CA1274838A - Trifluoromethylation process - Google Patents
Trifluoromethylation processInfo
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- CA1274838A CA1274838A CA000545647A CA545647A CA1274838A CA 1274838 A CA1274838 A CA 1274838A CA 000545647 A CA000545647 A CA 000545647A CA 545647 A CA545647 A CA 545647A CA 1274838 A CA1274838 A CA 1274838A
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- alkoxy
- iodo
- bromo
- trifluoroacetate
- aromatic
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Abstract
ABSTRACT
TRIFLUOROMETHYLATION PROCESS
Trifluoromethylaromatic compounds are prepared by reacting the corresponding aromatic bromide or iodide with potassium trifluoroacetate in the presence of cuprous iodide and a dipolar aprotic solvent.
TRIFLUOROMETHYLATION PROCESS
Trifluoromethylaromatic compounds are prepared by reacting the corresponding aromatic bromide or iodide with potassium trifluoroacetate in the presence of cuprous iodide and a dipolar aprotic solvent.
Description
~7~
Case 5489 TRIFLUOROMETHYL~TION PROCESS
This invention relates to trifluoromethylaromatic compounds and more particularly to a process for preparing them.
As disclosed in Matsui et al., Chemistry Letters, 1981, pp. 1719-1720, it is known that aromatic iodides can be trifluoromethylated by reacting them with a large excess of sodium trifluoroacetate in the presence of cuprous iodide and a dipolar aprotic solvent. Matsui et al. also show that some trifluoromethylation occurs when an aromatic bromide is employed in the reaction instead of an iodide but that the yield of product is quite low.
United States patent 4,590,010 (Ramachandran et al.) teaches that the technique of Matsui et al. is applicable to the trifluoromethylation of 6-alkoxy-5-halo-l-cyanonaphthalenes and the corresponding naphthoate esters -- compounds which, like the compounds of Matsui et al., give better yields of the desired products when the halo substituent is iodo. Ramachandran et al. indicate that other trifluoroacetate salts can be used in their process, but they disclose a preference for using sodium trifluoroacetate as the trifluoromethylating agent.
It has been found that the use of sodium tri-fluoroacetate as a trifluoromethylating agent has several " J.~
disadvantages. As mentioned above, sodium trifluoro-acetate has to be used in considerable excess, and it does not provide acceptable yields of product from aromatic bromides. Moreover, its use requires a longer reaction time than would be desired, and it leads to the formation of relatively large amounts of by-products.
An object of this invention is to provide a novel process for preparing trifluoromethylaromatic compounds.
Another object is to provide such a process wherein 10 the trifluoromethylaromatic compounds can be prepared in high yields from aromatic iodides or aromatic bromides.
A further object is to provide such a process which utilizes a trifluoromethylating agent that is more selective than sodium trifluoroacetate, can be used in 15 smaller amounts, and does not require as long a reaction time.
These and other objects are attained by reacting an aromatic bromide or iodide with potassium trifluoroacetate in the presence of cuprous iodide and a dipolar aprotic 20 solvent.
Aromatic halides utilizable in the practice of the invention are substituted and unsubstituted aromatic iodides and bromides wherein any substituents are inert substituents (i.e., substituents that do not prevent the 25 reaction from occurring) such as alkyl, alkoxy, alkylthio, - aryl, aryloxy, arylthio, cyano, nitro, acylamino, alkyl-amino, tertiary amino, sulfonamido, sulfone, sulfonyl, ~ 74~
phosphino, perfluoroalkyl, chloro, fluoro, ester, alde-hyde, ketone, acetal, and sulfono groups. The aromatic ring may be a carbocyclic ring such as a benzene, naphthalene or anthracene ring or a five- or six-membered heterocyclic ring having aromatic character,e.g., a pyridine, quinoline, isoquinoline, thiophene, pyrrole, or furan ring. Exemplary of such compounds are iodobenzene, 3-iodotoluene, 4-chloroiodobenzene, 4-iodomethoxybenzene, l-iodonaphthalene, 3-iodoaniline, l-iodo-3-nitrobenzene, 2-iodothiophene, 4-iodoiso-quinoline, 2 iodopyridine, 3-iodoquinoline, and the corresponding bromides.
