CA1125784A - Process for manufacturing racemic parahydroxymandelic acid - Google Patents
Process for manufacturing racemic parahydroxymandelic acidInfo
- Publication number
- CA1125784A CA1125784A CA337,999A CA337999A CA1125784A CA 1125784 A CA1125784 A CA 1125784A CA 337999 A CA337999 A CA 337999A CA 1125784 A CA1125784 A CA 1125784A
- Authority
- CA
- Canada
- Prior art keywords
- acid
- glyoxylic acid
- phenol
- water
- racemic
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims abstract description 25
- YHXHKYRQLYQUIH-UHFFFAOYSA-N 4-hydroxymandelic acid Chemical compound OC(=O)C(O)C1=CC=C(O)C=C1 YHXHKYRQLYQUIH-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 6
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims abstract description 72
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 28
- 238000009833 condensation Methods 0.000 claims description 13
- 230000005494 condensation Effects 0.000 claims description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 8
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- -1 racemic parahydroxymandelic acid mono-hydrate Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000012736 aqueous medium Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000001117 sulphuric acid Substances 0.000 description 4
- 235000011149 sulphuric acid Nutrition 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229960001867 guaiacol Drugs 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- 238000005705 Cannizzaro reaction Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RGHMISIYKIHAJW-UHFFFAOYSA-N 3,4-dihydroxymandelic acid Chemical compound OC(=O)C(O)C1=CC=C(O)C(O)=C1 RGHMISIYKIHAJW-UHFFFAOYSA-N 0.000 description 1
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- CGQCWMIAEPEHNQ-UHFFFAOYSA-N Vanillylmandelic acid Chemical compound COC1=CC(C(O)C(O)=O)=CC=C1O CGQCWMIAEPEHNQ-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 229910001023 sodium amalgam Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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
Abstract
ABSTRACT OF THE DISCLOSURE
The present invention relates to a process for manufacturing racemic parahydroxymandelic acid. The process comprises condensing glyoxylic acid with an excess of phenol in water in the presence of an alkaline agent, at a temperature comprised between 30 and 100°C. The invention enables racemic parahydroxy-mandelic acid to be manufactured under easier temperature con-ditions and in shorter times resulting in higher productivity of the plant.
The present invention relates to a process for manufacturing racemic parahydroxymandelic acid. The process comprises condensing glyoxylic acid with an excess of phenol in water in the presence of an alkaline agent, at a temperature comprised between 30 and 100°C. The invention enables racemic parahydroxy-mandelic acid to be manufactured under easier temperature con-ditions and in shorter times resulting in higher productivity of the plant.
Description
li2578~
1 BACKGROUND OF I'HE INVENTION
1. Field of the _vention The present invention relates to a process for manufacturing racemic parahydroxymandelic acid by the conden-sation of glyoxylic acid with phenol, in an alkaline medium.
1 BACKGROUND OF I'HE INVENTION
1. Field of the _vention The present invention relates to a process for manufacturing racemic parahydroxymandelic acid by the conden-sation of glyoxylic acid with phenol, in an alkaline medium.
2. D _ ri ~ on of the Prior Art_ _ _ _ _ _ It is known that carbonyl derivatives such as glyoxylic acid or chloral condense in an alkaline aqueous medium on phenol rings substituted or unsubstituted by hydroxyl, alkoxyl and/or alkyl groups possessing at least one proton on the para position, to provide racemic arylglycolic acids either directly, or by the hydrolysis of racemic aryltrichloromethylcarbinols (HOUBEN-WEYL, phenole 6/lc, pages 1022-1~58, G. THIEM~ Verlag Stuttgart, 1976).
Racemic arylglycolic acids are valuable starting materials since it is known how to convert them into aromatic aldehydes (P. HEBERT, ~ull. Soc. Chim. France, 27, 4th serie, 45-55, 1920). In particular racemic parahydroxymandelie acid provides by decarboxylating oxidation, parahydroxybenzaldehyde (NAGAI SHIGEKI et Coll., Japanese Patent Application No.
76-128 934).
