MXPA97001911A - Catalyst for halogenac - Google Patents

Abstract

The present invention relates to: N, N-disubstituted formamides, wherein the substituents are selected to provide formamides having low volatility, which are useful as halogenation catalysts. Such catalysts are usually less dangerous to use compared to typical formamide halogenation catalysts, because the toxic catalyst products are also less volatile. Methods for using said catalyst are provided

Description

CATALYST FOR HALOGENATION The present invention relates to N, N-disubstituted formamides which act as halogenation catalysts and to the use thereof to transform organic hydroxyl transformation groups and thiol groups to organohalides. Many reactions for the conversion of thiol and organic hydroxyl groups to organohalides (for example, the preparation of carboxylic acid chlorides from carboxylic acids) are increased by the presence of N-alkylated formamides. Very often, said reactions require the presence of said catalysts. Formamide N, N-dimethyl is one of the most commonly used. Unfortunately, under standard halogenation conditions, the use of the N, N-di-lower alkyl formamides results in the formation of N, N-dialkylcarbomoyl-low halides, which have been discovered to be animal carcinogens. Said halides are particularly dangerous because of their high volatility. U.S. Patent No. 4,880,576 discloses N, N-dialkylformamides which act as chlorination catalysts, wherein one alkyl group is a Ci-C4 alkyl group, with methyl as the preferred group, and the other alkyl group contains at least nine carbon atoms . The use of said catalysts prevents the formation of highly volatile N, N-dialkylcarbamoyl chlorides. However, a limitation in the utility of said catalysts is to obtain the appropriate secondary amine, wherein one alkyl group is small (methyl is preferred) and the other is long, greater than nine carbons. In addition, although volatility is reduced, it is not eliminated, so that there is still a risk to workers and the environment through the exposure of any N, N-dialkylcarbamoyl halide that may be formed. We have discovered that it is not necessary to limit one or both of the alkyl groups of the formamide to less than four carbons to maintain the activity of the halogenation catalyst. When both alkyl groups are long, any N, N-dialkylcarbamoyl halide, which may be formed during the halogenation reaction, will have a very slow volatility resulting in a lower risk to workers and the environment. The present invention is the use of a compound, or mixture of compounds, which act as a halogenation catalyst, of the formula I: wherein R1 and R2 are independently selected from: a. C5-C30 alkyl, C5-C30 alkenyl substituted or unsubstituted C5-C30 alkynyl and linked groups; and b. substituted and unsubstituted amino and polyaminoalkyl or substituted and unsubstituted amino and polyaminoalkenyl; wherein the substituents are independently selected from any functional group that does not react with the substrate to be halogenated or the halogenation agent to be used. Examples of said substituents include alkyl, aryl, halogen, alkoxy, cyano, nitro, formyl and haloalkyl. A second embodiment of this invention is the use of a compound, or mixture of compounds, which act as a halogenation catalyst, of formula I: where one of R1 and R2 is selected, independently, from: a. C1-C30 alkyl C2-C30 alkenyl, substituted or unsubstituted C2-C3 alkynyl, and attached groups; already. substituted and unsubstituted amino and polyaminoalkyl and substituted and unsubstituted amino and polyaminoalkenyl; wherein the substituents are independently selected from any functional group that does not react with the substrate to be halogenated or the halogenation agent to be used; and the other of R1 and R2 is a polymer. The terms "alkyl", "alkenyl" and "alkynyl" include a straight chain, branched chain and cyclic groups. The term "aryl" means phenyl, naphthyl and five- and six-membered aromatic heterocycle. The term "attached" means that the groups R 1 and R 2 together with the nitrogen, to which they are attached, form a cyclic group such as piperidine and, 3-di-4-piperidylpropane. The terms "polyaminoalkyl" and "polyaminoalkenyl" mean an alkyl or alkenyl substituted with one or more amino groups. Said amino groups can be primary, secondary or cyclic amino groups. The amino groups can be of different types within the same polyaminoalkyl or polyaminoalkenyl group. Examples of such groups include diaminoalkyls of the formula R ^ ICHO) -alkyl-N (CHO) R2, wherein R1 and R2 are as defined above, the triaminoalkyls such as bis- (3-aminopropyl) amine and polyaminoalkyls contain cyclic amino groups. The term "polymer" means any polymer functionalized with one or more amino groups, wherein the amino group is capable of forming a formamide and the resulting formamide-functionalized polymer does not react under the anticipated reaction conditions by halogenation. Examples of such polymers include acrylic and styrenic anion exchange resins, of weak base. Preferred polymers include functionalized ion exchange resins. The alkyl groups which are preferred are the groups R1 and R2. Alkyl groups, wherein the groups contain more than ten carbon atoms, are more preferred because the resulting halogenated product is easily separated from the catalyst. Because of their low cost and high molecular weight, the catalysts formed using mixed amines are preferred, wherein the alkyl groups contain from twelve to twenty-four carbons, such as the