AN IMPROVED PROCESS FOR PREPARATION OF PURE ALDOXIME

CROSS-REFERENCE TO RELATED APPLICATIONS AND PRIORITY The present application claims priority from Indian Patent Application number

201921051588 filed on 12 ^th December 2019, incorporated herein by a reference.

FIELD OF INVENTION

The present invention relates to an improved process for preparation of aldoxime of formula (I) with high purity and high yield. The present invention further relates to the process which is fast, simple, highly efficient, and reproducible.

BACKGROUND OF INVENTION

An oxime is a chemical compound belonging to the imines class with the general formula RR'C=NOH, where R is an organic side-chain and R may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime.

The oximes have large scale of application in the field of synthetic organic chemistry. An oxime is an intermediate in the industrial production of caprolactam, a precursor to Nylon 6. Oximes are commonly used as ligands and sequestering agents for metal ions. Oxime compounds are used as antidotes for nerve agents. A nerve agent inactivates acetylcholinesterase by phosphorylation. Oxime compounds can reactivate acetylcholinesterase by attaching to phosphorus, forming an oxime-phosphonate, which then splits away from the acetylcholinesterase molecule. Oxime nerve-agent antidotes are pralidoxime (also known as 2-PAM), obidoxime, methoxime, HI-6, Hl-7, and TMB-4. The effectiveness of the oxime treatment depends on the particular nerve agent used. Due to the nucleophilic character of oximes, they have been widely used for the preparation of a variety of nitrogen-containing compounds such as amides, hydroximinoyl chlorides, nitrones and nitriles. Oximation has attracted intensive attention for several decades as an efficient method for characterization and purification of carbonyl compounds. Oximes were usually prepared by the reaction of carbonyl compounds and hydroxylamine hydrochloride with adjustment of pH using a basic aqueous medium.

The description of W02008023248 discloses the process of preparing pyridine-2- carbaldehyde oxime from 2-pyridine carboxaldehyde and hydroxylamine hydrochloride using sodium acetate and methanol. The reaction takes place within 2 hours at 20-30°C.

The reaction mixture was evaporated under vacuum to provide a crude mass. To the crude mass was stirred with water to effect precipitation and the separate solid was filtered under suction, dried under vacuum to provide pyridine-2-carbaldehyde oxime product in 85% yield. The Japanese patent application JP2016166153 discloses the catalytic transoximation reaction under mild conditions. When the transoximation reaction is carried out in the presence of perchloric acid and / or perchloric acid metal salt, the catalyst and water hydrolyzes the oxime compound ethyl acetohydroxamate, sequentially generates hydroxylamine, and reacts with the aldehyde to produce an aldoxime compound, which can be used under harsh reaction conditions without using expensive catalysts and reagents. A method for producing an aldoxime compound including a step of transoximing an aldehyde compound and an oxime compound in the presence of perchloric acid and / or a perchloric acid metal salt in an organic solvent and water. Although reaction temperature is not specifically limited, 10-40°C is preferable and 20- 30°C is more preferable. Above 40°C, the solvent tends to volatilize. Moreover, although reaction time is not specifically limited, 12 to 72 hours are preferable and 24 to 72 hours are more preferable. If it is less than 12 hours, the reaction tends to be incomplete.

Another PCT application WO 2010093341 discloses process for preparation ofPyridine-

2-carboxaldehyde oxime. To a solution of pyridine-2-carboxaldehyde in ethanol at 0°C, was added water and hydroxylamine hydrochloride. Aqueous sodium hydroxide was added dropwise and the reaction mixture warmed to room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layers were washed with water, dried, filtered and evaporated to yield oxime as a white solid.

