CA1097372A - N-alkyldiphenylamines - Google Patents
N-alkyldiphenylaminesInfo
- Publication number
- CA1097372A CA1097372A CA258,782A CA258782A CA1097372A CA 1097372 A CA1097372 A CA 1097372A CA 258782 A CA258782 A CA 258782A CA 1097372 A CA1097372 A CA 1097372A
- Authority
- CA
- Canada
- Prior art keywords
- dinitro
- methyl
- trifluoromethyl
- diphenylamine
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/07—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms
- C07C205/11—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings
- C07C205/12—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings the six-membered aromatic ring or a condensed ring system containing that ring being substituted by halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/44—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
- C07C211/52—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
Abstract
ABSTRACT OF THE DISCLOSURE
The present invention relates to novel diphenyl-amines having small alkyl substituents on the amino nitro-gen, which are useful as intermediates for the preparation of rodenticidal diphenylamines. One phenyl ring has 2,4-dinitro-6-trifluoromethyl substitution, and the other is substituted with no more than one methyl or trifluoromethyl group. The diphenylamines have the following structure:
The present invention relates to novel diphenyl-amines having small alkyl substituents on the amino nitro-gen, which are useful as intermediates for the preparation of rodenticidal diphenylamines. One phenyl ring has 2,4-dinitro-6-trifluoromethyl substitution, and the other is substituted with no more than one methyl or trifluoromethyl group. The diphenylamines have the following structure:
Description
7;~7;~
The present invention relates to novel diphenyl-amines havlng small alkyl substituents on the amino nitro-gen, which are useful as intermediates for the preparation of rodenticidal diphenylamines. One phenyl ring has 2,4-dinitro-6-trifluoromethyl substitution, and the other is substituted with no more than one methyl or trifluoromethyl group.
This invention belongs to the rodenticidal and - organic chemical arts and provides new intermediates for the preparation of rodenticides.
Rodenticides have long been the subject of re-search. Rats and mice carry many diseases, and create havoc when they share the habitations of mankind. They soil and contaminate buildings, and destroy buildinss and their contents by their tunneling and nest building. The animals, when present in numbers, consume or contaminate great amounts of food.
Many kinds of rodenticides have been discovered and many are still in use. Probably the best all round existing rodenticide is the organic chemical compound, warfarin. Rodents, however, are developing resistance to existing rodenticides. The metallic poisons, such as arsenic and thallium compounds, are used to a degree but are obviously quite dangerous to people and to useful animals.
Tertiary diphenylamines such as those of this invention have not previously been known. Secondary di-phenylamines, however, have previously been known to be fungicides and insecticides.
X-48~9 -~-~397372 The present invention provides novel diphenyl-amine compounds of the formula qlO2 R1 R2 02N~ j~R3 wherein R represents methyl, ethyl or propyl;
Rl and R2 independently represent hydrogen, me~hyl or tri-fluoromethyl;
10 R3 represents hydrogen or methyl; ---provided that no more than one of Rl, R2 and R3 represents a group other than hydrogen. ~: -The present invention also provides a process for preparing novel diphenylamine compounds of formula I
wherein the symbols have the meanings stated above, which comprises reacting a 2-halo-3,5-dinitrobenzotrifluoride ~ ~ compound of the formula . -.~ qJOz ~ 20 2~-\ 9_x III
~F3 wherein X i5 halo, with an aniline compound of ~he ormula ,~ , ~ : R3- ~ ~ ~ NH2 III
., , , ~g~37Z
wherein Rl, R2, and R3 are as defined above;
follo~ed by N-alkylating the compound so obtained.
All of the compounds described in this document will be named as diphenylamines for the sake of consistency, even though the rules of nomenclature might call for some compounds to be named otherwise.
All percentages and parts described hereafter refer to percentages and parts by w~ight, and all tempera- -tures are on the Celsius scale.
The following exemplary compounds are mentioned only to assure that the reader fully understands the in-vention.
N,2-dimethyl-2',4'-dinitro-6'-trifluoromethyl-diphenylamine N-ethyl-3-methyl-2',4'-dinitro-6'-trifluoromethyl-diphenylamine 4-methyl-2',4'-dinitro-N-propyl-6'-trifluoro-methyldiphenylamine
The present invention relates to novel diphenyl-amines havlng small alkyl substituents on the amino nitro-gen, which are useful as intermediates for the preparation of rodenticidal diphenylamines. One phenyl ring has 2,4-dinitro-6-trifluoromethyl substitution, and the other is substituted with no more than one methyl or trifluoromethyl group.
This invention belongs to the rodenticidal and - organic chemical arts and provides new intermediates for the preparation of rodenticides.
Rodenticides have long been the subject of re-search. Rats and mice carry many diseases, and create havoc when they share the habitations of mankind. They soil and contaminate buildings, and destroy buildinss and their contents by their tunneling and nest building. The animals, when present in numbers, consume or contaminate great amounts of food.
