USOO9212162B1

(12) United States Patent (10) Patent No.: US 9.212,162 B1

BristoW et al. (45) Date of Patent: Dec. 15, 2015

(54) PROCESS FOR THE PREPARATION OF (56) References Cited

POLYMORPHS OF MIDACLOPRID
PUBLICATIONS
(71) Applicant: ROTAM AGROCHEM
INTERNATIONAL COMPANY Kapoor et al., “Ethyl 2- etc.” Acta Cryst. (2012) E68,0987. Sup-1-
LIMITED, Chai Wan (HK) sup-7.*
Kirk-Othmer Encyclopedia of Chemical Technology Copyright 2002
(72) Inventors: James Timothy Bristow, Hong Kong by John Wiley & Sons, Inc. pp. 95-147, Article Online Posting date:
(CN); Yifan Wu, Chai Wan (HK) Aug. 16, 2002.*
(73) Assignee: ROTAM AGROCHEM * cited by examiner
INTERNATIONAL COMPANY., LTD,
Chai Wan, Hong Kong (CN) Primary Examiner — Patricia L Morris
(74) Attorney, Agent, or Firm — Dickinson Wright PLLC
*) Notice: Subject to any disclaimer, the term of this
(*) NG is St. or adjusted under 35 (57) ABSTRACT
U.S.C. 154(b) by 0 days. A process for the preparation of a Form I crystalline poly
morph of imidacloprid, including: (i) dissolving imidacloprid
(21) Appl. No.: 14/313,632 in an appropriate amount of aqueous solvent or mixture of
Solvents to obtain an aqueous solution; (ii) cooling the aque
(22) Filed: Jun. 24, 2014 ous solution slowly, thereby forming crystals of polymorph
Form I of imidacloprid; (iii) isolating the crystals. A process
(51) Int. Cl. for the preparation of a Form II crystalline polymorph of
CO7D 40/06 (2006.01) imidacloprid, comprising: dissolving imidacloprid in an
(52) U.S. Cl. appropriate amount of non-aqueous solvent or mixture of
CPC .................................... C07D401/06 (2013.01) non-aqueous solvents to obtain a non-aqueous solution; (ii)
(58) Field of Classification Search cooling the solution rapidly, thereby forming crystals of poly
CPC ..................................................... CO7D401 f(06 morph Form II of imidacloprid; (iii) isolating the crystals.
USPC ....................................................... 546/274.7
See application file for complete search history. 8 Claims, 2 Drawing Sheets
U.S. Patent Dec. 15, 2015 Sheet 2 of 2 US 9.212,162 B1

FIGURE 3

s
88: a 33 °C
3:

S83 8. : 33 8 8: 23.
ixteers: ire (:
 US 9,212,162 B1
1. 2
PROCESS FOR THE PREPARATION OF TABLE 1-continued
POLYMORPHS OF MIDACLOPRID
28 d-value IIo
BACKGROUND 14.OOO 6.32OS 2
14.400 6.1459 2
15.42O 5.7415 2
1. Field 15.980 S.S416 6
Disclosed herein are methods for selectively producing 16.040 5.5210 8
crystal polymorphs of the compound 1-((6-Chloro-3-pyridi 16.980 S.2174 2
nyl)methyl)-N-nitro-imidazolidinimine, also known as imi 10
17.060
18.48O
5.1931
4.7972
3
4
dacloprid. 19.220 4.6141 1OO
2. Description of Related Art 1966O 4.51.18 5
Solid exist in either amorphous or crystalline forms. In the 19.720 4.4982 7
case of crystalline forms, molecules are positioned in 3-di 21160 4.1952 5
21.300 4.168O 4
mensional lattice sites. Crystallization of solids from solution 15 23.OOO 3.8636 3
is known in the art, for example by mixing the desired com 23.08O 3.8504 3
pound in an appropriate amount of solvent or mixture of 23.200 3.83O8 4
Solvents, heating to achieve dissolution, and cooling to pre 23.440 3.7921 4
cipitate the product. Alternatively, the compound can be dis 23.560 3.7730 7
23.980 3.7079 2
Solved in one solvent, and a second solvent is added, until 24.440 3.6391 7
precipitation is achieved. Also, the reaction can be seeded 24.96O 3.S645 2
with the appropriate compound in order to induce crystalli 25.360 3.5092 2
Zation, as known in the art. 25.740 3.4582 11
When a compound recrystallizes from a solution or slurry, 27.28O 3.2664 2
