Title of Invention

A PROCESS FOR THE MANUFACTURE OF 5-NONYL SALICYLALDOXIME.

Abstract

The invention relates to a process for producing 5-nonyl salicylaldoxime that comprises of converting nonyl phenol to a 5-nonyl aldehyde in a two-step reaction using a novel catalyst mixture, followed by the oximation of the said aldehyde using hydroxylamine sulphate, and that the said catalytic process of aldehyde production is the main invention, in that the effective use of the catalyst mixture helps the reaction proceed at a faster and controlled rate which leads to a higher yield of aldehyde, as a result of complete conversion of all the reactants to the final products.

Full Text

THE PATENT ACT 1970 (39 of 1970) & The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) 1. TITLE OF THE INVENTION A PROCESS FOR THE MANUFACTURE OF 5-NONYL SALICYLALDOXIME. 2. APPLICANT (S) (a) NAME: Star Orechem International (Pvt.) Ltd. (b) NATIONALITY: an Indian Company (c) ADDRESS: F/2, Jagat Plaza, Law College Square, Amravati Road, NAGPUR-440010 3. PREMABLE TO THE DESCRIPTION PROVISIONAL The following specification describes the invention. COMPLETE The following specification particularly describes the invention and the manner in which it is to be performed. The present invention relates to a process for producing 5-nonyl salicylaldoxime. Description of the prior Art Aldehydes and their derivatives are useful in many applications, e.g. in perfumes, pesticides, stabilizing agents and as intermediates in the preparation of numerous compounds of industrial importance, including the oximes which are used in hydrometallurgical extraction processes, especially the aryl aldoxime having long aliphatic chain like nonyl, dodecyl etc. which provides the hydrophobicity to aryl aldoxime and consequently, the efficiency as solvent extraction reagent. Aryl aldoxime or its derivatives are used for the solvent extraction of metals like copper, nickel, zinc, cobalt etc. In the solvent extraction process of copper, low-grade oxide ore is initially treated with dilute sulfuric acid (H2SO4). Copper and other base metals dissolve as sulfates. The solution of metal sulfates is then treated with salicylaldoxime solution in kerosene. Copper selectively reacts with the oxime and is transferred to the organic phase as a chelate. This reaction favorably takes place at high acidity, pH range of 1.5 to 4.5. The organic phase is then treated with a solution of pure copper in sulfuric acid of higher concentration, 25 -35 gpl copper in 160 - 180 gpl sulfuric acid. Pure copper transfers from organic phase to the aqueous phase. The aqueous solution is then subjected to the process of electro winning to produce cathode copper of about 99.99% purity. The organic phase with the aryl aldoxime from which copper has been removed is re-circulated 2 to the extraction stage for treating fresh solution of copper sulfate with impurities. Since the aryl oxime is used for purification and concentration of copper ions selectively, it is desirable that the aryl aldehyde and consequently, the aryl salicylaldoxime, is produced in a pure form free from aryl dialdehydes. Contaminations in aryl salicylaldoxime also cause emulsification or crud formation at the interface during extraction process, resulting in loss of solvents and metal in the raffinate. This emphasizes the need for preparation of pure aryl salicylaldoxime. GB 751845 describes a method for the manufacture of saligenin (o-hydroxybenzyl alcohol), by reacting phenol with formaldehyde at about 70°C, in presence of a basic alkaline earth metal as a condensing agent like calcium oxide and an alcohol like methanol as solvent under substantially anhydrous conditions; the yield of the saligenin is about 50%. US 4150120 disclosed a catalytic process for preparing 2- hydroxy 3-nonylbenzaldehyde from 2-nonylphenol, paraformaldehyde in presence of a catalyst consisting of anhydrous stannous and / or stannic chloride and an aprotic binder like 4-picolline, the yield are about 65%. It is also known from the equivalent patent (GB 1530248) and JCS (Perkin I) 1980 p.1862 et al. that a —CHO group may be selectively introduced into the 2-position relative to the -OH group of a phenol, by reacting formaldehyde with the phenol, in the presence of an amine and anhydrous tin chloride. In the latter 3 reference it is postulated that the tin chloride reacts with phenol to produce a tin phenoxide, which then acts as a catalyst for the introduction of the formyl group into the ring in a position adjacent to the OH group. The amine is believed to be required to absorb the HC1 which is produced during the formation of the phenoxide and lesser or greater quantities of amine than are required for this purpose are shown to have an adverse effect on both yield and selectivity. It is shown that strongly basic amines, which can form stable complexes with tin phenoxide, are less satisfactory for the reaction. Support for the mechanism is found in the reaction of formaldehyde with phenol in the presence of tin phenoxide itself although the yield is only reported as fair. In another article by some of the authors of the above-mentioned article [JCS (Perkin II) 1980 P.407 et al.] it is shown that the dehydrogenation of a 2-hydroxymethylphenol to the 2-formylphenol using a ketone or aldehyde as hydride acceptor and tin phenoxide as catalyst is adversely affected by the presence of amine. Furthermore dehydrogenation does not proceed if the aldehyde is aliphatic. The process considered in the GB 1530248 has a number of disadvantages particularly for operation on a commercial scale. The presence of formaldehyde and HC1 or the amine hydrochloride salt and the by-product methanol in the same reaction mixture is expected to lead to the formation of