Racemie parahydroxymandelie aeid is prepared either by hydrolysis of the cyanhydrin of parahydroxyben~aldehyde (Beil X, page 410), or by reduction with a sodium amalgam of parahydroxyphenylglyoxylic aeid (Beil. X, 1st supple. page 199), or by eondensation of glyoxylic acid with phenol (RIEDEL DE HAEN
A.G., German Patent No. 621,567; HAARMANN and REIMER, G.m.b.H., French Patent No. 2,132,364), or lastly by hydrolysis of para-hydroxyphenyltrichloromethylcarbinol derived from the con-densation of chloral with phenol (H. HAAKH and A. SMOLA, Austrian Patent No. 141,159).
llZS'~
1 However, carbonyl derivatives in an alkaline aqueous medium and particularly glyoxylic acid are subject to the Cannizzaro reaction; when hot, glyoxylic acid decomposes completely into oxalic and glycolic acids (BOETTINGER, Ber. 13, 1931 (1880)).
It is to avoid this Cannizzaro reaction becomingpreponderant and destroying the glyoxylic acid utilized that the condensation processes of glyoxylic acid with phenolic rings in an alkaline aqueous medium are carried out at a temperatur~
close to room temperature. Thus in the process described in German Patent No. 621,567, an aqueous alkaline solution of phenol and of glyoxylic acid are left for several days at ambient temperature. In French Patent No. 2,132,364, the condensation of the glyoxylic acid with an excess of phenol is carried out in 10% caustic soda solution, for 36 hours between 15 and 25C.
More generally, the processes of preparing racemic arylglycolic acids by condensation of glyoxylic acid on a phenolic ring are carried Ollt at a temperature below 25C.
J. GOOD.~AN et Coll., (Biochem. Biophys. Acta, 156, 364-7, 1968) condense glyoxylic acid with guaiacol in 68 hours at 25C, whereas J. KAMLET, (U.S.A. Patent No. 2,640,083), operates for 48 hours between 15 and 20C to prepare racemic 4-hydroxy-3-methoxy mandelic acid.
A.I. FATIADI and R. SCHAFFER, (J. Research Nat. Bur.
Stand., Sect. A, 78A, 411-12, 1972), studied the temperature factor on the condensation of glyoxylic acid on guaiacol; they concluded that any rise in temperature was detrimental to the yield and recommend carrying out this condensation by introducing the glyoxylic acid into an alkaline aqueous solution 1125~7~i~
1 of guaiacol cooled to 0C over 4 hours and then leaving it for 20 hours from 0 to 20C. For the manufacture of racemic 3,4-dihydroxy mandelic acid, the NIPPON SYNTHETIC CHEMICAL INDUSTRY Co.
Ltd. in Japanese Patent Application No. 75-29522, teaches carrying out the condensation of the glyoxylic acid with pyrocatechol over 2 hours at 5 to 8C, then for 24 hours at 10-15C
and finally over 24 hours at ambient temperature.
It is obvious that these methods :
low temperatures - long reaction times, result in a reduction of the productivity of the plant, an increase in investment and lend themselves with difficulty to large tonnage industrial production.
Accordingly, it is an object of the present invention to provide a method for the manufacture of racemic parahydroxy-mandelic acid which improves these temperature and time reaction restrictions.
It is another object of the invention to provide such a method which improves the productivity of the installation.
It is a further object of the invention to provide such a process which lends itself more readily to large scale production.
Other objects and advantages of the invention will be apparent from the description which follows.
GENERAL DESCRIPTION OF THE INVENTION
Applicants have now discovered surprisingly and unexpectedly that the condensation of glyoxylic acid with phenol in an alkaline aqueous medium could be carried out very easily at temperatures comprised between 30 and 100C, whilst preserving good selectivity, providing excellent yields and considerably shortening the reaction time.
i~Z5~8~
1 Accordiny to the invention, there is provided a process, comprising reacting glyoxylic acid with an excess of phenol in water in the presence of an alkaline agent at a temperature comprised between 30 and 100C for some minutes, then after neutralization of the reaction medium, removal of the uncon-verted phenol by extraction with a water immiscible organic solvent, and then, after acidification of the aqueous phase at pH 0.5, extraction of the desired acid wit~ a water immiscible solvent. The racemic parahydroxymandelic acid is thus isolated after evaporation oE the ex-traction solvent.
More precisely, the process comprises condensing between 30 and 100C, preferably between 70 and 100C and advantageously between 70 and 85C, in a nitrogen atmosphere, 1 mole of 50% glyoxylic acid in water with 2 to 3 moles of phenol in 2 liters of water containing 2 to 3 moles of sodium hydroxide for a time less than or equal to 70 minutes, then neutralizing the solution with 50~ sulphuric acid in water, then extracting the unconverted phenol with 1,2-dichloro-ethane.