amines that are derived from the natural fats. Another embodiment of this invention is a method for converting a substrate into an organohalide, comprising the following steps: a. forming a mixture comprising the substrate, a halogenating agent and one or more catalysts of the formula: where R1 and R2 are, independently, selected from: i. C5-C3o alkyl, C5-C30 alkenyl, substituted or unsubstituted C5-C30 alkynyl, and attached groups; and ii. substituted and unsubstituted amino and polyaminoalkyl and substituted and unsubstituted amino and polyaminoalkenyl; wherein the substituents are independently selected from any functional group that does not react with the substrate to be halogenated or the halogenization agent; and b. keep the mixture at a temperature where the organohalide formation occurs at an acceptable rate. An alternative embodiment of the present invention is a method for converting a substrate into an organohalide, comprising the following steps: a. forming a mixture comprising the substrate, a halogenating agent and one or more catalysts of the formula: H wherein one of R1 and R2 is independently selected from: i. C1-C30 alkyl C2-C3o alkenyl, substituted or unsubstituted C2-C30 alkynyl, and attached groups; and ii. substituted and unsubstituted amino and polyaminoalkyl and substituted and unsubstituted amino and polyaminoalkenyl; wherein the substituents are selected, independently, from any functional group that does not react with the substrate to be halogenated or the halogenating agent; and the other of R1 and R2 is a polymer; and b. keep the mixture at a temperature where the organohalide formation occurs at an acceptable rate. The term "substrate" means an organic compound that contains one or more thiol or hydroxyl groups, known to those skilled in the art that are capable of being replaced by a halogen, using typical halogenation agents. Examples of such substrates include carboxylic acids such as benzoic acid, haxanoic acid, trichloroacetic acid and succinic acid; N-heterocyclic compounds bearing a hydroxyl group adjacent to nitrogen, or their tautomeric forms, such as 2-hydroxypyridine, 2,6-dihydroxy-4-phenyl-1,3,5-trizine and 8-hydroxyquinoline; phenols such as picric acid; heterocyclic thiols such as tizola-2-thiol; and sulfonic acids. The mixture can be formed either by combining the components at the same time or by gradually adding one or more of the components. The preferred method for forming the mixture is to gradually add the halogenating agent to a premix of the remaining components. In such cases, the temperature of the premix may be at, above or below the temperature of stage b. The halogenation reaction can also be used for other types of conversions such as benzaldehyde to benzal chloride, certain dehydration reactions, halogenation of nucleoside and nucleotide coupling, preparation of alkyl halides from alcohols, and the conversion of secondary amides to iminochlorides. The catalyst of the present invention is particularly useful for halogenating substrates, such as trichloroacetic, terephthalic and dicarboxylic pyridine acids which are difficult to be halogenated in the presence of a catalyst. The method can be conducted in the absence or presence of a solvent. When a solvent is used, it must be reasonably inert to the reaction conditions. Preferred solvents include aromatic and non-aromatic hydrocarbons such as cyclohexane, toluene and xylenes; ethers and polyethers such as diethyl ether, di-n-butyl ether and diglyme; esters such as ethyl acetate and n-butyl; and haloalkyls and haloaryls such as methylene chloride, dichloroethane and chlorobenzene. The halogenating agent may be one or more of the agents that are typically used for the halogenation of organic hydroxyl groups. Preferred agents include thionyl chloride, sulfuryl chloride, phosphorous trichloride, phosphorous pentachloride, phosphorous oxychloride, phosgene, oxalyl chloride and phosgene substitutes such as di or tri-phosgene., the triphenylphosphine-chloro complex, and its corresponding bromo analogs. The temperatures at which the mixture is formed and maintained are not critical. Equal or different temperatures can be chosen for each stage in the method. Temperatures should be chosen to ensure that the reaction proceeds at an acceptable and controlled rate. The factors to consider in the choice of temperatures include the mixing and boiling points of the components of the mixture and the stability of the reactants and the products, particularly the halogenation agent itself. The organohalide can be separated from the reaction mixture using common separation techniques. The preferred method for organohalides, which are sufficiently volatile, is to separate them from the catalyst through a distillation process. This allows the residual catalyst to be reused simply by filling the reaction vessel with additional substrate, halogenating agent and, when used, solvent. Thus, the method can be conducted either in series or continuously. Other reasonable methods of separation can also be employed, such as precipitating the catalyst by cooling it and then separating it from the organohalide solution using filtration, crystallizing the organohalide (or any subsequent product produced through subsequent reactions) and stirring the catalyst in solution in a liquor. mother or, if it is a polymer-based catalyst, using a simple physical separation. Alternatively, the organohalide mixture can be used in subsequent reactions without isolating the organohalide.

