TITLE HERBICIDAL TRICYCLIC HETEROCYCLES AND BICYCLIC UREAS

BACKGROUND OF THE INVENTION This invention comprises tricyclic imides, pyrazoles, and triazolones, and bicyclic ureas wherein one of the rings is a fused cyclopropane, and their agriculturally-suitable salts, for weed control in crops.

EP-A-493,323 discloses bicyclic imide herbicides, WO 93/15074 discloses bicyclic pyrazole herbicides, and U.S.4,213,773 discloses bicyclic triazolone herbicides, but they lack the fused cyclopropane ring present in the compounds of this invention.

SUMMARY OF THE INVENTION The compounds of this invention are compounds of Formulae I-IV:

π

m IV wherein Q is

Q-l Q-3

R ¹ is independently hydrogen; halogen or C!-C ₃ alkyl; R ² is independently hydrogen; fluorine; chlorine; or bromine; V is O or S; X is halogen or cyano; m is 1 or 2; p is 0 or 1 provided that when m is 2, then p is 0; W is O or S; R ³ is halogen;

R ⁴ is H; C _r C ₈ alkyl; C _r C ₈ haloalkyl; halogen; OH; OR9; SH; S(O) _n R9; COR9; CO ₂ R ⁹ ; C(O)SR9; OJNR ^{1 !} R ¹² ; CHO; CR ¹ ^NOR ¹⁸ ; CH=CR ¹⁹ CO ₂ R ⁹ ;

CH ₂ CHR ¹⁹ CO2R ⁹ ; CO ₂ N=CR ¹³ R ¹⁴ ; NO ₂ ; CN; NHSO ₂ R ¹⁵ ;

NHSO ₂ NHR ¹⁵ ; NR ⁹ R ² J NH ₂ or phenyl optionally substituted with R ²¹ ; n is 0, 1 or 2;

R ⁵ is C _r C ₂ alkyl; C _r C ₂ haloalkyl; OCH ₃ ; SCH ₃ ; OCHF ₂ ; halogen; CN or NO ₂ ; R ⁶ is H; C _r C ₃ alkyl or halogen;

R ⁷ is H; C _] -C ₃ alkyl; halogen; C]-C ₃ haloalkyl; cyclopropyl; vinyl; C alkynyl;

CN; C(O)R ²⁰ ; CO ₂ R ²⁰ ; C(O)NR ²⁰ R ²² ; CR ¹⁶ R ¹⁷ CN; CR ¹⁶ R ¹⁷ C(O)R ² 0;

CR ¹⁶ R ¹⁷ CO ₂ R ²⁰ ; CR16R17 _C (O)NR ² 0R ²² ; CHR^OH; CHRl6oC(O)R ² 0 or

OCHR ¹⁶ OC(O)NR ²⁰ R ²² ; or when Q is Q-2, R ⁶ and R ⁷ can be taken together with the carbon to which they are attached to form C=O;

R ⁸ is H; C _r C ₆ alkyl; C _r C ₆ haloalkyl; C ₂ -C ₆ alkoxyalkyl; C ₃ -C ₆ alkenyl; C ₃ -C ₆

or

R9 is C!-C ₈ alkyl; C ₃ -C ₈ cycloalkyl; C ₃ -C ₈ alkenyl; C ₃ -C ₈ alkynyl; C _r C ₈ haloalkyl; C ₂ -C ₈ alkoxyalkyl; C ₂ -C ₈ alkylthioalkyl; C ₂ -C ₈ alkylsulfinylalkyl; C ₂ -C ₈ alkylsulfonylalkyl; C ₄ -C ₈ alkoxy alkoxyalkyl;

C ₄ -C ₈ cycloalkylalkyl; C ₆ -C ₈ cycloalkoxy alkyl; C ₄ -C ₈ alkenyloxyalkyl;

C -C ₈ alkynyloxyalkyl; C ₃ -C ₈ haloalkoxy alkyl; C ₄ -C ₈ haloalkenyloxyalkyl; C ₄ -C haloalkynyloxy alkyl; Cg-C ₈ cycloalkylthioalkyl; C ₄ -C ₈ alkenylthioalkyl; C ₄ -C ₈ alkynylthioalkyl; Cι-C ₄ alkyl substituted with phenoxy or benzyloxy, each ring optionally substituted with halogen, C---C3 alkyl or C _r C ₃ haloalkyl; C ₄ -C ₈ trialkylsilylalkyl; C ₃ -C ₈ cyanoalkyl; C ₃ -C ₈ halocycloalkyl; C3-C ₈ haloalkenyl; C ₅ -C ₈ alkoxy alkenyl; C ₅ -C haloalkoxy alkenyl; C ₅ -C ₈ alkylthioalkenyl; C3- haloalkynyl; C ₅ -C ₈ alkoxy alkynyl; C ₅ -C ₈ haloalkoxyalkynyl; C ₅ -C ₈ alkylthioalkynyl; C ₂ -C ₈ alkylcarbonyl; benzyl optionally substituted with halogen, C-t-C ₃ alkyl or C _r C ₃ haloalkyl; CHR ¹⁶ COR ¹⁰ ; CHR ¹⁶ P(O)(OR ¹⁰ ) ₂ ; CHRl6p(S)(OR ¹⁰ ) ₂ ;

P(O)(OR ¹⁰ ) ₂ ; P(S)(OR ¹⁰ ) ₂ ; CHR ¹⁶ C(O)NR ¹¹ R ¹² ; CHRl6c(O)NH ₂ ; CHR ¹⁶ CO ₂ R ¹⁰ ; CO ₂ R ¹⁰ ; SO ₂ R ¹⁰ ; phenyl optionally substituted with R ²¹ ;

R ¹⁰ is C _r C ₆ alkyl; C _r C ₆ haloalkyl; C ₃ -C ₆ alkenyl or C ₃ -C ₆ alkynyl; R ^u and R ¹³ are independently H or C _r C ₄ alkyl;

R ¹² and R ¹⁴ are independently Cj-C alkyl or phenyl optionally substituted with halogen, C1-C3 alkyl or -C3 haloalkyl; or R ¹ - ^• and R ¹² are taken together along with the nitrogen to which they are attached to form a piperidinyl, pyrrolidinyl or morpholinyl ring, each ring optionally substituted with C1-C3 alkyl, phenyl or benzyl; or

R ¹³ and R ¹⁴ are taken together with the carbon to which they are attached to form

C3-C cycloalkyl; R ¹⁵ is C _r C ₄ alkyl or C _r C ₄ haloalkyl; R ¹⁶ and R ¹⁷ are independently H or C _r C ₅ alkyl; R ¹⁸ is H, C _r C ₆ alkyl, C ₃ -C ₆ alkenyl or C ₃ -C ₆ alkynyl;

