TITLE

Process for preparation of 2-hydroxybenzonitrile

FIELD OF INVENTION

The present invention relates to formation of 2-hydroxybenzonitrile by using salicylaldehyde and hydroxylamine, which is high yielding and more economical.

DESCRIPTION OF THE BACKGROUND

2-hydroxybenzonitrile is an important intermediate for the preparation of biologically active substances and its structural formula as;

Oximes and corresponding 2-hydroxybenzonitriles are important organic derivatives of aldehydes and they also play a vital role in pesticides and pharmaceuticals.

Oximes are prepared by the direct reaction of aldehydes with hydroxylamines in a two phase system with the use of any hydrocarbon solvents. However, the reaction times are very long enough to achieve high yields.

The preparation of 2-hydroxybenzonitrile is known in principle. However, only expensive reagents are described as dehydrating agents, which, moreover must further be used in stoichiometric or excess amounts.

US Patent no 5637750 discloses the route of preparing 2-hydroxybenzonitrile using phosgene and salicylaldoxime; however the use of phosgene which is a toxic gas is not easy industrially. The above patent also discloses the preparation of 2-hydroxybenzonitrile using Vilsmeier reagent prepared from dimethylformamide and thionyl chloride in excess, but usage of dimethylformamide and thionyl chloride in very large amounts are not economical. The above patent also discloses usage of sodium acetate in preparation of salicylaldoxime, which is not economical.

The use of thiophosphoric diamide (Bull. Soc. Chim. Belg. 86, 4 (1977)), thionyldiimidazole (Heterocycles 12, 1285 (1979)) and trichloromethyl chloroformate (Tetrahedron Lett. 2203 (1986)) as dehydrating agents is also known for the preparation of 2-hydroxybenzonitrile from 2-hydroxybenzamide.

Indian patent 198768 discloses the process for the preparation of 2-hydroxybenzonitriles by protecting the hydroxyl group of salicylamide by forming the acetyl/benzyl derivative, further dehydrating the resultant hydroxyl protected compound by dehydrating agents like thionyl chloride or phosphorous oxy chloride and cleaving the protected group by hydrolysis using mineral acids like hydrochloric acid, sulphuric acid or catalytically using palladium on Carbon catalyst or platinum on carbon catalyst, and the product is isolated by filtering of the catalyst and distilling the solvent. In the above process the use of palladium industrially is not economical and a low yielding process.

German patent DE2433245 disclosed the preparation of 2-hydroxybenzonitrile by reaction of the amide with phosgene in a non-polar solvent The nitrile is obtained in this reaction in a yield of >90%. Apart from the fact that phosgene must be used here in excess amounts; the use of phosgene in industrial processes is associated with considerable difficulties because of its extreme toxicity.

Another reaction which is known is the catalytic reaction of methyl 2-hydroxybenzoate with ammonia to give 2-hydroxybenzonitrile (Izv. Akad. Nauk. Kaz. SSR, Ser. Khim. 1987 (2), 62). The catalyst used in this case is boron phosphate. A problem in this process is the formation of methylamine from ammonia and methanol which originates from the methyl ester. In addition, 2-hydroxybenzonitrile has the tendency to convert irreversibly at temperatures of >100 degree C, in the liquid phase into a high-melting triazine. That is, the 2-hydroxybenzonitrile which is formed undergoes self condensation at higher temperatures to give triazine. The product yield is therefore poor. Furthermore, this procedure is not suitable as an industrial process, since the reactor clogs within a short time.

All of the methods described supra are only suitable for preparation of dehydrated products on the laboratory scale, since the reagents required are expensive and, furthermore, must be used in stoichiometric or excess amounts.

A need therefore continues to exist for an improved, industrially acceptable method which is simple, high yielding and more economical.

SUMMARY OF THE INVENTION

Accordingly, one object of the present invention is to provide a simple and economical process for preparation of 2-hydroxybenzonitrile in good yields.

Briefly, this object and other objects of the invention as hereinafter will become more readily apparent can be attained in a method of preparing 2-hydroxybenzonitrile by using salicylaldehyde as the starting material.

Another object of the invention is usage of hydroxylamine or its derivatives like hydroxylamine hydrochloride, hydroxylamine sulfate along with the salicylaldehyde as the starting material.

