U.S. patent application number 15/225396 was filed with the patent office on 2017-02-02 for labile esters of agrochemicals for controlled release and reduction of off-site movement.
The applicant listed for this patent is Monsanto Technology LLC. Invention is credited to David A. Morgenstern.
Application Number | 20170029355 15/225396 |
Document ID | / |
Family ID | 47221533 |
Filed Date | 2017-02-02 |
United States Patent
Application |
20170029355 |
Kind Code |
A1 |
Morgenstern; David A. |
February 2, 2017 |
LABILE ESTERS OF AGROCHEMICALS FOR CONTROLLED RELEASE AND REDUCTION
OF OFF-SITE MOVEMENT
Abstract
The present invention relates to esters of carboxylic acid
agrochemicals comprising a labile protecting group and having
formula (I). Certain of the esters of carboxylic acid agrochemicals
do not undergo hydrolysis to a significant degree in the dark, but
are cleaved to regenerate the parent carboxylic acid agrochemical
when exposed to light. Others of the esters of carboxylic acid
agrochemicals undergo hydrolysis under both light and dark
conditions. The present invention further relates to methods for
the controlled release of a carboxylic acid agrochemicals, and to
methods of controlling unwanted plants comprising applying to the
unwanted plants an ester of a carboxylic acid agrochemical.
Inventors: |
Morgenstern; David A.;
(Creve Coeur, MO) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Monsanto Technology LLC |
St. Louis |
MO |
US |
|
|
Family ID: |
47221533 |
Appl. No.: |
15/225396 |
Filed: |
August 1, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14351209 |
Apr 11, 2014 |
9402396 |
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PCT/US2012/059792 |
Oct 11, 2012 |
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15225396 |
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61545731 |
Oct 11, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07C 205/34 20130101;
C07D 241/44 20130101; C07D 237/32 20130101; C07C 65/21 20130101;
C07D 213/69 20130101; A01N 39/04 20130101; C07C 205/37 20130101;
C07D 213/64 20130101; C07C 205/56 20130101; C07D 237/16 20130101;
C07C 205/42 20130101; Y02P 20/55 20151101; A01N 43/58 20130101;
C07C 69/92 20130101; C07D 213/85 20130101; C07C 69/712 20130101;
C07D 215/32 20130101; A01N 43/42 20130101; C07D 237/26 20130101;
A01N 43/60 20130101; C07D 213/63 20130101; C07D 213/84 20130101;
C07C 255/55 20130101; A01N 43/40 20130101; Y02P 20/582 20151101;
A01N 37/38 20130101; C07D 241/18 20130101; A01N 37/40 20130101;
C07C 205/43 20130101 |
International
Class: |
C07C 65/21 20060101
C07C065/21; A01N 37/38 20060101 A01N037/38; C07C 205/42 20060101
C07C205/42; C07C 69/92 20060101 C07C069/92; C07D 237/26 20060101
C07D237/26; A01N 43/60 20060101 A01N043/60; C07D 213/64 20060101
C07D213/64; A01N 43/40 20060101 A01N043/40; C07D 237/16 20060101
C07D237/16; A01N 43/58 20060101 A01N043/58; A01N 37/40 20060101
A01N037/40; C07D 241/44 20060101 C07D241/44 |
Claims
1. An ester of a carboxylic acid agrochemical comprising a labile
protecting group and having the formula (I): ##STR00100## wherein
LPG is the labile protecting group, and the carboxylic acid
agrochemical has the formula (II): ##STR00101## wherein A
represents the remainder of the carboxylic acid agrochemical bonded
to the carboxylic acid moiety.
2. The ester of a carboxylic acid agrochemical of claim 1, wherein
the carboxylic acid agrochemical is a herbicide, a fungicide, an
insecticide, a plant health agent, or a plant growth regulator.
3. The ester of a carboxylic acid agrochemical of claim 2, wherein
the carboxylic acid agrochemical is a herbicide selected from the
group consisting of dicamba, 2,4-dichlorophenoxyacetic acid
(2,4-D), fenoxaprop, fenoxaprop-P, desmedipham, cyhalofop,
carfentrazone, flufenpyr, fluthiacet, fluroglycofen, pyraflufen,
flumiclorac, 4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB),
fluroxypyr, picloram, quinclorac, benazolin, clodinafop,
4-(2,4-dichlorophenoxy)butanoic acid (2,4-DB),
2,4,5-trichlorophenoxyacetic acid (2,4,5-T), dichlorprop,
dichlorprop-P, diethatyl, endothall, fluazifop, flufenpyr,
flumiclorac, fluoroglycofen, haloxyfop, indole-3-acetic acid,
indole-3-butyric acid, mecoprop, mecoprop-P, pyrafluren, fenoprop,
triclopyr, aminopyralid, bispyribac, chlorthal, imazamethabenz,
pyrothiobac, quinmerac, quizalofop, quizalofop-P, diclofop, and
lactofen.
4. The ester of a carboxylic acid agrochemical of claim 3, wherein
the carboxylic acid agrochemical is dicamba.
5. The ester of a carboxylic acid agrochemical of claim 3, wherein
the carboxylic acid agrochemical is 2,4-dichlorophenoxyacetic acid
(2,4-D).
6. The ester of a carboxylic acid agrochemical of claim 2, wherein
the carboxylic acid agrochemical is: a fungicide selected from the
group consisting of benalaxyl and picoxystrobin; a plant health
agent selected from the group consisting of salicylic acid and
3,6-dichlorosalicylic acid; or a plant growth regulator selected
from the group consisting of cloprop and 4-chlorophenoxyacetic acid
(4-CPA).
7. The ester of a carboxylic acid agrochemical of claim 1, wherein
the labile protecting group comprises a nitrophenyl moiety.
8. The ester of a carboxylic acid agrochemical of claim 7, wherein
the ester of a carboxylic acid agrochemical has the formula (III):
##STR00102## wherein R is C(R.sub.7R.sub.8), O, or S; R.sub.1 is
C(R.sub.9R.sub.10), O, or S; provided that when R is O or S,
R.sub.1 must be C(R.sub.9R.sub.10), and when R.sub.1 is O or S, R
must be C(R.sub.7R.sub.8); R.sub.7, R.sub.8, R.sub.9, and R.sub.10
are independently H, CH.sub.3, or CH.sub.2CH.sub.3; at least one of
R.sub.2 and R.sub.3 is NO.sub.2 and the other is H, acyclic
aliphatic, amine, NO.sub.2 or alkoxy; R.sub.4 is H, alkoxy, acyclic
aliphatic, amine, NO.sub.2, or an ester having the formula (IV):
##STR00103## wherein R.sub.11 is C.sub.1-C.sub.18 acyclic
aliphatic; R.sub.5 and R.sub.6 are independently H, alkoxy, acyclic
aliphatic, amine, or NO.sub.2; provided that if any of R.sub.2,
R.sub.3, R.sub.4, R.sub.5 and R.sub.6 is acyclic aliphatic, the
acyclic aliphatic does not comprise a double or triple bond between
the .alpha. and .beta. carbons; n is 0 or 1; and m is 0-3, provided
that if R is O and n is 0, m is at least 1.
9.-16. (canceled)
17. The ester of a carboxylic acid agrochemical of claim 1, wherein
the photolabile protecting group comprises a phenacylmethyl ester
moiety.
18. The ester of a carboxylic acid agrochemical of claim 17,
wherein the ester of a carboxylic acid agrochemical has the formula
(V): ##STR00104## wherein R.sub.2 is hydroxy, alkoxy, or
substituted alkoxy; and R.sub.1 and R.sub.3 are independently H,
hydroxy, alkoxy, substituted alkoxy, or C.sub.1-C.sub.18
unsubstituted or substituted acyclic aliphatic, provided that if
either of R.sub.1 and R.sub.3 is C.sub.1-C.sub.18 unsubstituted or
substituted acyclic aliphatic, the acyclic aliphatic does not
comprise a double or triple bond between the .alpha. and .beta.
carbons.
19.-22. (canceled)
23. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula (VI):
##STR00105## wherein at least one of R and R.sub.1 is N, and the
other of R and R.sub.1 is N or C--R.sub.5; R.sub.2 is N or CH;
R.sub.3 and R.sub.4 are H, acyclic alkyl, substituted acyclic
alkyl, or together form a phenyl ring; and R.sub.5 is H, acyclic
alkyl, or substituted acyclic alkyl.
24.-31. (canceled)
32. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula (VII):
##STR00106## wherein R.sub.1 and R.sub.2 are independently H or
C.sub.1-C.sub.8 alkyl, or together form a phenyl ring.
33.-35. (canceled)
36. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula (VIII):
##STR00107## wherein R.sub.1, R.sub.2, and R.sub.3 are alkyl.
37.-40. (canceled)
41. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula (IX):
##STR00108## wherein R.sub.1 and R.sub.2 are halogen.
42.-43. (canceled)
44. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula (X):
##STR00109##
45. (canceled)
46. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula (XI):
##STR00110##
47. (canceled)
48. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester is a substituted or unsubstituted aromatic ester of
dicamba or 2,4-dichlorophenoxyacetic acid (2,4-D).
49. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula:
##STR00111## wherein at least one of R.sub.1, R.sub.2, and R.sub.3
is an electron-donating group; and the others of R.sub.1, R.sub.2,
and R.sub.3 are independently H or an electron-donating group;
provided that none of R.sub.1, R.sub.2, and R.sub.3 is an
electron-withdrawing group.
50.-53. (canceled)
54. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula:
##STR00112## wherein at least one of R.sub.1, R.sub.2, and R.sub.3
is an electron-donating group; and the others of R.sub.1, R.sub.2,
and R.sub.3 are independently H or an electron-donating group;
provided that none of R.sub.1, R.sub.2, and R.sub.3 is an
electron-withdrawing group.
55.-58. (canceled)
59. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula:
##STR00113## wherein R is alkyl, aryl, or alkoxy; at least one of
R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 is an
electron-withdrawing group; and the others of R.sub.1, R.sub.2,
R.sub.3, R.sub.4, and R.sub.5 are independently H, alkyl, alkoxy,
dialkylamino or halogen.
60.-65. (canceled)
66. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula:
##STR00114## wherein R.sub.1 is an electron-withdrawing group; and
wherein R.sub.2 and R.sub.3 are independently H or alkyl.
67.-71. (canceled)
72. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula:
##STR00115## wherein R.sub.1 is alkyl and R.sub.2 is H, alkyl, or
aryl.
73.-75. (canceled)
76. The ester of a carboxylic acid agrochemical of claim 1, wherein
the ester of a carboxylic acid agrochemical has the formula:
##STR00116## wherein R.sub.1 is an electron-withdrawing group; and
R.sub.2 is H, a hydrocarbon, or an aromatic group.
77.-83. (canceled)
84. A composition comprising an ester of a carboxylic acid
agrochemical of claim 1.
85.-91. (canceled)
92. A method for the controlled release of a carboxylic acid
agrochemical comprising exposing an ester of a carboxylic acid
agrochemical of claim 1 to artificial or natural light, wherein the
natural light is optionally sunlight and the artificial light is
optionally incandescent light or fluorescent light.
93. (canceled)
94. A method of controlling unwanted plants comprising applying to
the unwanted plants an ester of a carboxylic acid agrochemical of
claim 1.
95. The method of claim 94, wherein the carboxylic acid
agrochemical is dicamba or 2,4-dichlorophenoxyacetic acid
(2,4-D).
96.-101. (canceled)
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 14/351,209, filed on Apr. 11, 2014, which is a U.S.
National of PCT Application No. PCT/US2012/059792, filed Oct. 11,
2012, which claims the benefit of U.S. Provisional Patent
Application Ser. No. 61/545,731, filed on Oct. 11, 2011. Each of
the above-cited applications is incorporated herein by reference in
its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to the field of agrochemistry,
and more particularly to esters of carboxylic acid agrochemicals
comprising a labile protecting group. The present invention further
relates to methods for the controlled release of a carboxylic acid
agrochemicals, and to methods of controlling unwanted plants
comprising applying to the unwanted plants an ester of a carboxylic
acid agrochemical.
BACKGROUND OF THE INVENTION
[0003] Agrochemicals are typically applied either as a solution or
as a suspension of a fine powder. It is often desirable for the
agrochemical to remain either near the surface of the soil (in the
case of many insecticides and pre-emergent herbicides, for example)
or within the root zone for active agents that are taken up through
the roots, such as fertilizers and certain herbicides. However, in
many cases, agrochemicals are rapidly depleted from the soil zone
in which they are most effective. Among the mechanisms of depletion
are metabolism by bacteria, surface runoff and wash-down deep into
the soil by rain, and volatilization. Such depletion leads to a
loss of efficacy, and can also result in contamination of surface
and groundwater.
[0004] One approach to extending residual activity and reducing the
offsite movement of an agrochemical involves impregnating the
agrochemical into an inert matrix. Under favorable conditions,
controlled release of the agrochemical can take place. For example,
U.S. Pat. No. 6,890,888 describes impregnating urea and other
fertilizers into expanded perlite, which can be soil-applied to
achieve controlled release. Agrochemicals can also be impregnated
into clays or polymer particles, as described, for example, in U.S.
Pat. No. 5,908,632 and the references cited therein. Alternatively,
an agrochemical can be chemically linked to a polymer. For example,
Kenawy et al. (J. Appl. Polymer Sci. 80: 415-21 (2001)) describes
linking 2,4-dichlorophenoxyacetic acid (2,4-D) to a polymer
backbone via an amide linkage.
[0005] For herbicides that can cause crop injury at high rate,
micro-encapsulation can reduce crop injury by providing controlled
release while reducing off-site movement. For example, Bollich et
al. (Weed Technology 14:89-93 (2000)) describes micro-encapsulation
of clomazone. Several commercial microencapsulated herbicides are
also available, for example, the COMMAND.RTM. (FMC Corp, clomazone)
and WARRANT.RTM. (Monsanto, acetochlor) products.
[0006] Achieving controlled release is particularly challenging for
agrochemicals that contain carboxylic acid groups. Such
agrochemicals are referred to herein as "carboxylic acid
agrochemicals." Carboxylic acid agrochemicals exist in the form of
salts or zwitterions when released in the field, rendering them
water soluble. Waterborne movement of agrochemicals containing
carboxylic acid groups is therefore facile. In addition, the water
solubility of these compounds leads to rapid leaching from matrices
which can be used for controlled release of other molecules and
complicates formation of microcapsules, a process which is
typically conducted in a 2-phase, water-organic mixture with the
active in the organic phase.
[0007] Alkyl esters of carboxylic acid agrochemicals exhibit
reduced water solubility. For example, as described in the
Herbicide Handbook (9.sup.th ed., 2007), the methyl ester of
diclofop, the ethyl esters of fenoxaprop-P and desmedipham, and the
butyl ester of cyhalofop along with many alkyl esters of 2,4-D are
used as herbicides. However, alkyl esters of certain carboxylic
acid agrochemicals hydrolyze rapidly in the soil, rendering them
more susceptible to microbial degradation. As a result, alkyl
esters of such carboxylic acid agrochemicals seldom if ever have
significant residual activity. On the other hand, hindered aromatic
esters previously known in the art typically hydrolyze far too
slowly and are not practical for controlled release of
agrochemicals.
[0008] Thus, there exists a need in the art for a method of
achieving controlled release of carboxylic acid agrochemicals. This
need is particularly acute for molecules which can cause damage to
crops in neighboring fields by volatilization, for example, the
auxin-mimic herbicides dicamba and 2,4-D.
SUMMARY OF THE INVENTION
[0009] The present invention is directed to esters of a carboxylic
acid agrochemicals comprising a photolabile or hydrolytically
labile protecting group and having the formula (I):
##STR00001##
[0010] In formula (I), LPG is the labile protecting group, and the
carboxylic acid agrochemical has the formula (II):
##STR00002##
wherein A represents the remainder of the carboxylic acid
agrochemical bonded to the carboxylic acid moiety.
[0011] In various embodiments, the ester of a carboxylic acid
agrochemical has a photolabile group that comprises a nitrophenyl
moiety. For example, in some embodiments, the ester of a carboxylic
acid agrochemical has the formula (III):
##STR00003##
wherein R is C(R.sub.7R.sub.8), O, or S; R.sub.1 is
C(R.sub.9R.sub.10), O, or S; provided that when R is O or S,
R.sub.1 must be C(R.sub.9R.sub.10), and when R.sub.1 is O or S, R
must be C(R.sub.7R.sub.8); R.sub.7, R.sub.8, R.sub.9, and R.sub.10
are independently H, CH.sub.3, or CH.sub.2CH.sub.3; at least one of
R.sub.2 and R.sub.3 is NO.sub.2 and the other is H, acyclic
aliphatic, amine, NO.sub.2 or alkoxy; R.sub.4 is H, alkoxy, acyclic
aliphatic, amine, NO.sub.2, or an ester having the formula
(IV):
##STR00004##
wherein R.sub.11 is C.sub.1-C.sub.18 acyclic aliphatic; R.sub.5 and
R.sub.6 are independently H, alkoxy, acyclic aliphatic, amine, or
NO.sub.2; provided that if any of R.sub.2, R.sub.3, R.sub.4,
R.sub.5 and R.sub.6 is acyclic aliphatic, the acyclic aliphatic
does not comprise a double or triple bond between the .alpha. and
.beta. carbons; n is 0 or 1; and m is 0-3, provided that if R is O
and n is 0, m is at least 1.
[0012] In other embodiments, the ester of a carboxylic acid
agrochemical has a photolabile group that comprises a
phenacylmethyl ester moiety. In some such embodiments, the ester of
a carboxylic acid agrochemical has the formula (V):
##STR00005##
wherein R.sub.2 is hydroxy, alkoxy, or substituted alkoxy; and
R.sub.1 and R.sub.3 are independently H, hydroxy, alkoxy,
substituted alkoxy, or C.sub.1-C.sub.18 unsubstituted or
substituted acyclic aliphatic, provided that if either of R.sub.1
and R.sub.3 is C.sub.1-C.sub.18 unsubstituted or substituted
acyclic aliphatic, the acyclic aliphatic does not comprise a double
or triple bond between the .alpha. and .beta. carbons.
[0013] In yet other embodiments, the ester of a carboxylic acid
agrochemical has the formula (VI):
##STR00006##
wherein at least one of R and R.sub.1 is N, and the other of R and
R.sub.1 is N or C--R.sub.5;
R.sub.2 is N or CH;
[0014] R.sub.3 and R.sub.4 are H, acyclic alkyl, substituted
acyclic alkyl, or together form a phenyl ring; and R.sub.5 is H,
acyclic alkyl, or substituted acyclic alkyl.
