Claims:We claim:

1) An improved process of preparation of imidacloprid in biphasic condition comprising of:

i. Adding alkali base to 2-nitroiminoimidazolidine (NII) in dimethylformamide(DMF) at 10-15°C to form a reaction mixture wherein,
a. alkali base is sodium hydroxide and is 1.1-1.30 eq.;
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. NII is 1.1-1.25 eq.;
b. CCMP is 1.0 eq. ;
c. 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. Further, adjusting the said reaction mixture to pH 4.5 to 5.0 by using strong acid and completely concentrated by vacuum distillation wherein,
a. strong acid is 30-35% Hydrochloric acid (HCl), preferably 35% or 98% sulphuric acid;
v. Adding water to said reaction mass and stirring for 2.0 hrs at 60-65°C followed by filtration at 60-65°C and washing with hot water to get crude Imidacloprid. The obtained imidacloprid has reduced content of unreacted NII <1 %;
vi. Charging the crude Imidacloprid in ethylene dichloride (1.5 w/w to 2.0 w/w of CCMP), water(1.5 w/w to 2.0 w/w of CCMP) and sodium hypochlorite solution (5 to 10% of CCMP), and stirring for 1.0 hr at 70-75°Cfollowed by layer separation and adjusting of pH of organic layer to 3.5-4.0 by strong acid solution. This reduces dimer impurities from crude imidacloprid and also improves color of imidacloprid;
vii. Stirring said reaction mass further for 1.0 hrs at 70-75°C, followed by cooling to 10-15°C and filtering, washing with chilled ethylene dichloride. It is then dried under vacuum to obtain pure imidacloprid.

2) A process as claimed in claim1 wherein, the purity of imidacloprid obtained is 98-99% and dimer impurity is less than 1%.

Dated this 15thday 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 IN BIPHASIC CONDITION"

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

BACKGROUND AND PRIOR ART
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.
US Pat. No. 7,297,798 discloses a process to form imidacloprid by reacting 2-chloro-5-chloromethyl pyridine (CCMP) with 2-nitroimino imidazolidine (NII) with the molar ratio of 1:1 to 1:12, in the presence of alkali metal hydroxide(sodium hydroxide) in an aprotic solvent(dimethyl formamide) at 45-60ºC under stirring. The yield of imidacloprid is poor and purity is 96.2%. Although the dimethylformamide recovered from the reaction mass is 100%, even then the impurities are not removed completely from the reaction mass. However, additional filtration of reaction mass is required for purification which increases the cost of operation when produced at commercial scale. Thus, the disclosed process is not only expensive but also ineffective in removing the impurities.
Indian Patent Application 698/DEL/2009 describes the process for preparation of imidacloprid which includes reacting 2-nitroiminoimidazolidine (NII) and chloro-5-chloromethyl pyridine (CCMP) in presence of base which is selected from alkali hydroxide and a phase transfer catalyst employing a water immiscible solvent and water as the biphasic solvent system, preferably dichloromethane. However, high volume of solvent is required for the reaction which is not commercially viable. Also, NII is added in two stages with an interval of 12 hrs. This increases the reaction time of the process. The isolation and purification of imidacloprid requires separate process which increases the operation cost. Also, the yield is very low and impurities are not removed effectively from imidacloprid. Thus, this process shows no added advantage of using phase transfer catalyst in bi-phasic condition and is also a time, energy and cost intensive process which makes it difficult and uneconomical process to use for commercial purpose.

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 the 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 in biphasic condition which significantly reduces impurities including dimer impurities.
Another object of the invention is to provide an improved process in biphasic condition for preparation of imidacloprid which gives highly pure imidacloprid.
Another object of the invention is to provide an improved process for preparation of imidacloprid in biphasic condition which gives high yield of imidacloprid.
Another object of the invention is to provide an improved process for preparation of imidacloprid in biphasic condition which is efficient.
Yet another object of the invention is to provide an improved process for preparation of imidacloprid in biphasic condition which is economical.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is an improved process for preparation of imidacloprid in biphasic condition which significantly reduces impurities including dimer impurities from imidacloprid in an efficient and economical manner to obtain high purity and 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) followed by treating crude imidacloprid in biphasic condition. The process is as follows:

1) Adding alkali base to 2-nitroiminoimidazolidine (NII) in dimethylformamide(DMF) at 10-15°C to form a reaction mixture wherein,
alkali base 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) Further, adjusting the said reaction mixture to pH 4.5 to 5.0 by using strong acid and completely concentrated by vacuum distillation wherein,
strong acid is 30-35% Hydrochloric acid (HCl), preferably 35% or 98% sulphuric acid.
5) Adding water to said reaction mass and stirring for 2.0 hrs at 60-65°C followed by filtration at 60-65°C and washing with hot water to get crude Imidacloprid. The obtained imidacloprid has reduced content of unreacted NII <1 %.
6) Charging the crude Imidacloprid in ethylene dichloride (1.5 w/w to 2.0 w/w of CCMP), water(1.5 w/w to 2.0 w/w of CCMP) and sodium hypochlorite solution (5 to 10% of CCMP), and stirring for 1.0 hr at 70-75°Cfollowed by layer separation and adjusting of pH of organic layer to 3.5-4.0 by strong acid solution. This reduces dimer impurities from crude imidacloprid and also improves color of imidacloprid.
7) Stirring said reaction mass further for 1.0 hrs at 70-75°C, followed by cooling to 10-15°C and filtering, washing with chilled ethylene dichloride. It is then dried under vacuum to obtain pure imidacloprid.

