NZ201388A - 2-phenyl-5-(alkoxy or alkylthio)methyl-3-(haloalkanoyl or alkoxycarbonylalkanoyl)oxazolidines - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £01 388 201 "T ^ (Ti Under the provisions of R1|V) latron 23 (I) the J '+ J Specir.ca::-:M been ante-dated^ to ..... /£. ZfiitJs/JSi 19^2.

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If Divisional Application out of New Zealand Patent Application No. 194070 dated 17 June 1980 Patents Form No. 5 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION -SUBSTITUTED OXAZOLIDINE HERBICIDE ANTIDOTES WE, STAUFFER CHEMICAL COMPANY, a corporation organized and existing under the laws of Delaware, United States of America, of Westport, Connecticut 06880, United States of America, hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement (followed by page 1A) -1ft- U L- R <S> -SUBSTITUTED OXAZOLIDINE HERBICIDE ANTIDOTES Background of the Invention While many herbicides are immediately toxic to a large number of weed pests, it is known that the effect of many herbicides upon important plant cultivations is either non-selective or not adequately selective. Thus, many herbicides damage not only the weeds to be controlled. but to a greater or lesser extent, the desirable cultivated plants as well. This holds true for many herbicidal compounds which have been commercially successful and are commercially available. These herbicides include types such as triazines, urea derivatives, halogenated acetanilides, carbamates, thiolcarbamates, and the like. Some examples of these compounds are described in U.S. Patent Nos. 2,913,327, 3,037,853, 3,175,897, 3,185,720, 3,198,786, 3,582,314 and 3,952,056.

The side effect of injury to a cultivated crop by various herbicides is particularly inconvenient and unfortunate. When used in the recommended amounts to control broadleaf weeds and grasses, serious malformation or stunting of the crop plants sometimes result. This abnormal growth in the crop plants results in loss of crop yield. The search continues for good selective herbicides.

Previous attempts are described to overcome this problem. The treatment of the crop seed with certain "hormonal" antagonistic agents prior to planting is described; see U.S. Patents 3,131,509 and 3,564,768. The protective agents, as well as the herbicide, in these prior processes are largely specific to certain cultivated plant species or in the nature of antagonistic agents. The prior antagonistic agents have not been notably successful. The aforementioned patents specifically exemplify and describe the treatment of seeds employing compounds of a different chemical class, not suggestive of the present invention.

U.S.Patents 3,989,503 and 4,124,372 and New Zealand Patent No: 179,998 disclose certain substituted oxazolidine compounds. However, none of these references anticipate or make obvious the particular compounds or the utility of the particular compounds as herbicidal antidotes for thiolcarbamate herbicides; in particular for S-n-propyl N,N-di-n-propyl thiolcarbamate, S-ethyl di-n-propyl thiolcarbamate, S-isopropyl 1-(5-ethyl-2-methyl-piperidine) carbothioate, S-ethyl diisobutyl thiolcarbamate, and S-ethyl cyclohexyl ethyl thiolcarbamate.

Description of the Invention It has been discovered that cultivated crop plants can be protected against injury by thiolcarbamate-type herbicides, and said injury can be decreased when the thiolcarbamate-type herbicides, each alone or in mixtures or combination with other compounds, are applied in a variety of ways.

Further, as an alternative effect, the tolerance of the crop plants to these herbicides can be substantially increased by adding to the soil an antidote compound of the type N-haloacyl oxazolidine substituted in the 5-position according to the following description: With oxy or thio-containing groups, therefore, the present invention also includes a two-part herbicide system comprising a first-part of one or more thiolcarbamate herbicides and a second-part of an effective antidote compound therefore, said antidote compounds corresponding to the following formula O ri R-C- CH2XR1 o v2 R3 -8 wherein X is oxygen or sulfur and is alkyl; R is selected from the group consisting of haloalkyl, and alkoxycarboalkyl; R2 is selected from the group consisting of phenyl, p-chloro-phenyl and p-bromophenyl; and R^ is selected from the group consisting of hydrogen and methyl.

In the above description, the following embodiments are intended for the various substituent groups: For R^ alkyl preferably includes those members which contain from 1 to 6 carbon atoms, inclusive, in both straight chain and branched chain configurations. As exemplary of the alkyl portion within the preferred embodiment are the following: Methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl and tert.-butyl. For R as haloalkyl preferably includes those members which contain from 1 to 4 carbon atoms, inclusive, and the term "halo" is chloro or bromo as mono, di, tri, tetra or hexa substitutions, that is from 1 to 6 halo substituents; and for R as alkoxycarboalkyl preferably includes those members having 3 to 6 carbon atoms, inclusive, such as methoxy propanoyl, methoxy ethanoyl (acetyl) , ethoxy propanoyl, ethoxy ethanoyl and the like. Other substituent groups are as indicated in carbon content in the above description.

As an alternative mode of action, the compounds of this invention may interfere with the normal herbicidal action of the thiolcarbamate-type and other herbicides, to render them selective in their action. The observation noted with the presence of the herein described antidote, is a decrease in phytotoxicity with respect to various crops, otherwise observed when various thiolcarbamate herbicides are used for weed control. Whichever mode of action is present, the corresponding beneficial and desirable effect is the continued herbicidal effect of the thiolcarbamate against weed species present in the crop, with the accompanying decreased herbicidal effect on desired crop species. This advantage and utility will become more apparent hereinafter.

