U.S. patent application number 14/313632 was filed with the patent office on 2015-12-24 for process for the preparation of polymorphs of imidacloprid.
The applicant listed for this patent is ROTAM AGROCHEM INTERNATIONAL COMPANY LIMITED. Invention is credited to James Timothy Bristow, Yifan WU.
Application Number | 20150368227 14/313632 |
Document ID | / |
Family ID | 54783086 |
Filed Date | 2015-12-24 |
United States Patent
Application |
20150368227 |
Kind Code |
A1 |
Bristow; James Timothy ; et
al. |
December 24, 2015 |
PROCESS FOR THE PREPARATION OF POLYMORPHS OF IMIDACLOPRID
Abstract
A process for the preparation of a Form I crystalline polymorph
of imidacloprid, including: (i) dissolving imidacloprid in an
appropriate amount of aqueous solvent or mixture of solvents to
obtain an aqueous solution; (ii) cooling the aqueous solution
slowly, thereby forming crystals of polymorph Form I of
imidacloprid; (iii) isolating the crystals. A process for the
preparation of a Form II crystalline polymorph of imidacloprid,
comprising: dissolving imidacloprid in an appropriate amount of
non-aqueous solvent or mixture of non-aqueous solvents to obtain a
non-aqueous solution; (ii) cooling the solution rapidly, thereby
forming crystals of polymorph Form II of imidacloprid; (iii)
isolating the crystals
Inventors: |
Bristow; James Timothy;
(Hong Kong, CN) ; WU; Yifan; (Chai Wan,
HK) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ROTAM AGROCHEM INTERNATIONAL COMPANY LIMITED |
Chai Wan |
|
HK |
|
|
Family ID: |
54783086 |
Appl. No.: |
14/313632 |
Filed: |
June 24, 2014 |
Current U.S.
Class: |
546/274.7 |
Current CPC
Class: |
C07D 401/06
20130101 |
International
Class: |
C07D 401/06 20060101
C07D401/06 |
Claims
1. A process for the preparation of a Form I crystalline polymorph
of imidacloprid, comprising: (i) dissolving imidacloprid in an
appropriate amount of aqueous solvent or mixture of solvents to
obtain an aqueous solution; (ii) cooling the aqueous solution
slowly, thereby forming crystals of polymorph Form I of
imidacloprid; (iii) isolating the crystals.
2. A process for the preparation of a Form II crystalline polymorph
of imidacloprid exhibiting an X-ray powder diffraction pattern
having characteristic peaks (expressed in degrees
2.theta.+/-0.2.degree. .theta.) at one or more of the following
positions: 4.580, 13.780, 18.420, 18.880 and 23.120, or exhibiting
a Differential Scanning calorimetry (DSC) thermogram which is
characterized by a predominant endotherm peak at about
136.5.degree. C., or both, comprising: (i) dissolving imidacloprid
in an amount of non-aqueous solvent or mixture of non-aqueous
solvents appropriate to obtain a non-aqueous solution, wherein the
non-aqueous solvent is selected from the group consisting of
methanol, ethanol, tetrahydrofuran, acetonitrile, methylene
chloride, isopropyl alcohol, acetone, N,N-dimethyl-formamide,
dimethyl sulfoxide, toluene, benzene, n-hexane, petroleum ether,
ethyl acetate, ether, dichloromethane, chloroform, and carbon
tetrachloride; (ii) cooling the solution rapidly, thereby forming
crystals of polymorph Form II of imidacloprid; (iii) isolating the
crystals.
3. The process according to claim 1, wherein step (i) comprises
heating the imidacloprid or the aqueous solvent or mixture of
solvents, or both.
4. The process according to claim 1, wherein in step (ii), the
solution is cooled slowly from a temperature above room temperature
to room temperature.
5. The process according to claim 1, wherein in step (ii), the
solution is cooled slowly to a temperature of 0-5.degree. C.
6. The process according to claim 1, wherein in step (i), the
aqueous solvent or mixture of solvents comprises one or more
solvents selected from the group consisting of methanol, ethanol,
tetrahydrofuran, acetonitrile, methylene chloride, isopropyl
alcohol, acetone, N,N-dimethyl-Formamide and dimethyl
sulfoxide.