R ¹⁹ and R ²⁴ are independently H, C _j -C alkyl or halogen; or R ⁹ and R ¹⁹ are taken together as C2-C3 alkylene; R20, R21 _{5 an} d R25 ar _e independently H or C _r C ₄ alkyl; R ²² is C _r C ₂ alkyl; C _r C ₂ haloalkyl; OCH ₃ ; SCH ₃ ; OCHF ₂ ; halogen; CN or NO ₂ ; and

R ²³ is H; C _r C ₅ alkyl; C _r C ₅ haloalkyl; C ₃ -C ₆ cycloalkyl; C ₃ -C ₆ halocycloalkyl; and phenyl optionally substituted with up to three substituents independently selected from the group halogen, NO2, cyano, C1-C2 alkyl, C _j -C ₂ haloalkyl, C-*-C ₂ alkoxy, and C-*-C ₂ haloalkoxy; and their corresponding N-oxides and agriculturally suitable salts.

Preferred compounds of Formulae I-IV for reasons including ease of synthesis and/or greater herbicidal efficacy are:

1. A compound of Formulae I-IV wherein R ¹ is hydrogen or halogen; R ² is hydrogen; chlorine; or fluorine;

R ⁴ is H; C _r C ₈ alkyl; C _r C ₈ haloalkyl; halogen; OH; OR ⁹ ; SH; S(O) _n R ⁹ ; COR ⁹ ; CO ₂ R ⁹ ; C(O)SR9; C(O)NR ^Π R ¹² ; CHO; CH=CHCO ₂ R ⁹ ; CO ₂ N=CR ¹³ R ¹⁴ ; NO ₂ ; CN; NHSO ₂ R ¹⁵ ; or NHSO ₂ NHR ¹⁵ ; and R ²³ is C _r C ₂ alkyl. 2. Compounds of Preferred 1 wherein

R ² is hydrogen or fluorine; and

R ⁹ is C _r C ₄ alkyl; C ₃ -C ₄ alkenyl; C ₃ -C ₄ alkynyl; C ₂ -C ₄ alkoxyalkyl; C _r C ₄ haloalkyl; C3-C ₄ haloalkenyl or CyC ₄ haloalkynyl. 3. Compounds of Preferred 2 wherein Q is Q-l or Q-5;

R ¹ and R ² are each hydrogen; and R ⁵ is halogen; CN; or NO ₂ . Specifically preferred is a compound of Preferred 3 selected from the group: (+/-)-2-[4-chloro-2-fluoro-5-(2-propynyloxy)phenyl]tetrahydr ocyclopropa[3,4]- pyrrolo[l,2-c]imidazole-l,3(2H,3aH)-dione and (+/-)-2J4-chloro-2-fluoro-5-

[(l-methyl-2-propynyl)oxy]phenyl]tetrahydrocyclopropa[3,4 ]-pyrrolo[l,2- c]imidazole- 1 ,3(2H,3aH)-dione. Another embodiment of the invention is an agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of a compound of Formulae I-IV with the substituents as defined above.

A further embodiment of the invention is a method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Formulae I-IV with the substituents as defined above.

DETAILS OF THE INVENTION Compounds of Formulae I-IV may exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be the more active. One skilled in the art knows how to separate said enantiomers, diastereomers and geometric isomers. Accordingly, the present invention comprises racemic mixtures, individual stereoisomers, and optically active mixtures.

In the above recitations, the term "alkyl" used either alone or in compound words such as "alkylthio" includes straight or branched alkyl such as methyl, ethyl, n-propyl,

isopropyl and the different butyl, pentyl and hexyl isomers. Examples of "alkylsulfonyl" include CH ₃ S(O) ₂ , CH ₃ CH ₂ S(O) ₂ , CH ₃ CH ₂ CH ₂ S(O) ₂ , (CH3) ₂ CHS(O) ₂ and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. Alkoxy includes methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. Alkenyl includes straight or branched chain alkenes such as vinyl, 1-propenyl, 2-propenyl and the different butenyl, pentenyl and hexenyl isomers. "Alkenyloxy" includes straight-chain or branched alkenyloxy moieties, examples include H ₂ C=CHCH ₂ O, (CH ₃ ) ₂ C=CHCH ₂ O, (CH ₃ )CH=CHCH ₂ O, (CH ₃ )CH=C(CH ₃ )CH ₂ O and CH ₂ =CHCH ₂ CH ₂ O. "Alkynyloxy" includes straight- chain or branched alkynyloxy moieties, examples include HC≡CCH ₂ O, CH ₃ C≡CCH ₂ O and CH ₃ C≡CCH ₂ CH ₂ O. Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

The term "halogen", either alone or in a compound word such as "haloalkyl", denotes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl can be partially or fully substituted with independently selected halogen atoms. Examples of haloalkyl include CH ₂ CH ₂ F, CF ₂ CF ₃ and CH ₂ CHFC1.

The total number of carbon atoms in a substituent group is indicated by the "C _j -Cj" prefix where i and j are numbers from 1 to 8. For example, C ₄ alkoxy designates the various isomers of an alkoxy group containing a total of 4 carbon atoms, examples including OCH ₂ CH ₂ CH ₂ CH ₃ , OCH ₂ CH(CH ₃ ) ₂ , OC(CH ₃ ) ₃ .

The compounds represented by Formulae I-IV can be prepared according to the methods illustrated below in Schemes 1-13. The definitions of Q, X, m, p, W, n, and R ¹ through R ²⁵ in the compounds of Formulae 1-15 below are as defined above in the Summary of the Invention.

As illustrated in Scheme 1, treatment of the cw-cyclopropane dicarboxylic acid of Formula 1 with urea and heating to 175-185°C affords the cw-dicarboximide of Formula 2 as described by G. C. Crockett et al. in Synth. Commun. (1981), 11, A1-A5A.

Scheme 1

wherein m- 1 is 0 or 1.

The diester of the diacid of Formula 1 is prepared by the method described by L. L. McCoy in J. Am. Chem. Soc, (1958), 80, 65-68. A mixture of cis- and trøH_ϊ-diesters are obtained and the desired c/s-isomer can be isolated by chromatography. The cw-diacid can be obtained by saponification of the diester using well-known methods.

Reduction of the cw-dicarboximide of Formula 2 with borane in an inert solvent, such as tetrahydrofuran (THF), followed by work-up with aqueous hydrochloric acid affords the azabicyclo[3J.0]hexane hydrochloride of Formula 3 (Scheme 2). The reduction is preferably conducted with heating, for example in THF at reflux, as described by H. C. Brown and P. Heim in J. Org. Chem., (1973), 38, 912-916.

