WO1989010347A1 - Procede de production d'aminophenols et de leurs derives d'amide - Google Patents

Procede de production d'aminophenols et de leurs derives d'amide Download PDF

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Publication number
WO1989010347A1
WO1989010347A1 PCT/US1989/001595 US8901595W WO8910347A1 WO 1989010347 A1 WO1989010347 A1 WO 1989010347A1 US 8901595 W US8901595 W US 8901595W WO 8910347 A1 WO8910347 A1 WO 8910347A1
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WO
WIPO (PCT)
Prior art keywords
aminophenol
dialkyl
hexane
making
acylation
Prior art date
Application number
PCT/US1989/001595
Other languages
English (en)
Inventor
Neil Dunski
Henry J. Buehler
Original Assignee
Mallinckrodt, Inc.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Mallinckrodt, Inc. filed Critical Mallinckrodt, Inc.
Publication of WO1989010347A1 publication Critical patent/WO1989010347A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/74—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C215/76—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/24—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/25—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton

Definitions

  • This invention relates to the production of aminophenols and their N-acylated amide derivatives which are ordinarily used as polymeric stabilizers or antioxidants. More particularly, this invention relates to the production of these antioxidant compounds under mild catalytic hydrogenation reaction conditions, where severe losses in product yield have been experienced in the past.
  • N-acylated aminophenols are known to be useful as antioxidants in many different compositions, such as rubbers, resins and other materials which are subject to the deleterious effects of oxidative aging.
  • These compounds are generally prepared by nitrosation or nitration of a phenol, followed by reduction of the nitroso-group or nitro-group to the corresponding amine, and subsequently N-acylating the amine.
  • Dale discloses that by carrying out the hydrogenation reaction in tetrahydrofuran (eliminating the hexane), increasing the pressure to 1,000 psi, and raising the temperature to 85°C, he could achieve a 100% yield, and that at 80°C over 15 hours, under pressure of at least 200 psi, he obtained 100% yield.
  • the reduction of 2,6-dialkyl-4-nitrosophenol to its corresponding aminophenol and the subsequent acylation are carried out in situ. Both reactions are conducted in a single aprotic organic reaction medium.
  • the aprotic organic solvents which form the in situ reaction medium of the present invention are aprotic organic liquids having at least the affinity for solubilizing small amounts of nitrosophenol as does hexane at room temperature or slightly above and which are inert to the acylation reaction.
  • Said solvents may be, for example, chlorinated hydrocarbons, such as chloroform and dichloromethane; aromatics, such as toluene or benzene; aliphatic hydrocarbons, such as hexane; and aprotic amides, such as N,N-dimethylformamide.
  • the in situ process is conducted in aprotic solvents, preferably toluene, N,N-dimethylformamide, hexane, dichloromethane, or mixtures thereof. It is critical in employing the process of this invention that the starting material should be a nitrosophenol rather than a nitrophenol. It is particularly preferred in the process of this invention to employ either N,N-dimethylformamide, hexane, or a mixture of hexane and dichloromethane because these solvents allow one to run these reactions at high concentrations of reactants and because these solvents are highly inert with regard to the reactions taking place.
  • aprotic solvents preferably toluene, N,N-dimethylformamide, hexane, dichloromethane, or mixtures thereof.
  • the preferred mixture of hexane and dichloromethane has a volume-to-volume ratio of 1.3 to 1.0 respectively.
  • High yields, relatively low material costs, and high solubility are experienced without the need for highly polar protic solvents such as methanol or ethanol normally used in these reactions, and little plugging of transfer lines during manufacture and filtration of the product is experienced with such solvents.
  • reaction medium it is preferred to catalytically hydrogenate 2,6-dialkyl-4-nitrosophenols in effective amounts of the above-described reaction medium.
  • the aprotic organic solvents forming the reaction medium serve to solubilize all the reaction product without resorting to high temperatures.
  • the amount of solvent utilized can be measured to maximize the amount of product produced per batch.
  • a particularly preferred 2,6-dialkyl-4-nitrosophenol has the formula
  • R 1 is tert-butyl and R 2 is tert-butyl, and is referred to as 2,6-di-tert-butyl-4-nitrosophenol.
  • the 2,6-dialkyl-4-nitrosophenols although readily available, may be prepared by well-known nitrosation processes.
  • the catalytic hydrogenation is conducted by contacting a mixture of the nitrosophenol and an aprotic organic solvent such as previously described with a metallic catalyst at a relatively low pressure in the presence of hydrogen gas.
  • the catalyst is preferably an insoluble particulate metallic material.
  • metal or metal oxides such as nickel, nickel oxides, chromium, cobalt, or noble metals such as platinum and palladium. But it is particularly preferred to employ noble metals such as platinum and palladium on an inert support such as carbon.
  • Hydrogenation may be carried out at temperatures from about 20 to about 50°C, preferably at room temperature.
  • the initial temperature is 23°C and the exothermicity is controlled so that the reaction temperature does not exceed 40°C for substantially complete conversion at greater than 90% in a reaction period of less than an hour.