it may crystallize with different spatial lattice arrangements, 25
28.06O
28.18O
3.1773
3.1641
4
2
a property referred to as “polymorphism', with the different 28.82O 3.0953 2
crystal forms individually being referred to as a “polymorph”. 29.02O 3.0744 17
Different polymorphic forms of a given Substance may also 29.100 3.0661 10
differ from each other with respect to one or more physical 29.62O 3.01.34 2
properties. Such as solubility, true density, crystal shape, com 30
29.720 3.0035 6
paction behavior, flow properties, and/or solid state stability. 30.240 2.9531 2

In the case of a chemical substance that exists in two (or

more) polymorphic forms having different thermodynamic
stabilities, the more unstable forms generally convert to the Form I of imidacloprid also exhibits a differential Scanning
more thermodynamically stable forms at a given temperature calorimetry (DSC) thermogram substantially as shown in
35
after a sufficient period of time. When this transformation is FIG. 1. This thermogram is characterized by a predominant
not rapid, the thermodynamically unstable form is referred to endotherm peak at about 145.7°C., as measured by Differ
as the “metastable' form. In general, the stable form exhibits ential Scanning calorimeter at a scan rate of 10° C. per
the highest melting point, the lowest solubility, and the maxi minute.
mum chemical stability of the different polymorphic forms. 40 Form II of imidacloprid exhibits an X-ray powder diffrac
However, the metastable form may exhibit sufficient chemi tion pattern Substantially as indicated in Table 2, having char
cal and physical stability under normal storage conditions to acteristic peaks (expressed in degrees 20 (+/-0.20) at one or
permit its use in a commercial form. Furthermore, the meta more of the following positions: 4.580, 13.780, 15.000,
stable form, although less stable than the most thermody 18.220, 18.420, 18.880 and 23.120.
namically stable polymorphic form, may exhibit properties 45
that are more desirable than those of the more stable form, TABLE 2
such as better formulative ability, improved dispersability in
water, and the like. 28 d-value IIo
It has been discovered that the compound imidacloprid 4.58O 19.2776 9
exists in two polymorphic forms: a thermodynamically stable 50 9.160 9.6465 1
form, known as Form I, and a metastable form, known as 9.32O 9.4815 1
Form II. The powder XRD patterns and data for the two 13.520 6.5438 1
polymorphic forms are also distinctly different. Form I exhib 13.78O 6.4210 29
14.8OO 5.9806 2
its an X-ray powder diffraction pattern Substantially as given 1S.OOO S.9014 7
in Table 1, having characteristic peaks (expressed in degrees 55 16.260 5.4468 1
20 (+/-0.20) at one or more of the following positions: 16.440 5.3875 4
18.22O 4.86SO 6
9.560, 16.040, 19.220, 19.720, 23.560, 24.440, 25.740, 18.42O 4.8126 100
29.020 and 29.100. 18.760 4.7262 3
18.88O 4.6964 6
TABLE 1. 60
21.22O 4.1835 O
22.08O 4.0225 2
28 d-value IIo 22.16O 4.OO81 1
22.840 3.8903 1
9.28O 9.5220 2 23.120 3.8438 7
9.S60 9.2437 2O 23.300 3.81.45 1
11.900 7.4308 2 23.62O 3.7636 2
13.140 6.7322 2 65 26.18O 3.4O11 2
13.82O 6.4O2S 2 26.28O 3.3884 1
 US 9,212,162 B1
4
TABLE 2-continued (1) dissolving imidacloprid in an appropriate amount of
non-aqueous solvent or mixture of non-aqueous solvents to
28 d-value IIo obtain a non-aqueous solution;
29.540 3.0214 2 (2) cooling the Solution rapidly, thereby forming crystals of
29.62O 3.0134 2 polymorph Form II of imidacloprid;
29.960 2.98OO 3
30.040 2.9723 3
(3) isolating the crystals.
