a representative procedure typical of the reaction for the chlorination and hydrolysis steps, the 5-methyleneoxazoline and the solvent are combined and the resulting solution is cooled to 0-5 ° C, using an ice bath. The TCIA is added gradually, keeping the reaction temperature below 30 ° C if possible. Once the TCIA has been added, the resulting aqueous paste is brought to room temperature and stirred until the reaction is complete, based on gas chromatographic analysis ("GC"). The by-product of cyanuric acid is removed by filtration and the solution is then washed with an appropriate base, such as a solution of sodium bicarbonate or sodium hydroxide, to remove some of the remaining cyanuric acid. The solution containing the 5-chloromethylene oxazoline is returned to the flask and heated to 60 ° C. The concentrated hydrochloric acid and water are added and the solution is stirred until hydrolysis is complete. The reaction mixture is cooled to room temperature and the desired a-chloroketone crystallizes upon cooling. The solid obtained is filtered, wash and dry to give the product. A second crop is often obtained by the concentration and cooling of the filtered solution.

Example 2; Representative Procedure Used for the Preparation of a-chloroketones Preparation of N- (l-chloro-3-methyl-2-oxobut-3-yl) -4- nitrobenzamide A solution of 4,4-dimethyl-5-methylene-2- (4-nitrophenyl) oxazoline (10.0 g, 43.1 mmoles) and ethyl acetate (35 ml) was cooled to 5 ° C using an ice bath. Trichloroisocyanuric acid (3.33 g, 14.3 mmol) was added in several portions over 15 minutes, in order to keep the reaction temperature below 40 ° C. When the addition was complete, the reaction mixture was cooled to 20 ° C and the ice bath was removed. The reaction was monitored by GC analysis in the disappearance of the starting material. After 1.5 hours, 0.25 g more (1.07 mmol) of the chlorinating agent was added, in order to complete this chlorination. When the reaction was complete, the mixture was filtered. The filtrate was washed with ethyl acetate (15 ml). The filtrate was transferred to a round bottom flask and heated to 60 ° C; Hydrochloric acid (0.85 g of a 37% solution) was added and # water (2.8 ml). The reaction mixture was stirred at 60 ° C for 5 hours, then cooled to room temperature. The resulting aqueous paste was stored in a refrigerator overnight. The mixture was filtered and the solids were rinsed with a cold filtering solution. The filtrate was concentrated to approximately half of its original volume by evaporation under reduced pressure. Hexane was gradually added until a cloudy solution was obtained; The flask was cooled in a refrigerator at 8 ° C overnight, then the aqueous slurry was filtered to obtain a second crop of crystals. Both harvests were dried at 60 ° C under vacuum, by supplying the N- (1-chloro-3-methyl-2-oxobut-3-yl) -4-nitrobenzamide (10.78 g, 88%) as a white solid, (melting point of 181-182 ° C). Following substantially the same procedure, the compounds shown in Table 2 were prepared from of the 5-methylene oxazolines.

Table 2: Preparation of the a-chlorocestones from a 5-methylene hexazoline and ßl TC A. Followed by Hydrolysis It will be understood that changes and variations may be made in this invention, without departing from the spirit and scope thereof, as defined by the following claims.

Claims (25)