Finally, the aqueous phase acidified to pH = 0.5 with 50%
sulphuric acid in water, is extracted with ethyl acetate.
In this way there is isolatedt after evaporation of the ethyl acetate, the crystalline, racemic parahydroxymandelic acid, monohydrate with a yield of 70 to 85% with respect to the glyoxylic acid utilized.
DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples are given purely by way of illustrative and non-limiting description of the invention.
EXAMPLE
A solution of 2~6 g (2 moles~ of 50% glyoxylic acid in water, 564 g (6 moles) of phenol and 160 g ~4 moles) of ~lZS~
1 caustic soda in pellets in 3.6 liters of water are heated for 30 minutes at 82C with stirring and under a nitrogen atmosphere.
AFter cooling to 40C, the reaction solution is brought to pH : 6.5 with 50% sulphuric acid in water, then after cooling to room temperature, the unconverted phenol is extracted by means of l,2-dichloro-ethane; 376 g of phenol, after evaporation of the solvent, are thus isolated. The aqueous phase is then acidified to pH 0.5 with 50% sulphuric acid in water and then, after saturation with sodium chloride, it is extracted several times with ethyl acetate. In this way, after evaporation of the ethyl acetate and drying under vacuum at 40C for 60 hours, 285 g of crystalline racemic parahydroxymandelic acid mono-hydrate are isolated, having a melting point in tube of 83-85C, namely a yield of 76.5% with respect to the glyoxylic acid utilized.
A solution of 296 g ~2 moles) of 50% glyoxylic acid in water, 564 g (6 moles2 of phenol and 160 g (4 moles~ of caustic soda in pellets in 3.6 liters of water are heated for 30 minutes at lQ0C with stirring and under a nitrogen atmosphere. Then procedure is as in Example 1. In this way the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 72% with respect to the glyoxylic acid utilized.
A solution of 296 g (2 moles) of 50% glyoxylic acid in water, 564 g ~6 moles) of phenol and 200 g (5 moles) of caustic soda in pellets in 3.6 liters of water is heated for
Racemic arylglycolic acids are valuable starting materials since it is known how to convert them into aromatic aldehydes (P. HEBERT, ~ull. Soc. Chim. France, 27, 4th serie, 45-55, 1920). In particular racemic parahydroxymandelie acid provides by decarboxylating oxidation, parahydroxybenzaldehyde (NAGAI SHIGEKI et Coll., Japanese Patent Application No.
76-128 934).
Racemie parahydroxymandelie aeid is prepared either by hydrolysis of the cyanhydrin of parahydroxyben~aldehyde (Beil X, page 410), or by reduction with a sodium amalgam of parahydroxyphenylglyoxylic aeid (Beil. X, 1st supple. page 199), or by eondensation of glyoxylic acid with phenol (RIEDEL DE HAEN
A.G., German Patent No. 621,567; HAARMANN and REIMER, G.m.b.H., French Patent No. 2,132,364), or lastly by hydrolysis of para-hydroxyphenyltrichloromethylcarbinol derived from the con-densation of chloral with phenol (H. HAAKH and A. SMOLA, Austrian Patent No. 141,159).
llZS'~
1 However, carbonyl derivatives in an alkaline aqueous medium and particularly glyoxylic acid are subject to the Cannizzaro reaction; when hot, glyoxylic acid decomposes completely into oxalic and glycolic acids (BOETTINGER, Ber. 13, 1931 (1880)).
It is to avoid this Cannizzaro reaction becomingpreponderant and destroying the glyoxylic acid utilized that the condensation processes of glyoxylic acid with phenolic rings in an alkaline aqueous medium are carried out at a temperatur~
close to room temperature. Thus in the process described in German Patent No. 621,567, an aqueous alkaline solution of phenol and of glyoxylic acid are left for several days at ambient temperature. In French Patent No. 2,132,364, the condensation of the glyoxylic acid with an excess of phenol is carried out in 10% caustic soda solution, for 36 hours between 15 and 25C.
More generally, the processes of preparing racemic arylglycolic acids by condensation of glyoxylic acid on a phenolic ring are carried Ollt at a temperature below 25C.