BRIEF DESCRIPTION OF DRAWINGS
Form II also exhibits a Differential Scanning calorimetry
(DSC) thermogram substantially as shown in FIG. 2, which is 10
Certain aspects of the embodiments described herein may
characterized by a predominant endotherm peak at about be more clearly understood by reference to the drawings,
136.5°C., as measured by Differential Scanning calorimeter which are intended to illustrate, but not limit, the invention,
at a scan rate of 10°C. per minute. and wherein:
A mixture of Form I and Form II of Imidacloprid also 15
FIG. 1 is a graph of a thermogram obtained by DSC of a
exhibits a Differential Scanning calorimetry (DSC) thermo Form I polymorph of imidacloprid;
gram substantially as shown in FIG.3, which is characterized FIG. 2 is a graph of a thermogram obtained by DSC of a
by two predominant endotherm peaks at about 138.2°C. and Form II polymorph of imidacloprid; and
145.7°C., as measured by Differential Scanning calorimeter FIG. 3 is a graph of a thermogram obtained by DSC of a
at a scan rate of 10°C. per minute. mixture of a Form I polymorph of imidacloprid and a Form II
Useful formulations of compounds containing both Form I polymorph of imidacloprid.
and Form II can be prepared in conventional ways. These
include preparation as dusts, pellets, Solutions, Suspensions, DETAILED DESCRIPTION OF SPECIFIC
emulsions, wettable powders, emulsifiable concentrates, and EMBODIMENTS
the like. In particular, the compound containing both Form I 25
and Form II may be formulated as solutions and Suspensions. The crystallization methods described herein may be used
The inventor found that compared to Form I. Form II is easier to effect the formation of Form I, or Form II, or mixtures
to formulate into liquid formulations, like Solutions, Suspen thereof, of imidacloprid. The presently disclosed crystalliza
sions, emulsions and emulsifiable concentrate. While both tion methods allow for selectively controlling the crystalliza
forms can be difficult to formulate into agrochemically 30 tion of polymorphic forms of imidacloprid.
acceptable formulation, imidacloprid in Form I is especially In one embodiment, Form I imidacloprid can be prepared
difficult to formulate into liquid formulations because of gel by crystallizing imidacloprid from an aqueous solvent or
formation. mixture of solvents. The term “aqueous solvent or mixture of
During the manufacturing process, Form I is more readily Solvents' as used herein means water, or a mixture of water
made when imidacloprid is recrystallised in aqueous solu 35
and one or more solvents selected from the group consisting
tion. Because Form I is so difficult to formulate into agro of methanol, ethanol, tetrahydrofuran, acetonitrile, methyl
chemically acceptable formulations, if the Form I material ene chloride, isopropyl alcohol, acetone, N,N-dimethyl-For
obtained during recrystallisation cannot be converted to Form mamide, dimethyl sulfoxide, wherein when a mixture of
II, then it must be disposed of resulting in lost revenue and water and solvent(s) is used, the weight ratio of water to
inefficient production processes. 40
solvent or solvent mixture is in the range of 99.9:1 to 1:9.
To date, there are no simple methods for controlling the Imidacloprid, or mixtures containing it, are dissolved with the
crystallization of polymorphic forms of imidacloprid. There
is thus an urgent and unmet need in the art for efficient method aqueous solvent or mixture of Solvents to obtain an aqueous
for selectively controlling the crystallization of polymorphic Solution of the imidacloprid dissolved in the aqueous solvent
forms of imidacloprid. 45 or mixture of solvents. The aqueous Solution is then cooled
slowly so as to form crystals of imidacloprid Form I, and then
SUMMARY the crystals.