Scheme 2

wherein m-1 is 0 or 1.

Alternatively, compounds of Formula 3 can be obtained by the cyclopropanation method (Scheme 3) described by B. Withop et al; in J. Am. Chem. Soc. (1971) 94, 3471-3477.

Scheme 3

The amine hydrochloride of Formula 3 is converted via a five step sequence to the α-aminoacid of Formula 7 as illustrated in Scheme 4. Purification of the intermediates is not necessary.

Scheme 4

Neutralization of the amine hydrochloride with a base, such as concentrated aqueous potassium hydroxide, liberates the free amine. Dissolution of the amine in an inert solvent, such as diethyl ether, and treatment with a solution of N-chlorosuccinimide (ΝCS) in an inert solvent such as ether, produces the chloramine of Formula 4. The solution of the chloramine is then treated with ethanolic potassium hydroxide to effect dehydrochlorination and give the imine of Formula 5. Once again, the imine is not purified but treated directly first with aqueous sodium bisulfite, and then with solid sodium cyanide to afford the aminonitrile of Formula 6. The reaction mixture is poured into water and extracted with a water-immiscible solvent such as ether. The organic layers are dried and evaporated under reduced pressure to afford the aminonitrile. No additional purification is necessary. The aminonitrile of Formula 6 can be converted to the aminoacid of Formula 7 by hydrolysis with aqueous barium hydroxide followed by neutralization with sulfuric acid. A mixture of epimers at the

carboxylic acid centers is obtained, and the individual diastereomers can be separated by chromatography.

Amides of Formula 9 can be prepared as outlined in Scheme 5. The acid of Formula 7 is reacted with an aniline of Formula 8 and a trialkylaluminum reagent (e.g., trimethylaluminum), in a non-coordinating solvent such as an aromatic hydrocarbon (e.g., benzene and toluene) or halogenated hydrocarbon (e.g., methylene chloride, chloroform, carbon tetrachloride, and dichlorobutane) to obtain the amide. Generally, the reaction requires 0J to 48 hours at a temperature of 0°C to 25°C to proceed to completion. The amides of Formula 9 are isolated by extraction into an organic solvent, aqueous wash, and removal of the solvent under reduced pressure. Purification can be accomplished by chromatography or recrystallization. Anilines of Formula 8 are known or can be prepared by known methods. For example, the synthesis of anilines of Formula 9 wherein Q is Q-l, Q-4, and Q-5 is described in U.S. 4,902,335. The anilines wherein Q is Q-2 and Q-3 can be prepared as described in U.S. 5,053,071 or by well known modifications thereof.

Scheme 5

The reaction illustrated in Scheme 5 can also be performed starting with the ester of the acid of Formula 7.

In addition, amides of Formula 9 can be generated using conventional

1,3-dicyclohexylcarbodiimide (DCC) procedures for coupling N-protected compounds of Formula 10 with amines of Formula 8 followed by removal of the protecting group according to the procedures outlined by Bodanszky, M. in Principles of Peptide

Synthesis, Volume 16, Springer- Verlag, New York, (1984) (Scheme 6).

10 8

Z = JV-protecting group

The tricyclic imide of Formula I can be prepared from the oc-aminoamide of Formula 9 by condensation with thiophosgene, phosgene (U=C1) or a phosgene equivalent as illustrated in Scheme 7. Treatment of the α-aminoamide with (thio)phosgene is preferably carried out in the presence of a tertiary-amine base such as triethylamine, pyridine, or NN-diisopropylethylamine, in an inert solvent such as dichloromethane or 1-chlorobutane. The phosgene can be added as a gas or as a solution in an inert solvent such as toluene. Suitable temperatures range from about 0°C to the reflux temperature of the solvent. Diphosgene (ClC(=O)OCCl ₃ ) and triphosgene (Cl3COC(=O)OCCl3) can also be used in a similar manner.

Scheme 7

Alternatively, the imides of Formula I where V = O can be prepared using lJ'-carbonyldiimidazole (U=l-imidazolyl, CDI). The amide of Formula 9 is dissolved in an inert solvent in which the CDI has sufficient solubility at the reaction temperature. Methylene chloride, 1-chlorobutane and toluene are three of many suitable inert solvents. The CDI is added as a solid or as a solution in an inert solvent at temperatures from 0°C to 100°C. When the reaction is complete, the resulting mixture is poured into a water-immiscible solvent and washed successively with dilute mineral acid, water, and brine. The organic liquid phase is separated, dried, and evaporated to isolate the product.

Compounds of Formula I can also be prepared by treating amides of Formula 9 with lJ'-carbonylditriazole (U=l,2,4-triazolyl, CDT) as described above for CDI. Additional base can be added to accelerate the reaction. Suitable bases include a trialkylamine, imidazole, pyridine, picoline or other substituted pyridine, or mixtures thereof. For both CDI and CDT, the carbonylating agent can be added as a pure compound, or as a solution of the pure compound in an inert solvent. For example, CDI can be first prepared by treatment of a solution of imidazole in an inert solvent with phosgene as described by Staab and Wendel (Org. Syntheses, Coll. Vol. 5, 201, (1973)), and then treated in situ with the amide of Formula 9 to afford I.

Compounds of Formula I can also be prepared from compounds of Formula II when R ²³ = H as shown in Scheme 8.

Scheme 8

Reflux

Intramolecular cyclization of II to give compounds in Formula I can be effected by heating II at elevated temperature between 5°C to 200°C in suitable inert organic solvents, e.g., an aromatic hydrocarbon such as benzene or toluene.

Compounds of Formula II can be prepared by first converting amines of Formula 8 to isocyanates or thiocyanates of Formula 10 using conventional diphosgene, triphosgene, or thiophosgene reaction with amines (Scheme 9). Generally, the triphosgene or the thiophosgene is contacted with amines as compound 8 at low temperature 0-25°C in the presence of a suitable base such as a tertiary amine, e.g., pyridine or triethylamine (with hydrocarbon solvents, e.g., toluene, chlorinated alkane such as chloroform or methylene chloride).

•J— Q

Compounds of Formula II can be obtained by contacting compounds of Formula 10 with compounds of Formula 3 (Scheme 10)

Scheme 10

V=C=N— Q π

10

The reaction is run in a suitable organic solvent, e.g., chlorinated alkane such as chloroform or methylene chloride, an aromatic hydrocarbon such as benzene or toluene, or an ether type solvent such as THF. For completion of the reaction, it is sometimes necessary to heat the reaction mixture to reflux.

