CA1059133A - N-haloacyl (4 and 5-spirocycloaliphatic) oxazolidines - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
Certain N-haloacyl 4-spirocycloaliphatic oxazolidines, wherein the haloacyl group contains 2 to 4 carbon atoms, the remaining ring-carbon atom valences are satisfied by hydrogen or C1-6 alkyl groups and said spirocycloaliphatic group contains 5 to 12 carbon atoms being selected from the group consisting of cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl and C1-6 lower alkyl derivatives thereof, are selective herbicides for crop protection.

Description

Thls lnventlon relates to sub~tltuted oxazol- - -ldlneq and more partlculàrly to N-haloacyl (2-alkylated) oxazolidlneq, herblcldal composltlons contalnlng same, - ;
and a process for controlling plant growth wlth qame~
The closest art known to applicants ls Canadlan Patent No. 1011339.
The oxazolldine ring ls a 5-member carbocyclic rlng havlng an atom at the one-positlon and a nitrogen ;
atom at..the three-posltlon, thuQ:
/ l C5 -C~ L
N3 ,_ 4 Varlous derlvatives hereto~ore have been suggested for use as herbicldes, lnsectlcldes, microblocides, microbio~tats, and pharmaceutlcals.
The lnventlon ls concerned with N-haloacyl 4-splrocycloallphatlc~oxazolldinesl, wherein the haloacyl group contain~ 2 to 4 carbon atoms, the 2-carbon atom valences are satis~ied with at least one Cl 6 alkyl group, the remalning ring-carbon atom valences are ~ati-qfied by hydrogen or Cl 6 alkyl groups and ~aid splrocycloallphatlc group contains 5 to 12 carbon atoms

-2-l()S9133 belng selected from the group consisting of cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl and Cl_6 lower alkyl substituted derivatlves thereof.
Another aspect of this invention is a herbicidal composition comprising about 1-98% of such oxazolidine and an agriculturally acceptable carrier therefor.
Still another aspect of this inventlon ls a pro-ces~ for controlling growth of vegetation which comprlses applying to the locus of such vegetation such oxazolidine lD at the rate of about 0~5-15 pounds per acre~
The sub~ect compounds can be depicted structurally as follows:
2 / - C ~R6 ~ C ¦~ R7 / ¦ R

Rl 5 Rl is a C2 4 haloacyl group, e.g., chloroacetyl;
R2 and R3 are lndependentlY a Cl_l2 alkyl group or a hydrogen;
R6 and R7 are individually hydrogen atoms or lower (Cl 6) alkyl groups; R4 and R5 are taken together -to form an alkylene or a lower-alkyl substltuted alkylene thus forming a qpirocycloaliphatic ring wlth the 4 to 5 ring carbon atom.
The haloacyl group of the oxazolidine nitrogen atom is of special importance f~r achieving herblcidal effectlveness. For efficiency and economy the advan-tageous haloacyl groups are chlorinated, preferably mDnochlor-inated, but multlple halogenation can ~e practiced, The halogen of , ' ' : ' said haloacyl group also can be bromine, iodine and/or fluorine. Additionally, such haloacyl group advantageously is haloacetyl for efficiency and economy, but halopropionyl and halobutyryl radicals (normal and isomeric) also can be used.
In general, for efficiency and economy of prepa-ration and general herbicidal use the alkylation on the 2-carbon atom of the oxazolidine ring advantageously is at least one Cl_l2 straight or branched chain alkyl group, frequently two alkyl groups (in such instances often un-symmetrical alkylation), and especially lower (Cl_6) alkyla-tion. It is, of course, within the skill of the art to re-place at least such higher molecular weight alkyl radicals with alkenyl radicals, or even the propyl radical with an allyl radical, or to replace hydrogen atoms on any such hydrocarbyl group with halogen, carbonitrile, nitro, alkoxy, mercapto, amido, ester, thioester and hydroxy group.
Oxazolidine derivatives wherein the substituent groups at the 4 and/or 5 ring position taken together represent an alkylene group provide particularly effective herbicides and are represented by the formula:
f R3 ~ N3 4C ~CH2)n Compounds wherein n is 5 and where R2 and R3 are lower alkyl are especially preferred because of their ease of preparation and their herbicidal selectivity. Spirocycloaliphatic sub-stitution at the 4-ring position are preferred because of '. , ' ~ ' ' ' , .
, .~ -.