In a preferred embodiment, the process includes preparing
It has been found that embodiments disclosed herein sat an aqueous solution of the imidacloprid in one or more of the
isfy this heretofore unmet need in that they provide a process 50 aforementioned aqueous solvent or mixture of solvents by
for selectively controlling the crystallization of polymorphic applying heat until dissolution is complete, then cooling the
forms of imidacloprid. aqueous solution slowly at a cooling rate of about 1° C./15-30
In another aspect, the embodiments disclosed herein pro min until crystals appear, and then isolating the crystals.
vide a process for readily converting Form I polymorph into In another embodiment, Form II imidacloprid can be pre
Form II polymorph. 55 pared by crystallizing imidacloprid from a non-aqueous sol
In one aspect, there is provided a process for the prepara vent or mixture of non-aqueous solvents. As used herein, the
tion of a crystalline polymorph Form I of imidacloprid, com term “nonaqueous solvent or mixture of non-aqueous sol
prising: vents' means one or more solvents selected from the group
(1) dissolving imidacloprid in an appropriate amount of consisting of methanol, ethanol, tetrahydrofuran, acetoni
aqueous solvent or mixture of solvents to obtain an aqueous 60 trile, methylene chloride, isopropyl alcohol, acetone, N.N-
Solution; dimethylformamide(DMF), dimethyl sulfoxide(DMSO),
(2) cooling the aqueous solution slowly, thereby forming toluene, benzene, n-Hexane, petroleum ether, ethyl acetate,
crystals of polymorph Form I of imidacloprid; ether, dichloromethane, chloroformand carbon tetrachloride,
(3) isolating the crystals. in the absence of water. Imidacloprid, or mixtures containing
In another aspect, there is provided a process for the prepa 65 it, are dissolved with the nonaqueous solvent or mixture of
ration of a crystalline polymorph Form II of imidacloprid, nonaqueous solvents to obtain a non-aqueous solution of the
comprising: imidacloprid dissolved in the aqueous solvent or mixture of
 US 9,212,162 B1
5 6
Solvents. The nonaqueous solution is then cooled rapidly so dacloprid Form II, a mixture of imidacloprid Form I and Form
as to form crystals of imidacloprid Form II, and then isolating II, or any other form of imidacloprid known in the art.
the crystals. For example, in one embodiment, Form I of imidacloprid
In a preferred embodiment, the process includes preparing can be prepared by crystallizing imidacloprid from an aque
a non-aqueous solution of the imidacloprid in one or more of 5 ous solvent or a mixture of Solvents selected from the group
the aforementioned non-aqueous solvents by applying heat consisting of methanol, ethanol, tetrahydrofuran, acetoni
until dissolution is complete, cooling the non-aqueous solu trile, methylene chloride, isopropyl alcohol, acetone, N.N-
tion rapidly at a cooling rate of about 1-2°C./min until crys dimethyl-Formamide, dimethyl sulfoxide; and isolating the
tals appear, and then isolating the crystals. Form I of imida resulting crystals. In a currently preferred embodiment, the
cloprid. 10 process includes preparing an aqueous solution of imidaclo
In one embodiment is disclosed a method that provides the prid in one or more of the aforementioned solvents, by apply
crystalline polymorphic form of imidacloprid designated ing heat to reflux temperature until dissolution is complete,
Form I. This polymorph may be characterized by, for and slowly cooling the solution to room temperature (defined
example, DSC or X-Ray powder diffraction. hereinas about 20°C. to about 25°C.). However, the solution
For example, as shown in Table 1. Form I of imidacloprid 15 can be slowly cooled to lower temperatures, for example 0°
exhibits an X-ray powder diffraction pattern having charac C.-5°C. The crystals are then isolated by any conventional
teristic peaks (expressed in degrees 20+/-0.20) at one or method known in the art, for example by filtration, centrifu
more of the following positions: 9.560, 16.040, 19.220, gation, etc. Form II of imidacloprid
19.720, 23.560, 24.440, 25.740, 29.020 and 29.110. The In another embodiment is disclosed a method that provides
X-ray powder diffraction pattern can be determined using a 20 the crystalline polymorphic form of imidacloprid designated
Rigaku automated powder diffractometer D/max-rB Form II. This polymorph may be characterized by, for
12KWunder the following conditions: example, by DSC or X-ray powder diffraction spectrometry.
