FORM 2
The Patent Act 1970,
(39 of 1970)
&
The Patent rule 2003
Provisional Specification
(See Section 10 and Rule 13)
1. TITLE OF THE INVENTION
Process for preparing aromatic hydroxy and alkoxy aldehydes


2. APPLICANT(S)
(a) NAME : GHARDA CHEMICALS LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: B-27/29, MIDC, PHASE 1,
DOMBIVLI (E), DIST. THANE 421 203 MAHARASHTRA, INDIA
3. PREAMBLE TO THE DESCRIPTION
The following specification describes the invention.


Field of the Invention
The present invention relates to the use of a new catalyst for the oxidation of hydroxylated and alkoxylated derivatives of the phenyl glyoxylic acid to obtain hydroxylated and alkoxylated aromatic aldehyde derivatives. The invention particularly describes the preparation of vanillin and ethyl vanillin. The scope of the present invention further extends to a novel method of isolation of the hydroxylated and alkoxylated aromatic aldehyde derivatives as the alkali metal salt present in the oxidation mass using excess alkali hydroxide for salting out and recovery of alkali values of the excess alkali hydroxide as bicarbonate by use of carbon dioxide gas. The method achieves the dual purposes of purification of the product as well as recovering the economic value of alkali used as bicarbonate, which can be used in the process as such as well as after conversion to alkali hydroxide by established methods. This novel method avoids the large effluent stream containing dissolved salts, which has been a perennial problem in this process.
Background of the Invention
Aromatic hydroxy and alkoxy aldehydes are important chemicals used directly or as intermediates in various fields such as pharmaceutical, cosmetic, food and other industrial uses. Vanillin, ethyl vanillin, protocatechuic aldehyde, veratrole, piperonal etc. are examples of such use. Vanillin and ethyl vanillin are important industrial products used as a flavoring agent in food and in cosmetics. Vanillin is produced both synthetically and from natural sources and consumption in the world is in the range of 16000- 17000 TPA.
Various processes have been established for the preparation of the hydroxylated and alkoxylated phenyl glyoxylates, which are the starting material for this process. The process invariably uses glyoxylic acid for condensing with alkoxylated phenols in the alkaline condition. Conditions have been standardized to get high para selectivity and yield.

Various processes have been known for oxidation of the hydroxylated and alkoxylated phenyl glyoxylic acid derivatives.
The US Patent 4165341 (1979) describes preparation of 4-hydroxy-3-methoxy mandelic acid by condensation of guaiacol with glyoxylic acid in alkaline medium and oxidation of the mass with air using copper oxide catalyst in an autoclave to give Vanillin.
The UK patent 2055795A (1979) describes a process for substituted glycolic acids of general formula ArCHOH.COOH and oxidation by air in presence of catalyst comprising organic or inorganic copper compounds in acidic medium.
UK patent 1377243 (1972) describes oxidation of aromatic glycolic acids in aqueous medium at pH more acidic than 5 using FeCI3 or CuCI2 catalyst to give aromatic aldehydes.
Canadian patent 1123010 (1979) describes oxidation of hydroxy and alkoxy mandelic acids using CuCI2 catalyst in the acidic medium to give the corresponding aldehyde derivatives.
German patent DE 2115551 describes oxidation of phenyl glycolic acids in the presence of Fe(lll) or Cu(ll) catalyst to give 4-hydroxy-3-methoxy benzaldehydes.
New J. Chem., 2004, 28, 62 - 66 describes oxidation of substituted phenyl mandelic acids to give corresponding aldehyde^ in a medium of DMSO - NaOH system, using CoCI2 catalyst. The method is cumbersome and apart from cost, not commercially useful due to need of DMSO, particularly for flavoring agents like Vanillin and Ethyl Vanillin.
Japanese patent JP 76, 128934 describes oxidation of p-hydroxy mandelic acid derivatives to corresponding aldehydes using CoO catalyst complex using aniline. The disadvantages are need of large quantity catalyst (upto 40 mole %) and need of aniline

as a complexing agent. The use of aniline is not acceptable while preparing flavoring agents and hence not commercially useful.
In most of the processes, the oxidation of hydroxylated and alkoxylated phenyl glyoxylic acid derivatives is carried out in alkaline medium. Though oxidation have been reported in acidic medium also, in our opinion they are not effective and fail to give good quality product and yield. However, both in alkaline and acidic medium, the catalysts reported are mainly copper salts either alone or mixed with others metal salts like Fe, Mn etc. The catalysts used invariably is in large quantity, generally 0.1 to 1.0 molar equivalents to the substrate giving problems of recovery of the metal, high cost involved, lower yield and pollution. These processes are all unsatisfactory for industrial practice.
Summary of the Invention
Our research to overcome these problems in the oxidation step led to the invention that use of small quantity of cobalt salt is highly effective in bringing about oxidation of hydroxylated and alkoxylated phenyl glyoxylic acid derivatives at lower temperature. Though cobalt salt is a known catalyst for bringing about oxidation of various organic compounds, particularly in acidic medium, its use in small quantity for the effective oxidation of hydroxy mandelic acids has not been reported in literature.
Our invention further extends to the method of isolation of the oxidized product, i.e. the hydroxylated and alkoxylated aromatic aldehyde derivatives as the alkali metal salt using excess alkali hydroxide for salting out and recovery of alkali values of the excess alkali hydroxide as bicarbonate by use of carbon dioxide gas.
Detailed Description
The present invention is described in detail in the following. The cobalt compounds for use as catalysts in the present process are preferably its chloride, acetate, nitrate, sulphate, oxide or carbonate. The catalyst, since used in ppm levels does not pose recovery or pollution problems. The catalyst quantity to be used is in the range of 25 to 350 ppm of the oxidation mass with more preferred quantity being 150 ppm. The

