Claims:We claim:

1) An improved process of preparation of imidacloprid comprising of:

i. Adding alkali base to 2-nitroiminoimidazolidine (NII) in dimethylformamide(DMF) at 10-15°C
ii. Adding a solution of 2-chloro-5-chloromethyl pyridine (CCMP) in dimethylformamide (DMF)to said reaction mixture in 5 to 6 hours wherein,
a. alkali is sodium hydroxide and is 1.1.-1.30 eq.
b. NII is 1.1-1.25 eq.
c. CCMP is 1.0 eq.
d. DMF is 6.0 w/w to 7.0 w/w with respect to CCMP

iii. Allowing said reaction mixture to stir for another 2 hours at the same temperature at 10-15°C and continuously stirring throughout the duration;

iv. Adjusting the said reaction mixture to pH 4.5 to 5.0 by using strong acid and concentrated by vacuum distillation to recover dimethylformamide (DMF) up to 80-90% to form the reaction mass wherein,

Strong acid is 30-35% hydrochloric acid (HCl),preferably 35%

v. Adding solvent 1.30 to 1.35 w/w with respect to CCMP and stirring for 2.0 hrs at 70°C followed by cooling up to 15°C and stirring for 1.0 hrs to obtain crystallized reaction mass. Filtering the said reaction mass and washing with chilled alcohol to obtain crude Imidacloprid; wherein,
a. the ratio of Dimethylformamide: alcoholic solvent in the range of Dimethylformamide (40% to 50%): Alcoholic Solvent(50% to 60%) in reaction mass;

b. solvent selected from alcoholic solvent or ether or ketonic solvent is added once dimethylformamide (DMF) is recovered after the condensation reaction; wherein further:,
c. Alcoholic solvent is ethanol, methanol, propanol or long chain alcohol range from C6 to C12 and specially C6 to C9;
d. Ketonic solvent is either acetone, or methyl-ethyl ketone; and ether is either diethyl ether or petroleum ether;

vi. Charging the crude imidacloprid in water and strength of 8-15% sodium hypochlorite solution preferably, 10% sodium hypochlorite solution and stirring for 1 hour at 60-70°C preferably at 65°C and adjusting the pH ~4.0-5.0 by strong acid solution wherein,
a. strong acid is 30-35% hydrochloric acid (HCl), preferably 35%

vii. Stirring said reaction mass further for 4.0 hrs at 60-70°C preferably 65-70°C, followed by filtering at 60-70°C preferably at 65°C and washing with hot water followed by drying under vacuum to obtain pure imidacloprid.

2) A process as claimed in claim 1 wherein, alcoholic solvent is ethanol, methanol, propanol and long chain alcohol range from C6 to C12 and specially C6 to C9.

3) A process as claimed in claim 1 wherein, dimethylformamide (DMF) is recovered upto 80-90% to form an reaction mass.

4) A process as claimed in claim1 wherein, the purity of imidacloprid obtained is 98-99.5% and dimer impurity is less than 1%.

Dated this 12thday of July, 2016.

__________________________
GOPI J. TRIVEDI(Ms.)
(Authorized Patent Agent of the Applicant)

To,
The Controller of Patents,
The Patent Office,
Mumbai.
, Description:FORM – 2

THE PATENTS ACT, 1970
(39 of 1970)

COMPLETE SPECIFICATION
(See section 10; rule 13)

“AN IMPROVED PROCESS FOR THE PREPARATION OF IMIDACLOPRID"

Meghmani Organics Ltd.
An Indian Enterprise
A Company Incorporated under the Indian Companies Act,
Meghmani House, Shreenivas Society,
Paldi, Ahmedabad-380007
Gujarat State, INDIA

The following specification particularly describes the nature of this invention and manner in which it is to be performed:-

FIELD OF INVENTION

The present invention relates to an improved process for the preparation of imidacloprid.More particularly,the present invention relates to an improved process for the preparation of imidacloprid which has significantly reduces impurities including dimer impurities in an efficient and economical manner.

BACKGROUND
Imidacloprid (1[(6-chloro-3-pyridinyl) methyl]-N-nitro-2-imidazolidinimine) is a systemic neurotoxic insecticide, which belongs to the class of neo-nicotinoid pesticides. It was first disclosed in US patent No. 4,742,060. It has the following formula:

(C9H10ClN5O2)
Imidacloprid mimics nicotine and is used for the control of sucking insects such as termites, fleas, aphids, white flies, termites, turf insects, soil insects and some beetles. It is mainly used as pest control insecticide for agricultural purpose such as on cotton and vegetable crops, for seed treatments, indoor and outdoor insect control and pet products. Thus, it is an important pesticide which has a wide commercial application.