Copper(K-alpha1) radiation, 40 kV, 60 mA For example, as shown in Table 2. Form II of imidacloprid
C. Monochro: Monochromator (curved crystal) exhibits an X-ray powder diffraction pattern having charac
Divergence slit: "1 deg 25 teristic peaks (expressed in degrees 20+/-0.20) at one or
Scattering slit: “1 deg” more of the following positions: 4.580, 13.780, 18.420,
Receiving slit: “0.15 mm” 18.880 and 23.120. The X-Ray powder diffraction was mea
Scan mode: continuous sured as described above.
Scan speed: 4.000 deg./min Furthermore, as shown in FIG. 2, Form II also exhibits a
Scan step: 0.020 deg 30 Differential Scanning calorimetry (DSC) thermogram which
Scan axis: 2 Theta/Theta is characterized by a predominant endotherm peak at about
Scan range: 2.5000-s 45.000 deg. 136.5°C., as measured by Differential Scanning calorimeter
The samples were prepared by grinding using agate mortar at a scan rate of 10° C. per minute. As used herein, the term
and pestle. The obtained powder is then pressed into alumi “about 136.5°C. means from about 135° C. to about 138°C.
num sample holder with rectangular cavity of 20 mm 15 mm 35 Thus, an endotherm as measured by DSC on the instrument
and having a depth of 0.5 mm. identified above may vary by as much as +1.5°C.
Furthermore, as shown in FIG. 1, Form I also exhibits a In another embodiment are disclosed processes for prepar
Differential Scanning calorimetry (DSC) thermogram which ing the imidacloprid polymorph Form II. Form II can be
is characterized by a predominant endotherm peak at about prepared by dissolving imidacloprid in an appropriate
145.7°C., as measured by Differential Scanning calorimeter 40 amount of non-aqueous solvent or mixture of nonaqueous
at a scan rate of 10°C. per minute. Solvents selected from the group consisting of methanol,
In performing this measurement, weighted samples (2-4 ethanol, tetrahydrofuran, acetonitrile, methylene chloride,
mg) were purged with nitrogen flow during the measurements isopropyl alcohol, acetone, N,N-dimethyl-Formamide
at a scan rate of 10° C. per minute. Aluminum standard (DMF), dimethyl sulfoxide(DMSO), toluene, benzene,
pierced crucibles of 40 uL were used. The evaluation was 45 n-Hexane, petroleum ether, ethyl acetate, ether, dichlo
performed using STAR software. As used herein, the term romethane, chloroform, and carbon tetrachloride to obtain a
“about 145.7°C.” means a range of 144° C. to 147°C. In this non-aqueous solution.
regard, it should be understood that the endotherm measured In a currently preferred embodiment, the process includes
by a particular differential scanning calorimeter is dependent preparing a non-aqueous solution of imidacloprid in one or
upon a number of factors, including the rate of heating (i.e. 50 more of the aforementioned solvents by applying heat to
scan rate), the calibration standard utilized, instruments cali reflux temperature until dissolution is complete, and rapidly
bration, relative humidity, and the chemical purity of the cooling the solution to room temperature (i.e., in 15-30 min
sample being tested. Thus, an endotherm as measured by utes). Room temperature is defined herein as about 20°C. to
DSC on the instrument identified above may vary by as much about 25°C. However, the solution can be rapidly cooled to
as 1.6°C. 55 lower temperature, for example 0°C.-5°C. at a cooling rate of
In one embodiment, there are disclosed processes for pre about 1-2 C./mini. The crystals are then isolated by any
paring the imidacloprid polymorph Form I. Form I can be conventional method known in the art, for example by filtra
prepared by dissolving imidacloprid in an appropriate tion, centrifugation, etc.
amount of aqueous solvent or mixture of aqueous solvents The imidacloprid starting material used for preparing Form
(i.e., an amount of solvent Sufficient to dissolve the imidaclo- 60 II can be any form of imidacloprid including imidacloprid
prid), heating this mixture to reflux temperature to achieve prepared in accordance with U.S. Pat. No. 6,307,053, amor
dissolution, and cooling the Solution slowly to precipitate the phous imidacloprid, imidacloprid Form II, a mixture of imi
product. dacloprid Form I and Form II, or any other form of imidaclo
The imidacloprid starting material used for preparing Form prid known in the art.