7. The process according to claim 2, wherein step (i) comprises
heating the imidacloprid or the non-aqueous solvent or mixture of
solvents, or both.
8. The process according to claim 2, wherein in step (ii), the
solution is cooled rapidly from a temperature above room
temperature to room temperature.
9. 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.
10. The process according to claim 2, wherein in step (ii), the
solution is cooled rapidly to a temperature of 0-5.degree. C.
11. The process according to claim 2, wherein in step (ii), the
solution is cooled rapidly to a temperature of 0-5.degree. C. in
15-30 minutes.
12. 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.
13. The process according to claim 1, wherein the imidacloprid
dissolved in the aqueous solvent or mixture of solvents comprises
Form II polymorph of imidacloprid, or a mixture of Form I and Form
II polymorphs of imidacloprid.
14. The process according to claim 2, wherein the imidacloprid
dissolved in the non-aqueous solvent or mixture of solvents
comprises Form I polymorph of imidacloprid, or a mixture of Form I
and Form II polymorphs of imidacloprid.
Description
BACKGROUND
[0001] 1. Field
[0002] Disclosed herein are methods for selectively producing
crystal polymorphs of the compound
1-((6-Chloro-3-pyridinyl)methyl)-N-nitro-imidazolidinimine, also
known as imidacloprid.
[0003] 2. Description of Related Art
[0004] Solid exist in either amorphous or crystalline forms. In the
case of crystalline forms, molecules are positioned in
3-dimensional lattice sites. Crystallization of solids from
solution is known in the art, for example by mixing the desired
compound in an appropriate amount of solvent or mixture of
solvents, heating to achieve dissolution, and cooling to
precipitate the product. Alternatively, the compound can be
dissolved in one solvent, and a second solvent is added, until
precipitation is achieved. Also, the reaction can be seeded with
the appropriate compound in order to induce crystallization, as
known in the art.
[0005] When a compound recrystallizes from a solution or slurry, it
may crystallize with different spatial lattice arrangements, a
property referred to as "polymorphism", with the different crystal
forms individually being referred to as a "polymorph". Different
polymorphic forms of a given substance may also differ from each
other with respect to one or more physical properties, such as
solubility, true density, crystal shape, compaction behavior, flow
properties, and/or solid state stability.
[0006] 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 more
thermodynamically stable forms at a given temperature after a
sufficient period of time. When this transformation is not rapid,
the thermodynamically unstable form is referred to as the
"metastable" form. In general, the stable form exhibits the highest
melting point, the lowest solubility, and the maximum chemical
stability of the different polymorphic forms. However, the
metastable form may exhibit sufficient chemical and physical
stability under normal storage conditions to permit its use in a
commercial form. Furthermore, the metastable form, although less
stable than the most thermodynamically stable polymorphic form, may
exhibit properties that are more desirable than those of the more
stable form, such as better formulative ability, improved
dispersability in water, and the like.
[0007] It has been discovered that the compound imidacloprid exists
in two polymorphic forms: a thermodynamically stable form, known as
Form I, and a metastable form, known as Form II. The powder XRD
patterns and data for the two polymorphic forms are also distinctly
different. Form I exhibits an X-ray powder diffraction pattern
substantially as given in Table 1, having characteristic peaks
(expressed in degrees 2.theta. (+/-0.2.degree. .theta.) at one or
more of the following positions: 9.560, 16.040, 19.220, 19.720,
23.560, 24.440, 25.740, 29.020 and 29.100.