[0015] In still other embodiments, the ester of a carboxylic acid
agrochemical has the formula (VII):
##STR00007##
wherein R.sub.1 and R.sub.2 are independently H or C.sub.1-C.sub.8
alkyl, or together form a phenyl ring.
[0016] In various other embodiments, the ester of a carboxylic acid
agrochemical has the formula (VIII):
##STR00008##
wherein R.sub.1, R.sub.2, and R.sub.3 are alkyl.
[0017] Moreover, in some embodiments, the ester of a carboxylic
acid agrochemical has the formula (IX):
##STR00009##
wherein R.sub.1 and R.sub.2 are halogen.
[0018] In other embodiments, the ester of a carboxylic acid
agrochemical has the formula (X):
##STR00010##
[0019] In yet other embodiments, the ester of a carboxylic acid
agrochemical has the formula (XI):
##STR00011##
[0020] In other embodiments, the ester of a carboxylic acid
agrochemical has the formula (XII):
##STR00012##
wherein at least one of R.sub.1, R.sub.2, and R.sub.3 is an
electron-donating group; and the others of R.sub.1, R.sub.2, and
R.sub.3 are independently H or an electron-donating group; provided
that none of R.sub.1, R.sub.2, and R.sub.3 is an
electron-withdrawing group.
[0021] In still other embodiments, the ester of a carboxylic acid
agrochemical has the formula (XIII):
##STR00013##
wherein at least one of R.sub.1, R.sub.2, and R.sub.3 is an
electron-donating group; and the others of R.sub.1, R.sub.2, and
R.sub.3 are independently H or an electron-donating group; provided
that none of R.sub.1, R.sub.2, and R.sub.3 is an
electron-withdrawing group.
[0022] In other embodiments, the ester of a carboxylic acid
agrochemical has the formula (XIV):
##STR00014##
wherein R is alkyl, aryl, or alkoxy; at least one of R.sub.1,
R.sub.2, R.sub.3, R.sub.4, and R.sub.5 is an electron-withdrawing
group; and the others of R.sub.1, R.sub.2, R.sub.3, R.sub.4, and
R.sub.5 are independently H, alkyl, alkoxy, dialkylamino, or
halogen.
[0023] In further embodiments, the ester of a carboxylic acid
agrochemical has the formula (XV):
##STR00015##
wherein R.sub.1 is an electron-withdrawing group; and wherein
R.sub.2 and R.sub.3 are independently H or alkyl.
[0024] In still further embodiments, the ester of a carboxylic acid
agrochemical has the formula (XVI):
##STR00016##
wherein R.sub.1 is alkyl and R.sub.2 is H, alkyl, or aryl.
[0025] In yet other embodiments, the ester of a carboxylic acid
agrochemical has the formula (XVII):
##STR00017##
wherein R.sub.1 is an electron-withdrawing group; and R.sub.2 is H,
a hydrocarbon, or an aromatic group.
[0026] In addition, in various embodiments, the ester of a
carboxylic acid agrochemical is a substituted or unsubstituted
aromatic ester of dicamba or 2,4-dichlorophenoxyacetic acid
(2,4-D).
[0027] The present invention is further directed to agrochemical
compositions comprising any of the esters of carboxylic acid
agrochemicals described herein.
[0028] The present invention is also directed to methods for the
use of the esters of carboxylic acid agrochemicals. In some
embodiments, the present invention is directed to methods for the
controlled release of a carboxylic acid agrochemical. Some such
methods comprise exposing an ester of a carboxylic acid
agrochemical as described herein to artificial or natural light.
Other of these methods comprise exposing an ester of a carboxylic
acid agrochemical as described herein to aqueous conditions.
[0029] In other embodiments, the present invention is directed to a
method of controlling unwanted plants. Such methods comprise
applying to the unwanted plants an ester of a carboxylic acid
agrochemical as described herein.
[0030] In yet other embodiments, the invention relates to a method
for the controlled release of a compound comprising exposing the
compound to natural or artificial light or exposing the compound to
aqueous conditions, wherein the compound has been chemically
modified to have an ester linkage to a labile protecting group
having one of the following structures:
##STR00018##
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIG. 1 is a schematic diagram showing a process for the
preparation of 2-nitrobenzyl esters of carboxylic acid
agrochemicals.
[0032] FIG. 2 is a schematic diagram showing a process for the
preparation of 4-methyoxyphenacylmethyl esters of carboxylic acid
agrochemicals.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0033] It has now been discovered that certain esters of carboxylic
acid agrochemicals do not undergo hydrolysis to a significant
degree in the dark, but are cleaved to regenerate the parent
carboxylic acid compound when exposed to light. Such esters of
carboxylic acid agrochemicals are of value for reducing volatility,
off-site movement, and aqueous solubility of the agrochemical.
Reducing the aqueous solubility improves residual activity by
reducing washoff and washdown into the soil and facilitating
controlled release technologies such as suspension concentrates and
micro-encapsulation.
[0034] It has additionally been discovered that certain esters of
carboxylic acid agrochemicals undergo conversion to the
agronomically active acid by hydrolysis under typical agronomic
conditions, while still others undergo both hydrolysis and
photolysis.
[0035] Described herein are esters of carboxylic acid agrochemicals
comprising a photolabile or hydrolytically labile protecting group
having the formula (I):
##STR00019##
In formula (I), LPG represents the labile protecting group, and the
carboxylic acid agrochemical has the formula (II):
##STR00020##
wherein A represents the remainder of the carboxylic acid
agrochemical bonded to the carboxylic acid moiety. Some of these
esters of carboxylic acid agrochemicals undergo photo-induced
cleavage substantially to a carboxylic acid agrochemical of formula
(II) when exposed to natural or artificial light. Others of these
esters undergo hydrolytic conversion substantially to a carboxylic
acid agrochemical of formula (II) when exposed to moisture in the
environment. These hydrolytically labile esters are suitably
formulated as an emulsifiable concentrates in non-aqueous organic
solvents in order to prevent premature hydrolysis.
[0036] The photolabile protecting groups of the esters of
carboxylic acid agrochemicals described herein contain an aromatic
moiety. The aromatic moiety is typically somewhat hindered to
prevent rapid hydrolysis of the ester in the absence of light.
These esters are stable to hydrolysis so long as they are not
exposed to high levels of light during storage, but convert to the
agronomically active compound when exposed to natural or artificial
light, for example when exposed to sunlight following application
of an agrochemical formulation containing the ester to a field
(e.g., by spraying). Esters of formulas (III), (V), (VI) (VIII),
(IX), (X), (XI), (XIII), (XIV), and (XV) undergo photolysis.
[0037] Esters of aromatic carboxylic acid agrochemicals, such as
dicamba, are typically resistant to hydrolysis under typical
agronomic conditions. However, esters of carboxylic acid
agrochemicals of formulas (VI), (VII), (XII), (XIV), (XV), (XVI),
and (XVII) undergo hydrolysis at typical agronomic temperatures at
rates (days to weeks) which provide good activity while reducing
offsite movement. The esters of formulas (VI), (XIV), and (XV)
undergo both hydrolysis and photolysis.
Carboxylic Acid Agrochemicals
[0038] Generally, any agrochemical that contains a carboxylic acid
moiety can be esterified to form the labile esters described
herein. Thus, many different types of agrochemicals can be
esterified to form the labile esters. For example, the agrochemical
can be a herbicide, a fungicide, an insecticide, a plant health
agent, or a plant growth regulator. Other types of agrochemicals
can also be used to form the labile esters, so long as the
agrochemical has a carboxylic acid moiety.
[0039] In various embodiments, the carboxylic acid agrochemical is
an auxin-mimic herbicide such as dicamba or
2,4-dichlorophenoxyacetic acid (2,4-D). For example, in certain
embodiments of the present invention, the ester of a carboxylic
acid agrochemical is a substituted or unsubstituted aromatic ester
of dicamba or 2,4-D.
[0040] Suitable herbicides also include, but are not limited to
fenoxaprop, fenoxaprop-P, desmedipham, cyhalofop, carfentrazone,
flufenpyr, fluthiacet, fluroglycofen, pyraflufen, flumiclorac,
4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB), fluroxypyr,
picloram, quinclorac, benazolin, clodinafop,
4-(2,4-dichlorophenoxy)butanoic acid (2,4-DB),
2,4,5-trichlorophenoxyacetic acid (2,4,5-T), dichlorprop,
dichlorprop-P, diethatyl, endothall, fluazifop, flufenpyr,
flumiclorac, fluoroglycofen, haloxyfop, indole-3-acetic acid,
indole-3-butyric acid, mecoprop, mecoprop-P, pyrafluren, fenoprop,
triclopyr, aminopyralid, bispyribac, chlorthal, imazamethabenz,
pyrothiobac, quinmerac, quizalofop, quizalofop-P, diclofop, and
lactofen. The structure of lactofen includes an ethyl ester which
is hydrolyzed rapidly in situ to form the active form of the
herbicide. The term "lactofen" as used herein refers to the active
form of the herbicide, which includes a carboxylic acid moiety.
[0041] Suitable fungicides include, but are not limited to,
benalaxyl and picoxystrobin. The terms "benalaxyl" and
"picoxystrobin" are used in the art to refer to both the active
forms of the compounds, which include carboxylic acid moieties, and
to the methyl esters of the compounds. As used herein, the terms
"benalaxyl" and "picoxystrobin" refer to the active forms of the
compounds.
[0042] Suitable plant health agents include, but are not limited
to, salicylic acid and 3,6-dichlorosalicylic acid. Suitable plant
growth regulators include, but are not limited to cloprop and
4-chlorophenoxyacetic acid (4-CPA).
[0043] Typically, the labile esters are esters of agrochemicals
that contain an aromatic carboxylic acid (e.g., dicamba). Aromatic
carboxylic acids are more resistant to hydrolysis, thus providing
better control of the release rate.
[0044] Although the following description of the labile esters and
their synthesis, formulation, and use focuses on esters of dicamba
and 2,4-D, the person having ordinary skill in the art will
recognize that the same principles and methodology are applicable
to other carboxylic acid agrochemicals.
Esters of Carboxylic Acid Agrochemicals Comprising a Labile
Protecting Group
[0045] A. Nitrophenyl Esters
[0046] Several classes of esters of carboxylic acid agrochemicals
have been found to undergo photo-induced cleavage to form the
agronomically active carboxylic acid agrochemical when exposed to
natural or artificial light. The first of these classes are the
nitrophenyl esters. In the nitrophenyl esters, the photolabile
protecting group of the ester of a carboxylic acid agrochemical
comprises a nitrophenyl moiety. These nitrophenyl esters of
carboxylic acid agrochemicals typically have the formula (III):
##STR00021##
wherein R is C(R.sub.7R.sub.8), O, or S; R.sub.1 is
C(R.sub.9R.sub.10), O, or S; provided that when R is O or S,
R.sub.1 must be C(R.sub.9R.sub.10), and when R.sub.1 is O or S, R
must be C(R.sub.7R.sub.8); R.sub.7, R.sub.8, R.sub.9, and R.sub.10
are independently H, CH.sub.3, or CH.sub.2CH.sub.3; at least one of
R.sub.2 and R.sub.3 is NO.sub.2 and the other is H, acyclic
aliphatic, amine, NO.sub.2 or alkoxy; R.sub.4 is H, alkoxy, acyclic
aliphatic, amine, NO.sub.2, or an ester having the formula
(IV):
##STR00022##
wherein R.sub.11 is C.sub.1-C.sub.18 acyclic aliphatic; R.sub.5 and
R.sub.6 are independently H, alkoxy, acyclic aliphatic, amine, or
NO.sub.2; provided that if any of R.sub.2, R.sub.3, R.sub.4,
R.sub.5 and R.sub.6 is acyclic aliphatic, the acyclic aliphatic
does not comprise a double or triple bond between the .alpha. and
.beta. carbons; n is 0 or 1; and m is 0-3, provided that if R is O
and n is 0, m is at least 1.
[0047] The nitrophenyl esters contain a nitrophenyl group linked to
the oxygen of the carboxylate moiety by a chain that typically
comprises no more than five bonds in the main chain (i.e.,
exclusive of any branching). Typically, the nitrophenyl esters are
2-nitrophenyl esters, but 3-nitrophenyl esters have also been found
to undergo photolysis. Thus, in various embodiments, R.sub.2 is
NO.sub.2. In other embodiments, R.sub.3 is NO.sub.2.
[0048] The chain linking the nitrophenyl group to the carboxylate
typically comprises two to five bonds in the main chain, and may
also comprise one or more alkyl branches. The linker chain
typically comprises carbon, oxygen, and/or sulfur atoms, and more
typically comprises carbon and oxygen atoms. Thus, in various
embodiments, R is C(R.sub.7R.sub.8) or oxygen. If the linker chain
comprises one or more alkyl branches, the alkyl branches are
typically methyl or ethyl. In certain embodiments, it is preferred
that there are no branches or one branch at any given carbon atom
in the linker chain. Thus, for example, in various embodiments, R
is C(R.sub.7R.sub.8) and one of R.sub.7 and R.sub.8 is H and the
other is H, CH.sub.3, or CH.sub.2CH.sub.3. Similarly, in various
other embodiments, R.sub.1 is C(R.sub.9R.sub.10) and one of R.sub.9
and R.sub.10 is H and the other is H, CH.sub.3, or
CH.sub.2CH.sub.3. In some other embodiments, the chain linking the
nitrophenyl group to the carboxylate does not have any branching.
For example, in some embodiments, R is C(R.sub.7R.sub.8) and
R.sub.7 and R.sub.8 are both H.
[0049] In some embodiments, the linker chain is unbranched and
comprises a C.sub.1-C.sub.4 alkyl chain. For example, in various
embodiments, R is C(R.sub.7R.sub.8), R.sub.7 and R.sub.8 are both
H, n is 0, and m is 0, and the linker chain thus comprises a single
CH.sub.2 moiety. In other embodiments, R is C(R.sub.7R.sub.8);
R.sub.1 is C(R.sub.9R.sub.10); R.sub.7, R.sub.8, R.sub.9, and
R.sub.10 are all H; n is 1; and m is 0. In these embodiments, the
linker chain comprises a C.sub.2 alkyl moiety. In yet other
embodiments, R is C(R.sub.7R.sub.8), R.sub.7 and R.sub.8 are both
H, n is 0, and m is 1-3, and the linker chain comprises a
C.sub.2-C.sub.4 alkyl moiety.
[0050] In still other embodiments, the linker chain comprises an
oxygen or sulfur atom. In some embodiments, R is C(R.sub.7R.sub.8)
and R.sub.1 is O. In other embodiments, R is O and R.sub.1 is
C(R.sub.9R.sub.10). For example, in various embodiments, R is
C(R.sub.7R.sub.8), R.sub.7 and R.sub.8 are both H, R.sub.1 is O, n
is 1, and m is 2. In various other embodiments, R is O, R.sub.1 is
C(R.sub.9R.sub.10), R.sub.9 and R.sub.10 are both H, n is 1, and m
is 1.
[0051] In addition to the nitro group(s) that must be present at
one or both of the 2- and 3-positions, the nitrophenyl esters may
also have additional substituents on the phenyl ring. For example,
in some embodiments, at least one of R.sub.2, R.sub.3, R.sub.4,
R.sub.5, and R.sub.6 is acyclic aliphatic. However, if any of
R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 is acyclic
aliphatic, it is preferred that the acyclic aliphatic does not
comprise a double or triple bond between the .alpha. and .beta.
carbons. In embodiments where at least one of R.sub.2, R.sub.3,
R.sub.4, R.sub.5, and R.sub.6 is acyclic aliphatic, the acyclic
aliphatic typically is C.sub.1-C.sub.18 acyclic aliphatic, and more
typically C.sub.1-C.sub.18 alkyl.
[0052] In various other embodiments, at least one of R.sub.2,
R.sub.3, R.sub.4, R.sub.5, and R.sub.6 is alkoxy. In such
embodiments, the alkoxy is typically C.sub.1-C.sub.18 alkoxy, for
example methoxy. In some embodiments, both of R.sub.4 and R.sub.5
are alkoxy, for example methoxy.
[0053] In yet other embodiments, at least one of R.sub.2, R.sub.3,
R.sub.4, R.sub.5, and R.sub.6 is amine. In such embodiments, the
amine may be NH.sub.2 or a substituted amine. If the amine is a
substituted amine, it is preferred that there is not an amide at
the ring position adjacent to the nitro group, because such an
amide would be susceptible to photocleavage.
[0054] Particular examples of nitrophenyl esters of carboxylic acid
agrochemicals of formula (III) include compounds wherein: [0055]
R.sub.2 is NO.sub.2; each of R.sub.3, R.sub.4, R.sub.5, and R.sub.6
is H; R is C(R.sub.7R.sub.8); R.sub.7 and R.sub.8 are both H; n is
0; and m is 0; [0056] R.sub.2 is NO.sub.2, each of R.sub.3 and
R.sub.6 is H, each of R.sub.4 and R.sub.5 are methoxy, R is
C(R.sub.7R.sub.8), R.sub.7 and R.sub.8 are both H, n is 0, and m is
0; [0057] R.sub.3 is NO.sub.2; each of R.sub.2, R.sub.4, R.sub.5,
and R.sub.6 is H; R is C(R.sub.7R.sub.8); R.sub.7 and R.sub.8 are
both H; n is 0; and m is 0; [0058] R.sub.2 is NO.sub.2; each of
R.sub.3, R.sub.4, R.sub.5, and R.sub.6 is H; R is
C(R.sub.7R.sub.8); R.sub.1 is C(R.sub.9R.sub.10); R.sub.7, R.sub.8,
R.sub.9, and R.sub.10 are all H; n is 1; and m is 0; [0059] R.sub.2
is NO.sub.2; each of R.sub.3, R.sub.4, R.sub.5, and R.sub.6 is H; R
is O; R.sub.1 is C(R.sub.9R.sub.10); R.sub.9 and R.sub.10 are both
H; n is 1; and m is 1; or [0060] R.sub.2 is NO.sub.2; each of
R.sub.3, R.sub.4, R.sub.5, and R.sub.6 is H; R is
C(R.sub.7R.sub.8); R.sub.7 and R.sub.8 are both H; R.sub.1 is O, n
is 1, and m is 2.
[0061] Thus, where the carboxylic acid agrochemical is dicamba,
particular examples of the nitrophenyl esters of formula (III)
include the following compounds:
##STR00023##
[0062] The 2-nitrobenzyl (1a) and 2-nitrophenethyl (2) esters of
dicamba can readily be prepared by esterification with the parent
alcohol or, in the case of the 2-nitrobenzyl ester, by halide
displacement from 2-nitrobenzyl chloride or 2-nitrobenzyl bromide.
Syntheses for these compounds are described in the Examples
below.