their herbicidal effectiveness and ease of preparation.
In general, we have found that the most herbicidally effec-tive of the instant compounds are those having alkylation on the 4 or 5 carbon atoms of the oxazolidine ring, parti-cularly those having plural alkylation and cycloalkylationat the 4-carbon atom.
Application dosages of these herbicides, based on the active ingredient, suitably can be fairly high, but for economy generally are about 15 pounds per acre or below, advantageously not more than about 8 pounds per acre, and generally 0.5-8 pounds per acre, although dosages as high as 40 pounds per acre can be used.
By crop plants is meant not only agricultural -crops which are used for food supply of man and animals, but also includes other plants such as lawn grass species where broad leaf and other undesirable weeds are to be con- ~
trolled, suppressed, or eradicated. In general, oxazolidines --of this invention are effective in the elimination or con-trol of weeds including coffeeweed (Sesbania, spp.), pigweed ~ -tAmara_thus, spp.), crabgrass (Digitario, spp.), barnyard grass (Echinochloa, spp.), without significant injury to the specific crops such as ccrn, cotton, peanuts, and soybeans.
The compounds of the present invention are, in general, herbicidal in both pre- and post-emergent applica-tions. For pre-emergent control of undesirable vegetation, the herbicidal compounds 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.

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For post-emergent applicationsj the herbicidal compounds will be applied directly to the foliage and other plant parts. Generally, the herbicidal compounds of the inven-tion are effective against weed grasses as well as broad-leaved weeds. Some may be selective with respect to thetype of application and/or type of weed.
Although compounds of the present invention can be used alone as herbicides, it is generally desirable to apply the compounds in herbicidal compositions comprising one or more of the herbicidal compounds intimately admix-ed with a biologically inert carrier. The carrier may be a liquid diluent or a solid, e.g., in the form of dust powder or granules. In the herbicidal composition, the active herbicidal compounds can be from about 0.01 to 95%
by weight of the entire composition.
Suitable liquid diluent carriers include water and organic solvents, e.g., hydrocarbons such as benzene, toluene, kerosene, diesel oil, fuel oil, and petroleum naphtha. Suitable solid carriers are natural clays such as kaolinite, atapulgite, and montmorillonite. In addi-tion, talcs, pyrophillite, diatomaceous silica, synthetic fine silicas, calcium aluminosilicate and tricalcium phos-phate are suitable carriers. Organic materials such as walnutshell flour, cottonseed hulls, wheat flour, wood flour or redwood-bark flour may also be used as solid carriers.
The herbicidal composition will also usually con tain a minor amount of a surface-active agent. Such sur-face agent~ are those comroonly known as wetting agents, 0 dispersing agents and emulsifying agents and can be anionic, ~ 059~33cationic or nonionic in character. The herbicidal composi-tions may also contain other pesticides, adjuvants, stabil-izers, conditioners, fillers and the like.
The amount of herbicidal compound or composition administered 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 exposed areas such as fields -- as well as the desired type of control. Generally, for both pre- and post-emergent control, the herbicidal com-pounds of the invention are applied at rates of 0.2 to 80 kg/ha, and the preferred rate is in the range 0.5 to 40 kg/ha.
The characteristic of a good selective herbicide is that when it is applied near or on the foliage of the crop plant, only the weed species is killed while the valu-able crop plants are not harmed beyond the point of recovery, thus, allowing a high percentage (85-100 per cent) to mature to harvestable crops. We have found the following compounds representative of the types most efficacious as selective herbicides:

3-(a-chloroacetyl)-2,2-dimethyl-4-cyclohexanespiro oxazolidine 3-(~-bromopropionyl)-2,2-diethyl-4-cyclohexanespiro oxazolidine 3-(y-fluoropropionyl)-2,2-dimethyl-4-cyclohexanespiro oxazolidine 3-(a-chloroacetyl)-2,2-dimethyl-4-cycloheptanespiro oxazolidine 3-(a-chloroacetyl)-2,2,5-trimethyl-4-cyclohexanespiro oxazolidine 3-(a-chloroacetyl)-2,2-dimethyl-5-cyclohexanespiro oxazolidine 3-(a-chloroacetyl)-~,2,4-trimethyl-5-cyclohexanespiro oxazolidine ~, .
.