Another objective of the invention is usage of the base can be any alkali metal carbonates, alkali hydroxide such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide and potassium hydroxide.

At another objective of the invention is molar ratio of salicylaldehyde to hydroxylamine to base is 1.0:0.5:0.5 to 1.0:2.0:2.0, preferably in the range of 1.0:0.5:0.5 to 1.0:1.0:1.0 and most preferably in the range of 1.0:0.5:0.5 to 1.0:0.75:0.75.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A more complete appreciation of the invention and many of the advantages thereof will be readily obtained as the same becomes better understood by the detailed description of the preferred embodiment with reference to the examples herein disclosed.

The present invention explains the method of preparing the 2-hydroxybenzonitrile using salicylaldehyde and hydroxylamine in high yielding and more economical.

Salicylaldehyde (2-hydroxybenzaldehyde) is the chemical compound with the
formula C6H4CHO-2-OH. Along with 3-hydroxybenzaldehyde and 4-
hydroxybenzaldehyde, it is one of the three isomers of hydroxybenzaldehyde. This colourless oily liquid has a bitter almond odour at higher concentration and a characteristic buckwheat aroma at lower concentration. Salicylaldehyde was identified as a characteristic aroma component of buckwheat Salicylaldehyde is a key precursor to a variety chelating agents, some of which are commercially important It can be prepared from phenol and chloroform by heating with sodium hydroxide or potassium hydroxide in a Reimer -Tiemann reaction:

Salicylaldehyde is a common highly-functionalized aromatic hydrocarbon that has often been exploited as a precursor to still other chemicals.

Hydroxylamine is an inorganic compound with the formula NH3OH. The pure material is a white, unstable crystalline, hygroscopic compound. However hydroxylamine is almost always provided and used as an aqueous solution. It is used to prepare oximes, an important functional group. It is also an intermediate in biological nitrification. The oxidation of NH3is mediated by the enzyme hydroxylamine oxidoreductase (HAO). NH3OH can be produced via several routes. The main route is via Raschig synthesis.

The present invention explains the use of salicylaldehyde and hydroxylamine or its derivatives like hydroxylamine hydrochloride, hydroxylamine sulfate in molar ratio to produce salicylaldoxime using a base.

The base used here can be any alkali metal carbonates, alkali hydroxide such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide and potassium hydroxide.

Hydroxylamine used in the present invention is in molar ratio, salicylaldehyde to hydroxylamine or its derivates in molar ratios like 1: 0.5 to 1:2, preferably in 1:0.5 to 1.0, and most preferably 1.0: 0.5 to 1.0: 0.7.

The base used in the present invention is used in molar ratio to the hydroxylamine used.

The molar ratio of salicylaldehyde to hydroxylamine to base is 1.0:0.5:0.5 to 1.0:2.0:2.0, preferably in the range of 1.0:0.5:0.5 to 1.0:1.0:1.0 and most preferably in the range of 1.0:0.5:0.5 to 1.0:0.75:0.75.

The present invention provides the preparation of salicylaldoxime at a temperature, i.e. from 0 to 100, preferably from 30 to 100and most preferably 30 to 50C.

The process for producing 2-hydroxybenzonitrile can be done using acid chloride and salicylaldoxime. The acid chlorides are like thionyl chloride, sulfuryl chloride, phosphorous oxychloride, phosgene, diphosgene, triphosgene, and most preferably thionyl chloride and triphosgene.

The solvent used is by the choice where salicylaldoxime is soluble. The solvent must be inert in nature and hydrocarbon and chlorinated solvents such as toluene, xylene, dichloroethane, dichloromethane, chlorobenzene, dichlorobenzene can be used and most preferably toluene and xylene where dehydration can also be done easily.

The following examples illustrate the process for producing 2-hydroxybenzonitrile economically and with high yield.

Example 1:

Into a 1000ml round bottomed 4-neck flask equipped with thermometer and reflux condenser, were charged salicylaldehyde (122gms), water (300gms) and Hydroxylammoniumsulphate (98.4gms) and stirring continued at 35°C. Then Sodium carbonate (63.6gms) solution in 100ml water was added to the reaction mass slowly over a period of 45min. After addition of sodium carbonate solution, stirring was continued for another 4 hrs and sample was analysed on GC for the completion of salicylaldehyde. Then 500gms of Toluene were added to the reaction mass and layers were separated.