[0063] The solubility of the nitrophenyl esters in organic solvents
increases as the length of the linker chain increases, and this
increased solubility enables higher loading to be achieved in
emulsifiable concentrate formulations. However, for nitrophenyl
esters having linkers comprising more than two atoms (for example,
compounds 3 and 4 above) the rate of photolysis decreases. A
compound such as compound 2 would be suitable for emulsifiable
concentrate formulations intended for post-emergent weed control.
On the other hand, a compound such as compound 1a would be suitable
for suspension concentrate or wettable granule formulations due to
its higher melting point and lower cost.
[0064] It has also been discovered that analogs of 1a, such as 1b
and 1c, are also effective herbicides. Compound 1b, the
6-nitroveratryl ester of dicamba, is significantly less soluble
than 1a and is therefore better suited to suspension concentrates.
Compound 1c, the 3-nitrobenzyl ester of dicamba, undergoes slower
and less efficient photolysis than the 2-nitrobenzyl ester, 1a.
[0065] Field tests of emulsifiable concentrates of compounds 1a and
2 showed them to be slightly more effective than the diglycolamine
salt of dicamba for control of broadleaf weeds. Similar activity
was seen in greenhouse tests of post-emergent control of
velvetleaf, described in further detail in the Examples below.
Without being bound to any particular theory, the somewhat better
performance in the field is thought to be due to the availability
of ultraviolet light outdoors. Thus, compounds 1a and 2 are
particularly suitable for post-emergent control of broadleaf weeds,
especially where minimizing off-site movement is a priority.
[0066] In other embodiments, the carboxylic acid agrochemical is
2,4-D. In such embodiments, particular examples of the nitrophenyl
esters of formula (III) include the following compounds:
##STR00024##
[0067] B. Phenacylmethyl Esters
[0068] Another class of esters of carboxylic acid agrochemicals
that have been found to undergo photo-induced cleavage to form the
agronomically active carboxylic acid agrochemical when exposed to
natural or artificial light are the phenacylmethyl esters. This
class of esters includes esters of carboxylic acid agrochemicals
comprising a photolabile protecting group which includes a
phenacylmethyl ester moiety. The phenacylmethyl esters typically
have the formula (V):
##STR00025##
wherein R.sub.2 is hydroxy, alkoxy, or substituted alkoxy; and
R.sub.1 and R.sub.3 are independently H, hydroxy, alkoxy,
substituted alkoxy, or C.sub.1-C.sub.18 unsubstituted or
substituted acyclic aliphatic, provided that if either of R.sub.1
and R.sub.3 is C.sub.1-C.sub.18 unsubstituted or substituted
acyclic aliphatic, the acyclic aliphatic does not comprise a double
or triple bond between the .alpha. and .beta. carbons.
[0069] In various embodiments, at least one of R.sub.1, R.sub.2,
and R.sub.3 is alkoxy or substituted alkoxy. In such embodiments,
the alkoxy or substituted alkoxy can have the formula:
--O--CH.sub.2--R.sub.4, wherein R.sub.4 is H, C.sub.1-C.sub.17
unsubstituted or substituted acyclic aliphatic, an amine, an
aliphatic amine, an aliphatic diamine, a carboxylic acid, a
sulfonic acid, hydroxy, an aliphatic ring, or an aromatic ring.
[0070] For example, in some embodiments, R.sub.2 is alkoxy and
R.sub.1 and R.sub.3 are both H. In various other embodiments,
R.sub.2 is hydroxy and R.sub.1 and R.sub.3 are both H.
[0071] Particular examples of phenacylmethyl esters of formula (V)
include compounds wherein R.sub.2 is methoxy or n-butoxy, and
R.sub.1 and R.sub.3 are both H. For example, where the carboxylic
acid agrochemical is dicamba, particular examples of the
phenacylmethyl esters of formula (V) include the following
compounds.
##STR00026##
[0072] The 4-methoxyphenacyl methyl ester of dicamba (9) and the
analogous 4-n-butoxyphenacyl methyl ester (10) can readily be
prepared from dicamba in high yield, as described below in the
Examples. Both of these compounds undergo photo-release to release
dicamba. In vitro studies described below in the Examples indicate
that the photo-efficiency of dicamba generation from compound 9 is
virtually 100%. Compound 9 is relatively insoluble and is best
suited for use in suspension concentrates; however, an emulsifiable
concentrate of 9 in monochlorobenzene was shown to be effective for
post-emergent control of broadleaf weeds, as described in the
Examples below. It has also been found that efficient photo-release
of 9 in a suspension concentrate formulation occurs over several
weeks, further demonstrating the ability of 9 to provide extended
pre-emergent weed control.
[0073] Compound 10 is a liquid at room temperature and is also
effective for post-emergent broadleaf weed control when formulated
as an emulsifiable concentrate, as described in the Example
below.
[0074] In other embodiments, the carboxylic acid agrochemical is
2,4-D. In such embodiments, particular examples of the
phenacylmethyl esters of formula (V) include the following
compounds:
##STR00027##
[0075] C. Other Esters
[0076] It has further been discovered that certain other aromatic
esters of carboxylic acid agrochemicals also provide for efficient
release of an active agrochemical. For example, in various
embodiments, the esters of the carboxylic acid agrochemicals have
the formula (VI):
##STR00028##
wherein at least one of R and R.sub.1 is N, and the other of R and
R.sub.1 is N or C--R.sub.5;
R.sub.2 is N or CH;
[0077] R.sub.3 and R.sub.4 are H, acyclic alkyl, substituted
acyclic alkyl, or together form a phenyl ring; and R.sub.5 is H,
acyclic alkyl, or substituted acyclic alkyl.
[0078] In the esters of carboxylic acid agrochemicals of formula
(VI), one or both of R and R.sub.1 are nitrogen. It has been
discovered that compounds having a nitrogen atom at one or both of
these positions achieve efficient release of the agrochemical. Such
release generally occurs through hydrolysis, although photolysis
can also contribute. Compounds of formulas VII, XII, and XIII,
discussed below, also have nitrogen-containing aromatic rings and
undergo hydrolysis under typical agronomic conditions. Without
being bound to any particular theory, it is believed that a ring
nitrogen atom adjacent to the phenolic carbon of the ester
stabilizes adducts with water or hydroxide by a mechanism similar
to that shown below for the 2-hydroxypyridine ester of dicamba:
##STR00029##
[0079] As described below, some esters of this type, such as the
2-quinoxalinol ester of dicamba, also under photolysis to yield the
carboxylic acid agrochemical. Without being bound to any particular
theory, it is believed that in the case of photolysis, the nitrogen
atoms at the R and/or R.sub.1 positions serve two functions: (1)
blocking sites .alpha. to the ester in order to prevent
recombination and ketone formation after photo-induced cleavage of
the ester; and (2) inhibiting recombination by enabling the
aromatic hydroxy group to tautomerize to the keto form, preventing
recombination.
[0080] In various embodiments of the esters of carboxylic acid
agrochemicals of formula (VI), R.sub.1 is C--R.sub.5 and R.sub.5 is
H, alkyl (e.g., methyl), or substituted alkyl.
[0081] In addition, in various embodiments, R.sub.2 can also be
nitrogen. In other embodiments, R.sub.2 is CH.
[0082] In the esters of carboxylic acid agrochemicals of formula
(VI), R.sub.3 and R.sub.4 are H, acyclic alkyl, substituted acyclic
alkyl, or together form a phenyl ring. Typically, R.sub.3 and
R.sub.4 are both H or together form a phenyl ring.
[0083] In various embodiments of the esters of carboxylic acid
agrochemicals of formula (VI), at least one of R.sub.3, R.sub.4,
and R.sub.5 is C.sub.1-C.sub.18 acyclic alkyl or C.sub.1-C.sub.18
substituted acyclic alkyl. The C.sub.1-C.sub.18 substituted acyclic
alkyl can be substituted with, for example, one or more hydroxy
groups or one or more sulfonic acid groups.
[0084] Particular examples of the esters of carboxylic acid
agrochemicals of formula (VI) include compounds wherein:
[0085] R and R.sub.2 are N; R.sub.1 is C--R.sub.5; R.sub.3 and
R.sub.4 together form a phenyl ring; and R.sub.5 is H;
[0086] R and R.sub.2 are N; R.sub.1 is C--R.sub.5; R.sub.3 and
R.sub.4 together form a phenyl ring; and R.sub.5 is methyl; or
[0087] R is N; R.sub.1 is C--R.sub.5; R.sub.2 is CH; and R.sub.3,
R.sub.4, and R.sub.5 are all H.
[0088] Thus, for example, where the carboxylic acid agrochemical is
dicamba, particular examples of the esters of carboxylic acid
agrochemicals of formula (VI) include the following compounds:
##STR00030##
[0089] A proposed scheme for the photo release of dicamba from the
2-quinoxalinol ester 13a is shown below:
##STR00031##
Although the mechanistic detail in this scheme is not firmly
established, the outstanding efficacy of the photo and
hydrolytically-labile 2-quinoxalinol protecting group is shown in
the Examples below.
[0090] When used as an emulsifiable concentrate, the 2-quinoxalinol
ester of dicamba, 13a, has similar post-emergent activity for
control of broadleaf weeds as the diglycolamine salt of dicamba,
while exhibiting superior extended pre-emergent control of Palmer
amaranth at 21 and 44 days after treatment. The 2-hydroxypyridine
ester 14 also undergoes efficient cleavage to form dicamba, as
shown in the Examples below. Ester 14 is readily soluble in organic
solvents and can be formulated as an emulsifiable concentrate or a
suspension concentrate.
[0091] In other embodiments, the carboxylic acid agrochemical is
2,4-D. In such embodiments, particular examples of the esters of
formula (VI) include the following compounds:
##STR00032##
[0092] In other various embodiments, the ester is a diester of a
carboxylic acid agrochemical having the formula (VII):
##STR00033##
wherein R.sub.1 and R.sub.2 are independently H or C.sub.1-C.sub.8
alkyl, or together form a phenyl ring. R.sub.1 and R.sub.2 are
typically both H, or together form a phenyl ring.
[0093] In various embodiments, the carboxylic acid agrochemical is
dicamba, and examples of the diesters of formula (VII) include the
following compounds:
##STR00034##
[0094] Like the esters of formula VI, the esters of formula VII
generally revert to the parent carboxylic acid by hydrolysis rather
than by photolysis. The maleic hydrazide and phthalhydrazide
diesters (17 and 18) undergo efficient cleavage to form dicamba.
The phthalhydrazide diester, 18, is highly insoluble and is
preferably formulated as a suspension concentrate. The maleic
hydrazide diester, 17, is readily soluble in organic solvents and
can be formulated as an emulsifiable concentrate or a suspension
concentrate.
[0095] In various other embodiments, the carboxylic acid
agrochemical is 2,4-D, and examples of the diesters of formula
(VII) include the following compounds:
##STR00035##
[0096] In yet other embodiments, the ester of a carboxylic acid
agrochemical has the formula (VIII):
##STR00036##
wherein R.sub.1, R.sub.2, and R.sub.3 are alkyl.
[0097] In the esters of formula (VIII), the substitutions ortho and
para to the ester block ketone formation. Typically, at least one
of the ortho substituents is branched to prevent recombination of
the phenol and acyl photo-fragments. For example, an isopropyl or
tertiary butyl substituent can be present at the ortho position.
Thus, typically at least one of R.sub.1 and R.sub.3 is branched
alkyl, e.g., isopropyl or t-butyl.
[0098] In addition, in various embodiments of the esters of formula
(VIII), at least one of R.sub.1 and R.sub.2 is methyl. As one
example, in a particular embodiment R.sub.1 and R.sub.2 are both
methyl and R.sub.3 is t-butyl. Where the carboxylic acid
agrochemical is dicamba, this ester of formula (VIII) has the
following structure:
##STR00037##
[0099] Ester 21 has been shown to undergo photo-release of dicamba
in vitro. In addition, the substituted phenol byproducts formed
upon photo-release of the agrochemical from the esters of formula
(VIII) are effective anti-oxidants and can provide plant health
benefits under some circumstances.
[0100] In other embodiments of the esters of formula (VIII), the
carboxylic acid agrochemical is 2,4-D. Thus, for example, an ester
of formula (VIII) can have the following structure:
##STR00038##
[0101] In yet other various embodiments, a phenolic agrochemical
can be incorporated into the photolabile ester of a carboxylic acid
agrochemical, thereby affording a photo-labile ester which provides
photo-release of two different agrochemicals that may have
different modes of action. In some such embodiments, the ester of a
carboxylic acid agrochemical has the formula (IX):
##STR00039##
wherein R.sub.1 and R.sub.2 are halogen.
[0102] In the esters of formula (IX), the phenolic agrochemical is
typically chloroxynil, bromoxynil, or ioxynil. Thus, typically,
R.sub.1 and R.sub.2 are both chloro (where the phenolic
agrochemical is chloroxynil), R.sub.1 and R.sub.2 are both bromo
(where the phenolic agrochemical is bromoxynil), or R.sub.1 and
R.sub.2 are both iodo (where the phenolic agrochemical is ioxynil).
The chloroxynil, bromoxynil, and ioxynil esters of dicamba have the
following structures:
##STR00040##
[0103] The chloroxynil, bromoxynil and ioxynil esters of dicamba
(23a, 23b, and 23c) provide photo-release of dicamba and an
herbicide with a second mode of action. Chloroxynil, bromoxynil,
and ioxynil esters can also be used to provide photo-release of
other carboxylic acid agrochemicals. For example, the chloroxynil,
bromoxynil, and ioxynil esters of 2,4-D have the following
structures:
##STR00041##
[0104] Similarly, the fungicide quinolinol can be used to form a
photo-labile ester of a carboxylic acid agrochemical. In such
embodiments, the ester of a carboxylic acid agrochemical has the
formula (X):
##STR00042##
For example, the quinolinol esters of dicamba and 2,4-D have the
following structures:
##STR00043##
[0105] In other embodiments, the herbicide medinoterb can be used
to form a photo-labile ester of a carboxylic acid agrochemical. In
such embodiments, the ester of a carboxylic acid agrochemical has
the formula (XI):
##STR00044##
For example, the medinoterb esters of dicamba and 2,4-D have the
following structures:
##STR00045##
[0106] D. Activated Benzylic Esters
[0107] In some embodiments, the ester of a carboxylic acid
agrochemical has the formula (XII):
##STR00046##
wherein at least one of R.sub.1, R.sub.2, and R.sub.3 is an
electron-donating group; and the others of R.sub.1, R.sub.2, and
R.sub.3 are independently H or an electron-donating group; provided
that none of R.sub.1, R.sub.2, and R.sub.3 is an
electron-withdrawing group.
[0108] Suitable electron-donating groups include alkoxy (e.g.
methoxy), alkyl, amino, alkylamino, and dialkylamino.
[0109] In embodiments wherein the electron-donating group is alkyl,
alkylamino, or dialkylamino the alkyl is typically C.sub.1-C.sub.18
alkyl.
[0110] In embodiments wherein the electron-donating group is
alkoxy, the alkoxy is typically C.sub.1-C.sub.18 alkoxy. For
instance, in certain embodiments, at least one of R.sub.1, R.sub.2,
and R.sub.3 is methoxy. For example, in some embodiments, R.sub.2
is methoxy and R.sub.1 and R.sub.3 are both H. Where the carboxylic
acid agrochemical is dicamba, this ester of formula (XII) has the
following structure:
##STR00047##
[0111] In other embodiments of the esters of formula (XII), the
carboxylic acid agrochemical is 2,4-D. Where the carboxylic acid
agrochemical is 2,4-D, a particular example of a compound of
formula (XII) has the following structure:
##STR00048##
[0112] Unactivated benzylic esters of aromatic carboxylic acids
such as dicamba are resistant to hydrolysis under typical agronomic
conditions. However, activated benzylic esters of formula (XII),
particularly those containing alkoxy or dialkylamino groups in the
ortho or para position, undergo hydrolysis by the mechanism shown
below, in which elimination of the dicamba anion occurs directly
followed by hydrolysis of the stabilized benzylic cation. The
4-methoxybenzyl ester of dicamba, 29a, is suitable for the fast
release of dicamba. Such rapid hydrolysis is useful in dry soil
(which slows the rate of hydrolysis) or when physical methods such
as encapsulation are used to govern the rate of ester release to
the environment.
##STR00049##
[0113] E. Activated Phenolic Esters
[0114] In still other embodiments, the ester of a carboxylic acid
agrochemical has the formula (XIII):
##STR00050##
wherein at least one of R.sub.1, R.sub.2, and R.sub.3 is an
electron-donating group; and the others of R.sub.1, R.sub.2, and
R.sub.3 are independently H or an electron-donating group; provided
that none of R.sub.1, R.sub.2, and R.sub.3 is an
electron-withdrawing group.
[0115] Suitable electron-donating groups include alkoxy (e.g.,
methoxy), alkyl, amino, alkylamino, and dialkylamino.
[0116] In embodiments wherein the electron-donating group is alkyl,
alkylamino, or dialkylamino the alkyl is typically C.sub.1-C.sub.18
alkyl.
[0117] In embodiments wherein the electron-donating group is
alkoxy, the alkoxy is typically C.sub.1-C.sub.18 alkoxy. For
instance, in certain embodiments, at least one of R.sub.1, R.sub.2,
and R.sub.3 is methoxy. For example, in some embodiments, R.sub.2
is methoxy and R.sub.1 and R.sub.3 are H. Where the carboxylic acid
agrochemical is dicamba, this ester of formula (XIII) has the
following structure:
##STR00051##
[0118] In other embodiments of the esters of formula (XIII), the
carboxylic acid agrochemical is 2,4-D. Where the carboxylic acid
agrochemical is 2,4-D, a particular example of a compound of
formula (XIII) has the following structure:
##STR00052##
[0119] Methoxy and dialkylamino groups promote the photolysis of
phenolic esters of carboxylic acid agrochemicals by a mechanism
similar to that by which they promote hydrolysis of benzylic
esters. In both cases, the effect is to promote the elimination of
the carboxylate anion and a stabilized cation, as shown below for
the 4-methoxyphenyl ester of dicamba, 30a. Thus esters of
structural formula (XIII) undergo photo-release of carboxylic
acids. Photo-release is significantly slower than for esters of
formula (III) or (V), providing further suppression of volatility
and a more extended release of the active agrochemical.
##STR00053##
[0120] F. Benzylic Esters Prepared by the Baylis-Hillman
Reaction
[0121] In other embodiments, the ester of a carboxylic acid
agrochemical is a benzylic ester having the formula (XIV):
##STR00054##
wherein R is alkyl, aryl, or alkoxy; at least one of R.sub.1,
R.sub.2, R.sub.3, R.sub.4, and R.sub.5 is an electron-withdrawing
group; and the others of R.sub.1, R.sub.2, R.sub.3, R.sub.4, and
R.sub.5 are independently H, alkyl, alkoxy, dialkylamino, or
halogen.
