Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
  • C07F9/02—Phosphorus compounds
  • C07F9/28—Phosphorus compounds with one or more P—C bonds
  • C07F9/46—Phosphinous acids [R2POH], [R2P(= O)H]: Thiophosphinous acids including[R2PSH]; [R2P(=S)H]; Aminophosphines [R2PNH2]; Derivatives thereof
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
  • C07F9/02—Phosphorus compounds
  • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
  • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
  • C07F9/572—Five-membered rings

Definitions

• the present invention relates to a process for manufacturing L-phenylalanine which makes it possible to obtain this product in a chemically and optically pure form in a simple manner. It is known to produce L-phenylalanine, an important intermediate in the synthesis of aspartame, by the enzymatic route or else from hydantoin.
• the object of the present invention therefore consists in obtaining in a simple manner L-phenylalanine in a chemically and optically pure form.
• the process which is the subject of the present invention consists in hydrogenating acetamidocinnamic acid in the presence of a metal M complex from group VIII of the Periodic Table and then in hydrolyzing the product resulting from the hydrogenation reaction and it is characterized in that that the hydrogenation reaction is carried out in the presence of a solvent, under pressure greater than or equal to atmospheric pressure, at a temperature of -50 ° C to + 10 ° C, for a duration less than or equal to 300 minutes , the molar ratio of acetamidocinnamic acid to said metal being greater than or equal to 100, the metal complex M being chosen from, on the one hand, those of formula MZq_ r L r and, on the other hand, those of formula (Zq_ r L r ) + A ⁇ , in which r is equal to 1 or 2, q is the degree of coordination of the
• Ri is chosen from the hydrogen atom and the hydrocarbon radicals
• R3 and R4 are chosen from the hydrogen atom and the hydrocarbon radicals optionally carrying at least one function chosen from alcohol, thiol, thioether, ine, imine functions , acid, ester, a ide and ether, and
• R5 and Rs are chosen from the hydrogen atom and the optionally functionalized hydro ⁇ carbon radicals.
• the molar ratio of acetamidocinnamic acid to metal M is preferably between 100 and 300.
• the ligands L used in the context of the present invention constitute the family of aminophosphine-phosphinites.
• radical R are in particular methyl, ethyl, isopropyl, tert-butyl, cyclohexyl and phenyl radicals.
• the most common example of the hydrocarbon radical Ri is the methyl radical.
• anion A "coordinating and sterically hindered is meant in particular the anions perchlorate, tetrafluoro- and tetraphenylborate, hexafluorophosphate.
• metals M which may be commonly used there may be mentioned iron, nickel, cobalt, rhodium, ruthenium, iridium, palladium, platinum.
• L ligands can be manufactured by a process consisting in reacting in a hydrocarbon solvent, at a temperature between -50 ⁇ C and 80 ⁇ C and under an inert gas atmosphere an optically active amino alcohol of general formula
• Y is chosen from halogen atoms and amino radicals, said compound being in a molar ratio, relative to the amino alcohol, greater than or equal to 2.
• Des preferred hydrocarbon solvents are benzene or toluene.
• a compound in which Y is a halogen atom it is preferred to use a compound in which Y is a halogen atom.
• tertiary amine such as for example triethylamine
• the chiral phosphorus ligand is isolated successively by filtration of the precipitate followed by evaporation of the hydrocarbon solvent under vacuum. It is generally in the form of a viscous oil.
• the chiral amino alcohols of formula (II) are most often either commercial or easily accessible products by reduction of natural amino acids (or of their formylated methyl esters).
• R3 or R4 of the amino alcohol of formula (II) carries a function, this can be introduced by a well known functionalization reaction, for example the ester function will be introduced by esterification of the function corresponding acid (case of carbalcoxy hydroxyprolines).
• prolinol hydroxy-proline
• ephedrines N-methylated aminoacools derived from the following natural amino acids: phenylglycine, phenylalanine, leucine, valine, alanine.
• the L ligands can be identified in particular using their proton, carbon 13 and phosphorus 31 nuclear magnetic resonance spectra, as well as their specific rotary power.
• Table II summarizes the identification data for certain aminophosphine-phosphinites, in which R is the phenyl radical, according to the amino alcohol or the amino acid from which they are derived. In this table (° .
• the hydrogenation reaction according to the invention makes it possible to obtain, with an excellent chemical yield, N-acetyl- (S) -phenylalanine with an optical yield generally greater than or equal to 85%.
• a variation of the process according to the invention, consisting in subjecting, before hydrolysis, the product resulting from said hydrogenation reaction to at least one recrystallization in ethanol makes it possible to dramatically improve the ren ⁇ D-optically N-acetyl- (S) -phenylalanine. According to this variant, an optical rendering at least equal to 99% can be easily achieved.
• R is the cyclohexyl radical
• the product resulting from the hydrogenation reaction of Example 3 is subjected to a recrystallization operation in ethanol, at the end of which the optical purity reaches 99.4%.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Biochemistry (AREA)
• General Health & Medical Sciences (AREA)
• Molecular Biology (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

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Publications (1)

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Citations (1)

• 1985
  • 1985-01-30 FR FR8501276A patent/FR2576593A1/fr not_active Withdrawn
• 1986
  • 1986-01-29 EP EP86900792A patent/EP0210210B1/fr not_active Expired
  • 1986-01-29 DE DE8686900792T patent/DE3661264D1/de not_active Expired
  • 1986-01-29 JP JP61500809A patent/JPS62501907A/ja active Granted
  • 1986-01-29 WO PCT/FR1986/000025 patent/WO1986004578A1/fr not_active Ceased
  • 1986-01-30 CA CA000500662A patent/CA1247643A/fr not_active Expired

Patent Citations (1)

Non-Patent Citations (3)

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