HRP940883A2 - Process for the preparation of n-arylhalopyrolidones - Google Patents

Description

The basis of the invention

The present invention describes an improved process for the preparation of N-arylhalopyrrolidone in the presence of a catalyst comprising a copper compound together with an amine.

Some N-arylhalopyrrolidones are known to be useful as general purpose herbicides. Such compounds and their utility are disclosed, for example, in U.S. Pat. Patent 4,110,105 to Eugene G. Teach.

One process for obtaining them is disclosed in the U.S. Patent 4,110,105 and additional U.S. Pat. Patent 4,210,589, which is part of the previous one. According to these references, the compounds are obtained by intramolecular cyclization of α -halogen-containing N-2-alkenylamide in the presence of a catalytic amount of ferrous iron.

Another U.S. Patent No. 4,132,713 to Michael D. Broadhurst, discloses an improved process for making such compounds using catalysts other than ferric iron. In particular, the catalyst from the U.S. Patent 4,132,713 contains one or more of the transition metals vanadium, molybdenum, ruthenium, silver and copper. The metal-containing compound can be in several forms including complexes with common complexing reagents such as triphenylphosphine, carbon monoxide, and tertiary amines. Examples of tertiary amines found to be useful in this process are pyridine, 2,2'-dipyridyl, 2,2'-dipyridylamine and tetramethylenediamine. The last mentioned compound, however, is really a bifunctional primary amine, having the formula N2N(CH2)4NH2. Among the copper-containing compounds specifically disclosed in this patent are cupric chloride and cupric oxide.

When using catalysts containing copper with a tertiary amine complexing reagent, the process can be carried out at a temperature of from about 60°C to about 200°C, preferably from about 80°C to about 150°C. Table II. in the US Patent 4,132,713 shows results for obtaining the compound 3-chloro-4-chloromethyl-1-(m-trifluoromethylphenyl)-2-pyrrolidone

[image]

using cuprous oxide and cuprous chloride differently complexed with several tertiary amines. The procedure was performed at times ranging from 2.5 to 11 hours with yields reaching up to 65% of the theoretical. Obtaining the product on a larger scale is described in example 14 of the patent. Other examples show the preparation of related compounds by this technique.

Extract from the invention

It has now been found that an improvement over the process generally described in the U.S. Patent 4,132,713 can be achieved by performing the reaction in the presence of a catalyst comprising a copper compound together with an amine selected from the group consisting of:

(a) primary amines having the formula RNH2, in which R is a normal or branched chain alkyl group having 1 to 20 carbon atoms, optionally substituted with hydroxy; or

(b) secondary amines having the formula R1NHR2 in which R1 and R2 are independently normal or branched chain alkyl groups having from 1 to 20 carbon atoms, optionally substituted with hydroxy, excluding branched chain alkyl groups having a branch at an alpha carbon atom.

Detailed description of the invention

The N-2-alkyl-α-haloamide used as a starting material in the process according to the present invention can be obtained by any conventional technique known in science. Several techniques are given in U.S. Patent 4,132,713.

The N-arylhalopiridones obtained according to the present invention have the general formula:

[image]

X is selected from the group consisting of hydrogen, chlorine, bromine and fluorine;

Y is selected from the group consisting of hydrogen, chlorine, bromine and fluorine;

Z is selected from the group consisting of chlorine and bromine;

R! is selected from the group consisting of hydrogen and C1-C4 alkyl;

R2 is selected from the group consisting of hydrogen, C1-C4 alkyl, acetyl, chlorine, bromine, fluorine, trifluoromethyl iodo, nitro, cyano C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl, trifluoromethylsulfonyl, pentafluoropropionamido, and 3 -methylureido; and

R 3 is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, chlorine and trifluoromethyl.

A class of preferred products are those in which R3 is trifluoromethyl and R2 is hydrogen or fluoro. One primary product is 3-chloro-4-chloromethyl-1-(m-trifluoromethylphenyl)-2-pyrrolidone (X = chlorine, Y = hydrogen, Z = chlorine, R1 = hydrogen, R2 = hydrogen, R3 = 3-trifluoromethyl) .

The cyclization of N-2-alkenyl-α-haloamide is carried out in the presence of a catalyst that includes a copper compound. The copper compound is primarily cupric chloride, cupric chloride or cupric oxide, with cupric chloride being the most suitable.