1. i * CLAIMS 1. A process for the preparation of a 2- substituted-4,4-disubstituted-5-methylene-l, 3-oxazoline of the formula (I), by the cyclization of an alkyl ketone, of the formula (II), in the presence of an acetylating agent, an acid catalyst, a suitable solvent or an excess of the acetylating agent, and at an appropriate reaction temperature 10 * - wherein 15 Z is alkyl or substituted alkyl, substituted aryl or aryl, heteroaryl or substituted heteroaryl, or phenylene; R is a hydrogen atom or an alkyl group; and R1 and R2 are each, independently, an alkyl or substituted alkyl group, or R1 and R, together with the carbon atom to which they are attached, form a cyclic structure.
2. 2. The process of claim 1, wherein Z is an alkyl group (C ^ -Cs), phenyl or substituted phenyl, with up to three substituents, independently selected from the group consisting of: halogen, (C1-C4) alkyl, (C 1 -C 4) alkoxy, (C 2 -C 4) alkynyl, nitro and cyano, 2-naphthyl, 3-pyridyl and 1,4-phenylene, - R is a hydrogen atom or an alkyl group (C 4 -C 4), and R1 and R2 are each, independently, a (C1-C4) alkyl group, or R1 and R2, together with the carbon atom to which they are attached, form a cyclopentyl or cyclohexyl ring.
3. 3. The process of claim 2, wherein Z is 3-heptyl, 4-halophenyl, 2,6-dihalophenyl, 4- (C 1 -C 4) alkyl-phenyl, -3,5-dihalophenyl, 3, 5-dialkyl (C1 -C4) - phenyl, 4-alkyl (C 1 -C 4) -3,5-dihalophenyl, 4-cyano-3,5-dihalophenyl, 4-alkoxy (C 1 -C 4) -3,5-dihalophenyl, 4-nitrophenyl, 2-naphthyl, 3-pyridyl or 1,4-phenylene; R is a hydrogen atom, methyl or ethyl, and R1 and R2 are each, independently, a methyl or ethyl group, or R1 and R2, together with the carbon atom to which they join / form a cyclohexyl ring.
4. 4. The process of claim 3, wherein Z is 4-chlorophenyl, 2,6-difluorophenyl, 3,5-dimethylphenyl, 3,5-dichloro-4-methylphenyl, 4-nitrophenyl, 1,4-phenylene, 2-naphyl. , 3-pyridyl or 3-heptyl; * R is a hydrogen atom and R1 and R2 are each, independently, methyl or ethyl.
5. 5. The process of claim 1, wherein the solvent is an ester, an ether, an aliphatic hydrocarbon, a chlorinated hydrocarbon, an aromatic hydrocarbon or a chlorinated aromatic compound.
6. 6. The process of claim 5, wherein the solvent is ethyl acetate, butyl acetate, tert-butyl methyl ether, heptane, chloroform, aromatic hydrocarbons, toluene or monochlorobenzene.
7. 7. The process of claim 1, wherein the acetylating agent is acetic anhydride or isopropenyl acetate.
8. 8. The method of claim 1, wherein the acetylating agent is isopropenyl acetate.
9. 9. The process of claim 7, wherein an excess of the acetylating agent is used in place of a solvent.
10. 10. The method of claim 1, which uses a solvent and approximately 1.0 to 15 equivalents of the acetylating agent per equivalent of the alkyl ketone.
11. 11. The method of claim 10, wherein the amount of the acetylating agent is about 5 from 1.25 to 10 equivalents per equivalent of the alkyl ketone.
12. 12. The process of claim 1, wherein the acid catalyst is a mineral acid or an organic acid.
13. 13. The process of claim 12, wherein the acid is sulfuric acid or methanesulfonic acid, p-toluenesulfonic acid, trichloroacetic acid or trifluoroacetic acid.
14. 14. The process of claim 13, wherein the acid is sulfuric acid, methanesulfonic acid or t-p-toluenesulfonic acid.
15. 15. The process of claim 12, wherein the amount of the acid catalyst used is about 0.01 to 1.5 equivalents per equivalent of the alkyl ketone.
16. 16. The method of claim 15, wherein the amount of the acid catalyst is approximately 0. 01 to 1.0 equivalents per equivalent of the alkyl ketone.
17. 17. The process of claim 14, wherein the amount of the acid catalyst is approximately 5 0.05 equivalent per equivalent of the alkyl ketone.
18. 18. The method of claim 1, wherein the reaction temperature is about 20 ° C until ^ _w the reflux temperature of the solvent system used.
19. 19. The method of claim 18, wherein the reaction temperature is about 25 up to 130 ° C.
20. 20. The process of claim 19, wherein the reaction temperature is about 60 to 120 ° C.
21. 21. The method of claim 8, wherein the reaction temperature is about 80 to 100 ° C.
22. 22. The process of claim 1, further comprising the chlotion of a 5-methylenexazoline, of the formula (I), which uses the trichloroisocyanuric acid as a 20 chloting agent, to produce a 5- (chloromethylene) oxazoline of the formula (III), followed by hydrolysis of 5- (chloromethylene) oxazoline, of the formula (III), using an aqueous acid, to produce the chloroketone of the formula (IV): wherein: Z is alkyl or substituted alkyl, substituted aryl or aryl, heteroaryl or substituted heteroaryl, or phenylene; R is a hydrogen atom or an alkyl group; and R1 and R2 are each, independently, an alkyl or substituted alkyl group, or R1 and R2, together with the carbon atom to which they are attached, form a cyclic structure.
23. 23. The process of claim 22, wherein Z is an alkyl group (Ci-Cg), phenyl or substituted phenyl, with up to three substituents, selected, > independently of the group consisting of: halogen, alkyl (CX-C), alkoxy (C 1 -C 4), alkynyl (C 2 -C), nitro and cyano, 2-naphthyl, 3-pyridyl and 1,4-phenylene; R is a hydrogen atom or an alkyl group (C? ~ * C4), and R1 and R2 are each, independently, a (C1-C4) alkyl group, or R1 and R2, together with the carbon atom to which they are attached, form a cyclopentyl or cyclohexyl .
24. 24. The process of claim 23, wherein 15 Z is 3-heptyl, 4-halophenyl, 2,6-dihalophenyl, 4-w (C 1 -C 4) alkylphenyl, 3,5-dihalophenyl, 3,5-dialkyl ( C1-C4) - phenyl, 4-alkyl (C 1 -C 4) -3,5-dihalophenyl, 4-cyano-3,5-dihalophenyl, 4-alkoxy (C 1 -C 4) -3,5-dihalophenyl, 4-nitrophenyl , 2-naphthyl, 3-pyridyl or 1,4-phenylene; R is a hydrogen atom, a methyl or ethyl group; and R1 and R2 are each, independently, a methyl or ethyl group, or R1 and R2, together with the carbon atom to which they are attached, form a cyclohexyl .
25. 25. The process of claim 24, wherein Z is 4-chlorophenyl, 2,6-difluorophenyl, 3,5-dimethylphenyl, 3,5-dichloro-4-methylphenyl, 4-nitrophenyl, 1,4- 5 phenylene. , 2-naphyl, 3-pyridyl or 3-heptyl; R is a hydrogen atom and R1 and R2 are each, independently, methyl or ethyl.