DESC:FIELD OF THE INVENTION

The present invention relates to a process of synthetically preparing pheromones. More particularly, it relates to preparing a pheromone 4-methyl-5-nonanone.

BACKGROUND OF THE INVENTION

Rhynchophorus ferrugineus O. (Curculionidae: Coleoptera), commonly known as the red palm weevil is the most economically harmful pest of coconut, oil palm, date palm and ornamental trees throughout the Middle East, South and South-East Asia, North Africa and South Europe where plays a principal role in the farming production and human diet.
The invasive red palm weevil is widely distributed in all continents and has been reported on 24 palm species belongs to 16 different genera. The larval stages of this insect feed within the trunk of palms and this behaviour frequently kills the tree. Because of the concealed nature of the larvae, effective methods for the management of the red and other palm weevils have been difficult to develop.
Current strategies for management of R. ferrugineus infestations involve monthly surveys of all palms in infested regions. Infested palms are removed and infected parts are sectioned and buried or burned. As a preventative measure all palms in infested areas are sprayed to run off with a variety of insecticides. Environmental pollution and economic costs of continuous insecticide spraying, more environmentally and economically acceptable alternatives are being sought to aid in the management of this pest.
Current methods recommended for the management of R. ferrugineus have focused on integrated pest management (IPM) involving surveillance, pheromone lures, cuttural control and chemical treatments. Aggregation pheromones have been reported as effective tools for monitoring and trapping Red Palm Weevil (RPW) in the field because it has more promising effect than the sex pheromone, both males and females are attracted, which is beneficial to the farming community. The male produced aggregation pheromone to be a mixture of 4-methyl-5-nonanol (ferrugineol) and 4-methyl-5-nonanone (ferrugineone) and attracts both male and female pests.
In order to make this compound widely available for use in insect control, economic large scale synthetic conversion processes are required. The presently known synthetic routes for the preparation of 4-methyl-5-nonanol and 4-methyl-5-nonanone have been facing the hurdle of requirement of multiple reaction steps and consequent low overall product yield.
Therefore, it is required to have an economical method for the preparation of sex pheromones 4-methyl-5-nonanol and 4-methyl-5-nonanone, which involves the synthesis of the said compounds in a relatively mild conditions with high yield while using readily available, inexpensive starting materials and also avoiding multiplicity of steps.

SUMMARY OF THE INVENTION

The present disclosure provides a process for preparation of 4-methyl-5-nonanone.

In an embodiment of the present invention, the process for preparation of 4-methyl-5-nonanone includes following steps: (a) reacting grignard reagent with 2-methylpentanal in presence of first set of organic solvent(s) to prepare 4-methyl-5-nonanol, wherein the first set of organic solvent(s) are selected from a group consisting of diethyl ether and tetrahydrofuran, wherein the said reaction is carried out at a temperature ranging between 10°C to 20°C, more preferably between 10°C to 15°C, and for a duration of 2 to 4 hours, more preferably 2 to 3 hours; and (b) reacting the 4-methyl-5-nonanol with oxidizing agent(s) in presence of second set of organic solvent(s), to form 4-methyl-5-nonanone, wherein the reaction is carried out at a temperature ranging between 10°C to 20°C, preferably between 15°C to 20°C, and for a duration of 1 to 5 hours, preferably 1 to 2 hours.

DETAILED DISCUSSION OF THE INVENTION

Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular. Generally, nomenclatures used in connection with techniques of chemistry described herein are those well-known and commonly used in the art. In case of conflict, the present specification, including definitions, will control. The materials, methods, and examples are illustrative only and not intended to be limiting.

It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.

The term “comprising” as used herein is synonymous with “including” or “containing,” and is inclusive or open-ended and does not exclude additional, unrecited members, elements or process steps.

The present invention discloses a process for 4-methyl-5-nonanone which is one of sex pheromone naturally secreting by Rhynchophorus ferrugineus F. The same could be used individually or in combination with other pheromones as a lure for attracting the insects in the insect traps for catching insects of the aforementioned specie. The use of pheromones to control insect is an eco-friendly way as compared to the present methods of using chemical pesticides. A relatively mild conditions with high yield while using readily available, inexpensive starting materials and also avoiding multiplicity of steps.