[0122] Suitable electron withdrawing groups include nitro, ester,
and sulfonate. Thus, for example, in certain compounds of formula
(XIV), at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4, and
R.sub.5 is nitro.
[0123] In embodiments wherein one or more of R, R.sub.1, R.sub.2,
R.sub.3, R.sub.4, and R.sub.5 is alkyl, the alkyl is typically
C.sub.1-C.sub.18 alkyl. Thus, for example, in some embodiments, one
or more of R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 is
methyl or ethyl.
[0124] When one or more of R, R.sub.1, R.sub.2, R.sub.3, R.sub.4,
and R.sub.5 is alkoxy, the alkoxy is suitably C.sub.1-C.sub.18
alkoxy (e.g., methoxy or ethoxy).
[0125] Typical R substituents include methyl, ethyl, substituted
phenoxy, and C.sub.1-C.sub.18 alkoxy. For example, in certain
embodiments, R is ethoxy.
[0126] Particular examples of esters of formula (XIV) include
compounds wherein:
[0127] R is ethoxy, R.sub.1 is nitro, and each of R.sub.2, R.sub.3,
R.sub.4, and R.sub.5 are H;
[0128] R is ethoxy, R.sub.2 is nitro, and each of R.sub.1, R.sub.3,
R.sub.4, and R.sub.5 are H; or
[0129] R is ethoxy, R.sub.3 is nitro, and each of R.sub.1, R.sub.2,
R.sub.4, and R.sub.5 are H.
[0130] Thus, where the carboxylic acid agrochemical is dicamba,
particular examples of the esters of formula (XIV) include the
following compounds:
##STR00055##
[0131] In other embodiments of the esters of formula (XIV), the
carboxylic acid agrochemical is 2,4-D. For such embodiments,
particular examples of the esters of formula (XIV) include the
following compounds:
##STR00056##
[0132] Hydrolytically labile esters of aromatic carboxylic acids of
formula (XIV) can be conveniently prepared via the Baylis-Hillman
reaction followed by esterification with the carboxylic acid
agrochemical. The Baylis-Hillman reaction is reviewed in Drewes S.
E., Roos G. H. P., "Synthetic Potential of the Tertiary
Amine-Catalysed Reaction of Activated Vinyl Carbanions with
Aldehyde," Tetrahedron, 1988, 44, 4653-70) and Basavaiah, D., Rao,
P. D., Hyma, R. S., "The Baylis-Hillman Reaction: A Novel
Carbon-Carbon Bond Forming Reaction," Tetrandedron, 1996, 8001-62.
The parent alcohols of the present invention are obtained by
reaction of a vinyl compounds with an electron-withdrawing group
and a substituted benzaldehyde catalyzed by a tertiary amine,
preferably diazabicyclo[2,2,2] octane, commonly known as "DABCO" or
quinuclidine. Suitable benzaldehydes include nitrobenzaldehydes,
particularly when substituted in an ortho orientation. Suitable
vinyl compounds include vinyl esters, particularly ethyl
acrylate.
[0133] The synthesis of a typical parent alcohol by the
Baylis-Hillman pathway is shown below. The dicamba ester of this
alcohol is designated structure 31a. Two related structures, 31b
and 31c, shown above, are also useful for controlled release of
dicamba. Laboratory synthetic procedures for esters 31a, 31b, and
31c are given below in the Examples, using reaction times of
several days at room temperature. For larger-scale production, it
is suitable to conduct the reactions at elevated pressure, which
greatly accelerates the rate of the Baylis-Hillman reaction, as
described in the literature (Hill, J. S., Isaacs, N. S., Tetr.
Lett., 1986, 5007.)
##STR00057##
[0134] The Baylis-Hillman synthesis represents a high yield
conversion of low-cost benzaldehydes to benzylic alcohols. In
addition, the carbonyl group introduced beta to the benzylic carbon
renders the agrochemical ester more hydrolytically labile. The rate
of hydrolysis can be enhanced by adding activating groups such as
methoxy or dialkylamino to the ortho or para positions of the
aromatic ring or conversely reduced by the addition of
electron-withdrawing groups such as esters, sulfonates, or nitro
groups. Moreover, when a nitro group is present on the ring alpha
to the benzylic position, the ester is rendered photo-labile.
[0135] G. Esters Obtained by Michael Addition of Activated Olefins
to Maleic Hydrazide
[0136] In further embodiments, the ester of a carboxylic acid
agrochemical has the formula (XV):
##STR00058##
wherein R.sub.1 is an electron-withdrawing group; and wherein
R.sub.2 and R.sub.3 are independently H or alkyl.
[0137] Suitable electron-withdrawing groups include, for example,
nitriles, ketones, aldehydes, esters, carboxylates, and nitro.
[0138] In some embodiments of the compounds of formula (XV), both
R.sub.2 and R.sub.3 are H. In other embodiments, one or both of
R.sub.2 and R.sub.3 are alkyl, typically C.sub.1-C.sub.18
alkyl.
[0139] Particular examples of carboxylic acid agrochemicals of
formula (XV) include compounds wherein:
[0140] R.sub.1 is --COCH.sub.3 and R.sub.2 and R.sub.3 are both
H;
[0141] R.sub.1 is --CH.dbd.O and R.sub.2 and R.sub.3 are both H;
or
[0142] R.sub.1 is --CN and R.sub.2 and R.sub.3 are both H;
[0143] R.sub.1 is --COOCH.sub.2CH.sub.3 and R.sub.2 and R.sub.3 are
both H.
[0144] Thus, where the carboxylic acid agrochemical is dicamba,
particular examples of the esters of formula (XV) include the
following compounds:
##STR00059##
[0145] In other embodiments of the esters of formula (XV), the
carboxylic acid agrochemical is 2,4-D. For such embodiments,
particular examples of the esters of formula (XV) include the
following compounds:
##STR00060##
[0146] The useful class of esters of structural formula (XV) is
obtained by forming an ester of a carboxylic acid agrochemical with
an alcohol obtained by base-catalyzed Michael addition of maleic
hydrazide to vinyl compounds activated with electron-withdrawing
groups. Esters 32a, 33a and 34a, shown above, are obtained by
Michael addition of methyl vinyl ketone, acrolein, and
acrylonitrile, respectively to maleic hydrazide. The dicamba esters
of the Michael adducts can release dicamba by hydrolysis (since
there is a nitrogen alpha to the ester linkage) or a combination of
hydrolysis and photolysis. The utility of esters of formula (XV) is
also due to the fact that the physical properties of the ester can
be modified. Ester 34a is an insoluble solid which can be
formulated as a suspension concentrate while esters 32a and 33a are
effectively room-temperature liquids (although 32a undergoes some
crystallization over a period of weeks) and can be formulated as
high-loading emulsifiable concentrates. The synthesis of these
esters is described in the Examples.
[0147] H. Di-Alkylated Hydroxypyridine Esters of Carboxylic Acid
Agrochemicals
[0148] In still further embodiments, the ester of a carboxylic acid
agrochemical has the formula (XVI):
##STR00061##
wherein R.sub.1 is alkyl and R.sub.2 is H, alkyl, or aryl.
[0149] The compounds of formula (XVI) are symmetrically substituted
with alkyl groups at the R.sub.1 positions. R.sub.1 is typically
C.sub.1-C.sub.18 alkyl. For example, in some esters of formula
(XVI), R.sub.1 is tertiary-butyl.
[0150] In some embodiments, R.sub.2 is H. In other embodiments,
R.sub.2 is alkyl, typically C.sub.1-C.sub.18 alkyl. In still other
embodiments, R.sub.2 is aryl. When R.sub.2 is aryl, the aromatic
ring optionally contains nitrogen and is optionally substituted
with up to three C.sub.1-C.sub.18 alkyl groups.
[0151] In a particular example of an ester of a carboxylic acid
agrochemical of formula (XVI), R.sub.1 is tertiary-butyl and
R.sub.2 is H. Thus, where the carboxylic acid agrochemical is
dicamba, a particular example of a compound of formula (XVI) has
the structure:
##STR00062##
[0152] In other embodiments of the esters of formula (XVI), the
carboxylic acid agrochemical is 2,4-D. Where the carboxylic acid
agrochemical is 2,4-D, a particular example of a compound of
formula (XVI) has the following structure:
##STR00063##
[0153] The solubility of the 2-hydroxypyridine ester of dicamba
(compound 14) and other carboxylic acid agrochemicals can be
improved and the activity modulated by symmetrical substitution of
the ring with alkyl groups (R.sub.1 in formula XVI). A convenient
synthetic route involving condensation of beta-diketones with
2-cyanoacetamide also adds a nitrile group to the ring. A typical
ester of formula (XVI) is the dicamba ester designated compound
36a, where R.sub.1 is tertiary butyl and R.sub.2 is hydrogen. The
synthesis and activity of 36a are described in the Examples.
[0154] I. Pyridine Diesters of Carboxylic Acid Agrochemicals
[0155] In yet other embodiments, the ester of a carboxylic acid
agrochemical has the formula (XVII):
##STR00064##
wherein R.sub.1 is an electron-withdrawing group; and R.sub.2 is H,
a hydrocarbon, or an aromatic group.
[0156] Suitable electron-withdrawing groups include, for example,
cyano, carboxylalkyl, aldehyde, and nitro. In certain embodiments,
R.sub.1 is cyano. Where R.sub.1 is carboxyalkyl, the alkyl is
typically C.sub.1 to C.sub.12 alkyl.
[0157] In some embodiments of the esters of formula (XVII), R.sub.2
is H. In other embodiments, R.sub.2 is a hydrocarbon. Suitable
hydrocarbons include C1-C18 alkyl. In still other embodiments,
R.sub.2 is an aromatic group. The aromatic ring optionally contains
nitrogen and is optionally substituted with up to three
C.sub.1-C.sub.18 alkyl groups. In certain embodiments, R.sub.2 is
phenyl.
[0158] In a particular example of an ester of a carboxylic acid
agrochemical of formula (XVII), both R.sub.1 is cyano and R.sub.2
is phenyl. Thus, where the carboxylic acid agrochemical is dicamba,
a particular example of a compound of formula (XVII) has the
structure:
##STR00065##
[0159] In other embodiments of the esters of formula (XVII), the
carboxylic acid agrochemical is 2,4-D. Where the carboxylic acid
agrochemical is 2,4-D, a particular example of a compound of
formula (XVII) has the following structure:
##STR00066##
[0160] The liquid, hydrolytically labile esters of carboxylic acid
agrochemicals of formula (XVII) can be obtained by a method
involving the double Knoevagel condensation of an aldehyde with two
equivalents of 2-cyanoacetamide, yielding a nucleus with two
phenolic groups which can be esterified, both adjacent to a ring
nitrogen which sensitizes the ester to hydrolysis. A general
outline of the synthesis is shown below. Two equivalents of
2-cyanoacetamide are condensed with an aldehyde under basic
conditions which is followed, without isolation, by ring closure
under neutral conditions. Ring oxidation is facile in the presence
of air or other oxidants.
##STR00067##
A useful example of esters of formula (XVII) is the ester
designated 37a (shown above). Its synthesis and hydrolysis under
typical agronomic conditions are described in the Examples.
Synthesis of the Esters of Carboxylic Acid Agrochemicals
[0161] As explained in greater detail in the Examples below, the
esters of the present invention can be prepared by esterification
of the appropriate alcohol with the carboxylic acid agrochemical or
reaction of the acid chloride of the agrochemical with the alcohol.
The use of dimethylamino pyridine ("DMAP") improves reaction rates
and yields when using the acid chloride route, as illustrated in
the Examples below for dicamba and 2,4-D esters.
[0162] Photo-labile esters of 2,4-D can be prepared similarly to
the dicamba esters. Most esters are easily prepared from the acid
chloride of 2,4-D. 2,4-D acid chloride and ester synthesis is
described in M. S. Newman, et al., J. Am. Chem. Soc. 69:718-23
(1947). The synthesis of the 2,4-D esters 5a, 11, and 15a is
described in the Examples below.
[0163] Thus, the esters of the present invention can be prepared
from the acid chloride of dicamba, 2,4-D and other herbicides. The
acid chloride is also a convenient intermediate to other esters of
the present invention.
[0164] The 2-nitrobenzyl esters of dicamba (1) and 2,4-D (5a) are
economically prepared from the reaction of 2-nitrobenzyl chloride
with dicamba or 2,4-D in the presence of a base as described in
Example 4 below. The bases are typically organic amines,
particularly triethylamine. It has been found that use of a
slightly substoichiometric amount of base relative to dicamba or
2,4-D is preferred as this prevents reaction of free amine with
2-nitrobenzyl chloride.
[0165] A typical process for the preparation of 1a is illustrated
in FIG. 1. The process can be performed continuously or
semi-continuously, but in either case the amine base is regenerated
by reaction with a strong aqueous base such as sodium hydroxide and
is recycled along with unreacted starting materials and ester that
has not precipitated. This method is also applicable to the
2-nitrobenzyl ester of 2,4-D, 5a. Preferably, an excess of
2-nitrobenzyl chloride is present in the reaction mixture and a
polar, hydrophobic solvent such a methylene chloride or
1,2-dichlorobenzene is utilized. 2-nitrobenzyl bromide can also be
used in this process, as described in Example 14.
[0166] 2-nitrobenzyl chloride is typically prepared by chlorination
of 2-nitrotoluene. Selective monochlorination of toluene at partial
conversion is known and is described in Chlorotoluenes, in
Kirk-Othmer Encyclopedia of Chemical Technology (5th ed. 2004). An
alternative synthetic method is o-nitration of benzyl chloride, but
para nitration also occurs, reducing yield.
[0167] A similar process can be used for the synthesis of the
4-methoxyphenacylmethyl esters 9 and 11. FIG. 2 illustrates this
process for the 4-methoxyphenacylmethyl ester of dicamba (9). The
primary difference is that 4-methoxy-.alpha.-chloroacetophenone is
reacted with the carboxylate. As described in Example 8, this
intermediate is conveniently prepared by Friedel Crafts acylation
of anisole with chloroacetyl chloride. Either polar or non-polar
hydrophobic solvents can be used.
Compositions
[0168] The esters of carboxylic acid agrochemicals described herein
can be incorporated into useful agrochemical compositions. The
esters are typically formulated as emulsifiable concentrates in
organic solvents or as suspension concentrates. In several cases,
the emulsifiable concentrate formulations of the dicamba esters
provide equal or superior post-emergent control of broadleaf weeds
as compared to the diglycolamine salt of dicamba, while greatly
reducing dicamba volatility. In addition, improved pre-emergent
control of broadleaf weeds can be achieved. The 2,4-D esters are
significantly less soluble than dicamba esters, however, and are
therefore typically formulated as suspension concentrates.
[0169] The compositions of the esters of carboxylic acid
agrochemicals typically comprise one or more adjuvants. Typical
adjuvants include, but are not limited to, solvents, surfactants,
dispersants, antifreeze agents, antifoam agents, thickeners,
bacteriostats, wetting agents, dyes, and combinations or mixtures
thereof.
[0170] The solvent may comprise, for example, an aromatic
hydrocarbon, monochlorobenzene, a naphthalenic organic solvent,
isophorone, a carboxylic acid esters, a carboxylic acid diesters, a
pyrrolidone, or a combination or mixture thereof
[0171] Typical surfactants include nonionic surfactants and anionic
surfactants, and typically a mixture of a nonionic surfactant and
an anionic surfactant is used. Typical surfactants include, but are
not limited to, ethoxylated alkyl alcohols, ethoxylated vegetable
oils (e.g., ethoxylated castor oil), sulfonates (e.g., an
alkylbenzene sulfonate calcium salt), or a combination or mixture
thereof.
[0172] Dispersants that are typically used in the ester
compositions include, but are not limited to lignosulfonate,
sulfonated naphthalene-formaldehyde condensates, polymeric
dispersants, or a combination or mixture thereof. Typical
antifreeze agents include, but are not limited to, propylene
glycol, glycerin, or a combination or mixture thereof. The antifoam
agent is typically a silicone antifoam agent, but other antifoam
agents may also be used. Typical thickeners include, but are not
limited to, xanthan gum, silicas, clays, or a combination or
mixture thereof.
[0173] For most applications, particularly for fungicides and
post-emergent herbicides, the esters are typically formulated as
emulsifiable concentrates in agronomically acceptable organic
solvents. The solvents typically have a flashpoint above 65.degree.
C. and reasonable solubility for the ester. The choice of solvent
depends on various factors, including solubility, other actives
that may be included in the formulation, and cost. Typical solvents
include naphthalenic organic solvents, isophorone,
monochlorobenzene, carboxylic acid esters and diesters, and
pyrrolidones. The use of a mixture of a nonionic surfactant,
preferably ethoxylated alkyl alcohols or vegetable oils and an
anionic surfactant, preferably a sulfonate, is typical for the
emulsification system. Typically, the ester is present at a
concentration of from about 20 percent to about 50 percent in the
emulsifiable concentrate formulations.
[0174] For pre-emergent herbicides, suspension concentrates are the
typical formulations. Relatively high-melting and water-insoluble
esters such as 2-nitrobenzyl, 4-methoxyphenacylmethyl, and
2-quinoxalinol esters (such as 1a, 9, and 13a, respectively, for
dicamba) are typically formulated as suspension concentrates. The
concentration of the ester particles in the suspension concentrate
formulations is typically about 20 percent to about 50 percent.
[0175] Formulation of suspension concentrates of water-insoluble
solids is known in the art and is discussed in T. F. Tadros,
Surfactants in Agrochemicals, pp. 133-82 (1995). The photo-labile
esters of the present invention are typically milled to a mean
particle size of from about 0.5 to about 10 .mu.m, more typically
from about 1 to about 5 .mu.m, for ease of formulation and in order
to achieve efficient photo-release in the field. Bead milling is
the preferred milling method.
[0176] The particles are typically dispersed using a polymeric
dispersant. Such dispersants are known in the art and typically
have a comb structure with hydrophobic backbone. Hydrophilic
"teeth" protruding from the backbone can be anionic, such as maleic
or acrylic acid salts or nonionic polyethylene oxide chains.
Lignosulfonates are also typical dispersants and have similar
properties. The formulations also typically include an antifreeze,
for example propylene glycol or glycerin, as well as agents to
raise viscosity such as xanthan gum, silicas or clays.
Bacteriostats, antifoam agents, wetting agents, and dyes can also
be added to the formulation as appropriate.