chloromethyl ethers and methyl chloride, which are carcinogenic. The yield and selectivity of the process 4 also appear to depend upon the use of about 10 mole % of the tin chloride and up to 40 mole % of the amine based upon the phenol which would make commercial operation of the process very expensive and pose serious disposal problems for the effluent. In GB751845, saligenin (hydroxybenzyl alcohol) is produced by reacting phenol with formaldehyde, wherein present invention aldehyde i.e. 5-nonyl salicyladehyde is produced by reacting nonyl phenol magnesium complex and paraformaldehyde. In US4150120 and GB1530248, 2-hydroxy 3-nonylbenzaldehyde is produced using catalyst stannous chloride (Lewis acid) and picolline or amine, while in present invention nonyl salicylaldehyde is produced using stannous chloride and magnesium methoxide. In all above patents the aldehyde is present in the free form leading to the formation of by products and residue to discard in high quantity and yields are about 65%, in present invention aldehyde is present in the metallic complex form and is not available for further reaction to form by products, the metallic complex (nonyl phenol magnesium methoxide complex) also helps aldehyde group to attach at ortho position. Formaldehyde utilization is also improved which a favorable effect on unit has cost of the product. 5 Detail disclosure of the invention According to the present invention there is provided a process for the preparation of a nonyl salicylaldoxime, which comprises the reaction in an anhydrous medium of formaldehyde with nonylphenol magnesium methoxide complex, in the presence of a tin compound. The tin compound is conveniently formed, for example tin chlorides, oxides, hydroxides or nitrates. Tin dichloride (stannous chloride) is an especially preferred as catalyst. The reaction conveniently takes place in the solvent that is to be used for the reaction of the formaldehyde and nonylphenol magnesium methoxide complex. The aryloxy magnesium salt is made from arlyoxy magnesium intermediate. The arlyoxy magnesium intermediate can be prepared by any of the methods known to those skilled in the art. Such methods include , reacting magnesium in the form of its alkoxide, e.g. methoxide ,with a reactant capable of providing the aryloxy group, i.e. a phenolic compound, such as e.g. paranonyl phenol, in the presence of a non-polar solvent, to form paranonyl phenol magnesium methoxide complex, which also absorb the liberated hydrochloride by reaction with tin compound. In the present invention the rate of formation of magnesium methoxide is enhances by introduction of a catalyst, stannous chloride in combination with the another catalyst iodine, already known in the prior art, Journal of Medicinal Chemistry, (1993) 36(6), pp 758-764 and in US 2965663 processes for preparing metal alkyls and alkoxides. By use of this catalyst combination the conversion of methanol to methoxide is preferably in the molar ratio of 1.1:1. Although the slight excess of methanol is maintained in the system to provide fluidity to the reactants, while the presence of toluene leads to the formation of azotrope (methanol: toluene = 69: 31) with excess of methanol- The phenol may be substituted in any or all positions, other than the 2-position, by groups which do not interfere with the course of the present process and which preferably are electron repelling or weakly electron attracting. It has now been found that good selectivity for the formylation of phenols in the 2-position can be achieved in the absence of any carcinogenic by-products by the reaction of formaldehyde with the para nonylphenol magnesium methoxide complex in the presence of a relatively low levels of a tin compound, provided the tin compound is such that, on extraction with water, the aqueous medium has a pH of from 6 to 8. The substantially anhydrous conditions required by the formylation reaction for production of the magnesium bis (2-formyphenoxide) may be conveniently provided by the use of substantially anhydrous reactants together with conventional techniques, for example distillation, for removal of adventitious moisture. It is usually advantageous to perform the reaction in the presence of a substantially anhydrous solvent system. Suitable solvent systems typically comprise an inert non-polar or low polarity organic solvent and/or a polar organic solvent capable of acting as a legend with respect to magnesium atoms. Suitable non-polar liquids are for example benzene, toluene, xylene, mesitylene, cumene, cymene, and chlorinated aromatic hydrocarbons such as monochlorobenzene, and orthodichlorobenzene. Toluene and xylene are especially preferred solvents. Both free gaseous formaldehyde, solutions of formaldehyde in anhydrous solvent and polymeric forms, such as paraformaldehyde and other conventional reagents which release formaldehyde may be used in the present process. Paraformaldehyde is found to be an especially convenient source of formaldehyde. If high conversion of the phenol is required the molar ratio of formaldehyde to phenol should be at least in the range 0.5:1 to 4:1 and is preferably in the range 0.5:1 to 1.7:1, as approximately half moles of formaldehyde being reduced to methanol and other by products. The formylation reaction used to prepare the magnesium bis (2-formaphenoxide) is suitably performed at a reflux temperature within the range from about 65°C to about 90°C , by-products of the reaction, for example methanol, methyl formate and methylal, preferably being removed from the reaction mixture as they are formed. The reflux temperature, in any particular case, will depend upon the constitution of the solvent system and upon the pressure being exerted on the reaction zone. Formylation may be satisfactorily performed at atmospheric pressure. The aldehyde formed is separated from small quantities of dialdehydes and other impurities by the use of Short Path Distillation Unit (SPDU) at 160°C to 240°C under 1mm Hg, more preferably at 170 to 190°C at 0.1mm Hg, to obtain high yield of substantially pure form of 5-nonyl salicylaldehyde. The use of SPDU enables the purification at low temperature, which prevents the degradation of aldehydes, and oximes occurring at high temperature during fractionation at about 180 - 200°C, as practiced by other workers. The process of the present invention is especially suitable for the manufacture of 5-alkylsalicyladoxime. 