Therefore, the terms "antidote", "herbicide antidote" or"antidotal amount", are meant to describe that effect which £DYb 8* tends to counteract the normal injurious herbicidal response that the herbicide might otherwise produce. Whether it is to be termed a remedy, interferant, protectant, antagonist or the like, will depend upon the mode of action. The mode of action is varied, but the effect which is desirable, is the result of the method of treating the seed, soil or furrow in which a crop is planted. above formula as described above can be prepared by several different procedures depending upon the starting materials: starting material for the compounds within this invention may be prepared by amination of 1,2-epoxy-3-alkoxy propane (I) with aqueous ammonia or ammonium hydroxide to produce a l-amino-3-alkoxy isopropanol (II). Subsequent reaction and cyclization with benzaldehyde or a substituted benzaldehyde, phenyl or substituted phenyl ketone (III) , yields the N-substituted 2,2-dialkyl 5-alkoxy-oxazolidine product (IV). This sequence of reactions is depicted in the following equations: The compounds of this invention represented by the When X is oxygen and is alkyl, the requisite ch2 chch2or1 + nh3/h20 oh ^ nh2ch2chch2or1 (I) (II) OH O h h h v: 1_ch2orx ®2 R3 (II) (III) (iv) wherein R^, R2 and R^ have the same significance as previously defined.

When X is sulfur and is alkyl, the requisite starting material for the compounds within this invention may be prepared by thionation with a mercaptan (VI) of epichlorohydrin (V) to produce the 1-chloro-alkyl thio-2-propanol (VII), this is followed by reformation of the epoxide (VIII). Amination of the 1,2-epoxy-O-alkyithio-propane (VIII) with ammonia or aqueous ammonia produces a l-amino-3-alkylthio-2-propanol (IX). Subsequent reaction and cyclization with benzaldehyde or a substituted benzaldehyde, phenyl or substituted phenyl ketone (III) yields the N-unsubstituted 2,2-dialkyl-methyl-oxazolidirie product (X), this sequence of reactions is depicted by the following equations: ,0\ oh A CH2CHCH2C1 + R SH (v) (VI) R1SCH2-CH-CH2C1 (VII) OH 0.

I /\ R1SCH2-CH-CH2C1 + NaOH(Pwd) RjSCH^H-C^ + NaCl (vii) (viii) R1SCH2CH-CH2 + NH3 or NH4OH ^ R1SCH2CH-CH2NH2 OH ,AH-( (VIII) (ix) OH o R1SCH2CHCH2NH + R2CR3 (IX) (III) H H H nh; R2 R3 (x) 0 CH2SR1 + H2O With reference to the above procedures: The N-acyl-substituted compounds of the invention or alkoxycazboalkyl wherein R is haloalky]/, may be prepared by direct acylaj of a 5-substituted oxazolidine compound with an acid^ in the presence of a hydrogen chloride acceptor, sui 2 013 8 triethylamine or an inorganic base, such as sodium hydroxide.

In the above reaction, the reaction is performed in the presence of an inert organic solvent, such as benzene. A solvent is normally employed to facilitate the reaction and aid in the work-up of the product. Where good chemical practice dictates a catalyst was used as specified, in some instances a catalyst is not required. The reaction temperatures can vary from -10°C to 90°C. The reaction pressure may be atmospheric, subatmospheric or superatmospheric. However, for convenience of conducting the reactions, the pressure is generally atmospheric. The reaction time will, of course, vary depending upon the reactants and reaction temperature. Generally, the reaction time is from 0.25 to 24 hours. After the reaction is complete, the product is recovered by filtration, extraction and drying. The product can be purified further by trituration with hexane or recrystallization from a suitable solvent. In most instances, the structure was confirmed by analytical techniques, such as infrared spectroscopy, nuclear magnetic resonance or mass spectroscopy.

In preparing the oxazolidine intermediates it was found that it was unnecessary to isolate and purify the compounds before use. The volume of the oxazolidine solution was adjusted to give a 25 percent w/v solution (4 milliliters - 1 gram) and aliquots were then used for subsequent reactions.

Representative of the above general scheme of reactions, are the following preparations employing specific starting materials and intermediates.

'J > - ^ _ j j Preparation of Intermediate; l-Chloro-3-ethylthio-2-propanol .

Sixty five and two tenths (65.2) grams of ethyl mercaptan was added dropwise with stirring to 9 2.5 grams of epichlorohydrin and 2 grams of zinc chloride in 500 milliliters of dioxane. The mixture was heated to 40°C and the heating removed while the mixture remained at 35-40°C for 3/4 hours. The mixture was then heated at 40°C for 1 1/2 hours and then to reflux at which point the temperature >10 was 105°C. Yield after stripping was 103 grams, nD30 1.4862. The product was not further purified. The structure was confirmed by infrared and nuclear magnetic resonance spectroscopy.

Preparation of Intermediate: |15 Ethyl 1,2-epoxyprop-3-yl sulfide • One hundred and twenty seven (127.0) grams of 1-chloro-3-ethylthio-2-propanol was added dropwise with vigorous stirring to 82 grams of powdered NaOH in 500 milliliters of diethyl ether. The temperature was kept below 30°C with a water bath and addition took 4 0 minutes.

The product was filtered and the ether stripped off giving 8 0.8 grams of product nD 1.4567. The structure was confirmed by infrared and nuclear magnetic resonance spectroscopy and used in subsequent reactions without puri-25 fication.