The prior art processes for preparing oximes however suffer from inherent drawbacks and inconvenience, such as long reaction time, low production yield, additional reaction steps, usage of number of organic solvents, additional processing steps for purification of crude product, usage of expensive chemicals, catalyst and toxic organic solvents either alone or in combination, necessity of external heating to expedite product formation and cooling of reaction mixture in order to precipitate product, chemical degradation or colour change of product attributed to harsh reaction condition, extraction of product in organic solvent and concentration of product under reduced pressure or by downward distillation method, need of dehydrating agents to obtain moisture free product in low to satisfactory reaction yields. Further, there is requirement of several steps for the purification of final product once the final product is obtained. These additional processes of purification involve several steps such as washing of product with appropriate solvent to get rid from impurities co-precipitated with product, column chromatography, crystallization technique and charcoal treatment to crude product to remove coloured impurities. The purification process, therefore, is lengthy, expensive and increases process time.

Hence, there is a long felt need in field of chemical synthesis for development of a process for preparing the oximes which will overcome the drawbacks of prior art process. The inventors of the present invention, therefore, have come up with an improved process for preparing the aldoxime wherein the said process is simple, with minimum processing steps, provides high yield with maximum purity and without the usage of any organic solvents and/or limited use of co-solvent. The present invention discloses the process of oximation of aldehydes to obtain aldoxime. The present invention eliminates the usage of external heat and long reaction time, by implementing the concept of in-situ heat generation. The in-situ heat generation takes place in presence of strong or weak base and increases the temperature of reaction mixture to more than 70°C and accelerates the process. The product thus obtained is pure, with high yield and obtained in very less time as low as less than 3 hours in comparison with overnight process as disclosed in the prior art. As the present invention minimises the usage of organic solvents and additional co-solvents, there are less impurities in final product. Hence, the present process eliminates the lengthy and expensive processing steps of purification of final yield.

OBJECTIVE OF INVENTION The main object of the present invention is to provide an improved process for the preparation of aldoximes of formula (I), wherein the said process is simple, economical, user- friendly and commercially viable.

Another objective of the present invention is to provide a process for the preparation of aldoxime of formula (I), wherein the process is carried out at room temperature and without any additional organic solvents and/or with limited use of cosolvents.

Yet another objective of the present invention is to provide a process for the preparation of an aldoxime of formula (I) with a high yield and high chemical purity.

Yet another objective of the present invention is to provide a process for the preparation of an aldoxime of formula (I) with a yield of the final product is more than 90 percent. SUMMARY OF THE INVENTION

Present invention provides a simple, highly efficient, economical, industrially viable and reproducible process for preparation of aldoximes provide high yield of pure aldoxime.

In one aspect, the present invention provides an improved process for preparation of aldoxime wherein the said process is carried out at room temperature and without additional organic solvents and/or with limited use of cosolvents. In yet another aspect, the present invention provides the process for preparing aldoxime using inexpensive raw materials merely in aqueous media and generation of in situ heat that expedites the rate of reaction and provides the final product within as less as 3 hours.

In yet another aspect, the present invention provides the process for preparing aldoxime, wherein the said process does not involve use of any catalyst or any aqueous work up, does not require any complex purification process such as column chromatography or recrystallization method, does not require any drying agents such as Na ₂ SC> ₄ , MgCCb, or CaCb and the like in order to dehydrate product and make product moisture free, does not need product concentration with complex process such as downword distillation or under reduced pressure/vacuum distillation.

In yet another aspect, the present invention provides an improved process for the preparation of aldoxime of formula (I), which is synthesized in the higher yield under oximation reaction of aldehyde with hydroxylamine hydrochloride merely in aqueous medium using of in situ heat generation. where, R= H, alkyl, alkyl halide, heterocyclic aromatic ring, substituted or unsubstituted heterocyclic aromatic ring, halide group, mono-, di-, tri-substituted aromatic group, macrocyclic groups including but not limiting to porphyrins and dendrimers.

In yet another aspect, the present invention provides an improved process for the preparation of aldoxime of formula (I) where R= H, alkyl, alkyl halide, heterocyclic aromatic ring, substituted or unsubstituted heterocyclic aromatic ring, halide group, mono-, di-, tri-substituted aromatic group, macrocyclic groups including but not limiting to porphyrins and dendrimers, wherein the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding water soluble strong or weak base in the reaction mixture of step (i); iii) adding suitable aldehyde in above solution; iv) stirring the mixture of step (iii) for less than 3 hours; v) a pure aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.

