Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
  • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
  • C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form

Definitions

• the present invention relates to a new process for the preparation of racemic ortho or para-hydroxyarylglycolic acids and the new products resulting therefrom.
• Racemic hydroxyarylglycolic acids have been precious raw materials in organic synthesis since the work of P. Hébert, Bull. Soc. Chim. France, 1920, 27 (4th series). 45-55 confirmed their degradation into carbonyl derivative by decarboxylating oxidation.
• any rise in temperature is detrimental to the condensation yield of glyoxylic acid on gaiacol in order to access racemic 4-hydroxy-3-methoxy-3-mandelic acid and these authors recommend carrying out this condensation by introducing glyoxylic acid in 4 hours into an alkaline aqueous solution and cooled to 0 ° C. of gaiacol, then abandoning the reaction medium for 20 hours from 0 to 20 ° C.
• the company NIPPON SYNTHETIC CHEMICAL INDUSTRY Co for the manufacture of racemic 3,4-dihydroxy mandelic acid.
• glyoxylic acid quickly condenses in an alkaline aqueous medium, at a temperature between 35-50 and 100 ° C, advantageously between 50 and 100 ° C and better still between 50 and 85 ° C on an excess or not a phenolic aromatic derivative other than phenol, having at least one nuclear proton in the ortho or para position of the phenolic hydroxyl group, to provide a racemic ortho or para-hydroxyarylglycolic acid.
• This condensation is not regioselective as a result of the resonance of the phenolate anion communicating at the ortho and para vertices with a certain carbanion character.
• the percentage of isomers present at the end of treatment in the crude reaction product can be evaluated either by nuclear magnetic resonance spectroscopy of the proton or by potentiometric analysis in a non-aqueous medium using tetrabutylammonium hydroxide.
• NMR nuclear magnetic resonance spectroscopy
• the methine proton in the benzylic position of ortho-hydroxyaryl glycolic acids resonates at weaker fields than its counterpart of parahydroxyaryl glycolic acids.
• the orthohydroxyarylglycolic acids are more acidic than the corresponding para isomers.
• by assaying the phenol function in aqueous medium it is noted in very many cases that it cannot be dosed when it is in the ortho position of the 2-hydroxy-acetic acid side chain.
• the phenolic aromatic derivatives which can be used as starting products are for example ga ⁇ acol, 2-ethoxyphenol (guéthol), pyrocatechol, orthocresol, para-cresol, ortho-tertiobutylphenol, paratertiobutylphenol, ortho- chlorophenol, meta-ethylphenol, metafluorophenol, dimethoxy-2, 6 phenol, ⁇ -naphthol and the like.
• one condenses for a few tens of minutes between 50 and 100 ° C, advantageously for 45 minutes from 50 to 85 ° C, under a nitrogen atmosphere, one mole of glyoxylic acid at 50% in water with one to four moles, preferably two to three moles and more especially three moles of phenolic aromatic derivative, other than phenol, having at least one nuclear proton in ortho or para of the phenolic hydroxyl group in solution in 1 to 4 liters of water containing from 2 to 4 moles of sodium hydroxide, preferably from 2 to 3 liters of water containing from 2 to 3 moles of sodium hydroxide and advantageously in 1.8 liters of water containing 2.25 moles of hydroxide of sodium, then the reaction medium is neutralized to pH 6.5 with concentrated hydrochloric acid, then the starting phenolic aromatic derivative is not transformed with ethyl acetate, finally after acidification of the aqueous phase to pH 0.5 with concentrated hydrochloric acid, the or ortho and / or parahydr
• the residual aqueous phase then acidified to pH 0.5 with concentrated hydrochloric acid is washed with ethyl acetate, to extract the desired product.
• Example 2 The procedure is as in Example 1, but the guaiacol is replaced by the 1.5 mol ortho-cresol (162.2 g). At the end of the treatment, 0.97 mol (105 g) of unconverted ortho-cresol is recovered and 120 g of crystallized product are collected having a melting point of 105 ° C. After recrystallization from 120 volumes of dichloroethane and drying under vacuum at 80 ° C at constant weight, 68 g (0.373 mole) of 4-hydroxy-3-methyl-mandelic acid having a melting point 7. of 114 + 1 ° C are isolated. or a yield of 74.6% relative to the glyoxylic acid used.
• Example 2 The procedure is as in Example 1, but the guaiacol is replaced by 1.5 moles (162.2 g) of para-cresol. At the end of the treatment, 1.12 mol (121.1 g) of unconverted para-cresol are recovered and 78 g of crystallized product are collected which provide, after recrystallization from 2 volumes of nitromethane and drying under vacuum at constant weight at 80 °. C, 42.5 g (0.233 mole) of 2-hydroxy-5-methyl mandelic acid racemic having a melting point of 104 + 1 ° C or a yield of 46.6% relative to the glyoxylic acid used .
• Phenol function 5.44 meq / g
• the 4-ethyl-2-hydroxy-mandelic acid racemic is isolated having a melting point of 98 + 2 ° C.

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• Chemical & Material Sciences (AREA)
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• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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• 1979
  • 1979-07-25 FR FR7919171A patent/FR2462415A1/fr active Granted
• 1980
  • 1980-07-24 DE DE8080401102T patent/DE3060708D1/de not_active Expired
  • 1980-07-24 WO PCT/FR1980/000126 patent/WO1981000254A1/fr not_active Ceased
  • 1980-07-24 JP JP50176080A patent/JPS56500885A/ja active Pending
  • 1980-07-24 EP EP80401102A patent/EP0023459B1/fr not_active Expired
  • 1980-07-24 US US06/243,965 patent/US4339602A/en not_active Expired - Fee Related

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