Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
  • C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
  • C07C209/30—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds
  • C07C209/32—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups
  • C07C209/36—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst

Definitions

• the present invention relates to a process for preparing 4-aminodiphenyl- amines intermediates.
• 4-Aminodiphenylamines are widely used as intermediates in the manufacture of alkylated derivatives having utility as antiozonants and antioxidants, as stabilizers for monomers and polymers, and in various specialty applications.
• 4-aminodiphenylamine (4- ADPA) with methylisobutyl ketone provides N-(1 ,3-dimethylbutyl)-N'-phenyl-p- phenylene-diamine, which is a useful antiozonant for the protection of various rubber products.
• 4-Aminodiphenylamine derivatives can be prepared in various ways.
• An attractive synthesis is the reaction of an optionally substituted aniline with an optionally substituted nitrobenzene in the presence of a base, as disclosed, for example, in U.S. 5,608,111 (to Stern et al.) and U.S. 5,739,403 (to Reinartz et al.).
• U.S. 5,608,111 describes a process for the preparation of an optionally substituted 4-ADPA wherein in a first step optionally substituted aniline and optionally substituted nitrobenzene are reacted (coupled) in the presence of a base.
• aniline and nitrobenzene are, reacted in the presence of tetramethylammonium hydroxide as the base, and water and aniline are azeotropically removed during the coupling reaction.
• EP publication 566 783 describes a method of manufacture of 4- nitrodiphenylamine by the reaction of nitrobenzene with aniline in the medium of a polar aprotic solvent in a strongly alkaline reaction system.
• a phase transfer catalyst such as tetrabutylammonium hydrogen sulfate is employed. This reference requires that the reaction be carried out in an oxygen-free atmosphere in order to prevent undesirable side reactions caused by oxidation.
• US Patent No. 5,453,541 teaches that an external desiccant, such as anhydrous sodium sulfate, may be used to absorb excess water in an anaerobic or aerobic process for producing one or more 4-ADPA intermediates in which substituted aniline derivatives and nitrobenzene are brought into reactive contact.
• an external desiccant such as anhydrous sodium sulfate
• the objective of the present invention is to provide a superior method for producing one or more 4-ADPA intermediates by reacting aniline and nitrobenzene in the presence of a strong base and a phase transfer catalyst, or in the presence of an organic base and an inorganic salt or a metal organic salt.
• the present invention is for a method of producing 4-aminodiphenylamine or substituted derivatives thereof comprising the steps of: (a) bringing an aniline or aniline derivative and nitrobenzene or nitrobenzene derivative into reactive contact; (b) obtaining a 4-aminodiphenylamine intermediate product by reacting the aniline or aniline derivative and nitrobenzene or nitrobenzene derivative in a confined zone at a suitable time, pressure and temperature, in the presence of a mixture comprising a strong base, an oxidant and a phase transfer catalyst selected from the group of compounds defined by: [(R 4 )e-Y-(RiR 2 R 3 N + )] c X- a b I
• the present invention is a method of producing 4-aminodiphenylamine or substituted derivatives thereof comprising the steps of:
• R-i, R 2 , R 3 are the same or different and selected from any straight chain or branched aikyl group containing from Ci to C 2 o
• Y is aikyl, aryl , aikyl aryl or benzyl and substituted derivatives thereof
• Z is a substituent selected from the group consisting of hydroxyl, halo, and other hetero atoms
• b and c are whole number integers of value 1 , 2 or 3 and d is a whole number integer of value 0 to 4
• the present invention is a method of producing 4- aminodiphenylamine or substituted derivatives thereof comprising the steps of: (a) bringing an aniline or aniline derivative and nitrobenzene or nitrobenzene derivative into reactive contact; and (b) obtaining a 4-aminodiphenylamine intermediate product by reacting the aniline or aniline derivative and nitrobenzene or nitrobenzene derivative in a confined zone at a suitable time, pressure and temperature, in the presence of a mixture comprising an inorganic salt or metal organic salt, or mixtures thereof, having a cation that would be a suitable cation of a strong inorganic base, an oxidant and one or more of an organic base selected from the group of compounds defined by:
• the present invention is directed to a method, as described above, for making intermediates of 4-ADPA that has superior yield and selectivity for those intermediates.
• Such intermediates comprise 4-nitroso- and/or 4- nitrodiphenylamines (p-NDPA and 4-NDPA, respectively) and salts thereof.
• the intermediates may then be hydrogenated to produce 4-aminodiphenylamine.
• Other effective phase transfer catalysts fitting formula I can be derived from examples in the literature, such as C. M. Starks and C. Liotta, Phase Transfer Catalysis, Principles and Techniques, Academic Press, 1978 and W. E. Keller, Fluka- Compendium, Vol. 1,2,3, Georg Thieme Verlag, New York, 1986, 1987, 1992.
• Phase transfer catalysts known or believed to be particularly effective in the method of the invention include tetramethylammonium chloride, tetramethylammonium fluoride, tetramethylammonium hydroxide, bis- tetramethylammonium carbonate, tetramethylammonium formate and tetramethylammonium acetate; tetrabutylammonium hydrogensulfate and tetrabutylammonium sulfate; methyltributylammonium chloride; and benzyltrimethylammonium hydroxide (Triton B), tricaprylmethylammonium chloride (Aliquat 336), tetrabutylammonium chloride, tetramethylammonium nitrate, cetyltrimethylammonium chloride and choline hydroxide .
• Triton B tricaprylmethylammonium chloride
• Phase transfer catalysts of the present invention have several advantages over crown ethers, such as 18-crown-6, which were described as effective with alkali metal hydroxides in references such as US Patent No. 5,117,063 and International publication WO 01/14312 discussed above.
• the most obvious disadvantages of crown ethers are very high initial cost and high toxicity.
• most crown ethers have poor solubility in water, so they cannot be recovered for recycle with an aqueous base stream.
• the boiling points of crown ethers are high enough that they cannot be recovered by distillation without an extra distillation step. Even for the class of crown ethers that have good solubility in water, solubility in organics is also good, so that there will be a high loss to the organic product stream.
• crown ethers are known chelating agents, so that there is a high probability of unacceptable loss of expensive hydrogenation catalyst metal, due to complexation with the crown ether.
• the molar ratio of phase transfer catalyst to nitrobenzene reactant is preferably from about 0.05:1 to about 1.2:1.
• the method of the present invention may also start with an organic base and an inorganic salt or a metal organic salt as in the above third embodiment.
• the organic base is defined by formula III in that embodiment.
• Organic bases known or believed to be particularly effective for the second and third embodiments include quaternary ammonium hydroxides selected from the group consisting of, but not limited to, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, methyltributylammonium hydroxide, benzyltrimethylammonium hydroxide (Triton B), tricaprylmethylammonium hydroxide, cetyltrimethylammonium hydroxide and choiine hydroxide, and equivalent quaternary ammonium alkoxides, acetates, carbonates, bicarbonates, cyanides, phenolics, phosphates, hydrogen phosphates, hypochlorites, borates, hydrogen borates, dihydrogen borates, sulfides, silicates,
• strong inorganic base as used with respect to the meaning of a cation of an inorganic salt or metal organic salt is intended to mean a base that is capable of abstracting a proton from the nitrogen of an aniline or aniline derivative, and may include any base having a pK b less that about 9.4, which is the pK b of aniline.
• Various aniline derivatives may have different pK b values, but a pK b of about 9.4 is employed as a general guide.
• the base will preferably have a pK b less than about 7.4.
• anion "X" of formula III is intended to mean an anion also having a pK b value as discussed above with respect to the strong inorganic base.
• aniline most effectively couples with nitrobenzene
• certain aniline derivatives comprising amides such as formanilide, phenylurea and carbanilide as well as the thiocarbanilide can be substituted to produce 4-ADPA intermediates.
• the reactants of the method of the invention are referred to as "aniline” and “nitrobenzene”, and when it is 4-ADPA that is being manufactured the reactants are in fact aniline and nitrobenzene, it is understood that the reactants may also comprise substituted aniline and substituted nitrobenzene.