In yet another aspect, the present invention an improved process for the preparation of pyridine-2-aldoxime of formula (II), wherein the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding water soluble strong or weak base in the reaction mixture of step (i); iii) adding 2-pyridine aldehyde in above solution; iv) stirring the mixture of step (iii) for less than 3 hours; a pure pyridine-2-aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.

In yet another aspect, the present invention an improved process for the preparation of pyridine-3-aldoxime of formula (IV), wherein the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding 3 -pyridine aldehyde in above solution; iii) adding water soluble strong or weak base in the reaction mixture of step (ii); iv) stirring the mixture of step (iii) for less than 3 hours; a pure pyridine-3 -aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.

DETAILED DESCRIPTION OF THE INVENTION

Any terms used herein such as but not limited to “includes,” “comprises,” “has,” “consists,” “contains” and grammatical variants thereof do not specify an exact limitation or restriction and certainly do not exclude the possible addition of one or more features or elements, unless otherwise stated, and furthermore must not be taken to exclude the possible removal of one or more of the listed features and elements, unless otherwise stated with the limiting language “must comprise” or “needs to include.”

The term “some” as used herein is defined as “none, or one, or more than one, or all.” Accordingly, the terms “none,” “one,” “more than one,” “more than one, but not all” or “all” would all fall under the definition of “some.” The term “some embodiments” may refer to no embodiments, to one embodiment, to several embodiments, or to all embodiments. Accordingly, the term “some embodiments” is defined as meaning “no embodiment, or one embodiment, or more than one embodiment, or all embodiments.”

It must also be noted that, the singular forms “a”, “an”, and “the” include plural references unless the context clearly dictated otherwise, although any methods similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present invention, wherein the exemplary methods are described. The disclosed embodiments are merely exemplary of the disclosure, which may be embodied in various forms.

Various modifications to the embodiments may be readily apparent to those skilled in the art and the generic principles herein may be applied to other embodiments. However, one of the ordinary skill in the art may readily recognize that the present invention is not intended to be limited to the embodiments illustrated but is to be accorded the widest scope consistant with the principles and features described herein. Unless otherwise defined, all terms, and especially any technical and/or scientific terms, used herein may be taken to have the same meaning as commonly understood by one having an ordinary skill in the art.

No terminology in this application should be construed as indicating any non-claimed element as essential or critical. The use of any and all examples, or exemplary language provided herein, is intended merely to better illuminate example embodiments and does not pose a limitation on the scope of the claims appended hereto unless otherwise claimed. The terminology and structure employed herein is for describing, teaching and illuminating some embodiments and their specific features and elements and does not limit, restrict or reduce the spirit and scope of the invention.

Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. Where a specific range of values is provided, it is understood that each intervening value, to the tenth of the limit of that range and any other stated or intenvening value in that stated range, is included therein. All smaller sub-ranges are also included.

The present invention discloses an improved process for preparing aldoximes.

In one embodiment, the present invention provides the improved process for preparing aldoxime.

In other embodiment, the present invention provides the improved process for preparing aldoxime from aldehyde, wherein the said process is carried out in presence of water and water-soluble base.

In yet another embodiment, the present invention provides the improved process for preparing an aldoxime, wherein the water-soluble base is selected from but not limiting to the strong or weak bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate and the like.

In yet another embodiment, the present invention provides the improved process for preparing aldoxime from aldehyde, wherein the said aldehyde undergoes oximation reaction in presence of hydroxylamine hydrochloride and water with strong or weak water-soluble base to obtain the pure aldoxime.

In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the aldoxime thus obtained is in the polymorphic crystalline form or amorphous form. In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the aldoxime thus obtained is highly pure and crystalline in nature.