The tricyclic imides of Formula I and bicyclic ureas of Formula II can be isolated by extraction into an organic solvent, aqueous wash, and removal of the solvent under reduced pressure. Additional purification can be accomplished by chromatography or recrystallization. Compounds of Formula III can be made by the reaction of sydnones of Formula

11 with appropriately substituted alkynes 12 (Scheme 11).

Scheme 11

11

The reaction takes place at elevated temperatures generally between 80°C and 200°C. The reaction may be performed in a variety of solvents with aromatic hydrocarbons such as xylenes preferred.

The sydnones of Formula 11 can be made using procedures known in the art (see S. D. Larsen and E. Martinsorough, Tetrahedron Lett. 1989, 4625 and D. Ranganathan and S. Bamezai, Tetrahedron Lett. 1983, 1067).

Scheme 12 shows how compounds of Formula HI can also be prepared by coupling compounds of Formula 13, with aryl halides or sulfonates 14 in the presence of palladium catalysts as described by Yamanoka et al., Heterocycles, 33, 813-818 (1992). Compounds of Formula 13, can be made by sydnone cycloaddition as described in Scheme 11 using stannylated acetylenes.

Scheme 12

13 14

Y=Br, I, OSθ2CF3

The compounds in Formula IV may be made as shown in Scheme 13.

Scheme 13

15 IV

The conversion of the amidrazones 15, or their acid salts (e.g., hydrochlorides), to the compounds of Formula IV is accomplished by reaction with either diphosgene, triphosgene or thiophosgene. The reaction is run in a suitable inert organic solvent, e.g., benzene, toluene, CHCI3 or CH2C1 ₂ with a suitable base such as pyridine or a

tertiary amine, e.g., Et3N. The product of the reaction can be isolated by extraction into organic solvent, aqueous wash, and removal of the solvent under reduced pressure. Purification of the crude material is accomplished by standard techniques, e.g., crystallization, chromatography or distillation. The amidrazones 15, may be prepared by methods similar to those described in

US Patent No. 4,213,773.

It is recognized that some reagents and reaction conditions described above for preparing compounds of Formulae I-TV may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences into the synthesis will aid in obtaining the desired products. The use and choice of the protecting group will be apparent to one skilled in chemical synthesis.

In the following Examples, all *H NMR spectra were measured in CDCI3 solution at 300 MHz unless otherwise indicated. EXAMPLE 1

Preparation of (+/-V2-r4-chloro-2-fluoro-5-(2-propynyloxy phenyiy tetrahydrocyclopropar3.4]pyrroloπ.2-c1imidazole-1.3f2H.3aHV dione Step A: Preparation of diethyl c/s-1.2-cyclopropanedicarboxylate

To a stirred suspension of 32.8 g (818.8 mmol) of 60% sodium hydride mineral oil dispersion in 200 mL of toluene under nitrogen, was added between 10 to 20 mL of a blend of ethyl acrylate (81.2 g, 810.7 mmol) and ethyl chloroacetate (99.4 g, 810.7 mmol) followed by several drops of ethanol. After an induction period of about 1 h, steady gas and heat evolution began with the reaction mixture temperature reaching 35°C. The remaining mixed ester reagent was carefully added dropwise with ice-bath cooling so as to maintain a reaction temperature of 30-80°C. After the addition was complete (4 h), the mixture was cooled to room temperature and carefully poured into water (300 mL). The organic layer was separated and dried (MgSO ₄ ) and evaporated to a dry residue. The dry residue was chromatographed on silica gel using 10% ethyl acetate in hexane as the eluant. The fractions containing the desired compound were combined and evaporated to dryness under reduced pressure to give 53.0 g of the title compound of Step A as a clear oil (35% yield). IR (neat, cm" ¹⁾ : 1728.9 (C=O); ^] H NMR: 64.20-4.12 (m,4H), 2.14-2.05 (t,2H), 1.71-1.62 (qJH), 1.31-1.20 (m,7H). Step B: Preparation of c -1.2-cyclopropanedicarboxylic acid

A stirred mixture of diethyl cw-l,2-cyclopropanedicarboxylate (53.0 g, 284.6 mmol) and sodium hydroxide (32.4 g, 809.1 mmol) in water (200 mL) was heated at reflux for 5 h. The mixture was then allowed to stir at room temperature overnight. The ethanol formed was evaporated under reduced pressure and the remaining aqueous

solution was acidified with a slight excess of concentrated aqueous HCl (74.8 mL, 892.8 mmol). The mixture was evaporated to dryness under reduced pressure, and the residue was washed with hot ethyl acetate (3 times with 200 mL). The ethyl acetate layer was separated, dried (MgSO ₄ ) and evaporated to dryness under reduced pressure to give 35.5 g of the title compound of Step B as a white solid (96% yield); m.p. 122-124°C. IR (mineral oil, cm" ¹ ), 1691.0 (C=O); 2600-3100, broad (OH). Step C: Preparation of c/s-1.2-cvclopropanedicarboximide

A well-blended mixture of cw-l,2-cyclopropanedicarboxylic acid (5.0 g, 38.4 mmol) and urea (2.54 g, 42.24 mmol) in a round-bottom flask fitted with a condenser and magnetic stir bar, was immersed in a preheated oil bath (180°C) and heated at 180°C for 35 min with stirring. Gas evolution was observed during heating. The reaction mixture was then allowed to cool to room temperature. The mixture was then chromatographed on silica gel using 5% methanol in methylene chloride to obtain 2.4 g of the title compound of Step C as a white solid (56% yield); m.p. 93-94°C; IR (mineral oil, cm" ¹ ) 1678.9, 1758.3 (C=O).

Step D: Preparation of 3-azabicycIor3J.01hexene hydrochloride salt

To a stirred solution of borane tetrahydrofuran complex (1.0 M, 35 mL, 135.0 mmol) under nitrogen and cooled to 0°C, was added cw-l,2-cyclopropanedicarboximide (5.0 g, 45.05 mmol) portionwise via solid addition funnel. The mixture was heated at reflux for 6 h. The reaction mixture was allowed to cool to 0°C, and then 6N aqueous HCl was added dropwise until the pH was approximately 3. The resultant mixture was stirred for an additional 1 h. The mixture was then made basic to pH 9 with 50% aqueous NaOH. Ethyl acetate (300 mL) and water (100 mL) were then added. The organic layer was separated and added to ethanol (100 mL). The solution was acidified to pH 6 with concentrated aqueous HCl and then evaporated to dryness under reduced pressure. The residue was triturated with cold 2-propanol. Evaporation of the 2-propanol under reduced pressure yielded 3.59 g of the title compound of Step D as a white solid (67% yield); m.p. 125-127°C. Step E: Preparation of f+/-)-3-azabicyclor3J.01hexane-2-carboxylic acid The compound, 3-azabicyclo[3.1.Ojhexene hydrochloride salt ( 15.0 g,