The Imidacloprid is formed by compensating a pyridyl compound with a heterocyclic diamine compound in the presence of an alkali base and aprotic solvent. Most commonly, imidacloprid is prepared by condensing2-chloro-5-chloromethyl pyridine (CCMP) with 2-nitroimino imidazolidine (NII)in the presence of alkali base and aprotic solvent as shown below. The solvent is generally recovered after the completion of process.

CCMP NII IMIDACLOPRID DIMER

However, during the preparation of imidacloprid many impurities including dimer impurities (3-8%) are also formed which are not easily removable.Such impurities reduce the purity of imidacloprid and also interfere with the functioning of imidacloprid thereby reducing its efficacy. For commercial purpose, the purity of imidacloprid should be atleast 95%. Various processes include certain process steps to reduce such impurities from imidacloprid.
PRIOR ART
US. Pat. Nos. 4,742,060 and 6,465,492 disclose that the most widely used compound is imidacloprid, a neonicotinoids insecticide. These compounds are synthesized by condensing a pyridyl compound with a heterocyclic diamine compound in the presence of an alkali base in an aprotic solvent. The alkaline base is either sodium hydride (NaH) or an alkali carbonate.When alkali carbonate is used in the aforementioned condensation reaction, a relatively large amount of dimer impurities is generated. Hence, NaH is preferred over alkali carbonate for this single-sided condensation reaction. However, NaH is difficult to handle as it has a tendency to catch fire when it comes in contact with air. Also, transportation and safety concerns related to use of sodium hydride makes it an expensive and difficult process to use for commercial purpose.
US Pat. No. 6,307,053 discloses a process for preparing imidacloprid wherein a stoichiometric amount of 2-chloro-5-chloromethyl pyridine is gradually added into a mixture of a corresponding stoichiometric amount of 2-nitroiminoimidazolidine and the aprotic solvent (acetonitrile) in the presence of an alkali carbonate (potassium carbonate) under reflux condition to form imidacloprid. However,as mentioned in the above prior art there is generation of large amount of dimer impurity due to whichthe purity of imidacloprid obtained is less than 95% and yield is also low. Also, excess amount of alkali base and aprotic solvent is required during the process which is not commercially viable. Thus, this renders it difficult to use this process to obtain desired imidacloprid in an cost-effective manner for commercial purpose.
Chinese Pat. No. CN101921261B discloses a synthetic process of separation and recovery of imidacloprid which comprises of reacting 2-nitroiminoimidazolidine (NII) in aproticsolvent (dimethyl formamide), sodium hydroxide (NaOH) and chloro-5-chloromethyl pyridine (CCMP), initial distillation of the reaction solution after the condensation reaction after the dimethylformamide extraction to obtain imidacloprid. However, reactant NII is used in excess in the reaction mixture and is then finally separated from the mass. This not only increases the number of extraction steps to separate NII and imidacloprid but also consumes lot of energy which invariably increases the operation cost. Also, it does not remove the impurities effectively. Thus, this makes it undesirable to use the process for commercial application.
Indian Patent no.181755 describes a process for the preparation of imidacloprid by the nitration of 1-(2-Chloro-5-pyridylmethyl)-2-iminoimidazolidine hydrobromide. However, in this process the consumption of intermediates is higher than required. Also the reactionconditions are longer which along with use of excess reactants is not commercially viable. Also, filtrationof imidacloprid is a major issue during commercial process which further increases the cost. Also, it fails to remove dimer impurity and thus obtain highly pure imidacloprid.

Thus, existing processes fail to provide imidacloprid with high purity and high yield. Hence, there is an unmet need to develop a process for preparation of imidacloprid which significantly reduces impurities including dimer impurities from imidacloprid in an simple yet efficient and cost-effective manner.