In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the aldoxime thus obtained in the form of E isomer or Z isomer or both. In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the aldoxime thus prepared is selected from group consisting of but not limiting to 2-pyridine aldoxime, 3-pyridine aldoxime, 2-chloro benzaldehyde oxime, anisaldehyde oxime, salicaldehyde oxime, dimethylglyoxime, 2- thiophene aldehyde oxime, 4-chlorobenzaldehyde oxime, 2, 4-dichlorobenzaldehyde oxime, 2, 6-dichlorobenzaldehyde oxime, 2-Nitro benzaldehyde oxime, 4- (dimethylamino) benzaldehyde oxime, 2-hydroxybenzaldehyde oxime, ketoxime, methoxime, 2,3-dimethoxy benzaldehyde oxime, 2-hydroxy 4-diethylamino benzaldehyde oxime, benzaldehyde oxime and the like. In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the said aldoximes having the structures not limiting to follows:

Wherein R= H, alkyl, alkyl halide, heterocyclic aromatic ring, substituted or unsubstituted heterocyclic aromatic ring, halide group, mono-, di-,tri-substituted aromatic group, macrocyclic groups including but not limiting to porphyrins and dendrimers.

In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the said aldoximes having the structures not limiting to follows: Wherein R= H, alkyl, alkyl halide, heterocyclic aromatic ring, substituted or unsubstituted heterocyclic aromatic ring, halide group, mono-, di-, tri-substituted aromatic group, macrocyclic groups including but not limiting to porphyrins and dendrimers, or any other group selected from but not limited to as follows:

In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the aldehyde used for preparing aldoxime is selected from group consisting of but not limiting to 2-pyridine aldehyde, 3 -pyridine aldehyde, 2- chloro benzaldehyde, anisaldehyde, salicaldehyde, 2-thiophene aldehyde, 2-chloro benzaldehyde, 4-chloro benzaldehyde 2,6-dichlorobenzaldehyde, 4- methoxybenzaldehyde, 2,3-dimethoxy benzaldehyde, 4-tolualdehyde, 3-pyridyl carbaldehyde, 4-pyridyl carbaldehyde, 2-salisaldehyde, 2,3-dimethoxy benzaldehyde, 2- hydroxy 4-diethylamine benzaldehyde, benzaldehyde and the like. In yet other embodiment, the present invention provides the improved process for preparing aldoxime, wherein the said process is carried out at room temperature and within very less time of less than 3 hours more specifically, less than 2 hours.

In yet other embodiment, the present invention provides the improved process for preparing aldoxime, wherein the said process is carried out at temperature below 50°C. In yet another embodiment the present invention provides the improved process for preparing aldoxime, wherein the said process implements the concept of in-situ heat generation and does not require any external heating for reaction to take place. In yet another embodiment the present invention provides the improved process for preparing aldoxime, wherein the yield of aldoxime thus obtained is more than 90% of crude aldoxime.

In yet another embodiment the present invention provides the improved process for preparing aldoxime, wherein said pure aldoxime is in the form of powder or crystalline or crystalline powdered form.

In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the said process takes place within the pH range of 8-12, more specifically, within the pH range of 9-11. In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the said process eliminates the lengthy and expensive conventional steps for purification of final product.

In yet another embodiment, the present invention provides an improved process for the preparation of aldoxime of formula (I), where R= H, alkyl, alkyl halide, heterocyclic aromatic ring, substituted or unsubstituted heterocyclic aromatic ring, halide group, mono-, di-, tri- substituted aromatic group macrocyclic groups including but not limiting to porphyrins and dendrimers. wherein the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding water soluble strong or weak base in the reaction mixture of step (i); iii) adding suitable aldehyde in above solution; iv) stirring the mixture of step (iii) for less than 3 hours; v) a pure aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.

In yet another embodiment, the present invention provides an improved process for the preparation of pyridine- 2-aldoxime of formula (II), wherein the said process comprises the steps of: i) preparing a solution of hydroxylaminehydrochloride and water; ii) adding water soluble strong or weak base in the reaction mixture of step (i); iii) adding 2-pyridine aldehyde in above solution; iv) stirring the mixture of step (iii) for less than 3 hours; v) a pure pyridine-2-aldoxime thus obtained is separated from the reaction mixture. wherein the sequence of the above processing steps can be interchangeable in any possible order.