125.43 mmol), was added to a saturated aqueous solution of potassium hydroxide (40 mL). The mixture was stirred at room temperature for 10 min and then washed with diethyl ether (3 times with 100 mL). The ether layer was dried (MgSO ₄ ) and then added dropwise to a solution of N-chlorosuccinimide (29.7 g, 221.9 mmol) in diethyl ether (200 mL). The resultant mixture was stirred at ambient temperature for 3 h. Then, the mixture was filtered and the filtrate was washed with H ₂ O (2 times with 50 mL), brine (50 mL) and dried (MgSO ₄ ). The dried filtrate was added dropwise over

a 30 min period to a solution of potassium hydroxide (8.28 g, 125.43 mmol) in absolute ethanol (300 mL). The resultant mixture was stirred at room temperature overnight. Filtration removed the inorganic salts, which were washed with ether. The combined filtrate and ether washings, which contained the imine, were treated with 13.05 g (125.4 mmol) of sodium bisulfite in 100 mL of water. After stirring vigorously for 15 min at room temperature, the two-phase mixture was treated with 6.48 g (125.43 mmol) of solid sodium cyanide. After stirring 2 h more at room temperature, the upper organic layer was decanted away and the aqueous layer was extracted with diethyl ether (2 times with 300 mL). The combined organic layer and ether extracts were dried (MgSO ) and evaporated to dryness under reduced pressure to afford 12J g of

3-azabicyclo[3J.0]hexane-2-carbonitrile. IR (neat, cm" ¹ ): 2245.9 (CN). This crude product was used in the next reaction without further purification. A stirred solution of 12J g (112.0 mmol) of the crude carbonitrile and barium hydroxide hydrate (35.9 g, 114 mmol) in water (300 mL) was heated at reflux for 7 h. The reaction mixture was cooled to room temperature and acidified to pH 6 with concentrated sulfuric acid. The resulting white suspension was filtered through a Celite® bed, and the filtrate was allowed to settle for 30 min. The clear solution was decanted and evaporated under reduced pressure to dryness to give 9.8 g of the title compound of Step E as a white solid (69% yield), m.p. 211-213°C; IR (mineral oil, cm" ¹ ): 1629.5 (C=O), 2600-3200 broad (OH).

Step F: Preparation of N-r4-chloro-2-fluoro-5-f2-propynyloxy)phenyl]-3- azabicyclo-r3.1.Olhexane-2-carboxamide To a mixture of 2.36 g (11.79 mmol) of 4-chloro-2-fluoro-5-(2-propynyl)oxy- aniline and 1.5 g (11.79 mmol) of (+/-)-3-azabicyclo[3J.0]hexane-2-carboxylic acid in methylene chloride (150 mL) stirred under nitrogen and cooled to 5°C was added trimethylaluminum dropwise (2.0 M, 11.8 mL, 23.58 mmol). The resultant mixture was stirred at room temperature for 48 h. Water (100 mL) was added dropwise at ice-bath temperature. The solid inorganic material which formed was filtered, and the filtrate was dried (MgSO ₄ ) and evaporated under reduced pressure to dryness. Flash chromatography on silica gel yielded 1.3 g of the product of Step F as a tan solid; m.p. 113-115°C. IR (mineral oil, cm ^"1 ): 1687J (C=O); 2123.5 (C≡C). Step G: Preparation of ( ^" +/- -2-[ ^" 4-chloro-2-fluoro-5-(2-propynyloxy)phenyll- tetrahydrocyclopropar3.41pyπOlori.2-c1imidazole-1.3(2H.3aH) -dione Triphosgene (256 mg, 0.86 mmol) in 10 mL of dioxane was added dropwise at 0°C to a stirred mixture of 80 mg, (2.59 mmol) of the product of Step F and triethylamine (1.8 mL, 12.95 mmol). The mixture was stirred at room temperature for 30 min. Evaporation of the mixture under reduced pressure gave a dry residue. Flash

chromatography of the residue on silica gel gave 0.4 g of the title compound of Step G, a compound of the invention; m.p. 52-54°C; IR (mineral oil, cm" ¹ ): 1784, 1722 (C=O); 2120 (C≡C); ^] H NMR: 50.60-0.64 (m,lH), 1.20-1.31 (mJH), 2.00-2.09 (mJH), 2J0- 2.20 (mJH), 2.60 (sJH), 3J 1-3J9 (ddJH), 4J8-4.23 (m,2H), 4.76-4.77 (d,2H), 7.02- 7.06 (dJH), 7.29-7.32 (dJH).

EXAMPLE 2 Preparation of Ethyl 3-| ^" 2-chloro-4-fluoro-5-Chexahvdro-1.3-dioxo- cyclopropar3.41pyrτolori.2-climidazol-2 ⁽ 3H -yl phenyll-2-propenoate Step A: Preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid A blend of 70% nitric acid (64.5 gm) and concentrated sulfuric acid (65 mL) was added dropwise over an hour period to a suspension of 2-chloro-4-fluoro-benzoic acid (125.0 gm, 716 mL). The white suspension was stirred mechanically for 30 minutes at ambient temperature. The thick white suspension was carefully poured into ice- water (100 mL). Ethyl acetate (800 mL) was added. The organic layer was separated, dried (MgSO ) and evaporated to dryness under vacuum to give the title compound of Step A as a white solid (156.0 gm, 99%); m.p. 134-136°C; IR (cm" ¹ ), C=O (1719.8). This intermediate was used without further purification. Step B: Preparation of 2-chloro-4-fluoro-5-nitrobenzenemethanol

To a stirred solution of compound in Step A, Example 2 (120.0 gm, 546.45 mmol, in THF (400 mL), under N ₂ , at room temperature was slowly added Borane - THF complex 1.0 M (726.8 mL, 726.8 mmol, Aldrich) over a 2-hour period (ice-bath used to keep temperature at 20-25 °C). The resultant solution was stirred at room temperature for 3 hours followed by the solution being heated to reflux for 1 hour. H ₂ O (30 mL) was added very slowly dropwise at 5°C (ice-bath). The solution turned dark and H ₂ O (1 L) and ethyl acetate (1 L) were added. The light yellow organic layer was separated, dried (MgSO ₄ ) and evaporated to dryness under vacuum. The residue was chromatographed on silica gel using 20% ethyl acetate in hexane. The desired fractions were combined and evaporated under vacuum to obtain the title compound of Step B as a soft-yellow solid (91.3 gm, 81%); m.p. 39-4PC, IR (nujol, cm" ¹ ): 3321.2 (OH); --H NMR 6: 2J8-2.22 (tJH), 4.81-4.83 (d,2H), 7.34-7.36 (dJH), 8.30-8.33 (dJH). Step C: Preparation of 2-chloro-4-fluoro-5-nitrobenzaldehyde

To a suspension of PCC (48.46 gm, 224.0 mmol, Aldrich) under N , at room temperature, was rapidly added a solution of the compound of Step B, Example 2, (30.82 gm, 1.49.9 mmol) in methylene chloride (100 mL). The mixture turned dark and slowly became homogeneous. The dark mixture was stirred at room temperature for 3.5 hours.