Any amount of catalyst can be used, depending on the desired rate of the reaction. The more the catalyst is used, the faster the halogenation will proceed. It is preferred that the use of the catalyst be maintained at a rate of 0.01 to 100 mole percent of the substrate to balance the benefit of the increased rate of reaction against the cost of the catalyst. The use of 0.5 to 5 mole percent is more preferred. An advantage of the catalysts of this invention is that they are relatively non-volatile. As a result, when the organohalide is separated from the reaction mixture by distillation, the catalyst remains behind and can be reused. In addition, any resulting carbamoyl halide that can be formed as a product in the halogenation, similarly, is not volatile and, therefore, less hazardous. The catalyst can be prepared using a general process, comprising the following steps: (a) forming a mixture comprising an amine of the formula HNR1R2, wherein R1 and R2 are as described above, one or more equivalents of formamide and one or more equivalents of an acid; (b) heating the mixture to a temperature equal to or lower than its boiling point to form the catalyst; and (c) separating the catalyst from the mixture. Although the amount of formamide used in this reaction is not critical, at least one equivalent is required.

We have found that using up to twenty equivalents does not adversely affect the reaction. Cosolvents that do not interfere with the reaction can also be used. Also, the amount of acid is not critical as long as at least one equivalent is used. The use of one to three equivalents of acid is preferred; it is more preferred to use only a slight excess, that is, approximately 1.1 equivalents. Strong and protic acids are preferred. Sulfuric acid is more preferred because it is soluble in water and non-volatile. Other acids such as phosphoric acid, polyphosphoric acid, formic acid and hydrochloric acid are also preferred. In cases where the R groups contain from twelve to twenty-four carbons, the catalyst product followed will solidify when the mixture is cooled. Under these circumstances, the catalyst is easily separated from the mixture. Following, in particular at elevated temperatures, the catalyst can be separated from the mixture as a non-miscible liquid that is easily isolated. The following examples describe in detail some of the embodiments of this invention.

Example 1 - Preparation of Dioctylformamide (DOF) Reagent MW Amount Moles Eq. Dioctylamine 241 5.0 gr. 0.021 1 Formamide 45 2.5 gr. 0.056 2.7 37% acid 36.5 6.1 gr. 0.062 2.9 hydrochloric Cumene 40 gr.

To a 100 ml three-necked flask equipped with a thermometer, a magnetic stirrer and a condenser on top of a Dean-Stark trap were added dioctylamine, hydrochloric acid and cumene. The mixture was heated to reflux (-150 ° C) to remove the water. After all water was removed (-1 hr.) The mixture was cooled to 120 ° C and 2.5 gr. of formamide. The resulting mixture was stirred at 120 ° C overnight. The reaction was completed during this period, as determined by GC analysis. The mixture was cooled to room temperature and washed with water (3 x 30 ml.). The top layer of the product was then concentrated in vacuo at 70 ° C. Upon cooling, a yellowish oil was obtained (5.3 g, 95% yield). Its identity as dioctylformamide was confirmed by NMR and GCMS.

Example 2 - Preparation of Di (tallow hygrogenated) formamide (DTF) R2 = C? 6H33, C18H37, plus minor amounts of H, Ci4H29, Ci5H3? , Reagent MW Amount Moles Eq. Di (tallow hydro-) 480.5 * 50.1 gr. 0.104 1 genate) amine Formamide 45 50.5 gr. 1.12 10.8 Conc.H2S04 98 11.8 gr. 0.116 1.12 Water (each wash) 80 gr. * Calculated molecular weight, based on the expected composition The Di (hydrogenated tallow) amine and formamide were added to a round bottom flask removes, with cavity of 500 ml., top agitator and nitrogen inertia. The flask was heated using a hot sleeve and stirred until the reaction mixture reached a temperature of 85 ° C. The di (hydrogenated tallow) amine was mixed at this temperature. The sulfuric acid was added and the mixture was then heated to 115 ° C. The reaction was directed by gas chromatography. Between 2 and 4.5 hours after the mixture reached 115 ° C, the conversion was completed, as judged by the disappearance of two of the three large chromatographic points by gas, of the amine (in our analysis, the third point large was co-eluded with one of the product points). The mixture was cooled to minus 100 ° C and 80 g was added. of cold water. Then, the mixture was heated to 90 ° C and the lower aqueous layer was removed. Two more washes were conducted with 80 gr. of water at 90 ° C. The top layer of the product was drained to a crystallizing disk and dried in vacuo at 70 ° C (as a mixture). Upon cooling to room temperature, the product (51.9 grams, 98% yield) was a slightly brown, waxy solid (mp 44-46 ° C).

Example 3 - Preparation of a diacid chloride of pyridine, using DOF (Pyridine di-acid) (Pyridine diacid chloride) Reagent MW Amount Moles Eq.

Pyridine diuretic 341.2 50.0 gr. 0.146 1 n-butyl ether 130.0 50.0 gr. Dioctylformamide 269.0 2.0 gr. 0.0074 0.05 Thionyl chloride 119.0 52.1 gr. 0.438 3.0 Pyridine diacid, n-butyl ether was added (reaction solvent) and dioctylformamide to a 250 ml flask. equipped with a magnetic stirrer, a distillation / reflux head, nitrogen inertia and a caustic scrubber. With ice water in the condenser, the flask was heated using a heat cap at 95 ° C. Using a syringe pump, thionyl chloride was added for 3 hours to the reaction mixture. The reaction was determined to be complete, based on an online FTIR analysis, when the addition of thionyl chloride was terminated. The excess thionyl chloride and then the n-butyl ether were removed under vacuum at final conditions of 100 ° C temperature and 15 mm. Hg pressure. Then, the pressure was reduced to 1-2 mm. Hg and the temperature reached 130 ° C to distill the pyridine diacid chloride. A total of 47.8 of the product was obtained (86.2% of revenue).

Example 4 - Preparation of a pyridine diacid chloride, using DTF (Pyridine di-acid) (Pyridine diacid chloride Reagent MW Amount Moles Eq. Pyridine diuretic 341.2 58.4 gr. 0.171 1 N-butyl acetate 61.4 gr. Di (hydrogenated tallow) 508.0 * 1.75 gr. 0.0034 0.020 formamide (DTF) Thionyl chloride 119.0 46.5 gr. 0.391 2.28 * Calculated average molecular weight, based on the expected composition. Pyridine diacid, n-butyl acetate (reaction solvent) and di (hydrogenated tallow) formamide were added to a 200 ml flask. equipped with a magnetic stirrer, a distillation / reflux head, nitrogen inertia and a caustic scrubber. With ice water in the condenser, the flask was heated using a hot oil bath with stirring. Although the di (hydrogenated tallow) formamide did not dissolve at room temperature, the contents of the flask became homogeneous on heating at 90 ° C. Using a syringe pump, the thlonyl chloride was added for 3 hours to the reaction mixture. The mixture was stirred at 90 ° C for an additional 2.5 hours. The excess thionyl chloride and then the n-butyl acetate solvent were removed under vacuum at final conditions of 100 ° C temperature and 15 mm. Hg pressure. Then, the pressure was reduced to 1-2 mm. Hg to evaporate the pyridine diacid chloride. After a preceding cut of 2.7 grams was removed, the flask temperature was increased to 130 ° C resulting in 56.9 grams of diacid chloride distillate (91% net yield after adjusting to the samples). The flask was treated with solvent of n-butyl acetate and dilute aqueous sodium hydroxide and then the residues were effectively removed from the container and the carbamoyl chlorides that could have formed were decomposed.

Claims (8)

Claims

1. The use of a compound that acts as a halogenation catalyst, of the formula: where R1 and R are independently selected from: a. C5-C30 alkyl, C5-C30 alkenyl substituted or unsubstituted C5-C30 alkynyl, and attached groups; and b. substituted and unsubstituted amino and polyaminoalkyl and substituted and unsubstituted amino and polyaminoalkenyl; wherein the substituents are independently selected from any functional group that does not react with the substrate to be halogenated or the halogenation agent to be used; and mixtures of these.

2. The use of a compound that acts as a halogenation catalyst, of the formula: where R1 and R are independently selected from: a. C1-C30 alkyl C2-C30 alkenyl, C2-C30 alkynyl, and attached groups "; and b. substituted and unsubstituted amino and polyaminoalkyl and substituted and unsubstituted amino and polyaminoalkenyl; wherein the substituents are independently selected from any functional group that does not react with the substrate to be halogenated or the halogenation agent to be used; and the other R1 and R2 is a polymer; and mixtures of these.

3. A method for converting a substrate to an organohalide, comprising the following steps: a. forming a mixture comprising a substrate, a halogenating agent and one or more catalysts of the formula: wherein R1 and R2 are independently selected from: i.C5-C30 alkyl, C5-C30 alkenyl, substituted or unsubstituted C5-C30 alkynyl, and linked groups; and ii. substituted and unsubstituted amino and polyaminoalkyl and substituted and unsubstituted amino and polyaminoalkenyl; wherein the substituents are independently selected from any functional group that does not react with the substrate to be halogenated or the halogenating agent; and b maintaining the mixture at a temperature where the formation of the organohalide occurs within an acceptable index.

4. A method for converting a substrate into an organohalide, comprising the following steps: a. forming a mixture comprising the substrate, a halogenating agent and one or more catalysts of the formula: R2 wherein one of R1 and R2 is independently selected from: i. C 1 -C 30 alkyl, C 2 -C 3 alkenyl substituted or unsubstituted C 2 -C 30 alkynyl, and attached groups; and ii. substituted and unsubstituted amino and polyaminoalkyl and substituted and unsubstituted amino and polyaminoalkenyl; wherein the substituents are independently selected from any functional group that does not react with the substrate to be halogenated or the halogenating agent; and the other R1 and R2 is a polymer; and b.maintaining the mixture at a temperature where the formation of the organohalide occurs within an acceptable index.

5. The method according to claim 3, wherein the mixture further comprises one or more solvents.

6. The method according to claim 4, wherein the mixture further comprises one or more solvents.

7. The method according to claim 3, wherein the catalyst is reused.

8. The method according to claim 4, wherein the catalyst is reused.