[0177] An alternative approach for the formulation of pre-emergent
herbicides is micro-encapsulation of a solution of the photo-labile
esters. In this case, high solubility esters such as 2 and 3 are
typically used.
[0178] In various embodiments, the ester of a carboxylic acid
agrochemical in the composition is an ester of dicamba or 2,4-D.
The compositions may also comprise one or more additional
agrochemicals. For example, the compositions may include a second
agrochemical, such as a herbicide, a fungicide, an insecticide, a
plant health agent, or a plant growth regulator. In some
embodiments, the second agrochemical is an herbicide, such as
glyphosate or an agronomically acceptable salt or ester thereof.
Thus, for example, in some embodiments, the ester of a carboxylic
acid agrochemical in the composition is an ester of dicamba, and
the composition further comprises glyphosate or an agronomically
acceptable salt or ester of glyphosate. In concentrate
compositions, the glyphosate concentration is typically about 200
grams acid equivalent (a.e.)/L to about 400 grams a.e./L.
Determination of the Efficacy of Labile Esters
[0179] The efficacy of the photolabile esters can be assayed in
vitro, or in greenhouse or field experiments. A useful in vitro
assay for post-emergent activity involves photolysis of a dilute
solution of the esters using simulated sunlight. This is
conveniently achieved by photolysis of a solution of the ester in
an organic solvent which is miscible with water and to which some
water has been added. As described in the Examples, photolysis in
acetonitrile or tetrahydrofuran containing 10% water by weight is
effective. Low concentrations of the ester should be used so that
the entire volume is exposed to sunlight. Since the maximum
extinction coefficient of the typical esters above 220 nm is in the
range of 1000-10,000 M.sup.-1 cm.sup.-1, a concentration of 0.1 mM
is effective. Photolysis in a quartz tube exposed to simulated or
actual sunlight is a typical protocol.
[0180] Suspension concentrate formulations of photo-labile esters
can be screened in vitro for pre-emergent activity by a similar
protocol. The suspension concentrate is typically diluted in water
to a concentration of about 0.1 mM and photolyzed in a quartz tube.
The samples are typically filtered before analysis.
[0181] The in vitro assay is a useful screening tool for esters and
formulations and has proven generally effective at predicting
greenhouse and field performance. Formulations of photo-labile
esters of agrochemicals can be tested under greenhouse and field
conditions under the same protocols used for other agrochemicals.
However, as can be seen in the Examples below, esters such as the
4-methoxy and 4-n-butoxyphenacyl methyl esters (9 and 10 in the
case of dicamba), whose absorbance spectrum is predominantly in the
ultraviolet range, perform worse in the greenhouse than in in vitro
or field experiments due to screening of ultraviolet light by the
greenhouse roof.
[0182] Similar assays can be performed using water instead of
organic solvents. Because of the limited solubility of some esters
in water, the assay is performed at lower concentrations, e.g.,
0.01 mM, as in the Examples below. This assay can identify
photo-labile esters, but is more effective in characterizing
hydrolytically labile esters and ranking their rates of
hydrolysis.
[0183] Emulsifiable and suspension concentrates of 1a, 2, 9, 13a,
14, 17, 30a, 32a, and 36a have proven effective for the control of
a number of broadleaf weeds in field testing, as have emulsifiable
concentrates of 2 and 10. These weeds include Sesbania macrocarpa,
morning glory, velvetleaf, Palmer amaranth, fat hen, and
sicklepod.
Use of the Esters
[0184] The esters of carboxylic acid agrochemicals described herein
can be used for the controlled release of the carboxylic acid
agrochemical. In particular, in various embodiments, the invention
relates to a method for the controlled release of a carboxylic acid
agrochemical comprising exposing a photolabile ester of the
carboxylic acid agrochemical to natural light (e.g., sunlight) or
artificial light (e.g., incandescent or fluorescent light). In
other embodiments, the invention relates to a method for the
controlled release of a carboxylic acid agrochemical comprising
exposing a hydrolytically labile ester of the carboxylic acid
agrochemical to aqueous conditions (e.g., rainwater or irrigation
water).
[0185] The esters of carboxylic acid herbicides described herein
can also be used to control unwanted plants. In various
embodiments, such methods comprise applying to the unwanted plants
a herbicidal composition of the present invention comprising an
ester of a carboxylic acid herbicide, for example, an ester of
dicamba or 2,4-D. This may be accomplished, for example, by
diluting, as necessary, the emulsion concentrate or suspension
concentrate compositions described above to produce an application
mixture, and applying the mixture to the unwanted plants. Such
methods may further comprise applying a second herbicide to the
unwanted plants, e.g., glyphosate or an agronomically acceptable
salt or ester of glyphosate. In various embodiments, the carboxylic
acid herbicide is dicamba and the second herbicide is glyphosate or
an agronomically acceptable salt or ester thereof. The second
herbicide can be applied to the unwanted plants before,
concurrently with, or after application of the ester of a
carboxylic acid herbicide. As described above, in some embodiments,
the ester of a carboxylic acid herbicide and the second herbicide
are combined into a single formulation prior to application to the
unwanted plants.
Herbicidal Methods of Use
[0186] In herbicidal methods of the present invention, an
application mixture (e.g., comprising a dilution of an ester of a
carboxylic acid herbicide concentrate composition of the present
invention), typically comprising from about 0.1 to about 50 g
a.e./L herbicide, is formed and then applied to the foliage of a
plant or plants or an area where plants are to be planted at an
application rate sufficient to give a commercially acceptable rate
of weed control. This application rate is usually expressed as
amount of herbicide per unit area treated, e.g., grams acid
equivalent per hectare (g a.e./ha). Depending on plant species and
growing conditions, the period of time required to achieve a
commercially acceptable rate of weed control can be as short as a
week or as long as three weeks, four weeks or longer.
[0187] In some embodiments of the present invention, crop plants
include, for example, corn, peanuts, potatoes, soybeans, canola,
alfalfa, sugarcane, sugarbeets, peanuts, grain sorghum (milo),
field beans, rice, sunflowers, wheat and cotton. In certain
embodiments, the crop plant is selected from the group consisting
of soybeans, cotton, peanuts, rice, wheat, canola, alfalfa,
sugarcane, sorghum, and sunflowers. In various embodiments, the
crop plant is selected from the group consisting of corn, soybean
and cotton.
[0188] Crop plants include hybrids, inbreds, and transgenic or
genetically modified plants having specific traits or combinations
of traits including, without limitation, herbicide tolerance (e.g.,
resistance to carboxylic acid herbicides or other herbicides),
Bacillus thuringiensis (Bt), high oil, high lysine, high starch,
nutritional density, and drought resistance. In some embodiments,
the crop plants are resistant to carboxylic acid herbicides (e.g.,
dicamba and/or 2,4-D) and/or other herbicides (e.g.,
glyphosate).
[0189] The application mixture comprising an ester of a carboxylic
acid herbicide of the present invention can be applied prior to
planting of crop plants that are susceptible to the carboxylic acid
herbicide (e.g., dicamba-susceptible or 2,4-D-susceptible crop
plants not having a trait providing tolerance to the carboxylic
acid herbicide), such as, for example, from about two to about
three weeks before planting. Crop plants that are not susceptible
to the carboxylic acid herbicide (e.g., corn with respect to auxin
herbicides), or transgenic or genetically modified crop plants
having one or more traits providing tolerance to the carboxylic
acid herbicide typically have no pre-planting restriction and the
application mixture can be applied before planting such crops, at
planting, pre-emergence (i.e., during the interval after planting
of the crop plant up to, but not including, emergence of the crop
plant) or post-emergence to the crop plants. For example, the
application mixture comprising an ester of a carboxylic acid
herbicide of the present invention can be applied at planting or
post-emergence to the crop plants having a trait providing
tolerance to the carboxylic acid herbicide to control weeds
susceptible to the carboxylic acid herbicide in a field of the crop
plants and/or adjacent to a field of the crop plants. In another
example, in some embodiments of the present invention, an ester of
a carboxylic acid herbicide of the present invention (e.g., an
ester of dicamba or 2,4-D) is combined with glyphosate co-herbicide
(or a salt or ester thereof) in the application mixture and the
crop plant comprises a glyphosate-tolerant trait and the crop plant
is further either (i) a plant species not susceptible to the
carboxylic acid herbicide or (ii) comprises one or more traits
providing tolerance to the carboxylic acid herbicide. Accordingly,
such embodiments are useful to control (i) glyphosate susceptible
plants and (ii) glyphosate resistant volunteer crop plants and/or
weeds that are susceptible to the carboxylic acid herbicide growing
in a field of (iii) crop plants tolerant to glyphosate and the
carboxylic acid herbicide.
[0190] The application mixture comprising an ester of a carboxylic
acid herbicide of the present invention can be applied pre-emergent
or post-emergent to the weeds. Applying pre-emergent to the weeds
generally refers applying the application mixture formulation at
any time during an interval from about 40 days, from about 30, from
about 25 days, from about 20 days, from about 15 days, from about
10 days, or from about 5 days pre-emergence of the weeds. Applying
post-emergent to the weeds generally refers to applying the
formulation at any time during an interval up to about 1 day after
emergence, up to about 2 days after emergence, up to about 3 days
after emergence, up to about 4 days after emergence, up to about 5
days after emergence, up to about 10 days after emergence, up to
about 15 days after emergence, or up to about 20 days or longer
after emergence of the weeds.
[0191] Weed control mentioned herein refers to any observable
measure of control of plant growth, which can include one or more
of the actions of (1) killing, (2) inhibiting growth, reproduction
or proliferation, and (3) removing, destroying, or otherwise
diminishing the occurrence and activity of plants. Weed control can
be measured by any of the various methods known in the art. For
example, weed control can be determined as a percentage as compared
to untreated plants following a standard procedure wherein a visual
assessment of plant mortality and growth reduction is made by one
skilled in the art specially trained to make such assessments. In
another control measurement method, control is defined as a mean
plant weight reduction percentage between treated and untreated
plants. In yet another control measurement method, control can be
defined as the percentage of plants that fail to emerge following a
pre-emergence herbicide application. A "commercially acceptable
rate of weed control" varies with the weed species, degree of
infestation, environmental conditions, and the associated crop
plant. Typically, commercially effective weed control is defined as
the destruction (or inhibition) of at least about 60%, about 65%,
about 70%, about 75%, about 80%, or even at least about 85%, or
even at least about 90%. Although it is generally preferable from a
commercial viewpoint that about 80-85% or more of the weeds be
destroyed, commercially acceptable weed control can occur at much
lower destruction or inhibition levels, particularly with some very
noxious, herbicide-resistant plants.
Novel Photo-Labile Protecting Groups
[0192] It has also been discovered that 2-quinoxalinol, maleic
hydrazide, and phthalhydrazide moieties can be used as photolabile
protecting groups. These moieties can be used in a method for the
photo-release of a compound, wherein the method comprises exposing
the compound to natural or artificial light, and the compound has
been chemically modified to have an ester linkage to a photolabile
protecting group having one of the following structures:
##STR00068##
EXAMPLES
Example 1
Synthesis of the Acid Chloride of Dicamba
##STR00069##
[0194] The reaction was performed in a 1-liter, 3-neck round-bottom
flask with a mechanical stirrer. The flask was immersed in an oil
bath that was initially at room temperature. In order to avoid loss
of thionyl chloride from the reaction mixture, a water-cooled
reflux condenser was attached to one neck of the flask and the
other neck was plugged after dicamba addition was complete. 323 g
of thionyl chloride was added to the flask and the oil bath heater
was switched on with a setpoint of 80.degree. C. 400 g of dicamba
was added through one neck over about ten minutes. Evolution of HCl
gas began during addition and subsided after about 90 minutes. The
reaction was continued for about an hour after gas evolution
subsided. About 475 g of crude liquid product was recovered.
[0195] Two batches of crude dicamba acid chloride were combined in
a 2-liter flask that was connected to a vacuum distillation
apparatus. The flask was insulated with glass wool and placed in a
heating mantle. Heat was applied and a small (40 g) fore-run
containing residual thionyl chloride was discarded. Vacuum was then
applied and the product distilled at 210.degree. C., 220 torr (29.3
kPa). 793 g of product was recovered.
Example 2
Synthesis of the Acid Chloride of 2,4-D
##STR00070##
[0197] The reaction was performed in a mechanically stirred
1-liter, 3-neck round-bottom flask. One neck was connected to a 500
ml, 3-neck round-bottom flask through a latex tube connected to a
glass gas dispersion tube immersed in 350 g of 50% NaOH plus 150 ml
of water within the flask. The caustic flask was connected to
vacuum through a tube with a pinchcock clamp to control the
vacuum.
[0198] The reaction flask was immersed in an oil bath that was not
heated initially. 350 g of thionyl chloride was added and heating
and stirring initiated. 500 g of 2,4-D acid was added over 51
minutes.
[0199] The acid chloride was purified by vacuum distillation
between 145.degree. C. and 180.degree. C. at pressure from 104 to
160 torr (13.9 to 21.3 kPa). 291 g of acid chloride was recovered
from the distillation.
Example 3
Synthesis of the 2-Nitrobenzyl Ester of Dicamba, 1a, from the
Alcohol
##STR00071##
[0201] 76.6 g of 2-nitrobenzyl alcohol (0.5 mol, Aldrich), 52.6 g
of triethylamine (0.52 mol), and 1.9 g of DMAP (Aldrich, 0.03
equiv.) were combined with 200 ml of CH.sub.2Cl.sub.2 in a 1-liter
flask equipped with a stirbar. 119.7 g of dicamba acid chloride
(0.5 mol). The mixture grew warm over five minutes but no refluxing
occurred.
[0202] After stirring for four hours, 20 g of NaHCO.sub.3 in 300 ml
of water was added in order to extract the DMAP and most of the
((CH.sub.2CH.sub.3).sub.3NH.sup.+)(Cl.sup.-) as well as free
dicamba. The organic phase was separated and dried over 10 g of
MgSO.sub.4. After filtration, the solvent was removed using a
rotary evaporator. The product precipitated in the flask. It was
scraped out, rinsed with CH.sub.2Cl.sub.2 and methyl-t-butyl ether
and dried overnight at 80.degree. C. under 24'' Hg (81.3 kPa)
vacuum with nitrogen purge. 110.2 g were recovered (62% yield).
Example 4
Synthesis of the 2-Nitrobenzyl Ester of Dicamba, 1a, Via
2-Nitrobenzyl Chloride
##STR00072##
[0204] 99 g of 2-nitrobenzyl chloride (0.58 mol, Acros), 127 g of
dicamba (1.0 equiv,), 58 g of triethylamine (1.0 equiv.), and 300
ml of CH.sub.2Cl.sub.2 were combined in a 1-liter round-bottom
flask equipped with a stirbar. The flask was immersed in a
78.degree. C. oil bath and refluxed for 18 hours with a
water-cooled condenser attached. A white precipitate formed during
this time ((CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.-).
[0205] The reaction mixture was extracted with a solution of 10 g
of NaHCO.sub.3 in 400 ml of water. The organic phase was isolated
by decantation and a separatory funnel and dried over 15 g of
MgSO.sub.4. After filtration, the solvent was removed using a
rotary evaporator. A heavy orange precipitate formed over about an
hour. The solid was recovered by filtration and rinsed with
methyl-t-butyl ether to remove the orange color. The off-white
solid was dried over a weekend at 55.degree. C. under 24'' Hg (81.3
kPa) vacuum with nitrogen purge. 126.1 g was recovered (0.35 mol,
61%).
[0206] Compound 1c can be synthesized by methods similar to those
described above for 1a, except that 3-nitrobenzyl alcohol or
3-nitrobenzyl chloride is used as the starting material.
Example 5
Synthesis of the 6-Nitroveratryl Alcohol Ester of Dicamba, 1b
##STR00073##
[0208] 10.7 g of 6-nitroveratryl alcohol (0.050 mol, Alfa Aesar),
12.0 g of dicamba acid chloride (1.0 equiv.), 1.0 equiv of
triethylamine, 0.05 equiv. of DMAP and 285 g of CHCl.sub.3 were
combined in an Erlenmeyer flask. Dissolution of the alcohol was
incomplete. The mixture was stirred for 70 hours, wrapped in
foil.
[0209] After reaction, solution of 1.2 equivalents (6.3 g) of
Na.sub.2CO.sub.3 in 100 ml of water was added to the mixture in
order to hydrolyze unreacted dicamba acid chloride and extract it
into water. The mixture was stirred for 30-60 minutes and the
organic (lower) layer was removed and then washed with 5 g of
NaHCO.sub.3 in 50 ml of water using a separatory funnel. The
CHCl.sub.3 solutions stirred over 10 g of MgSO.sub.4 in order to
remove residual water. The MgSO.sub.4 was filtered and the solvent
removed on a rotary evaporator.
[0210] The concentrate initially gave an oil, but a solid formed
upon standing at room temperature. The suspension was rinsed into a
fritted Buchner funnel using methyl-t-butyl ether, rinsed with more
methyl-t-butyl ether, and transferred to a bottle. 13.0 g of a fine
solid was recovered. The dark yellow filtrate was discarded.
[0211] The solid was dried under vacuum with nitrogen purge at
60.degree. C. for three hours. 11.6 g of a fine yellow powder was
obtained after drying (56% of theoretical).
Example 6
Synthesis of the 2-Nitrophenethyl Ester of Dicamba, 2
##STR00074##
[0213] 49.8 g of 2-nitrophenethyl alcohol (Aldrich, 0.30 mol), 33.1
g of triethylamine (1.1 equiv.), 74.9 g of dicamba acid chloride
(1.05 equiv.), 1.82 g of DMAP (5 mol %), and 150 ml of
CH.sub.2Cl.sub.2 were combined in a 500-ml round-bottom flask
equipped with a stirbar and stirred overnight at room temperature.
Mild heat evolution was noted initially, but the solution did not
boil.
[0214] After 15 hours, a heavy precipitate was observed. 15 g of
Na.sub.2CO.sub.3 in 200 ml of water was added to extract the
precipitate (HN(CH.sub.2CH.sub.3).sub.3.sup.+Cl.sup.-) and
hydrolyze residual dicamba acid chloride. The aqueous layer was
separated and the organic layer washed with 12 g of NaHCO.sub.3 in
150 ml of water to extract DMAP and residual organic salts. The
organic layer was then dried over 10 g of MgSO.sub.4, filtered, and
concentrated on a rotary evaporator. Crystallization occurred on
cooling. The product was recovered by filtration, rinsed with
methyl-t-butyl ether, and dried under 24'' Hg (81.3 kPa) vacuum at
45.degree. C. with nitrogen purge for two hours. 66 g of a light
yellow crystalline solid was recovered (0.18 mol, 60% yield).