3-(~-chloropropionyl)-2-methyl-2-propyl-4(3'-methyl-cyclohexane)spiro oxazolidine 3-(~-chloropropionyl)-2,2-dipropyl-4(4'-methylcyclo-hexane)spiro oxazolidine 3~ chloroacetyl)-4-cy_lohexanespiro oxazolidine 3~ chloroacetyl)-2-methyl-4-cyclohexanespiro oxazolidine The unacylated oxazolidine intermediates for pre-paring the subject compounds can be synthesized conveniently by reacting substituted amino alkanols with ketones. A sub-stantial list of these compounds is given in the review article "The Oxazolidines", E.D. Bergman, Chem. Rev., 53, 309 (1953). Usually, the amino alcohol and the ketone are heated together in an inert hydrocarbon solver.t, and by-product water is separated from the condensed azeotropicmixture of hydrocarbon and water in a Dean-Stark water separator. The solvent is then evaporated and the product purified by distillation under reduced pressure. Suitable reaction solvents are water-immiscible hydrocarbons such as benzene, toluene and the like. Benzene is a preferred solv-ent because of its low boiling point.
The N-haloacyl oxazolidines of this invention can be synthesized by reacting the corresponding intermediate oxazolidine with the desired haloalkylcarbonyl halide, e.g., the chloride (also described as a haloacyl chloride) at a temperature in the range of about 50C. to about 250C. in the presence of an acid-acceptor. The reaction is prefer-ably carried out in an organic solvent, inert under the con-ditions of the reaction as for example, acetonitrile, benz-ene, xylene and the like; hydrocarbon solvents are generallypreferred. The acid-acceptor is generally a basic substance which forms water soluble by-products, easily separable from , . .
. .
., ,: ,, :, , .

the main reaction product. Although the acid-acceptor can sometimes be alkali metal salts of weak acids, such as sodium or potassium carbonate or acetate, it is preferable to use a tertiary amine. Useful and common tertiary amines are, for example, triethylamine and pyridine; frequently the crystalline hydrohalide formed as a by-product is in-soluble in the reaction solvent and easily removed by fil-tration. When a hydrocarbon solvent is used the product is soluble in the reaction solvent and workup is convenient-ly carried out by iltering the by-product amine hydro-halide, washing the remaining organic phase with water, and removing the reaction solvent by evaporation or distilla-tion. Thereafter, the product can usually be purified by conventional dic:tillation procedures including ones at sub-atmospheric pressure.
The follcwing examples are intended to illustratethe invention but not to limit the scope thereof, parts and percentages being by weight unless otherwise indicated.

3-(~-Chloroacetyl)-2,2-DimethYl-4-CYclohexanespiro Oxazolidine ~-¦ ~CH

A solution of 10 g. (0.078 mol) l-(hydroxymethyl) cyclohexyl amine [M.S. Newman and W.M. Edwards J. Amer.
Chem. Soc. 76 1840 (1954)] and 5 g. (0.12 mol) acetone in 100 ml. benzene was heated under reflux for 7 hours in a flask equipped with a Dean-Stark trap. A total of 3. 2 ml.
of water was separated and removed from the reaction mix-_g_ 105~133 ture with the trap. The benzene and excess acetone were then evap~rated under reduced pressure to give 11.5 g. of 2,2-dimethyl-4-cyclohexanespiro oxazolidine, as a pale yellow oil. The NMR spectrum of the product showed a sharp singlet for the 2,2-dimethyl groups at 1.48 (rela-tive to tetramethylsilane).
A 3.7 g. (0.033 mole) sample of chloroacetyl chloride was added dropwise to an ice bath-cooled solu-tion of 5 g. (0.03 mol) 2,2-dimethyl-4-cyclohexanespiro oxazolidine, prepared as described above; and 3.3 g.
(0.033 mole) of triethylamine in 25 ml. methylene chloride.
After the addition was completed, the ice bath was re-moved and the reaction mixture was stirred at ambient temperature for a half hour. The reaction mixture was then washed with 20 ml. water, dried over magnesium sulfate and evaporated under reduced pressure to give a dark brown oil. The oil was chromatographed on silica gel (hexane/-benzene/methylene chloride eluants) to give the N-acetylat-ed product (RE 19,970) as a white solid (2.8 g.) which melted at 81-83C. after recrystallization from hexane/- ~benzene. Elemental analysis for C12H20ClNO2 showed: %Cl, - -calc. 14.4, found 13.3.