Preparation of Intermediate: . 2-Hydroxy-3-aminopropyl ethyl sulfide .

Eighty seven and eight tenths (87.8) grams of ethyl 1,2-epoxyprop-3-yl sulfide was added dropwise with stirring to 1 liter of aqueous 2 8 percent ammonia solution, cooled to 0°C overnight in an icebox and maintained in an ice bath. The epoxide was added over 45 minutes and the reaction mixture was allowed to warm to room temperature and stand overnight. The water and ammonia were stripped off under vacuum and the only residue distilled to give 59.1 grams of the title compound, b.p. 101-105°C at 1.4-2 milli-30 meters, nQ 1.4910. The structure was confirmed by infrared and nuclear magnetic resonance spectroscopy. 201388 In preparing the oxazolidine intermediate it was found that it was unnecessary to isolate and purify the compounds before use. The volume of the oxazolidine solution was adjusted to give a 25% w/v solution (4 milliliters = 1 gram) and aliquots were then used for subsequent reactions. Both the 5-oxymethyl and 5-thiomethyl substituted oxazolidines can be prepared by similar reactions. Preparation of Intermediate; 1-Amino-3-isopropoxy-isopropanol .

Sixty three (63.0) grams of 3-isopropoxy-l, 2-epoxy- propane was added dropwise with stirring to 1 liter of 28 percent aqueous ammonia, cooled to 0°C and kept in an icebox overnight. The solution was allowed to warm to room temperature and stored in a loosely stoppered container for five days in a hood. The water and ammonia was stripped off under vacuum and the only residue distilled to give 38 grams of the title compound, b.p. 77.5°C at 0.5 millimeters, nD 1.4200. The structure was confirmed by infrared and nuclear magnetic resonance spectroscopy.

Preparation of Intermediate: 2-p-Chlorophenyl-5-methoxymethyl-oxazolidine .

Twelve and six tenths (12.6) grams of l-amino-3-methoxy-2-propanol and 16.9 grams of p-chlorobenzaldehyde were combined in 150 milliliters of benzene and heated to reflux under a modified Dean-Stark apparatus until about 2.5 milliliters of water were azeotropically removed. An additional 50 milliliters of benzene was distilled over and the mixture was cooled to room temperature and the volume was adjusted to 109.2 milliliters, so that 4 milliliters = 1 gram of intermediate. Aliquots of this solution were used in subsequent reactions.

Preparation of Intermediate: 2-Phenyl-5-ethylthiomethyl-oxazolidine .

Thirteen and five tenths (13.5) grams of 2-hydroxy- 3-aminopropyl ethyl sulfide and 10.6 grams of benzaldehyde were combined in 100 milliliters of benzene and refluxed under a modified Dean-Stark apparatus until about 2 milliliters of water had been azeotropically removed.

I The mixture was cooled to room temperature and the volume adjusted to 89.2 milliliters {4 milliliters = 1 gram).

Aliquots of this mixture were used in subsequent reactions.

The compounds of the present invention and their preparation are more particularly illustrated by the following examples. Following the examples of preparation is a table of compounds which are prepared according to the procedures described herein. Compound numbers have been assigned to them and are used for identification throughout J.0 the balance of the specification.

EXAMPLE I Preparation of 2-p-chlorophenyl-3-(2,3-dibromopropionyl)-5- methoxymethyl-oxazolidine.

To 20.8 milliliters of 25 percent w/v, p-chloro- ^5 phenyl-5-methoxymethyl-oxazolidine solution in 50 milliliters of benzene was added 5 grams of 2 ,3-dibromopropionyl chloride.

To this solution was added 1.6 grams of 50% sodium hydroxide.

After washing with water, drying and removal of the benzene in vacuo, there was obtained 4.8 qrams of the title compound, 30 nQ 1.5478. Analytical data supports the structure.

EXAMPLE II Preparation of 2-p-chlorophenyl~3-(2,3-dibromopropionyl)-5-propoxymethyl-oxazolidine.

In a similar manner as Example I, 17.9 milliliters of 25 percent w/v, 2-£-chlorophenyl-oxazolidine solution 2 5 in 50 milliliters of benzene and 4.4. grams of 2,3-dibromo propionyl chloride was added 1.4 grams of 50% sodium hydroxide. After the appropriate work-up procedure, there was obtained a yield of 6.4 grams of the title compound, n 1.5310. Analytical data supports the structure.

EXAMPLE III Preparation of 2-p-chlorophenyl-3-( 3-carbomethoxypropionyl)-5-propoxymethyl-oxazolidine.

To 25.6 milliliters of 25 percent w/v, 2-£-chlorophenyl-5-propoxymethyl-oxazolidine solution in 50 milliliters of benzene was added 3.8 grams of 3-carbomethoxy- propionyl chloride. To this reaction mixture was added 2 grams of 50% sodium hydroxide. Upon completion of the reaction solvent, benzene, was removed in vacuo. There was obtained 6.0 grams of the title compound, nQ 1.4975. Analytical data supports the structure.

EXAMPLE IV Preparation of 2-phenyl-3-(3-carbomethoxypropionyl)-5-methoxy- methyl-oxazolidine.

To 19.3 milliliters of 25 percent w/v, 2-phenyl-5- methoxymethyl-oxazolidine solution in 50 milliliters of benzene with 3.8 grams of 3-carbomethoxypropionyl chloride was added 2.0 grams of 50% sodium hydroxide. After the reaction was complete the mixture was washed with water, separated, dried and the organic solvent removed in vacuo.