OBJECT OF THE INVENTION
The main object of the invention is to provide an improved process for preparation of imidacloprid which significantly reduces impurities including dimer impurities.
Another object of the invention is to provide an improved process for preparation of imidacloprid which gives highly pure imidacloprid.
Another object of the invention is to provide an improved process for preparation of imidacloprid which gives high yield of imidacloprid.
Another object of the invention is to provide an improved process for preparation of imidacloprid which is efficient.
Yet another object of the invention is to provide an improved process for preparation of imidacloprid which is economical.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is an improved process for preparation of imidacloprid which significantly reduces impurities including dimer impurities from imidacloprid in an efficient and economical manner to obtain high purityand high yield of imidacloprid.
The present invention is an improved process for preparation of imidacloprid which comprises of condensing 2-chloro-5-chloromethyl pyridine (CCMP) with 2-nitroimino imidazolidine (NII) in the presence of alkali base and aprotic solvent, specifically dimethylformamide(DMF). The process is as follows:

1) Adding alkali base to 2-nitroiminoimidazolidine (NII) in dimethylformamide(DMF) at 10-15°C wherein,
Alkali is sodium hydroxide and is 1.1.-1.30 eq.
2) Adding a solution of 2-chloro-5-chloromethyl pyridine (CCMP) in dimethylformamide (DMF)to said reaction mixture in 5 to 6 hours wherein,
NII is 1.1-1.25 eq.
CCMP is 1.0 eq.
DMF is 6.0 w/w to 7.0 w/w with respect to CCMP
3) Allowing said reaction mixture to stir for another 2 hours at the same temperature at 10-15°C and continuously stirring throughout the duration.
4) Adjusting the said reaction mixture to pH 4.5 to 5.0 by using strong acid and concentrated by vacuum distillation to recover dimethylformamide (DMF) upto 80-90% to form the reaction mass wherein,
strong acid is 30-35% hydrochloric acid (HCl) , preferably 35% HCl.

5) Adding solvent 1.30 to 1.35 w/w with respect to CCMP and stirring for 2.0 hrs at 70°C followed by cooling upto 15°C and stirring for 1.0 hrs to obtain crystallized reaction mass. Filtering the said reaction mass and washing with chilled alcohol to obtain crude Imidacloprid. The obtained imidacloprid has reduced impurities including dimer impurity less than 1.0%; wherein,

the ratio of Dimethylformamide: alcoholic solvent in the range of Dimethylformamide (40% to 50%): Alcoholic Solvent(50% to 60%) in reaction mass;

Solvent selected from alcoholic solvent or ether or ketonic solvent is added once dimethylformamide (DMF) is recovered after the condensation reaction; wherein further:,
Alcoholic solvent is ethanol, methanol, propanol or long chain alcohol range from C6 to C12 and specially C6 to C9;
Ketonic solvent is either acetone, or methyl-ethyl ketone; and ether is either diethyl ether or petroleum ether;

6) Charging the crude imidacloprid in water and 8-15% strength of sodium hypochlorite solution, preferably 10% sodium hypochlorite solution and stirring for 1 hour at 60-70°C preferably at 65°C and adjusting the pH ~4.0-5.0 by strong acid solution wherein,
strong acid is 30-35% hydrochloric acid (HCl) preferably 35% HCl

7) Stirring said reaction mass further for 4.0 hrs at 60-70°C preferably 65-70°C, followed by filtering at 60-70°C preferably at 65°C and washing with hot water followed by drying under vacuum to obtain pure imidacloprid.

The imidacloprid thus obtained from the above process is 98-99.5% pure with the yield of 90-115gm.
The following experiments were conducted while establishing the efficiency of removal of dimer impurities using the above mentioned process:
Following experimental example are illustrative of the invention but not limit of the scope there of:

Example:01
Adding sodium hydroxide (31.01 g.) to 2-nitroiminoimidazolidine (NII) (100 g.) in dimethyl-formamide (DMF)(608 ml). Bringing the temperature of the reaction mixture to 8 to 12°C in a water bath. Adding a solution of 2-chloro-5-chloromethyl pyridine (CCMP) (100 g,) in dimethylformamide (70 ml) to the reaction mixture in 5-6 hours. Further, cooking the reaction mixture for another 2.0 hours at the same temperature while stirring the reaction mixture throughout. On completion, adjusting the reaction mixture the pH ~4.5 to 5.0 by 35% HCl solution and concentrating by vacuum distillation up to 85% recovery of charged DMF. Adding methanol (130 g.) to concentrated mass and stirring for 2.0 hrs at 70°C followed by cooling upto 15°C and stirring for 1.0 hrs. Filtering the mass and washing with chilled methanol (30 ml) to get crude Imidacloprid (wet weight-170.0 g, Dimer impurity-0.68%).

Charging crude imidacloprid in 300 g. of water and 6.0 g. of 10% sodium hypochlorite solution, stirring for 1.0 hr. at 65°C then adjust the pH ~4.0-5.0 by 35%HCl solution. Stirring the mass further for 4.0 hrs. at 65-70°C, filtered at 65°C and washing with 125 g hot water. Drying the product under vacuum to obtain purified imidacloprid.