3-(~-Chloroacetyl)-2-Methyl-2-Propyl-4-Cyclohexanespiro 2~ Ox_zolidine _ _ A solution of 11 g. (0.085 mol) l-(hydroxymethyl)-cyclohexyl amine and 8.1 g. (0.94 mole) 2-pentanone in 150 ml. benzene was heated under reflux in a flask equipped with a Dean-Stark trap for water removal. After refluxing for a ..

, , ~ ,, " "'''' ' ',, ~(~59~33 total of 19 hours, NMR analysis of the reaction showed that only a trace amount of l-(hydroxymethyl)cyclohexyl amine re-mained in the reaction mixture. The reaction mixture was then evaporated under reduced pressure to give the crude 2-~ethyl-2-propyl-4-cyclohexanespiro oxazolidine product, -as an oil.
A 5.4 g. (0.047 mol) sample of chloroacetyl chloride was added dropwise to an ice bath-cooled solution of 8.5 g. (0.043 mol) 2-methyl-2-propyl-4-cyclohexanespiro oxazolidine, prepared as described above, and 4.8 g. (0.047 mol) triethylamine in 50 ml. methylene chloride. After the addition was completed, the ice bath was removed and the reaction mixture stirred at ambient temperature for 2-1/2 hours. The reaction mixture was then washed with 25 ml.
water, dried over magnesium sulfate, and evaporated under reduced pressure to give a dark brown oil. The oil was chromatographed on silica gel (benzene eluant) to give the N-acetylated product as a brown oil. Elemental analysis for C14H24ClNO2 showed: %Cl, calc. 13.0, found 13.9.

EVALUATION AS PRE-EMERCENCE HERBICIDE
An acetone solution of the test compound was pre-pared by mixing 750 mg. of the compound, 220 mg. of a non-ionic surfactant and 25 ml. of acetone. This solution was added to approximately 125 ml. of water containing 156 mg.
of ~urfactant.
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 33 mcg./cm2. The pot was watered and placed in a greenhouse. The pot was watered inte~-mittently and was observed for seedling emergence, health of emerging seedlings, etc., for a 3-week period. At the end of this period, the herbicidal effectiveness of the compound was rated based on the physiological observations.
A 0 to 100 scale was used, 0 representing no phytotoxicity, 100 representing complete kill.

The compound of Example 1 was tested as a pre-emergence herbicide using a procedure similar to that of Example 3. The selectivity in protecting sweet corn, wheat, oats, sorghum and rice while effectively controlling Bermuda Grass, Yellow Nutsedge, Johnson Grass, Cheat Grass, Yellow Foxtail and Rye Grass is shown in Table 1.

The compound of Example 1 was further evaluated as a pre-emergence herbicide using the commercial herbicides Atrazine and Lasso as controls. The selectivity of this compound in protecting pea, cotton, soybean, sugarbeets and ~ -alfalfa is shown in Table 2.

EVALUATION AS POST-EMERGENT HERBICIDE
The test compound was formulated in the same -~
manner as described above for the pre-emergent test. The concentration of the test compound in this formulation was 5000 ppm. This formulation was uniformly sprayed on 2 similar pots of 24-day old plants tapproximately 15 to 25 plants per pot) at a dose of 33 mcg./cm.2 After the plants had dried, they were placed in a greenhouse and then water-ed intermittently at their bases, as needed. The plants were observed periodically for phytotoxic effects and lOS9133 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 compound of Example 1 was effective in controlling the growth of Wild Oats, ~vena fatua (25) and Watergrass, Echinochloa crusgalli (80).

When the spirocyclohexane group in the compound of Example 1 is replaced by a spirocycloaliphatic group con-taining S to 12 carbon atoms including cyclopentyl, cyclo-hexenyl, cycloheptyl and the 3- and 4-methyl substituted derivatives thereof such compounds will exhibit herbicidal properties essentially equivalent to that of the compound of Example 1.

