WO2002060882A2 - Procede de preparation d'amino-diaryl triazines substitues - Google Patents

Procede de preparation d'amino-diaryl triazines substitues Download PDF

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Publication number
WO2002060882A2
WO2002060882A2 PCT/EP2002/000626 EP0200626W WO02060882A2 WO 2002060882 A2 WO2002060882 A2 WO 2002060882A2 EP 0200626 W EP0200626 W EP 0200626W WO 02060882 A2 WO02060882 A2 WO 02060882A2
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Prior art keywords
formula
compound
process according
alkyl
friedel
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PCT/EP2002/000626
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English (en)
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WO2002060882A3 (fr
Inventor
Christof Wehrli
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Roche Vitamins Ag
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Publication date
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Priority to AU2002247649A priority Critical patent/AU2002247649A1/en
Publication of WO2002060882A2 publication Critical patent/WO2002060882A2/fr
Publication of WO2002060882A3 publication Critical patent/WO2002060882A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • C07D251/40—Nitrogen atoms
    • C07D251/42—One nitrogen atom
    • C07D251/44—One nitrogen atom with halogen atoms attached to the two other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
    • C07D251/22—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms

Definitions

  • R and R 1 independently are alkyl, hydroxyalkyl, alkenyl, alkynyl, or alkyl ether groups substituted by one or more hydroxy and/or alkoxy groups, and Ar represents one of the residues
  • R 2 is hydroxy, alkyl, alkenyl, alkynyl, or an alkyl, alkenyl, alkynyl ether residue, or polyalkyl ether residue optionally substituted by one or more hydroxy and/or alkoxy groups and R 3 is hydrogen or signifies a residue R 2 and in which the hydroxy group is present in the ⁇ -position to the bonding to the triazine nucleus, with the number of C and O atoms present in R and R 1 being a total of 8 to 42, especially 8 to 18, and the number of O atoms corresponding to at most half of the C atoms, are useful as UV-A filters and are disclosed in EP 780,382.
  • these compounds can be prepared by a process which comprises reacting cyanuric chloride with an amine NH(R,R') in the presence of an equimolar amount of aqueous sodium hydroxide solution and subsequently submitting the amino- substituted dichloro triazine reaction product of the formula II
  • the reaction of the cyanuric chloride with the substituted amine NH(R,R 1 ) can be improved by carrying out the reaction in an anhydrous aromatic hydrocarbon, such as anhydrous benzene, toluene or xylene, preferably anhydrous toluene, first at low temperature to form a mixture of a compound of formula II and the amine hydrochloride, NH(R,R 1 ) • HC1, and unreacted cyanuric chloride, and subsequently heating said mixture to convert the remaining cyanuric chloride and amine hydrochloride to the desired dichloro triazine of formula II. In this manner, the formation of sodium chloride that has to be disposed of as waste is avoided.
  • anhydrous aromatic hydrocarbon such as anhydrous benzene, toluene or xylene, preferably anhydrous toluene
  • the Friedel-Crafts reaction can be carried out by using methanesulfonic acid as the catalyst which can be recovered thus avoiding the formation of waste which is produced in the work-up procedure of the conventional Friedel-Crafts reaction as disclosed in EP 780,382 where aluminum trichloride is used as a catalyst.
  • the product of the Friedel-Crafts reaction i.e. the compound of formula I can be isolated from the Friedel-Crafts reaction mixture as an adduct with solvents that form an adduct with the compounds of formula I such as lower alkyl nitriles or lower alkanoic acid lower alkyl esters. From the adduct, the compound of formula I can be obtained in high purity by heating and/or applying reduced pressure.
  • the present invention relates to a process for the preparation of compounds of the general formula II as defined above, which process comprises reacting cyanuric chloride with a substituted amine NH(R,R 1 ) in substantially equimolar amounts in an anhydrous aromatic hydrocarbon first at low temperature to form a mixture of a compound of formula II and the amine hydrochloride, NH(R,R 1 ) • HC1, and unreacted cyanuric chloride, and subsequently heating said mixture to convert the remaining cyanuric chloride and amine hydrochloride to the desired dichloro triazine of formula II.
  • the invention in another aspect relates to a process for the preparation of compounds of the general formula I as defined above, which process comprises submitting a compound of the general formula II as defined above to a Friedel-Crafts reaction with an appropriate aryl hydrocarbon ArH to obtain a reaction mixture containing a compound of the formula I, and working up the reaction mixture by adding water and an organic solvent that is substantially water-immiscible, separating, drying and concentrating the solvent phase, isolating the compound of formula I as an adduct with an appropriate solvent, and decomposing subsequently the adduct to obtain the compound of formula I in pure form.
