Herbicidal esters of 2-bromo-4-methylimidazole-5-carboxylic acid

BACKGROUND OF THE INVENTION 
Compounds having the structural formula 
##STR2## 
wherein R is hydrogen, alkyl or substituted alkyl and Y is hydrogen, 
alkyl, substituted alkyl, halogen, cyano or nitro are described in U.S. 
Pat. No. 3,501,286 as being herbicides. 
A compound of the formula 
##STR3## 
is taught by Pyman and Timmis, J. Chem. Soc., pp. 494-498 (1923). However, 
no utility for this compound is taught other than its use as an 
intermediate in the preparation of pharmaceuticals. 
DESCRIPTION OF THE INVENTION 
This invention relates to esters of 2-bromo-4-methylimidazole-5-carboxylic 
acid as herbicides. The novel compounds of this invention have the 
following structural formula (A) 
##STR4## 
wherein R is C.sub.1 -C.sub.10 alkyl, preferably C.sub.2 -C.sub.6 alkyl, 
more preferably C.sub.2 -C.sub.5 alkyl, most preferably isopropyl, 
isobutyl, isopentyl or sec-pentyl; C.sub.3 -C.sub.8 cycloalkyl, preferably 
C.sub.4 -C.sub.6 cycloalkyl, more preferably cyclopentyl or cyclohexyl; 
C.sub.3 -C.sub.8 cycloalkylalkyl wherein the alkyl has 1 to 6 carbon 
atoms, preferably cyclopropylmethyl or cyclopentylmethyl; C.sub.3 
-C.sub.10 alkenyl, preferably allyl or 2-methyl-3-butenyl-1; C.sub.5 
-C.sub.8 cycloalkenyl; benzyl or or di-substituted benzyl wherein the 
substituents are C.sub.1 -C.sub.4 alkyl, halogen, nitro or C.sub.1 
-C.sub.4 haloalkyl and Y is substituted or unsubstituted C.sub.1 -C.sub.8 
alkoxy, preferably C.sub.2 -C.sub.4 alkoxy, wherein the substituent is 
halogen, more preferably trichloroethoxy, C.sub.1 -C.sub.8 thioalkyl, 
preferably C.sub.1 -C.sub.4 thioalkyl; C.sub.3 -C.sub.6 alkenyloxy, 
preferably allyloxy; C.sub.3 -C.sub.6 thioalkenyl, preferably thioallyl; 
C.sub.6 -C.sub.10 aryloxy(thio) preferably phenoxy; substituted C.sub.6 
-C.sub.12 aryl alkoxy(thio), preferably benzyloxy. Suitable compounds 
within the above genus are those wherein R is either C.sub.2 -C.sub.6 
alkyl or isopropyl, isobutyl or sec-pentyl and Y is C.sub.2 -C.sub.4 
alkoxy, C.sub.1 -C.sub.4 thioalkyl or phenoxy. 
The structural formula (A) when R and Y are as defined is intended to 
define compounds of either of the following two structural isomers 
##STR5## 
or mixtures of the two isomers in any proportion. 
Both isomers are herbicidally active. 
In the above description of the compounds of this invention alkyl includes 
both straight and branched configurations; for example, methyl, ethyl, 
n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl, the 
amyls, the hexyls, the heptyls, the nonyls and the decyls. 
The compounds of this invention are active herbicides of a general type. 
That is, they are herbicidally effective against a wide range of plant 
species. The method of controlling undesirable vegetation of the present 
invention comprises applying an herbicidally effective amount of the 
above-described compounds to the area where control is desired. 
The compounds of the present invention can be prepared by the following 
general method. 
##STR6## 
wherein R is as defined and TEC is a transesterification catalyst such as 
Ti(O-alkyl).sub.4, preferably Ti(isopropoxy).sub.4. 
##STR7## 
wherein R is as defined, 
##STR8## 
is a haloformate or a halothioformate wherein Y is as defined and X is 
chlorine. 
Generally, for step (1) at least one mole of the alcohol is used for the 
reaction with the ethyl ester to prepare the imidazoles. Preferably, a 
slight mole excess of the alcohol is used. The reaction mixture is 
refluxed until completion of the reaction. The reaction product is 
recovered by removing the volatile materials. Atmospheric, subatmospheric 
or superatmospheric pressures can be used, depending on the boiling point 
of the solvent used. Ethanol is conveniently stripped at elevated 
temperatures and reduced pressure. 
Reaction step (2) is run in a solvent such as tetrahydrofuran, at a 
temperature of about 25.degree., preferably room temperature, using equal 
mole amounts of the two reactants and a hydride base. Preferably, the 
hydride base is sodium hydride. 
The reaction product is a mixture of (1) and (3) isomers and is worked up 
by conventional techniques. 
The following example teaches the synthesis of a representative compound of 
this invention.

EXAMPLE I 
Isopropyl ester of 2-Bromo-4-methyl-5-imidazolecarboxylic acid 
##STR9## 
To a suspension of 6.4 grams (g) (2.7.times.10.sup.-2 moles) of 
ethyl-2-bromo-4-methyl-5-imidazole carboxylate in 70 milliliters (ml) 
isopropanol was added 0.6 ml (2.4.times.10.sup.-3 moles) tetraisopropyl 
titanate. The resulting mixture was heated to reflux for 3 days, then 
concentrated in vacuo to one-half the original volume. The solution was 
cooled on ice and the precipitated crystalline solid was filtered and air 
dried to give 3.4 g of the desired product. 
EXAMPLE II 
Ethyl ester of 1- and 
3-(S-Methylthioformyl)-2-bromo-4-methylimidazolecarboyxlic acid 
##STR10## 
To a suspension of 257 milligrams (mg) (1.07.times.10.sup.-2 moles) of 
sodium hydride in 20 ml of anhydrous tetrahydrofuran was added, in 
portions, 2 g (8.58.times.10.sup.-3 moles) of the ethyl ester of 
2-bromo-4-methyl-5-imidazolecarboxylate. The resulting suspension was 
cooled to 0.degree. C. and 858 ul (8.58.times.10.sup.-3 moles) of 
methylthiochloroformate was added dropwise. The reaction mixture was 
stirred overnight at room temperature. The precipitated sodium chloride 
was removed by filtration and concentration of the filtrate in vacuo gave 
2.1 g (81%) of ethyl 1- and 
3-(S-methylthioformyl)-2-bromo-4-methyl-5-imidazolecarboxylate as a dark 
oil. 
The following is a table of certain selected compounds that are preparable 
according to the procedure described herein. Compound numbers are assigned 
to each compound and are used throughout the remainder of the application. 
TABLE I 
______________________________________ 
##STR11## 
Compound 
Number R Y m.p. .degree.C. 
______________________________________ 
1 ethyl Sn-propyl yellow oil 
2 ethyl Sethyl yellow oil 
3 isopropyl Sn-propyl yellow oil 
4 ethyl Smethyl yellow oil 
5 isopropyl Smethyl yellow oil 
6 isopropyl Sn-butyl orange oil 
7 isopropyl Sisopropyl yellow oil 
8 ethyl Sn-butyl dark oil 
9 ethyl Si-propyl yellow oil 
10 isopropyl Sethyl yellow oil 
11 isobutyl Smethyl yellow oil 
12 sec-butyl Smethyl yellow oil 
13 cyclopentyl Smethyl yellow oil 
14 allyl Smethyl yellow oil 
15 n-butyl Smethyl dark oil 
16 n-propyl Smethyl dark oil 
17 2-(5-methylpentyl) 
Smethyl dark oil 
18 sec-pentyl Smethyl yellow oil 
19 isopropyl ethoxy yellow oil 
20 ethyl ethoxy 63-64 
21 isopropyl OCH.sub.2 CCl.sub.3 
colorless oil 
22 isopropyl n-butoxy colorless oil 
23 ethyl n-butoxy colorless oil 
24 ethyl allyloxy waxy solid 
25 ethyl OCH.sub.2 CCl.sub.3 
tan solid 
26 isopropyl phenoxy yellow oil 
27 sec-butyl OCH.sub.2 CCl.sub.3 
orange oil 
28 sec-butyl benzyloxy yellow oil 
______________________________________ 
Herbicidal Screening Tests 
As previously mentioned, the herein described compounds produced in the 
above-described manner are phytotoxic compounds which are useful and 
valuable in controlling various plant species. Selected compounds of this 
invention were tested as herbicides in the following manner. 
Pre-emergence herbicide test. On the day preceding treatment, seeds of 
eight different weed species are planted in loamy sand soil in individual 
rows using one species per row across the width of a flat. The seeds used 
are green foxtail (FT) (Setaria viridis), watergrass (WG) (Echinochloa 
crusgalli), wild oat (WO) (Avena fatua), annual morningglory (AMG) 
(Ipomoea lacunosa), velvetleaf (VL) (Abutilon theophrasti), Indian mustard 
(MD) (Brassica juncea), curly dock (CD) (Rumex crispus), and yellow 
nutsedge (YNG) (Cyperus esculentus). Ample seeds are planted to give about 
20 to 40 seedlings per row, after emergence, depending upon the size of 
the plants. 
Using an analytical balance, 600 milligrams (mg) of the compound to be 
tested are weighed out on a piece of glassine weighing paper. The paper 
and compound are placed in a 60 milliliter (ml) wide-mouth clear bottle 
and dissolved in 45 ml of acetone or substituted solvent. Eighteen ml of 
this solution are transferred to a 60 ml wide-mouth clear bottle and 
diluted with 22 ml of a water and acetone mixture (19:1) containing enough 
polyoxyethylene sorbitan monolaurate emulsifier to give a final solution 
of 0.5% (v/v). The solution is then sprayed on a seeded flat on a linear 
spray table calibrated to deliver 80 gallons per acre (748 L/ha). The 
application rate is 4 lb/acre (4.48 Kg/ha). 
After treatment, the flats are placed in the greenhouse at a temperature of 
70.degree. to 80.degree. F. and watered by sprinkling. Two weeks after 
treatment, the degree of injury or control is determined by comparison 
with untreated check plants of the same age. The injury rating from 0 to 
100% is recorded for each species as percent control with 0% representing 
no injury and 100% representing complete control. 
The results of the tests are shown in the following Table II. 
TABLE II 
______________________________________ 
Pre-Emergence Herbicidal Activity 
Application Rate - 4.48 kg/ha 
Cmpd. 
No. FT WG WO AMG VL MD CD YNG 
______________________________________ 
1 0 0 0 0 0 0 0 0 
2 0 0 0 0 0 0 0 0 
3 90 90 80 60 90 90 100 0 
4 0 0 0 0 60 60 0 0 
5 100 100 90 80 100 100 90 0 
6 100 90 80 100 100 100 80 30 
7 90 90 60 100 100 100 85 10 
8 20 20 20 60 60 60 80 60 
9 0 0 10 20 0 0 100 0 
10 100 100 40 60 100 100 60 10 
11 0 0 0 0 0 0 0 0 
12 100 100 85 100 100 100 70 0 
13 25 100 70 60 100 100 100 0 
14 80 90 70 100 95 100 80 0 
15 10 75 60 0 100 100 40 0 
16 90 90 65 70 100 100 100 0 
17 0 60 0 0 0 0 20 0 
18 40 30 0 20 100 100 90 0 
19 100 100 80 100 100 100 80 0 
20 20 0 0 40 0 0 80 0 
21 100 100 90 100 100 100 100 0 
22 100 100 60 100 100 100 100 0 
23 0 0 0 0 0 0 0 0 
24 0 0 0 0 0 0 0 0 
25 0 0 0 0 0 0 0 0 
26 100 100 90 100 100 100 90 0 
27 85 100 20 0 70 95 60 0 
28 -- -- -- -- -- -- -- -- 
______________________________________ 
-- = Not tested. 
Post-Emergence Herbicide Test: This test is conducted in an identical 
manner to the testing procedure for the pre-emergence herbicide test, 
except the seeds of the eight different weed species are planted 10-12 
days before treatment. Also, watering of the treated flats is confined to 
the soil surface and not to the foliage of the sprouted plants. 
The results of the post-emergence herbicide test are reported in Table III. 
TABLE III 
______________________________________ 
Post-Emergence Herbicidal Activity 
Application Rate - 4.48 kg/ha 
Cmpd. 
No. FT WG WO AMG VL MD CD YNG 
______________________________________ 
1 60 40 10 40 10 60 80 0 
2 60 40 70 50 60 40 40 0 
3 100 100 100 100 100 100 100 0 
4 40 20 10 90 90 100 80 0 
5 100 100 100 90 100 100 80 20 
6 100 100 100 100 100 100 100 0 
7 100 60 40 100 100 100 85 20 
8 0 0 0 85 100 100 40 0 
9 0 0 0 85 100 100 0 20 
10 100 160 190 95 100 100 90 0 
11 90 40 40 90 90 90 60 0 
12 100 100 100 100 100 100 100 15 
13 100 100 100 85 70 100 100 10 
14 100 35 75 100 100 100 100 0 
15 100 75 60 100 80 80 70 0 
16 90 90 65 70 100 100 100 0 
17 0 60 0 0 0 0 20 0 
18 100 80 100 100 100 100 70 0 
19 100 100 100 100 100 100 95 0 
20 20 20 10 60 100 100 60 0 
21 100 100 100 100 100 100 100 0 
22 100 100 100 100 100 100 100 0 
23 90 70 10 100 80 80 100 0 
24 90 40 40 100 100 100 100 0 
25 80 20 0 80 90 60 80 0 
26 100 90 100 100 100 100 100 0 
27 85 80 55 100 100 100 100 20 
28 100 85 100 100 100 100 80 30 
______________________________________ 
The compounds of the present invention are useful as herbicides, and can be 
applied in a variety of ways at various concentrations. In practice, the 
compounds herein defined are formulated into herbicidal compositions, by 
admixture, in herbicidally effective amounts, with the adjuvants and 
carriers normally employed for facilitating the dispersion of active 
ingredients for agricultural applications, recognizing the fact that the 
formulation and mode of application of a toxicant may affect the activity 
of the materials in a given application. Thus, these active herbicidal 
compounds may be formulated as granules of relatively large particle size, 
as wettable powders, as emulsifiable concentrates, as powdery dusts, as 
solutions or as any of several other known types of formulations, 
depending upon the desired mode of application. Preferred formulations for 
pre-emergence herbicidal applications are wettable powders, emulsifiable 
concentrates and granules. These formulations may contain as little as 
about 0.5% to as much as about 95% or more by weight of active ingredient. 
A herbicidally effective amount depends upon the nature of the seeds or 
plants to be controlled and the rate of application varies from about 0.05 
to approximately 25 pounds per acre, preferably from about 0.1 to about 10 
pounds per acre. 
Wettable powders are in the form of finely divided particles which disperse 
readily in water or other dispersants. The wettable powder is ultimately 
applied to the soil either as a dry dust or as a dispersion in water or 
other liquid. Typical carriers for wettable powders include fuller's 
earth, kaolin clays, silicas and other readily wet organic or inorganic 
diluents. Wettable powders normally are prepared to contain about 5% to 
about 95% of the active ingredient and usually also contain a small amount 
of wetting, dispersing, or emulsifying agent to facilitate wetting and 
dispersion. 
Emulsifiable concentrates are homogeneous liquid compositions which are 
dispersible in water or other dispersant, and may consist entirely of the 
active compound with a liquid or solid emulsifying agent, or may also 
contain a liquid carrier, such as xylene, heavy aromatic naphtha, 
isophorone and other non-volatile organic solvents. For herbicidal 
application, these concentrates are dispersed in water or other liquid 
carrier and normally applied as a spray to the area to be treated. The 
percentage by weight of the essential active ingredient may vary according 
to the manner in which the composition is to be applied, but in general 
comprises about 0.5% to 95% of active ingredient by weight of the 
herbicidal composition. 
Granular formulations wherein the toxicant is carried on relatively coarse 
particles, are usually applied without dilution to the area in which 
suppression of vegetation is desired. Typical carriers for granular 
formulations include sand, fuller's earth, bentonite clays, vermiculite, 
perlite and other organic or inorganic materials which absorb or which may 
be coated with the toxicant. Granular formulations normally are prepared 
to contain about 5% to about 25% of active ingredients which may include 
surface-active agents such as wetting agents, dispersing agents or 
emulsifiers; oil such as heavy aromatic naphthas, kerosene or other 
petroleum fractions, or vegetable oils; and/or stickers such as dextrins, 
glue or synthetic resins. 
Typical wetting, dispersing or emulsifying agents used in agricultural 
formulations include, for example, the alkyl and alkylaryl sulfonates and 
sulfates and their sodium salts; polyhydroxy alcohols; and other types of 
surface-active agents, many of which are available in commerce. The 
surface-active agent, when used, normally comprises from 0.1% to 15% by 
weight of the herbicidal composition. 
Dusts, which are free-flowing admixtures of the active ingredient with 
finely divided solids such as talc, clays, flours and other organic and 
inorganic solids which act as dispersants and carriers for the toxicant, 
are useful formulations for soil-incorporating application. 
Pastes, which are homogeneous suspensions of a finely divided solid 
toxicant in a liquid carrier such as water or oil, are employed for 
specific purposes. These formulations normally contain about 5% to about 
95% of active ingredient by weight, and may also contain small amounts of 
a wetting, dispersing or emulsifying agent to facilitate dispersion. For 
application, the pastes are normally diluted and applied as a spray to the 
area to be affected. 
Other useful formulations for herbicidal applications include simple 
solutions of the active ingredient in a dispersant in which it is 
completely soluble at the desired concentration, such as acetone, 
alkylated naphthalenes, xylene and other organic solvents. Pressurized 
sprays, typically aerosols, wherein the active ingredient is dispersed in 
finely-divided form as a result of vaporization of a low boiling 
dispersant solvent carrier, such as the Freons, may also be used. 
The phytotoxic compositions of this invention are applied to the plants in 
the conventional manner. Thus, the dust and liquid compositions can be 
applied to the plant by the use of power-dusters, boom and hand sprayers 
and spray dusters. The compositions can also be applied from airplanes as 
a dust or a spray because they are effective in very low dosages. In order 
to modify or control growth of germinating seeds or emerging seedlings, as 
a typical example, the dust and liquid compositions are applied to the 
soil according to conventional methods and are distributed in the soil to 
a depth of at least 1/2 inch below the soil surface. It is not necessary 
that the phytotoxic compositions be admixed with the soil particles since 
these compositions can also be applied merely by spraying or sprinkling 
the surface of the soil. The phytotoxic compositions of this invention can 
also be applied by addition to irrigation water supplied to the field to 
be treated. This method of application permits the penetration of the 
compositions into the soil as the water is absorbed therein. Dust 
compositions, granular compositions or liquid formulations applied to the 
surface of the soil can be distributed below the surface of the soil by 
conventional means such as discing, dragging or mixing operations. 
The phytotoxic compositions of this invention can also contain other 
additaments, for example, fertilizers and other herbicides, pesticides and 
the like, used as adjuvant or in combination with any of the 
above-described adjuvants. Other phytotoxic compounds useful in 
combination with the above-described compounds include, for example, 
2,4-dichlorophenoxyacetic acids, 2,4,5-trichlorophenoxyacetic acid, 
2-methyl-4-chlorophenoxyacetic acid and the salts, esters and amides 
thereof, triazine derivatives, such as 
2,4-bis(3-methoxypropylamino)-6-methylthio-s-triazine, 
2-chloro-4-ethylamino-6-isopropylamino-s-triazine, and 
2-ethylamino-4-isopropyl-amino-6-methyl-mercapto-s-triazine; urea 
derivatives, such as 3-(3,5-dichlorophenyl)-1,1-dimethylurea and 
3-(p-chlorophenyl)-1,1-dimethylurea; and acetamides such as 
N,N-diallyl-.alpha.-chloroacetamide, and the like; benzoic acids such as 
3-amino-2,5-dichlorobenzoic acid; thiocarbamates such as S-propyl 
N,N-dipropylthiocarbamate, S-ethyl N,N-dipropylthiocarbamate, S-ethyl 
cyclohexylethylthiocarbamate, S-ethyl hexahydro-1H-azepine-1-carbothioate 
and the like; anilines such as 
4-(methylsulfonyl)-2,6-dinitro-N,N-substituted aniline, 
4-trifluoromethyl-2,6-dinitro-N,N-di-n-propyl aniline, 
4-trifluoromethyl-2,6-dinitro-N-ethyl-N-butyl aniline, 
2-[4-(2,4-dichlorophenoxy)phenoxy]propanoic acid, 
2-[1-ethoxyimino)butyl]-5-[2-ethylthio)propyl]-3-hydroxy-2-cyclohexene-1-o 
ne, 
(.+-.)-butyl-2-[4-[(5-trifluoromethyll)-2-pyridinyl)oxy]phenoxy]propanate, 
sodium 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, 
3-isopropyl-1H-2,1,3-benzothiadiazine-4(3H)-one-2,2-dioxide, and 
4-amino-6-tert-butyl-3-(methylthio)-as-triazin-5(4H)-one or 
(4-amino-6-(1,1-dimethylethyl)-3-(methylthio)-1,2,4-triazin-5(4H)-one). 
Fertilizers useful in combination with the active ingredients include, for 
example, ammonium nitrate, urea and superphosphate. Other useful 
additaments include materials in which plant organisms take root and grow 
such as compost, manure, humus, sand, and the like.