The organic phase after dehydration contained 99% pure Salicylaldoxime with a yield of 90%.

Example 2:

The salicylaldoxime (35gms) prepared as per example 1 is charged into 2000 ml round bottomed flask equipped with reflux condenser. Toluene (180gms) and dimethylformamide (lgm) were charged. A caustic scrubber is connected to the outlet of condenser. The reaction mass is cooled to 20°C and thionyl chloride (50% solution in toluene; 60gms) is slowly added over a period of 2 hrs without exceeding 30°C. After completion of addition of thionyl chloride, reaction mass is stirred for another 1 hr at this temperature and slowly raised to 40°C and stirred for another 1 hr, to ensure the completion of reaction.

Toluene is recovered by distillation, followed by controlled addition of water to the reaction mass. Dichloroethane is added to the reaction mass. The layers are separated and dichloroethane is recovered from the organic layer to leave 2-hydroxybenzonitrile crude of purity 96%. The overall yield of 2-hydroxybenzonitrile based on salicylaldehyde is 75%.

Example 3;

The salicylaldoxime (35gms) prepared as per example 1 is charged into 2000 ml round bottomed flask equipped with reflux condenser to which a caustic scrubber is connected, along with toluene (180gms). The reaction mass is stirred at 40°C and triphosgene (30% solution in toluene; 100gms) is slowly added over a period of 2 hrs without exceeding 50°C. After completion of addition of triphosgene, reaction mass is stirred for another 1 hr at this temperature and slowly raised to 60°C and stirred for another 2 hrs. After completion of reaction, isolation of product is done as per example 2. The overall yield of 2-hydroxybenzonitrile based on salicylaldehyde is 78%.

Having now fully described the invention, it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit or scope of the invention as set forth herein.

We claim:

1. The process for preparation of 2-hydroxybenzonitriIe using salicylaldehyde as the starting material by a reaction, comprising;

(a), salicylaldehyde and hydroxylamine or its derivatives in a molar ratio to produce salicylaldoxime using a base.

(b). And further reacting salicylaldoxime with acid chloride to produce hydroxybenzonitrile.

2. The process for preparation of 2-hydroxybenzonitrile as claimed in claim 1(a), wherein hydroxylamine derivatives like hydroxylamine hydrochloride, or hydroxylamine sulfate are used.

3. The process for preparation of 2-hydroxybenzonitrile as claimed in claim 1(a), wherein the base used in the reaction are from any alkali metal hydroxide, alkali metal carbonates or alkali metal hydrogen carbonates.

4. The process for preparation of 2-hydroxybenzonitrile as claimed in claim 1(b), wherein the reacting the substrates is in a two phase system using any solvent and water or using only water.

5. The process for preparation of 2-hydroxybenzonitrile as claimed in claim 4, wherein the solvent used is by the choice where salicylaldoxime is soluble, and inert in nature.

6. The process for preparation of 2-hydroxybenzonitrile as claimed in claim 5, wherein solvents used are like toluene, xylene, dichloroethane, dichloromethane, chlorobenzene, dichlorobenzene and most preferably but not limited to toluene and xylene where dehydration can be done easily.

7. The process for preparation of 2-hydroxybenzonitrile as claimed in claim 1, wherein the operating temperature conditions are between 0 to 100C preferably from 30 to 100 and most preferably but not limited to 30 to 50C.

8. The process for preparation of 2-hydroxybenzonitrile as claimed in claim 1, wherein the molar ratio of salicylaldehyde to hydroxylamine or its derivatives is 1: 0.5 to 1:2, preferably in 1:0.5 to 1.0, and most preferably but not limited to 1.0: 0.5 to 1.0: 0.7.

9. The process for preparation of 2-hydroxybenzonitrile as claimed in claim 1, wherein the molar ratio of salicylaldehyde to hydroxylamine to base is 1.0:0.5:0.5 to 1.0:2.0:2.0, preferably in the range of 1.0:0.5:0.5 to 1.0:1.0:1.0 and most preferably but not limited to in the range of 1.0:0.5:0.5 to 1.0:0.75:0.75.