In yet another embodiment, the present invention provides an improved process for the preparation of aldoxime of formula (I), Where R= H, alkyl, alkyl halide, heterocyclic aromatic ring, substituted or unsubstituted heterocyclic aromatic ring, halide group, mono-, di-, tri-substituted aromatic group, macrocyclic groups including but not limiting to porphyrins and dendrimers. wherein the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding suitable aldehyde in above solution; iii)adding water soluble strong or weak base in the reaction mixture of step (ii); iv) stirring the mixture of step (iii) for less than 3 hours; v) a pure aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.

In yet another embodiment, the present invention provides an improved process for the preparation of aldoxime, wherein the sequence of processing steps can be interchangeable in any possible order. In another embodiment, one step or all step may be performed in in-situ manner.

The present invention may be further illustrated by way of following examples and experimental analysis, which should not be construed to limit the scope of the invention in anyway.

Experimental Observations: Example no. 1:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C. To this solution a strong or weak base (selected from group but not limiting to NaHCCb, Na ₂ CC> ₃ , NaOH, NaOAc, KOH) was added in order to keep the temperature below 50°C and pH of the solution below 9.5. To this warm solution was slowly added 3 -pyridine aldehyde by keeping temperature below 83°C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 3- pyridine aldoxime of formula IV.

Example no. 2:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution a strong or weak base (selected from group but not limiting to NaHCCb, NaiCCL, NaOH, NaOAc, KOH)was added in order to keep temperature below 41 °C and PH of the solution 6.6. To this solution was slowly added 3-pyridine aldehyde by keeping temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 3 -pyridine oxime.

Example no. 3:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C. To this solution a strong or weak base (selected from group but not limiting to NaHCCb, NaiCCL, NaOH, NaOAc, KOH) was added in order to keep the temperature below 50°C and pH of the solution below 9.5. To this warm solution was slowly added 2-Chloro benzaldehyde by keeping temperature below 83°C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-

Chloro benzaldehyde oxime of formula III.

Example no. 4: A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution 2-Chloro benzaldehyde was added in order to keep temperature below 20°C. To this solution NaOH was added till product precipitation was observed by keeping temperature below 74°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-Chloro benzaldehyde oxime.

Example no. 5:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution 2-pyridine aldehyde (93.3 mM) was added in order to keep temperature below 20°C. To this solution NaOH was added till product precipitation was observed by keeping temperature below 74°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-pyridine oxime. (Melting point:

110-112°C; Yield: 97.7%)

Example no. 6:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution KOH was added in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added 2-pyridine aldehyde (23 mM) by keeping temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2-pyridine oxime (96.9%). Example no. 7:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C. To this solution NaOH was added in order to keep the temperature below 50°C and pH of the solution below 9.5. To this warm solution was slowly added 4-Chlorobenzaldehyde by keeping temperature below 83°C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within

3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 4- Chlorobenzaldehyde oxime of formula V.

Example no. 8:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of 35% aq. Methanol in order to keep the pH of solution below 2.6 and temperature below 25°C. To this solution was added KOH in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added anisaldehydeby keeping temperature below 53 °C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered anisaldehyde oxime of formula VI.

Example no. 9:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of 35% aq. Methanol in order to keep the pH of solution below 2.6 and temperature of the solution should not exceed above 25°C. To this solution NaOH was added in order to keep temperature below 43°C and pH of the solution 8.9. To this solution was slowly added 2-pyridine aldehyde (23 mM) by keeping temperature below 52°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2-pyridine aldoxime. Example no. 10:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of 35% aq. Methanol in order to keep the pH of solution below 2.6 and temperature below 25°C. To this solution was added KOH in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added 2-pyridine aldehyde (23 mM) by keeping temperature below 53 °C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2-pyridine aldoxime.

Example no. 11:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C. To this solution a strong or weak base (selected from group but not limiting to NaHCC , NaiCC , NaOH, NaOAc, KOH) was added in order to keep the temperature below 50°C and pH of the solution below 9.5. To this warm solution was slowly added 2-pyridine aldehyde (0.23M) by keeping temperature below 83°C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-pyridine aldoxime of formula II. (Melting point: 110-112 °C; yield: 92.6%).