There was obtained 6.8 grams of the title compound, nQ 1.4913. Analytical data supports the structure.

EXAMPLE V Preparation of 2-phenyl-3-chloroacetyl-5-ethylthiomethyl- oxazolidine.

To a reaction mixture of 10.1 milliliters of percent w/v, 2-phenyl-5-ethylthiomethyl-oxazolidine solution in 25 milliliters benzene, 2.5 grams of triethyl- amine were added dropwise. Cooling in an ice bath and vigorous stirring was maintained during the addition of the chloride and triethylamine, then allowed to stir one hour at room temperature. Upon completion of the reaction, the mixture was washed with water, dried and the solvent removed in vacuo. There was obtained a yield of 6.0 grams of the title compound, nD 1.5410.

? Q 1 3 TABLE I 0 R-C-N R>ki7 0 CH2XR1 Compounds; Compound Physical Number R XRX R, h.

Constant 1 chci2.: 0ch3 P" -ci phenyl H 1.5530 2 CH2BrCHBr 0ch3 P" -ci phenyl H 1.5478 3 CH2BrCH2 och3 P" -ci phenyl H 1.5341 4 ch2cich2 och3 P" -ci phenyl h 1.5248 ch3oc(o)ch2ch2 och3 P" -ci phenyl H 1.5094 6 chci2 0- n-C3H^ P" -ci phenyl H 1.5171 7 CH2BrCHBr 0- n-C3H^ P- -ci phenyl H 1.5310 8 ch2brch2 0- n-C3H^ P" -ci phenyl H 1.5195 9 ch2cich2 0- n_C3H7 P" -ci phenyl H 1.5088 CH3OC(o)CH2CH2 0- n-C3H7 P' -ci phenyl H 1.4975 11 chci2 0CH3 phenyl H. 1.5230 12 CH2C1CH2 0CH3 phenyl H 1.5130 13 CH30C(0)CH2CH2 och3 phenyl H 1.4913 14 CH3CHC1 och3 phenyl H 1.5075 CHC12 0- "n_C3H7 phenyl H 1.5065 16 ch2brch2 0- "n~C3H7 phenyl H 1.5090 17 ch2cich2 0- -n-C3H7 phenyl H 1.5010 18 CH3OC(0)CG2CH2 0- -n-C3H^ phenyl h 1.4868 &01Z2S TABLE 1 (cont'd): Compounds: Compound Physical Number R XRX h.

Constant 19 CH3CHC1 0-n-C3H7 phenyl H 1.4979 CHC12 och3 p-Br phenyl H 1.5363 21 CH2BrCHBr 0-n-C3H7 p-Br phenyl H 1.5390 22 ch3oc(o)ch2ch2 0-n-C3H7 p-Br phenyl H 1.5032 23 chci2 °-n-C5Hii phenyl H 1.4960 24 CH2BrCHBr 0-n_C5Hll phenyl h 1.5123 ch3oc(o)ch2ch2 O-n-C^H^^ phenyl H 1.4940 26 ch2ci SC2H5 phenyl H 1.5410 27 CH2BrCHBr SC2h5 phenyl h 1. 5580 28 CH2BrCH2 SC2h5 phenyl H 1.5461 The herbicidal compound employed in the utility of this invention is an active thiolcarbamate herbicide of a general type. That is, it is a member of the class of herbicidally active compounds effective against a wide rang^ <y of plant species, and may have no discrimination between desirable and undesirable plant species. The method of con-trolling vegetation comprises applying a herbicidally effective amount of the herein described herbicidal composition to the area or plant locus where control is desired. The herbicidal composition as set forth in this invention include those wherein the antidote is as described above and the preferred active herbicidal compound is selected from the class of thiolcarbamate herbicides and includes the following representative members: S-ethyl dipropyl thiolcarbamate, S-ethyl diisobutyl thiolcarbamate, S-propyl di-n-propyl thiolcarbamate, S-ethyl cyclohexyl ethyl thiolcarbamate, S-ethyl hexahydro-lH-azepine-l-carbothioate, 2,3,3-trichloro-allyl N,N-diisopropyl thiolcarbamate, S-isopropyl-1-(5-ethyl-3-methyl-piperidine) carbothioate and S-4-chlorobenzyl diethyl thiolcarbamate.

As an embodiment within the scope of the present invention is a two-part or package herbicide system consisting essentially of a first-part of one or more thiol-carbamate herbicides and a second-part of an antidote compound therefor. It is understood that the antidote compound is used in an effective amount to render the two-part herbicide system selective in decreasing phytotoxic effects to desired or beneficial crops and yet phytotoxic to the undesirable or unwanted vegetation. Thus the soil treated by such a system becomes extremely useful and desirable, allowing previously injured crops to be planted in said treated soil, otherwise injured by the herbicide when used alone. Hence, soil treated with herbicide and antidote as described herein is beneficial, desirable and useful. Likewise, seed treated with the antidote compound is a useful and desirable product.

An herbicide as used herein means a compound which controls or modifies the growth of vegetation or plants. Such controlling or modifying effects include all deviations from natural development; for example, killing, retardation, defoliation, desiccation, regulation, stunting, tillering, stimulation, dwarfing and the like. By "plants" it is meant germinant seeds, emerging seedlings and established vegetation including the roots and above-ground portions.