J. GOOD.~AN et Coll., (Biochem. Biophys. Acta, 156, 364-7, 1968) condense glyoxylic acid with guaiacol in 68 hours at 25C, whereas J. KAMLET, (U.S.A. Patent No. 2,640,083), operates for 48 hours between 15 and 20C to prepare racemic 4-hydroxy-3-methoxy mandelic acid.
A.I. FATIADI and R. SCHAFFER, (J. Research Nat. Bur.
Stand., Sect. A, 78A, 411-12, 1972), studied the temperature factor on the condensation of glyoxylic acid on guaiacol; they concluded that any rise in temperature was detrimental to the yield and recommend carrying out this condensation by introducing the glyoxylic acid into an alkaline aqueous solution 1125~7~i~
1 of guaiacol cooled to 0C over 4 hours and then leaving it for 20 hours from 0 to 20C. For the manufacture of racemic 3,4-dihydroxy mandelic acid, the NIPPON SYNTHETIC CHEMICAL INDUSTRY Co.
Ltd. in Japanese Patent Application No. 75-29522, teaches carrying out the condensation of the glyoxylic acid with pyrocatechol over 2 hours at 5 to 8C, then for 24 hours at 10-15C
and finally over 24 hours at ambient temperature.
It is obvious that these methods :
low temperatures - long reaction times, result in a reduction of the productivity of the plant, an increase in investment and lend themselves with difficulty to large tonnage industrial production.
Accordingly, it is an object of the present invention to provide a method for the manufacture of racemic parahydroxy-mandelic acid which improves these temperature and time reaction restrictions.
It is another object of the invention to provide such a method which improves the productivity of the installation.
It is a further object of the invention to provide such a process which lends itself more readily to large scale production.
Other objects and advantages of the invention will be apparent from the description which follows.
GENERAL DESCRIPTION OF THE INVENTION
Applicants have now discovered surprisingly and unexpectedly that the condensation of glyoxylic acid with phenol in an alkaline aqueous medium could be carried out very easily at temperatures comprised between 30 and 100C, whilst preserving good selectivity, providing excellent yields and considerably shortening the reaction time.
i~Z5~8~
1 Accordiny to the invention, there is provided a process, comprising reacting glyoxylic acid with an excess of phenol in water in the presence of an alkaline agent at a temperature comprised between 30 and 100C for some minutes, then after neutralization of the reaction medium, removal of the uncon-verted phenol by extraction with a water immiscible organic solvent, and then, after acidification of the aqueous phase at pH 0.5, extraction of the desired acid wit~ a water immiscible solvent. The racemic parahydroxymandelic acid is thus isolated after evaporation oE the ex-traction solvent.
More precisely, the process comprises condensing between 30 and 100C, preferably between 70 and 100C and advantageously between 70 and 85C, in a nitrogen atmosphere, 1 mole of 50% glyoxylic acid in water with 2 to 3 moles of phenol in 2 liters of water containing 2 to 3 moles of sodium hydroxide for a time less than or equal to 70 minutes, then neutralizing the solution with 50~ sulphuric acid in water, then extracting the unconverted phenol with 1,2-dichloro-ethane.
Finally, the aqueous phase acidified to pH = 0.5 with 50%
sulphuric acid in water, is extracted with ethyl acetate.
In this way there is isolatedt after evaporation of the ethyl acetate, the crystalline, racemic parahydroxymandelic acid, monohydrate with a yield of 70 to 85% with respect to the glyoxylic acid utilized.
DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples are given purely by way of illustrative and non-limiting description of the invention.
EXAMPLE
A solution of 2~6 g (2 moles~ of 50% glyoxylic acid in water, 564 g (6 moles) of phenol and 160 g ~4 moles) of ~lZS~
1 caustic soda in pellets in 3.6 liters of water are heated for 30 minutes at 82C with stirring and under a nitrogen atmosphere.
AFter cooling to 40C, the reaction solution is brought to pH : 6.5 with 50% sulphuric acid in water, then after cooling to room temperature, the unconverted phenol is extracted by means of l,2-dichloro-ethane; 376 g of phenol, after evaporation of the solvent, are thus isolated. The aqueous phase is then acidified to pH 0.5 with 50% sulphuric acid in water and then, after saturation with sodium chloride, it is extracted several times with ethyl acetate. In this way, after evaporation of the ethyl acetate and drying under vacuum at 40C for 60 hours, 285 g of crystalline racemic parahydroxymandelic acid mono-hydrate are isolated, having a melting point in tube of 83-85C, namely a yield of 76.5% with respect to the glyoxylic acid utilized.
