WO2015071741A1 - A molecular complex of imidacloprid and a process for production thereof - Google Patents
A molecular complex of imidacloprid and a process for production thereof Download PDFInfo
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- WO2015071741A1 WO2015071741A1 PCT/IB2014/002440 IB2014002440W WO2015071741A1 WO 2015071741 A1 WO2015071741 A1 WO 2015071741A1 IB 2014002440 W IB2014002440 W IB 2014002440W WO 2015071741 A1 WO2015071741 A1 WO 2015071741A1
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- Prior art keywords
- imidacloprid
- molecular complex
- phenolic compound
- salicylic acid
- catechol
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
Definitions
- the present disclosure relates to a molecular complex of Imidacloprid and a process for production thereof.
- imidacloprid is a systemic insecticide which acts/serves as an insect neurotoxin. This insecticide is effective for controlling aphids, whiteflies, thrips, scales, psyllids, plant bugs and various other harmful pest species in a variety of different crops.
- Imidacloprid is colorless crystalline solid with a weak characteristic odor and high water solubility.
- imidacloprid goes through a series of cycles of solubilization and re-crystallization leading to the generation of large and undesirable particles. These particles cause problems such as blockage of spray nozzles during application of the product.
- solubilization and recrystallisation it is difficult to maintain imidacloprid products as a homogeneous formulation that leads to issues during transfer to dilution tanks and in ensuring correct concentration of imidacloprid on dilution.
- WO 20101 18833 discloses co-crystal of imidacloprid and oxalic acids as a co- former.
- the molecular complex of imidacloprid disclosed in this document is found to have high water solubility with a higher melting point than pure imidacloprid.
- the present disclosure relates to a molecular complex comprising imidacloprid and a phenolic compound having a formula (II)
- R includes -OH, -COOH, -CI, -Br, -CONH 2 , -CH 3 , alkyl, aryl, allyl, formyl or amine group.
- the present disclosure also relates to a process for preparing a molecular complex of imidacloprid and a phenolic compound, the phenolic compound having a formula (II),
- R includes -OH, -COOH, -CI, -Br, -CONH 2 , -CH 3 , alkyl, aryl, allyl, formyl or amine group.
- the process comprises mixing imidacloprid and the phenolic compound in a 1 : 1 stoichiometric ratio followed by grinding to form a dry mixture; adding a solvent to the dry mixture followed by grinding to obtain a wet mixture; and air drying the wet mixture to obtain the molecular complex.
- Figure I illustrates the IR spectra of Imidacloprid.
- Figure 2 illustrates the IR spectra of Salicylic acid.
- Figure 3 illustrates the IR spectra of a sample of molecular complex of Imidacloprid with salicylic acid.
- Figure 4 illustrates the IR spectra of catechol.
- Figure 5 illustrates the IR spectra of a sample of molecular complex of imidacloprid with catechol.
- Figure 6 illustrates a comparison PXRD profile of a sample of molecular complex of imidacloprid with salicylic acid, ground mixture of imidacloprid and salicylic acid, salicylic acid and imidacloprid melt form.
- Figure 7 illustrates a comparison PXRD profile of a sample of molecular complex of imidacloprid with catechol, catechol and imidacloprid melt form.
- Figure 8 illustrates the comparison DSC profile of a sample of molecular complex of imidacloprid with salicylic acid, imidacloprid melt form and salicylic acid.
- Figure 9 illustrates the comparison DSC profile of a sample of molecular complex of imidacloprid with catechol, imidacloprid melt form and catechol.
- FIG. 10 illustrates the HPLC profile of Imidacloprid
- Figure 11 illustrates the of degradation study profile conducted on imidacloprid, molecular complex of imidacloprid with salicylic acid and molecular complex of imidacloprid with catechol.
- the disclosure relates to molecular complex of imidacloprid with a phenolic compound as a co-former.
- the molecular complex of imidacloprid with the phenolic compound as the co-former is hereinafter referred to as "molecular complex of imidacloprid" for the sake of simplicity.