I according to the disclosed process can be any form of 65 The invention will now be described further by reference to
imidacloprid including imidacloprid prepared in accordance the following examples, which are intended to illustrate, but
with U.S. Pat. No. 6,307,053, amorphous imidacloprid, imi not limit, the scope of the appended claims.
 US 9,212,162 B1
7 8
EXAMPLE1 plete dissolution of the imidacloprid was observed. The solu
tion was then rapidly cooled to 0-5°C. at a cooling rate of
Synthesis of Imidacloprid about 1-2°C./min and crystals were formed from the solu
tion. The crystals were filtered out and dried at 40-50°C. in an
7.8 g (60 mmol) of 2-nitroiminoimidazolidine and 12.1 g 5 oven. The crystals were characterized as imidacloprid Form II
(87.5 mmol) of potassium carbonate were dissolved in 60 ml using X-ray powder diffraction and DSC.
of acetonitrile in a reflux flask. The mixture is heated to a
EXAMPLE 6
temperature Sufficient for achieving reflux operating condi
tion. 8.1 g (50.0 mole) of 2-chloro-5-chloromethyl pyridine is 10 Preparation of Imidacloprid Form II
dissolved in 40 ml of acetonitrile, and is dropwisely and
continuously added into the flask under the reflux condition 2 g of imidacloprid prepared according to Example 1 were
for a period of 0.5 hr, i.e. the addition rate is about 1.5 heated in 10 ml of methylene chloride to reflux temperature
ml/minute (the addition rate at the onset of the reaction cor until complete dissolution of the imidacloprid was observed.
responds to 0.0278 equivalent of 2-chloro-5-chloromethyl 15 The solution was then rapidly cooled to 0-5°C. at a cooling
pyridine per equivalent of 2-nitroiminoimidazolidine per rate of about 1-2°C./min and crystals were formed from the
minute) After completion of the reaction, the mixture is sub solution. The crystals were filtered out and dried at 40-50° C.
jected to filtration. The filtrate is concentrated, and is further in an oven. The crystals were characterized as imidacloprid
purified. Form II using X-ray powder diffraction and DSC.
EXAMPLE 2
EXAMPLE 7
Preparation of Imidacloprid Form I Preparation of Imidacloprid Form II
2 g of imidacloprid prepared according to Example 1 were 2g of imidacloprid Form I prepared according to Examples
heated in 10 ml of a mixture of methanol and water to reflux 25
temperature (ratio of methanol: water-1: 1) until complete 2-4 were heated in 10 ml of methanol to reflux temperature
dissolution of the imidacloprid was observed. The solution until complete dissolution of the imidacloprid was observed.
was then slowly cooled to 0-5°C. at a cooling rate of about 1° The solution was then rapidly cooled to 0-5°C. at a cooling
C./15-30 min and crystals were formed from the solution. The rate of about 1-2°C./min and crystals were formed from the
crystals were filtered out and dried at 40-50° C. in an oven. 30 solution. The crystals were filtered out and dried at 40-50° C.
The crystals were characterized as imidacloprid Form I using in an oven. The crystals were characterized as imidacloprid
X-ray powder diffraction and DSC. Form II using X-ray powder diffraction and DSC.