The catalyst can be present either as an undissolved solid in the reaction mixture, or as dissolved in a solution with the starting amide or solvent, when a solvent is used. In general, the catalyst is primarily dissolved. The reaction will proceed without stirring, whether the catalyst is undissolved or in solution. However, when stirring is used, the course of the reaction will be greatly aided. Mixing can be achieved by any conventional means, for example, stirring, passing an inert gas, using baffles in the reaction vessel, or performing the reaction at reflux.

The amount of copper-containing catalyst that will make up the catalytic amount will be the amount that serves to increase the reaction rate. Larger amounts will cause a larger increase. The amount used in each individual application will be determined to a large extent by individual production needs. Apart from considerations such as grade, required reaction time and system capacity, the amount of catalyst is not a critical feature of the invention and can vary over a wide range. Most conveniently, an amount of catalyst is used that comprises from about 0.1 to about 20 mole percent, based on the initial amount of N-2-alkenylamide.

The primary amounts of catalyst are: for cupro or cupric chloride - from about 1 to 10 mol percent; for cupric oxide - from about 1 to about 5 mol percent.

Amines found to be useful in the improved process of this invention are some primary and secondary aliphatic amines.

Primary amines are of the RNH2 type, where R is a normal or branched chain alkyl group, having from 1 to 20 carbon atoms, optionally substituted with hydroxy. Such amines include, for example, ethylamine, propylamine, various butylamines, and amines containing multiple alkyl groups. One example of a hydroxide substituted alkyl amine is 6-hydroxyhexylamine.

Secondary amines are R1NHR2, where R1 and R2 are alkyl groups preferably of 1 to 12 carbon atoms. These alkyl groups may be straight chain or branched chain groups, optionally substituted with hydroxy, provided that if they are branched chain, the branching is other than at the alpha carbon atom. Secondary amines containing alpha branched alkyl groups, such as isopropyl, sec-butyl and the like, do not give favorable results in this process. Alkyl groups R1 and R2 can be the same or different, primarily they are the same. A primary class of secondary amines are those in which R1 and R2 are identical normal chain alkyl groups having from 1 to 12 carbon atoms. The primary members of this class are di(n-butyl) and di(n-propyl)amines.

If necessary, different solvents can be used in this reaction. Such solvents may include aliphatic compounds such as heptane or octane, alcohols such as tertiary butyl alcohol, and aromatic compounds such as toluene or xylene. The primary solvents are toluene and tertiary butyl alcohol. Other solvents such as those mentioned in U.S. Patent 4,132,713 can be used if necessary.

The amount of amine used can vary widely according to cost and desired effects. In general, the amine is used in an amount of about 5 to 60 mol percent based on the starting N-alkenyl-α-haloamide, and preferably from about 10 to about 40 mol percent.

The temperature at which the procedure is performed is generally from about 50°C to about 150°C. The primary optional regions will vary depending on the nature of the copper-containing catalyst, the amine, the solvent (if any), the α-haloamide concentration in the substrate. In general, cupro chlorides and lower molecular weight amines containing up to eight carbon atoms per alkyl group are best at temperatures from about 60 to about 90°C.

Since the reaction takes place in the liquid phase, the operating pressure is not a significant parameter, and can vary widely, depending on convenience, economy and construction materials. The reaction is most conveniently carried out at or near ambient pressure.

If the reaction is carried out in the presence of a solvent, under reflux or at close to atmospheric pressure, the temperature can be the normal reflux temperature of the solvent, or it can be lower. A temperature of about 85°C has been found to be suitable for solvents such as toluene and tertiary butyl alcohol.

The concentration of α-haloamide in the solvent can vary. However, as the concentration increases from about 20 wt.% to about 60 wt. % selectivity - reaction yields usually decrease, with less desirable products and larger amounts of "resin" being obtained. This is especially true for amines with higher molecular weights and cupric oxide catalysts. Therefore, for good results, the amide concentration in the solvent should be at a maximum of about 65 te. % most suitable around 40 wt. %.

The order of adding materials is not a significant parameter. However, it is preferable to premix the catalyst and amine, and then add the α-haloamide, as this can be produced in slightly improved yield.