- Molecular complex herein refers to a substance which is in a solid form or solid formulations, comprising of at least two pure substances which interact with each other through hydrogen bonding or any other non covalent interaction.
- Molecular complex includes co-crystals, solvates, hydrates or eutectic combinations or solid solutions, in which at least one of the pure substance is present in a solid form.
- 'co-former' refers to a pure or substantially pure substance which is not imidacloprid and which, together with imidacloprid in stoichiometric ratio, forms an adduct having one melting point.
- Imidacloprid refers to all polymorphs, solvates, and hydrates of the substance having the formula (I):
- the co-former is a phenolic compound that is a compound having at least one phenolic group that can be represented by the general formula (II)
- R includes -OH, -COOH, -CI, -Br, -CONH 2 , -CH 3 , alkyl, aryl, allyl, formyl or amine group.
- the co-former is catechol.
- the melting point of the molecular complex of imidacloprid with catechol measured as a single melting endotherm by differential scanning calorimetry, is around 99.9 °C.
- the co-former is salicylic acid.
- the melting point of the molecular complex of imidacloprid with salicylic acid measured as a single melting endotherm by differential scanning calorimetry is around 104 °C.
- the stoichiometric ratio of imidacloprid to the phenolic compound in the molecular complex of imidacloprid is 1 : 1.
- the present disclosure also provides a method for producing a molecular complex of imidacloprid.
- the process comprises of admixing imidacloprid and a phenolic compound in a 1 : 1 stoichiometric ratio to form a dry mixture, grinding said dry mixture for a predetermined period of time, adding to the ground dry mixture a solvent to obtain a wet mixture, grinding the wet mixture and air drying the same to obtain the molecular complex of imidacloprid.
- the process comprises of admixing imidacloprid and the phenolic compound in a 1 : 1 stoichiometric ratio to form a dry mixture, grinding said dry mixture for a predetermined period of time, adding to the ground dry mixture a solvent and grinding the same to obtain a wet mixture, heating the wet mixture, transferring the heated wet mixture to a glass vessel and air drying to obtain molecular complex of imidacloprid.
- the heating may be carried out at a temperature around 100°C for 10 minutes.
- the heating may be carried out under nitrogen atmosphere.
- the co-former is a phenolic compound that is a compound having at least one phenolic group that can be represented by the general formula (II).
- the grinding of the dry mixture may be carried out for 10 to 15 minutes.
- the grinding of the wet mixture may be carried out for about 30 minutes.
- the grinding may be carried out in any suitable apparatus for grinding solids. Such apparatus includes but is not limited to mortar mills, vibrator mills or ball mills.
- the solvent is any suitable solvent including but not limited to acetonitrile, ethanol or their mixture.
- the amount of solvent added is in a range of 0.5 ml to 10 ml.
- Imidacloprid and catechol are weighed in 1 : 1 molar ratio and ground using mortar and pestle for around 15 to 20 minutes followed by addition of 0.5 ml acetonitrile/ethanol and further continued to ground for another 30 min and finally air dried to obtain molecular complex of imidacloprid with catechol.
- Imidacloprid and salicylic acid are weighed in 1 : 1 molar ratio and ground using mortar and pestle for around 1 to 20 minutes followed by addition of acetonitrile/ethanol and further continued to ground for another 30 minutes.
- the ground mixture was taken in a glass tube under nitrogen atmosphere and heated to 100 °C for 10 minutes.
- the heated materials transferred in a glass vessel and air dried to obtain free flowing solid of molecular complex of Imidacloprid with salicylic acid.
- FT-IR Fourier transformed infrared spectra
- FT-IR spectra of molecular complexes obtained from examples 1 and 2 were compared with individual compounds and it was found that there are significant changes in IR spectral band of functional group regions to confirm the formation novel molecular complex.
- Molecular complex of imidacloprid with salicylic acid shows a shift of 10 cm "1 in carbonyl spectral region as observed from Table 1. Moreover some shifts in -CH regions also observed in molecular complexes. Table 1.