Evaluation Procedure and Method . » Flats to be used for growing the crops and weed species were filled with loamy sand soil. Various methods of application were employed, such as pre-plant incorporation (PPI) of 1) the herbicide and antidote separately, and 2) as a tank mix (PPI-TM) with the herbicide and antidote together. The application was by incorporation, whereinafter the seeds of the crops and weeds were planted in the treated soil; application by an in-furrow (IF) treatment of the seeds and surrounding soil in which the herbicide had been applied previously to the soil; and ZQ 1388 treatment of the crop seeds (ST) with an antidote candidate prior to planting in herbicide treated soil; application to the surface of the soil prior to emergence of the growing plants, (1) as separate application (PES) of herbicide antidote and (2) as a tank mix (PES-TM).

Stock solutions of representative thiolcarbamate herbicides and antidote candidates were prepared as follows: Herbicides A. S-ethyl di-n-propyl thiolcarbamate -EPTC - EPTAM0 6E - 4133 mg. dissolved in 800 ml. water such that 5 ml. applied to the soil from a planting flat is equivalent to 5 lb/A PPI or 3744 mg. dissolved in 600 ml. of water, 5 ml. of which was equivalent to 6 lb/A PPI B. S-isopropyl l-(5-ethyl -2-methyl-piperidine) carbothioate (R-12001) technical, the following is a listing of various stock solutions prepared, also included is the lb/A equivalence per 5 ml. pre-plant incorporated. 120 mg/150 ml acetone 176 mg/150 ml acetone 117 mg/175 ml acetone 975 mg/250 ml acetone 585 mg/125 ml acetone ml ■= 1 lb/A PPI 5 ml = 1.5 lb/A PPI 5 ml - 2 lb/A PPI 5 ml = 5 lb/A PPI 5 ml = 6 lb/A PPI C. S-ethyl di-isobutyl thiolcarbamate -sutan (r) 6E or s-ethyl cyclohexyl ethyl thiolcarbamate - roneet (r) 6e - 390 mg. dissolved in 125 ml. water such that 5 ml. applied to the soil from a planting flat is equivalent to 3 lb/A. For 4 lb/A 1456 rag. was dissolved in 350 ml. water, such that 5 ml. was equivalent to the desired amount.

D. S-ethyl hexahydro-lH-azepine-l-carbothioate ordram(lt) 8E - 164 mg. dissolved in 75 ml. water such that 5 ml. is equivalent to 2 lb/A applied to the soil from a planting flat pre-plant incorporated. "15 " E. S-prOpyl di-n-propyl thiolcarbamate -VERNAM@- 6E (80%), the following is a listing of various stock solutions prepared, also included is the lb/A equivalence for 5 ml. pre-plant incorporated: 122 mg/125 ml h2o ml = 1 lb/A PPI • 183 mg/150 ml h2o ml = 1. lb/A PPI 975 mg/250 ml h2o ml = 4 lb/A PPI 2632 mg/450 ml h2o ml = 6 lb/A PPI 3412 mg/500 ml h2o ml = 7 lb/A PPI Antidotes F. For each candidate compound employed in the seed treatment method of application, 250 mg. active ingredient was dissolved in 15 2.5 ml. acetone, with 1% Tween 20(r) (poly- oxyethylene sorbitan monolaurate) such that 0.5 ml. of solution per 10 gm. of seeds is equal to l/27„ w/w.

G. For each candidate compound employed in the 20 "in-furrow" method of application, 95 mg. .of active ingredient was dissolved in ml. of acetone with 1% Tween 20(H), such that 1.5 ml. applied to the seed and soil in the furrow, in one-half of the flat was equivalent to 5 lb/A. When 1.0 lb/A is desired 0.3 ml. was used.

H. For each candidate compound employed in the "tank mix" pre-plant incorporation•test or separately applied pre-plant incorporated test, 50 mg. of active ingredient was dis solved in 100 ml. of acetone with 17„ Tween 20(§), such that when 10 ml. of the stock solution was further dissolved in 90 ml. of acetone, 4 ml. was equivalent to 3^^ 1/20 lb/A PPI. When 39 mg. of the com- pound was dissolved in 10 ml. of acetone, 5 ml. was equivalent to 5 lb/A PPI, and 1 ml. was equivalent to 1 lb/A PPI. When 16 mg. was dissolved in 20 ml., 10 ml. was h 0 equivalent to 2 lb/A PPI and when 16 mg. was dissolved in 40 ml., 5 ml. was equivalent to 0 5 lb/A PPI.

In-furrow application of the antidote employed the above stock solutions. As a preparatory step, a one pint -16' - 2 013 8 8 sample of soil was removed from each flat to be retained and used, later to cover the seeds after treatment with the stock solutions. The soil was leveled before planting. The herbicide stock solution was applied respectively to separate flats and pre-plant incorporated in the soil from the planting flat at the equivalent rate of 1 lb/A active ingredient or the indicated rate.

Rows 1/4-inch deep were made lengthwise in each treated flat preparatory to seeding. After seeding, the flats were sectioned into two equal portions using a wooden barrier and 1-1/2 milliliters of additive stock solution was atomized directly onto the exposed seed and soil in the open furrow in one-half of the flat. The untreated section of the flat served as an herbicide check and also made it possible to observe any lateral movement of the antidote through the soil. The seeds were covered withjrhe one pint sample of untreated soil which had been removed earlier.