The primary sum of parameters for performing this procedure is:

copper catalyst: 3 - 8 mol %

amine: 20 - 40 mol %

solvent: toluene

temperature: 75 - 95°C

concentration of amide in the solvent: 15 - 30 %

The pyrrolidone obtained by the reaction can be regenerated from the reaction mixture by any conventional technique, such as solvent extraction, crystallization, sublimation, or distillation.

Compared to the copper/tertiary amine complexes described in U.S. Pat. In Patent 4,132,713, the use of a copper catalyst with a primary or secondary aliphatic amine of the type described herein produces the desired compound in higher yield, with a corresponding reduction in the production of non-volatile side products ("resin"), and an overall reduction in the required reaction time.

The following examples illustrate the course of the procedure, in relation to obtaining the compound 3-chloro-4-chloromethyl-1(m-trifluoro-methylphenyl)-2-pyrrolidone.

Example 1

200 (g) (0.567 mol) N-allyl-3'-trifluoromethyl-2,2-dichloroacetanilide, 2.79 g (0.028 mol) cuprous chloride, 28.5 milliliters (ml) (0.169 mol) di -(n-butyl)-amine, and 891 ml of toluene. The mixture is heated to a temperature of 85-90°C and stirred for 2 hours and 25 minutes. At the end of this time, a sample of the reaction mixture is analyzed by gas chromatography and shows 95.0 surface percent of the desired product.

The reaction mixture was washed three times with 125 ml of 3.0 M hydrochloric acid. The mixture was then separated into phases and vacuumed with an aspirator for one hour at 40°C and under high vacuum for one hour at 55°C, giving a crude yield of 192.89 g. Gas chromatography analysis showed a purity of 86.8%, corresponding to corrected yield of 94.5% of the desired product. Distillation of the sample showed that the product contains 5.8% by weight of non-volatile resins. The structure of the desired product was confirmed by mass spectroscopy.

Comparative example 1

This example illustrates a process flow using a cupric oxide/pyridine catalyst as in the U.S. Patent 4,132,713.

200 g (0.586 mol) of N-allyl-3'-trifluoromethyl-2,2-dichloroacetanilide, 8.25 g (0.058 mol) of cupric oxide, 18.7 ml (0.023 mol) of pyridine and 135 ml of toluene. The mixture is heated to reflux at 115°C, and stirred for a total of one hour, 20 minutes. The mixture is filtered, then washed three times with 100 ml of 3.0 M hydrochloric acid. The mixture was then dephased and extracted first with an aspirator, then under high vacuum for one hour at 55°C to give a crude yield of 186.80 g. By gas chromatography, the product was shown to be 80.0% pure, corresponding to the corrected yield of 81.7% of the desired product. The product contained 14.8% resins by weight, as determined by distillation. The structure of the desired product was confirmed by mass spectroscopy.

Example 2

0.157 g (0.00158 mol) of cuprous chloride, 1.6 ml (0.0091 mol) of di-(n-butyl)amine, and 40 ml of toluene are mixed in a flask. The mixture is stirred to dissolve the cuprous chloride. 11.22 g (0.0334 mol) of the acetanilide used in Example 1 was then added, along with an additional 10 ml of toluene. The resulting mixture was heated to 85-95°C and stirred for 1.5 hours.

At the end of this time, the mixture was cooled, washed with 3 M hydrochloric acid and suctioned under vacuum to give 11.81 g of an orange oil, which was analyzed by mass spectroscopy and shown to be the desired pyrrolidone product. Gas chromatographic analysis of the product showed that it is 85.4% pure, which corresponds to a correct yield of 96.7%. Distillation of one quantity of the product showed that it contains 3.1% by weight of "resin".

Example 3 - 12

The following examples represent the process of the present invention, with other primary and secondary alkyl amines. These examples are all performed according to the following procedure.

The same acenilide as in examples 1 and 2 was mixed with 5 mol percent of cuprous chloride and 28 mol percent of said amine, using tertiary butyl alcohol or toluene as solvent. Reactions were performed at an average of 85°C, or about 115°C when indicated, for the indicated time. The concentration of acetanilide in the solvent was about 20-21% by weight except where indicated.