The present invention provides for an easy to implement protocol while using easily available raw materials/ingredients. Therefore, overall cost of the production of 4-methyl-5-nonanone remains under check, at the same time this process also enhances yield significantly thereby bringing down the overall cost of production.

Structure of 4-methyl-5-nonanone
In one of the embodiments of the present invention, the process broadly includes following steps:
(A) preparation of 4-methyl-5-nonanol: reacting grignard reagent, which is prepared in situ with 2-methylpentanal in presence of first set of organic solvent(s); and
(B) preparation of 4-methyl-5-nonanone: reacting the 4-methyl-5-nonanol with suitable oxidizing agent(s) and second set of organic solvent(s).
A. Preparation of 4-methyl-5-nonanol
The process starts with in situ preparation of grignard reagent by the reaction of primary alkyl halides of butane with magnesium metal, which further reacts with 2-methylpentanal in presence of first set of one or more organic solvents. The present step is performed utilizing reagents and techniques known in the art with suitable sources of alkyl halide. The reaction works well if the alkyl halide is primary group, however it is usually poor with secondary alkyl halide. Tertiary alkyl halide cannot form grignard reagent. Presently preferred source of alkyl halide is a primary alkyl halide, where the halide component of the primary alkyl halide can either be chloride or bromide or iodide. The first set of organic solvents are selected from a group consisting of diethyl ether and tetrahydrofuran. The combining of grignard reagent and 2-methylpentanal is carried out at a temperature ranging between 10°C to 20°C, more preferably between 10°C to 15°C. The grignard reagent and 2-methylpentanal are allowed to react during their mixing for a duration of 2 hours to 4 hours, more preferably 2 hours to 3 hours.
Alternatively, instead of preparing the grignard reagent, it can be directly used for the purpose of combining with 2-methylpentanal to produce the 4-methyl-5-nonanol.
B. Preparation of 4-methyl-5-nonanone
The 4-methyl-5-nonanol is reacted with oxidizing agents in the presence of second set of one or more organic solvents, to form 4-methyl-5-nonanone. The one or more oxidizing agents are selected from a group consisting of pyridinium chlorochromate, pyridinium dichromate, manganese dioxide, jone’s reagent, mixture of DMSO and oxalyl chloride, sodium dichromate, potassium dichromate, carbonyl chloride and selenium dioxide. More preferably pyridinium chlorochromate and Jone’s reagent. The one or more organic solvents are selected from a group consisting of chloroform, dichloromethane, diethyl ether, tetrahydrofuran, 1,4-dioxane, acetone, dimethyl sulfoxide and water, more preferably dichloromethane and acetone. The reacting of 4-methyl-5-nonanol with oxidizing agent was carried out at a temperature ranging between 10°C to 20°C. Preferably between 15°C to 20°C. The 4-methyl-5-nonanol with oxidizing agent are allowed to react during their mixing for a duration of 1 hour to 5 hours, preferably 1 hour to 2 hours.