- Powder X-ray Diffraction (PXRD) profiles were obtained from 5 to 10 mg of lightly ground sample including samples from Example 1 and 2 placed over Zero background silica flat sample stage.
- X-ray diffraction data was collected on a PANalytical "X"pertPRO diffractometer on a Cu source ( a - 1.5418) powered by 40kV and 30mA with a proportional counter radiation detector. Data collection was done with step size 0.020°, 0.50 second per step over 5-70 ° 2 ⁇ . Data was analyzed using Xpert Viewer software.
- PXRD profile data presented for the region where significant peaks were observed. Analysis:
- FIG. 6 illustrates a comparison PXRD profile of a sampled of molecular complex of imidacloprid with salicylic acid, ground mixture of imidacloprid and salicylic acid, salicylic acid and imidacloprid melt form.
- FIG. 7 illustrates a comparison PXRD profile of a sample of molecular complex of imidaclopnd with catechol, catechol and imidaclopnd melt form.
- DSC Differential Scanning Calorimetric
- FIG. 8 illustrates the comparison DSC profile of a sample of molecular complex of imidacloprid with salicylic acid, imidacloprid melt form and salicylic acid.
- Molecular complex of imidacloprid with catechol also shows a lowering of melting point.
- the melting point of the molecular complex of imidacloprid was measured at 100 °C that is lower than that for imidacloprid (melting at 142 °C) and catechol (melting at 105 °C).
- Figure 9 illustrates the comparison DSC profile of a sample of molecular complexes of imidacloprid with catechol, imidacloprid melt form and catechol.
- HPLC High-performance liquid chromatography
- Example 7 Degradation profile study of Imidacloprid and its molecular complexes under UV exposure
- % degradation [(AUC at 0 hour - AUC at 24 hour) / AUC at 0 hr]* 100 Technical Specification of HPLC:
- Figure 11 illustrates the HPLC profile of degradation study conducted on imidacloprid, molecular complex of imidacloprid with salicylic acid and molecular complex of imidacloprid with catechol.
- a molecular complex comprising imidacloprid and a phenolic compound having a formula (II) R includes -OH, -COOH, -CI, -Br, -CONH 2 , -CH 3 , alkyl, aryl, allyl, formyl or amine group.
- Such molecular complex(s), wherein the phenolic compound is salicylic acid is salicylic acid.
- R includes -OH, -COOH, -CI, -Br, -CONH 2 , -CH 3 , alkyl, aryl, allyl, formyl or amine group, the process comprising mixing imidacloprid and the phenolic compound in a 1 : 1 stoichiometric ratio followed by grinding to form a dry mixture; adding a solvent to the dry mixture followed by grinding to obtain a wet mixture; and air drying the wet mixture to obtain the molecular complex.
- the molecular complex of imidacloprid as disclosed has reduced water solubility and better hydrolytic stability as compared to commercially available versions of Imidacloprid.
- the disclosed molecular complex of imidacloprid also has better stability. Being less water soluble than the commercially available imidacloprid, said molecular complex, does not leach readily and provides long duration control of soil insects.
- use of co-formers such as catechol and salicylic acid additionally provide health benefits to the plant and improve plant wellbeing.
Abstract
A molecular complex comprising imidacloprid and a phenolic compound having a formula (II); R includes -OH, -COOH, -CI, -Br, -CONH2, -CH3, alkyl, aryl, allyl, formyl or amine group is disclosed. A process for preparation of said molecular complex is also disclosed.
Description
A MOLECULAR COMPLEX OF IMIDACLOPRID AND A PROCESS FOR
PRODUCTION THEREOF
The present disclosure relates to a molecular complex of Imidacloprid and a process for production thereof.
BACKGROUND
imidacloprid is a systemic insecticide which acts/serves as an insect neurotoxin. This insecticide is effective for controlling aphids, whiteflies, thrips, scales, psyllids, plant bugs and various other harmful pest species in a variety of different crops.
Imidacloprid is colorless crystalline solid with a weak characteristic odor and high water solubility.