TABLE-US-00001 TABLE 1 2.theta. d-value I/I.sub.0 9.280 9.5220 2
9.560 9.2437 20 11.900 7.4308 2 13.140 6.7322 2 13.820 6.4025 2
14.000 6.3205 2 14.400 6.1459 2 15.420 5.7415 2 15.980 5.5416 6
16.040 5.5210 8 16.980 5.2174 2 17.060 5.1931 3 18.480 4.7972 4
19.220 4.6141 100 19.660 4.5118 5 19.720 4.4982 7 21.160 4.1952 5
21.300 4.1680 4 23.000 3.8636 3 23.080 3.8504 3 23.200 3.8308 4
23.440 3.7921 4 23.560 3.7730 7 23.980 3.7079 2 24.440 3.6391 7
24.960 3.5645 2 25.360 3.5092 2 25.740 3.4582 11 27.280 3.2664 2
28.060 3.1773 4 28.180 3.1641 2 28.820 3.0953 2 29.020 3.0744 17
29.100 3.0661 10 29.620 3.0134 2 29.720 3.0035 6 30.240 2.9531
2
[0008] Form I of imidacloprid also exhibits a differential Scanning
calorimetry (DSC) thermogram substantially as shown in FIG. 1. This
thermogram is characterized by a predominant endotherm peak at
about 145.7.degree. C., as measured by Differential Scanning
calorimeter at a scan rate of 10.degree. C. per minute.
[0009] Form II of imidacloprid exhibits an X-ray powder diffraction
pattern substantially as indicated in Table 2, having
characteristic peaks (expressed in degrees 2.theta. (+/-0.2.degree.
.theta.) at one or more of the following positions: 4.580, 13.780,
15.000, 18.220, 18.420, 18.880 and 23.120.
TABLE-US-00002 TABLE 2 2.theta. d-value I/I.sub.0 4.580 19.2776 9
9.160 9.6465 1 9.320 9.4815 1 13.520 6.5438 1 13.780 6.4210 29
14.800 5.9806 2 15.000 5.9014 7 16.260 5.4468 1 16.440 5.3875 4
18.220 4.8650 6 18.420 4.8126 100 18/760 4.7262 3 18.880 4.6964 6
21.220 4.1835 0 22.080 4.0225 2 22.160 4.0081 1 22.840 3.8903 1
23.120 3.8438 7 23.300 3.8145 1 23.620 3.7636 2 26.180 3.4011 2
26.280 3.3884 1 29.540 3.0214 2 29.620 3.0134 2 29.960 2.9800 3
30.040 2.9723 3
[0010] Form II also exhibits a Differential Scanning calorimetry
(DSC) thermogram substantially as shown in FIG. 2, which is
characterized by a predominant endotherm peak at about
136.5.degree. C., as measured by Differential Scanning calorimeter
at a scan rate of 10.degree. C. per minute.
[0011] A mixture of Form I and Form II of Imidacloprid also
exhibits a Differential Scanning calorimetry (DSC) thermogram
substantially as shown in FIG. 3, which is characterized by two
predominant endotherm peaks at about 138.2.degree. C. and
145.7.degree. C., as measured by Differential Scanning calorimeter
at a scan rate of 10.degree. C. per minute.
[0012] Useful formulations of compounds containing both Form I and
Form II can be prepared in conventional ways. These include
preparation as dusts, pellets, solutions, suspensions, emulsions,
wettable powders, emulsifiable concentrates, and the like. In
particular, the compound containing both Form I and Form II may be
formulated as solutions and suspensions. The inventor found that
compared to Form I, Form II is easier to formulate into liquid
formulations, like solutions, suspensions, emulsions and
emulsifiable concentrate. While both forms can be difficult to
formulate into agrochemically acceptable formulation, imidacloprid
in Form I is especially difficult to formulate into liquid
formulations because of gel formation.
[0013] During the manufacturing process, Form I is more readily
made when imidacloprid is recrystallised in aqueous solution.
Because Form I is so difficult to formulate into agrochemically
acceptable formulations, if the Form I material obtained during
recrystallisation cannot be converted to Form II, then it must be
disposed of, resulting in lost revenue and inefficient production
processes.
[0014] To date, there are no simple methods for controlling the
crystallization of polymorphic forms of imidacloprid. There is thus
an urgent and unmet need in the art for efficient method for
selectively controlling the crystallization of polymorphic forms of
imidacloprid.
SUMMARY
[0015] It has been found that embodiments disclosed herein satisfy
this heretofore unmet need in that they provide a process for
selectively controlling the crystallization of polymorphic forms of
imidacloprid.
[0016] In another aspect, the embodiments disclosed herein provide
a process for readily converting Form I polymorph into Form II
polymorph.
[0017] In one aspect, there is provided a process for the
preparation of a crystalline polymorph Form I of imidacloprid,
comprising: [0018] (1) dissolving imidacloprid in an appropriate
amount of aqueous solvent or mixture of solvents to obtain an
aqueous solution; [0019] (2) cooling the aqueous solution slowly,
thereby forming crystals of polymorph Form I of imidacloprid;
[0020] (3) isolating the crystals.
[0021] In another aspect, there is provided a process for the
preparation of a crystalline polymorph Form II of imidacloprid,
comprising: [0022] (1) dissolving imidacloprid in an appropriate
amount of non-aqueous solvent or mixture of non-aqueous solvents to
obtain a non-aqueous solution; [0023] (2) cooling the solution
rapidly, thereby forming crystals of polymorph Form II of
imidacloprid; [0024] (3) isolating the crystals.
BRIEF DESCRIPTION OF DRAWINGS
[0025] Certain aspects of the embodiments described herein may be
more clearly understood by reference to the drawings, which are
intended to illustrate, but not limit, the invention, and
wherein:
[0026] FIG. 1 is a graph of a thermogram obtained by DSC of a Form
I polymorph of imidacloprid;
[0027] FIG. 2 is a graph of a thermogram obtained by DSC of a Form
II polymorph of imidacloprid; and
[0028] FIG. 3 is a graph of a thermogram obtained by DSC of a
mixture of a Form I polymorph of imidacloprid and a Form II
polymorph of imidacloprid.
DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS
[0029] The crystallization methods described herein may be used to
effect the formation of Form I, or Form II, or mixtures thereof, of
imidacloprid. The presently disclosed crystallization methods allow
for selectively controlling the crystallization of polymorphic
forms of imidacloprid.
[0030] In one embodiment, Form I imidacloprid can be prepared by
crystallizing imidacloprid from an aqueous solvent or mixture of
solvents. The term "aqueous solvent or mixture of solvents" as used
herein means water, or a mixture of water and one or more solvents
selected from the group consisting of methanol, ethanol,
tetrahydrofuran, acetonitrile, methylene chloride, isopropyl
alcohol, acetone, N,N-dimethyl-Formamide, dimethyl sulfoxide,
wherein when a mixture of water and solvent(s) is used, the weight
ratio of water to solvent or solvent mixture is in the range of
99.9:1 to 1:9. Imidacloprid, or mixtures containing it, are
dissolved with the aqueous solvent or mixture of solvents to obtain
an aqueous solution of the imidacloprid dissolved in the aqueous
solvent or mixture of solvents. The aqueous solution is then cooled
slowly so as to form crystals of imidacloprid Form I, and then the
crystals.
[0031] In a preferred embodiment, the process includes preparing an
aqueous solution of the imidacloprid in one or more of the
aforementioned aqueous solvent or mixture of solvents by applying
heat until dissolution is complete, then cooling the aqueous
solution slowly at a cooling rate of about 1.degree. C. /15-30 min
until crystals appear, and then isolating the crystals.
[0032] In another embodiment, Form II imidacloprid can be prepared
by crystallizing imidacloprid from a non-aqueous solvent or mixture
of non-aqueous solvents. As used herein, the term "nonaqueous
solvent or mixture of non-aqueous solvents" means one or more
solvents selected from the group consisting of methanol, ethanol,
tetrahydrofuran, acetonitrile, methylene chloride, isopropyl
alcohol, acetone, N,N-dimethylformamide (DMF), dimethyl sulfoxide
(DMSO), toluene, benzene, n-Hexane, petroleum ether, ethyl acetate,
ether, dichloromethane, chloroform and carbon tetrachloride, in the
absence of water. Imidacloprid, or mixtures containing it, are
dissolved with the nonaqueous solvent or mixture of nonaqueous
solvents to obtain a non-aqueous solution of the imidacloprid
dissolved in the aqueous solvent or mixture of solvents. The
nonaqueous solution is then cooled rapidly so as to form crystals
of imidacloprid Form II, and then isolating the crystals.
[0033] In a preferred embodiment, the process includes preparing a
non-aqueous solution of the imidacloprid in one or more of the
aforementioned non-aqueous solvents by applying heat until
dissolution is complete, cooling the non-aqueous solution rapidly
at a cooling rate of about 1-2.degree. C./min until crystals
appear, and then isolating the crystals. Form I of
imidacloprid.
[0034] In one embodiment is disclosed a method that provides the
crystalline polymorphic form of imidacloprid designated Form I.
This polymorph may be characterized by, for example, DSC or X-Ray
powder diffraction.
[0035] For example, as shown in Table 1, Form I of imidacloprid
exhibits an X-ray powder diffraction pattern having characteristic
peaks (expressed in degrees 2.theta.+/-0.2.degree. .theta.) at one
or more of the following positions: 9.560, 16.040, 19.220, 19.720,
23.560, 24.440, 25.740, 29.020 and 29.110. The X-ray powder
diffraction pattern can be determined using a Rigaku automated
powder diffractometer-D/max-rB 12KWunder the following conditions:
[0036] Copper(K-alpha1) radiation, 40 kv, 60 mA [0037] C. Monochro:
Monochromator (curved crystal) [0038] Divergence slit: "1deg"
[0039] Scattering slit: "1deg" [0040] Receiving slit: "0.15 mm"
[0041] Scan mode: continuous [0042] Scan speed: 4.000 deg./min
[0043] Scan step: 0.020 deg [0044] Scan axis: 2 Theta/Theta [0045]
Scan range: 2.5000->45.000 deg.
[0046] The samples were prepared by grinding using agate mortar and
pestle. The obtained powder is then pressed into aluminum sample
holder with rectangular cavity of 20 mm*15 mm and having a depth of
0.5 mm.
[0047] Furthermore, as shown in FIG. 1, Form I also exhibits a
Differential Scanning calorimetry (DSC) thermogram which is
characterized by a predominant endotherm peak at about
145.7.degree. C., as measured by Differential Scanning calorimeter
at a scan rate of 10.degree. C. per minute.
[0048] In performing this measurement, weighted samples (2-4 mg)
were purged with nitrogen flow during the measurements at a scan
rate of 10.degree. C. per minute. Aluminum standard pierced
crucibles of 40 .mu.L were used. The evaluation was performed using
STAR software. As used herein, the term "about 145.7.degree. C."
means a range of 144.degree. C. to 147.degree. C. In this regard,
it should be understood that the endotherm measured by a particular
differential scanning calorimeter is dependent upon a number of
factors, including the rate of heating (i.e. scan rate), the
calibration standard utilized, instruments calibration, relative
humidity, and the chemical purity of the sample being tested. Thus,
an endotherm as measured by DSC on the instrument identified above
may vary by as much as .+-.1.6.degree. C.
[0049] In one embodiment, there are disclosed processes for
preparing the imidacloprid polymorph Form I. Form I can be prepared
by dissolving imidacloprid in an appropriate amount of aqueous
solvent or mixture of aqueous solvents (i.e., an amount of solvent
sufficient to dissolve the imidacloprid), heating this mixture to
reflux temperature to achieve dissolution, and cooling the solution
slowly to precipitate the product.
[0050] The imidacloprid starting material used for preparing Form I
according to the disclosed process can be any form of imidacloprid
including imidacloprid prepared in accordance with U.S. Pat. No.
6,307,053, amorphous imidacloprid, imidacloprid Form II, a mixture
of imidacloprid Form I and Form II, or any other form of
imidacloprid known in the art.
[0051] For example, in one embodiment, Form I of imidacloprid can
be prepared by crystallizing imidacloprid from an aqueous solvent
or a mixture of solvents selected from the group consisting of
methanol, ethanol, tetrahydrofuran, acetonitrile, methylene
chloride, isopropyl alcohol, acetone, N,N-dimethyl-Formamide,
dimethyl sulfoxide; and isolating the resulting crystals. In a
currently preferred embodiment, the process includes preparing an
aqueous solution of imidacloprid in one or more of the
aforementioned solvents, by applying heat to reflux temperature
until dissolution is complete, and slowly cooling the solution to
room temperature (defined herein as about 20.degree. C. to about
25.degree. C.). However, the solution can be slowly cooled to lower
temperatures, for example 0.degree. C.-5.degree. C. The crystals
are then isolated by any conventional method known in the art, for
example by filtration, centrifugation, etc. Form II of
imidacloprid
[0052] In another embodiment is disclosed a method that provides
the crystalline polymorphic form of imidacloprid designated Form
II. This polymorph may be characterized by, for example, by DSC or
X-ray powder diffraction spectrometry.
[0053] For example, as shown in Table 2, Form II of imidacloprid
exhibits an X-ray powder diffraction pattern having characteristic
peaks (expressed in degrees 2.theta.+/-0.2.degree. .theta.) at one
or more of the following positions: 4.580, 13.780, 18.420, 18.880
and 23.120. The X-Ray powder diffraction was measured as described
above.
[0054] Furthermore, as shown in FIG. 2, Form II also exhibits a
Differential Scanning calorimetry (DSC) thermogram which is
characterized by a predominant endotherm peak at about
136.5.degree. C., as measured by Differential Scanning calorimeter
at a scan rate of 10.degree. C. per minute. As used herein, the
term "about 136.5.degree. C." means from about 135.degree. C. to
about 138.degree. C. Thus, an endotherm as measured by DSC on the
instrument identified above may vary by as much as .+-.1.5.degree.
C.
[0055] In another embodiment are disclosed processes for preparing
the imidacloprid polymorph Form II. Form II can be prepared by
dissolving imidacloprid in an appropriate amount of non-aqueous
solvent or mixture of nonaqueous solvents selected from the group
consisting of methanol, ethanol, tetrahydrofuran, acetonitrile,
methylene chloride, isopropyl alcohol, acetone,
N,N-dimethyl-Formamide (DMF), dimethyl sulfoxide (DMSO), toluene,
benzene, n-Hexane, petroleum ether, ethyl acetate, ether,
dichloromethane, chloroform, and carbon tetrachloride to obtain a
non-aqueous solution.
[0056] In a currently preferred embodiment, the process includes
preparing a non-aqueous solution of imidacloprid in one or more of
the aforementioned solvents by applying heat to reflux temperature
until dissolution is complete, and rapidly cooling the solution to
room temperature (i.e., in 15-30 minutes). Room temperature is
defined herein as about 20.degree. C. to about 25.degree. C.
However, the solution can be rapidly cooled to lower temperature,
for example 0.degree. C.-5.degree. C. at a cooling rate of about
1-2.degree. C./mini. The crystals are then isolated by any
conventional method known in the art, for example by filtration,
centrifugation, etc.
[0057] The imidacloprid starting material used for preparing Form
II can be any form of imidacloprid including imidacloprid prepared
in accordance with U.S. Pat. No. 6,307,053, amorphous imidacloprid,
imidacloprid Form II, a mixture of imidacloprid Form I and Form II,
or any other form of imidacloprid known in the art.
[0058] The invention will now be described further by reference to
the following examples, which are intended to illustrate, but not
limit, the scope of the appended claims.
Example 1
Synthesis of Imidacloprid
[0059] 7.8 g (60 mmol) of 2-nitroiminoimidazolidine and 12.1 g
(87.5 mmol) of potassium carbonate were dissolved in 60 ml of
acetonitrile in a reflux flask. The mixture is heated to a
temperature sufficient for achieving reflux operating condition.
8.1 g (50.0 mole) of 2-chloro-5-chloromethyl pyridine is dissolved
in 40 ml of acetonitrile, and is dropwisely and continuously added
into the flask under the reflux condition for a period of 0.5 hr,
i.e. the addition rate is about 1.5 ml/minute (the addition rate at
the onset of the reaction corresponds to 0.0278 equivalent of
2-chloro-5-chloromethyl pyridine per equivalent of
2-nitroiminoimidazolidine per minute) After completion of the
reaction, the mixture is subjected to filtration. The filtrate is
concentrated, and is further purified.
Example 2
Preparation of Imidacloprid Form I
[0060] 2 g of imidacloprid prepared according to Example 1 were
heated in 10 ml of a mixture of methanol and water to reflux
temperature (ratio of methanol:water=1:1) until complete
dissolution of the imidacloprid was observed. The solution was then
slowly cooled to 0-5.degree. C. at a cooling rate of about
1.degree. C./15-30 min and crystals were formed from the solution.
The crystals were filtered out and dried at 40-50.degree. C. in an
oven. The crystals were characterized as imidacloprid Form I using
X-ray powder diffraction and DSC.
Example 3
Preparation of Imidacloprid Form I
[0061] 2 g of imidacloprid prepared according to Example 1 were
heated in 10 ml of a mixture of methanol and water (ratio of
methanol:water=1:2) to reflux temperature until complete
dissolution of the imidacloprid was observed. The solution was then
slowly cooled to 0-5.degree. C. at a cooling rate of about
1.degree. C./15-30 min and crystals were formed from the solution.
The crystals were filtered out and dried at 40-50.degree. C. in an
oven. The crystals were characterized as imidacloprid Form I using
X-ray powder diffraction and DSC.
Example 4
Preparation of Imidacloprid Form I
[0062] 2 g of imidacloprid prepared according to Example 1 were
heated in 10 ml of a mixture of DMF and water (DMF: water=9:1) to
reflux temperature until complete dissolution of the imidacloprid
was observed. The solution was then slowly cooled to 20-25.degree.
C. at a cooling rate of about 1.degree. C./15-30 min and crystals
were formed from the solution. The crystals were filtered out and
dried at 40-50.degree. C. in an oven. The crystals were
characterized as Imidacloprid Form I using X-ray powder diffraction
and DSC.
Example 5
Preparation of Imidacloprid Form II
[0063] 2 g of imidacloprid prepared according to Example 1 were
heated in 10 ml of methanol to reflux temperature until complete
dissolution of the imidacloprid was observed. The solution was then
rapidly cooled to 0-5.degree. C. at a cooling rate of about
1-2.degree. C./min and crystals were formed from the solution. The
crystals were filtered out and dried at 40-50.degree. C. in an
oven. The crystals were characterized as imidacloprid Form II using
X-ray powder diffraction and DSC.
Example 6
Preparation of Imidacloprid Form II
[0064] 2 g of imidacloprid prepared according to Example 1 were
heated in 10 ml of methylene chloride to reflux temperature until
complete dissolution of the imidacloprid was observed. The solution
was then rapidly cooled to 0-5.degree. C. at a cooling rate of
about 1-2.degree. C./min and crystals were formed from the
solution. The crystals were filtered out and dried at 40-50.degree.
C. in an oven. The crystals were characterized as imidacloprid Form
II using X-ray powder diffraction and DSC.
Example 7
Preparation of Imidacloprid Form II
[0065] 2 g of imidacloprid Form I prepared according to Examples
2-4 were heated in 10 ml of methanol to reflux temperature until
complete dissolution of the imidacloprid was observed. The solution
was then rapidly cooled to 0-5.degree. C. at a cooling rate of
about 1-2.degree. C./min and crystals were formed from the
solution. The crystals were filtered out and dried at 40-50.degree.
C. in an oven. The crystals were characterized as imidacloprid Form
II using X-ray powder diffraction and DSC.
Example 8
Preparation of Imidacloprid Form II
[0066] 2 g of of a mixture Form I and Form II imidacloprid prepared
according to Example 1 were heated in 10 ml of methanol to reflux
temperature until complete dissolution of the imidacloprid was
observed. The solution was then rapidly cooled to 0-5.degree. C. at
a cooling rate of about 1-2.degree. C./min and crystals were formed
from the solution. The crystals were filtered out and dried at
40-50.degree. C. in an oven. The crystals were characterized as
Imidacloprid Form II using X-ray powder diffraction and DSC.
[0067] The invention having been described by reference to certain
specific embodiments and examples, it will be understood that these
specific embodiments and examples are intended to illustrate the
invention, and not to limit the scope of the appended claims.
* * * * *