A solution of 296 g ~2 moles) of 50% glyoxylic acid in water, 564 g (6 moles2 of phenol and 160 g (4 moles~ of caustic soda in pellets in 3.6 liters of water are heated for 30 minutes at lQ0C with stirring and under a nitrogen atmosphere. Then procedure is as in Example 1. In this way the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 72% with respect to the glyoxylic acid utilized.
A solution of 296 g (2 moles) of 50% glyoxylic acid in water, 564 g ~6 moles) of phenol and 200 g (5 moles) of caustic soda in pellets in 3.6 liters of water is heated for
3~ 1 hour at 50C, with stirring and under a nitrogen atmosphere.
~12S~
1 Then procedure is as in Example 1. In this way the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 78~ with respect to the glyoxylic acid utilized.
A solution of 296 g (2 moles) of 50~ glyoxylic acid in water, 564 g (6 moles) of phenol and 180 g (4.5 moles) of caustic soda in pellets in 3.6 liters of water is heated for 30 minutes from 30 to 85C, then cooled in 30 minutes to 40C, with stirring and under a nitrogen atmosphere. Then procedure as is in Example 1. In this way the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 81% with respect to the glyoxylic acid utilized.
A solution of 296 g (2 moles) of 50~ glyoxylic acid in water, 564 g (6 molesl of phenol and 160 g (4 moles) of caustic soda in pellets in 3.6 liters of water are heated for 30 minutes at 70C, with stirring and under a nitrogen atmosphere. Procedure is then as in Example 1. In this way the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 83.5~ with respect to the glyoxylic acid utilized.
.
Into a solution of 133.2 g ~0.9 mole) of 50~ glyoxylic acid in water and 990 g of water heated under reflux in a nitrogen atmosphere, is introduced with siirring and at once, a hot solution prepared at that moment by dissolving under reflux in a nitrogen atmosphere 253.8 g (2.7 moles) of phenol and 81 g (2.025 moles2 of sodium hydroxide in pellets in 630 g of water is introduced. The resulting solution is then kept llZS'~&14 1 stirred and under a nitrogen atmosphere, at 100C for 5 minutes, then the solution is neutralized while hot to a pH of 6.5 with 6N hydrochloric acid. ~fter cooling to room temperature, procedure is as in Example 1. In this way 169 g (1.8 mole) of phenol is recovered and then the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 67.5~ with respec-t to the glyoxylic acid utilized.
~12S~
1 Then procedure is as in Example 1. In this way the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 78~ with respect to the glyoxylic acid utilized.
A solution of 296 g (2 moles) of 50~ glyoxylic acid in water, 564 g (6 moles) of phenol and 180 g (4.5 moles) of caustic soda in pellets in 3.6 liters of water is heated for 30 minutes from 30 to 85C, then cooled in 30 minutes to 40C, with stirring and under a nitrogen atmosphere. Then procedure as is in Example 1. In this way the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 81% with respect to the glyoxylic acid utilized.
A solution of 296 g (2 moles) of 50~ glyoxylic acid in water, 564 g (6 molesl of phenol and 160 g (4 moles) of caustic soda in pellets in 3.6 liters of water are heated for 30 minutes at 70C, with stirring and under a nitrogen atmosphere. Procedure is then as in Example 1. In this way the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 83.5~ with respect to the glyoxylic acid utilized.
.
Into a solution of 133.2 g ~0.9 mole) of 50~ glyoxylic acid in water and 990 g of water heated under reflux in a nitrogen atmosphere, is introduced with siirring and at once, a hot solution prepared at that moment by dissolving under reflux in a nitrogen atmosphere 253.8 g (2.7 moles) of phenol and 81 g (2.025 moles2 of sodium hydroxide in pellets in 630 g of water is introduced. The resulting solution is then kept llZS'~&14 1 stirred and under a nitrogen atmosphere, at 100C for 5 minutes, then the solution is neutralized while hot to a pH of 6.5 with 6N hydrochloric acid. ~fter cooling to room temperature, procedure is as in Example 1. In this way 169 g (1.8 mole) of phenol is recovered and then the racemic parahydroxymandelic acid monohydrate is isolated with a yield of 67.5~ with respec-t to the glyoxylic acid utilized.