Due to its high water solubility imidacloprid rapidly leaches from soil thereby limiting its use for long duration control of soil insects.
Additionally, during storage as water based formulations imidacloprid goes through a series of cycles of solubilization and re-crystallization leading to the generation of large and undesirable particles. These particles cause problems such as blockage of spray nozzles during application of the product. In addition, due to the solubilization and recrystallisation it is difficult to maintain imidacloprid products as a homogeneous formulation that leads to issues during transfer to dilution tanks and in ensuring correct concentration of imidacloprid on dilution.
WO 20101 18833 discloses co-crystal of imidacloprid and oxalic acids as a co- former. The molecular complex of imidacloprid disclosed in this document is found to have high water solubility with a higher melting point than pure imidacloprid.
There is thus a need for a new formulation of Imidacloprid that will overcome the above mentioned problems whilst still retaining its advantageous insecticidal properties. Such a formulation should be stable, have reduced water solubility and better hydrolytic stability.
SUMMARY
The present disclosure relates to a molecular complex comprising imidacloprid and a phenolic compound having a formula (II)
R includes -OH, -COOH, -CI, -Br, -CONH2, -CH3, alkyl, aryl, allyl, formyl or amine group.
The present disclosure also relates to a process for preparing a molecular complex of imidacloprid and a phenolic compound, the phenolic compound having a formula (II),
R includes -OH, -COOH, -CI, -Br, -CONH2, -CH3, alkyl, aryl, allyl, formyl or amine group. The process comprises mixing imidacloprid and the phenolic compound in a 1 : 1 stoichiometric ratio followed by grinding to form a dry mixture; adding a solvent to the dry mixture followed by grinding to obtain a wet mixture; and air drying the wet mixture to obtain the molecular complex.
BRIEF DESCRIPTION OF ACCOMPANYING FIGURES
Figure I illustrates the IR spectra of Imidacloprid.
Figure 2 illustrates the IR spectra of Salicylic acid.
Figure 3 illustrates the IR spectra of a sample of molecular complex of Imidacloprid with salicylic acid.
Figure 4 illustrates the IR spectra of catechol.
Figure 5 illustrates the IR spectra of a sample of molecular complex of imidacloprid with catechol.
Figure 6 illustrates a comparison PXRD profile of a sample of molecular complex of imidacloprid with salicylic acid, ground mixture of imidacloprid and salicylic acid, salicylic acid and imidacloprid melt form.
Figure 7 illustrates a comparison PXRD profile of a sample of molecular complex of imidacloprid with catechol, catechol and imidacloprid melt form.
Figure 8 illustrates the comparison DSC profile of a sample of molecular complex of imidacloprid with salicylic acid, imidacloprid melt form and salicylic acid.
Figure 9 illustrates the comparison DSC profile of a sample of molecular complex of imidacloprid with catechol, imidacloprid melt form and catechol.
Figure 10 illustrates the HPLC profile of Imidacloprid
Figure 11 illustrates the of degradation study profile conducted on imidacloprid, molecular complex of imidacloprid with salicylic acid and molecular complex of imidacloprid with catechol.
DETAILED DESCRIPTION
For the purpose of promoting an understanding of the principles of the invention, reference will now be made to embodiments and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention
is thereby intended, such alterations and further modifications in the disclosed process, and such further applications of the principles of the invention therein being contemplated as would normally occur to one skilled in the art to which the invention relates.
it will be understood by those skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be restrictive thereof.
Reference throughout this specification to "one embodiment" "an embodiment" or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrase "in one embodiment", "in an embodiment" and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.
The disclosure relates to molecular complex of imidacloprid with a phenolic compound as a co-former. The molecular complex of imidacloprid with the phenolic compound as the co-former is hereinafter referred to as "molecular complex of imidacloprid" for the sake of simplicity.