• Typical examples of substituted anilines that may be used in accordance with the process of the present invention include but are not limited to 2-methoxyaniline, 4-methoxyaniline, 4-chloroaniline, p-toluidine, 4-nitroaniline, 3-bromoaniline, 3- bromo-4-aminotoluene, p-aminobenzoic acid, 2,4-diaminotoluene, 2,5- dichloroaniline, 1,4-phenylene diamine, 4,4'-methylene dianiline, 1 ,3,5- triaminobenzene, and mixtures thereof.
• Typical examples of substituted nitrobenzenes that may be used in accordance with the process of the present invention include but are not limited to o- and m-methylnitrobenzene, o- and m- ethylnitrobenzene, o- and m-methoxynitrobenzene, and mixtures thereof.
• the method of the invention includes the step wherein the 4-ADPA intermediates or substituted derivatives thereof from step (b) are subjected to a hydrogenation reaction involving the use of a hydrogenation catalyst. Details concerning choice of catalyst and other aspects of the hydrogenation reaction may be found in U.S. Patent No. 6,140,538, incorporated by reference herein.
• the present invention further relates to a process for preparing alkylated derivatives of 4-aminodiphenylamines, in particular for preparing aikyl derivatives of 4-ADPA itself, which are useful for the protection of rubber products, in which process an optionally substituted aniline and an optionally substituted nitrobenzene are coupled and subsequently reduced according to the invention process, after which the 4-aminodiphenylamine so obtained is reductively alkylated to an alkylated derivative of the 4-aminodiphenylamine according to methods known to the person skilled in this technical field.
• the 4-ADPA and a suitable ketone, or aldehyde are reacted in the presence of hydrogen and platinum-on-carbon as catalyst.
• Suitable ketones include methylisobutyl ketone, acetone, methylisoamyl ketone, and 2-octanone. See for example U.S. 4,463,191, and Banerjee et al, J. Chem. Soc. Chem. Comm. 18, 1275-1276 (1988).
• Suitable catalysts can be the same as, but not limited to, those described above for obtaining the 4-ADPA.
• the reduction is conducted in the presence of water, e.g. water is added to the reaction mixture.
• water e.g. water is added to the reaction mixture.
• suitable base used during the reaction of the aniline or substituted aniline derivative and the nitrobenzene or substituted nitrobenzene derivative
• the amount of water added is preferably at least the amount needed to extract the base from the organic phase.
• the addition of water is also preferred for reductive alkylation, if it is carried out in the presence of the suitable base, which is water-soluble.
• the molar ratio of aniline to nitrobenzene in the process according to the present invention is not particularly important, as the process will be effective with an excess of either.
• Strong bases particularly effective in the first embodiment of the process of the present invention include potassium hydroxide, sodium hydroxide, cesium hydroxide, rubidium hydroxide and potassium-t-butoxide. It is preferred that mole ratio of strong base to nitrobenzene is greater than about 1 : 1. A particularly preferred mole ratio of strong base to nitrobenzene is about 2:1 to about 6:1. Inorganic salts and metal organic salts that may be used in conjunction with the organic base in the third embodiment of the process of the invention have a cation that would be a suitable cation of a strong inorganic base.
• inorganic salts and metal organic salts are selected from the group consisting of, but not limited to, the fluoride, chloride, bromide, sulfate, hydrogen sulfate, nitrate, phosphate, dihydrogen phosphate, formate, acetate, oxalate, malonate, citrate, tartrate, maleate, chlorate, perchlorate, chromate, rhenate and carbonate salts of cesium, rubidium, potassium and sodium.
• the inorganic salt or metal organic salt may be used in molar ratio to nitrobenzene from about 0.05:1 to about 6.5:1.
• Inorganic salts and metal organic salts known or believed to be particularly effective in the third embodiment method of the present invention are those that afford acceptable solubility for the inorganic salt or metal organic salt -organic base combination in the reaction medium, including the fluoride, chloride, bromide, sulfate, hydrogen sulfate, nitrate, phosphate, formate, acetate and carbonate salts of cesium, rubidium, potassium and sodium and mixtures thereof. It is preferred that mole ratio of organic base used with an inorganic salt or metal organic salt to nitrobenzene is greater than or equal to about 1 :1. It is also preferred that mole ratio of inorganic salt or metal organic salt to organic - base is greater than or equal to about 1:1. A particularly preferred mole ratio of organic base to nitrobenzene is about 1.1:1 to about 6:1.