Out-Put- 112.0 g. (Purity-98.22%, AI-96.87%, Dimer impurity-0.60%& NII-0.59%)

Example: 02
Adding sodium hydroxide (31.01 g.) to 2-nitroiminoimidazolidine (100 g) in dimethyl-formamide (608 ml). Bringing the temperature of the reaction mixture to 10 to 15°C in a water bath. Adding a solution of 2-chloro-5-chloromethyl pyridine (100 g.) in dimethylformamide (70 ml) to the reaction mixture in 5-6 hours. Further, cooking the reaction mixture for another 2.0 hours at the same temperature while stirring the reaction mixture throughout. On completion, adjusting the reaction mixture to pH ~4.5 to 5.0 by 35% HCl solution and concentrating by vacuum distillation up to 80% recovery of charged DMF. Methanol (130 g.) was added to concentrated mass and stirring for 2.0 hrs at 70°C followed by cooling upto 15°C and stirring for 1.0 hrs. Filtering the mass and washing with chilled methanol (30 ml) to get crude Imidacloprid (170.0g, Dimer impurity-0.13%).

Charging crude imidacloprid in 300 g. of water and 6.0 g. of 10% sodium hypochlorite solution, stirring for 1.0 hr. at 65°C then adjusting the pH ~4.0-5.0 by 35%HCl solution. Stirring the mass for 4.0 hrs to 65-70°C, filtering at 65°C and washing with 125 g hot water. Drying the product under vacuum to obtain pure Imidacloprid.
Out-Put- 106.0 g. (Purity-99.54%, AI-98.21%, Dimer impurity-0.14%& NII-0.29%)

Example: 03
Adding sodium hydroxide (31.01 g.) to 2-nitroiminoimidazolidine (100 g.) in dimethyl-formamide (608 ml). Bringing the temperature of the reaction mixture to10 to 15°C in a water bath. Adding a solution of 2-chloro-5-chloromethyl pyridine (100 g,) in dimethylformamide (70 ml) to the reaction mixture in 5-6 hours. Cooking the reaction mixture another 2.0 hours at the same temperature while stirring the reaction mixture throughout. On completion, adjusting the reaction mixture to the pH ~4.5 to 5.0 by 35% HCl solution and concentrating by vacuum distillation up to 90% recovery of charged DMF. Adding ethanol (130 g.) to concentrated mass and stirring for 2.0 hrs at 70°C followed by cooling upto 15°C and stirring for 1.0 hrs. Filtering the mass and washing with chilled Ethanol (30 ml) to get crude Imidacloprid (175 g, Dimer impurity-2.81%).

Charging crude imidacloprid in 300 g. of water and 6.0 g. of 10% sodium hypochlorite solution, stirring for 1.0 hr. at 65°C then adjusting the pH ~4.0-5.0 by 35%HCl solution. Further, stirring the mass for 4.0 hrs to 65-70°C, filtering at 65°C and washing with 125 g hot water. Drying the product under vacuum to obtain pure Imidacloprid.
Out-Put- 118.0 g. (Purity-96.50%, AI-94.35%, Dimer impurity-2.84% & NII-0.24%)

Example: 04
Adding sodium hydroxide (31.01 g.) to 2-nitroiminoimidazolidine (100 g.) in dimethyl-formamide (608 ml). Bringing the temperature of the reaction mixture to10 to 15°C in a water bath. Adding a solution of 2-chloro-5-chloromethyl pyridine (100 g,) in dimethylformamide (70 ml) to the reaction mixture in 5-6 hours. Cooking the reaction mixture another 2.0 hours at the same temperature while stirring the reaction mixture throughout. On completion, adjusting the reaction mixture to the pH ~4.5 to 5.0 by 35% HCl solution and concentrating by vacuum distillation up to 85% recovery of charged DMF. Adding ethanol (130 g.) to concentrated mass and stirring for 2.0 hrs at 70°C followed by cooling upto 15°C and stirring for 1.0 hrs. Filtering the mass and washing with chilled Ethanol (30 ml) to get crude Imidacloprid (132 g, Dimer impurity-0.66%).