  • the positive pressure for hydrogen ranges from about 50 to about 60 psi.
  • the hydrogenation under such pressures at the above-described preferred temperatures results in substantially complete hydrogenation within 30 minutes, although stirring of the mixture under the hydrogen atmosphere can be maintained for a total of one hour if desired.
  • N-acylating agent It is particularly preferred to employ acid chlorides such as stearoyl chloride, lauroyl chloride, acetyl chloride or acryloyl chloride.
  • acid chlorides such as stearoyl chloride, lauroyl chloride, acetyl chloride or acryloyl chloride.
  • acylation may be completed by the use of acetic anhydride or other materials such as hexanoic anhydride, lauric anhydride or stearic anhydride.
  • the N-acylating agent is added directly to the reaction medium in substantially stoichiometric amounts, although it may be desirable to employ a slight molar excess of from 1.0 to 10.0 percent.
  • a substituent such as triethylamine, sodium carbonate or pyridine may be used to tie up the hydrochloric acid produced during the acylation step.
  • Such substituents are added in molar equivalent to the acid chloride used. It is also preferred to continue to conduct the in situ reaction at this acylation stage under an oxygen-free environment with, for example, nitrogen. It has been found that the acylation yield is substantially enhanced by the exclusion of protic organic solvents. Although hydrogenation of nitrosophenol proceeds very rapidly when protic solvents such as ethanol or methanol are used, the acylation reaction is adversely impacted because the acylating agent reacts with any residual protic solvent producing undesirable by-products such as ethyl or methyl esters and low yields of the desired amide produce.
  • protic solvents such as ethanol or methanol
  • a 2-liter Parr bomb was charged with 23.50 g (0.1 mole) 2,6-di-tert-butyl-4-nitrosophenol, 1.0 g of 5% Pd on C catalyst and 600 ml toluene. After purging the assembled bomb with nitrogen, it was pressurized to 50 psi with hydrogen. The mixture was stirred vigorously and uptake of hydrogen was noted. The hydrogenation step producing 2 , 6-d i-tert-butyl-4-aminophenol was completed within 15 minutes. A temperature rise from 23°C to 25°C was. observed during the hydrogenation. The mixture was allowed to stir under hydrogen atmosphere for a total of 1 hour.
  • a 2-liter Parr bomb was charged with 11.75 g (0.05 mole) 2,6-di-tert-butyl-4-nitrosophenol, 0.5 g of 5% Pd/C catalyst and 600 ml toluene.
  • the material was hydrogenated to 2,6-di-tertbutyl-4-aminophenol.
  • Nitrogen-purged solution of 15.89 g (0.15 mole) sodium carbonate in 50 ml water was added to the bomb followed by 16.29 g (0.054 mole) nitrogen-purged stearoyl chloride. The mixture was stirred for 2 hours.
  • the solution was transferred under nitrogen pressure to a nitrogen-purged 2-liter round bottom flask.
  • the catalyst was removed on a glass-sintered funnel placed between the bomb and the round bottom flask.
  • Nitro-purged triethylamine, 10.12 g (0.1 mole) was added to the DMF solution followed by slow addition of 30.3 g (0.1 mole) nitrogen-purged stearoyl chloride.
  • the DMF solution was added to 2 liters of water containing a few ml of H 2 SO 4 .
  • the product precipitated out of solution and was collected by filtration. It was washed with water and hexane and dried overnight. A total of 42.3 g (87%) was obtained.
  • a 2-liter Parr bomb was charged with 210.5 g of 44.6% water wet (0.5 mole) 2,6-di-tert-butyl-4-nitrosophenol, 2.0 g of 5% Pd/C catalyst, 300 ml dichloromethane and 400 ml hexane.
  • the nitrogen-purged system was pressurized to 50 psi with hydrogen and the rate of hydrogen uptake noted. Hydrogenation was completed within one hour.
  • Triethylamine, 58.22 g (0.575 moled) was purged with nitrogen and under nitrogen pressure transferred into the Parr bomb at the end of the hydrogenation. Similarly was added 159.1 g (0.526 mole) of nitrogen-purged stearoyl chloride.
  • Acetic anhydride 56.2 g (0.55 mole) was nitrogen purged and under nitrogen pressure transferred into the Parr bomb at the end of the hydrogenation step. The mixture was stirred for one hour and then heated to 65°C prior to removing the content from the bomb and filtering off the catalyst. The filtrate was cooled down to 5°C and the product precipitated out.
  • a 2-liter Parr bomb was charged with 25.1 g (0.1 mole) of 4-nitro-2,6-di-tert-butylphenol, 0.5 g 5% Pd/C catalyst and 400 ml toluene.
  • the bomb was purged with nitrogen followed by a hydrogen purge. After pressuring the bomb to 62 psi with hydrogen, the contents were stirred for 2 hours at 40°C. A sample was then removed and analyzed. A very small amount was reduced to the desired amine.
  • a 2-liter Parr bomb was charged with 25.1 g (0.1 mole) of 4-nitro-2,6-di-tert-butylphenol, 0.65 g 5% Pd/C catalyst and 500 ml methanol.
  • the bomb was purged with nitrogen followed by a hydrogen purge. After pressuring the bomb with hydrogen to 60 psi the stirrer was turned on with the content at room temperature.
  • the bomb containing the amine product (described in Example 8) was vented to remove hydrogen and the system was purged with nitrogen. To the bomb was then added 10.6 g sodium carbonate in about 80 ml deaerated water. A deaerated solution of 32.75 g (7.5% excess) stearoyl chloride in 100 ml toluene was prepared and added slowly to the bomb. Stirring continued for 2 hours.
  • the product was isolated from the reaction mixture and crystallized from hexane yielding 230 g (47% yield). The remaining material was identified as methyl stearate which resulted from the reaction of stearoyl chloride with the solvent methanol.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

On produit des dialkylaminophénols N-acylés à des rendements supérieurs dans des conditions de réactions douces, à l'aide d'un nouveau procédé commençant avec l'hydrogénation catalytique de dialkylnitrosophénols dans un milieu de réaction organique aprotique. On peut ensuite procéder à l'acylation sans isoler l'aminophénol du milieu de réaction.
PCT/US1989/001595 1988-04-18 1989-04-14 Procede de production d'aminophenols et de leurs derives d'amide WO1989010347A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US18253388A 1988-04-18 1988-04-18
US182,533 1988-04-18

Publications (1)

Publication Number Publication Date
WO1989010347A1 true WO1989010347A1 (fr) 1989-11-02

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AU (1) AU3426989A (fr)
CA (1) CA1309419C (fr)
WO (1) WO1989010347A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991012229A1 (fr) * 1990-02-12 1991-08-22 National Research Council Of Canada Procede de preparation de derives acyles de composes acylables
EP0457730A2 (fr) * 1990-05-18 1991-11-21 Ciba-Geigy Ag Procédé pour la préparation des dérivés thio de l'alkylhydroxyanilino-triazine
EP0608896A1 (fr) * 1993-01-29 1994-08-03 Sumitomo Chemical Company, Limited Procédé de préparation d'amides aromatiques utilisables comme coupleur cyan en photographie en couleurs

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1978433A (en) * 1931-03-23 1934-10-30 Merck & Co Inc Process for preparing para-secalkylamino-phenols
FR1417451A (fr) * 1963-11-22 1965-11-12 Monsanto Chemicals Procédé de fabrication de composés aminés
FR1432356A (fr) * 1964-05-06 1966-03-18 Ici Ltd Dérivés du phénol
US4205151A (en) * 1975-04-04 1980-05-27 Dynapol Polymeric N-substituted maleimide antioxidants
FR2533559A1 (fr) * 1982-09-27 1984-03-30 Benzaria Jacques Procede pour la preparation de n-acetyl p-aminophenol

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1978433A (en) * 1931-03-23 1934-10-30 Merck & Co Inc Process for preparing para-secalkylamino-phenols
FR1417451A (fr) * 1963-11-22 1965-11-12 Monsanto Chemicals Procédé de fabrication de composés aminés
FR1432356A (fr) * 1964-05-06 1966-03-18 Ici Ltd Dérivés du phénol
US4205151A (en) * 1975-04-04 1980-05-27 Dynapol Polymeric N-substituted maleimide antioxidants
FR2533559A1 (fr) * 1982-09-27 1984-03-30 Benzaria Jacques Procede pour la preparation de n-acetyl p-aminophenol

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991012229A1 (fr) * 1990-02-12 1991-08-22 National Research Council Of Canada Procede de preparation de derives acyles de composes acylables
EP0457730A2 (fr) * 1990-05-18 1991-11-21 Ciba-Geigy Ag Procédé pour la préparation des dérivés thio de l'alkylhydroxyanilino-triazine
US5086173A (en) * 1990-05-18 1992-02-04 Ciba-Geigy Corporation Process for the preparation of alkylhydroxyanilinothiotriazine derivatives
EP0457730A3 (en) * 1990-05-18 1992-08-26 Ciba-Geigy Ag Process for preparation of thioderivatives of alkylhydroxyanilinotriazine
EP0608896A1 (fr) * 1993-01-29 1994-08-03 Sumitomo Chemical Company, Limited Procédé de préparation d'amides aromatiques utilisables comme coupleur cyan en photographie en couleurs

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CA1309419C (fr) 1992-10-27
AU3426989A (en) 1989-11-24

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