"Molecular complex" herein refers to a substance which is in a solid form or solid formulations, comprising of at least two pure substances which interact with each other through hydrogen bonding or any other non covalent interaction. Molecular complex includes co-crystals, solvates, hydrates or eutectic combinations or solid solutions, in which at least one of the pure substance is present in a solid form.
The term 'co-former' as used herein refers to a pure or substantially pure substance which is not imidacloprid and which, together with imidacloprid in stoichiometric ratio, forms an adduct having one melting point.
Imidacloprid refers to all polymorphs, solvates, and hydrates of the substance having the formula (I):
The co-former is a phenolic compound that is a compound having at least one phenolic group that can be represented by the general formula (II)
(II)
Wherein R includes -OH, -COOH, -CI, -Br, -CONH2, -CH3, alkyl, aryl, allyl, formyl or amine group.
In accordance with an embodiment, the co-former is catechol. Where the co-former is catechol, the melting point of the molecular complex of imidacloprid with catechol, measured as a single melting endotherm by differential scanning calorimetry, is around 99.9 °C.
In accordance with an alternate embodiment, the co-former is salicylic acid. Where the co-former is salicylic acid, the melting point of the molecular complex of imidacloprid with salicylic acid measured as a single melting endotherm by differential scanning calorimetry, is around 104 °C.
In accordance with an aspect, the stoichiometric ratio of imidacloprid to the phenolic compound in the molecular complex of imidacloprid is 1 : 1.
The present disclosure also provides a method for producing a molecular complex of imidacloprid.
In accordance with an embodiment, the process comprises of admixing imidacloprid and a phenolic compound in a 1 : 1 stoichiometric ratio to form a dry mixture, grinding said dry mixture for a predetermined period of time, adding to the ground dry mixture a solvent to obtain a wet mixture, grinding the wet mixture and air drying the same to obtain the molecular complex of imidacloprid.
In accordance with an alternate embodiment the process comprises of admixing imidacloprid and the phenolic compound in a 1 : 1 stoichiometric ratio to form a dry mixture, grinding said dry mixture for a predetermined period of time, adding to the ground dry mixture a solvent and grinding the same to obtain a wet mixture, heating the wet mixture, transferring the heated wet mixture to a glass vessel and air drying to obtain molecular complex of imidacloprid. The heating may be carried out at a temperature around 100°C for 10 minutes. The heating may be carried out under nitrogen atmosphere.
The co-former is a phenolic compound that is a compound having at least one phenolic group that can be represented by the general formula (II).
The grinding of the dry mixture may be carried out for 10 to 15 minutes. The grinding of the wet mixture may be carried out for about 30 minutes. The grinding may be carried out in any suitable apparatus for grinding solids. Such apparatus includes but is not limited to mortar mills, vibrator mills or ball mills.
In accordance with an embodiment the solvent is any suitable solvent including but not limited to acetonitrile, ethanol or their mixture. The amount of solvent added is in a range of 0.5 ml to 10 ml.
EXAMPLES
Example 1
Imidacloprid and catechol are weighed in 1 : 1 molar ratio and ground using mortar and pestle for around 15 to 20 minutes followed by addition of 0.5 ml acetonitrile/ethanol and further continued to ground for another 30 min and finally air dried to obtain molecular complex of imidacloprid with catechol.
Example 2
Imidacloprid and salicylic acid are weighed in 1 : 1 molar ratio and ground using mortar and pestle for around 1 to 20 minutes followed by addition of acetonitrile/ethanol and further continued to ground for another 30 minutes. The ground mixture was taken in a glass tube under nitrogen atmosphere and heated to 100 °C for 10 minutes. The heated materials transferred in a glass vessel and air dried to obtain free flowing solid of molecular complex of Imidacloprid with salicylic acid.
Example 3: Infrared Spectroscopy
Technical Details:
Fourier transformed infrared spectra (FT-IR) were collected on a Bruker Vertex 70 model. The samples were mixed with potassium bromide ( Br) and data was collected in the spectral range 400-4000 cm"' with an average of 512 scan of 2 cm"1 resolution.