Example no. 12:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution salicaldehyde was added in order to keep temperature below 20°C. To this solution NaOH was added till product precipitation was observed by keeping temperature below 74°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline salicaldehyde oxime of formula VII. Example no. 13:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C. To this solution NaOH was added in order to keep the temperature below 50°C and pH of the solution below 9.5. To this warm solution was slowly added 2,6-dichlorobenzaldehyde by keeping temperature below 83°C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2,6-dichlorobenzaldehyde oxime of formula VIII.

Example no. 14:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution KOH was added in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added 2-thiophene aldehyde by keeping temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2-thiophene aldehyde oxime of formula IX.

Example no. 15:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C. To this solution sodium bicarbonate was added in order to keep the temperature below 50°C and pH of the solution below 9.5. To this warm solution was slowly added 2-pyridine aldehyde (0.23M) by keeping temperature below 83°C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-pyridine oxime of formula II.

Example no. 16: A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution 2-pyridine aldehyde (93.3 mM) was added in order to keep temperature below 20°C. To this solution sodium carbonate was added till product precipitation was observed by keeping temperature below 74°C.

Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-pyridine oxime.

Example no. 17:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution sodium acetate was added in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added 2-pyridine aldehyde (23 mM) by keeping temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2-pyridine oxime.

Example no. 18:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of 35% aq. Methanol in order to keep the pH of solution below 2.6 and temperature of the solution should not exceed above 25°C. To this solution NaOH was added in order to keep temperature below 43°C and pH of the solution 8.9. To this solution was slowly added 2,3-dimethoxy benzaldehyde by keeping temperature below 52°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2,3- dimethoxy benzaldehyde oxime of formula X. Example no. 19:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C. To this solution sodium bicarbonate was added in order to keep the temperature below 50°C and pH of the solution below 9.5. To this warm solution was slowly 2-hydroxy 4-diethylamine benzaldehyde by keeping temperature below 83 °C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC.

Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-hydroxy 4-diethylamino benzaldehyde oxime of formula XI.

Example no. 20: A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution 4-Chlorobenzaldehyde was added in order to keep temperature below 20°C. To this solution sodium carbonate was added till product precipitation was observed by keeping temperature below 74°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours.

Reaction mass was filtered and was dried in oven to obtain crystalline 4- Chlorobenzaldehyde oxime.

Example no. 21:

A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution KOH was added in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added benzaldehyde by keeping temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered benzaldehyde oxime of formula XII.

Analytical evaluation of aldehyde oximes:

Table no. 01: NMR spectral data of 2-Pyridine aldoxime: NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

Table no. 02: NMR spectral data 3-Pyridine aldoxime: NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

Table no. 03: NMR spectral data 2-Chloro benzaldehyde oxime:

NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

Table no. 04: NMR spectral data 4-Chloro benzaldehyde oxime:

NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

Table no. 05: NMR spectral data Anisaldehyde oxime:

NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows: Table no. 06: NMR spectral data Salicaldehyde oxime:

NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows: Table no. 07: NMR spectral data 2,6-Dichlorobenzaldehyde oxime:

NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

Table no. 08: NMR spectral data 2- Thiophene Aldehyde oxime: NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

Table no. 09: NMR spectral data 2,3-dimethoxy benzaldehyde oxime:

NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

Table no. 10: NMR spectral data 2-hydroxy 4-diethylamino benzaldehyde oxime:

NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

Table no. 11: NMR spectral data benzaldehyde oxime:

NMR experiment was carried out on 400 MHz (JEOL) instrument using Chloroform-D as solvent. The proton assignment was as follows:

The embodiments, examples, and alternatives of the preceding paragraphs or the description and drawings, including any of their various aspects or respective individual features, may be taken independently or in any combination. Features described in connection with one embodiment are applicable to all embodiments unless such features are incompatible. While certain present preferred embodiments of the invention have been illustrated and described herein, it is to be understood that the invention is not limited thereto.