• the combination might also provide better results than could be obtained with one salt.
• inorganic salts and metal organic salts with the organic base is also believed to reduce undesirable base decomposition.
• an organic base with an inorganic salt or a metal organic salt will give some in situ formation of the equivalent inorganic base and a phase transfer catalyst, wherein the anion in formula I for the so formed phase transfer catalyst is the anion from the salt.
• tetramethylammonium hydroxide plus potassium bromide will give some KOH plus tetramethylammonium bromide.
• the invention would include the direct use of an inorganic base with any phase transfer catalyst that can be formed in situ, such as tetramethylammonium bromide, in lieu of tetramethylammonium hydroxide and a bromide salt as separate ingredients.
• phase transfer catalyst such as tetramethylammonium bromide, in lieu of tetramethylammonium hydroxide and a bromide salt as separate ingredients.
• a particularly preferred combination of strong base and phase transfer catalyst is potassium hydroxide and tetraalkylammonium halide.
• a preferred halide is chloride.
• a particularly preferred combination of organic base and inorganic salt is tetraalkylammonium hydroxide and a salt in which the anion is a halide, such as potassium halide.
• a preferred halide anion is chloride.
• the reactive contact of the process of the first embodiment of the invention is carried out in the presence of an oxidant.
• the oxidant may be free oxygen, or comprise an oxidizing agent such as a peroxide, particularly hydrogen peroxide. Nitrobenzene may also function as an oxidizing agent.
• the oxidant may advantageously need to be present only for part of the time during which the aniline and nitrobenzene react.
• Such partial oxidative conditions are particularly effective for improving selectivity.
• an inorganic salt with a fluoride anion is employed in the reaction mixture of the third embodiment under partial oxidative conditions. It is believed that better results, conversion and selectivity, would also be obtained under partial oxidative conditions when the salt anion is sulfate, carbonate, or nitrate and other anions that give relatively low selectivity.
• TMAH is used as a strong base that can also function as a phase transfer catalyst for the second embodiment.
• partial oxidative conditions would also be effective for combinations of inorganic base and phase transfer catalyst that give low selectivity.
• the oxidant used in the second and third embodiments of the invention may be the same as in the first embodiment.
• the reactive contact may be carried out at a temperature of from about
• reaction time is typically less than about 3.5 hours. It is advantageous to agitate the reaction mixture during the entire reaction.
• the reactions of step (b) of the first, second and third embodiments of the present method may be carried out in the presence of not greater than about 10:1 moles water to moles nitrobenzene.
• the amount of water does not include the water that hydrates with the reactants and/or with compounds formed in the process.
• the reaction may be carried out with a continuous distillation of aniline-water azeotrope.
• the first embodiment of the invention may be carried out with the phase transfer catalyst being tetramethylammonium bromide and the strong base comprising one or more inorganic bases.
• the aqueous phase may be reused to form a new reaction mixture.
• Fresh base and phase transfer catalyst or organic base and inorganic salt or metal organic salt are added to replace losses by decomposition, by-product formation and solubility in the separated organic phase.
• Excess Aniline recovered by distillation from the reaction product mixture may be combined with make-up fresh aniline for recycle to form a new reaction mixture.
• Recovery of excess nitrobenzene is preferably carried out prior to hydrogenation of the 4-ADPA intermediate by a separation step and the recovered nitrobenzene may be combined with make-up fresh nitrobenzene for use in the process, or hydrogenated to aniline.
• the method of the present invention for the preparation of 4- aminodiphenylamines intermediates may be conducted as a batch process or may be performed continuously using means and equipment well known to the skilled person.