Analysis:
FT-IR spectra of molecular complexes obtained from examples 1 and 2 were compared with individual compounds and it was found that there are significant changes in IR spectral band of functional group regions to confirm the formation novel molecular complex.
Molecular complex of imidacloprid with salicylic acid shows a shift of 10 cm"1 in carbonyl spectral region as observed from Table 1. Moreover some shifts in -CH regions also observed in molecular complexes. Table 1. IR spectral band for imidacloprid, salicylic acid and imidacloprid- salicylic acid molecular complex.
Molecular complex of imidacloprid with catechol shows a shift of 46 cm"1 in hydroxyl functional group spectral region of catechol as observed from Table 2.
Table 2. IR spectral band for imidacloprid, catechol and imidacloprid- catechol molecular complex.
There were significant differences of 1 100-1600 cm ' in spectral band in the molecular complexs that further confirms the formation of novel materials. IR spectral profiles are illustrated in Figures 1 to 5. Example 4: Powder X-ray Diffraction-
Technical Details:
Powder X-ray Diffraction (PXRD) profiles were obtained from 5 to 10 mg of lightly ground sample including samples from Example 1 and 2 placed over Zero background silica flat sample stage. X-ray diffraction data was collected on a PANalytical "X"pertPRO diffractometer on a Cu source ( a - 1.5418) powered by 40kV and 30mA with a proportional counter radiation detector. Data collection was done with step size 0.020°, 0.50 second per step over 5-70 ° 2Θ. Data was analyzed using Xpert Viewer software. PXRD profile data presented for the region where significant peaks were observed. Analysis:
Molecular complex of imidacloprid with salicylic acid gave different PXRD profile than physical mixtures of imidacloprid and salicylic acid. Though some high intensity peaks for imidacloprid and salicylic acid were present in molecular complex, overall pattern shows some difference which is common in case of molecular complexes. Figure 6 illustrates a comparison PXRD profile of a sampled of molecular complex of imidacloprid with salicylic acid, ground mixture of imidacloprid and salicylic acid, salicylic acid and imidacloprid melt form.
Molecular complex of imidacloprid with catechol gave completely distinct PXRD profile than of imidacloprid and salicylic acid, which confirm the formation of molecular
complex. Figure 7 illustrates a comparison PXRD profile of a sample of molecular complex of imidaclopnd with catechol, catechol and imidaclopnd melt form.
Example 5: Differential Scanning Calorimetry
Technical Details:
Differential Scanning Calorimetric (DSC) thermograms of the samples including samples from Example 1 and 2 were recorded on a Mettler DSC1 instrument. The thermal behavior of the samples, placed in vented aluminum pans, was studied under nitrogen purge with a heating rate of 10 °C min"1 covering the temperature range 30 °C to 300 °C.
Analysis:
Molecular complex of imidacloprid with salicylic acid gave completely different DSC profile with a melting endotherm at 104 °C then imidacloprid (melting at 142 °C) and salicylic acid (melting at 159 °C). Figure 8 illustrates the comparison DSC profile of a sample of molecular complex of imidacloprid with salicylic acid, imidacloprid melt form and salicylic acid.
Molecular complex of imidacloprid with catechol also shows a lowering of melting point. The melting point of the molecular complex of imidacloprid was measured at 100 °C that is lower than that for imidacloprid (melting at 142 °C) and catechol (melting at 105 °C). Figure 9 illustrates the comparison DSC profile of a sample of molecular complexes of imidacloprid with catechol, imidacloprid melt form and catechol.
Both molecular complexes show a single sharp melting endotherm that further authenticates the formation of novel molecular complex.
