Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
ii~l'77 o ~
--1--
HERBICIDAL SUBSTITUTED 2-[1-(OXYAMINO)-
ALKYLIDENE]-5-(2 -ETHYLTHIOPROPYL)-CYCLOHEXANE-1,3-DIONES
BACKGROUND OF THE INVENTION
United States Patent No. 4,011,256 discloses herbicidal
cyclohexane-1,3-diones.
SUMMARY OF THE INVENTION
-
This invention relates to novel herbicidal compounds,
compositions and methods of use thereof. It has been found that
novel haloalkenyl and haloaryl-substituted 2-[1-(oxyamino)-alkyl-
idene]-5-(2-ethylthiopropyl)-cyclohexane-1,3-diones are particu-
larly useful as grassy herbicides in both pre- and post-emergent
applications. Moreover, these compounds have excellent soil
stability.
DESCRIPTION OF THE INVENTION
The compounds of the invention have the structural
formula (I):
R~ ~NO-R
¦ (I)
o ~oR5
R4
2/ \ 3
R R
wherein R is propyl;
Rl is trans 3-chloroallyl or 4-chlorobenzyl;
77~78
--2--
One of R2 or R3 is hydrogen and the other is 2-ethyl-
thiopropyl;
R4 is hydrogen;
R5 is hydrogen, a cation, or
o
_CR6
wherein R6 is alkyl of 1 to 6 carbon atoms or aryl of
6 to 10 caxbon atoms.
In terms of desirable phytotoxic properties most
preferably Rl is trans 3-chloroallyl. The salts (i.e. R5 is a
~ation) are of interest to improve solubility and ease of formu-
lation. The esters (R5 is -C(O)R6) are of interest because they
hydrolyze in the field to the parent R5 is hydrogen compound.
Representative R5 groups are hydrogen, NH4+, Na , K ,
Ca , acetyl, propionyl, butyryl, isobutyryl, isovaleryl, 3,3-
dimethylbutyryl, benzoyl, l-naphthoyl, 2-naphthoyl. Preferably
R5 is hydrogen.
The compounds of my invention may be prepared
according to the following scheme:
~2i~77~
--3--
O \\ ~ OCR
R2 ~ + RCX R ~ + HX (1)
(II) (IIa) (III)
R O
\C~
III AlC13 ~ OH (2)
~ ~4
R2 / R3
(IIIa)
\ ~
IIIa + H2~0Rl HCl > ~ HCl
(IV) (Ia)
The appropriate intermediates of the formula (IV) may
be made accordin~ to the following reaction sequence:
~r
~777~3
--4--
NOH + R Cl > ~ oRl + HCl (4)
(V) (Va) (VI)
VI 1. Hydrazine ~ H2NORl HCl (5)
2. HCl
(IV)
Compounds of the formula (I) wherein R5 is other than
hydrogen may be prepared according to conventional procedures by
treating the hydroxy compound (Ia) with an appropriate basic salt
to yield compounds wherein R is Na , NH4 , Ca , etc. Similarly,
the hydroxy compound (Ia) may be acylated by treatment with an
appropriate acid halide to yield compounds wherein R5 is
o
_CR6
Reaction (1) above may be performed at ambient
temperature employing substantially equimolar amounts of the dione
(II) and acid halide (IIa). Preferably the acid chloride (X=Cl)
is used. The reaction may be conducted in an organic solvent,
such as, halogenated hydrocarbons, ethers or glycols. It is
preferred that a base be present, such as an organic amine or
alkali metal carbonate salt, in order to quench the hydrogen halide
which is evolved. Preferred organic amines are pyridine and trial-
kylamines such as triethylamine. Pressure conditions are critical
and atmospheric pressure may be conveniently employed.
"
~21777~
5--
Reaction (2) may be performed in an inert organic
solvent, such as, halogenated hydrocarbons or ethers. At least
two moles of aluminum chloride per mole of ester (III) is used.
Upon work-up, the crude product must be quenched with a proton-
donor, preferably a mineral acid such as hydrochloric acid, to
produce the trione (IIIa).
Reaction (3) is a conventional oxime forming condensa-
tion~ Since the hydrochloride salt (IV) is employed, it is first
neutralized with a base, preferably an alkali metal alkoxide,
before combining with the trione (IIIa) or the free base from
reaction 5 can be used directly. The reaction may be performed in
an inert organic solvent, preferably lower alcohols.
Reaction (4) is a conventional alkylation and may
be performed in inert organic solvents such as dimethylsulfoxide,
acetonitrile, ethers, glycol ethers or hydrocarbons. The reaction
is performed in presence of a base, such as potassium carbonate
at ambient temperature.
Reaction (5) may be performed at elevated temperatures
preferably 30-100C. The phthalimide (VI) is preferably heated
at atmospheric pressure with slight molar excess of hydrazine in
an inert organic solvent, such as a lower alcohol, to reflux
temperature. The crude mixture is then cooled and optionally
quenched with a mineral acid, preferably hydrochloric acid,
yielding the product salt (IV) or the free base can be used directly
in reaction 3.
As an alternative to reactions (1) and (2) above the
trione (IIIa) may be formed in one step by treating the dione (II)
with the acid halide (IIa) in a halogenated hydrocarbon solvent,
~lZ1777~3
preferably carbon tetrachloride, in the presence of trifluoromethyl
sulfonic acid. Typically, the reaction is performed at elevated
temperature (30-150C) and is complete within 90 hours but yields
a mixture of products. Since the combined reaction time of
reactions (1) and (2) is about 24 hours, and results in a purer
product, the two-step sequence of reactions (1) and (2) is pre-
ferred to the one-step alternative.
The starting materials of Formula II can be prepared
by known procedures or obvious modification thereof (e.g. substi-
tution of appropriate starting material). The compounds of FormulaII can be conveniently prepared by the following process schematically
represented by the following overall reaction equations
C=CHC-CH3 + H2C(COR )2 ~ W
(A) (B) (1) R2 ~ (IIa)
IIa base ~ OH (3) ~ R3
(C) (IIb)
wherein R4 is alkyl of 1 through 3 carbon atoms and
R2 and R3 are as defined hereinabove.
These reactions are conventional type reactions and
G \ ,i
lZl'7778
--7--
can be conducted in the usual manner. The first reaction step
is typically conducted by contacting compound A with a compound
B and a base (e.g. alkali metal alkoxides) under reactive conditions
preferably in an inert solvent (e.g. alkanol, e.g. ethanol).
Typically, the reaction is conducted at about from 60 to 110C
using about from 0.5 to 1.5 moles, preferably 0.9 to 1.1 moles,
of compound A and of the base per mole of compound B.
In the second step the ester moiety of compound IIa
is base hydrolyzed to the carboxylic acid, for example, by contac-
ting metallic sodium in alkanol (e.g. ethanol) or alkali metalhydrogen at temperatures in the range of about from 60 to 110C.
By combining the reactants Steps 1 and 2 can be conducted together.
In the third step, compound C can be decarboxylated
via treatment with a strong inorganic acid (e.g. hydrochloric acid,
sulfuric acid). This step is typically conducted at temperatures
in the range of 25 to 110C and can be conveniently conducted in
situ after completion of the base hydrolyzation, Step 2.
The compounds of Formula IIIa can also be prepared
by reacting the compounds of Formula II with the corresponding
anhydride in the presence of an organic base, preferably in an
excess of anhydride or inert organic solvent. Typically, this
reaction is conducted at temperatures in the range of about from
50 to 110C using about from 5 to 0.5 moles of anhydride per mole
of compound II.
The respective products of the above reactions can
be isolated and purified by conventional techniques such as
chromatography, distillation, crystallization, etc., when
appropriate.
1~7778
Definitions
The terms "oxyaminoalkylidene" and "oxyiminoalkyl"
refer to the radical having the formula
-ON = R-
wherein R is alkyl. For example, the terms "1-allyloxyaminobutyli-
dene" and "l-allyloxyiminobutyl" refer to the radical having the
formula
CH2=CH--CH20N= I (CH2 ) 2CH3
Also as is well recognized in the case of the
compounds of formula I where R5 is hydrogen, the compounds are
generally referred to as cyclohexane-1,3-diones rather than
3-hydroxycyclohex-2-en-1-ones.
EXAMPLE 1
Trans-2-[1-(3-chloroallyloxyimino)butyl]-5-(2-
ethylthiopropyl)cyclohexane-1,3-dione
(a) 86.6 g of crotonaldehyde was added dropwise
to a mixture containing 64.0 g of ethanethiol and 2 ml of triethyl-
amine in 500 ml of acetonitrile at room temperature (about 20-25C).
The resulting mixture was stirred overnight (about 15 hours) at
room temperature and then rotary evaporated to remove acetonitrile~
The residue was dissolved in 300 ml of ~thyl ether, washed twice
with water, dried over magnesium sulfate and then concentrated by
evaporation affording a yellow liquid concentrate of beta-ethylthio-
butyraldehyde.
777~
g
(b) A mixture containing 15.9 g of beta-ethylthio-
butyraldehyde and 38.2 g of triphenylphosphoranylidene-2-propanone
in 300 ml of methylene chloride was refluxed overnight and then
evaporated affording a thick residue. The residue was mixed with
hexane and filtered. The filtrate was evaporated under vacuum and
the residue then distilled under vacuum affording 6-ethylthio-3-
hepten-2-one.
(c) 2.53 g of metallic sodium were added to 100 ml of
ethanol at room temperature. To this was then added 17.6 g of
diethyl malonate, with stirring, and then 17.2 g of 6-ethylthio-
3-hepten-2-one was added. The resulting mixture was then refluxed
for four hours and then an aqueous sodium hydroxide solution,
containing 9.5 g of sodium hydroxide in 75 ml of water, was added
and the mixture refluxed for another two hours. The mixture was
cooled to 50C and then acidified by the addition of concentrated
hydrochloric acid. The mixture was then warm until decarboxylation
was complete and then evaporated to a liquid residue. The residue
was mixed with ethyl ether, washed with water, and evaporated to a
brown liquid. The liquid was base, acid extracted affording
5-(2-ethylthiopropyl) cyclohexane-1,3-dione.
(d) 0.2 g of metallic sodium was dissolved in 1
ml of methanol and then added to 3.2 g of 5-(2-ethylthiopropyl)
cyclohexane-1,3-dione. 20 ml of butyric anhydride was added and
the mixture then refluxed for three hours. The mixture was then
evaporated and the residue mixed with methylene chloride and then
extracted with aqueous 5 wt.~ sodium hydroxide. The base extract
was washed with methylene ehloride, then acidified with concentrated
hydrochloric acid and then extracted into methylene chloride.
12i7778
--10--
This was then evaporated affording 2-butyryl-5-(2-ethylthiopropyl)
cyclohexane-1,3-dione.
(e) 0.38 g of sodium methoxide, 10 ml of methanol,
and 1.0 g of 3-chloroallyloxyamine hydrochloride (H2NOCH2CH=CHCl)
were admixed together and then stirred for 10 minutes at room
temperature. 2 g of 2-butyryl-5-(2-ethylthiopropyl)cyclohexane-1,
3-dione was added and the resulting mixture stirred for about two
days at room temperature. The mixture was then concentrated by
evaporation and the concentrate mixed with 60 ml of diethyl ether
and 40 ml of water. The ether layer was extracted with 40 ml
of aqueous 2 wt. % sodium hydroxide solution, washed with 20 ml of
water, dried over anhydrous magnesium sulfate and evaporated
affording a minor amount of the title compound as the trans isomer.
The 2% sodium hydroxide solution extract was acidified
to about pH 1 with aqueous 6N hydrochloric acid and then extracted
with 100 ml of methylene chloride. The organic layer was washed
with 40 ml of water, dried over magnesium sulfate and then
evaporated affording the trans isomer of the title compound as
the residue (Compound No. 1 of Table A hereinbelow). The major
portion of the title compound was recovered from the sodium
hydroxide extract.
EXAMPLE 2
This example illustrates the preparation of the acyloxy
compounds of the invention.
To a reaction mixture containing 3~0 g (0.01) mol of
2-[1-(3'-chloroallyloxyamino)-butylidene]-5-(2-ethylthiopropyl)-
cyclohexane-1,3-dione and 0.87 gm (0.011 mol) of pyridine in 20 ml
-
121777~
--11--
of methylene chloride stirred at 0C is added 0.89 gm (0.011 mol)
of acetyl chloride. The mixture is then stirred at room temperature
for 2 hours. The mixture is then worked up by washing with water,
drying with anhydrous magnesium sulfate, and filtered. lhe filtrate
is evaporated under vacuum affording 3-acetyloxy-2-[1~3'-chloro-
allyloxyamino)-butylidene]-5-(2-ethylthiopropyl)-cyclohex-2-en
one.
Similarly, by following the same procedure, the
corresponding 3-acetyloxy derivative of each of the products listed
in Table A hereinbelow are respectively prepared.
EXAMPLE 3
This example illustrates the preparation of the
salts of the present invention.
To 3.0 gm (0.01 mol) of 2-[1-(3'-chloroallyloxyamino)-
butylidene]-5-(2-ethylthiopropyl)-cyclohexane-1,3-dione in 10 ml
of acetone is added 0.4 gm (0.01 mol) of sodium hydroxide
dissolved in 2 ml of water. The solvents are evaporated under
vacuum affording the 3-hydroxy sodium salt of 2-[1-(3'-chloroallyl-
oxyamino)-butylidene]-3-hydroxy-5-(2-ethylthiopropyl)-cyclohex-2-
en-l-one.
Similarly, by following the same procedure, the sodium
salts of each of the products listed in Table A hereinbelow are
respectively prepared.
UTILITY
The compounds of the present invention are, in general,
herbicidal in both pre- and post-emergent applications. For pre-
emergent control of undesirable vegetation, the herbicidal compounds
:` '
~Z31~77~
-12~
will be applied in herbicidally effective amounts to the locus
or growth medium of the vegetation, e.g., soil infested with seeds
and/or seedlings of such vegetation. Such application will inhibit
the growth of or kill the seeds, germinating seeds and seedlings.
For post-emergent applications, the herbicidal compounds will be
applied directly to the foliage and other plant parts. Generally,
the herbicidal compounds of the invention are especially effective
against grassy weeds and by proper dosage regulation can be
safely applied for the control or prevention of grasses in broad
leaf crops. The compounds of the invention exhibit excellent soil
stability. This is particularly advantageous for pre-emergence
application.
The compounds, when applied to growing plants above
the ground in such an amount that the compounds will not kill
beneficial plants, also show efficient plant growth regulating or
retarding effects and may be advantageously employed, for example,
to prevent or retard the growth of lateral buds in plants and to
promote the thinning out of superfluous fruits in various fruit
trees.
The compounds can be applied in any of a variety of
compositions. In general, the compounds can be extended with a
carrier material of the kind used and commonly referred to in the
art such as inert solids, water and organic liquids.
The compounds will be included in such compositions
in sufficient amount so that they can exert an herbicidal or
growth-regulating effect. Usually from about 0.5 to 95% by weight
of the compounds are included in such formulations.
1~177 7~
-13-
Solid composltions can be made with inert powders.
The compositions thus can be homogeneous powders that can be used
as such, diluted with inert solids to form dusts, or suspended in
a suitable liquid medium for spray application. The powders
usually comprise the active ingredient admixed with minor amounts
of conditioning agent. Natural clays, either absorptive, such as
attapulgite, or relatively non-absorptive, such as china clays,
diatomaceous earth, synthetic fine silica, calcium silicate and
other inert solid carriers of the kind conventionally employed in
powdered herbicidal compositions can be used. The active ingredient
usually makes up from 0.5-90~ of these powder compositions. The
solids ordinarily should be very finely divided. For conversion
of the powders to dusts, talc, pyrophyllite, and the like, are
customarily used.
Liquid compositions including the active compounds
described above can be prepared by admixing the compound with a
suitable liquid diluent medium. Typical of the liquid media
commonly employed ar~ methanol, benzene, toluene, and the like.
The active ingredient usually makes up about 0.5 to 50% of these
liquid compositions. Some of these compositions are designated to
be used as such, ancl others to be extended with large quantities
of water.
Compositions in the form of wettable powders or
liquids can also include one or more surface-active agents, such
as wetting, dispersing or emulsifying agents. The surface-active
agents cause th~ compositions of wettable powders or licluids to
disperse or emulsify easily in water to give aqueous sprays.
~Z1~778
-14-
The surface-active agents employed can be of the
anionic, cationic or nonionic type. They include, for example,
sodium long-chain carboxylates, alkyl aryl sulfonates, sodium
lauryl sulfate, polyethylene oxides, lignin sulfonates and other
surface-active agents.
When used as a pre-emergent treatment, it is desirable
to include a fertilizer, an insecticide, a fungicide or another
herbicide.
The amount of active compound or composition admini-
stered will vary with the particular plant part or plant growth
medium which is to be contacted, the general location of application
-- i.e,, sheltered areas such as greenhouses, as compared to ex-
posed areas such as fields -- as well as the desired type of
control. Generally for both pre- and post-emergent herbicidal
control, the compounds of the invention are applied at rates of 0.2
to 60 kg/ha, and the preferred rate is in the range 0.5 to 40 kg/ha.
For plant growth regulating or retarding activity, it is essential
to apply the compounds at a concentration not so high as to kill the
plants. Therefore, the application rates for plant growth regulat-
ing or retarding activity will generally be lower than the rate
used ~or killing the plants. Generally, such rates vary from 0.1
to 5 kg/ha, and preferably from 0.1 to 3 kg/ha.
Herbicidal tests on representative compounds of the
invention were made using the following methods.
Pre-Emergent Herbicidal Test
An acetone solution of the test compound was prepared
by mixing 500 mg of the compound, 158 mg of a nonionic surfactant
and 20 ml of acetone. Twenty ml of this solution was added to
1~
:~Z~77'7~
80 ml of water to give the test solution.
Seeds of the test vegetation were planted in a pot of
soil and the test solution was sprayed uniformly onto the soil
surface at a dose of 27.5 micrograms/cm2. The pot was watered
and placed in a greenhouse. The pot was watered intermittently
and observed for seedling emergence, health of emerging seedlings,
etc., for a 3-week period. At the end of this period, the herbi-
cidal effectiveness of the compound was rated based on the physio-
logical observations. A 0-to-100 scale was used~ 0 representing
no phytotoxicity, 100 representing complete kill. The results
of these tests appear in Table I.
In follow-up tests, the procedure above was repeated
using diluted test solution which was sprayed onto the soil surface
at various dosages. The results of these tests appear in Table
II.
Post-Emergent ~erbicidal Test
.
The test compound was formulated in the same manner
as described above for the pre-emergent test. This formulation
was uniformly sprayed on 2 similar pots of 24-day-old plants
(approximately 15 to 25 plants per pot) at a dose of 27.5 micro-
grams/cm2. After the plants had dried, they were placed in a
greenhouse and then watered intermittently at their bases, as
needed. The plants were observed periodically for phytotoxic
effects and physiological and morphological responses to the
treatment. After 3 weeks, the herbicidal effectiveness of the
compound was rated based on these observations. A 0-to-100 scale
was used, 0 representing no phytotoxicity and 100 representing
complete kill. The results of these tests appear in Table I.
~Z~77i~3
-16-
In follow-up tests, the procedure above was repeated
using diluted test solution which was sprayed onto the soil surface
at various dosages. The results of these tests appear in Table II.
" 1~177~8
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TABLE I - HERBICIDAL AC_IVIT
Pre/Post % Control (27.5 gamma/cm2~
No. L M P _ W O
1 0/~0 0/20 0/0 100/100100/10~100/100
2 0/30 0/10 0/18 100/100 100/100 100/100
L = Lambsquarter (Chenopodium album
M = Mustard (Brassica arvensis)
P = Pigweed (Amaranthus retroflexus)
C = Crabgrass (Digitaria sanguinalis)
W = Watergrass (Echinochloa crusgalli)
O = Wild Oats (Avenua fatua)
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Obviously many modifications and variations of the
invention, described hereinabove and below in the claims, can be
made without departing from the essence and scope thereof.