oxidation is carried out at a temperature range of 50°C to 135°C and optimum range from the kinetics and other aspects being 90°C to 100°C. Oxidation is carried out with air or oxygen or a mixture thereof at atmospheric pressure or upto 10 atm pressure with optimum being 5 atm where air is used. Oxidation is carried out with excess alkali, viz., NaOH or KOH. The alkali carbonates can also be used, however the oxidation is sluggish. Though oxidations under acidic conditions are also reported, we prefer to carry out the oxidation in aqueous NaOH solution due to reasons of the solubility and inherent stability of o- and p-hydroxy benzaldehyde system. In acidic medium the-CHO group is susceptible to further oxidation. The quantity of alkali used has a profound influence on the rate of oxidation and the optimum quality required is 2.5 moles NaOH per mole of the substrate. Use of NaOH is the preferred base from the cost point of view, though KOH can also be used.
Our invention further extends to the method of isolation of the oxidized product. Conventional method of isolation is acidification of the oxidation mass and extraction using solvent. This method has drawbacks such as use of large quantity of acid to neutralize the alkali, subsequent salt generation and resultant non-biodegradability of the effluent stream. The method also suffers from the drawback that all the impurities produced during oxidation is precipitated alongwith the product and renders purification of the product difficult.
To overcome these drawbacks, a unique process was developed in which the oxidation solution is partially concentrated and cooling gave precipitation of sodium salt of vanillin in more than 99% purity. The excess alkali present helped in salting out the product and the filtrate contained all the alkali values. Now to this alkali, C02 gas is passed wherein the sparingly soluble NaHC03 precipitated out. The NaHC03 solids are filtered out and partially used internally for neutralizing glyoxylic acid and rest of it is converted to Na2CO3 by established process with internal re-circulation of C02. The filtrate after isolating NaHCO3, which is now with alkali, is acidified and impure mixture of vanillin is separated and purified by fractional distillation.


NaOH + CO2 → NaHCO3
The aqueous filtrate containing low dissolved solids is now amenable to biological treatment. Thus, the method is remarkable that it meets the requirements of purity, cost reduction by recovery of alkali value and environmental safety.
Following examples represent the preferred embodiments of the invention, however the described conditions are given by way of examples only and are non-limiting.
Examples
Example 1
Oxidation :
1500 ml of An aqueous solution containing 0.9 g moles of 4-hydroxy-3-methoxy mandelic acid, prepared by condensation of excess sodium guaiacolate and sodium glyoxylate at pH 10.5 from which unreacted guaiacol was extracted and removed, is taken in an autoclave. 2.6 moles NaOH flakes and 150 mg cobalt acetate are added to the mass. The mass is heated to 90°C under 3 kg/cm,2 pressure of air passing with continuous venting of unreacted air. A total oxygen of 2.25 moles per substrate is passed over 4 hours.
When the oxidation is completed, pressure is reduced to atmospheric and 400 ml water is distilled out from the mass. The mass is now slowly cooled to 20°C. The crystallized solids of sodium vanillin is filtered and washed with cold water. The solids are taken with 50 ml water and acidified to pH 5 using 50% H2S04 to ppt vanillin which is filtered. The solids are subjected to distillation under vacuum yielding 110 g vanillin (80% yield) with

purity >99% by HPLC method. This vanillin is subjected to standard crystallization purification from aqueous 30% ethanol giving flavour grade vanillin.
Isolation of NaHCO3 :
The main aqueous filtrate having excess NaOH after isolation of sodium vanillin is taken in the autoclave. CO2 gas is passed into the autoclave upto a pressure of 2 kg/cm2 at 30°C and CO2 passing is continued till there is no more consumption. The mass is now cooled to 10°C and the thick precipitate of NaHCO3 is filtered. The wet cake, equivalent to 225 g NaHCO3 dry solids having 99% purity is used for glyoxylic acid neutralization and for conversion to Na2CO3 by standard Solvay process.
Isolation of Vanillin from filtrate:
The filtrate and wash after isolation of NaHCO3 is acidified using 50% H2SO4 to pH 5. The organics are extracted using toluene solvent. The accumulated toluene layer is concentrated and the residue fractionally distilled to collect vanillin fraction. The pure vanillin fraction, which is 95% purity is subjected to regular crystallization purification to yield an additional 10% overall yield. Thus total yield of vanillin is 90%.
Example 2 :
The procedure in example-1 is repeated with 4-hydroxy-3-ethoxy mandelic acid under the same conditions to result 72% yield of Ethyl Vanillin and further 8% of Ethyl Vanillin isolated from filtrate (total yield 80%).
Dated 07th day of January 2009