Example 6: Equilibrium Solubility Determination
Equilibrium solubility was measured with using High-performance liquid chromatography (HPLC). HPLC measurements were carried out on a Waters HPLC instrument with 515 HPLC pump, Waters 717 plus auto sampler and Waters 2487 Dual λ absorbance detector. A reverse phase Merck Purospher STAR RP-18 endcapped column (250 x 4.6mm, 5μηι) was used for elution of samples under an isocratic condition. The mobile phase consisted of 60% acetonitrile in water. The mixed reagent was degassed using a sonicator system from Cole Parmer (model 08895-10). The samples were detected using an UV detector at a wavelength of 270 nm at room temperature. An injection volume of 5 μΐ,. was used. Flow, rate was maintained at 1.0 ml/minute. Figure 10 illustrates the HPLC profile of Imidacloprid
Equilibrium solubility was measured on imidacloprid and its molecular complex with salicylic acid and catechol at 30 °C. It was found that solubility of imidacloprid reduced by approximately 12 % in molecular complex of imidacloprid with salicylic acid, whereas solubility was reduced by approximately 15 % in molecular complex of imidacloprid with catechol. Table 3 discloses the solubility data obtained.
Table 3: Comparison of solubility of samples of imidacloprid molecular complex and pure imidacloprid.
Degradation study was conducted on Imidacloprid standard and molecular complexes of imidacloprid and salicyclic acid [IM:SA (1 : 1)] and molecular complexes of imidacloprid and catechol [IM:CA (1 : 1)] using HPLC. Degradation was determined by calculating Area under curve (AUC) obtained by HPLC at λπ^χ 270nm.
Following formula was used to calculate the % degradation:
% degradation = [(AUC at 0 hour - AUC at 24 hour) / AUC at 0 hr]* 100 Technical Specification of HPLC:
Waters 717plus autosampler with UV-2487 detector system) with the experimental conditions of Column, C-18 (30X2.1 mm); particle size, 1.5μηι; (Merck, Purospher); flow rate - lml/min; mobile phase, water: Acetonitrile (60:40), injection volume - ΙΟμί; dual wavelength at 270nm and 230nm UV detector system. Binary gradient system was used as the elution for inadacloprid.
HPLC Study
An amount of ~1 mg of Imidacloprid standard and each molecular complex was dissolved in 10 ml of water. After that the solution was filtered through 0.45μ filters. Filtrate was diluted by adding 10 ml of water. The diluted samples were then allowed to incubate at 40°C for 10 minutes into water bath. The samples were allowed to completely solubilise in water and exposed to the Ultra-violet (UV) radiation for 24 hours. Samples were taken at specified intervals for testing. The samples were tested using HPLC. The samples were run for 10 minutes. The HPLC profile of solubility of Imidacloprid from individual molecular complexes is as follows-
Area under curve (AUC) at kmax 270nm
Degradation of Imidacloprid
Figure 11 illustrates the HPLC profile of degradation study conducted on imidacloprid, molecular complex of imidacloprid with salicylic acid and molecular complex of imidacloprid with catechol.
Specific Embodiments are disclosed below:
A molecular complex comprising imidacloprid and a phenolic compound having a formula (II)
R includes -OH, -COOH, -CI, -Br, -CONH2, -CH3, alkyl, aryl, allyl, formyl or amine group.
Such molecular complex(s), wherein imidacloprid and the phenolic compound are in a stoichiometric ratio of 1 : 1.
Such molecular complex(s), wherein the phenolic compound is catechol.
Such molecular complex(s), wherein the molecular complex has a melting point of around 99.9°C.
Such molecular complex(s), wherein the phenolic compound is salicylic acid.
Such molecular complex(s), wherein the molecular complex has a melting point of around 104°C.
Further specific embodiments are disclosed below:
A process for preparing a molecular complex of imidacloprid and a phenolic compound, the phenolic compound having a formula (II),
R includes -OH, -COOH, -CI, -Br, -CONH2, -CH3, alkyl, aryl, allyl, formyl or amine group, the process comprising mixing imidacloprid and the phenolic compound in a 1 : 1 stoichiometric ratio followed by grinding to form a dry mixture; adding a solvent to the dry mixture followed by grinding to obtain a wet mixture; and air drying the wet mixture to obtain the molecular complex.
Such process(s), wherein the wet mixture is heated to around 100°C prior to air drying.
Such process(s), wherein the wet mixture is heated under a nitrogen atmosphere.
Such process(s), wherein the phenolic compound is selected from a group consisting of catechol and salicylic acid.
Such process(s), wherein the solvent is added to the dry mixture in a range of 0.5 ml to 10ml with respect to 1 to 10 gram of dry mixture.
Such process(s), wherein the solvent is selected from acetonitrile, ethanol and mixtures thereof.
INDUSTRTICAL APPLICABILITY
The molecular complex of imidacloprid as disclosed has reduced water solubility and better hydrolytic stability as compared to commercially available versions of Imidacloprid. The disclosed molecular complex of imidacloprid also has better stability. Being less water soluble than the commercially available imidacloprid, said molecular complex, does not leach readily and provides long duration control of soil insects. Moreover, use of co-formers such as catechol and salicylic acid additionally provide health benefits to the plant and improve plant wellbeing.
Claims
CLAIM:
R includes -OH, -COOH, -CI, -Br, -CONH2, -CH3, alkyl, aryl, allyl, formyl or amine group.
A molecular complex as claimed in claim 1 , wherein imidacloprid and the phenolic compound are in a stoichiometric ratio of 1 : 1.
A molecular complex as claimed in claim 1 , wherein the phenolic compound is catechol.
A molecular complex as claimed in claim 3, wherein the molecular complex has a melting point of around 99.9°C.
A molecular complex as claimed in claim 1 , wherein the phenolic compound is salicylic acid.
A molecular complex as claimed in claim 5, wherein the molecular complex has a melting point of around 104°C.
A process for preparing a molecular complex of imidacloprid and a phenolic compound, the phenolic compound having a formula (II),
R includes -OH, -COOH, -CI, -Br, -CONH2, -CH3, alkyl, aryl, allyl, formyl or amine group, the process comprising:
mixing imidacloprid and the phenolic compound in a 1 : 1 stoichiometric ratio followed by grinding to form a dry mixture;
adding a solvent to the dry mixture followed by grinding to obtain a wet mixture; and
air drying the wet mixture to obtain the molecular complex.
8. A process as claimed in claim 7, wherein the wet mixture is heated to around 100°C prior to air drying. 9. A process as claimed in claim 8, wherein the wet mixture is heated under a nitrogen atmosphere.
A process as claimed in claim 7, wherein the phenolic compound is selected from a group consisting of catechol and salicylic acid.
A process as claimed in claim 7, wherein the solvent is added to the dry mixture in a range of 0.5 ml to 10ml with respect to 1 to 10 gram of dry mixture.
12. A process as claimed in claim 7, wherein the solvent is selected from acetonitrile, ethanol and mixtures thereof.
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EP3348143A1 (en) * | 2017-01-17 | 2018-07-18 | Evergreen Animal Health LLC | Novel spot-on active substance formulation |
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WO2004095926A2 (en) * | 2003-04-28 | 2004-11-11 | Monsanto Technology, Llc | Treatment of plants and plant propagation materials with an antioxidant to improve plant health and/or yield |
WO2008151781A2 (en) * | 2007-06-14 | 2008-12-18 | Syngenta Participations Ag | Pesticidal combinations comprising insecticides and plant activators |
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WO2004095926A2 (en) * | 2003-04-28 | 2004-11-11 | Monsanto Technology, Llc | Treatment of plants and plant propagation materials with an antioxidant to improve plant health and/or yield |
WO2008151781A2 (en) * | 2007-06-14 | 2008-12-18 | Syngenta Participations Ag | Pesticidal combinations comprising insecticides and plant activators |
Cited By (3)
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EP3348143A1 (en) * | 2017-01-17 | 2018-07-18 | Evergreen Animal Health LLC | Novel spot-on active substance formulation |
WO2018136233A1 (en) * | 2017-01-17 | 2018-07-26 | Evergreen Animal Health, Llc | Novel spot-on active substance formulation |
US11278022B2 (en) | 2017-01-17 | 2022-03-22 | Evergreen Animal Health, Llc | Spot-on active substance formulation |
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