• the reactive contact in step (a) in the first, second and third embodiments of the method of the invention may occur in a suitable solvent system.
• a suitable solvent system comprises a polar aprotic solvent.
• the polar aprotic solvent may be selected form the group consisting of, but not limited to, dimethyl sulfoxide, benzyl ether, 1-Methyl-2-pyrrolidinone and N,N-dimethylformamide.
• the invention in its second embodiment, is a method where the strong base also functions as a phase transfer catalyst and the reaction may be in the absence of an alkali metal hydroxide.
• the strong base/phase transfer catalyst is defined by formula II above.
• a flow of air was supplied to the reactor headspace during all or part of charging reactants, heat-up to reaction temperature, nitrobenzene feed and hold, resulting in free oxygen being present during the reaction, except where indicated.
• Water was removed from the reaction mixture by azeotropic distillation with aniline.
• the reaction can also be effective without the azeotropic removal of water with aniline.
• Eluent A is 75% v/v water, 15% v/v acetonitrile and 10% v/v methanol.
• Eluent B is 60% v/v acetonitrile and 40% v/v methanol. Detection is UV at 254 nm.
• Conversion for examples 1-10 is calculated by sum addition of known components plus any unknown peaks (assigned an arbitrary mole weight value of 216, aniline + nitrobenzene) as analyzed. In some instances, sum conversion is greater than 100% due to the formation of derivatives from aniline only. Conversion for examples 11-16 is calculated based on the amount of, unreacted nitrobenzene remaining in the final coupling reaction mass. Conversion is assumed to be 100% if no nitrobenzene is detected.
• An Recr refers to compounds from which aniline may be easily recovered and is a sum total of frans-azobenzene and azoxybenzene;
• Olers are aniline and nitrobenzene coupling by-products e.g. phenazine, N- oxy-phenazine, 2-NDPA, 4-phenazo-diphenylamine and any unknowns.
• Example 1 illustrates that 4-ADPA intermediates may be formed from aniline and nitrobenzene in the presence of an inorganic base (potassium hydroxide) and phase transfer catalyst (tetramethylammonium chloride, TMACI) in a solvent-free system under relatively mild conditions. Yield of desired products is dependent on the amount of phase transfer catalyst added.
• an inorganic base potassium hydroxide
• phase transfer catalyst tetramethylammonium chloride, TMACI
• Example 2 demonstrates that any of several phase transfer catalysts may 15 be used with KOH to produce p-NDPA and 4-NDPA from aniline and nitrobenzene. Results are arranged in order of descending yield.
• phase transfer catalyst Charge to 50-mL round bottom flask equipped with magnetic stirrer: aniline (99%, 22.58 grams, 240 mmoles), nitrobenzene (99%, 4.97 grams, 40 20 mmoles), potassium hydroxide (86% ground powder, 7.83 grams, 120 mmoles) and the indicated phase transfer catalyst given in Table 3 below where the amount of phase transfer catalyst is equal to the limiting reagent charge. (NOTE: Some experiments run on 20 or 30 mmole scale as denoted.) Reaction was allowed to proceed for 1 hour at 60°C in a stoppered flask. Contents were then sampled and analyzed by HPLC.
• Tetramethylammonium chloride, fluoride, hydroxide, carbonate, formate and acetate; tetrabutylammonium hydrogensulfate and sulfate; methyltributylammonium chloride; and benzyltrimethylammonium hydroxide (Triton B) are most effective as phase transfer catalysts in combination with an inorganic base.
• Others such as tricaprylmethylammonium chloride (Aliquat 336), tetrabutylammonium chloride, tetramethylammonium nitrate, and choline hydroxide are moderately efficient. Bromide and iodide salts and the zwitterion betaine are not as suitable. Periodic trends are observed for the tetramethylammonium salts as yield, conversion and selectivity are all decreased when going down in the series from fluoride to iodide.
• Tetrabutylammonium sulfate 75% aq., 15.49 gms ⁇ 99.2% 56.1 21.2 20.1 1.8
• Tetramethylammonium carbonate 60% aq., 97.6% 46.6 24.6 23.7 2.8
• Tetramethylammonium acetate 95%, 5.61 gms 104.3% 25.9 43.1 35.0 0.4
• Tetramethylammonium chloride 97%, 4.52 gms 98.8% 24.3 37.1 30.8 6.6
• Methyltributylammonium chloride 75% aq., 12.58 gms 81.7% 23.5 30.6 22.2 5.4
• Tricaprylmethylammonium chloride 99+%, 67.0% 19.1 21.3 19.6 7.0
• Tetramethylammonium nitrate 96%, 5.67 gms 61.3% 12.0 27.4 19.6 2.4