Charging crude imidacloprid in 300 g. of water and 6.0 g. of 10% sodium hypochlorite solution, stirring for 1.0 hr. at 65°C then adjusting the pH ~4.0-5.0 by 35%HCl solution. Further, stirring the mass for 4.0 hrs to 65-70°C, filtering at 65°C and washing with 125 g hot water. Drying the product under vacuum to obtain pure Imidacloprid.
Out-Put-96.0 g. (Purity-98.35%, AI-96.76%, Dimer impurity-0.68%& NII-0.61%)

Example: 05
Adding sodium hydroxide (31.01 g.) to 2-nitroiminoimidazolidine (100 g.) in dimethyl-formamide (608 ml). Bringing the temperature of the reaction mixture to 10 to 15°C in a water bath. Adding a solution of 2-chloro-5-chloromethyl pyridine (100 g,) in dimethylformamide (70 ml) to the reaction mixture in 5-6 hours. Cooking the reaction mixture for another 2.0 hours at the same temperature while stirring the reaction mixture throughout. On completion, adjusting the reaction mixture to the pH ~4.5 to 5.0 by 35% HCl solution and concentrating by vacuum distillation up to 85% recovery of charged DMF. Adding 2-Propanol (130 g.) to concentrated mass and stirring for 2.0 hrs at 70°C followed by cooling up to 15°C and stirring for 1.0 hrs. Filtering the mass and washing with chilled 2-Propanol (30 ml) to get crude Imidacloprid (96 g, Dimer impurity-1.00%).

Charging the Crude Imidacloprid in 300 g. of water and 6.0 g. of 10% sodium hypochlorite solution, stirring for 1.0 hr. at 65°C then adjusting the pH ~4.0-5.0 by 35% HCl solution. Further, stirring the mass for 4.0 hrs to 65-70°C, filtered at 65°C and washing with 125 g hot water. Drying the product under vacuum to obtain pure Imidacloprid.

Out-Put-90.0 g. (Purity-98.38%, AI-96.26%, Dimer Impurity-1.35%& NII-0.29%)

The following experiments were conducted while establishing the efficiency of removal of dimer impurities using the above mentioned process:
Raw Material Experiment No. 1 Experiment No.2 Experiment No.3
CCMP (gm) 100 100 100
NII (gm) 100 100 100
DMF (gm) 644 644 644
In-Process-% HPLC Imidacloprid 68.9 68.4 68.2
NII 24.03 24.04 24.52
Dimer 5.27 5.94 5.65
% DMF Recovery 85 80 90
Methanol Charged (gm) 130 130 130
Crude
Analysis-%HPLC Imidacloprid 80.04 81.56 76.68
NII 18.85 18.25 20.13
Dimer 0.68 0.13 2.81
Pure Imidacloprid %HPLC
(Water purified) Imidacloprid 98.22 99.54 96.9
NII 0.59 0.29 0.24
Dimer 0.60 0.14 2.84
Table 1.Experimental study by using Dimethylformamide + Methanol

The above table shows the efficiency in removing the dimer impurities by using said process. As seen in the table, initially the purity of imidacloprid obtained by the existing reaction i.e. by condensing 2-chloro-5-chloromethyl pyridine (CCMP) with 2-nitroimino imidazolidine (NII) in the presence of alkali base and aprotic solvent is very low and the dimer impurities are also higher. However, referring to experiment number 1 and 2, it can be seen that with the use said process wherein, said aprotic solvent i.e. dimethylformamide is not recovered completely but in the range upto 80 - 85% helps to remove the dimer impurities from the reaction mass.Also, it can be seen that dimer is not soluble in methanol alone but is soluble in combination of dimethylformamide and methanol.Also,the ratio of Dimethylformamide: alcoholic solvent in the range of Dimethylformamide(40% to 50%): Alcoholic Solvent (50% to 60%) in reaction mass removes dimer impurity completely from imidacloprid.The solubility of dimer impurity is increased by using with above specific ratio of solvent mixture and also minimizes the loss of imidacloprid obtained after the process.

In comparison, referring to experiment number 3 it can be seen that if quantity of dimethylformamide recovered from reaction mass is 90% or more, the higher amount of dimer remains in final imidacloprid.It was thus obtained that it is crucial to not to completely recover aprotic solvent (dimethylformamide) from the reaction mixture, but to recover dimethylformamide in a range of 80-90%.
The above experiments thus shows that said process for preparation and purification of imidacloprid can effectively remove dimer impurities from the imidacloprid with a purity of 98-99.5%.
From the above examples it can be seen that the present invention is an improved process for preparation of imidacloprid which significantly reduce impurities including dimer impurities upto less than 1% in an simple, efficient and economical process.
Having described what is considered the best form presently contemplated for embodying the present invention, various alterations, modifications, and/or alternative applications of the invention will be promptly apparent to those skilled in the art. Therefore, it is to be understood that the present invention is not limited to the practical aspects of the actual preferred embodiments hereby described and that any such modifications and variations must be considered as being within the spirit and the scope of the invention, as described in the above description.