The reaction mixture was washed with dilute aqueous hydrochloric acid, the solvent was removed and the products distilled. The reaction products were analyzed for percentage by weight of the desired pyrrolidone, and non-volatile by-products (“resin”). The results of these experiments are shown in the following table I.

Table I

[image]

* Corrected for unreacted starting material, if any.

** Toluene used as solvent.

*** Toluene used as solvent, temperature = 115°C, concentration of acetonilide in the solvent 61 wt. %.

Comparative example 2

The procedure is carried out as described for Examples 3-12 above with tertiary butyl alcohol, and cuprous chloride, at 85°C, but using pyridine as the amine, rather than the primary or secondary amine. The obtained results were as follows:

- pyrrolidone yield (corrected for unreacted starting material 89.0 wt.

- resins (corrected for unreacted starting material 6.5 wt.

- reaction time 320 min

Thus, when using pyridine, the tertiary amine described in U.S. Pat. Patent 4,132,713, with the same amount of cuprous chloride as in Examples 3-14, required nearly 2.5 times as long to complete the reaction to obtain usable yields as with primary and secondary amines.

Examples 15 - 18

These examples demonstrate a process flow using cupric chloride in combination with lower and higher molecular weight amines. The procedure is performed as above; experiments using tertiary butyl alcohol as a solvent were performed at 85°C, with an acetanilide concentration of 21% by weight, those using toluene as a solvent were performed at 115°C, with an acetanilide concentration of 61% by weight. The results are summarized in the following Table II.

Table II

[image]

* corrected for unreacted starting material, if any.

The foregoing examples are intended to illustrate the flow of the subject process, and are not intended to limit the scope of the invention, except as defined in the following claims.

Claims (9)

1. Procedure for the preparation of N-arylhalopyrrolidone of the formula [image] where X is hydrogen, chlorine, bromine or fluorine; Y is hydrogen, chlorine, bromine or fluorine; Z is chlorine or bromine; R 1 is hydrogen or C 1 -C 4 alkyl; R 2 is hydrogen or C 1 -C 4 -alkyl, acetyl, chlorine, bromine, fluorine, iodo, trifluoromethyl, nitro, cyano, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, trifluoromethylthio, trifluoromethysulfinyl, trifluoromethylsulfonyl, pentafluoropropionamide or 3-methylureide; and R3 is hydrogen, C1-C4alkyl, chlorine or trifluoromethyl, by internal cyclization of the corresponding N-2-alkenyl-α-haloamide at a temperature of 50 to 150°C in the presence of a catalyst containing copper and an amine, indicated by the fact that an amine is used which is: (a) a primary amine of the formula RNH2, in which R is a straight or branched chain alkyl group, with 1 to 20 carbon atoms, optionally substituted with hydroxy; or (b) a secondary amine of the formula R1NHR2, wherein R1 and R2 are each individually straight or branched chain alkyl groups of 1 to 20 carbon atoms, optionally substituted with hydroxy, excluding branched chain alkyl groups having branching on the alpha carbon atom. 2. The method according to claim 1 in which a solvent is used, characterized in that N-2-alkenyl-α-haloamide is used in a concentration of 65% by weight. or less, the amine is used in an amount of 5 to 60 mol percent based on the initial N-2-alkenyl-α-haloamide, and a catalyst containing copper is used in the amount of 0.1 to 20.0 mol percent based on the initial N-2 -alkenyl-α-haloamide. 3. The method according to claim 1 or 2, characterized in that the copper catalyst contains copper chloride. 4. The process according to any of claims 1 to 3, characterized in that the temperature is from 70°C to 90°C. 5. The method according to any of claims 1 to 4, characterized in that the copper catalyst contains copper oxide or copper chloride. 6. The method according to any one of claims 1 to 5, characterized in that the amine is di(n-butyl)amine or di(n-propyl)amine. 7. The method according to any claim from 1 to 6, characterized in that the copper catalyst is used in an amount of 2.5 to 5 mol percent based on α-haloamide. 8. Process according to any claim from 1 to 7, characterized in that the time required for a complete reaction is from 30 to 180 minutes. 9. The process according to any one of claims 1 to 8, characterized in that X is chlorine, Y is hydrogen, Z is chlorine, R1 is hydrogen, R2 is hydrogen and R3 is trifluoromethyl.