Claims (7)
1. Process for manufacturing racemic parahydroxymandelic acid, comprising condensing glyoxylic acid with an excess of phenol in water in the presence of an alkaline agent, at a temperature comprised between 70° and 100°C.
2. Process according to claim 1, wherein the condensation is carried out at a temperature comprised between 70 and 85°C.
3. Process according to claim 1, in which the alkaline agent is sodium or potassium hydroxide.
4. Process according to claim 1, in which the condensation is carried out in the presence of 2 to 3 moles of sodium or potassium hydroxide per mole of glyoxylic acid.
5. Process according to claim 1, wherein the condensation is carried out in 1 to 3 liters of water per mole of glyoxylic acid.
6. Process according to claim 1, in which 1 mole of glyoxylic acid is condensed with an excess of 2 to 3 moles of phenol.
7. Process according to claim 1, in which the condensation of the glyoxylic acid with excess phenol in water, in the presence of an alkaline agent,is carried out in a time less than or equal to 70 minutes.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7831123 | 1978-11-03 | ||
| FR7831123A FR2440350A1 (en) | 1978-11-03 | 1978-11-03 | PROCESS FOR PRODUCING RACEMIC PARAHYDROXYMANDELIC ACID |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1125784A true CA1125784A (en) | 1982-06-15 |
Family
ID=9214433
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA337,999A Expired CA1125784A (en) | 1978-11-03 | 1979-10-19 | Process for manufacturing racemic parahydroxymandelic acid |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5564546A (en) |
| BE (1) | BE879359A (en) |
| CA (1) | CA1125784A (en) |
| CH (1) | CH642047A5 (en) |
| DE (1) | DE2944295C2 (en) |
| FR (1) | FR2440350A1 (en) |
| GB (1) | GB2034308B (en) |
| IE (1) | IE49308B1 (en) |
| IT (1) | IT1124842B (en) |
| NL (1) | NL189910C (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2462415A1 (en) * | 1979-07-25 | 1981-02-13 | Hoechst France | PROCESS FOR PREPARING RACEMIC HYDROXYARYLGLYCOLIC ACIDS AND PRODUCTS THEREOF |
| FR2495137A1 (en) * | 1980-11-28 | 1982-06-04 | Hoechst France | Para-hydroxy-mandelic acid continuous prepn. - from glyoxylic acid, phenol and sodium hydroxide in aq. soln. in reactors arranged in series |
| TW206220B (en) * | 1991-07-01 | 1993-05-21 | Ciba Geigy Ag | |
| US5252643A (en) * | 1991-07-01 | 1993-10-12 | Ciba-Geigy Corporation | Thiomethylated benzofuran-2-ones |
| EP0545861B1 (en) * | 1991-11-29 | 1995-12-27 | Ciba-Geigy Ag | Diphenylacetic acid derivatives as stabilisers for organic material |
| NL9300801A (en) * | 1992-05-22 | 1993-12-16 | Ciba Geigy | 3- (ACYLOXYPHENYL) BENZOFURAN-2-ON AS STABILIZERS. |
| TW260686B (en) * | 1992-05-22 | 1995-10-21 | Ciba Geigy | |
| GB2267490B (en) * | 1992-05-22 | 1995-08-09 | Ciba Geigy Ag | 3-(Carboxymethoxyphenyl)benzofuran-2-one stabilisers |
| MX9305489A (en) * | 1992-09-23 | 1994-03-31 | Ciba Geigy Ag | 3- (DIHIDROBENZOFURAN-5-IL) BENZOFURAN-2-ONAS, STABILIZERS. |
| TW255902B (en) * | 1992-09-23 | 1995-09-01 | Ciba Geigy | |
| FR2705669B1 (en) * | 1993-05-28 | 1995-08-25 | Hoechst France | Process for the preparation of hydroxyphenylacetic acids. |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE617763C (en) * | 1932-03-22 | 1935-08-24 | J D Riedel E De Haeen Akt Ges | Process for the production of aromatic oxyaldehydes |
| DE621567C (en) * | 1932-06-25 | 1935-11-09 | J D Riedel E De Haeen A G | Process for the production of aromatic oxyaldehydes |