Many kinds of rodenticides have been discovered and many are still in use. Probably the best all round existing rodenticide is the organic chemical compound, warfarin. Rodents, however, are developing resistance to existing rodenticides. The metallic poisons, such as arsenic and thallium compounds, are used to a degree but are obviously quite dangerous to people and to useful animals.
Tertiary diphenylamines such as those of this invention have not previously been known. Secondary di-phenylamines, however, have previously been known to be fungicides and insecticides.
X-48~9 -~-~397372 The present invention provides novel diphenyl-amine compounds of the formula qlO2 R1 R2 02N~ j~R3 wherein R represents methyl, ethyl or propyl;
Rl and R2 independently represent hydrogen, me~hyl or tri-fluoromethyl;
10 R3 represents hydrogen or methyl; ---provided that no more than one of Rl, R2 and R3 represents a group other than hydrogen. ~: -The present invention also provides a process for preparing novel diphenylamine compounds of formula I
wherein the symbols have the meanings stated above, which comprises reacting a 2-halo-3,5-dinitrobenzotrifluoride ~ ~ compound of the formula . -.~ qJOz ~ 20 2~-\ 9_x III
~F3 wherein X i5 halo, with an aniline compound of ~he ormula ,~ , ~ : R3- ~ ~ ~ NH2 III
., , , ~g~37Z
wherein Rl, R2, and R3 are as defined above;
follo~ed by N-alkylating the compound so obtained.
All of the compounds described in this document will be named as diphenylamines for the sake of consistency, even though the rules of nomenclature might call for some compounds to be named otherwise.
All percentages and parts described hereafter refer to percentages and parts by w~ight, and all tempera- -tures are on the Celsius scale.
The following exemplary compounds are mentioned only to assure that the reader fully understands the in-vention.
N,2-dimethyl-2',4'-dinitro-6'-trifluoromethyl-diphenylamine N-ethyl-3-methyl-2',4'-dinitro-6'-trifluoromethyl-diphenylamine 4-methyl-2',4'-dinitro-N-propyl-6'-trifluoro-methyldiphenylamine
2-methyl-2',4'-dinitro-N-propyl-6'-trifluoro-methyldiphenylamine 2,4-dinitro-N-propyl-3',6-bis(trifluoromethyl)di-phenyla~ine N-ethyl-Z,4-dinitro-2',6-bis(trifluoromethyl)di-phenylamine
3-methyl-2',4'-dinitro-N~propyl-6'-tri~luoro-methyldiphenylamine N-ethyl-4-methyl-2',4'-dinitro-5'-trifluoromethyl-diphenylamine The pre~erred compounds of this invention are N-methyl-2,4-dinitro-6-trifluoromethyldiphenylamine, N-X-486g -4-~L~9737;i~
ethyl-2, 4-dini tro-6-trifluoromethyldiphenylamine, 2,4-dinitro-N-propyl-6-trifluo~omethyldiphenylamine, N-methyl-2,4-dinitro-3',6-bis(trifluoromethyl)diphenylamine, and N-methyl-2,4-dinitro-21,6-bis(trifluoromethyl)diphenylamine.
The compounds of formula I are made by the fol-lowing process.
NOz ~ ~Z
02 f ~ hal~H~ ~-R3 ~
CF3 . .
O~N~ ~Ra /__ Fs alkylation --\
.
In the above formula, the term "halo" refers to any of the four common halogen atoms r of which chlorine and fluorine are preferred and chlorine is usually the most convenient.
The individual steps of the above process are not extraordinary in organic chemistry, and are conducted as a skilled organic chemist would expect. The coupling re-actions which join the aniline and benzotrifluoride rings are most readily carried out at relatively low temperatures X-48~9 -5-37~
in the range o~ -20 to 10 in dimethylformamide in the presence of sodium hydride. Other media are likewise useful. The reactions may be carried out, for example, in alkanols such as ethanol, in which solvents the reaction temperature may be higher, in the range of 10~ to 25.
Other solvents, including ketones such as acetone and methyl ethyl ketone and ethers including diethyl ether and tetra-hydrofuran, are satisfactory reaction solvents.
In general, a strong base is needed to serve as acid scavenger. Sodium hydride, as mentioned above, is generally the most useful base, but other bases including inorganic bases such as sodium hydroxide and sodium car-bonate, and organic tertiary amines such as pyridine and triethylamine, as well as a simple excess of the aniline starting compound, may be used.
N-Alkylation of the diphenylamines is performed with reagents such as a dialkyl sulfate or an alkyl halide in the prPsence of a base. When a dialkyl sulfate is used, the preferred reaction solvent is acetone. Other solvents, such as tetrahydrofuran, dioxane and diethyl ether, are also useful, as are alkanes such as hexane and octane. Dimethyl-formamide is th~ preferred solvent or alkylations with alkyl halides, although acetone is also excellent. Other solvents as described above may ke used.
The preferred bases for use in the alkylation reactions are those which have a dehydrating effect, parti-cularly sodium carbonate. However, other inorganic bases, such as the alkali metal carbonates, bicarbonates and hydroxides, can be used, as can the alkali metal hydrides.
X-4~69 -6-The amount of base used depends upon the reaction temperature. The higher the reaction temperature in the alkylation step, the greater excess of base is needed. When the reaction temperature is approximately ambient, a small excess of base should be used, such as 2 moles of base per mole of diphenylamine. When very high reaction temperatures such as 100 are used, a large excess of base should be used, in the range of 10-fold.
It will be recognized that it is important to avoid contamination of the alkylation reaction mixture with water.
In general, alkylations with dialkyl sulfates are best performed at about 80~, although temperatures from ap-proximately room temperature to the reflux temp~rature ma~
be used. Conditions close to room temperature, such as from 20 to 35, are preferred for alkyl halide alkylations, but elevated temperatures up even to as high as 150 may be used.
The starting substituted anilines and phenyl halides are readily obtained by methods which are commonly known in the chemical literature.
The trifluoromethyl-substituted anilines are best prepared, as chemists will recognize, by first obtaining a carboxylic acid-substituted aniline having the acid groups at the locations of the desired trifluoromethyls. The acid group is fluorinated with sulfur tetrafluoride.
The following examples, showing the preparation of typical compounds o~ formula I, are presented to assure that organic chemists can easily obtain any desired compound.
X-486g _7_ ~7372 The products of the examples were identified by nuclear magnetic resonance analysis, elemental microanalysis, thin~layer chromatography, and in some instances, by mass spectrophotometry and infrared analysis.
Example 1 N-methyl-2,4-dinitro-6-trifluoromethyldiphenylamine A 27 g. portion of 2-chloro-3,5-dinitro~enzotri-fluoride was added to 20 g. of aniline and 75 ml. of ethanol.
After brief stirring at room temperature, the reaction mixture was seeded with a small sample of the desired in-termediate product, and a precipitate formed immediately.
The precipitate was separated by filtration and identified as 28.5 g. of 2,4-dinitro-6-trifluoromethyldiphenylamine.
The intermediate product was N-methylated in two different ways, ~oth of which will be shown for tha sake of clarity.
A. A 3.3 g. portion of the intermediate diphenyl-amine was taken up in 15 ml. of dimethylformamide, and 1O3 g. of sodium hydride was added. The mixture was stirred at room temperature, and l.S ml. of methyl iodide was added with the evolution of heat~ After 1-1/2 hours, another 2 ml. of methyl lodide was added, and the mixture was warmed slightly. After 2 hours more, the reaction mixture was added to a large amount of cold water, and the aqueous layer was decanted. The remaining oil was taken up in diethyl ether and stirred with magnesium sulfate and charcoal.
After the solids were filtered away, the solution was evaporated to dryness to produce 2.4 g. of a dark red oil, which solidified upon cooling. The solid was heated with 37~
petroleum ether, cooled and filtered to produce 2.4 g. of N-methyl-2,4-dinitro-6-trifluoromethyldiphenylaminé, m.p.
84-86.
TheoreticalFound C49.28% 49.24%
H 2.95 3.05 N 12.31 12.31 B. Eleven g. of the intermediate diphenylamine was combined with 45 ml. of dioxane, 14 g. of sodium car-bonate and 6 ml. of dimethyl sulfate and stirred at refluxtemperature for 24 hours. Twelve ml. of additional dimethyl sulfate and lO g. of sodium carbonate were then added, and the mixture was stirred at reflux temperature for 2 hours more. It was then poured into water and stirred for 4 hours. The aqueous layer was then decanted and the residue was taken up in methylene chloride and filtered. The solute was identified as approximately lO g. of crude N-methyl-2,4-dinitro-6-trifluoromethyldiphenylamine.
Example 2 -2,4-dinitro-N-~ro~y~6 trlfluorometh~ldiphen~lamine A 5 g. portion of the diphenylamine intermediate prepared in the first step of Example l was alkylated with propyl iodide in 80 ml. of dimethylformamide in the presence of 20 g. of sodium carbonate. The reaction mixture was stirred at 110 for 72 hours. The product was recovered by quenching the reaction mixture with water, extracting with methylene chloride, and evaporating the solvent under vacuum. Purification of the crude product on a silica gel chromatographic column, eluting with toluene, produced 1.2 ~09~3~2 g. of pure product, a liquid, NMR peaks at 0.93 (triplet), 1.35-2.05, 3.59, 6.45-6.78, 6.82-7.38, 8.63 and 8.76 ppm.
Example _ N-methyl-2,4-dinitro-2',6-bis(triEluoromethyl)diphenylamine Following the general process of Example 1, 4.8 g.
of 2-aminobenzotrifluoride was coupled with 8.1 g. of 2-chloro-3,5-dinitrobenzotrifluoride to produce 4.5 g. of 2,4-dinitro-2',6-bis(trifluoromethyl)diphenylamine, after purification over a silica gel column with methylene chloride as the eluting solventO
A 2 g. portion of the above intermediate was alkylated with 5 ml. of dimethyl sulfate in acetone in the presence of sodium carbonate. The product was recrystal-lized from ethanol to produce 75 mg. of N-methyl-2,4-di-nitro-2',6-bis(trifluoromethyl)diphenylamine, m.p. 148-Theoretical Found C4~.02% 43.73%
H 2.22 2.26 N 10.27 lO.09 Example 4 -N,4-dimethyl-2',4'-dinitro-6'-trifluoromethyldiphenylamine A 10 g. portion of p-toluidine was coupled with 12.6 g. of 2-chloro-3,5-dinitrobenzotrifluoride in ethanol according to the general process of Example 1. The inter-mediate product was recovered by filtration and identified as 10.1 g. of 4-methyl-2',4'-dinitro-6'-trifluoromethyldi-phenylamine.
X-48~9 -10-- .
~9~ 7Z
A 1 g. portion of the above intermediate was alkylated with 5 ml. of methyl iodide in 12 ml. of acetone in the presence of 5 g. of sodium carbonate. The mixture was stirred at reflux temperature for 96 hours. The mixture was then evaporated to dryness and the residue was digested with two 150-ml. portions of hot hexane. The hexane was filtered hot, and the filtrate was evaporated to dryness under vacuum. The residue was recrystallized from ethanol to produce 750 mg. of N,4-dimethyl-2',4'-dinitro-6'-tri-fluoromethyldiphenylamine, m.p. 124-125.
Theo~eticalFound -C 50.71% 50.51 H 3.40 3.35 N 11.83 11.75 Example 5 N-methyl-2,4-dinitro-3',6-bis(trifluorom~yl)diphenylamine Twenty g. of 3-aminobenzotrifluoride was coupled with 16.8 g. of 2-chloro-3,5-dinitrobenzotrifluoride in 200 ml. of anhydrous ethanol at reflux temperature overnight.
The ethanol was then removed under vacuum and the product was separated from the hydrochloride salt byproduct by dissolving it in toluene~ The toluene was then evaporated under vacuum and the intermediate product was recrystallized from ethanol to produce about 13 g. of 2,4-dinitro-3',6-bis(trifluoromethyl)diphenylamine, m.p. 99-100.
A 4 g. portion of the above intermediate was then alkylated with 10 ml. of dimethyl sulfate in acetone in the ~737;~
presence of sodium carbonate according to the process of .
Example lB. The product was recrystallized from ethanol to collect 2 g. of N-methyl-2,4-dinitro-3',6-bis(trifluoro-methyl)diphenylamine, m.p. 108-109.
Theoretical Found C 44.02% 44.01%
H 2.22 2.35 N 10.27 10.23 Example 6 N,2-dimethyl-2',4'-dinitro-6'-trifluoromethyldiphenylamine Fifteen g. of o-toluidine was coupled with 18.9 g.
of 2-chloro-3,5-dinitrobenzotrifluoride in 150 ml. of e~hanol at reflux temperature overnight. A precipitate formed when the mixture was cooled. The precipitate was collected and identified as 6.8 g~ of 2-methyl-2',4' di-nitro-6'-trifluoromethyldiphenylamine.
The above intermediate was alkylated with 20 ml.
of dimethyl sulfate in 25 ml. of acetone in the presence of 12 g. of sodium carbonate. The mixture was held at reflux temperature for 24 hours, and was then diluted with 50 ml.
of water. The aqueous layer was decanted and the residue was taken up in methylene chloride, washed with water, filtered, and evaporated to dryness~ The residue left after evaporating was purified by chromatography on a silica gel column with 1:1 pentane:methylene chloride as the eluting solvent. Four g. of pure N,2-dimethyl-2',4'-dinitro-6'-trifluoromethyldiphenylamine, m.p. 106-108, was collected.
Theoretical Found C 50.71% 50.88%
H 3.40 3.46 N 11.83 12.08 The intermediates of formula I are used in the preparation of an important series o~ rodenticides by halogenating or nitrating the aniline ring appropriately.
Th~ reactions follow the usual practice of organic ch~mistry.
For example, halogenations are usually best per-formed with the elemental hal~gen in acetic acid, or in methylene chloride or the like halogenated solvent~ in-cluding chloroform or carbon tetrachloride. ~oom temper-ature halogenation is usually effective, but increased speed of reaction i5 obtainable by slight elevation of the re-action temperature in the range of 25-50. Chlorination is best done with the elemental gaseous halogen, but bromina-tion may be done with such agents as N-bromosuccinimide and dibromoisocyanuric acid, although reaction with elemental bromine is usually quite satisfac ory.
Iodination is best carried out with iodine mono-chloride as the reagent.
When a compound having no 4-substituent is to be made, it will often be necessary to block the 4-position before halogenating. It is most convenient to use a sul-fonic acid as the blocking group, because it is readily added and readily removed.
Insertion of nitro groups on the aniline ring is readily accomplished with concentrated nitric acid in acetic acid solution at room temperature. Other nitration re-X-4~6~ -13-actions may also be used, such as a mixture of concentrated nitric and sulfuric acids at elevated temperatures. In general, no solvent is used in nitration reactions other than the acids themselves.
X-~69 -14-
ethyl-2, 4-dini tro-6-trifluoromethyldiphenylamine, 2,4-dinitro-N-propyl-6-trifluo~omethyldiphenylamine, N-methyl-2,4-dinitro-3',6-bis(trifluoromethyl)diphenylamine, and N-methyl-2,4-dinitro-21,6-bis(trifluoromethyl)diphenylamine.
The compounds of formula I are made by the fol-lowing process.
NOz ~ ~Z
02 f ~ hal~H~ ~-R3 ~
CF3 . .
O~N~ ~Ra /__ Fs alkylation --\
.
In the above formula, the term "halo" refers to any of the four common halogen atoms r of which chlorine and fluorine are preferred and chlorine is usually the most convenient.
The individual steps of the above process are not extraordinary in organic chemistry, and are conducted as a skilled organic chemist would expect. The coupling re-actions which join the aniline and benzotrifluoride rings are most readily carried out at relatively low temperatures X-48~9 -5-37~
in the range o~ -20 to 10 in dimethylformamide in the presence of sodium hydride. Other media are likewise useful. The reactions may be carried out, for example, in alkanols such as ethanol, in which solvents the reaction temperature may be higher, in the range of 10~ to 25.
Other solvents, including ketones such as acetone and methyl ethyl ketone and ethers including diethyl ether and tetra-hydrofuran, are satisfactory reaction solvents.
In general, a strong base is needed to serve as acid scavenger. Sodium hydride, as mentioned above, is generally the most useful base, but other bases including inorganic bases such as sodium hydroxide and sodium car-bonate, and organic tertiary amines such as pyridine and triethylamine, as well as a simple excess of the aniline starting compound, may be used.
N-Alkylation of the diphenylamines is performed with reagents such as a dialkyl sulfate or an alkyl halide in the prPsence of a base. When a dialkyl sulfate is used, the preferred reaction solvent is acetone. Other solvents, such as tetrahydrofuran, dioxane and diethyl ether, are also useful, as are alkanes such as hexane and octane. Dimethyl-formamide is th~ preferred solvent or alkylations with alkyl halides, although acetone is also excellent. Other solvents as described above may ke used.
The preferred bases for use in the alkylation reactions are those which have a dehydrating effect, parti-cularly sodium carbonate. However, other inorganic bases, such as the alkali metal carbonates, bicarbonates and hydroxides, can be used, as can the alkali metal hydrides.
X-4~69 -6-The amount of base used depends upon the reaction temperature. The higher the reaction temperature in the alkylation step, the greater excess of base is needed. When the reaction temperature is approximately ambient, a small excess of base should be used, such as 2 moles of base per mole of diphenylamine. When very high reaction temperatures such as 100 are used, a large excess of base should be used, in the range of 10-fold.
It will be recognized that it is important to avoid contamination of the alkylation reaction mixture with water.
In general, alkylations with dialkyl sulfates are best performed at about 80~, although temperatures from ap-proximately room temperature to the reflux temp~rature ma~
be used. Conditions close to room temperature, such as from 20 to 35, are preferred for alkyl halide alkylations, but elevated temperatures up even to as high as 150 may be used.
The starting substituted anilines and phenyl halides are readily obtained by methods which are commonly known in the chemical literature.
The trifluoromethyl-substituted anilines are best prepared, as chemists will recognize, by first obtaining a carboxylic acid-substituted aniline having the acid groups at the locations of the desired trifluoromethyls. The acid group is fluorinated with sulfur tetrafluoride.
The following examples, showing the preparation of typical compounds o~ formula I, are presented to assure that organic chemists can easily obtain any desired compound.
X-486g _7_ ~7372 The products of the examples were identified by nuclear magnetic resonance analysis, elemental microanalysis, thin~layer chromatography, and in some instances, by mass spectrophotometry and infrared analysis.
Example 1 N-methyl-2,4-dinitro-6-trifluoromethyldiphenylamine A 27 g. portion of 2-chloro-3,5-dinitro~enzotri-fluoride was added to 20 g. of aniline and 75 ml. of ethanol.
After brief stirring at room temperature, the reaction mixture was seeded with a small sample of the desired in-termediate product, and a precipitate formed immediately.
The precipitate was separated by filtration and identified as 28.5 g. of 2,4-dinitro-6-trifluoromethyldiphenylamine.
The intermediate product was N-methylated in two different ways, ~oth of which will be shown for tha sake of clarity.
A. A 3.3 g. portion of the intermediate diphenyl-amine was taken up in 15 ml. of dimethylformamide, and 1O3 g. of sodium hydride was added. The mixture was stirred at room temperature, and l.S ml. of methyl iodide was added with the evolution of heat~ After 1-1/2 hours, another 2 ml. of methyl lodide was added, and the mixture was warmed slightly. After 2 hours more, the reaction mixture was added to a large amount of cold water, and the aqueous layer was decanted. The remaining oil was taken up in diethyl ether and stirred with magnesium sulfate and charcoal.
After the solids were filtered away, the solution was evaporated to dryness to produce 2.4 g. of a dark red oil, which solidified upon cooling. The solid was heated with 37~
petroleum ether, cooled and filtered to produce 2.4 g. of N-methyl-2,4-dinitro-6-trifluoromethyldiphenylaminé, m.p.
84-86.
TheoreticalFound C49.28% 49.24%
H 2.95 3.05 N 12.31 12.31 B. Eleven g. of the intermediate diphenylamine was combined with 45 ml. of dioxane, 14 g. of sodium car-bonate and 6 ml. of dimethyl sulfate and stirred at refluxtemperature for 24 hours. Twelve ml. of additional dimethyl sulfate and lO g. of sodium carbonate were then added, and the mixture was stirred at reflux temperature for 2 hours more. It was then poured into water and stirred for 4 hours. The aqueous layer was then decanted and the residue was taken up in methylene chloride and filtered. The solute was identified as approximately lO g. of crude N-methyl-2,4-dinitro-6-trifluoromethyldiphenylamine.
Example 2 -2,4-dinitro-N-~ro~y~6 trlfluorometh~ldiphen~lamine A 5 g. portion of the diphenylamine intermediate prepared in the first step of Example l was alkylated with propyl iodide in 80 ml. of dimethylformamide in the presence of 20 g. of sodium carbonate. The reaction mixture was stirred at 110 for 72 hours. The product was recovered by quenching the reaction mixture with water, extracting with methylene chloride, and evaporating the solvent under vacuum. Purification of the crude product on a silica gel chromatographic column, eluting with toluene, produced 1.2 ~09~3~2 g. of pure product, a liquid, NMR peaks at 0.93 (triplet), 1.35-2.05, 3.59, 6.45-6.78, 6.82-7.38, 8.63 and 8.76 ppm.
Example _ N-methyl-2,4-dinitro-2',6-bis(triEluoromethyl)diphenylamine Following the general process of Example 1, 4.8 g.
of 2-aminobenzotrifluoride was coupled with 8.1 g. of 2-chloro-3,5-dinitrobenzotrifluoride to produce 4.5 g. of 2,4-dinitro-2',6-bis(trifluoromethyl)diphenylamine, after purification over a silica gel column with methylene chloride as the eluting solventO
A 2 g. portion of the above intermediate was alkylated with 5 ml. of dimethyl sulfate in acetone in the presence of sodium carbonate. The product was recrystal-lized from ethanol to produce 75 mg. of N-methyl-2,4-di-nitro-2',6-bis(trifluoromethyl)diphenylamine, m.p. 148-Theoretical Found C4~.02% 43.73%
H 2.22 2.26 N 10.27 lO.09 Example 4 -N,4-dimethyl-2',4'-dinitro-6'-trifluoromethyldiphenylamine A 10 g. portion of p-toluidine was coupled with 12.6 g. of 2-chloro-3,5-dinitrobenzotrifluoride in ethanol according to the general process of Example 1. The inter-mediate product was recovered by filtration and identified as 10.1 g. of 4-methyl-2',4'-dinitro-6'-trifluoromethyldi-phenylamine.
X-48~9 -10-- .
~9~ 7Z
A 1 g. portion of the above intermediate was alkylated with 5 ml. of methyl iodide in 12 ml. of acetone in the presence of 5 g. of sodium carbonate. The mixture was stirred at reflux temperature for 96 hours. The mixture was then evaporated to dryness and the residue was digested with two 150-ml. portions of hot hexane. The hexane was filtered hot, and the filtrate was evaporated to dryness under vacuum. The residue was recrystallized from ethanol to produce 750 mg. of N,4-dimethyl-2',4'-dinitro-6'-tri-fluoromethyldiphenylamine, m.p. 124-125.
Theo~eticalFound -C 50.71% 50.51 H 3.40 3.35 N 11.83 11.75 Example 5 N-methyl-2,4-dinitro-3',6-bis(trifluorom~yl)diphenylamine Twenty g. of 3-aminobenzotrifluoride was coupled with 16.8 g. of 2-chloro-3,5-dinitrobenzotrifluoride in 200 ml. of anhydrous ethanol at reflux temperature overnight.
The ethanol was then removed under vacuum and the product was separated from the hydrochloride salt byproduct by dissolving it in toluene~ The toluene was then evaporated under vacuum and the intermediate product was recrystallized from ethanol to produce about 13 g. of 2,4-dinitro-3',6-bis(trifluoromethyl)diphenylamine, m.p. 99-100.
A 4 g. portion of the above intermediate was then alkylated with 10 ml. of dimethyl sulfate in acetone in the ~737;~
presence of sodium carbonate according to the process of .
Example lB. The product was recrystallized from ethanol to collect 2 g. of N-methyl-2,4-dinitro-3',6-bis(trifluoro-methyl)diphenylamine, m.p. 108-109.
Theoretical Found C 44.02% 44.01%
H 2.22 2.35 N 10.27 10.23 Example 6 N,2-dimethyl-2',4'-dinitro-6'-trifluoromethyldiphenylamine Fifteen g. of o-toluidine was coupled with 18.9 g.
of 2-chloro-3,5-dinitrobenzotrifluoride in 150 ml. of e~hanol at reflux temperature overnight. A precipitate formed when the mixture was cooled. The precipitate was collected and identified as 6.8 g~ of 2-methyl-2',4' di-nitro-6'-trifluoromethyldiphenylamine.
The above intermediate was alkylated with 20 ml.
of dimethyl sulfate in 25 ml. of acetone in the presence of 12 g. of sodium carbonate. The mixture was held at reflux temperature for 24 hours, and was then diluted with 50 ml.
of water. The aqueous layer was decanted and the residue was taken up in methylene chloride, washed with water, filtered, and evaporated to dryness~ The residue left after evaporating was purified by chromatography on a silica gel column with 1:1 pentane:methylene chloride as the eluting solvent. Four g. of pure N,2-dimethyl-2',4'-dinitro-6'-trifluoromethyldiphenylamine, m.p. 106-108, was collected.
Theoretical Found C 50.71% 50.88%
H 3.40 3.46 N 11.83 12.08 The intermediates of formula I are used in the preparation of an important series o~ rodenticides by halogenating or nitrating the aniline ring appropriately.
Th~ reactions follow the usual practice of organic ch~mistry.
For example, halogenations are usually best per-formed with the elemental hal~gen in acetic acid, or in methylene chloride or the like halogenated solvent~ in-cluding chloroform or carbon tetrachloride. ~oom temper-ature halogenation is usually effective, but increased speed of reaction i5 obtainable by slight elevation of the re-action temperature in the range of 25-50. Chlorination is best done with the elemental gaseous halogen, but bromina-tion may be done with such agents as N-bromosuccinimide and dibromoisocyanuric acid, although reaction with elemental bromine is usually quite satisfac ory.
Iodination is best carried out with iodine mono-chloride as the reagent.
When a compound having no 4-substituent is to be made, it will often be necessary to block the 4-position before halogenating. It is most convenient to use a sul-fonic acid as the blocking group, because it is readily added and readily removed.
Insertion of nitro groups on the aniline ring is readily accomplished with concentrated nitric acid in acetic acid solution at room temperature. Other nitration re-X-4~6~ -13-actions may also be used, such as a mixture of concentrated nitric and sulfuric acids at elevated temperatures. In general, no solvent is used in nitration reactions other than the acids themselves.
X-~69 -14-
Claims (5)
1. A diphenylamine compound of the formula I
wherein R represents methyl, ethyl or propyl;
R1 and R2 independently represent hydrogen, methyl or tri-fluoromethyl;
R3 represents hydrogen or methyl;
provided that no more than one of R1, R2 and R3 represents a group other than hydrogen.
wherein R represents methyl, ethyl or propyl;
R1 and R2 independently represent hydrogen, methyl or tri-fluoromethyl;
R3 represents hydrogen or methyl;
provided that no more than one of R1, R2 and R3 represents a group other than hydrogen.
2. A compound of Claim 1 wherein R1 represents hydrogen or trifluoromethyl.
3. A compound of Claim 2 wherein R2 repre-sents hydrogen or trifluoromethyl.
4. A compound of claim 3 wherein R3 represents hydrogen.
5. Any of the following compounds of claim 4:
N-methyl-2,4-dinitro-6-trifluoromethyldiphenyl-amine 2,4-dinitro-N-propyl-6-trifluoromethyldiphenyl-amine N-methyl-2,4-dinitro-3',6-bis(trifluoromethyl)-diphenylamine N-methyl-2,4-dinitro-2',6-bis(trifluoromethyl)-diphenylamine.
N-methyl-2,4-dinitro-6-trifluoromethyldiphenyl-amine 2,4-dinitro-N-propyl-6-trifluoromethyldiphenyl-amine N-methyl-2,4-dinitro-3',6-bis(trifluoromethyl)-diphenylamine N-methyl-2,4-dinitro-2',6-bis(trifluoromethyl)-diphenylamine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70602376A | 1976-07-21 | 1976-07-21 | |
| US706,023 | 1976-07-21 |
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| Publication Number | Publication Date |
|---|---|
| CA1097372A true CA1097372A (en) | 1981-03-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA258,782A Expired CA1097372A (en) | 1976-07-21 | 1976-08-10 | N-alkyldiphenylamines |
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| Country | Link |
|---|---|
| JP (1) | JPS601298B2 (en) |
| AR (1) | AR226409A1 (en) |
| AT (1) | AT343624B (en) |
| BE (1) | BE846205A (en) |
| BG (1) | BG28845A3 (en) |
| BR (1) | BR7607892A (en) |
| CA (1) | CA1097372A (en) |
| CH (1) | CH605615A5 (en) |
| CS (1) | CS189032B2 (en) |
| DD (1) | DD127399A5 (en) |
| DE (1) | DE2640462C2 (en) |
| DK (1) | DK431276A (en) |
| EG (1) | EG12450A (en) |
| ES (1) | ES451903A1 (en) |
| FI (1) | FI762497A (en) |
| FR (1) | FR2359116A1 (en) |
| GB (1) | GB1548702A (en) |
| GR (1) | GR61183B (en) |
| HU (1) | HU174434B (en) |
| IE (1) | IE43614B1 (en) |
| IL (1) | IL50259A (en) |
| IN (1) | IN141827B (en) |
| IT (1) | IT1065258B (en) |
| MX (1) | MX4392E (en) |
| NL (1) | NL7610048A (en) |
| NO (1) | NO143023C (en) |
| PH (1) | PH12432A (en) |
| PL (1) | PL102578B1 (en) |
| PT (1) | PT65677B (en) |
| RO (1) | RO70078A (en) |
| SE (1) | SE435276B (en) |
| SU (1) | SU628811A3 (en) |
| YU (1) | YU214876A (en) |
| ZA (1) | ZA764842B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4316988A (en) * | 1976-07-21 | 1982-02-23 | Eli Lilly And Company | N-Alkyldiphenylamines |
| US4215145A (en) | 1978-12-05 | 1980-07-29 | E. I. Du Pont De Nemours And Company | Miticidal, fungicidal, and ovicidal sulfenamides |
| US4323580A (en) | 1980-01-24 | 1982-04-06 | E. I. Du Pont De Nemours And Company | Miticidal, fungicidal and ovicidal diphenylsulfenamides |
| US4298613A (en) | 1980-05-05 | 1981-11-03 | E. I. Du Pont De Nemours And Company | Agricultural heterocyclic sulfenamides |
| US4341772A (en) * | 1980-05-05 | 1982-07-27 | E. I. Du Pont De Nemours And Company | Agricultural phosphorus-containing sulfenamides |
| IL64149A0 (en) * | 1981-03-19 | 1982-01-31 | Lilly Co Eli | N-alkylated diphenylamine derivatives,method of preparing them and an insecticidal,arachnicidal and ectoparasiticidal composition containing them |
| US4407820A (en) | 1981-03-19 | 1983-10-04 | Eli Lilly And Company | Diphenylamine compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2212825A (en) * | 1937-12-31 | 1940-08-27 | Du Pont | Nitro-trifluoromethyl-aryl amines and process for making them |
-
1976
- 1976-07-25 PL PL1976192659A patent/PL102578B1/en not_active IP Right Cessation
- 1976-08-10 CA CA258,782A patent/CA1097372A/en not_active Expired
- 1976-08-10 IE IE1766/76A patent/IE43614B1/en not_active IP Right Cessation
- 1976-08-11 ZA ZA00764842A patent/ZA764842B/en unknown
- 1976-08-11 GR GR51456A patent/GR61183B/en unknown
- 1976-08-12 IL IL50259A patent/IL50259A/en unknown
- 1976-08-12 IN IN1466/CAL/76A patent/IN141827B/en unknown
- 1976-08-17 GB GB34127/76A patent/GB1548702A/en not_active Expired
- 1976-08-20 PH PH18815A patent/PH12432A/en unknown
- 1976-08-25 IT IT26532/76A patent/IT1065258B/en active
- 1976-08-30 SE SE7609586A patent/SE435276B/en unknown
- 1976-08-30 MX MX764867U patent/MX4392E/en unknown
- 1976-08-31 FI FI762497A patent/FI762497A/fi not_active Application Discontinuation
- 1976-08-31 AR AR264525A patent/AR226409A1/en active
- 1976-09-01 YU YU02148/76A patent/YU214876A/en unknown
- 1976-09-07 AT AT664176A patent/AT343624B/en not_active IP Right Cessation
- 1976-09-08 DE DE2640462A patent/DE2640462C2/en not_active Expired
- 1976-09-09 CH CH1148076A patent/CH605615A5/xx not_active IP Right Cessation
- 1976-09-10 HU HU76EI696A patent/HU174434B/en unknown
- 1976-09-10 DD DD194748A patent/DD127399A5/xx unknown
- 1976-09-10 NL NL7610048A patent/NL7610048A/en not_active Application Discontinuation
- 1976-09-13 SU SU762395606A patent/SU628811A3/en active
- 1976-09-15 FR FR7627685A patent/FR2359116A1/en active Granted
- 1976-09-15 BE BE1007626A patent/BE846205A/en not_active IP Right Cessation
- 1976-09-16 CS CS766025A patent/CS189032B2/en unknown
- 1976-09-17 NO NO763192A patent/NO143023C/en unknown
- 1976-09-17 RO RO7687564A patent/RO70078A/en unknown
- 1976-09-24 DK DK431276A patent/DK431276A/en not_active Application Discontinuation
- 1976-09-27 ES ES451903A patent/ES451903A1/en not_active Expired
- 1976-10-04 PT PT65677A patent/PT65677B/en unknown
- 1976-10-13 EG EG631/76A patent/EG12450A/en active
- 1976-10-28 BG BG7634548A patent/BG28845A3/en unknown
- 1976-11-18 JP JP51139413A patent/JPS601298B2/en not_active Expired
- 1976-11-25 BR BR7607892A patent/BR7607892A/en unknown
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