Reaction Scheme

EXAMPLES

The present invention is explained further in the following specific examples which are only by way of illustration and are not to be construed as limiting the scope of the invention.
Example 1: Synthesis of 4-methyl-5-nonanol
A 1 litre multineck flask equipped with a condenser, addition funnel, thermometer, nitrogen inlet and calcium chloride drying tube. 18.2g of magnesium turnings was transferred to the flask using solid funnel and 250ml of THF was added with stirring followed by 0.5g of Iodine was added. 102.6g of n-butyl bromide was dissolved in 200ml of THF and added slowly to the reaction mass through addition funnel, without raising temperature more than 40 °C. After addition completes, the reaction mixture was heated for 1hour at 50 to 55 °C. The reaction mixture was cooled below 15 °C and 50g of 2-methylpentanal in 50ml of THF, was added drop wise during a period of about one hour with the same temperature. The reaction mixture was heated for 1hour at 55 to 60 °C and progress of reaction monitored by Gas Chromatography (GC). The reaction mixture was cooled below 20 °C and saturated ammonium chloride solution was added until clear solution appears. Separated the organic layer and aqueous layer was re-extracted with 200ml of ethyl acetate. The combined organic layer was washed with 2X100ml of saturated sodium chloride solution and dried over anhydrous sodium sulphate. Removal of the organic solvent under vacuum below 40 °C to obtain 84.12g of crude product which is further purified by distillation offered pure 60.4g of 4-methyl-5-nonanol.
Example 2A: Synthesis of 4-Methyl-5-nonanone.
A 1 litre multineck flask equipped with a condenser, addition funnel, thermometer and calcium chloride drying tube. Charged 30g of 4-methyl-5-nonanol, 150ml of acetone and stirred for 10minutes at room temperature (RT). Reaction mixture was cooled to 10 °C and charged Jone’s reagent (prepared by dissolving 30g of chromium trioxide in 56ml of water followed by addition of 25.2ml of con. sulphuric acid under cooling condition) without raising temperature more than 10 °C. The reaction mass was allowed to RT, stirred for 2hours and monitored by GC. The reaction mixture was filtered through celite bed and filtrate was concentrated under vacuum. The crude product was dissolved in 120ml of water and extracted with 2X60ml of hexane. The combined organic layer was washed with 100ml of water, dried over anhydrous sodium sulphate and concentrated under vacuum to obtain 26.87g of crude product which is further purified by distillation offered pure 22.4g of 4-methyl-5-nonanone.
Example 2B: Synthesis of 4-Methyl-5-nonanone
A 1 litre multineck flask equipped with a condenser, addition funnel, thermometer and calcium chloride drying tube. 30g of 4-methyl-5-nonanol, 200ml of dichloromethane and 10g of silica gel was added to the flask. Reaction mixture was cooled to 10 °C and 81.3g of pyridinium chlorochromate was added portion wise without raising more than 10 °C. The reaction was monitored using TLC. The reaction mixture was filtered through celite and filtrate was concentrated under vacuum. The crude product obtained was extracted with 2X60ml of hexane. The combined hexane layer was filtered through celite and washed with 2X50ml water. Separated the hexane layer, dried over anhydrous sodium sulphate and concentrated under vacuum to obtain 24.52g of crude product which is further purified by distillation offered pure 20.14g of 4-methyl-5-nonanone.
Availability of the 4-methyl-5-nonanol and 4-methyl-5-nonanone at cheaper price would motivate and enable people to use 4-methyl-5-nonanol and 4-methyl-5-nonanone for controlling the red palm weevil, which is really effective as well as eco-friendly. In longer run, this could be really bring down the conventional pesticide and subsequently may also result in reduction in pollution of water and soil.
While the invention has been described in detail with reference to preferred embodiments thereof, it will be apparent to one skilled in the art that various changes can be made, and equivalents employed, without departing from the scope of the invention. ,CLAIMS:
1. A process for preparation of 4-methyl-5-nonanone, comprising:

reacting grignard reagent with 2-methylpentanal in presence of first set of one or more organic solvents to prepare 4-methyl-5-nonanol,

wherein the first set of one or more organic solvents are selected from a group consisting of diethyl ether and tetrahydrofuran,

wherein the reaction is carried out at a temperature ranging between 10°C to 20°C, more preferably between 10°C to 15°C, and for a duration of 2 to 4 hours, more preferably 2 to 3 hours; and

reacting the 4-methyl-5-nonanol with one or more oxidizing agents in presence of second set of one or more organic solvents, to form 4-methyl-5-nonanone,

wherein the reaction is carried out at a temperature ranging between 10°C to 20°C, preferably between 15°C to 20°C, and for a duration of 1 to 5 hours, preferably 1 to 2 hours.

2. The process as claimed in claim 1, wherein the one or more oxidizing agents are selected from a group consisting of pyridinium chlorochromate, pyridinium dichromate, manganese dioxide, jone’s reagent, mixture of DMSO and oxalyl chloride, sodium dichromate, potassium dichromate, carbonyl chloride and selenium dioxide.

3. The process as claimed in claim 1, wherein the second set of one or more organic solvents are selected from a group consisting of chloroform, dichloromethane, diethyl ether, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, acetone and water.