| DE2115551C3 (en) * | 1971-03-31 | 1980-01-10 | Haarmann & Reimer Gmbh, 3450 Holzminden | Process for the production of aromatic hydroxyaldehydes |
-
1978
- 1978-11-03 FR FR7831123A patent/FR2440350A1/en active Granted
-
1979
- 1979-10-11 BE BE0/197604A patent/BE879359A/en not_active IP Right Cessation
- 1979-10-18 CH CH938079A patent/CH642047A5/en not_active IP Right Cessation
- 1979-10-19 CA CA337,999A patent/CA1125784A/en not_active Expired
- 1979-10-29 JP JP13972579A patent/JPS5564546A/en active Pending
- 1979-10-29 GB GB7937472A patent/GB2034308B/en not_active Expired
- 1979-10-30 IT IT26924/79A patent/IT1124842B/en active
- 1979-11-02 IE IE2108/79A patent/IE49308B1/en not_active IP Right Cessation
- 1979-11-02 DE DE2944295A patent/DE2944295C2/en not_active Expired
- 1979-11-05 NL NLAANVRAGE7908100,A patent/NL189910C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NL189910C (en) | 1993-09-01 |
| IT7926924A0 (en) | 1979-10-30 |
| FR2440350A1 (en) | 1980-05-30 |
| GB2034308B (en) | 1983-03-30 |
| GB2034308A (en) | 1980-06-04 |
| FR2440350B1 (en) | 1981-05-22 |
| DE2944295A1 (en) | 1980-05-08 |
| BE879359A (en) | 1980-04-11 |
| CH642047A5 (en) | 1984-03-30 |
| IE792108L (en) | 1980-05-03 |
| IE49308B1 (en) | 1985-09-18 |
| NL7908100A (en) | 1980-05-07 |
| DE2944295C2 (en) | 1982-02-04 |
| NL189910B (en) | 1993-04-01 |
| JPS5564546A (en) | 1980-05-15 |
| IT1124842B (en) | 1986-05-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1125784A (en) | Process for manufacturing racemic parahydroxymandelic acid | |
| Thoer et al. | The Reimer-Tiemann reaction in slightly hydrated solid-liquid medium: a new method for the synthesis of formyl and diformyl phenols | |
| US3935257A (en) | Chemical compounds | |
| JPH051776B2 (en) | ||
| US4259521A (en) | Process for resolving DL-mandelic acid | |
| JP3968158B2 (en) | Method for purifying o-phthalaldehyde | |
| US4408070A (en) | Pure crystalline racemic sodium parahydroxymandelate, process for its preparation and uses thereof | |
| CN115572272A (en) | Preparation method of febuxostat and aldehyde ester intermediate thereof | |
| Reeve et al. | Stereochemical study of the mechanism of the conversion of phenyl (trichloromethyl) carbinol to. alpha.-methoxyphenylacetic acid | |
| DK143332B (en) | PROCEDURE FOR THE PREPARATION OF ORTHOH HYDROXYAL CHYLED PHENOLS | |
| EP2419394A1 (en) | Process for the preparation of 2,4,6-octatriene-1-oic acid and 2,4,6-octatriene-1-ol | |
| US2304537A (en) | Preparation of alpha-chlormethyl naphthalene | |
| US4504678A (en) | Pure crystalline racemic sodium parahydroxymandelate, process for its preparation and uses thereof | |
| JPH02149586A (en) | Production of aryl metaborate and use thereof for production of 0-hydroxybenzyl alcohol | |
| US4260815A (en) | Process for preparing a solution of DL-mandelic acid | |
| Marvel et al. | A CONVENIENT SYNTHESIS OF dl-GLUTAMIC ACID | |
| US5302748A (en) | Esterification process | |
| US3912772A (en) | Process for the preparation of {60 -alkyl hydracrylic acids and {60 -alkyl acrylic acids. | |
| US2768967A (en) | Process for manufacture of 2, 5 diketo-8-nonen-3-ol | |
| US2463734A (en) | Racemization of optical isomers | |
| SU379557A1 (en) | WAY OF OBTAINING 2,4-DIALKYL-2,4--DINITROPENTANDIOLOV-1,5 | |
| US3024250A (en) | Certificate of correction | |
| US2847460A (en) | 6-methyl-3-cyclohexene-1-acrylic acid | |
| JPH01113336A (en) | Production of alkylphenoxyacetic acid | |
| US2967874A (en) | Process for increasing the chain length of levulinic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |