U.S. patent application number 15/268734 was filed with the patent office on 2018-03-22 for manufacturing method for and insecticidal compositions comprising thiocyclam hydrochloride.
The applicant listed for this patent is Arysta Lifescience North America, LLC.. Invention is credited to Samantha Besse, Cameron S. Gibb, Chandra S. Kanugala, Kamal L. Kataria, Christopher L. Larson, Thomas C. Lovelace, Joseph A. Moore, III, Mark T. Singleton, Balraju Vadla, Srinivas Vollala.
Application Number | 20180079739 15/268734 |
Document ID | / |
Family ID | 61617865 |
Filed Date | 2018-03-22 |
United States Patent
Application |
20180079739 |
Kind Code |
A1 |
Gibb; Cameron S. ; et
al. |
March 22, 2018 |
Manufacturing Method For and Insecticidal Compositions Comprising
Thiocyclam Hydrochloride
Abstract
A method for manufacturing an insecticidal compound and
insecticidal compositions comprising the insecticidal compound and
methods of use are presented herein. The manufacturing method
presented herein allows for a high purity grade of thiocyclam
hydrochloride to be synthesized. The insecticidal compositions
comprising the thiocyclam hydrochloride can be used for prevention
of crop destruction by insects. The use of thiocyclam hydrochloride
in insecticidal compositions as described herein can achieve
greater efficacy than previously known insecticides, by eliminating
the insect pests more reliably and efficiently.
Inventors: |
Gibb; Cameron S.; (Apex,
NC) ; Larson; Christopher L.; (Cary, NC) ;
Singleton; Mark T.; (Morris, CT) ; Kataria; Kamal
L.; (Maharashtra State, IN) ; Besse; Samantha;
(Daban, FR) ; Moore, III; Joseph A.; (Wake Forest,
NC) ; Lovelace; Thomas C.; (Apex, NC) ;
Kanugala; Chandra S.; (Telangana, IN) ; Vollala;
Srinivas; (Telangana, IN) ; Vadla; Balraju;
(Telangana, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Arysta Lifescience North America, LLC. |
Cary |
NC |
US |
|
|
Family ID: |
61617865 |
Appl. No.: |
15/268734 |
Filed: |
September 19, 2016 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A01N 43/80 20130101;
C07D 341/00 20130101; A01N 43/32 20130101 |
International
Class: |
C07D 341/00 20060101
C07D341/00; A01N 43/32 20060101 A01N043/32; A01N 43/80 20060101
A01N043/80 |
Claims
1. A method of manufacturing N,N-dimethyl-1,2,3-trithian-5-ylamine
hydrochloride comprising the steps of: a) providing a mixture of
thiosulfuric acid S,S'-[2-(dimethylamino)trimethylene] ester
monosodium salt and sodium hydroxide; b) adding an aqueous saline
solution to the mixture of thiosulfuric acid
S,S'-[2-(dimethylamino)trimethylene] ester monosodium salt and
sodium hydroxide, wherein the aqueous saline solution is added over
the course of at least 3 hours; c) separating the phases of the
mixture; d) collecting the solids from the mixture using
filtration; c) washing the solids with organic solvent; and f)
drying the solids, wherein the dried solids are
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride.
2. The method according to claim 1, wherein the organic solvent
comprises methyl-t-butyl ether, toluene, isopropanol or mixtures
thereof.
3. The method according to claim 1, wherein the aqueous saline
solution comprises sodium chloride.
4. The method according to claim 1, wherein the temperature during
step b) is between -10 to -25.degree. C.
5. The method according to claim 4, wherein the temperature during
step b) is between -15 to -20.degree. C.
6. The method according to claim 1, wherein 2M ethereal
hydrochloric acid is added to the mixture after step c) and before
step d).
7. The method according to claim 1, wherein 2M hydrochloric acid in
isopropanol is added to the mixture after step c) and before step
d).
8. The method according to claim 1, wherein the aqueous saline
solution comprises sodium sulfide.
9. The method according to claim 1, wherein the purity of the
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride is greater than
90%.
10. The method according to claim 9, wherein the purity of the
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride is greater than
95%.
11. The method according to claim 1, wherein the % yield of
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride is greater than
30%.
12. The method according to claim 11, wherein the % yield of
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride is greater than
60%.
13. An insecticidal composition wherein the composition comprises:
a) N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride and/or
solvate thereof; b) one or more auxiliary component; and c)
optionally, a safener.
14. An insecticidal composition according to claim 13, wherein the
composition comprises from about 1-10 parts by weight
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride.
15. An insecticidal composition according to claim 14, wherein the
composition comprises about 1 part by weight
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride.
16. The insecticidal composition according to claim 13, wherein the
safener is selected from the group isoxadifen-ethyl,
1,8-dicarboxylic anhydride, mefenpyr-diethyl, fenchlorazole-ethyl,
cloquintocet-mexyl, and combinations of the foregoing.
17. The insecticidal composition according to claim 16, wherein the
safener comprises isoxadifen-ethyl.
18. The insecticidal composition according to claim 16, wherein
relative to 1 part by weight of the
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride, the safener
comprises about 0.1 to 10 parts by weight.
19. The insecticidal composition according to claim 13 that
comprises an auxiliary selected from the group consisting of an
emulsifier, a thickener, a surfactant, an inert solid carrier, an
organic suspending medium, or combinations of the foregoing.
20. The insecticidal composition according to claim 19, wherein the
auxiliary is an emulsifier selected from the group consisting of a
fatty alcohol-polyoxyethylene ether, dehydrated sorbitol
polyoxyethylene ether, dibenzyl phenol polyoxyethylene ether,
polyoxyethylene dehydrated sorbitol ether monooleate, styryl phenol
polyoxyethylene ether, fatty amine polyoxyethylene ether, and
combinations of one or more of the foregoing.
21. The insecticidal composition according to claim 19, wherein the
auxiliary is a thickener selected from the group consisting of
polyvinylpyrrolidone, xanthan gum, aluminium-magnesium silicate,
polyvinyl alcohol and polyvinyl acetate, and combinations of one or
more of the foregoing.
22. The insecticidal composition according to claim 19, wherein the
auxiallry is a surfactant selected from the group consisting of
sodium methylene bis-naphthalene sulfonate, sodium lignin
sulfonate, calcium lignosulphonate, calcium dodecyl benzene
sulfonate, sodium succinate, diisobutyl naphthalene sulfonic acid
sodium salt (nekal BX), sodium laurylsulfate, and combinations of
one or more of the foregoing.
23. The insecticidal composition according to claim 19, wherein the
auxiallry is an inert solid carrier selected from the group
consisting of clay, silica, diatomaceous earth, kaolin,
attapulgite, moat-morillonite, bentonite, talcum powder, white
carbon black, calcium carbonate, and combinations of one or more of
the foregoing.
24. The insecticidal composition according to claim 19, wherein the
auxiliary is an organic suspending medium selected from the group
consisting of soybean oil, rapeseed oil, corn oil, sunflower oil,
cottonseed oil, linseed oil, coconut oil, palm oil, peanut oil,
olive oil, castor oil, transesterification products thereof, and
combinations of one or more of the foregoing.
25. The insecticidal composition according to claim 13, wherein a
ratio of the part by weight of the
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride to the parts by
weight of the one or more auxiliary is 1: (0.2-15).
26. The insecticidal composition of claim 13, wherein the
composition is in the form of a solution, emulsifiable concentrate,
wettable powder, suspension, powder, dust, paste, soluble powder,
granules, suspo-emulsion concentrate, oil spray, aerosol, natural
and synthetic materials impregnated with the composition, or as
capsules in polymeric substances.
27. The insecticidal composition of claim 26, wherein the
composition is in the form of an emulsifiable concentrate, wettable
powder, granules, dust, oil spray, or aerosol.
28. A method for prevention of insects for a crop using a
insecticidal composition comprising; a)
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride and/or a
solvate thereof; b) one or more auxiliary compounds; and c)
optionally, a safener; and wherein an insecticidally effective
amount of the insecticidal composition is applied to a crop.
29. The method according to claim 28, wherein the crop comprises at
least one of radish and bean.
30. The method according to claim 28, wherein the insects comprise
at least one of codling moths, soybean loopers, aphids, and white
flies.
31. The method according to claim 28, wherein the insecticidal
composition comprises: i) about 1 part by weight
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride and/or a
solvate thereof; ii) about 0.01-90 parts by weight of one or more
auxilliary; and iii) optionally, about 0.1-10 parts by weight
safener.
32. The method according to claim 28, wherein an application rate
of the insecticidal composition is in a range from 0.0225 g/m.sup.2
to 0.7500 g/m.sup.2.
33. The method according to claim 28, wherein the insecticidal
composition is in the form of a solution, emulsifiable concentrate,
wettable powder, suspension, powder, dust, paste, soluble powder,
granules, suspo-emulsion concentrate, oil spray, aerosol, natural
and synthetic materials impregnated with the composition, or as
capsules in polymeric substances.
34. The method according to claim 28, wherein the composition is in
the form of an emulsifiable concentrate, wettable powder, granules,
dust, oil spray, or aerosol.
Description
FIELD OF THE INVENTION
[0001] Embodiments herein relate generally to the manufacturing and
use of the compound thiocyclam hydrochloride and/or solvate
thereof, to control insect pests on plants, plant parts and locus
thereof, including agricultural crops.
BACKGROUND OF THE INVENTION
[0002] Insecticides are pesticides that are formulated to kill,
harm, repel or mitigate one or more species of insect. Insecticides
work in different ways. Some insecticides disrupt the nervous
system, whereas others may damage their exoskeletons, repel them or
control them by some other means. They can also be packaged in
various forms including sprays, dusts, gels, and baits. Because of
these factors, each insecticide can pose a different level of risk
to non-target insects, people, pets and the environment.
[0003] Insecticides are chemicals used to control insects by
killing them or preventing them from engaging in behaviors deemed
undesirable or destructive. They are classified based on their
structure and mode of action. Many insecticides act upon the
nervous system of the insect (e.g., Cholinesterase (ChE)
inhibition) while others act as growth regulators or
endotoxins.
[0004] Insecticides are commonly used in agricultural, public
health, and industrial applications, as well as household and
commercial uses (e.g., control of roaches and termites). The most
commonly used insecticides are the organophosphates, pyrethroids
and carbamates. The USDA has reported that insecticides accounted
for 12% of total pesticides applied to the surveyed crops. Corn and
cotton account for the largest shares of insecticide use in the
United States.
[0005] Insecticides include substances such as ovicides and
larvicides used against insect eggs and larvae, respectively.
Insecticides are claimed to be a major factor behind the increase
in agricultural 20th century's productivity. Nearly all
insecticides have the potential to significantly alter ecosystems;
many are toxic to humans and some concentrate along the food
chain.
[0006] Insecticides can be classified in two major groups: systemic
insecticides, which have residual or long term activity; and
contact insecticides, which have no residual activity.
[0007] Systemic insecticides become incorporated and distributed
systemically throughout the whole plant. When insects feed on the
plant, they ingest the insecticide. Systemic insecticides produced
by transgenic plants are called plant-incorporated protectants. For
instance, a gene that codes for a specific Bacillus thuringiensis
biocidal protein was introduced into corn and other species. The
plant manufactures the protein, which kills the insect when
consumed. Systemic insecticides have activity pertaining to their
residue which is called "residual activity" or long-term
activity.
[0008] Contact insecticides are toxic to insects upon direct
contact. These insecticides commonly fall into three categories.
First, there are natural insecticides, such as nicotine, pyrethrum
and neem extracts, made by plants as defenses against insects.
Second there are inorganic insecticides, which are metals such as
arsenates, copper and fluorine compounds.
[0009] Third are organic insecticides, which are organic chemical
compounds, typically working by direct contact with the insect or
eggs and larvae.
[0010] Insecticides are applied in various formulations and
delivery systems such as sprays, baits, and slow-release diffusion.
Efficacy can be related to the quality of pesticide application,
with small droplets, such as aerosols often improving
performance.
[0011] Current treatments for controlling insects typically include
chemicals, biologicals, and/or non-chemical methods such as
systemic acquired resistance inducers to provide resistant crop
strains, GMO's, and hatching stimulants and inhibitors to clear
loci prior to planting. Each of these current treatments and
methods has one or more drawbacks, including toxicity, cost,
availability, reliability, and high application amounts. New
insecticidal compositions also face elevated government regulations
and public scrutiny as to their environmental and ecological
impacts.
[0012] While it is difficult to isolate the effect of one pest in
an ecological system, the estimated overall average yearly yield
loss due to insects is estimated at around 10-15% worldwide, with a
monetary value estimated in the billions of dollars. There are a
wide variety of insects that insecticides target in the
agricultural industry.
[0013] Insects (from Latin insectum, a calque of Greek
e.nu..tau.o.mu.o.nu. [entomon], "cut into sections") are a class of
invertebrates within the arthropod phylum that have a chitinous
exoskeleton, a three-part body (head, thorax and abdomen), three
pairs of jointed legs, compound eyes and one pair of antennae. They
are the most diverse group of animals on the planet, including more
than a million described species and representing more than half of
all known living organisms. The number of insect species is
estimated to be between six and ten million, and potentially
represent over 90% of the differing animal life forms on Earth.
Insects may be found in nearly all environments.
[0014] In insects, there are nicotinic acetylcholine receptors
(nAChR) in the parts of the postsynaptic membrane connecting
nerves. Nereistoxin based compounds have long been known as agents
that act on this location. Currently, common insecticides for
preventing and killing target insects include compounds such as
cartap hydrochloride, for use in agricultural crops.
##STR00001##
[0015] Cartap, as shown in FIG. 1, is a pesticide that was first
introduced into the market in Japan in 1967. Its commercial names
include Padan, Kritap, AG-Tap, Thiobel, and Vegetox. The basic
chemical structure is S, S-[2-(dimethylamino)-1, 3-propanediyl]
dicarbamothioate. The residue left by this type pesticide poses a
threat to human health and therefore it would be desirable to find
alternative compounds to those such as cartap, that can be applied
at reduced concentrations with similar, or ideally, increased
efficacy as an insecticide.
[0016] Embodiments herein provide manufacturing of an insecticidal
compound and compositions and methods that can overcome reduced
efficiency and high application concentrations of current
insecticides.
SUMMARY OF THE INVENTION
[0017] It is an object of the current invention to provide a method
of manufacturing a novel insecticide compound.
[0018] It is an object of the current invention to provide a method
of manufacturing thiocyclam hydrochloride.
[0019] It is another object of the current invention to provide a
method of manufacturing thiocyclam hydrochloride with 90% or higher
purity.
[0020] It is yet another object of the current invention to provide
a method of manufacturing thiocyclam hydrochloride with 95% or
higher purity.
[0021] It is an object of the current invention to provide a method
of manufacturing thiocyclam hydrochloride with greater than 30%
yield.
[0022] It is an object of the current invention to provide a method
of manufacturing thiocyclam hydrochloride with greater than 60%
yield.
[0023] It is an object of the present invention to provide an
insecticidal composition effective against insect pests.
[0024] It is another object of the present invention to provide an
insecticidal composition that is effective against moths, soybean
looper, aphids, and white flies.
[0025] It is still another object of the present invention to
provide an improved insecticidal composition that is effective
against insects and that can be readily applied to crops.
[0026] It is still another object of the present invention to
provide an improved insecticidal composition that is effective on
radish and bean crops.
[0027] It is still another object of the present invention to
provide an insecticidal composition that is effective against
insect pests that comprises thiocyclam hydrochloride and/or solvate
thereof.
[0028] It is still another object of the present invention to
develop a new class of insecticides with novel activity and which
are highly effective when applied directly to crops and used in
chemirrigation processes.
[0029] It is yet another object of the present invention to provide
an improved insecticide composition with high efficacy at a low
dose of thiocyclam hydrochloride and/or solvate thereof.
[0030] To that end, in one embodiment, the present invention
relates generally to a method of manufacturing
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride comprising the
steps of: [0031] a) providing a mixture of thiosulfuric acid
S,S'-[2-(dimethylamino)trimethylene] ester monosodium salt and
sodium hydroxide; [0032] b) adding an aqueous saline solution to
the mixture of thiosulfuric acid
S,S'-[2-(dimethylamino)trimethylene] ester monosodium salt and
sodium hydroxide, wherein the aqueous saline solution is added over
the course of at least 3 hours; [0033] c) separating the phases of
the mixture; [0034] d) collecting the solids from the mixture using
filtration; [0035] e) washing the solids with organic solvent; and
[0036] f) drying the solids, [0037] wherein the dried solids are
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride.
[0038] In another preferred embodiment, the present invention
relates generally to an insecticidal composition wherein the
composition comprises: [0039] i)
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride and/or solvate
thereof; [0040] ii) one or more auxiliary component; and [0041]
iii) optionally, a safener.
[0042] In yet another preferred embodiment, the present invention
relates generally to a method for prevention of insects on a crop
using an insecticidal composition comprising; [0043] i)
N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride and/or a
solvate thereof; [0044] ii) one or more auxiliary compounds; and
[0045] iii) optionally, a safener; and
[0046] wherein an insecticidally effective amount of the
insecticidal composition is applied to a crop.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0047] Below is a detailed description of various exemplary
embodiments. It shall be understood that the embodiments described
herein are only used for illustrating and explaining, rather than
being limiting. Included herein are novel manufacturing methods for
the active ingredient in the inventive insecticidal compositions
and methods for using such compositions.
[0048] The method of manufacturing thiocyclam hydrochloride is
described in the reaction scheme below and in the following
examples. The inventors were surprisingly able to achieve
acceptable yields and high purity of the insecticidal compound.
High purity could not previously be achieved in production methods
of thiocyclam hydrochloride and therefore its use in insecticidal
compositions has not been found effective compared to other known
insecticidal compounds. This is the first known effective synthetic
method for thiocyclam hydrochloride.
##STR00002##
Example 1
[0049] An aqueous saline solution of Na.sub.2S.9H.sub.2O (17.1 g)
was added to a stirring mixture of Monosultap (25 g), sodium
hydroxide (2.86 g) and toluene/saline over 4.5 hours maintaining
the temperature at -16 to -18.degree. C. The reaction mixture was
stirred at -16 to -18.degree. C. until complete then filtered to
remove inorganic salts. The cake was washed with toluene and
combined with the filtrates. The phases were separated and the
toluene solution was washed with water, then brine, and dried over
sodium sulfate. 2M ethereal hydrochloric acid (50 mL) was added and
the mixture was stirred for 1 hour. The solids formed were
collected by filtration, washed with MTBE and dried to give
thiocyclam hydrochloride in 87% yield (14.2 g) and 97.9% purity
with 0.36% residual toluene.
Example 2
[0050] An aqueous saline solution of Na.sub.2S.9H.sub.2O (15.3 g)
was added to a stirring mixture of Monosultap (25 g), sodium
hydroxide (3.16 g) and toluene/saline over 4 hours maintaining the
temperature at -15 to -18.degree. C. The reaction mixture was
stirred at -15.degree. C. until complete then filtered to remove
inorganic salts. The cake was washed with toluene and the wash was
combined with the filtrates. The phases were separated and the
toluene solution was washed with water, then brine, and dried over
sodium sulfate. 2M ethereal hydrochloric acid (50 mL) was added and
the mixture was stirred for 1 hour. The solids formed were
collected by filtration, washed with ice-cold MTBE and dried to
give thiocyclam hydrochloride in 76% yield (12.4 g) and 98.3%
purity bearing 0.22% residual toluene.
Example 3
[0051] An aqueous saline solution of Na.sub.2S.9H.sub.2O (92.6 g)
was added to a stirring mixture of Monosultap (100 g), sodium
hydroxide (11.3 g) and toluene/saline/isopropanol over 5.5 hours
maintaining the temperature at -20.degree. C. The reaction mixture
was stirred at -20.degree. C. until complete then the phases were
separated. The toluene solution was washed with water, then brine,
and dried over sodium sulfate. 2M hydrochloric acid in isopropanol
(224 mL) was added to the batch over 30 minutes and the mixture was
stirred for 1 hour. The solids formed were collected by filtration,
washed with isopropanol and dried to give thiocyclam hydrochloride
in 60% yield (37.0 g) and 95.6% purity.
Example 4
[0052] A mixture of Monosultap (450 g), sodium hydroxide (51.3 g)
and saline was added to a reactor containing toluene at -15 to
-20.degree. C. An aqueous saline solution of Na.sub.2S.9H.sub.2O
(308 g) was added to the batch over 4 hours maintaining the
temperature at -15.degree. C. The reaction mixture was stirred at
-15.degree. C. until complete then the phases were separated. After
an aqueous work-up, the organics were dried over magnesium sulfate
and 2M ethereal hydrochloric acid (710 mL) was added. The mixture
was stirred for 1 hour then the solids formed were collected by
filtration. The cake was washed with toluene and dried to give
thiocyclam hydrochloride in 68% yield (214 g) and 94.2% purity
containing 0.55% residual toluene.
Example 5
[0053] An aqueous saline solution of Na.sub.2S.9H.sub.2O (239.5 g)
was added to a stirring mixture of Monosultap (350 g), sodium
hydroxide (39.9 g) and toluene/saline over 3.5 hours maintaining
the temperature at -16 to -18.degree. C. The reaction mixture was
stirred at -16 to -18.degree. C. until complete then filtered to
remove inorganic salts. The cake was washed with toluene and the
wash was combined with the filtrates. The phases were separated and
the toluene solution was washed with water, then brine, and dried
over sodium sulfate. 2M ethereal hydrochloric acid (680 mL) was
added to the batch over 30 minutes and the mixture was stirred for
1 hour. The solids formed were collected by filtration, washed with
ice-cold MTBE and dried to give thiocyclam hydrochloride in 33%
yield (76.1 g) and 95.2% purity with 0.05% residual toluene.
[0054] The starting material in this novel reaction is Monosultap,
which is a trade name for thiosulfuric acid
S,S'-[2-(dimethylamino)trimethylene] ester monosodium salt,
available from Sigma Aldrich. The CAS no. for Monosultap is
29547-00-0, the empirical formula is
C.sub.5H.sub.12NNaO.sub.6S.sub.4 and its molecular weight is
333.40.
[0055] Thiocyclam hydrochloride is the common name for the compound
of N,N-dimethyl-1,2,3-trithian-5-ylamine hydrochloride, with a
molecular formula of C.sub.5H.sub.12ClNS.sub.3, a relative
molecular weight of 217.803, and with a structure of Formula
(2).
##STR00003##
[0056] In some embodiments, there are provided insecticidal
compositions comprising thiocyclam hydrochloride, as synthesized by
the current inventors, wherein the lethal dose and lethal
concentration of active insecticide is much lower than previously
studied insecticides, therefore making thiocyclam hydrochloride an
effective insecticide. These compositions are particularly useful
in the elimination of target insects on agricultural crops.
[0057] Target sucking insects may include mosquitoes (for example
Aedes aegypti, Aedes vexans, Culex quinquefasciatus, Culex
tarsalis, Anopheles albimanus, Anopheles stephensi, Mansonia
titillans), moth gnats (for example Phlebotomus papatasii), gnats
(for example Culicoides furens), buffalo gnats (for example
Simulium damnosum), stinging flies (for example Stomoxys
calcitrans), tsetse flies (for example Glossina morsitans
morsitans), horse flies (for example Tabanus nigrovittatus,
Haematopota pluvialis, Chrysops caecutiens), true flies (for
example Musca domestica, Musca autumnalis, Musca vetustissima,
Fannia canicularis), flesh flies (for example Sarcophaga carnaria),
myiasis-causing flies (for example Lucilia cuprina, Chrysomyia
chloropyga, Hypoderma bovis, Hypoderma lineatum, Dermatobia
hominis, Oestrus ovis, Gasterophilus intestinalis, Cochliomyia
hominivorax), bugs (for example Cimex lectularius, Rhodnius
prolixus, Triatoma infestans), lice (for example Pediculus humanis,
Haematopinus suis, Damalina ovis), fleas (for example Pulex
irritans, Xenopsylla cheopis, Ctenocephalides canis,
Ctenocephalides felis), and sand fleas (Tunga penetrans). The
current composition is especially effective for eliminating aphids
and white flies.
[0058] Additional target species are Lepidoptera (moths and
butterflies), which is the second largest order in the class
Insecta. Nearly all lepidopteran larvae are called caterpillars.
They have a well-developed head with chewing mouthparts. In
addition to three pairs of legs on the thorax, they have two to
eight pairs of fleshy abdominal prolegs that are structurally
different from the thoracic legs. Most lepidopteran larvae are
herbivores; some species eat foliage, some burrow into stems or
roots, and some are leaf-miners.
[0059] The composition and method of the present invention were
found to be particularly advantageous for use in the control of
insects in crops. Suitable target crops include, for example,
cereals, including wheat, barley, rye, oats, rice, maize, sorghum,
millet and manioc; beets, including sugar beets and fodder beets;
fruits, including pomes, stone fruit and soft fruit, such as
apples, pears, plums, peaches, almonds, cherries, or berries, for
example strawberries, raspberries and blackberries; leguminous
plants, including beans, lentils, peas and soybeans; oil plants,
including rape, mustard, poppy, olives, sunflowers, coconut, castor
oil plants, cocoa beans and groundnuts; cucurbitaceae, including
marrows, cucumbers and melons; fibrous plants, including cotton,
flax, hemp and jute; citrus fruit, including oranges, lemons,
grapefruit and mandarins; vegetables, including spinach, lettuce,
asparagus, cabbages, carrots, onions, tomatoes, potatoes and
paprika; lauraceae, including avocados, cinnamon and camphor; as
well as tobacco, nuts, coffee, aubergines, sugar cane, tea, pepper,
vines, hops, bananas, natural rubber plants, eucalyptus, and
ornamental plants. Examples of some preferred crops for
insecticidal treatment include radish and beans.
[0060] As used herein, the term "insecticide" refers to a compound
used to control (including prevention, reduction or elimination)
parasitic insects. "Controlling insects" as used in the present
invention means killing insects or preventing insects from
developing or growing. Controlling insects as used herein also
encompasses controlling insect progeny (development of viable cysts
and/or egg masses). The compound described herein, may be used to
keep an agricultural crop healthy and may be used curatively,
preventively or systematically to control insects.
[0061] "Agricultural crops" as described herein, may refer to a
wide variety of agricultural plants. When using the compounds
described herein to keep a plant healthy, the controlling of
insects includes the reduction of damage to plants and increased
yield of the crop. The current invention achieves this endeavor by
efficiently ridding a plant of insect pests by using a low
concentration of the insecticidal composition to rid the crop of
larger populations of insects than previous insecticides could
eliminate.
[0062] Insecticidal effects typically relate to diminishing the
occurrence or activity of the target insect. Such effects on the
insect include necrosis, death, retarded growth, diminished
mobility, lessened ability to remain on the host plant, reduced
feeding and inhibition of reproduction. These effects on insects
provide control (including prevention, reduction or elimination) of
parasitic infestation of the plant. Therefore the term "control" of
a parasitic insect means achieving a pesticidal effect on the
insect. The expressions "insecticidally effective amount" and
"biologically effective amount" in the context of applying a
chemical compound to control a parasitic insect refer an amount of
the compound that is sufficient to protect an agricultural crop
from destruction by such insects.
[0063] In the embodiments herein, the total content of components
in the insecticidal composition is 100 weight percent.
[0064] The insecticidal compositions of the present invention may
further contain one or more agriculturally acceptable auxiliaries.
The auxiliaries employed in the insecticidal composition and their
amounts will depend in part upon the type of formulation or
composition and/or the manner in which the formulation is to be
applied. Suitable auxiliaries include, but are not limited to
formulation adjuvant or components, such as solvents, surfactants,
stabilizers, anti-foaming agents, anti-freezing agents, defoamers,
emulsifiers, preservatives, antioxidants, colorants, thickeners and
inert fillers and these auxiliaries may be used individually in the
agrochemical composition or as a combination of one or more
auxiliaries. Auxiliaries may be present in the composition anywhere
from 0.01-90 parts by weight.
[0065] For example, the composition may comprise one or more
solvents, which may be organic or inorganic. Suitable solvents are
those that thoroughly dissolve the agrochemically active substance
employed. Examples of suitable solvents include water, aromatic
solvents, such as xylene (for example solvent products commercially
available from Solvesso.TM.), mineral oils, animal oils, vegetable
oils, alcohols, for example methanol, butanol, pentanol, and benzyl
alcohol; ketones, for example cyclohexanone, and
gamma-butyrolactone, pyrrolidones, such as NMP, and NOP, acetates,
such as glycol diacetate, glycols, fatty acid dimethylamides, fatty
acids, and fatty acid esters.
[0066] The composition may optionally include one or more
surfactants. Suitable surfactants are generally known in the art
and include, but are not limited to, alkali metal, alkaline earth
metal and ammonium salts of lignosulfonic acid, naphthalenesulfonic
acid, phenolsulfonic acid, dibutylnaphthalenesulfonic acid,
alkylarylsulfonates, alkyl sulfates, alkylsulfonatcs,
arylsulfonates, fatty alcohol sulfates, fatty acids and sulfated
fatty alcohol glycol ethers, furthermore condensates of sulfonated
naphthalene and naphthalene derivatives with formaldehyde,
condensates of naphthalene or of naphthalenesulfonic acid with
phenol, octylphenol, nonylphenol, alkylphenyl polyglycol ethers,
tributylphenyl polyglycol ether, tristearylphenyl polyglycol ether,
alkylaryl polyether alcohols, alcohol and fatty alcohol/ethylene
oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl
ethers, ethoxylated polyoxypropylene, lauryl alcohol polyglycol
ether acetal, sorbitol esters, lignin-sulfite waste liquors and
methylcellulose and ethylene oxide/propylene oxide block
copolymers.
[0067] The composition may optionally comprise one or more
polymeric stabilizers. Suitable polymeric stabilizers that may be
used in the present invention include, but are not limited to,
polypropylene, polyisobutylene, polyisoprene, copolymers of
monoolefins and diolefins, polyacrylates, polystyrene, polyvinyl
acetate, polyurethanes or polyamides.
[0068] The composition may include an anti-foaming agent. Suitable
anti-foam agents include, for example, mixtures of
polydimethylsiloxanes and perfluroalkylphosphonic acids, such as
silicone anti-foam agents.
[0069] One or more preservatives may also be present in the
composition. Suitable examples include, for example, Preventol.RTM.
(commercially available from Bayer AG) and Proxel.RTM.
(commercially available from Bayer AG).
[0070] Furthermore, the composition may also include one or more
antioxidants, such as butylated hydroxytoluene.
[0071] The compositions may further comprise one or more solid
adherents. Such adherents are known in the art and available
commercially. They include organic adhesives, including tackifiers,
such as celluloses of substituted celluloses, natural and synthetic
polymers in the form of powders, granules, or lattices, and
inorganic adhesives such as gypsum, silica, or cement.
[0072] The compositions may include one or more inert fillers,
including, for example, natural ground minerals, such as kaolins,
aluminas, talc, chalk, quartz, attapulgite, montmorillonite, and
diatomaceous earth, or synthetic ground minerals, such as highly
dispersed silicic acid, aluminum oxide, silicates, and calcium
phosphates and calcium hydrogen phosphates. Suitable inert fillers
for granules include, for example, crushed and fractionated natural
minerals, such as calcite, marble, pumice, sepiolite, and dolomite,
or synthetic granules of inorganic and organic ground materials, as
well as granules of organic material, such as sawdust, coconut
husks, corn cobs, and tobacco stalks.
[0073] The compositions may also include one or more thickeners,
including, for example, gums, such as xanthan gum, PVOH, cellulose
and its derivatives, clay hydrated silicates, magnesium aluminum
silicates or a mixture thereof.
[0074] The insecticidal composition further may include a safener.
The safener, also called antidote, may comprise, at least one of
isoxadifen-ethyl, 1,8-dicarboxylic anhydride, mefenpyr-diethyl,
fenchlorazole-ethyl, and cloquintocet-mexyl, and in some
embodiments, isoxadifen-ethyl.
[0075] The dosage of the safener may be a conventional dosage used
for matching the thiocyclam hydrochloride. In some embodiments,
relative to 1 part by weight of thiocyclam hydrochloride, the
safener has a content of from 0.1 to 10 parts by weight, or in some
embodiments, from 0.5 to 5 parts by weight.
[0076] In some embodiments of the present invention, the
insecticidal composition may be applied and used in pure form, or
more preferably together with at least one of the auxiliaries, as
described above.
[0077] The composition of the present invention may also comprise
other active ingredients for achieving specific effects, for
example, bactericides, fungicides, nematicides, molluscicides or
herbicides. Suitable compounds are known in the art.
[0078] The insecticidal composition of the present invention may be
formulated in different ways, depending upon the circumstances of
its use. Suitable formulation techniques are known in the art and
include water-dispersible powders, dusts, pastes, water-dispersible
granules, solutions, emulsifiable concentrates, emulsions,
suspension concentrates, aerosols, or microencapsulation
suspensions.
[0079] Examples of formulation types for use in the present
invention include the following: [0080] A) Water-soluble
concentrates, in which thiocyclam hydrochloride and/or solvate
thereof is dissolved in a water-soluble solvent. One or more
wetting agents and/or other auxiliaries may be included. The active
compound dissolves upon dilution with water. [0081] B) Emulsifiable
concentrates, in which thiocyclam hydrochloride and/or solvate
thereof is dissolved in a water-immiscible solvent, preferably with
the addition of one or more non-anionic emulsifiers and anionic
emulsifiers. The mixture is agitated, for example by stirring, to
get a uniform formulation. Dilution with water provides a stable
emulsion. [0082] C) Emulsions, in which thiocyclam hydrochloride
and/or solvate thereof is dissolved in one or more suitable water
immiscible solvents, preferably with the addition of one or more
non-anionic emulsifiers and anionic emulsifiers. The resulting
mixture is introduced into water by appropriate means, such as an
emulsifying machine, to provide a homogeneous emulsion. Dilution
with water gives a stable emulsion. [0083] D) Suspensions, in which
thiocyclam hydrochloride and/or solvate thereof is comminuted in an
agitated ball mill, preferably with the addition of one or more
dispersants and wetting agents, and water or solvent to give a fine
active compound suspension. Dilution with water gives a stable
suspension of the active compound. [0084] E) Water-dispersible
granules and/or water-soluble granules in which thiocyclam
hydrochloride and/or solvate thereof is ground finely, preferably
with the addition of one or more dispersants and wetting agents,
and prepared as water-dispersible or water-soluble granules by
means of suitable techniques, for example by extrusion, drying in a
spray tower, or by processing in a fluidized bed. Dilution with
water gives a stable dispersion or solution of the active compound.