The mixture was added to diethyl ether (800 mL) and filtered through Florisil®. The remaining black residue was washed with Et ₂ O (2 x 200 mL) and filtered through Florisil®. The diethyl ether portions were combined, dried over magnesium sulfate and evaporated to dryness. The dry residue was chromatographed on silica gel using 10% ethyl acetate in hexane. Fractions of desired product were combined and evaporated under vacuum to give the title compound of Step C (20.2 gm, 66%) as a yellow oil. IR (neat, cπr ¹ ): 1703.3 (C=O); ^! H NMR δ: 7.47-7.51 (dJH), 8.65-8.68 (dJH), 10.41 (sJH). Step D: Preparation of Ethyl 3-( 2-chloro-4-fluoro-5-nitropheny -2-propenoate A stirred mixture of the compound of Step C, Example 2, (11.5 gm, 56.51 mmol),

(carbethoxymethyl)triphenylphosphonium bromide (24.2 gm, 56.51 mmol) and triethylamine (50 mL) in benzene (200 mL), under N ₂ , was heated to reflux for 1 hour. Water (200 mL) and ethyl acetate (200 mL) were added. The organic layer was separated, dried over magnesium sulfate and evaporated under reduce pressure to dryness. The residue was chromatographed on silica gel using hexane:EtOAc (15:5) mixture as eluent. The fractions were combined and evaporated under reduce pressure to obtain the title compound of Step D (9.3 gm, 60%) as a yellow solid; m.p. 86-88°C, IR (nujol, cm- ¹ ): 1716.8 (C=O); ^! H NMR δ: 1.33-1.38 (t,3H), 4.29-4.31 (q,2H), 6.44- 6.54 (dJH), 7.40-7.44 (dJH), 7.93-7.99 (dJH), 8.34-8.38 (dJH). Step E: Preparation of Ethyl 3-( ^" 5-amino-2-chloro-4-fluoro-2-propenoate

A stirred solution of the compound of Step D, Example 2, (3.5 gm, 12.8 mmol) in acetic acid (30 mL) was heated to reflux under N ₂ . The heat source was removed and iron powder (2.2 gm) was added portionwise. The dark mixture was heated to reflux for 10 minutes and a thick precipitate formed. Water (100 mL) and ethyl acetate (100 mL) were added. The organic layer was separated, dried over magnesium sulfate, filtered through 0.5 cm of silica gel and evaporated to dryness under vacuum. The residue was chromatographed on silica gel using 10% ethyl acetate in hexane. Fractions containing the desired compound were combined and evaporated under reduce pressure to yield the title compound of Step E as a yellow solid (2.79 gm, 89%); m.p. 123-124°C; IR (nujol, cm- ¹ ): 1704 (C=O), 3212 and 3388 (NH ₂ ); ^l K NMR δ: 1.31-1.36 (t,3H), 3.79 (broad s,2H), 4.26-4.28 (q,2H), 6.26-6.31 (dJH), 6.99-7.02 (dJH), 7.05-7.08 (dJH), 7.93- 7.99 (dJH).

Step F: Preparation of Phenylmethyl 2-πT4-chloro-5-f3-ethoxy-3-oxo-l-propenylV 2-f luorophenyll amine! carbonyll -3-azabicyclo \3 J .01 hexane-3 -carboxylate A mixture of the compound of Step D, Example 2, (2.7 gm, 11.09 mmol), CBZ protected (+/-)-3-azabicyclo[3J.0]hexane-2-carboxylic acid (3.76 gm, 14,41 mmol), DCC (2.97 gm, 14.41 mmol), and DMAP (39 mg, 1.4 mmol) in methylene chloride

(100 mL) was stirred at room temperature for 24 hours. The mixture was filtered and the filtrate was evaporated to dryness. The residue was chromatographed on silica gel using 25% of ethyl acetate in hexane as eluent. The combined desired fractions were evaporated under vacuum to yield the title compound of Step F as a white solid 1.52 gm, 63%; m.p. 58-60°C. IR (nujol, cm" ¹ ): 1710 (C=O); ^! H NMR δ: 0.22-0.28 (mJH), 0.75-0.89 (m,2H), 1J9-1.38 (m,5H), 3.43-3.79 (m,3H), 4.21-4.28 (m,2H), 5.01-5J3 (m,2H), 6.42-6.48 (dJH), 7.18-7.37 (m,7H), 7.95-8.00 (dJH). Step G: Preparation of Ethyl 3J5-rrf3-azabicvclor3J.01hexan-2-vn- carbonyll aminol -2-chloro-4-fluorophenyll -2-propenoate To a stirred solution of borontrifluoride etherate (2.27 mL, 2.62 gm, 18.5 mmol) and ethanethiol (4J mL, 3.44 gm, 55.5 mmol) under N ₂ , at room temperature was added dropwise a solution of the compound of Step F, Example 2, (900.0 mg, 1.85 mmol) in CH ₂ C1 ₂ (1 mL). The resultant solution was stirred at room temperature for 4 hours. Water (100 mL) and CH ₂ C1 ₂ (200 mL) were added and the mixture was basified to pH-10 with solution of sodium hydroxide. The organic layer was separated, dried over MgSO ₄ and evaporated to dryness under reduced pressure. The residue was chromatographed on silica gel using hexane:EtOAc (7:3) as eluent to give the title compound of step G as a white semi-solid 313 mg, 48%. IR (nujol, cm ^-1 ): 1671.3 and 1723.0 (C=O) and 3364.4 (NH); ^! H NMR δ: 0.05-0.07 (qJH), 0.70-85 (mJH), 1.31- 1.36 (t,3H), 2.02-2.09 (m,2H), 3.01-3.08 (broad s,2H), 3.72-3.76 (sJH), 4.08-4J8

(qJH), 4.25-4.28 (m,2H), 6.45-6.52 (dJH), 7.18-7.20 (dJH), 7.97-8.02 (dJH), 8.82-

8.85 (dJH), 9.98 (sJH).