For tank mixes to be applied as a pre-plant incorporated application, the following solutions and procedures were employed. Five milliliters (5 ml.) of herbicide stock solutions were each mixed with five milliliters (5 ml.) of antidote candidate stock solution such that the equivalent of 1 lb/A and 5 lb/A of herbicide and antidote, respectively, were applied and incorporated into the soil of each flat. For pre-plant incorporation, the mixed stock solutions were injected into the soil during incorporation in a 5-gallon rotary mixer. Other stock solutions were employed at indicated rates in the tank mix procedure.

In side-by-side tests with various weed species and crops, it was found that weed control was maintained while at the same time the crop species were protected or injury decreased, when compared to a check or control flat. The control flat contained no candidate antidote compound. The following table includes those results.

For seed treatment, 10 grams of seed in a suitable container was shaken with 0.5 milliliters of antidote stock _ 11 J. 201388 solution H, or other stock solution as indicated, such that the Seed treatment was equivalent to 0.5% w/w, 0.257o w/w, 0.125%, w/w or 0.1% w/w. Shaking was continued until the seeds were uniformly covered. The antidote compounds may be applied as liquid slurries and powder or dust treatments. The treated seeds were planted in soil in which herbicide stock solution had been pre-plant incorporated into the soil at a rate equivalent to 1 lb/A active ingredient.

All flats were placed on greenhouse benches where temperatures were maintained between 70-90°F. The soil was watered by sprinkling to assure good plant growth. Injury ratings were taken 2 and 4 weeks after the applications were made. Individual control flats treated with the herbicide alone were included to provide a basis for determining the amount of injury reduction provided by the herbicide antidotes. The results of these tests are tabulated in Table II, TABLE II, ANTIDOTE ACTIVITY Application Method: Seed Treatment - ST In-Furrow - IF Pre-Plant Incorporation - PPI Pre-Plant Incorporation-Tank Mix - PPI-TM - Crop Species: Barley - BA [Hordeum vulgare (L.)] Corn - CN [Zea maize] Cotton - CT [Gossypium. hirsutum] Milo (Grain Sorghum) - MO [Sorghum vulgare] Rice - RC [Dryza sativa] Soybeans - SOY [Glycine max] Wheat - WH [Triticum aestivum] Weed Species:, Green Foxtail Johnson Grass Nutsedge Shattercane Watergrass Wild Oats FT [Setaria viridis] JG [Sorghum halepense] NS [Cyperus esulentus] SC [Sorghum bicolor] WG [ Echinochloa crusgalli] WO [Avena fatua (L.)] Result = Percent injury with antidote present Percent injury of herbicide alone TABLE II (Cont'd) Antidote Compound Herbicide Method of Number PPI Application Rate (Herb. + Anti.) (lbs/A or % ST.) 1 VERNAM IF 6+5 EPTAM PPI 5+5 2 VERNAM IF 1.25+5 VERNAM IF 1 1/4+1 3 VERNAM IF 6+5 4 VERNAM IF 6+5 IF 5+5 VERNAM IF 6+5 VERNAM IF 5+1 +5 6 VERNAM IF 6+5 «/ • 7 VERNAM IF 1.25+5 IF 1.25+1 8 VERNAM IF 1.25+5 Cr°P % Injury Result Weed Result' CN CN BA BA SOY SOY SOY SOY SOY SOY CN BA BA /90 50/70 /90 30/80 /70 /70 30/6Q /70 20/60 0/60 40/90 /90 30/80 WG FT WG FT WG FT FT WO 100/100 100/100 I 95/95 95/95 95/95 95/95 70/70 95/95 BA 75/90 00 TABLE II (Coflt'd) Antidote Compound Herbicide Method of Number PPI Application Rate (Herb. + Anti.) (lbs/A or % ST.) 9 VERNAM IF 6+5 VERNAM IF 6+5 IF 5+1 11 VERNAM IF 6+5 SUTAN PPI-TM 6+1 PPI-TM 6+5 EPTAM PPI 5+0.5 +5 12 VERNAM IF 6+5 13 VERNAM IF 6+5 IF 5+5 i t Injury • Crop Result Weed Result SOY SOY SOY CN CT CT CN CN CN SOY SOY 60/70 /70 40/60 0/90 10/50 0/50 50/70 0/70 80/90 /70 30/60 WG FT JG NS JG NS WG FT WG FT 95/95 95/95 100/100 90/90 100/100 90/90 100/100 100/100 100/100 100/100 WG FT 95/95 95/95 TABLE II (Cont'd) Antidote Compound Herbicide Method of Number PPI Application Rate (Herb. + Anti.) (lbs/A or % ST.) 14 VERNAM- ■ IF 6+5.