[0085] F) Water-dispersible powders and water-soluble powders, in
which thiocyclam hydrochloride and/or solvate thereof is ground in
a suitable apparatus, such as a rotor-stator mill, preferably with
addition of one or more dispersants, wetting agents and silica gel.
Dilution with water gives a stable dispersion or solution of the
active compound. [0086] G) Granules, in which thiocyclam
hydrochloride and/or solvate thereof is finely ground in a suitable
apparatus, with addition of up to 99.5 parts by weight of carriers.
Granules can then be prepared either by suitable techniques, such
as extrusion, spray-drying or using a fluidized bed.
[0087] In general, the composition or formulation is prepared and
applied such that the insecticidal composition comprising
thiocyclam hydrochloride and/or solvate thereof is applied at any
suitable rate, as demanded by the insect to be treated. The
application rate may vary within wide ranges and depends upon such
factors as the type of application (i.e., foliar application, seed
dressing, application in the seed furrow, etc.), the target crop
plant, the particular insect(s) to be controlled, the climatic
circumstances prevailing in each case, as well as other factors
determined by the type of application, timing of application and
target crop. Typically, the application rate may be from about 1 to
about 2000 g of the insecticidal composition per hectare, and
depending on the various factors described above, may be 10 to 1000
g/ha, more preferably 10 to 500 g/ha, more preferably 10 to 200
g/ha.
[0088] According to the present invention, the use of the
insecticidal composition or formulation comprising thiocyclam
hydrochloride and/or solvate thereof may be applied at any suitable
time. In some embodiments, the composition is applied the locus of
the plant prior to planting, during planting, or after planting.
Such a treatment may take place by conventional methods known in
the art, including, for example, drip-irrigation, chem-irrigation,
and spray. In one embodiment, the insecticidal composition is
contacted with the plant, plant part, or a locus thereof
immediately before or immediately after the plant is
transplanted.
[0089] For application to plant foliage, the insecticidal
composition can be diluted up to about 600-fold or more with water,
more typically up to about 100-fold or up to about 40-fold.
Illustratively, a concentrate product can be applied at about 0.1
to about 30 liter/hectare (l/ha), for example about 5 to about 25
l/ha, in a total application volume after dilution of about 60 to
about 600 l/ha, for example about 80 to about 400 l/ha or about 100
to about 200 l/ha. Other concentrations of the concentrate
compositions disclosed herein can be used. One skilled in the art
will recognize that a particular system may dictate a good working
application rate which may depend in part on both the insects to be
controlled as well as the crop requiring protection. The dosage
range for the components of the inventive insecticidal composition
allows for use of a reduced amount of active ingredient when used
in the composition as described. The result is an inferior dosage
rate that provides a more efficient insecticide.
[0090] As used herein, the term "about" refers to a measurable
value such as a parameter, an amount, a temporal duration, and the
like and is meant to include variations of +/-15% or less,
preferably variations of +1-10% or less, more preferably variations
of +/-5% or less, even more preferably variations of +/-1% or less,
and still more preferably variations of +/-0.1% or less of and from
the particularly recited value, in so far as such variations are
appropriate to perform in the invention described herein.
Furthermore, it is also to be understood that the value to which
the modifier "about" refers is itself specifically disclosed
herein.
[0091] According to the present invention, the use of the
insecticidal composition comprising thiocyclam hydrochloride and/or
solvate thereof for treating plants, plant parts, or a locus
thereof is through the use of various processing methods carried
out directly on the plant or plant parts or to the environment, the
habitat or storage space of the plant or plant parts. These methods
include, for example, dipping, spraying, atomizing, irrigation,
evaporation, powdering, misting, fogging, spreading, foam, coating,
painting, spreading-on, watering, soaking, drip irrigation, and
chemirrigation.
[0092] While certain forms of thiocyclam are known for use as a
pesticide, the use of thiocyclam hydrochloride has not previously
been successfully manufactured and therefore not contemplated for
use as an insecticide. The reduced concentration and increased
efficiency provided by the use of the synthesized thiocyclam
hydrochloride were both surprising and unexpected. The following
are non-limiting examples, wherein thiocyclam hydrochloride is
compared to previously known insecticides, cartap and thiocyclam
oxalate.
[0093] These examples are merely illustrations and are not to be
understood as limiting the scope and underlying principles of the
invention in any way. Various modifications of the invention in
addition to those shown and described herein will become apparent
to those skilled in the art form after the following examples and
foregoing description. Such modifications are also intended to fall
within the scope of the appended claims.
Example 1
[0094] Codling Moth, Cydia pomonella--Neonate Larvae
[0095] Bioassay by diet incorporation
[0096] Mortality assessment 2 days after treatment.