Step H: Preparation of Ethyl S-fΣ-chloro^-fluoro-S-fhexahydro-l.S-dioxo- cyclopropar3.4]-pyrτolori.2-climidazol-2(3H)-yllphenvπ-2-p ropenoate To a stirred solution of the compound of Step G, Example 2, (300.0 mg,

0.85 mmol) and triethylamine (1J8 mL, 8.5 mmol) in CH ₂ C1 ₂ (50 mL), under N ₂ , at room temperature, was added dropwise a solution of triphosgene (84.0 mg, 0.28 mmol) in CH ₂ C1 ₂ (10 mL) over a period of 15 minutes. The solution was stirred at room temperature for 10 minutes. A mixture of CH ₂ C1 ₂ (100 mL) and H ₂ O (50 mL) was added. The organic layer was separated, dried over MgSO ₄ and concentrated under reduced pressure to dryness. The residue was chromatographed on silica gel using 25% ethyl acetate in hexane as eluent. Fractions containing the title compound were combined and evaporated under reduce pressure to yield the title compound, a compound of the invention, as a white solid (84.0 mg), 26%; m.p. 154-156°C, IR (nujol, cm- ¹ ): 1720.4 (C=O); ^! H NMR δ: 0.61-0.63 (qJH), 1.32-1.36 (m,4H), 2.01-2.03

(mJH), 2J 1-2J8 (mJH), 3J2-3J8 (dJH), 4.18-4.28 (m,4H), 6.37-6.41 (dJH), 7.32- 7.35 (dJH), 7.59-7.62 (dJH), 7.94-7.99 (dJH).

EXAMPLE 3 Preparation of 2-r7-fluoro-3.4-dihydro-3-oxo-4-(2-propynyP-2H- 1 ,4-benzoxazin-6- ylltetrahydrocyclopropa-13.41pyrrolori.2-c1imidazole-1.3(2H. 5H)-dione Step A: Preparation of Ethyl f5-fluoro-2-nitrophenoxy acetate A stirred mixture of 5-fiuoro-2-nitrophenol (100.0 gm, 0.64 mol), ethyl bromoacetate (77.6 mL, 116.9 gm, 0.78 mol) and K ₂ CO ₃ (175.9 gm, 1.27 mol) in acetonitrile (800 mL), under N ₂ , was heated to reflux for 1 hour. The reaction mixture was filtered and the filtrate was washed with brine (200 mL), dried (MgSO ₄ ) and evaporated to dryness to give the title compound of Step A, Example 3, as an orange solid (150.0 gm), 97%; m.p. 37-39°C; ^! H NMR δ: 1.28-1.32 (t,3H), 4.23-4.29 (m,2H), 4.77 (s,2H), 6.64-6.68 (dJH), 6.79-6.83 (tJH), 7.96-8.01 (qJH). Step B: Preparation of 7-fluoro-2H-l .4-benzoxazin-3(4H ^' )-one

To a solution of the compound of Step A, Example 3, (50.0 gm) in THF (100 mL), under N ₂ , was carefully added 10% Palladium on carbon (catalytic amount). The reaction vessel was pressurized with H ₂ (45 psi) and shaken on a Parr hydrogenator for 4 hours. The reaction mixture was filtered through a Celite® bed and the filtrate was evaporated to dryness under vacuum. The residue was triturated with Et ₂ O to obtain the title compound of Step B as a white solid (32.0 gm), 93%; m.p. 200-202°C; ^! H NMR δ: 4.58 (s,2H), 6.79-6.90 (m,3H), 10.72 (sJH). Step C: Preparation of 7-fluoro-6-nitro-2H-l .4-benzoxazin-3(4HVone

To a stirred solution of the compound of Step B, Example 3, (48.9 gm, 292.8 mmol) and concentrated H ₂ SO ₄ (100 mL), under N ₂ , was added a 26 mL mixture of HNO ₃ (69-71%) and concentrated H ₂ SO ₄ dropwise at 25-35°C (ice-bath). The resultant solution was stirred at room temperature for 10 minutes. 400 mL of ice water was added portionwise to the solution at 0°C (ice-bath) followed by the addition of EtOAc (1.5 L). The organic layer was separated, dried (MgSO ₄ ) and evaporated to dryness to give the title compound of Step C as a tan solid (60.0 gm), 96%; m.p. 200- 202°C; IR (nujol, cm" ¹ ): 1703.5 (C=O); ^} H NMR δ: 4.79 (s,2H), 7.26-7.29 (dJH), 7.63-7.64 (dJH), 11.05 (sJH). Step D: Preparation of 7-fluoro-6-nitro-4-f 2-propynylV2H- 1.4-benzoxazin- 3(4HVone To a stirred solution of the compound of Step C, Example 3, (4.0 gm, 18.86 mmol) in DMF (100 mL), under N ₂ , at 5°C (ice-bath) was added sodium hydride (60% in mineral oil, 753.0 mg, 18.86 mmol) portionwise. When gas evolution stopped, propargyl bromide (80%, 2.24 gm, 18.86 mmol) was added dropwise. The dark solution was stirred at room temperature for 17 hours. The reaction was carefully poured into water (150 mL) and EtOAc (600 mL) was added. The organic layer was

separated and evaporated to dryness. The residue was chromatographed on silica gel using 25% of ethyl acetate in hexane as eluent. Fractions of compound of interest were combined and evaporated to dryness to yield the title compound of Step D, Example 3, as a yellow solid (2.7 gm), 57%; m.p. 105-107°C; IR (nujol, cm' ¹ ): 1695.3 (C=O) and 2120.6 (C≡C); ^! H NMR δ: 4.76-4.81 (m,4H), 6.91-6.94 (dJH), 7.97-7.98 (dJH), 2.35 (sJH).

Step E: Preparation of 6-amino-7-fluoro-4-(2-propynyP-2H-1.4-benzoxazin- 3(4HVone Iron powder (6.0 gm, 107.9 mmol) was added portionwise over a 1.5 hour period under N ₂ , at room temperature, to a stirred solution of the compound of Step D,

Example 3, (2.7 gm, 10.8 mmol) in methanol (100 mL). NaOAc (1.67 gm) was added and the mixture was filtered. The filtrate was basified to pH 9 using 50% NaOH. The mixture was filtered and the filtrate was evaporated to dryness. Flash chromatography yielded the title compound as a tan solid (300 mg), 13%; m.p. 132-134°C; IR (nujol, cm" ¹ ): 3342 and 3287.8 (NH ₂ ) and 2100 (C≡C).