• Tetramethylammonium bromide 98%, 6.29 gms 36.5% 11.3 12.2 6.7 6.3
• Tetrabutylammonium bromide 99%, 13.03 gms 34.1% 8.3 14.2 5.8 5.7
• Tetramethylammonium iodide 99%, 8.12 gms 27.8% 2.4 8.0 5.8 11.6
• Tetrabutylphosphonium bromide 98%, 13.58 gms 25.6% 1.6 5.1 9.4 10.0
• Example 3 shows that nitrobenzene may be coupled with a variety of aniline derivatives to produce 4-ADPA intermediates.
• a stoichiometric amount of substrate as listed in Table 4 below; nitrobenzene (99%, 3.08 grams, 24.8 mmoles), potassium hydroxide (86% ground powder, 9.77 grams, 150 mmoles), tetramethylammonium chloride (97%, 2.74 grams, 24.3 mmoles), and water (2.84 grams) were charged to a 50-mL round bottom flask equipped with a magnetic stirrer. The reaction was allowed to proceed for 2 hours at 80°C in an open flask. Contents were then sampled and analyzed by HPLC.
• Phenylurea 97%, 3.40 grams, 24.2 mmoles 96.2% 19.2 38.8 13.5 24.8
• Example 4 illustrates the reaction of aniline and nitrobenzene using various bases in combination with tetramethylammonium chloride to produce 4-
• Potassium hydroxide is the preferred base but sodium hydroxide, cesium hydroxide, potassium f-butoxide and tetramethylammonium hydroxide are also suitable bases any of which may used in combination with tetramethylammonium chloride to obtain acceptable rates of conversion.
• Example 5 demonstrates the effect of increasing potassium hydroxide charge on aniline-nitrobenzene coupling products under otherwise constant reaction conditions with tetramethylammonium chloride as a phase transfer catalyst.
• Aniline (99%, 32.60 grams, 346.5 mmoles), nitrobenzene (99%, 6.16 grams, 49.5 mmoles), potassium hydroxide in the amount given in Table 7 below (86% ground powder, 16.31 grams, 250 mmoles) and tetramethylammonium chloride (97%, 5.48 grams, 48.5 mmoles) were charge to a 100-mL round bottom flask equipped with a Teflon paddle stirrer. The reaction was allowed to proceed for 1 hour with no application of external heat (some exotherm generated by dissolution of KOH in reaction water) in a stoppered flask. Contents were then sampled and analyzed by HPLC.
• Example 6 indicates the effect that the introduction of an oxidant has on the conversion of aniline and nitrobenzene to p-NDPA, 4-NDPA and by-products when utilizing a potassium hydroxide / tetramethylammonium chloride base-PTC system.
• a closed system is a stoppered flask.
• An open system is left unstoppered and open to the atmosphere.
• a three-necked flask is substituted for a single-necked flask, the system equipped with both a gas inlet and outlet line, and the appropriate gas swept across the reaction mass at a low flow rate.
• Example 7 shows how the ratio of 4-ADPA intermediates can be controlled by adjusting the amount of aniline charged into the reaction.
• Example 8 illustrates that the reaction between aniline and nitrobenzene using potassium hydroxide as a base in conjunction with tetramethylammonium chloride can be conducted over a wide range of temperatures.
• Reaction Temperature 20°C 9.3% 0.1 8.3 0.0 1.0 Reaction Temperature, 35°C 21.6% 0.5 19.5 0.2 1.4 Reaction Temperature, 50°C 25.2% 0.8 22.3 0.1 1.9 Reaction Temperature, 65°C 26.0% 0.6 22.8 0.4 2.2 Reaction Temperature, 80°C 34.4% 1.7 27.7 2.9 2.1 Reaction Temperature, 95°C 39.3% 2.3 27.8 7.5 1.7 Reaction Temperature, 110°C 53.8% 3.5 33.4 12.8 4.0 Reaction Temperature, 125°C 72.7% 9.1 34.0 17.3 12.4
• Reaction Temperature 20°C 8.3 89.0 0.01 Reaction Temperature, 35°C 20.0 92.3 0.03 Reaction Temperature, 50°C 23.1 91.8 0.04 Reaction Temperature, 65°C 23.4 90.0 0.03 Reaction Temperature, 80°C 29.4 85.6 0.06 Reaction Temperature, 95°C 30.1 76.7 0.08 Reaction Temperature, 110°C 37.0 68.7 0.11 Reaction Temperature, 125°C 43.1 59.2 0.27
• Example 9 emphasizes the effect of water in the reaction of aniline and nitrobenzene with a KOH-TMACI base/phase transfer system to form 4-ADPA intermediates.
• Example 2 The effect of too much water may also be noted from Example 2 and Table 3 where the effectiveness of a 60% aqueous solution of tetramethylammonium carbonate as a phase transfer catalyst is shown. Previous unreported data obtained from a dilute 25% solution indicated practically no conversion.
• EXAMPLE 10 The effect of too much water may also be noted from Example 2 and Table 3 where the effectiveness of a 60% aqueous solution of tetramethylammonium carbonate as a phase transfer catalyst is shown. Previous unreported data obtained from a dilute 25% solution indicated practically no conversion.
• Example 10 shows that the reaction may be carried out in any of several solvents.
• Example 11 demonstrates the reaction of aniline and nitrobenzene in combination with an aqueous solution of potassium hydroxide and tetramethyalammonium chloride by continuous distillation of the aniline-water azeotrope.
• This example demonstrates the reaction of aniline and nitrobenzene in the presence of an oxidant in combination with an aqueous solution of tetramethylammonium hydroxide and various inorganic salts by continuous distillation of the aniline-water azeotrope.
• the TMAH/salt combination represents an ionic mixture of a potential base recycle stream from a process comprising an inorganic base and phase transfer catalyst after reduction of the coupling reaction mass to 4-ADPA.
• the system pressure was regulated by adjusting the air bleed valve throughout the duration of the reaction cycle to maintain the desired temperature of 80°C and to complete the NB charge in approximately 75 minutes at a final pressure of 72 mm Hg.
• the mixture was held for 30 minutes at 70 mm Hg to insure completeness of reaction and then quenched with 25 mL water.
• Air was bled into the reactor headspace during the entire cycle of charging reactants, heating to reaction temperature, feeding nitrobenzene and holding for reaction completion.
• potassium carbonate and sodium sulfate have two equivalents of inorganic cation, so that the molar ratio is 0.575.
• Betaine i.e. (acetyl)trimethylammomnium hydroxide inner salt
• Betaine is a salt formed by the acetate group with the positively charged tetraalkylammonium group. So despite the name, the compound does not actually have hydroxide associated with the tetraalkylammonium group. However, when a strong base is added, betaine is converted to a compound that contains both an acetate salt group and a tetraalkylammonium hydroxide group.
• betaine is converted to a compound with a tetramethylammonium-acetate group and an (acetyl)trimethylammomnium hydroxide group.
• KOH the compound has a potassium -acetate group with the (acetyl)trimethylammomnium hydroxide group.
• the compound represents a metal organic salt and a organic base in one molecule.
• Betaine is known in the literature to be a phase transfer compound or PTC (Starks and Liotta, ibid), as it carries the inorganic or organic base into the organic phase. The results in Table 20 show that betaine has only a modest effect on selectivity or conversion with TMAH.
• Reaction conditions were comparable to those for Example 12, except as indicated. The results are shown in Table 21.
• Reaction 1 had comparable conditions to those for Example 12 throughout.
• Reaction 2 the air bleed was used only during nitrobenzene feed and was stopped when 75% of the feed was completed.
• Reaction 3 the nitrobenzene feed time was shortened to 45 minutes and the hold time was increased to 60 minutes, while the air bleed was used only during the nitrobenzene feed time. It is expected that higher selectivity will also be attained for sulfate, carbonate and nitrate by use of partial oxidative conditions.
• Table 21
• This example shows that use of an oxidant with a strong base, which also functions as a phase transfer catalyst, can increase selectivity.
• the reactions were done with azeotropic removal of water and aniline.
• Nitrobenzene was charged over about 80 minutes, after which the batch was held for 40 minutes at 70 mm Hg to insure completeness of reaction and then quenched with 25 mL water.
• Hydrogen peroxide was charged as 20.40 grams (0.03 moles) of a 5 wt.% aqueous solution concurrently with nitrobenzene. Since water can also affect selectivity, by protecting TMAH from degradation and shifting reaction equilibria, a control was run with 20.40 grams of water that was also fed concurrently with nitrobenzene. Runs 4 - 7 had slightly different conditions. The main difference was starting with 25 wt.% TMAH with removal of water and some aniline in the reactor prior to the nitrobenzene feed.
• the results in Table 22 show that hydrogen peroxide gives a larger selectivity improvement than water alone, showing that use of an oxidant can be beneficial.
• the results also show that addition of air as oxidant over the entire reactor cycle has a deleterious effect on selectivity. However, a selectivity improvement is obtained when the air addition is limited to part of the reaction cycle, showing that partial oxidative conditions can be beneficial.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
• Mobile Radio Communication Systems (AREA)