Example 7
Synthesis of the 2-(2-Nitrobenzoxy)Ethanol Ester of Dicamba, 4
##STR00075##
[0216] 20.64 g of 2-iodoethanol (0.12 mol, Aldrich), 13.4 g of
triethylamine (1.1 equiv.), 28.7 g of dicamba acid chloride (1.0
equiv.), 0.73 g of DMAP (0.05 equiv.), and 50 ml of dry
CH.sub.2Cl.sub.2 were combined in a round-bottom flask equipped
with a stirbar. Mild heat evolution was noted immediately after
adding the last component, DMAP.
[0217] After stirring for three hours, a solution of 5 g of
Na.sub.2CO.sub.3 in 70 ml of water was added to extract
(CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.- and hydrolyze residual
dicamba acid chloride. After stirring for an hour, 5 g of
NaHCO.sub.3 in 70 ml of water was added and stirred briefly to
extract DMAP. The yellow organic phase was isolated using a
separatory funnel and dried over MgSO.sub.4. After filtration, the
solvent was removed using a rotary evaporator to a light orange
low-viscosity residue (43.6 g, 97% of theoretical).
[0218] The residue was dissolved in 50 ml of CH.sub.2Cl.sub.2 in
around-bottom flask. 5.8 g of a 60% suspension of NaH in mineral
oil was added. (1.2 equiv. with respect to 2-iodoethanol used in
first step, Rohm and Haas via Aldrich). A solution of 18.4 g of
2-nitrobenzyl alcohol (1.0 equiv., Aldrich) in 100 ml of
CH.sub.2Cl.sub.2 was added over 26 minutes with a dropping funnel.
Light hydrogen evolution was observed initially. After five
minutes, a heavy precipitate formed, hydrogen evolution accelerated
significantly, and the solution grew warm but never refluxed. From
this time forward, the solution began to darken.
[0219] The mixture was stirred for four hours. Then 8 g of
NaHCO.sub.3 in 100 ml of water was added to neutralize residual
NaH. The mixture was then poured into a flask containing 450 ml of
water in order to extract NaI and separate the phases. More water
had to be used to isolate the organic layer because both phases
were dark in color. Adding water lightened the color of the aqueous
phase. The organic phase was dried over MgSO.sub.4, filtered, and
concentrated on a rotary evaporator. Diethyl ether was added,
leading to the formation of a small amount of a gummy precipitate.
The product was filtered and the filtrate again concentrated on a
rotary evaporator. 30.0 g of a red-purple liquid was collected (62%
of theoretical).
Example 8
Synthesis of p-Methoxy-.alpha.-Chloroacetophenone and the
4-Methoxyphenacyl Methyl Ester of Dicamba, 9
##STR00076##
[0221] 194.6 g of anisole (1.8 mol, anhydrous, Sigma), 169.4 g of
chloroacetyl chloride (1.5 mol, Sigma) and 250 g of CS.sub.2 were
combined in a 1-liter flanged reaction vessel with a rounded
bottom. The mixture was mechanically stirred and 227 g (1.7 mol) of
AlCl.sub.3 was added over 12 minutes.
[0222] After two hours of reaction, the reaction mixture was
carefully poured out into a 4-liter beaker containing 1.0 kg of ice
and 650 g of concentrated hydrochloric acid. The mixture was
agitated with a spatula. A light-colored precipitate formed as the
red color was discharged. 200 ml of CHCl.sub.3 was used to rinse
the reaction vessel and added to the beaker, forming a separate
organic layer on the bottom. The aqueous layer was mostly decanted
and the mixture was filtered. The water was immediately decanted
from the filtrate. More product precipitated in the filter flask
and it was recovered in the same Buchner funnel as the original
precipitate. The precipitate was rinsed with ethyl acetate and
dried overnight at 80.degree. C. under 24'' Hg (81.3 kPa) vacuum
with nitrogen purge. 220 g were recovered.
[0223] 150 g (0.81 mol) p-methoxy-.alpha.-chloroacetophenone
prepared as above was added to a 1-liter round-bottom flask along
with 197 g of dicamba acid (1.1 equiv), 90 g of triethylamine (1.1
equiv.) and 400 ml of THF. The mixture was refluxed in a 70.degree.
C. oil bath with a reflux condenser attached. Substantial solid
formation was visible within 10 minutes and the solution had set
up, freezing the stirbar, within 20 minutes.
[0224] After 3.7 hours of stirring, the contents of the flask were
poured into a beaker containing a solution of 30 g of NaHCO.sub.3
in 600 ml of water. The flask was rinsed out with a little more
water which was added to the beaker. A dark lower organic layer
formed along with a light-colored aqueous layer. After standing for
about ten minutes, a heavy white precipitate formed.
[0225] The mixture was given at least an hour to complete
precipitation. It was then recovered by filtration, rinsed with
methyl-t-butyl ether, and dried overnight at 80.degree. C. under
24'' Hg (81.3 kPa) vacuum with nitrogen purge. 252 g were recovered
(83%).
Example 9
Synthesis of the p-n-Butoxyphenacylmethyl Ester of Dicamba, 10
##STR00077##
[0227] 100 g of n-butyl phenyl ether (0.68 mol, Aldrich), 73.2 g of
chloroacetyl chloride (0.95 equiv), and 200 g of CS.sub.2 were
combined in a mechanically-stirred round-bottom reaction vessel
equipped with a water-cooled condenser. 100 g of AlCl.sub.3 (1.1
equiv.) was added over 10 minutes with stirring. Refluxing began
after 3 minutes and subsided after 20 minutes. Stirring was
continued for a total of two hours.
[0228] The reaction mixture was carefully poured out onto a mixture
of 900 g of ice and 400 g of conc. HCl. The mixture was stirred
with a spatula to ensure complete hydrolysis, then extracted twice
with diethyl ether (250 and 150 ml). The diethyl ether extracts
were stirred for 30 minutes with 100 g of conc. HCl. The ether
layer was then separated and stirred with a solution of 15 g of
Na.sub.2CO.sub.3 in 200 ml of water to remove HCl and residual
chloroacetic acid. It was again separated and dried over 20 g of
MgSO.sub.4.
[0229] 110.1 g of liquid product was recovered and combined with
1.0 equivalent of triethylamine and dicamba in THF in a
round-bottom flask equipped with a reflux condenser. The mixture
was stirred for 15 hours in a 75.degree. C. oil bath. A solution of
15 g of NaHCO.sub.3 in 300 ml of water was added and stirred
briefly, leading to phase separation.
[0230] The dark organic phase was separated and washed with 300 ml
of water. Roughly 100 ml each of CH.sub.2Cl.sub.2 and water were
added and stirred to improve phase separation. The organic layer
was isolated and the solvent removed using a rotary evaporator. 179
g were recovered (0.44 mol, 90% yield if pure).
Example 10
Synthesis of the 2-Quinoxalinol Ester of Dicamba, 13a
##STR00078##
[0232] 73.1 g of 2-quinoxalinol (0.5 mol, Aldrich), 1.2 g of DMAP
(0.02 equiv.), 120 g of dicamba acid chloride (1.0 equiv.), 53.1 g
of triethylamine (1.0 equiv.) and 300 ml of anhydrous
CH.sub.2Cl.sub.2 were combined in a 1-liter round-bottom flask. A
vigorous reaction ensued, with refluxing occurring within about two
minutes and the formation of a yellow color. Refluxing subsided
after about 20 minutes. The solubility of 2-quinoxalinol was
initially poor, but after 30 minutes the product appeared to be
dissolved and the white suspended solid appeared to be
(CH.sub.3CH.sub.2).sub.3NH.sup.+Cl.sup.-.
[0233] The reaction mixture was stirred for three hours. 15 g of
NaHCO.sub.3 in 300 ml of water was then added to extract
(CH.sub.3CH.sub.2).sub.3NH.sup.+Cl.sup.-, DMAP, and unreacted
dicamba acid chloride. The organic layer was isolated and dried
over 35 g of MgSO.sub.4. The solution was filtered and the solvent
removed with a rotary evaporator. The solid was recovered by
filtration, rinsed with ethyl acetate and diethyl ether to remove
the orange color, and dried at 60.degree. C. under 24'' Hg (81.3
kPa) vacuum with hydrogen purge. 116.0 g of a colorless,
crystalline solid was recovered (0.33 mol, 66% yield).
[0234] Compound 13b can be synthesized in a similar manner, using
3-methyl-2-quinoxalinol as the starting material.
Example 11
Synthesis of the 2-Hydroxypyridine Ester of Dicamba, 14
##STR00079##
[0236] 52.1 g of 2-hydroxypyridine (0.55 mol, Alfa Aesar), 55 g of
triethylamine (1.0 equiv.), 2.0 g of DMAP (3 mol percent), and
131.1 g of dicamba acid chloride (1.0 equiv.) were combined with
100 ml of CH.sub.2Cl.sub.2 in a round-bottom flask equipped with a
stirbar. The solution immediately took on a yellow color and boiled
vigorously within a minute as heavy white solid precipitated,
freezing the stirbar. Boiling subsided within five minutes.
[0237] The mixture was held without heating for two hours and then
added to a solution of 35 g of NaHCO.sub.3 in 500 ml of water to
extract unreacted dicamba, DMAP, and
(CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.-. The organic layer was
separated and concentrated on a rotary evaporator without vacuum.
Crystallization of a yellow solid began immediately afterwards. The
solid was recovered by filtration, rinsed with acetone and
methyl-t-butyl ether and dried overnight at 80.degree. C. under
24'' Hg (81.3 kPa) vacuum with nitrogen purge. 105.3 g were
recovered (64% yield).
Example 12
Synthesis of the Maleic Hydrazide Diester of Dicamba, 17
##STR00080##
[0239] 11.2 g of maleic hydrazide (0.10 mol, Sigma Aldrich) and 54
g of dicamba acid chloride (2.2 equiv) were combined with 100 mL of
pyridine in a round-bottom flask equipped with a stirbar. The
reaction mixture was initially lemon yellow with white suspended
solid. Heat evolution occurred immediately.
[0240] The reaction mixture was stirred for four hours. A solution
of 30 g of Na.sub.2CO.sub.3 in 300 ml of water was added in order
to neutralize any hydrochloride salt of the product and extract
pyridine into the aqueous phase. A liquid lower red phase separated
initially but a fine white solid crystallized beginning in about
half an hour. The mixture was stirred overnight to complete
crystallization. The solid recovered by filtration and rinsed with
water and methyl-t-butyl ether. The solid was then dried at
90.degree. C. under 24'' Hg (81.3 kPa) vacuum with nitrogen purge.
Yields varied from 68-84%.
Example 13
Synthesis of the Phthalhydrazide Diester of Dicamba, 18
##STR00081##
[0242] 8.3 g of phthalhydrazide (0.05 mol, Sigma Aldrich) and 27 g
of dicamba acid chloride (2.2 equiv.) were combined with 50 ml of
pyridine in a round-bottom flask equipped with a stirbar. Heat
evolution occurred immediately along with the formation of a
homogeneous orange solution. A precipitate began to form after 11
minutes.
[0243] The reaction mixture was stirred overnight (17 hours) and
added to a solution of 15 g of NaCO.sub.3 in 120 ml of water to
neutralize any hydrochloride salt of the product and extract
pyridine into the aqueous phase. Heavy precipitate persisted. The
mixture was stirred for two hours, then filtered. The solid was
rinsed with water and methyl-t-butyl ether and dried at 90.degree.
C. under 24'' Hg (81.3 kPa) vacuum with nitrogen purge. 18.7 g of
the diester, a light yellow powder, were recovered (66% of
theoretical).
Example 14
Synthesis of the 2-Nitrobenzyl Ester of 2,4-D, 5a
##STR00082##
[0245] 26.4 g of 2-nitrobenzyl bromide (0.11 mol, Acros) was
combined with 26.4 g of 2,4-D (1.05 equiv), 11.5 g of triethylamine
(1.0 equiv.) and 100 ml of dry THF in a250-ml round-bottom flask.
The mixture was refluxed overnight in a 73.degree. C. oil bath with
a water-cooled condenser attached, then poured into a flask
containing 15 g of NaHCO.sub.3 in 150 ml of water. A white solid
precipitated.
[0246] The solid was recovered by filtration, rinsed with deionized
water, and dried under 24'' Hg (81.3 kPa) vacuum with nitrogen
purge at 85.degree. C. 40.4 g were recovered (nearly
quantitative).
Example 15
Synthesis of the 4-Methoxy-Phenacylmethyl Ester of 2,4-D, 11
##STR00083##
[0248] 18.5 g of p-methoxy-.alpha.-chloroacetophenone from Example
8 was added to a 500 ml round-bottom flask equipped with a stirbar
along with 24.3 g of 2,4-D (1.1 equiv), 11.1 g of triethylamine
(1.1 equiv.), and 150 ml of THF. A water-cooled reflux condenser
was attached and the flask was immersed in a 80.degree. C. oil
bath.
[0249] The mixture was refluxed for 19 hours with stirring at which
time a finely divided white solid was seen in the flask, a mixture
of product and (CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.-. 10 of
NaHCO.sub.3 in 150 ml of water was then added to dissolve the
(CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.- and extract unreacted
2,4-D and triethylamine. A little CO.sub.2 bubbling was seen,
suggesting that some triethylamine had volatilized out. The
suspension was filtered, recovering a white product. The solid was
rinsed with diethyl ether and dried at 80.degree. C. under 24'' Hg
(81.3 kPa) vacuum with nitrogen purge. 17.7 g of white solid was
recovered (48%).
Example 16
Synthesis of the 2-Quinoxalinol Ester of 2,4-D, 15a
##STR00084##
[0251] 29.2 g of 2-quinoxalinol (Aldrich), 20.2 g of triethylamine
(1.0 equiv.), 0.73 g of DMAP (0.03 equiv.), 55.1 g of 2,4-D acid
chloride (1.15 equiv), and 200 ml of dry CH.sub.2Cl.sub.2 were
combined in a 500-ml round-bottom flask equipped with a stirbar.
Dissolution of the 2-quinoxalinol was only partial. Mild heat
evolution was observed immediately.
[0252] After 16 hours, the solution was still heterogeneous. 10 g
of NaHCO.sub.3 in 150 ml of water was added and stirred in order to
dissolve (CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.- and extract
dicamba and DMAP. The off-white solid was recovered by filtration,
rinsed with water, methanol, and diethyl ether, and dried under
24'' Hg (81.3 kPa) vacuum with nitrogen purge at 80.degree. C. 33.6
g were recovered (45% of theoretical).
Example 17
Synthesis of the Bromoxynil and Ioxynil Esters of Dicamba, 23b and
23c
##STR00085##
[0254] This Example describes the synthesis of the bromoxynil and
ioxynil esters of dicamba. For the bromoxynil ester, 10.4 g of
3,5-dibromo-4-hydroxybenzonitrile ("bromoxynil," 38 mmol, Acros)
was combined with 0.2 g of DMAP (5 mol %), 3.8 g of triethylamine
(1.0 equiv.), 50 ml of CH.sub.2Cl.sub.2, and 9.9 g of dicamba acid
chloride (1.1 equiv.) were combined in a round-bottom flask
equipped with a stirbar. The mixture was stirred at room
temperature for 4.5 hours before, a solution of 4 g of NaHCO.sub.3
in 60 ml of water was added to hydrolyze residual dicamba acid
chloride and extract (CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.-,
dicamba, and DMAP. After stirring for an hour, a fine white solid
was isolated by filtration, rinsed with methyl-t-butyl ether, and
dried overnight at 70.degree. C. under 24'' Hg (81.3 kPa) vacuum
with nitrogen purge. 11.65 g of a pure white powder was recovered
(65% of theoretical).
[0255] The ioxynil ester was prepared using the same procedure,
combining 11.8 g of 3,5-diiodo-4-hydroxybenzonitrile ("ioxynil," 32
mmol, Acros), 0.2 g of DMAP (5 mol %), 3.2 g of triethylamine (1.0
equiv.), 50 ml of CH.sub.2Cl.sub.2, and 8.4 g of dicamba acid
chloride (1.1 equiv.). The mixture was stirred for 22 hours before
adding a solution of 4 g of NaHCO.sub.3 in 60 ml of water.
Considerable suspended solid was present which was recovered by
filtration after an hour of stirring. The solid was dried for five
hours at 80.degree. C. under 24'' Hg (81.3 kPa) vacuum with
nitrogen purge. 11.7 g of a pure white fine solid was recovered
(64% of theoretical).
[0256] The chloroxynil ester of dicamba (23a) can be prepared in a
similar manner, using 3,5-dichloro-4-hydroxybenzonitrile
("chloroxynil") as the starting material.
Example 18
Synthesis of the 4-Methoxybenzyl Ester of Dicamba, 29a
##STR00086##
[0258] 138.2 g of 4-methoxybenzyl alcohol (1.0 mol, Aldrich) was
combined with 102 g of triethylamine (1.0 equiv.), 2.4 g of DMAP (2
mol %), 200 ml of acetonitrile, and 264 g of dicamba acid chloride
(1.1 equiv.). The mixture turned dark red and grew very hot, but
did not boil. Heavy precipitate had accumulated within an hour. The
mixture was stirred for 3.6 hours and then added to 60 g of
NaHCO.sub.3 in 800 ml of water in order to hydrolyze and extract
residual dicamba acid chloride and extract acetonitrile, DMAP and
(CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.-. The product separated as
a dark lower layer. The aqueous layer was decanted and washed with
500 ml of water. It was then concentrated on a rotary evaporator.
358.1 g of product was recovered as a low-viscosity liquid (105% of
theoretical).
Example 19
Synthesis of the 4-Methoxyphenol Ester of Dicamba, 30a
##STR00087##
[0260] 112 g of 4-methoxyphenol (0.9 mol, Alfa Aesar), 91 g of
triethylamine (1.0 equiv.), 1.1 g of DMAP (3 mol percent), and 216
g of dicamba acid chloride (1.0 equiv,) were combined with 600 ml
of CH.sub.2Cl.sub.2 in a 2-liter Erlenmeyer flask equipped with a
stirbar. Boiling and formation of a white precipitate began. After
11 hours of stirring, 40 g of NaHCO.sub.3 in 800 ml of water was
added to extract (CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.- and DMAP.
The organic phase was isolated using a separatory funnel and the
solvent removed with a rotary evaporator. The product was poured
into a beaker containing 100 ml of hexane. Crystallization of the
product as a white solid began upon cooling. The solid was
recovered in a Buchner funnel, washed with hexane, and dried at
50.degree. C. under 24'' Hg (81.3 kPa) vacuum with nitrogen purge.
280 g of product was recovered as a fine white crystalline powder
(95% of theory).