EXAMPLE 8
EXAMPLE 3
35
Preparation of Imidacloprid Form I Preparation of Imidacloprid Form II

2 g of imidacloprid prepared according to Example 1 were 2 g of of a mixture Form I and Form II imidacloprid
heated in 10 ml of a mixture of methanol and water (ratio of prepared according to Example 1 were heated in 10 ml of
methanol: water=1:2) to reflux temperature until complete 40 methanol to reflux temperature until complete dissolution of
dissolution of the imidacloprid was observed. The solution the imidacloprid was observed. The solution was then rapidly
was then slowly cooled to 0-5°C. at a cooling rate of about 1° cooled to 0-5°C. at a cooling rate of about 1-2°C/min and
C./15-30 min and crystals were formed from the solution. The crystals were formed from the solution. The crystals were
crystals were filtered out and dried at 40-50° C. in an oven. filtered out and dried at 40-50° C. in an oven. The crystals
The crystals were characterized as imidacloprid Form I using 45 were characterized as Imidacloprid Form II using X-ray pow
der diffraction and DSC.
X-ray powder diffraction and DSC. The invention having been described by reference to cer
EXAMPLE 4 tain specific embodiments and examples, it will be under
stood that these specific embodiments and examples are
Preparation of Imidacloprid Form I 50 intended to illustrate the invention, and not to limit the scope
of the appended claims.
2 g of imidacloprid prepared according to Example 1 were The invention claimed is:
heated in 10 ml of a mixture of DMF and water (DMF: 1. A process for the preparation of a Form II crystalline
water=9:1) to reflux temperature until complete dissolution polymorph of imidacloprid exhibiting an X-ray powder dif
of the imidacloprid was observed. The solution was then 55 fraction pattern having characteristic peaks (expressed in
slowly cooled to 20-25° C. at a cooling rate of about 1° degrees 20+/-0.20) at one or more of the following posi
C./15-30 min and crystals were formed from the solution. The tions: 4.580, 13.780, 18.420, 18.880 and 23.120, or exhibiting
crystals were filtered out and dried at 40-50° C. in an oven. a Differential Scanning calorimetry (DSC) thermogram
The crystals were characterized as Imidacloprid Form I using which is characterized by a predominant endotherm peak at
X-ray powder diffraction and DSC. 60 about 136.5°C., or both, comprising:
(i) dissolving imidacloprid in an amount of non-aqueous
EXAMPLE 5 Solvent or mixture of non-aqueous solvents appropriate
to obtain a non-aqueous solution, wherein the non-aque
Preparation of Imidacloprid Form II ous solvent is selected from the group consisting of
65 methanol, ethanol, tetrahydrofuran, acetonitrile, meth
2 g of imidacloprid prepared according to Example 1 were ylene chloride, isopropyl alcohol, acetone, N,N-dim
heated in 10 ml of methanol to reflux temperature until com ethyl-formamide, dimethylsulfoxide, toluene, benzene,
 US 9,212,162 B1
10
n-hexane, petroleum ether, ethyl acetate, ether, dichlo
romethane, chloroform, and carbon tetrachloride;
(ii) cooling the solution rapidly, thereby forming crystals of
polymorph Form II of imidacloprid;
(iii) isolating the crystals.
2. The process according to claim 1, wherein step (i) com
prises heating the imidacloprid or the non-aqueous solvent or
mixture of solvents, or both.
3. The process according to claim 2, wherein in step (ii), the
Solution is cooled rapidly from a temperature above room 10
temperature to room temperature.
4. The process according to claim 2, wherein in step (ii), the
Solution is cooled rapidly from a temperature above room
temperature to room temperature in 15-30 minutes.
5. The process according to claim 2, wherein in step (ii), the 15
solution is cooled rapidly to a temperature of 0-5°C.
6. The process according to claim 2, wherein in step (ii), the
solution is cooled rapidly to a temperature of 0-5°C. in 15-30
minutes.
7. The process according to claim 2, wherein in Step (i), the
non-aqueous solvent is selected from the group consisting of
methanol, and methylene chloride.
8. The process according to claim 2, wherein the imidaclo
prid dissolved in the non-aqueous solvent or mixture of Sol
vents comprises Form I polymorph of imidacloprid, or a 25
mixture of Form I and Form II polymorphs of imidacloprid.
k k k k k