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,~ o ,1 ~r ,i o ~ ~r ,i o 3-Acetyl-2,2-DimethYl-4-Cvclohexanespiro Oxazolidine Twenty-five grams (0.148 mole) 2,2-dimethyl-4-cyclohexanespiro oxazolidine dissolved in 275 ml. of an-hydrous ethyl ether was cooled in an ice bath and 5.6 grams(0.074 mole) of chloroacetyl chloride dissolved in 25 ml. of ethyl ether was added dropwise over a 30 minute period while maintaining the temperature between -15C. and -10C. The reaction mixture was allowed to return to room temperature and stirring was continued for 2.5 hours. An aliquot sample after washing with water indicated only one major product by gas/liquid chromatography. The white precipitate (12.9 grams) was filtered and the ether layer washed with 50 ml.
of 5 per cent HCl, 3 x 100 ml. of water and then dried over magnesium sulfate. The ether was removed by distillation leaving a viscous oil which was further evacuated under high vacuum to remove traces of solvent. The product, 8.3 grams, was obtained in a purity of 95% as characterized by glc, NMR, and infrared spectra. The NMR spectrum showed a broad 3-proton ringlet indicating the protons of the acetyl group at 2.2 ppm. and the infrared spectrum showed a strong carbonyl absorption at 1630 cm~l.

Comparative herbicidal tests were conducted on the compounds of Examples 1 and 8 as follows:
Seeds of the test plants were planted in a pot of soil. An acetone/water solution of each test compound and a small amount of a nonionic surfactant was sprayed uniformly onto the soil surface at the test concentration.
The pot was watered and placed in a greenhouse. The pot was : 1059133 then watered intermittently and was observed for seedling emergence, health of seedlings and other physiological responses for a 2-3 week period. At the end of the test period, the herbicidal effectiveness of each test compound was rated, based on the physiological observations. A O
to 100 scale was used, O representing no phytotoxicity and 100 representing complete kill. The results at 2.5 lb~
acre are tabulated in Table 3.
The comparative testing of the control ~N-acetyl) compound as a pre-emergent herbicide at a dosage level of 2.5 lbs./acre with the corresponding 3-N-chloroacetyl deriva-tive of 2,2-dimethyl-4-cyclohexanespiro oxazolidine is shcwn in Table 3. The control compound possessing no N-haloalkanoyl substitution at the 3-position of the oxazol-lS id~ne ring is devoid of herbicidal activity. In contrast, the N-chloroacetyl derivative is herbicidally effective ~-against the weed species wild oats, watergrass, grabgrass, lambsquarter, pigweed and mustard.

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When the compounds of the previous Examples are modified to compounds having cycloaliphatic spiro substitu-tion at the 5-position of the oxazolidine rin~ instead of the 4-spiro substitution, equally effective herbicidal re- .
sults will be obtained, compounds having non-symmetrical substitution at the 2-ring position being more effective herbicides than those having 2-position symmetry.

Claims (8)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. An N-haloacyl 4-spirocycloaliphatic oxazolidine, wherein the haloacyl group contains 2 to 4 carbon atoms, the remaining ring-carbon atom valences are satisfied by hydrogen or C1-6 alkyl groups and said spirocycloaliphatic group contains 5 to 12 carbon atoms being selected from the group consisting of cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl and C1-6 lower alkyl derivatives thereof.

2. The oxazolidine of claim 1, wherein halo is chloro.

3. The oxazolidine of claim 1, wherein said 4-spiro-cycloaliphatic group is cyclohexyl.

4. The oxazolidine of claim 1, wherein said haloacyl group is haloacetyl.

5. 3-(.alpha.-Chloroacetyl)-2,2-dimethyl-4-cyclohexanespiro oxazolidine.

6. A process for protecting crop plants from undesir able growth of vegetation which comprises applying to the locus thereof a herbicidally effective amount of an oxazolidine according to claim 1.

7. The process of claim 6, wherein the oxazolidine is a 4-spirocycloaliphatic oxazolidine.

8. The process of claim 6, wherein the oxazolidine is 3-(.alpha.-chloroacetyl)-2,2-dimethyl-4-cyclohexanespiro oxazolidine.