5-nonylsalicyladoxime may be prepared from 4-nonylphenol derived from phenol and propylene trimmer, and consisting of an isomeric mixture containing straight and branched nonyl groups, by following method. The present invention is a novel method for the manufacture of 5-nonyl salicylaldoxime and is more illustrative by the following examples: Example 1: A 2 liters round bottom 4 necked flask placed in a suitable heating mantle and equipped with stirrer, reflux condenser, thermometer and dropping funnel, is charged with 83g of toluene, 12.6g (0.525 mol) of magnesium powder, 0.06g of iodine and 2.7g of anhydrous stannous chloride. To this under stirring 272g of methanol - toluene azeotrope, obtained from the previous batch, is slowly added. The reaction mixture is heated to reflux (about 64°C) for 60 min to ensure the completion of Mg-methoxide formation. To this 220g (1.0 mol) of nonyl phenol is slowly added and reflux is continued for another hour. To this is added 265g of toluene and the temperature raised to 80°C at which temperature toluene-methanol azeotrope started distilling. This distillation is continued till all the azeotrope distilled over. Further portion of 0.9g of stannous chloride is charged to the above reaction mass and 33g (0.36 mol) of paraformaldehyde powder is added over a period of 30 to 40 min with a screw feeder. Stirring and temperature of 80°C are maintained for another 120min to ensure complete aldehyde formation. The product is cooled to about 50°C, neutralized with 40% sulfuric acid and allowed to settle. The lower aqueous layer is treated separately for recovery of magnesium sulfate and small quantities of magnesium chloride and stannous sulfate. The upper oily layer is washed free of acid and subjected to molecular distillation in short path distillation unit (SPDU) at 190°C and 0.1mm Hg. The low boilers are distilled and recycled while the high boilers are used as boiler fuel. 5-nonyl salicylaldehyde overheads are mixed with 250g of kerosene and subjected to oximation by the known process. 91g of hydroxylamine sulfate in 182g of water is mixed gently with aldehyde overheads for 120min at 60°C, to this 58g of sodium carbonate in 170g of water is added and mixed for 15min. Two layers are allowed to separate; lower layer being aqueous is drained for effluent treatment and recovery of sodium sulfate. The oxime in the upper layer is treated with 20% sulfuric acid, to remove metallic impurities and washed free of acid with demineralised water. The oxime is finally dehydrated in short path distillation unit (SPDU) at 95°C for 240 min at lmm Hg. Product is 95%by GC Example - 2: Repeat the above experiment, with 4.05g and 1.35g of stannous chloride, instead of adding 2.7g and 0.9g. The product is about 90% by GC. The difference in % is due to the formation of more impurities, in comparison to the Example - 1. We claim: 1. A process for the manufacture of 5-nonyl salicylaldoxime, comprising of the following steps: a. preparing an intermediate magnesium methoxide by suspending magnesium powder in toluene and reacting with methanol - toluene azeotrope, the reaction is carried under reflux condition; the reaction is accelerated by the using of a mixture of catalyst containing anhydrous stannous chloride and iodine (SnCU+b); b. treating above magnesium methoxide in the second reactor with nonyl phenol at 64-80° C, to give nonyl phenol magnesium complex; c. adding to the above nonyl phenol magnesium complex anhydrous SnCl2 as catalyst and paraformaldehyde powder using a screw feeder over for 120 min at 80°C, to produce formylated nonyl phenol magnesium complex; d. neutralizing above formylated nonyl phenol magnesium complex in a neutralization reactor; with dilute sulfuric acid for about 80 min at 40°C. 5-nonyl salicyialdehyde in the organic phase is separated and purified in a short path distillation unit (SPDU) at 195°C and 0.1mm He; e. obtaining 5-nonyl salicyialdehyde as an overhead in the short path distillation unit (SPDU) which is free from other low boiling and high boiling impurities; f. Transferring 5-nonyl salicyialdehyde to the oximation reactor, blending with equal amount of kerosene to give fluidity and treating with aqueous solution of hydroxylamine sulfate and aqueous soda ash over a period of I20min at 60 °C, after complete phase separation aqueous phase is drain for effluent treatment; treating organic phase containing oxime with 20% sulfuric acid and washing free of acid with water; g. dehydrating 5-nonyl salicylaldoxime in SPDU, wherein traces of moisture and some quantity of solvent (kerosene) are evaporated, time required is about 240 min at 95 C at 1mm Hg, finally producing 70% 5-nonyl salicylaldoxime + 30% kerosene; h. adjusting strength of 5-nony] salicylaldoxime with modifiers and additional kerosene as per requirement and stored in storage tanks. 2. A process for the manufacture of 5-nonyl salicylaldoxime as claimed is herein described with foregoing description and examples. Dated this 20th day of September 2005. Dr. Rajeshkumar H. Acharya Advocate & Patent Agent For & on behalf of the Applicant.