  • the invention relates to the novel adducts of the compounds of formula I, particularly the ethyl acetate and acetonitrile adducts.
  • substantially water-immiscible solvents for use in the work-up of the Friedel-Crafts reaction mixture are lower alkanoic acid lower alkyl esters having a boiling point of less than about 120 °C such as methyl acetate, ethyl acetate, propyl acetate, methyl formiate and ethyl formiate. Particularly preferred is ethylacetate.
  • Appropriate solvents for forming an adduct with the compounds of formula I are lower alkanoic acid lower alkyl esters having a boiling point of less than about 120 °C, and lower alkyl nitriles. Particularly preferred solvents for adduct formation are ethylacetate and acetonitrile.
  • the invention relates to the preparation of compounds of formula I and II, respectively, wherein Ar is 2,4-dihydroxyphenyl and R and R 1 are 2-ethylhexyl.
  • the reaction of cyanuric chloride with the amine NH RjR 1 ) is first carried out at low temperature, e.g., at about -20 °C to about 70 °C, preferably at -10 °C to about 20 °C, At low temperature, a mixture of about equimolar amounts of dichloro triazine of formula II, amine hydrohalogenide and unreacted cyanuric chloride is formed as can be readily determined by conventional analytical procedures such as gas chromatography.
  • reaction mixture is heated to elevated temperature, e.g., to reflux temperature thus converting unreacted cyanuric chloride and amine hydrohalogenide to the desired compound of formula II.
  • the subsequent Friedel-Crafts reaction can be carried out in the same solvent as used in the reaction of the cyanuric chloride with the amine, e.g., in benzene, toluene or xylene.
  • the reaction can be carried out with catalysts which are conventional for this particular reaction, i.e. Lewis acids such as aluminum chloride as disclosed in EP 780,382.
  • Lewis acids such as aluminum chloride as disclosed in EP 780,382.
  • methanesulfonic acid is used as the catalyst in the Friedel-Crafts reaction.
  • the hydrocarbon used as the solvent in the preceding amination reaction is removed prior to the Friedel-Crafts reaction and the Friedel-Crafts reaction is suitably carried out at a temperature of about 10 to 30°C. At this temperature, optimal yield and purity of the desired compound of formula I is achieved in a reaction time of about 2 days.
  • the amount of catalyst is suitably 2 to 4 g of methanesulfonic acid per mmole of substituted amino dichlorotriazine.
  • a Lewis acid such as aluminum chloride the Friedel-Crafts reaction can be carried out at about 70 to 100 °C and using about 1,5 to 3 mole of catalyst per mole of compound of formula II.
  • the Friedel-Crafts reaction mixture is worked up by adding water and, if required, an organic solvent to obtain a suspension comprising a solvent phase and an aqueous phase.
  • the suspension is filtered and the filter cake resuspended in an organic solvent that is substantially immiscible with water.
  • the organic phase is then washed with water until the suspension has dissolved.
  • the organic phase obtained after adding water to the Friedel-Crafts reaction is washed with water without prior separating the solids. In either case the organic phase is separated and concentrated. If an appropriate solvent that is capable to form an adduct or solvate was used an adduct or solvate of the compound of formula I is thus obtained.
  • the residue is recrystallised from a solvent that is capable to form such adduct or solvate.
  • the adduct or solvate of the compound of formula I is converted to the pure compound of formula I by heating, e.g. up to about 80 °C to about 120 °C and/or applying reduced pressure, e.g. 1 to 30 mbar.
  • the orange solution was diluted, at 6°-8°C by the dropwise addition of 500 ml of ethyl acetate. To this solution, 1000 ml of water were added at about 8°C to afford a suspension.
  • step b) The suspension obtained in step a) was filtered. The filter cake was then suspended in ethyl acetate. The suspension was extracted several times with water of approx. 45°C until all the suspension had dissolved. The organic phase was concentrated to 150 g. The solution was dried under reflux by azeotropic removal of water. The dry solution was left to crystallise with stirring at 0°C. The yellow suspension was sucked off and washed with ice cold ethyl acetate to yield the ethyl acetate adduct (solvate) of 4,4'-[6-[bis-(2- ethylhexyl)amino]-s-triazine-2,4-diyl]-diresorcinol.
  • step a The suspension obtained in Example 2, step a) was extracted several times for 25 minutes with water of approx. 45°C until all the suspension had dissolved.
  • the organic phase was evaporated to dryness and crystallised from acetonitrile at 0°C.
  • the yellow suspension was sucked off and washed with acetonitrile to yield the acetonitrile adduct (solvate) of 4,4'- [6- [bis-(2-ethylhexyl)amino]-s-triazine-2,4-diyl]-diresorcinol.
  • the reaction mixture was poured onto a stirred mixture of 600 ml ethylacetate and 350 ml water.
  • the organic phase was separated and washed three times with water.
  • the organic phase was evaporated to dryness and crystallised from acetonitrile at 0°C.
  • the yellow suspension was sucked off and washed with acetonitrile to yield the acetonitrile adduct (solvate) of 4,4'- [6- [bis- (2- ethylhexyl)amino]-s-triazine-2,4-diyl]-diresorcinol.