Priority Applications (12)

Applications Claiming Priority (4)

Publications (1)

Family

ID=26841060

Family Applications (1)

Country Status (15)

Cited By (9)

Families Citing this family (11)

Citations (4)

Family Cites Families (6)

• 2002
  • 2002-07-09 IL IL15999402A patent/IL159994A0/xx unknown
  • 2002-07-09 RU RU2004105163/04A patent/RU2280640C2/ru not_active IP Right Cessation
  • 2002-07-09 JP JP2003515487A patent/JP4603260B2/ja not_active Expired - Lifetime
  • 2002-07-09 HU HU0501066A patent/HUP0501066A2/hu unknown
  • 2002-07-09 EP EP02742396A patent/EP1414782A1/en not_active Withdrawn
  • 2002-07-09 PL PL374267A patent/PL206080B1/pl unknown
  • 2002-07-09 CN CNB028164474A patent/CN100546972C/zh not_active Expired - Lifetime
  • 2002-07-09 WO PCT/US2002/021508 patent/WO2003010126A1/en active Application Filing
  • 2002-07-09 BR BRPI0211391-0A patent/BR0211391B1/pt active IP Right Grant
  • 2002-07-09 RS YU3904A patent/RS3904A/sr unknown
  • 2002-07-09 MX MXPA04000665A patent/MXPA04000665A/es active IP Right Grant
  • 2002-07-09 AU AU2002315530A patent/AU2002315530B2/en not_active Ceased
  • 2002-07-09 CA CA002454603A patent/CA2454603A1/en not_active Abandoned
  • 2002-07-22 TW TW091116246A patent/TWI265919B/zh not_active IP Right Cessation
• 2004
  • 2004-01-22 NO NO20040292A patent/NO20040292L/no not_active Application Discontinuation

Patent Citations (6)

Non-Patent Citations (4)

Also Published As

Similar Documents

Legal Events