Documents:

1163-MUM-2005-ABSTRACT(21-9-2005).pdf

1163-MUM-2005-CANCELLED PAGES(18-8-2006).pdf

1163-MUM-2005-CLAIMS(21-9-2005).pdf

1163-mum-2005-claims(granted)-(3-10-2006).pdf

1163-mum-2005-claims.doc

1163-mum-2005-claims.pdf

1163-MUM-2005-CORRESPONDENCE(13-8-2012).pdf

1163-MUM-2005-CORRESPONDENCE(30-12-2005).pdf

1163-MUM-2005-CORRESPONDENCE(IPO)-(14-2-2007).pdf

1163-mum-2005-correspondence-received.pdf

1163-mum-2005-description (complete).pdf

1163-MUM-2005-DESCRIPTION(COMPLETE)-(21-9-2005).pdf

1163-mum-2005-description(granted)-(3-10-2006).pdf

1163-MUM-2005-FORM 1(18-8-2006).pdf

1163-MUM-2005-FORM 16(13-8-2012).pdf

1163-MUM-2005-FORM 2(COMPLETE)-(21-9-2005).pdf

1163-mum-2005-form 2(granted)-(3-10-2006).pdf

1163-MUM-2005-FORM 2(TITLE PAGE)-(21-9-2005).pdf

1163-mum-2005-form 2(title page)-(granted)-(3-10-2006).pdf

1163-mum-2005-form-1.pdf

1163-mum-2005-form-18.pdf

1163-mum-2005-form-2.doc

1163-mum-2005-form-2.pdf

1163-mum-2005-form-26.pdf

1163-mum-2005-form-3.pdf

1163-mum-2005-form-5.pdf

1163-mum-2005-form-9.pdf

1163-MUM-2005-MARKED COPY(18-8-2006).pdf

1163-MUM-2005-REPLY TO FIRST EXAMINATION REPORT(18-8-2006).pdf

1163-MUM-2005-SPECIFICATION(AMENDED)-(18-8-2006).pdf