In a preferred embodiment of the invention, the aromatic halide is a halonaphthalene corresponding to the formula:
Q
R ~
x R'm wherein R and R' are independently selected from chloro, fluoro, nitro, hydroxy, and alkyl and alkoxy substituents containing 1-6 carbons; Q is -CN or -COOR"; R" is satu-rated hydrocarbyl; X is bromo or iodo; and m is 0 or 1.
The halocyanonaphthalenes and halonaphthoates utilizable in the practice of the invention may be any compounds corresponding to the above halonaphthalene ~.~7~
~ormula, but they are pre~erably compounds wherein m is 0, X is in the 5 position, and ~ is an alkyl or alkoxy substituent in the 6-position. When the R and R' suh-stituents are alkyl or alkoxy, they are generally 5 straight-chain groups of 1-3 carbons or branched-chain groups of three or four carbons, such as methyl, ethyl, propyl, l-methylethyl, butyl, 2-methylpropyl, 1,1 dimethyl-ethyl, and the corresponding alkoxy groups, although, as indicated above, larger groups such as hexyl and hexanoxy lO are also utilizable. When the halonaphthalene is an ester, R" may be any saturated hydrocarbyl group (i.e., a hydrocarbyl group that is ~ree of aliphatic unsaturation) but is preferably an alkyl, cycloalkyl, aryl, alkaryl, or aralkyl group containing 1-10 carbons, e.g., methyl, 15 ethyl, propyl, cyclohexyl, phenyl, tolyl, and benzyl.
Particularly preferred halonaphthalenes are 6-alkoxy-5-bromo-1-cyanonaphthalenes, 6-alkoxy-5-iodo-1-cyano-naphthalenes, 6-alkoxy-5-bromo-1-naphthoates, and 6-alkoxy-5-iodo-1-naphthoates, especially those compounds 20 ~herein the alkoxy groups are methoxy.
The halonaphthoates are known compounds. The halocyanonaphthalenes are compounds that can be prepared by cyanating the appropriately substituted tetralone, e.g., 6-methoxytetralone, to ~orm the appropriately 25 substituted 1-cyano-3,4-dihydronaphthalene, e.g., 6-- methoxy-1-cyano-3,4-dihydronaphthalene, aromatizing the ` ~ ~7~3~
product in any suitable manner, and brominating or iodinating the esultant substituted 1-cyanonaphthalene by known techniques.
The amount of potassium trifluoroacetate reacted 5 with the aromatic halide is not critical and may be a considerable excess, such as the amounts of sodium trifluoroacetate that have been employed in the past.
However, since such large amounts of potassium tri-fluoroacetate are not required, the amount used is gen-10 erally in the range of 1-3 equivalents, most commonly 1.5-2 equivalents.
Dipolar aprotic solvents that may be utilized include, e.g., N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, hexamethylphosphoric triamide, and 15 dimethylsulfoxide. The particular solvent employed does not appear to be critical except in the sense that it should have an appropriate boiling point for use at the reaction temperatures to be utilized, but the preferred solvents are N,N-dimethylformamide and N,N-dimethyl-20 acetamide. The solvent is used in solvent amounts, e.g.,an amount such as to provide an organic solids concen-tration of up to about 15%~
The cuprous iodide may be employed in any suit-able amount, generally an amount in the range of 0.5-5 25 equivalents.
-1~7~3~
The reaction is conducted by combininy the ingre~dients in any convenient order and heating them at a suitable temperature, for example, reflux temperature, to accomplish the desired trifluoromethylation. Anhydrous conditions are preferably employed, an~ the temperature is generally in the range of 130-160C., preferably 1~0-155C.
After completion of the reaction, the product may be recovered by conventional techniques and/or subjected to further reactions to form derivatives. For example, products obtained by trifluoromethylating the preferred halocyanonaphthalenes and halonaphthoates can be subjected to reactions such as those taught by Sestanj et al. in U.S. Patent 4,439,617. Thus, e.g., (1) a (trifluoro-methyl)cyanonaphthalene or trifluoromethylnaphthoatepreared by the trifluoromethylation reaction may be hydrolyzed to the corresponding acid in the presence of a base such as sodium or potassium hydroxide, (2) the acid can be halogenated, e.g., by reaction with thionyl chloride, to form the corresponding acid halide, (2) the acid halide may be reacted with a saturated hydrocarbyl ester of an acid corresponding to the formula ZNHCH2COOH
(e.g., methyl, ethyl, propyl, cyclohexyl, phenyl, tolyl, or benzyl sarcosinate, the corresponding esters of amino-acetic acids having other N-substituents (Z3 containing ~ 1-6 carbons, such as N-ethyl and N-propyl) to form an amide corresponding to the formula:
~ ,V,~7~
O=c_N(z)_cH2coo CF3 R'm and (3) the amide may be thiated, e.g., with phosphorus pentasulfide or the like, and the product saponified and hydrolyzed to form a thioamide corresponding to the formula:
S=C-N(Z)-CH2COOH
/\~
Rt ~1--~
3 R'm The invention is advantageous in that it permits trifluoromethylaromatic compounds to be prepared in high yields from the corresponding aromatic bromides or iodides at a faster rate and with the use of less reagent than is required when sodium trifluoroacetate is employed. Also, the reaction is more selective than the sodium trifluoro-acetate reaction, so the product is l~ss contaminated with by-product. Additionally, the potassium trifluoroacetate reactions can be accomplished with higher concentrations of solids than are operable when sodium trifluoroacetate ~ is used, and the reactor productivity can thus be in-creased considerably.
~ X~7~
The following examples are given to illustrate the invention and are not intended as a limitation thereof.
COMPARATIVE EXAMPLE A
A mixture of one molar proportion of 6-methoxy-5-iodo-1-cyanonaphthalene (6-MICN), 2.3 molar proportions of sodium trifluoroacetate, and 1.9 molar proportions of CuI was stirred into 146 molar proportions of toluene, after which about 82 molar proportions of the toluene were stripped at lll~C. Then 83 molar proportions of dry N,N-dimethylacetamide (DMAC) were added, and the mixture was heated while distilling over the remainder of the toluene until the temperature reached 152C. Heating was stopped, another 0.7 molar proportion of sodium trifluoro-acetate was added, and the reaction mixture was heated back up to 152C. and stirred for 80 minutes at 152-155C.
to give a total reaction time of four hours. After cooling and workup, GC analysis showed the reaction mix-ture to contain 97.25 area % of the desired 6-methoxy-5-trifluoromethyl-1-cyanonaphthalene (6-MTCN).
COMPARA~IVE EXAMPLE B
Comparative Example A was essentially repeated except that the 6-MICN was replaced with 6-methoxy-5-bromo-1-cyanonaphthalene (6-MBCN) and the total reaction time was 6 hours. GC analysis of the final reaction 25 mixture showed 93.45 area % of 6-MTCN.
COMPARATIV2 :E:XA~qPLE C
Using the same general procedure as in Comparative Example A, one molar proportion of methyl 6-methoxy-5-bromo-1-naphthoate (MMBN) was reacted with 1.7 molar proportions of sodium trifluoroacetate in the presence of
Case 5489 TRIFLUOROMETHYL~TION PROCESS
This invention relates to trifluoromethylaromatic compounds and more particularly to a process for preparing them.
As disclosed in Matsui et al., Chemistry Letters, 1981, pp. 1719-1720, it is known that aromatic iodides can be trifluoromethylated by reacting them with a large excess of sodium trifluoroacetate in the presence of cuprous iodide and a dipolar aprotic solvent. Matsui et al. also show that some trifluoromethylation occurs when an aromatic bromide is employed in the reaction instead of an iodide but that the yield of product is quite low.
United States patent 4,590,010 (Ramachandran et al.) teaches that the technique of Matsui et al. is applicable to the trifluoromethylation of 6-alkoxy-5-halo-l-cyanonaphthalenes and the corresponding naphthoate esters -- compounds which, like the compounds of Matsui et al., give better yields of the desired products when the halo substituent is iodo. Ramachandran et al. indicate that other trifluoroacetate salts can be used in their process, but they disclose a preference for using sodium trifluoroacetate as the trifluoromethylating agent.
It has been found that the use of sodium tri-fluoroacetate as a trifluoromethylating agent has several " J.~
disadvantages. As mentioned above, sodium trifluoro-acetate has to be used in considerable excess, and it does not provide acceptable yields of product from aromatic bromides. Moreover, its use requires a longer reaction time than would be desired, and it leads to the formation of relatively large amounts of by-products.
An object of this invention is to provide a novel process for preparing trifluoromethylaromatic compounds.
Another object is to provide such a process wherein 10 the trifluoromethylaromatic compounds can be prepared in high yields from aromatic iodides or aromatic bromides.
A further object is to provide such a process which utilizes a trifluoromethylating agent that is more selective than sodium trifluoroacetate, can be used in 15 smaller amounts, and does not require as long a reaction time.
These and other objects are attained by reacting an aromatic bromide or iodide with potassium trifluoroacetate in the presence of cuprous iodide and a dipolar aprotic 20 solvent.
Aromatic halides utilizable in the practice of the invention are substituted and unsubstituted aromatic iodides and bromides wherein any substituents are inert substituents (i.e., substituents that do not prevent the 25 reaction from occurring) such as alkyl, alkoxy, alkylthio, - aryl, aryloxy, arylthio, cyano, nitro, acylamino, alkyl-amino, tertiary amino, sulfonamido, sulfone, sulfonyl, ~ 74~
phosphino, perfluoroalkyl, chloro, fluoro, ester, alde-hyde, ketone, acetal, and sulfono groups. The aromatic ring may be a carbocyclic ring such as a benzene, naphthalene or anthracene ring or a five- or six-membered heterocyclic ring having aromatic character,e.g., a pyridine, quinoline, isoquinoline, thiophene, pyrrole, or furan ring. Exemplary of such compounds are iodobenzene, 3-iodotoluene, 4-chloroiodobenzene, 4-iodomethoxybenzene, l-iodonaphthalene, 3-iodoaniline, l-iodo-3-nitrobenzene, 2-iodothiophene, 4-iodoiso-quinoline, 2 iodopyridine, 3-iodoquinoline, and the corresponding bromides.
In a preferred embodiment of the invention, the aromatic halide is a halonaphthalene corresponding to the formula:
Q
R ~
x R'm wherein R and R' are independently selected from chloro, fluoro, nitro, hydroxy, and alkyl and alkoxy substituents containing 1-6 carbons; Q is -CN or -COOR"; R" is satu-rated hydrocarbyl; X is bromo or iodo; and m is 0 or 1.
The halocyanonaphthalenes and halonaphthoates utilizable in the practice of the invention may be any compounds corresponding to the above halonaphthalene ~.~7~
~ormula, but they are pre~erably compounds wherein m is 0, X is in the 5 position, and ~ is an alkyl or alkoxy substituent in the 6-position. When the R and R' suh-stituents are alkyl or alkoxy, they are generally 5 straight-chain groups of 1-3 carbons or branched-chain groups of three or four carbons, such as methyl, ethyl, propyl, l-methylethyl, butyl, 2-methylpropyl, 1,1 dimethyl-ethyl, and the corresponding alkoxy groups, although, as indicated above, larger groups such as hexyl and hexanoxy lO are also utilizable. When the halonaphthalene is an ester, R" may be any saturated hydrocarbyl group (i.e., a hydrocarbyl group that is ~ree of aliphatic unsaturation) but is preferably an alkyl, cycloalkyl, aryl, alkaryl, or aralkyl group containing 1-10 carbons, e.g., methyl, 15 ethyl, propyl, cyclohexyl, phenyl, tolyl, and benzyl.
Particularly preferred halonaphthalenes are 6-alkoxy-5-bromo-1-cyanonaphthalenes, 6-alkoxy-5-iodo-1-cyano-naphthalenes, 6-alkoxy-5-bromo-1-naphthoates, and 6-alkoxy-5-iodo-1-naphthoates, especially those compounds 20 ~herein the alkoxy groups are methoxy.
The halonaphthoates are known compounds. The halocyanonaphthalenes are compounds that can be prepared by cyanating the appropriately substituted tetralone, e.g., 6-methoxytetralone, to ~orm the appropriately 25 substituted 1-cyano-3,4-dihydronaphthalene, e.g., 6-- methoxy-1-cyano-3,4-dihydronaphthalene, aromatizing the ` ~ ~7~3~
product in any suitable manner, and brominating or iodinating the esultant substituted 1-cyanonaphthalene by known techniques.
The amount of potassium trifluoroacetate reacted 5 with the aromatic halide is not critical and may be a considerable excess, such as the amounts of sodium trifluoroacetate that have been employed in the past.
However, since such large amounts of potassium tri-fluoroacetate are not required, the amount used is gen-10 erally in the range of 1-3 equivalents, most commonly 1.5-2 equivalents.
Dipolar aprotic solvents that may be utilized include, e.g., N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, hexamethylphosphoric triamide, and 15 dimethylsulfoxide. The particular solvent employed does not appear to be critical except in the sense that it should have an appropriate boiling point for use at the reaction temperatures to be utilized, but the preferred solvents are N,N-dimethylformamide and N,N-dimethyl-20 acetamide. The solvent is used in solvent amounts, e.g.,an amount such as to provide an organic solids concen-tration of up to about 15%~
The cuprous iodide may be employed in any suit-able amount, generally an amount in the range of 0.5-5 25 equivalents.
-1~7~3~
The reaction is conducted by combininy the ingre~dients in any convenient order and heating them at a suitable temperature, for example, reflux temperature, to accomplish the desired trifluoromethylation. Anhydrous conditions are preferably employed, an~ the temperature is generally in the range of 130-160C., preferably 1~0-155C.
After completion of the reaction, the product may be recovered by conventional techniques and/or subjected to further reactions to form derivatives. For example, products obtained by trifluoromethylating the preferred halocyanonaphthalenes and halonaphthoates can be subjected to reactions such as those taught by Sestanj et al. in U.S. Patent 4,439,617. Thus, e.g., (1) a (trifluoro-methyl)cyanonaphthalene or trifluoromethylnaphthoatepreared by the trifluoromethylation reaction may be hydrolyzed to the corresponding acid in the presence of a base such as sodium or potassium hydroxide, (2) the acid can be halogenated, e.g., by reaction with thionyl chloride, to form the corresponding acid halide, (2) the acid halide may be reacted with a saturated hydrocarbyl ester of an acid corresponding to the formula ZNHCH2COOH
(e.g., methyl, ethyl, propyl, cyclohexyl, phenyl, tolyl, or benzyl sarcosinate, the corresponding esters of amino-acetic acids having other N-substituents (Z3 containing ~ 1-6 carbons, such as N-ethyl and N-propyl) to form an amide corresponding to the formula:
~ ,V,~7~
O=c_N(z)_cH2coo CF3 R'm and (3) the amide may be thiated, e.g., with phosphorus pentasulfide or the like, and the product saponified and hydrolyzed to form a thioamide corresponding to the formula:
S=C-N(Z)-CH2COOH
/\~
Rt ~1--~
3 R'm The invention is advantageous in that it permits trifluoromethylaromatic compounds to be prepared in high yields from the corresponding aromatic bromides or iodides at a faster rate and with the use of less reagent than is required when sodium trifluoroacetate is employed. Also, the reaction is more selective than the sodium trifluoro-acetate reaction, so the product is l~ss contaminated with by-product. Additionally, the potassium trifluoroacetate reactions can be accomplished with higher concentrations of solids than are operable when sodium trifluoroacetate ~ is used, and the reactor productivity can thus be in-creased considerably.
~ X~7~
The following examples are given to illustrate the invention and are not intended as a limitation thereof.
COMPARATIVE EXAMPLE A
A mixture of one molar proportion of 6-methoxy-5-iodo-1-cyanonaphthalene (6-MICN), 2.3 molar proportions of sodium trifluoroacetate, and 1.9 molar proportions of CuI was stirred into 146 molar proportions of toluene, after which about 82 molar proportions of the toluene were stripped at lll~C. Then 83 molar proportions of dry N,N-dimethylacetamide (DMAC) were added, and the mixture was heated while distilling over the remainder of the toluene until the temperature reached 152C. Heating was stopped, another 0.7 molar proportion of sodium trifluoro-acetate was added, and the reaction mixture was heated back up to 152C. and stirred for 80 minutes at 152-155C.
to give a total reaction time of four hours. After cooling and workup, GC analysis showed the reaction mix-ture to contain 97.25 area % of the desired 6-methoxy-5-trifluoromethyl-1-cyanonaphthalene (6-MTCN).
COMPARA~IVE EXAMPLE B
Comparative Example A was essentially repeated except that the 6-MICN was replaced with 6-methoxy-5-bromo-1-cyanonaphthalene (6-MBCN) and the total reaction time was 6 hours. GC analysis of the final reaction 25 mixture showed 93.45 area % of 6-MTCN.
COMPARATIV2 :E:XA~qPLE C
Using the same general procedure as in Comparative Example A, one molar proportion of methyl 6-methoxy-5-bromo-1-naphthoate (MMBN) was reacted with 1.7 molar proportions of sodium trifluoroacetate in the presence of
2 molar proportions of CuI and 46 molar propor'cions of N,N-dimethylformamide (DMFj, with an additional 0.95 molar proportion of sodium trifluoroacetate being added during the course of the reaction. The total reaction time was 5 hours. After workup, the desir~d methyl 6-methoxy-5-trifluoromethyl-1-naphthoate (MMTN) was isolatsd in a 76% yield.
COMPARATIVE EXAMPLE D
A mixture of one molar proportion of 4-bromodi-phenyl ether, 1.99 molar proportions of CuI, and 1.7 molar proportions of sodium trifluoroacetate was stirred into 14 molar proportions of toluene, after which part of the toluene was stripped, 46 molar proportions of DMF were added, and the reaction mixture was heated up to 149C.
for thr~e hours. Heating was stopped, another molar proportion of sodium trifluoroacetate was added, and the mixture was heated up to 149C. for two hours. GC analy-sis of the product showed 47.5 area % of the desired 4-tri-fluoromethyldiphenyl ether, 26.5 area % of perfluoroalkyl homologs, and 22.8 area % of unreacted 4-~romodiphenyl ether.
~7~
EXAMPLE I
A mixture of one molar proportion of 6-MICN, l.g molar proportions of CuI, and 1.7 molar proportions of potassium trifluoroacetate was stirred into 10 molar 5 proportions of toluene after which part of the toluene was stripped, 40 molar proportions of DMF were added, and toluene and DMF were stripped until the temperature reached 149C. The temperature was maintained at 149-150C. for two hours, after which GC analysis showed that 10 all of the 6-MICN had been converted and more than 98% had been converted to 6-MTCN.
EXAMPLE II
A mixture of one molar proportion of 6-MBCN, 2 15 molar proportions of CuI, and 1.7 molar proportions of potassium trifluoroacetate was stirred into 15 molar proportions of toluene, after which part of the toluene was stripped and 66 molar proportions of DMF were added.
The reaction mixture was heated at 1~0-150C. for about 20 3.5 hours, cooled, worked up, and subjected to GC
analysis. the analysis showed substantially 100%
conversion to 6-MTCN and a trace formation of by-product.
EXAMPLE III
Example II was essentially repeated except that the - 25 solids concentration was doubled. Similar results were observed.
~'~7~
EXAMPLE IV
Example II was essentially repeated except that the amount of potassium trifluoroacetate used was 1.5 molar proportions, and 53 molar proportions of DMF were sub-5 stituted for the DMAC. The GC analysis showed 99.77 area% of 6-MTCN.
EXAMPLE V
Comparative Example C was essentially repeated except that the initial sodium trifluoroacetate was lO replaced with 1.75 molar proportions of potassium tri-fluoroacetate, no additional trifluoroacetate was added during the course of the reaction, and the reaction time was only 3.5 hours. GC analysis showed a conversion of 99.8%, and the isolated yield of product was a6%.
EXAMPLE VI
Comparative Example D was essentially repeated except that the initial sodium trifluoroacetate was replaced with 2.69 proportions of potassium trifluoro-acetate, no additional trifluoroacetate was added during 20 the course of the reaction, and the reaction time was 3.5 hours. GC analysis of the product showed 67 area % of the desired 4-trifluoromethyldiphenyl ether, 16.6 area % of perfluoroalkyl homologs, and 16.2 area % of unreacted 4-bromodiphenyl ether.
7~3~3 It is obvious that many variations may be made in the products and processes set forth above without departing from the spirit and scope of this invention.
COMPARATIVE EXAMPLE D
A mixture of one molar proportion of 4-bromodi-phenyl ether, 1.99 molar proportions of CuI, and 1.7 molar proportions of sodium trifluoroacetate was stirred into 14 molar proportions of toluene, after which part of the toluene was stripped, 46 molar proportions of DMF were added, and the reaction mixture was heated up to 149C.
for thr~e hours. Heating was stopped, another molar proportion of sodium trifluoroacetate was added, and the mixture was heated up to 149C. for two hours. GC analy-sis of the product showed 47.5 area % of the desired 4-tri-fluoromethyldiphenyl ether, 26.5 area % of perfluoroalkyl homologs, and 22.8 area % of unreacted 4-~romodiphenyl ether.
~7~
EXAMPLE I
A mixture of one molar proportion of 6-MICN, l.g molar proportions of CuI, and 1.7 molar proportions of potassium trifluoroacetate was stirred into 10 molar 5 proportions of toluene after which part of the toluene was stripped, 40 molar proportions of DMF were added, and toluene and DMF were stripped until the temperature reached 149C. The temperature was maintained at 149-150C. for two hours, after which GC analysis showed that 10 all of the 6-MICN had been converted and more than 98% had been converted to 6-MTCN.
EXAMPLE II
A mixture of one molar proportion of 6-MBCN, 2 15 molar proportions of CuI, and 1.7 molar proportions of potassium trifluoroacetate was stirred into 15 molar proportions of toluene, after which part of the toluene was stripped and 66 molar proportions of DMF were added.
The reaction mixture was heated at 1~0-150C. for about 20 3.5 hours, cooled, worked up, and subjected to GC
analysis. the analysis showed substantially 100%
conversion to 6-MTCN and a trace formation of by-product.
EXAMPLE III
Example II was essentially repeated except that the - 25 solids concentration was doubled. Similar results were observed.
~'~7~
EXAMPLE IV
Example II was essentially repeated except that the amount of potassium trifluoroacetate used was 1.5 molar proportions, and 53 molar proportions of DMF were sub-5 stituted for the DMAC. The GC analysis showed 99.77 area% of 6-MTCN.
EXAMPLE V
Comparative Example C was essentially repeated except that the initial sodium trifluoroacetate was lO replaced with 1.75 molar proportions of potassium tri-fluoroacetate, no additional trifluoroacetate was added during the course of the reaction, and the reaction time was only 3.5 hours. GC analysis showed a conversion of 99.8%, and the isolated yield of product was a6%.
EXAMPLE VI
Comparative Example D was essentially repeated except that the initial sodium trifluoroacetate was replaced with 2.69 proportions of potassium trifluoro-acetate, no additional trifluoroacetate was added during 20 the course of the reaction, and the reaction time was 3.5 hours. GC analysis of the product showed 67 area % of the desired 4-trifluoromethyldiphenyl ether, 16.6 area % of perfluoroalkyl homologs, and 16.2 area % of unreacted 4-bromodiphenyl ether.
7~3~3 It is obvious that many variations may be made in the products and processes set forth above without departing from the spirit and scope of this invention.
Claims (20)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. In a process for preparing a trifluoromethyl-aromatic compound by reacting an aromatic bromide or iodide with a trifluoroacetate in the presence of cuprous iodide and a dipolar aprotic solvent, the improvement which comprises employing potassium trifluoroacetate as the trifluoroacetate.
2. The process of claim 1 wherein the aromatic halide is a bromide.
3. The process of claim 1 wherein the aromatic halide is an iodide.
4. The process of claim 1 wherein the aromatic halide is a halonaphthalene corresponding to the formula:
wherein R and R' are independently selected from chloro, fluoro, nitro, hydroxy, and alkyl and alkoxy substituents containing 1-6 carbons; Q is -CN or -COOR"; R" is satu-rated hydrocarbyl; X is bromo or iodo; and m is 0 or 1.
wherein R and R' are independently selected from chloro, fluoro, nitro, hydroxy, and alkyl and alkoxy substituents containing 1-6 carbons; Q is -CN or -COOR"; R" is satu-rated hydrocarbyl; X is bromo or iodo; and m is 0 or 1.