IF 5+5 VERNAM IF 6+5 EPTAM PPI 5+5 16 SUTAN PPI-TM 6+1 17 VERNAM IF 6+5 18 VERNAM IF 6+5 19 VERNAM IF 6+5 SUTAN PPI-TM 6+5 VERNAM PPI 1.25+5 RONEET IF 3+1 % Injury Crop Result WeedResult SOY SOY CN CN CT SOY SOY SOY CT MO MO /70 30/60 /50 /70 50/70 50/70 40/50 45/100 40/75 WG FT /90 0/70 WG FT JG NS JG NS FT SC 95/95 95/95 100/100 100/100 100/100 90/90 100/100 90/90 80/80 95/95 I oo TABLE II (Cont'd) Antidote Compound Herbicide Method of Number PPI Application Rate v(Herb. + Anti.) (lbs/A or % ST.) SUTAN PPI-TM 6+1 RONEET PPI-TM 3+5 21 SUTAN PPI-TM 6+1 22 VERNAM IF 6+5 VERNAM IF 5+5 23 VERNAM IF 1.25+5 24 VERNAM IF 1.25+5 VERNAM IF 6+5 26 VERNAM IF 6+5 EPTAM PPI-TM 5+5 i 7. In j ury Crop Result Weed Result CT MO CT SOY SOY WH BA SOY CN CN 40/50 30/80 40/50 /70 30/60 WH 80/90 80/100 75/90 40/70 0/90 0/85 JG NS WG FT JG NS WG FT WG JG 100/100 90/90 100/100 100/100 100/100 90/90 95/95 95/95 98/98 98/98 I ro ro TABLE II (Cont'd) Compound Herbicide Number PPI 27 28 VERNAM VERNAM Antidote Method of Application IF PPI-TM IF IF Rate (Herb. + Anti.). (lbs/A or 7o ST.) 1.25+5 1.25+5 1.25+5 6+5 ; 7o In j ury Crop Result Weed Result" BA . 30/85 WH 60/80 WG 90/90 BA 60/85 CN 60/90 t>o N) O CO 201388 -24 ~ The compounds and compositions of this invention were employed in effective herbicidal compositions comprising the antidote and a thiolcarbamate herbicide as described hereinabove. The herbicidal compositions were tested in the above manner.

A preferred herbicidal compositions consists essentially of a thiolcarbamate herbicide and an anti-dotally effective amount of an antidote compound therefor corresponding to the formula described hereinabove, and known as 5-oxy or 5-thiomethyl substituted haloacyl oxazolidines.

The compositions of the present invention for the protection of cultivated crop plants comprise the active herbicidal compound and an antidote therefor selected from the above-described compounds. The compositions of herbicide and antidote can be prepared by conventional methods through the thorough mixing and grinding of the active herbicide agents and the antidote with suitable carriers and/or other distribution media, possibly with the addition of dispersion agents or solvents.

The antidote compounds and compositions of the present invention can be used in any convenient form. A solvent or inert carrier is not necessary in view of low volume spray technology which permits the use of neat technical grade materials as sprays.. Thus, the antidote compounds and composition with the thiolcarbamate herbicide can be formulated into emulsifiable liquids, emulsifiable concentrates, liquid, wettable powder, powders, granular or any other convenient form.

In its preferred form, a non-phytotoxic quantity of an herbicidal antidote compound is admixed with a selected herbicide and incorporated into the soil prior to or after planting the seed. It is to be understood, however, that the herbicide can be incorporated into the soil. Moreover, the crop seed Itself can be treated with a non-phytotoxic quantity of the compound and 201388 planted Into the soil which has been treated with herbicide', or untreated with the herbicide and subsequently treated with the herbicide. The. addition of the antidote compound does not affect the herbicidal activity of the herbicide. The alternative methods of application have been exemplified in the above examples.

The amount of antidote compound present can range between about 0.001 to about 30 parts by weight of antidote compound described herein per each part by weight of herbicide. The exact amount of antidote compound will usually be determined on economic ratios for the most effective amount usable. It is understood that a non-phytotoxic, but effective quantity of antidote compound will be employed in the herbicidal compositions and methods described herein.

After treatment with the antidote and herbicide, there is obtained as a resultant thereof, soil which is novel in composition. Said soil is improved in its capability to grow crops and to offer weed control. Further, said soil treated with herbicide and antidote has the particular utility for allowing seeds of crops otherwise injured by the herbicide, to be planted and grown. The herbicide has its utility in controlling undesirable vegetation; the antidote compound decreases the injury from the herbicide upon the crop species, and the soil treated with herbicide and antidote compound provides an improved media to grow the crop in the presence of an otherwise injurious herbicide.

In the utility of the present antidote compounds and improved herbicide system, the thiolcarbamate can be applied to the soil. Application of the herbicide to the soil can take place by pre-plant incorporation. In conjunction with the prior application of the herbicide employing the present invention crop seeds are planted. Seed planting is followed by application of the antidote as a pre-emergence surface application.

Claims (14)

-26- 2 0 1 3 8 8 This sequence of application of herbicide, seed planting and.antidote is unusual and fully effective in decreasing injury to the plant crop, otherwise injured by the thiolcarbamate herbicide. "27~ 2013 what we claim is;

1. Compounds according to the formula [—ch2XRI . R-c< I E2^ wherein X is oxygen or sulfur and is alkyl containing from 1 to 6 carbon atoms, inclusive; R is selected from the group consisting of haloalkyl containing from 1 to 4 carbon atoms, inclusive, and the term halo is chloro or bromof and alkoxycarboalkyl containing 3 to 6 carbon atoms, inclusive; R2 is selected from the group consisting of phenyl, p-chloro-phenyl and p-bromophenyl; and R^ is selected from the group consisting of hydrogen and methyl.