Example 20
Baylis-Hillman Condensation of Ethyl Acrylate with Ortho, Meta, and
Para-Nitrobenzaldehyde and Synthesis of the Dicamba Esters, 31a,
31b, and 31c
##STR00088##
[0262] 100 g of the nitrobenzaldehyde (0.66 mol, Alfa Aesar) was
combined with 80 g of ethyl acrylate (1.2 equiv., Alfa Aesar), 4.5
g of DABCO (6 mol %), and ethanol in a 500-ml flask equipped with a
stirbar. The mixtures were stirred for six days. 20 g of
NaHCO.sub.3 in 250 ml of water was added in order to neutralize and
extract DABCO along with most of the solvent and acrylate. A lower
organic layer separated which was isolated, dried over 25 g of
MgSO.sub.4, and concentrated on a rotary evaporator. The products
were yellow-orange liquids. Conversion of the aldehydes was
complete, but a small amount of residual ethyl acrylate was seen by
.sup.1H NMR.
##STR00089##
[0263] 100 g of the three products (0.40 mol) was combined with 1.5
g of DMAP (3 mol %), 40 g of (CH.sub.2CH.sub.3).sub.3N (1.0
equiv.), 100 ml of CH.sub.2Cl.sub.2, and 95 g of dicamba acid
chloride (1.0 equiv). Mild heat evolution was observed for the
ortho isomer, while the meta and para isomers exhibited mild
boiling. A precipitate formed in all three flasks within 30
minutes. The mixtures were stirred overnight (19 hours) at which
point the three reaction mixtures were gelatinous. 20 g of
NaHCO.sub.3 in 500 ml of water was added and the aqueous layer was
decanted. Another 500 ml of water added to extract residual
(CH.sub.2CH.sub.3).sub.3NH.sup.+Cl.sup.- and DMAP. The organic
layer was isolated and concentrated on a rotary evaporator. The
products were viscous liquids. .sup.1H NMR and FTIR confirmed the
identity and purity of the three esters.
Example 21
Synthesis of Dicamba Ester 32a Via Michael Addition of Methyl Vinyl
Ketone to Maleic Hydrazide
##STR00090##
[0265] 101 g of maleic hydrazide (0.90 mol, Alfa Aesar), 85 g of
methyl vinyl ketone (1.2 mol) and 650 ml of absolute ethanol were
combined in a 1-liter flask equipped with a stirbar. 0.5 g of 50%
NaOH was added. The flask was immersed in a 100.degree. C. oil bath
with a reflux condenser attached. After 7 hours of reaction, as
shown in the table below, the homogeneous mixture was poured out
into an Erlenmeyer flask and chilled at about 5.degree. C. for
about three hours. A heavy white precipitate formed which was
recovered by filtration rinsed with methyl-t-butyl ether and dried
at 70.degree. C. under 24'' Hg (81.3 kPa) vacuum with nitrogen
purge overnight. 141 g of product was recovered (86% of
theoretical).
##STR00091##
[0266] 170 g of the Michael addition product (0.93 mol) was
combined with 94 g of triethylamine (1.0 equiv.), 600 ml of
CH.sub.2Cl.sub.2, and 235 g of dicamba acid chloride (1.05 equiv)
in a 2-liter flask. The mixture boiled and turned yellow within a
minute as heavy precipitate formed, freezing the stirbar. It was
allowed to stand for 16 hours before a solution of 50 g of
NaHCO.sub.3 in 600 ml of water was adding, dissolving almost all of
the precipitate. The mixture was filtered and the organic layer was
isolated and concentrated on a rotary evaporator. 325 g of the
product was recovered as a viscous yellow liquid (90% of
theoretical).
Example 22
Synthesis of Dicamba Ester 33a Via Michael Addition of Acrolein to
Maleic Hydrazide
##STR00092##
[0268] 39.2 g of maleic hydrazide (0.35 mol, Alfa Aesar), 25.8 g of
acrolein (0.46 mol, Aldrich) and 200 ml of absolute ethanol were
combined in a 500 ml flask equipped with a stirbar. 0.5 g of 2.5N
NaOH was added. The flask was immersed in a 90.degree. C. oil bath
with a water-cooled reflux condenser attached. The mixture was
refluxed for two hours, at which point a heavy precipitate was seen
in the flask. The mixture was allowed to cool and the solid
recovered by filtration. The product, a white powder, was rinsed
with methyl-t-butyl ether and dried at 80.degree. C. under 24'' Hg
(81.3 kPa) vacuum with nitrogen purge. 53.7 g were recovered (91%
of theoretical). The .sup.1H NMR (CDCl.sub.3) showed the product to
be highly pure and entirely in the hemiaminal form.
##STR00093##
[0269] 33.6 g of the Michael adduct (0.20 mol) was combined with
0.5 g of DMAP (2 mol %), 20 g of triethylamine (1.0 equiv.) 250 ml
of CH.sub.2Cl.sub.2, and 53 g of dicamba acid chloride (1.1
equiv.). Reaction ensued immediately with the mild boiling and
formation of a yellow color. After stirring overnight (16 hours),
the mixture was combined with 30 g of NaHCO.sub.3 in 400 ml of
water and stirred for about 20 minutes. The pale yellow organic
layer was isolated and concentrated on a rotary evaporator. A pale
yellow, viscous liquid was recovered and placed in an 80.degree. C.
vacuum oven for 7 hours under 24'' Hg (81.3 kPa) vacuum with
nitrogen purge. 81.3 g were recovered (110% of theoretical).
Example 23
Synthesis of Dicamba Ester 34a Via Michael Addition of
Acrylonitrile to Maleic Hydrazide
##STR00094##
[0271] 44.8 g of maleic hydrazide (0.40 mol, Aldrich), 23.3 g of
acrylonitrile (0.44 mol, Aldrich) and 300 ml of absolute ethanol
were combined in a 500 ml flask equipped with a stirbar. 8 drops of
2.5N NaOH were added. The flask was immersed in a 100.degree. C.
oil bath and a reflux condenser attached. After 14 hours of
reaction, the mixture was filtered hot to remove some suspended
white solid. Precipitation of a white solid from the filtrate began
immediately thereafter. The flask was allowed to stand in a cold
room to complete precipitation.
##STR00095##
[0272] The solid was recovered by filtration and dried at
80.degree. C. under 24'' Hg (81.3 kPa) vacuum with nitrogen purge.
In order to clean up residual water and eliminate the sodium salts,
the product was suspended in a mixture of 10 g of acetic acid and
75 ml of water and stirred briefly. The solid was recovered by
filtration, rinsed with methyl-t-butyl ether and acetone, and dried
at 80.degree. C. under 24'' Hg (81.3 kPa) vacuum with nitrogen
purge. All of the dry product (7.06 g, 43 mmol) was combined with
4.3 g of triethylamine (1.0 equiv), 0.16 g of DMAP (3 mol %), 100
ml of CH.sub.2Cl.sub.2, and 11.3 g of dicamba acid chloride (1.1
equiv.) in a roundbottom flask equipped with a stirbar.
[0273] After 15 hours of stirring, 6 g of NaHCO.sub.3 in 80 ml of
water was added to the cloudy solution. A small amount of white
solid remained, which was filtered off, and the organic layer was
isolated and concentrated on a rotary evaporator. 11.2 g of a
viscous, light yellow liquid was recovered, but a good deal of
material remained in the flask. Both eventually crystallized and
were recovered by filtration and rinsed with CH.sub.2Cl.sub.2. The
off-white powder was dried at 80.degree. C. under 24'' Hg (81.3
kPa) vacuum with nitrogen purge.
Example 24
Synthesis of Dicamba Ester 36a
##STR00096##
[0275] 100 g of 2,2,6,6-tetramethyl-3,5-heptanedione (0.54 mol,
Alfa Aesar) was combined with 50 g of cyanoacetamide (1.1 equiv.),
12 g of piperazine (0.25 equiv), and 300 ml of absolute ethanol in
a 1-liter roundbottom flask equipped with a stirbar. A reflux
condenser was attached and the flask was refluxed in a 90.degree.
C. oil bath overnight (15 hours).
[0276] The mixture was then added to a solution of 40 g of
NaHCO.sub.3 in 600 ml of water in order to protonate the piperazine
and extract excess cyanoacetamide. The product separated as a clear
upper layer which was isolated. The water layer was rinsed with 200
ml of methyl-t-butyl ether which was isolated and combined with the
product. The organic phase was dried over 25 g of MgSO.sub.4, which
was then filtered and rinsed with additional methyl-t-butyl ether.
The filtrate was concentrated on a rotary evaporator. 130 g was
recovered (102% of theoretical).
##STR00097##
[0277] All of the product was combined with 55 g of triethylamine
(1.0 equiv. if pure), 1.3 g of DMAP (2 mol %), 100 ml of
CH.sub.2Cl.sub.2, and 149 g of dicamba acid chloride (1.15 equiv.)
and stirred at room temperature for 3 hours. Mild heat evolution
was noted and a heavy white precipitate formed within ten minutes.
After five hours of reaction, 30 g of NaHCO.sub.3 in 350 ml of
water was added. After stirring for a few minutes the organic layer
was separated and the solvent removed on a rotary evaporator. 225 g
of product was recovered as a dark liquid (95% of theoretical).
Example 25
Synthesis of a Pyridione Diester of Dicamba, 37a
##STR00098##
[0279] 42 g of 2-cyanoacetamide (0.5 mol, Alfa Aesar) and 53 g of
benzaldehyde (1.0 equiv., Alfa Aesar) and 1.3 g of 50% NaOH were
dissolved in 200 ml of absolute ethanol (enough for complete
dissolution at room temperature) in a 3-neck roundbottom flask
equipped with a stirbar. A gas dispersion tube was inserted through
one side neck, the other side neck was plugged, and a water-cooled
reflux condenser was attached to the center neck. The flask was
immersed in a 90.degree. C. oil bath and refluxed for 2.5 hours. 50
g of additional cyanoacetamide was then added along with another
100 ml of ethanol. 1 hour after the second cyanoacetamide addition,
gentle air bubbling was initiated.
[0280] After a further 1.5 hours of reaction (5 hours total), 1.0 g
of copper acetate monohydrate (1 mol %) in 5 g of acetic acid were
added with a few ml of ethanol used to rinse it into the flask. The
acetic acid neutralized the base in order to promote cyclization
and to maintain the solubility of the copper. Refluxing was
continued for a further 2 hours (7 hours total). The reaction
mixture was then poured out into a flask and allowed to cool. The
viscous liquid was placed in a vacuum oven at 80.degree. C. under
24'' Hg (81.3 kPa) vacuum with nitrogen purge to remove residual
ethanol and acetic acid. The resulting material, still highly
viscous, was transferred to ajar. 120 g was recovered (101% of
theoretical).
##STR00099##
[0281] The product was placed in a 100.degree. C. oven in order to
melt it, and 34.7 g (0.15 mol) was transferred to a 1-liter
roundbottom flask equipped with a stirbar. 0.5 g of DMAP (3 mol %)
was added along with 33 g of triethylamine (2.2 equiv.), 250 ml of
CHCl.sub.3, and 77 g of dicamba acid chloride (2.2 equiv.). The
flask was immersed in a 75.degree. C. oil bath and a water-cooled
reflux condenser was attached. The condensation product initially
formed a sticky mass in the bottom of the flask but the solution
was homogeneous and stirring well with reflux within 20
minutes.
[0282] After 4.5 hours of reaction, the mixture was added to a
solution of 15 g of NaHCO.sub.3 in 300 ml of water. The organic
layer was separated, washed with deionized water, and concentrated
on a rotary evaporator. 97 g of a dark, viscous liquid was
recovered (103% of theoretical). The .sup.1H NMR was consistent
with the assigned structure.
Example 26
In Vitro Testing of Dicamba Photo-Release from Photo-Labile Dicamba
Esters (Tetrahydrofuran Solvent)
[0283] This Example describes in vitro testing of dicamba
photo-release by homogeneous solutions of photo-labile dicamba
esters. The esters were dissolved in tetrahydrofuran (THF). Ester
concentration was 0.1 mM. 25 ml of the solution was transferred to
22 mm tubes fabricated from graded seal quartz tubing with a 19/22
tapered seal at the top, which was closed with a tapered glass plug
and secured with a plastic ring clamp. The solution was entirely
below the quartz-to-glass transition, ensuring that the entire
volume was exposed to the full spectrum.
[0284] The sealed tubes were placed in a Growth Chamber where they
were exposed to simulated sunlight for 14 hours per day at
35.degree. C. Dicamba concentrations in the solution were measured
during the course of the photolysis. As seen below, several esters
undergo near-quantitative conversion to dicamba over a period of
several days.
[0285] The results below, obtained using THF as a solvent,
demonstrate high conversion of the photo-labile esters to dicamba.
A sample of the initial solution was reserved in a glass vial away
from the light source and analyzed at the conclusion of the study,
providing a measurement of the amount of dicamba present without
illumination of the photolysis solution (the "dark control").
TABLE-US-00001 Conversion to dicamba Dark Control 2 3 5 7 9 11 12
15 Ester % dicamba 1 day days days days days days days days days 1a
1% 22% 33% 47% 66% 76% 2 0% 46% 54% 72% 84% 88% 98% 96% 95% 9 1%
76% 91% 90% 89% 89% 10 8% 16% 15% 16% 19% 20% 29% 35% 35% 13a 11%
28% 35% 43% 48% 61% 66% 68%
Example 27
In Vitro Testing of Dicamba Photo-Release from Photo-Labile Dicamba
Esters (Acetonitrile/10% Water Solvent)
[0286] This Example is another photolysis of photo-labile dicamba
esters, but using acetonitrile containing 10% water by weight as
the solvent. The experimental protocol is otherwise the same as in
Example 18.
TABLE-US-00002 Dark Conversion to dicamba Control % 2 3 5 11 13 15
Ester dicamba 1 day days days days 7 days days days days 19 days 2
0% 33% 56% 75% 93% 104% 107% 108% 96% 106% 10 8% 17% 19% 20% 24%
28% 32% 31% 32% 33% 14 0% 6% 9% 10% 12% 12% 19% 21% 25% 26%
Example 28
Emulsifiable Concentrate Formulations of Photo-Labile Esters of
Dicamba
[0287] This Example describes formulation of photo-labile esters of
dicamba as emulsifiable concentrates. In all cases, the
emulsification system was based on a combination of a castor oil
ethoxylate, typically SURFONIC CO-54 from Huntsman, and an
alkylbenzene sulfonate calcium salt, typically either NANSA EVM/2E,
also from Huntsman or WITCONATE P1220EH from Akzo Nobel. Aromatic
200 solvent from Exxon (a complex mixture of aromatic hydrocarbons)
was used except in the case of the phenacylmethyl ester whose low
solubility made it preferable to use monochlorobenzene, and in the
case of 4-n-butoxyphenacymethyl, for which no solvent was used. The
formulations and their designations are shown in the table
below.
TABLE-US-00003 Ester Ester Sol- Surfact. Surfact. Ester type ID wt
% vent.sup..dagger. 1.sup..dagger-dbl. 2* 2-nitrobenzyl 1a 15% A
200 P1220, 5% CO54, 5% 2-nitrophenethyl 2 15% A 200 P1220, 5% CO54,
5% 2-(2-nitro- 3 61% A 200 P1220, 5% CO54, 5% phenoxy)ethanol
2-(2-nitro- 4 63% A 200 P1220, 5% CO54, 5% benzoxy)ethanol
4-methoxy- 9 10% MCB P1220, 5% CO54, 5% phenacymethyl 4-n-butoxy-
10 90% None P1220, 5% CO54, 5% phenacymethyl 2-quinoxalinol 13a 17%
A 200 P1220, 5% CO54, 5% .sup..dagger.A200 = Aromatic 200, MCB =
monochlorobenzene .sup..dagger-dbl.P1220 = WITCONATE P-1220 EH
*CO54 = SURFONIC CO-54
Example 29
Efficacy of Photo-Labile Ester Formulations for Post-Emergent
Control of Velvetleaf
[0288] The efficacy of some photo-labile ester formulations from
Example 28 for post-emergent control of velvetleaf was tested in
the greenhouse. All formulations were tested at rates of 140, 280,
420, and 560 g dicamba equivalent per hectare rates and compared to
the diglycolamine salt of dicamba (CLARITY.RTM.) at the same rates
and untreated control plants. The velvetleaf plants were 10-15 cm
in height at the time of spraying. Percent control was evaluated
three weeks after treatment. The underperformance of the 4-methoxy
and 4-n-butoxyphenacyl esters in these data was likely due to
screening of ultraviolet light in the greenhouse. Other esters were
competitive with conventional salts of dicamba.
TABLE-US-00004 % Control of velvetleaf Ester 140 280 420 560 Ester
type ID g/ha g/ha g/ha g/ha Diglycolamine salt -- 44% 63% 68% 83%
2-nitrobenzyl 1a 46% 60% 75% 73% 2-nitrophenethyl 2 50% 69% 78% 90%
4-methoxyphenacymethyl 9 23% 19% 28% 29% 4-n-butoxyphenacymethyl 10
23% 33% 28% 33%
Example 30
Efficacy of Photo-Labile Ester Formulations for Post-Emergent
Control of Velvetleaf
[0289] The methodology of Example 29 was used to evaluate the
efficacy of several photo-labile esters of dicamba for
post-emergent control of velvetleaf as emulsifiable concentrate
formulations described in Example 28.
TABLE-US-00005 % Control of velvetleaf Ester 140 280 420 560 Ester
type ID g/ha g/ha g/ha g/ha Diglycolamine salt -- 54% 86% 96% 96%
2-(2-nitrophenoxy)ethanol 3 36% 57% 40% 43%
2-(2-nitrobenzoxy)ethanol 4 32% 52% 50% 51% 2-quinoxalinol 13a 44%
69% 70% 83%
Example 31
Emulsifiable Concentrate Formulations of Photo-Labile Dicamba
Esters Reduce Volatility Injury to Dicamba-Sensitive Plants
[0290] This Example demonstrates that emulsifiable concentrate
formulations of photo-labile dicamba esters reduce volatility
injury to dicamba-sensitive plants compared to the use of dicamba
salts under conditions which closely mimic field application. In
this case, the diglycolamine salt of dicamba (CLARITY.RTM.) was
used for comparison.
[0291] Dicamba photo-labile ester formulations from Example 28 were
mixed with a commercial glyphosate formulation (ROUNDUP
POWERMAX.RTM.) and diluted to provide a solution with a 0.5%
dicamba equivalent concentrate of the ester (or dicamba
diglycolamine salt) and 1.5% concentrate of glyphosate. The
mixtures were sprayed at a 10 gallon per acre (93.5 liters per
hectare) rate on soil in a plastic container ("humidome") with a
transparent lid. One soil container was sprayed with water as a
control. Four glyphosate-tolerant, dicamba-sensitive soy plants
between V2 and V3 stage were immediately placed on the sprayed soil
and the domes attached to the trays with binder clips. The soy
plants were in pots placed directly on the soil but with aluminum
foil wrapped around the bottom to prevent uptake of dicamba or
dicamba esters through the roots.