5. The process of claim 4 wherein the aromatic halide is a 6-alkoxy-5-bromo-1-cyanonaphthalene.
6. The process of claim 4 wherein the aromatic halide is a 6-alkoxy-5-iodo-1-cyanonaphthalene.
7. The process of claim 4 wherein the aromatic halide is a 6-alkoxy-5-bromo-1-naphthoate.
8. The process of claim 4 wherein the aromatic halide is a 6-alkoxy-5-iodo-1-naphthoate.
9. The process of claim 1 wherein the reaction is conducted at 130-160°C.
10. The process of claim 9 wherein the reaction is conducted at 140-155°C.
11. The process of claim 1 wherein the aromatic halide is reacted with 1-3 equivalents of potassium trifluoroacetate.
12. The process of claim 1 wherein the solvent is N,N-dimethylformamide.
13. The process of claim 1 wherein the solvent is N,N-dimethylacetamide.
14. A process which comprises reacting a halonaphthalene corresponding to the formula:
wherein R and R' are independently selected from chloro, fluoro, nitro, hydroxy, and alkyl and alkoxy substituents containing 1-6 carbons; Q is -CN or -COOR"; R" is satu-rated hydrocarbyl; X is bromo or iodo; and m is 0 or 1, with 1-3 equivalents of potassium trifluoroacetate in the presence of a dipolar aprotic solvent and 0.5-5 equiva-lents of cuprous iodide at 140-155°C. so as to form a tri-fluoromethylaromatic compound.
wherein R and R' are independently selected from chloro, fluoro, nitro, hydroxy, and alkyl and alkoxy substituents containing 1-6 carbons; Q is -CN or -COOR"; R" is satu-rated hydrocarbyl; X is bromo or iodo; and m is 0 or 1, with 1-3 equivalents of potassium trifluoroacetate in the presence of a dipolar aprotic solvent and 0.5-5 equiva-lents of cuprous iodide at 140-155°C. so as to form a tri-fluoromethylaromatic compound.
15. The process of claim 14 wherein the solvent is N,N-dimethylformamide.
16. The process of claim 14 wherein the solvent is N,N-dimethylacetamide.
17. The process of claim 14 wherein the halo-naphthalene is a 6-alkoxy-5-bromo-1-cyanonaphthalene.
18. The process of claim 14 wherein the halo-naphthalene is a 6-alkoxy-5-iodo-1-cyanonaphthalene.
19. The process of claim 14 wherein the halo-naphthalene is a 6-alkoxy-5-bromo-1-naphthoate.
20. The process of claim 14 wherein the halo-naphthalene is a 6-alkoxy-5-iodo-1-naphthoate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000545647A CA1274838A (en) | 1985-12-12 | 1987-08-28 | Trifluoromethylation process |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/808,304 US4808748A (en) | 1985-12-12 | 1985-12-12 | Trifluoromethylation process |
| CA000545647A CA1274838A (en) | 1985-12-12 | 1987-08-28 | Trifluoromethylation process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1274838A true CA1274838A (en) | 1990-10-02 |
Family
ID=25671484
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000545647A Expired - Fee Related CA1274838A (en) | 1985-12-12 | 1987-08-28 | Trifluoromethylation process |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1274838A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2447240A1 (en) | 2010-10-29 | 2012-05-02 | Saltigo GmbH | Copper-catalysed Process for the Production of Substituted or Unsubstituted Trifluormethylated Aryl and Heteroaryl Compounds |
-
1987
- 1987-08-28 CA CA000545647A patent/CA1274838A/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2447240A1 (en) | 2010-10-29 | 2012-05-02 | Saltigo GmbH | Copper-catalysed Process for the Production of Substituted or Unsubstituted Trifluormethylated Aryl and Heteroaryl Compounds |
| US8530666B2 (en) | 2010-10-29 | 2013-09-10 | Saltigo Gmbh | Copper-catalysed process for the production of substituted or unsubstituted trifluormethylated aryl and heteroaryl compounds |
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