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

Abstract

L'invention concerne un procédé de préparation d'amino-diaryl triazines consistant à faire réagir du chlorure cyanurique avec un amine substitué NH(R,R1) dans des quantités pratiquement équimolaires dans un hydrocarbure aromatique anhydre, dans un premier temps à basse température et, puis, à faire chauffer le mélange résultant afin de convertir le chlorure cyanurique restant et le chlorhydrate amine, à soumettre le composé résultant à une réaction de Friedel-Crafts avec un hydrocarbure d'aryle approprié, à façonner le mélange de réaction par addition d'eau et d'un solvant organique qui est pratiquement immiscible dans l'eau, à séparer, sécher et concentrer la phase de solvant, à isoler le composé souhaité comme un composé d'addition avec un solvant approprié, et à décomposer de manière subséquente ledit produit en vue d'obtenir l'amino-diaryle triazine substitué sous une forme pure.
PCT/EP2002/000626 2001-01-31 2002-01-23 Procede de preparation d'amino-diaryl triazines substitues WO2002060882A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002247649A AU2002247649A1 (en) 2001-01-31 2002-01-23 Process for the preparation of 2-(disubstituted-amino)-4,6-diaryl triazines

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP01102216 2001-01-31
EP01102216.7 2001-01-31

Publications (2)

Publication Number Publication Date
WO2002060882A2 true WO2002060882A2 (fr) 2002-08-08
WO2002060882A3 WO2002060882A3 (fr) 2002-11-28

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AU (1) AU2002247649A1 (fr)
WO (1) WO2002060882A2 (fr)

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US468308A (en) * 1892-02-02 Victor seidel
GB1018107A (en) * 1963-01-25 1966-01-26 Ciba Ltd New aryl-1,3,5-triazines,process for their preparation and their use
EP0029522A1 (fr) * 1979-11-06 1981-06-03 Hoechst Aktiengesellschaft Dérivés de la s-triazine, procédés pour leur préparation à partir d'halotriazinylamines et de polyamines, et leur utilisation comme stabilisants
US5059689A (en) * 1988-02-08 1991-10-22 Ciba-Geigy Corporation Tetramethylpiperidino-s-triazines
EP0775698A1 (fr) * 1995-11-23 1997-05-28 Ciba SC Holding AG Bis-résorcinol-triazines comme UV-absorbants
EP0790243A1 (fr) * 1996-02-12 1997-08-20 L'oreal Dérivés de s-triazine en tant que filtres UV
FR2757163A1 (fr) * 1996-12-13 1998-06-19 Oreal Nouveaux derives insolubles de s-triazine, leur procede de preparation, compositions les contenant et leurs utilisations
EP0878469A1 (fr) * 1997-05-16 1998-11-18 Ciba SC Holding AG Resorcinyl-triazines
US5874576A (en) * 1995-12-19 1999-02-23 Givaudan-Roure (International) Sa Light screening agents
EP0949251A1 (fr) * 1998-04-09 1999-10-13 Ciba SC Holding AG Diresorcinyltriazines comme agents de protection contre la lumière

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US468308A (en) * 1892-02-02 Victor seidel
GB1018107A (en) * 1963-01-25 1966-01-26 Ciba Ltd New aryl-1,3,5-triazines,process for their preparation and their use
EP0029522A1 (fr) * 1979-11-06 1981-06-03 Hoechst Aktiengesellschaft Dérivés de la s-triazine, procédés pour leur préparation à partir d'halotriazinylamines et de polyamines, et leur utilisation comme stabilisants
US5059689A (en) * 1988-02-08 1991-10-22 Ciba-Geigy Corporation Tetramethylpiperidino-s-triazines
EP0775698A1 (fr) * 1995-11-23 1997-05-28 Ciba SC Holding AG Bis-résorcinol-triazines comme UV-absorbants
US5874576A (en) * 1995-12-19 1999-02-23 Givaudan-Roure (International) Sa Light screening agents
EP0790243A1 (fr) * 1996-02-12 1997-08-20 L'oreal Dérivés de s-triazine en tant que filtres UV
FR2757163A1 (fr) * 1996-12-13 1998-06-19 Oreal Nouveaux derives insolubles de s-triazine, leur procede de preparation, compositions les contenant et leurs utilisations
EP0878469A1 (fr) * 1997-05-16 1998-11-18 Ciba SC Holding AG Resorcinyl-triazines
EP0949251A1 (fr) * 1998-04-09 1999-10-13 Ciba SC Holding AG Diresorcinyltriazines comme agents de protection contre la lumière

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BRUNETTI, H. ET AL: "Synthesis of asymmetrically substituted o-hydroxyphenyl-s-triazines" HELV. CHIM. ACTA (1972), 55(5), 1566-95, XP002034121 *

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Publication number Publication date
WO2002060882A3 (fr) 2002-11-28
AU2002247649A1 (en) 2002-08-12

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