[0097] a.i. refers to active ingredient
TABLE-US-00001 LC50 LC90 (.mu.g of (.mu.g of Purity a.i./ml a.i/ml
of of of D + 2 a.i. diet) min max diet) Min max Cartap 50% 10.14
7.98 12.87 104.80 74.72 157.80 Thiocyclam 87.5% 3.57 3.00 4.25
19.76 15.53 26.32 oxalate Thiocyclam 100% 2.57 2.14 3.09 10.80 8.41
14.79 HCl
Example 2
[0098] Soybean Looper, Chrysodeixis includens--3rd Larval Stage
[0099] Bioassay by diet surface incorporation
[0100] Mortality assessment 3 days after treatment
[0101] a.i. refers to active ingredient
TABLE-US-00002 LC50 (.mu.g of a.i./ml LC90 D + 3 Purity of a.i. of
diet) min max (.mu.g of a.i./ml) Min max Cartap 50% 53,069 31,907
106,810 908,897 346,473 4.64 .times. 10.sup.6 Thiocyclam 87.5%
173,363 52,529 2.38 .times. 10.sup.6 8.55 .times. 10.sup.6 906,914
1.53 .times. 10.sup.9 oxalate Thiocyclam 100% 8,992 6,520 12,564
251,759 145,956 504,401 HCl
Example 3
[0102] Aphids, Myzus persicae--Larvae
[0103] Study based on IRAC no 019 methods, application method
adapted
[0104] Plant: radish
[0105] Application on petri dish with larvae with a boom sprayer
apparatus
[0106] Assessment of mortality 3 and 4 days after application
[0107] a.i. refers to active ingredient
TABLE-US-00003 Purity of LD50 LD90 a.i. (g a.i./ha) min max (g
a.i./ha) D + 3 Cartap 50% <18.18 NA NA 36.70 Thiocyclam 87.5%
7.99 1.40 54.98 38.06 oxalate Thiocyclam 100% 12.04 0.40 358.91
30.51 HCl D + 4 Cartap 50% <18.18 NA NA 16 Thiocyclam 87.5% 5.35
2.60 10.27 29.57 oxalate Thiocyclam 100% 7.66 2.30 25.48 27.07
HCl
Example 4
[0108] White Flies, Trialeurodes vaporarium--Larvae
[0109] Study based on IRAC n.degree. 015 methods, stage and
application method adapted
[0110] Plant: bean
[0111] Application: On the petri dish with larvae with a boom
sprayer apparatus
[0112] Assessment of mortality at 7, 9 and 14 days after
application
[0113] a.i. refers to active ingredient
TABLE-US-00004 Purity of LD50 LD90 a.i. (g a.i./ha) min max (g
a.i./ha) D + 7 Cartap 50% 213.7 0.76 2.23 .times. 10.sup.8 2.3
.times. 10.sup.6 Thiocyclam 87.5% 19.5 16.4 24.8 54.2 oxalate
Thiocyclam 100% 2.22 0.71 4.15 1,899 HCl D + 9 Cartap 50% 15.6
0.027 8,923.2 4,566.3 Thiocyclam 87.5% 15.3 1.6 147.6 138.3 oxalate
Thiocyclam 100% 2.23 0.12 38.9 4,905 HCl D + 14 Cartap 50% 10.4
0.05 2,098.7 910.4 Thiocyclam 87.5% 15.7 1.12 219 153.1 oxalate
Thiocyclam 100% 0.82 0.018 386.3 7,910 HCl
[0114] LC stands for "Lethal Concentration". LC values refer to the
concentration of a chemical required to kill a certain proportion
of a population of pests. The concentration of the chemical that
kills 50 percent of the pests during the observation period is the
LC50 value and a concentration that kills 90 percent of a
population is LC90.
[0115] LD stands for "Lethal Dose". LD50 is the amount of an
ingested substance that kills 50 percent of a test sample and LC90
is the lethal dose that kills 90 percent of the test sample.
[0116] As can be seen from the results in the examples, thiocyclam
hydrochloride with high purity has been manufactured using the
methods described herein, so that a low concentration of thiocyclam
hydrochloride can be used to effectively eliminate insects similar
to or better than prior known insecticides.
[0117] In example 1, approximately 4 times less thiocyclam
hydrochloride was ingested by the moths at LC50 compared to cartap
and approximately 9 times less at LC90 compared to cartap. The
thiocyclam hydrochloride produced by the methods provided herein
also achieved an LC50 and LC90 at significantly lower
concentrations than thiocyclam oxalate. In example 2, the LC50 of
the soybean looper was achieved with approximately 6 times less
thiocyclam hydrochloride than cartap and approximately 20 times
less thiocyclam hydrochloride than thiocyclam oxalate. The LC90 of
the soybean looper was orders of magnitude smaller using thiocyclam
hydrochloride compared to thiocyclam oxalate, and the LC90 for
thiocyclam hydrochloride was more than three times lower than the
concentration of cartap. In example 3, all three insecticides
performed similarly to eliminate the aphids on radish plants. In
example 4, the thiocyclam hydrochloride outperforms the other
insecticides significantly for achieving LD50, on all assessment
days. At all assessment days, the LD90 was achieved at the lowest
concentration using thiocyclam oxalate. On days 7 and 9, thiocyclam
hydrochloride achieved the LD90 at a lower application
concentration compared to cartap.
[0118] The use of the thiocyclam hydrochloride composition
embodiments is in no way restricted to these genera, but also
extends in the same manner to other insects and other crops. The
novel high purity manufacturing method for thiocyclam hydrochloride
has surprisingly allowed for improved insecticidal qualities when
the thiocyclam hydrochloride is used in insecticidal compositions
and applied to agricultural crops.
[0119] The invention is generally disclosed herein using
affirmative language to describe the numerous embodiments. The
invention also specifically includes embodiments in which
particular subject matter is excluded, in full or in part, such as
substances or materials, method steps and conditions, protocols,
procedures, assays or analysis. Thus, even though the invention is
generally not expressed herein in terms of what the invention does
not include aspects that are not expressly included in the
invention are nevertheless disclosed herein.
[0120] A number of embodiments of the invention have been
described. Nevertheless, it will be understood that various
modifications may be made without departing from the spirit and
scope of the invention.
[0121] In addition, it shall be pointed out that specific technical
features described in the above specific embodiments, if
reconcilable, can be combined in any appropriate manner, and in
order to avoid unnecessary repetition, various possible combination
manners are not otherwise stated herein any more.
* * * * *