[0292] The closed containers were held for 24 hours in a growth
chamber which was maintained at 35.degree. C. with 40% relative
humidity. The plants were then removed and grown in a greenhouse
for three weeks. At this time plant injury and growth stage were
assessed compared to the control treated with water only.
[0293] Data from this experiment are given below. The use of
photo-labile esters largely prevents the retardation of plant
development as determined by growth stage while reducing plant
injury compared to dicamba salt formulations.
TABLE-US-00006 Ester type Ester ID % Injury Growth Stage
Diglycolamine salt -- 38% 6 2-nitrobenzyl 1a 8% 8 2-nitrophenethyl
2 13% 9 2-quinoxalinol 13a 18% 8 Untreated -- 0% 9
Example 32
An Emulsifiable Concentrate Formulation of Dicamba Ester 32a
Reduces Volatility Injury to Dicamba-Sensitive Plants
[0294] The method of Example 31 was used to assess the utility of
ester 32a for reducing volatility injury compared to an aqueous
dicamba salt solution, except that the dicamba and glyphosate acid
equivalents were 0.6% and 1.2% respectively, corresponding to
application rates of 0.5 and 1.0 lb/ac (0.56 and 1.12 kg/hectare).
Ester 32a was formulated as an emulsifiable concentrate with 30%
dicamba acid equivalent as shown below.
TABLE-US-00007 Ester 32a 52.3% Aromatic 200 (A 200) 42.7% NINATE
401-A* 3.5% STEPANTEX CO-40.sup..dagger. 1.5% *Alkylbenzene
sulfonate (Stepan) .sup..dagger.Castor oil ethoxylate (Stepan)
The average injury to soybeans 14 days after treatment was 19% for
dicamba ester 32a versus 60% for the dicamba diglycolamine
salt.
Example 33
Suspension Concentrate Formulations of Photo-Labile Esters of
Dicamba
[0295] This Example shows how three dicamba esters of the present
invention, 1a, 9, and 13a, can be formulated as suspension
concentrates which undergo photo-release of dicamba over a period
of several weeks when exposed to sunlight. 1a and 13a underwent
preliminary dry milling prior to dispersion, but this was
unnecessary for 9. The esters were initially dispersed in a
solution containing the dispersing agents, antifoam, and antifreeze
using a high shear mixer (Cowles dissolver). Size reduction was
then conducted using a horizontal bead mill with ceramic beads. The
xanthan gum thickener (KELZAN) was then added as a 1% solution in
water.
[0296] All formulations contained 0.07% of a silicone antifoam
(MAZU DF 100S) and 0.05% of a xanthan gum thickener (KELZAN). The
loading of dicamba ester was 35% (wt/wt) in all cases. The other
components of the formulations are given in the table below. Water
made up the balance of the formulation.
TABLE-US-00008 Mean Ester particle ID size Dispersant 1 Dispersant
2 Antifreeze 1a 3 .mu.m MORWET D425, AGRILAN 755, PG, 6.5% 2.6%
1.6% 9 8 .mu.m SOKALAN CP-9, INVALON, 5.8% Glycerin, 2.1% 11.9% 13a
3 .mu.m PLURIOL ES8898, EMULSON AG/TP1 PG, 6.5% 2.6% 3.3% Notes: PG
= propylene glycol. AGRILAN 755 (Akzo Nobel), SOKOLAN CP-9 (BASF),
PLURIOL ES8898 (BASF) and EMULSON AG/TP1 (Lamberti) are polymeric
dispersants. MORWET D-425 (Akzo Nobel) and INVALON are sulfonated
naphthalene-formaldehyde condensates.
Example 34
Efficacy of a Photolabile Ester of Dicamba in Reducing Dicamba
Volatility Under Realistic Agronomic Conditions
[0297] This Example illustrates the efficacy of photolabile in
reducing the volatility of dicamba under realistic agronomic
conditions. An emulsifiable concentrate of the 2-nitrobenzyl ester
of dicamba, 1a, was prepared using the Akzo Nobel surfactants
SPONTO 334 and 336 along with a castor oil ethoxylated, SURFONIC
CO-54, from Huntsman in Aromatic 200 solvent. The composition is
given below. The dicamba acid equivalent concentration is
8.84%.
TABLE-US-00009 Component Weight % 2-nitrobenzyl dicamba ester, 1a
14.25% Aromatic 200 80.75% SPONTO EC 334 2.25% SPONTO EC 336 2.25%
SURFONIC CO-54 0.50%
[0298] The emulsifiable concentrate of 1a was combined with a
commercial glyphosate formulation, ROUNDUP WEATHERMAX.RTM., and
sprayed on a test plot at a spray rate of 10 gallons per acre (9.35
liters per hectare). The glyphosate and dicamba rates were 1.0 and
0.5 lb/acre (1.12 and 0.56 kg/hectare) respectively on an acid
equivalent basis. The test plot area was approximately 0.05 acre
(0.02 hectare) planted with soybeans that were then shortly before
flowering. As a comparison, a mixture of the diglycolamine salt of
dicamba (CLARITY.RTM.) and ROUNDUP WEATHERMAX was sprayed at the
same rates.
[0299] Immediately after spraying, five air samplers were placed in
the four corners and the center of the plots. Airborne dicamba was
collected on a polyurethane foam (PUF) trap over the ensuing 24
hours and quantified. The maximum temperature during this period
was 86.degree. F. The average dicamba level from the five samplers
was 1.2 nanograms per cubic meter of air (ng/m.sup.3) compared to
11.1 ng/m.sup.3 for the diglycolamine dicamba salt control
formulation.
Example 35
In Vitro Testing of Dicamba Photo-Release and Hydrolytic Release
from Dicamba Esters in an Aqueous Medium
[0300] This Example describes the determination of photo-lability
and hydrolytic lability of dicamba esters in an aqueous medium. 1
mM solutions of the esters were prepared in acetonitrile (or 0.05
mM solutions of dicamba diesters). The solutions were then diluted
with deionized water to a concentration of 0.01 mM (or 0.005 mM for
diesters). The solutions were then transferred to quartz tubes and
amber bottles and held in a growth chamber by the procedure of
Example 26. A 14-hour day was generally used at a constant
temperature of 35.degree. C. Hydrolytic activity was assessed by
measuring the increase in dicamba concentration after day zero in
the amber (dark) bottles. In some cases, due to chromatographic
conditions, some dicamba was seen at time zero, but this was an
artifact. Photolysis manifested itself as increased conversion in
the quartz tubes compared to the dark control. The results of this
testing, presented in the table below, show that these dicamba
esters convert to dicamba partially or completely by a
photochemical mechanism.
TABLE-US-00010 Conversion to dicamba Day Day Day Day Day Ester Day
0 Day 1 Day 2 Day 3 Day 4 Day 7 10 11 14 21 28 1a Light 7% 13% 16%
18% 21% 29% 37% -- 54% 75% 107% Dark 7% 8% 8% 8% 7% 8% 8% -- 8% 8%
8% 2 Light 3% 78% 79% 75% 77% 78% 84% -- 82% 83% 86% Dark 3% 3% 3%
3% 3% 3% 3% -- 3% 3% 3% 13a Light 8% 9% 12% 13% 13% 15% -- 19% 20%
-- -- Dark 8% 7% 7% 8% 8% 9% -- 11% 12% -- -- 30a Light 6% -- --
14% -- -- -- -- 23% 29% 36% Dark 6% -- -- 5% -- -- -- -- 17% 17%
19% 32a Light 5% 14% 16% 18% 22% 27% -- -- 44% 50% 59% Dark 5% 12%
14% 17% 22% 34% -- -- 41% 55% 70%
Example 36
In Vitro Testing of Dicamba Photo-Release and Hydrolytic Release
from Dicamba Esters in an Aqueous Medium
[0301] This Example provides the results of an aqueous lability
test following the protocol of Example 35 for several dicamba
esters which convert to dicamba primarily by hydrolysis. As shown
by the results in the table below, conversion of the dark controls
generally equaled or exceeded conversion in the photolysis
solutions.
TABLE-US-00011 Conversion to Dicamba Day Day Day Day Ester Day 0
Day 1 Day 2 Day 3 Day 4 Day 7 10 14 21 28 14 Light 2% 61% 63% 64%
68% 67% -- 71% 71% 75% Dark 2% 68% 81% 84% 86% 92% -- 90% 91% 97%
17 Light 6% 18% 26% 33% 36% 42% -- 53% -- -- Dark 6% 16% 26% 35%
41% 49% -- 60% -- -- 29a Light 27% 75% 74% 75% 74% 76% -- 77% -- --
Dark 27% 81% 83% 83% 80% 84% -- 85% -- -- 31a Light 16% 45% 48% 46%
45% 46% 50% 51% 53% 53% Dark 16% 37% 43% 43% 44% 49% 50% 51% 49%
50% 33a Light 13% 18% 20% 19% 22% 23% 30% 42% 53% 57% Dark 13% 15%
18% 18% 22% 21% 28% 37% 50% 55% 34a Light 3% 10% 14% 16% 20% 29% --
48% 60% 71% Dark 3% 9% 14% 18% 23% 38% -- 56% 71% 87% 35a Light 19%
57% 58% 58% 62% 60% -- 64% 63% 65% Dark 19% 66% 69% 68% 71% 74% --
70% 70% 74% 36a Light 20% 57% 60% 58% 59% 63% -- -- 65% -- Dark 20%
59% 61% 60% 60% 65% -- -- 66% --
Example 37
Efficacy of Photo-Labile Ester Formulations for Post-Emergent
Control of Velvetleaf
[0302] The methodology of Example 29 was used to evaluate the
efficacy of several esters of dicamba which convert to dicamba by
hydrolysis for post-emergent control of velvetleaf as emulsifiable
concentrate formulations. The efficacy of esters which undergo
rapid hydrolysis (such as 14, 29a, and 35a) is similar to that of
the glycolamine salt, but slower hydrolyzing esters such as (32a
and 33a) exhibit reduced post-emergent efficacy.
TABLE-US-00012 % Control of velvetleaf 140 280 420 560 Ester ID
g/ha g/ha g/ha g/ha Diglycolamine salt 43.3% 65.8% 87.5% 90.0% 14
40.0% 58.3% 80.8% 85.0% 17 23.3% 41.7% 75.0% 73.3% 29a 30.0% 55.0%
74.2% 81.7% 30a 19.2% 12.5% 18.3% 15.0% 32a 12.5% 19.2% 33.3% 37.5%
33a 15.8% 27.5% 22.5% 30.8% 35a 35.8% 60.0% 85.0% 87.5% 36a 15.8%
26.7% 32.5% 66.7%
Example 38
Field Testing of Emulsifiable Concentrate Formulations of Dicamba
Esters 1a, 2, 9, and 13a
[0303] Four dicamba esters, 1a, 2, 9, and 13a, were formulated as
emulsifiable concentrates for field testing. All formulations
contained 5% each of a alkylbenzene sulfonate calcium salt
(Huntsman NANSA EVM 62/H or Akzo Nobel WITCONATE P-1220 EH) and
castor oil ethoxylate (Huntsman SURFONIC CO-54) as the emulsifiers
and Aromatic 200 (Exxon) or monochlorobenzene (MCB) as the solvent.
The formulations are given in the table below.
TABLE-US-00013 Ester Dicamba Ester wt. % Solvent.sup..dagger.
Surfactants.sup..dagger-dbl. ae* 1a 11.9% A 200, 78% .sup.
P1220/CO54 7.4% 2 20.6% A 200, 69% .sup. P1220/CO54 12.3% 9 9.9%
MCB, 80% EVM62H/CO54 5.9% 13a 13.6% A 200 76% EVM62H/CO54 8.6%
*Dicamba acid equivalent .sup..dagger.A200 = Aromatic 200, MCB =
monochlorobenzene .sup..dagger-dbl.P1220 = WITCONATE P-1220 EH,
CO54 = SURFONIC CO-54, EVM62H = NANSA EVM 62/H
[0304] The esters were compared to the diglycolamine salt of
dicamba (CLARITY.TM.) for post-emergent control of three broadleaf
weeds: velvetleaf, morning glory, and hemp sesbania. Rates of 280
and 420 g dicamba acid equivalent per hectare were used.
Nitrophenyl esters 1a and 2 were equivalent to the dicamba salt for
post-emergent control of all three types of weeds. Phenacylmethyl
ester 9 and quinoxalinol ester 13a were equivalent to the dicamba
salt for post-emergent control of morning glory and hemp sesbania,
and were nearly equivalent to the dicamba salt for post-emergent
control of velvetleaf. Evaluations were conducted at 11 or 21 days
after treatment. Locations and timing were identical for all
formulations tested.
TABLE-US-00014 % control, 280 g/ha Ester Velvetleaf Morning glory
Hemp sesbania Dicamba DGA salt 87 100 81 1a 86 100 95 2 85 94 92 9
79 98 86 13a 72 100 95
TABLE-US-00015 % control, 420 g/ha Ester Velvetleaf Morning glory
Hemp sesbania Dicamba DGA salt 91 100 88 1a 92 98 98 2 92 95 97 9
80 100 93 13a 84 100 98
Example 39
Field Testing of Dicamba Esters 1a, 9, 13a, 15, and 17 in the
Southern Hemisphere
[0305] Five dicamba esters (1a, 9, 13a, 14, and 17) were tested in
the field for post-emergent activity in the Southern Hemisphere.
The primary weeds were Euphorbia species. Ester 9 was tested as a
suspension concentrate using the formulation of Example 33 The
other esters were tested as emulsifiable concentrates having the
formulations shown in the table below. Akzo Nobel SPONTO EC 334 and
SPONTO EC 336 along with SURFONIC CO-54 and NANSA EVM 70/2E
(Huntsman) were used as emulsifiers and Aromatic 200 (A 200; Exxon)
was used as the solvent.
TABLE-US-00016 Ester Solvent Dicamba Ester wt. % (A 200)
.sup..dagger. Surfactants.sup..dagger-dbl. ae* 1a 14.3% 81% EC334,
2.3% 8.8% EC336, 2.3% CO54, 0.5% 13a 17.1% 78% EC334, 2.3% 10.8%
EC336, 2.3% CO54, 0.5% 14 17.2% 73% EVM70/2E, 5%, 12.8% CO-54, 5%
17 18.0% 72% EVM70/2E, 5%, 15.4% CO54, 5% *Dicamba acid equivalent
.sup..dagger. A200 = Aromatic 200 .sup..dagger-dbl.EC334 = SPONTO
EC 334; EC336 = SPONTO EC 336; CO54 = SURFONIC CO-54; EVM70/2E =
NANSA EVM 70/2E
[0306] The results of field tests at rates of 0.25 and 0.50 lb
dicamba acid equivalent (a.e.) per acre (0.28 and 0.56 kg dicamba
a.e. per hectare) are given in the table below. The diglycolamine
salt of dicamba (CLARITY.TM.) was used as a comparator.
TABLE-US-00017 % control, 0.25 lb/ac % control, 0.50 lb/ac Ester
(0.28 kg/hectare) (0.56 kg/hectare) DGA salt 53 70 1a 72 78 9* 54
62 13a 46 55 14 47 56 17 41 53 *Suspension concentrate
Example 40
Field Testing of Emulsifiable Concentrate Formulations of Dicamba
Esters 30a, 32a, and 36a
[0307] Three dicamba esters, 30a, 32a, and 36a, were formulated as
emulsifiable concentrates for field testing. All surfactants are
commercial materials from Stepan. The formulations are given in the
table below.
TABLE-US-00018 Ester Dicamba Ester wt. % Solvent.sup..dagger.
Surfactants.sup..dagger-dbl. ae* 30a 50.0% MCB, 45% TOXIMUL 8320,
5% 34% 32a 52.3% A 200, 43% NINATE 401-A, 3.5%, 30% STEPANTEX
CO-40, 1.5% 36a 68.9% A 200, 26.1% NINATE 401-A 2.5%, 35% STEPANTEX
CO-40, 2.5% *Dicamba acid equivalent .sup..dagger.A200 = Aromatic
200, MCB = monochlorobenzene .sup..dagger-dbl.TOXIMUL 8320 is a
butyl block copolymer, NINATE 401-A is an alkylbenzene sulfonate,
and STEPANTEX CO-40 is a castor oil ethoxylate
[0308] The formulations were tested in the field. Locations and
timing were identical for the three esters, but differed slightly
for the diglycolamine control. The esters were compared to the
diglycolamine salt of dicamba (CLARITY.TM.) for post-emergent
control of three broadleaf weeds: velvetleaf, morning glory, and
hemp sesbania. Rates of 280 and 560 g dicamba acid equivalent per
hectare were used. Ester 36a, which converts rapidly to dicamba by
hydrolysis has a post-emergent activity similar to the dicamba
salt. Ester 30a, which converts relatively slowly by photolysis is
less efficacious. Ester 32a, which exhibits an intermediate
conversion rate and ultra-low volatility in the closed humidome
assay, has an intermediate activity, as expected.
TABLE-US-00019 % control 19 days after treatment, 280 g/ha Ester
Velvetleaf Morning glory Hemp sesbania Dicamba DGA salt 78 .+-. 10
89 .+-. 11 89 .+-. 5 30a 56 .+-. 25 79 .+-. 7 50 .+-. 20 32a 59
.+-. 28 70 .+-. 24 76 .+-. 5 36a 72 .+-. 25 83 .+-. 4 82 .+-.
10
TABLE-US-00020 % control 19 days after treatment, 560 g/ha Ester
Velvetleaf Morning glory Hemp sesbania Dicamba DGA salt 91 .+-. 7
94 .+-. 12 96 .+-. 2 30a 65 .+-. 25 78 .+-. 10 67 .+-. 13 32a 68
.+-. 26 87 .+-. 10 91 .+-. 8 36a 84 .+-. 26 93 .+-. 5 98 .+-. 2
[0309] In view of the above, it will be seen that the several
objects of the invention are achieved and other advantageous
results attained.
[0310] As various changes could be made in the above compositions
and methods without departing from the scope of the invention, it
is intended that all matter contained in the above description and
shown in the accompanying figures shall be interpreted as
illustrative and not in a limiting sense.
[0311] When introducing elements of the present invention or the
preferred embodiments(s) thereof, the articles "a", "an", "the" and
"said" are intended to mean that there are one or more of the
elements. The terms "comprising", "including" and "having" are
intended to be inclusive and mean that there may be additional
elements other than the listed elements.
* * * * *