The imidacloprid thus obtained from the above process is 98-99% pure with the yield of 120-130gm.

The following experiments were conducted while establishing the efficiency of removal of dimer impurities using the above mentioned process:

Summary of the Experiment:
Example-01
Adding sodium hydroxide (31.01 g.) to 2-nitroiminoimidazolidine (100 g.) in dimethylformamide (608 ml) at 10-15°C. 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. Stirring the reaction mixture throughout. On completion, adjusting the reaction mixture the pH ~4.5 to 5.0 by 35% hydrochloric acid and solvent completely recovered by vacuum distillation. Charging water (300 g.) in to residual mass and stirring for 2.0 hrs. at 60-65°C,filtering the mass at 60-65°C and washing with 125 g hot water and partially drying to get crude Imidacloprid with NII content less than 1.0%.

Charging water (176 g), 1,2-dichloroethane (180g), 10% sodium hypochlorite(6.0 g) into crude Imidacloprid and raising the temperature up to 70-75°C and stirring for 1.0 hrs. Separating the aqueous layer from organic layer at 70-75°C. Adjusting the pH of organic layer to 3.5-4.0 by 35% hydrochloric acid then again stirring for 1.0 hrs. at 70-75°C then cooling to 10-15°C and stirring for 1.0 hrs. Filtering the mass and washing with chilled 1,2-dichloroethane (30 ml) and drying to obtain pure imidacloprid with dimer impurity less than 1.0%
Out-Put-125 g. (Purity-98.75%, AI-96.18%, Dimer impurity-0.80%& NII-0.14%)

Example-02
Adding sodium hydroxide (31.01 g.) to 2-nitroiminoimidazolidine (100 g.) in dimethylformamide (608 ml) at 10-15°C. 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. Stirring the reaction mixture throughout. On completion, adjusting the reaction mixture to the pH ~4.5 to 5.0 by sulphuric acid (98%) and recovering the solvent completely by vacuum distillation. Charging water (300 g.) in to residual mass and stirring for 2.0 hrs. at 60-65°C. Filtering the mass at 60-65°C and washing with 125 g hot water and partially drying to get crude Imidacloprid with NII content less than 1.0%.
Charging water (176 g), 1,2-dichloroethane (180g), 10% sodium hypochlorite(6.0 g) into crude Imidacloprid and raising the temperature up to 75°C and stirring for 2.0 hrs. Separating aqueous layer from organic layer at 70-75°C. Adjusting the pH of organic layer to 3.5-4.0 by sulphuric acid (98%) then again stirring for 4.0 hrs. at 70-75°C then cooling to 15°C and stirring for 1.0 hrs. Filtering the mass and washing with chilled 1,2-dichloroethane (30 ml) and drying to obtain imidacloprid with dimer impurity less than 1.0%
(Out-Put-128 g. (Purity-99.05%, AI-96.76%, Dimer impurity-0.40%& NII-0.10%)

Raw Material Experiment No. 1 Experiment No.2
CCMP (gm) 100 100
NII (gm) 100 100
DMF (gm) 644 644
In-Process-% HPLC Imidacloprid 68.65 67.45
NII 23.42 24.04
Dimer 7.51 7.20
% DMF Recovery 100 100
Water Charged (gm) 300 300
Crude
Analysis-%HPLC Imidacloprid 91.91 92.56
NII 0.50 0.25
Dimer 6.99 6.72
Bi-Phasic condition Water 176 176
EDC 180 180
Hypochlorite 6 6
Pure Imidacloprid %HPLC
(Biphasic purified) Imidacloprid 98.75 99.05
NII 0.14 0.10
Dimer 0.80 0.40
Table no.1 Summary of the experiment
The above table no.1 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 i.e. only 68.65% and 67.45% respectively and the dimer impurities are also higher. Further it can be seen that only when said imidacloprid is treated under biphasic condition in reaction mass dimer impurity is reduced efficiently and is less than 1% in imidacloprid. The solubility of dimer impurity is increased under biphasic condition and also minimizes the loss of imidacloprid obtained after the process with purity of imidacloprid in the range of 98-99%.

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%.
Comparison with existing prior art:
Reported process in Patent no.698/DEL/2009
Patent No / Example No Unit 698/DEL/2009
Example-1
CCMP & MDC gm 100 & 2.0Ltr
NII(Two lot) gm 86 + 18.4
DM Water gm 644
TBAB (Two lot) gm 20 + 5
% MDC Recovery % 100%
MeOH was charged gm 300
Crude Imida
(%NII) % <1
Purification in MeOH gm NA
Table 2. Reactants of the prior art 698/DEL/2009

For bi-phasic reaction, the said prior art used MDC (methylene dichloride) and water in reaction mass along with phase transfer catalyst. It also used high volume of solvent ~ 20 to 25 volumes. Further , 2-nitroiminoimidazolidine was added in two lots with interval of 12 hrs. The yield obtained by this process is very low ~50% (79 gm with respect to in-put CCMP 100 gm).
After completion of reaction the organic layer is separated and recovered to get the residual material. The residual solid is isolated from reaction vessel by slurring with alcoholic solvents under room temperature to reflux temperature.
In comparison, said invention efficiently removes dimer impurities from imidacloprid in biphasic condition. The amount of reactants used as well as their reaction time is also less as compared to the cited prior art thereby making it more economical.

Also, from the above illustrative examples it can be seen that the present invention is an improved process for preparation of imidacloprid in biphasic condition 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.