2. A herbicidal composition consisting essentially of a thiolcarbamate herbicide and a non-phytotoxic antidotally effective amount of an antidote compound therefor corresponding to the formula 0 II R-C- R„ R. -ch2xr1 0 wherein X is oxygen or sulfur and R^ is alkyl containing from 1 to 6 carbon atoms, inclusive; R is selected from the group consisting of haloalkyl containing from 1 to 4 carbon atoms, inclusive, and the term halo is chloro or bromo and alkoxycarboalkyl containing 3 to 6 carbon atoms, inclusive; R2 is selected from the group consisting of phenyl, p-chlorophenyl and p-bromophenyl; and R^ is selected from the group consisting of hydrogen and methyl. 20 .Op — 201388

3. a method of decreasing injury to crops, said injury due to a thiolcarbamate herbicide, comprising application to the soil in which the said crop is to be planted and grown, a non-phytotoxic antidotally effective amount of an antidote compound corresponding to the formula 0 _ CH~XR, R-C-N .6 wherein X is oxygen or sulfur and R^ is alkyl containing from 1 to 6 carbon atoms, inclusive; R is selected from the group consisting of haloalkyl containing from 1 to 4 carbon atoms, inclusive, and the term halo is chloro or bromo,and 10 alkoxycarboalkyl containing 3 to 6 carbon atoms, inclusive; R2 is selected from the group consisting of phenyl, p-chlorophenyl and p-bromophenyl; and R^ is selected from the group consisting of hydrogen and methyl.

4. A method of decreasing injury to crops, said 15 injury due to a thiolcarbamate herbicide, comprising applying into the seed furrow to the seed and adjacent soil in the open furrow prior to covering to achieve a planted state, a non-phytotoxic antidotally effective amount of a compound corresponding to the formula 2 1 0 R-C-N -ch2XR1 .0 r2 r3 wherein X is oxygen or sulfur and R^ is alkyl containing from 1 to 6 carbon atoms, inclusive; R is selected from the group consisting of haloalkyl containing from 1 to 4 carbon atoms, inclusive, and the term halo is chloro or bromo^ and alkoxycarboalkyl containing 3 to 6 carbon atoms, inclusive; 25 R2 is selected from the group consisting of phenyl, p-chloro- phenyl and p-bromophenyl; and R-> is selected from the group consisting of hydrogen and methyl. ° a* lU27JUN1984 \v , -29- 201388

5. A process for preparing compounds according to the formula ° X r-c-n .ch2XR1 R 2 "3 10 wherein X is oxygen or sulfur and R^ is alkyl containing from 1 to 6 carbon atoms, inclusive; R is selected from the group consisting of haloalkyl containing from 1 to 4 carbon atoms, inclusive, and the term halo is chloro or bromo and alkoxycarboalkyl containing 3 to 6 carbon atoms, inclusive; R2 is selected from the group consisting of phenyl, p-chloro-phenyl and p-bromophenyl; R^ is selected from the group consisting of hydrogen and methyl, said process comprising, in a single step, reacting a 5-substituted oxazolidine compound having the formula CH2XR1 (IVa) 15 20 and R2 and are as defined above wherein X is oxygen or sulfur, is alkyl/in an organic solvent with an acid chloride in the presence of a hydrogen chloride acceptor, to form the corresponding N-acyl-substituted compound wherein R is haloalkyl or alkoxycarboalkyl.

6. A process according to Claim 5 wherein in the compound of Formula IVa X is oxygen, R^ is alkyl and R2 is phenyl or p-chloro or p-bromophenyl, and R3 is hydrogen or methyl, and such compound is prepared by amination of a 1,2-epoxy-3-(alkoxy)-propane to produce a l-amino-3-(alkoxy)-2-propanol which is subsequently ZLo\ -&&8 -30- reacted with an aldehyde or ketone of the formula 0 R 2 C R 3 in which R2 is phenyl or p-chloro or p-bromo-phenyl and R^ is hydrogen or methyl to form an appropriate compound of Formula IVa. compound of Formula IVa X is sulfur, R1 is alkyl, R2 is p-chloro or p-bromo-phenyl and R^ is hydrogen or methyl, and such compound is prepared by thioation with a mercaptan of formula R^SH, where R1 is alkyl, of epichlorohydrin to produce a l-chloro-3-[alkyl-thio]-2-propanol, reforming such compound into an epoxide, amination of the l,2-epoxy-2-[alkyl-thio]-propane to produce a l-amino-3-[alkyl-thio]-2-propanol which is then reacted with an aldehyde or ketone of the formula

7. A process according to Claim 5 wherein in the 0 R 2 C R 3 -31- in which R2 is p-chloro or p-bromo-phenyl, and is hydrogen or methyl, to form an appropriate compound of Formula IVa.

8. The compound as claimed in Claim 1 in which R is CH2C1, XR.^ is SC2Hj-, R2 is phenyl and R^ is H.

9. A herbicidal composition as claimed in Claim 2 wherein the antidote compound is a compound as claimed in Claim 8.

10. A method of decreasing injury to crops as claimed in Claim 3 in which the antidote compound is a compound as claimed in Claim 8.

11. A method of decreasing injury to crops as claimed in Claim 4 in which the antidote compound is a compound as claimed in Claim 8.

12. Compounds of the formula given in Claim 1 as herein particularly described.

13. A herbicidal composition consisting essentially of a thiolcarbamate herbicide and a non-phytotoxic antidotally effective amount of a compound of the formula given in Claim 1, as herein particularly described.

14. A method of decreasing injury to crops, said injury due to a thiolcarbamate herbicide, substantially as herein described with reference to Table II herein.