Step F: Preparation of phenylmethyl 2-πT7-fluoro-3.4-dihydro-3-oxo-4-f2- propynyl)-2H- 1.4-benzoxazin-6-yllaminolcarbonyll- 1 -pyrrolidine- carboxylate A mixture of the compound of Step E, Example 3, (1.3 gm), CBZ protected (+/-)- 3-azabicyclo[3.1.0]hexane-2-carboxylic acid (2.3 gm), DCC (1.8 gm), DMAP (2.6 mg) in CH ₂ C1 ₂ (75 mL) was stirred at room temperature for 3 days. The reaction mixture was filtered and the filtrate was evaporated to dryness. Flash chromatography yielded the title compound of Step F as a white solid (1.41 gm), 51%; m.p. 72-74°C; IR (nujol, cm- ¹ ): 1691 (C=O) and 3285.9 (NH); ² H NMR δ: 0.21-0.25 (mJH), 0.83-0.85 (mJH), 1.62-1.68 (m,2H), 2.01-2.04 (mJH), 3.50-3.54 (mJH), 3.75-3.79 (dJH), 4.57-4.68 (m,3H), 5.07-5.09 (m,2H), 6.68-7.02 (dJH), 7.26-7.36 (m,7H), 8.30-8.32 (dJH) 8.82- 8.84 (sJH).

Step G: Preparation of N- r7-fluoro-3.4-dihydro-3-oxo-4-C2-propynyD-2H- 1.4- benzoxazin-6-yll-3-azabicyclor3.1.OIhexane-2-carboxamide To a solution of boron trifluoride etherate (1.57 gm, 10.8 mmol) and ethanethiol

(2.31 mL, 1.94 gm, 32.32 mmol) under Ν ₂ , at room temperature was added dropwise a solution of the compound of Step F, Example 3, (500.0 mg) in CH ₂ C1 ₂ (1 mL). The resultant clear solution was stirred at room temperature for 48 hours and the reaction was scrubbed with a bleach /50% NaOH / H ₂ O-20%. 30 mL of water was added dropwise at room temperature followed by CH ₂ C1 (30 mL). The aqueous layer was separated and basified to pH 10 using 50% NaOH. Additional 30 mL of CH ₂ C1 ₂ was added and the organic layer was separated, dried (MgSO ₄ ) and evaporated to dryness to

give the title compound of Step G as a white solid (200 mg), 57%; m.p. 196-198°C; IR (nujol, cm" ¹ ): 1676.0 (C=O), 3357.7 and 3301.7 (NH); ^! H NMR δ: 0.08-0.09 (mJH), 0.71-0.77 (mJH), 1.41-1.43 (mJH), 2.01-2.08 (mJH), 2J 1-2J7 (broad sJH), 2.31- 2.32 (mJH), 3.02 (s,2H), 3.72 (sJH), 4.61 (s,2H), 4.75-4.81 (dd,2H), 6.79-6.81 (dJH), 8.44-8.46 (dJH), 9.85 (broad sJH).

Step H: Preparation of 2-r7-fiuoro-3.4-dihydro-3-oxo-4-f2-propynylV2H- 1.4- benzoxazin-6-ylltetrahydrocyclopropar3.41-pyrrolon.2-climida zole- 1.3C2H.5HVdione A solution of triphosgene (57 mg) in CH ₂ C1 ₂ (1 mL) was added dropwise to a stirred solution of triethylamine (0.2 mL) and the compound of Step G, Example 3,

(190 mg) in CH ₂ Cl2 (50 mL) under N2 at room temperature. The solution was stirred at room temperature for 20 minutes. 30 mL of water was added. The organic layer was separated, dried (MgSO ₄ ) and evaporated to dryness. Flash chromatography yielded the title compound of Step H, a compound of the invention, as a white solid (127 mg), 62%; m.p. 217-219°C; IR (nujol, cm" ¹ ): 3253.6 and 2129.3 (C≡C), 1625 and 1715 (C=O).

^! H NMR δ: 0.61-0.64 (mJH), 1.22-1.31 (mJH), 2.01-2J 1 (mJH), 2J7-2.22 (mJH), 2.25 (sJH), 3J2-3J7 (ddJH), 4J7-4J8 (m,2H), 4.67-4.68 (s,4H), 6.84-6.93 (dJH), 7J l-7J4 (dJH).

EXAMPLE 4 Preparation of Methyl 2-chloro-4-fluoro-5-(hexahydro-1.3-dioxocyclo- propaf3.41pyrrolori.2-c1imidazol-2f3HVyl]benzoate Step A: Preparation of 5-amino-2-chloro-4-fluorobenzoic acid

A solution of the compound of Step A in Example 2 (25.0 gm) in acetic acid (100 mL), under N ₂ , was heated to reflux. The heat source was removed and iron powder (6.38 gm) was added portionwise. The resultant mixture was stirred at ambient temperature for 15 minutes. 200 mL of water was added followed by addition of 500 mL of ethyl acetate. The organic layer was separated, washed with brine (3 x 50 mL), dried over magnesium sulfate and evaporated to dryness to yield the title compound as a tan solid (14.4 gm), 67%; m.p. 105-107°C; IR (nujol, cm" ¹ ): 3396.9 and 3491.8 (NH ₂ ) and 1702.0 (C=O).

Step B: Preparation of Methyl 5-amino-2-chloro-4-fluorobenzoate

Thionyl chloride (18.09 gm) was added dropwise to a solution of the compound of Step A of Example 4 (10.0 gm) in methanol (100 mL) under N ₂ at 0°C (ice-bath). The ice-bath was removed and the solution was heated to reflux for 2 hours. The solution was cooled to room temperature and then poured slowly into water (300 mL). The aqueous solution was extracted with 500 mL ethyl acetate. The organic layer was separated and dried over magnesium sulfate. Evaporation to dryness followed by flash chromatography yielded the title compound as a tan solid (4.3 gm), 40%; m.p. 76-78°C; IR (nujol, cm- ¹ ): 3404.1, 3324.5, and 1706J; Η NMR δ: 3.87-3.91 (m,5H), 7.07-7.11 (dJH), 7.29-7.33 (dJH).

Step C: Preparation of Phenylmethyl 2-πT4-chloro-2-fluoro-5-(methoxy- carbonyl)phenvnaminol-carbonyll-3-azabicyclo-r3J .01hexane-3- carboxylate A solution of DCC (5.4 gm), DMAP (320 mg), CBZ protected (+/-)-3-azabicyclo[3J .0]hexane-2-carboxylic acid (6.8 gm) and the compound of Step B of Example 4 (4J gm) in CH ₂ C1 (150 mL), under N ₂ , was stirred at room temperature for 17 hours. The reaction mixture was filtered and the filtrate was evaporated to dryness. Flash chromatography yielded the title compound as a sticky white solid (4.8 gm), 53%; m.p. (semi-solid); IR (nujol, cm ^"1 ): 1708.6 and 3284.9; ^J H NMR δ: 1.21-1.24 (mJH), 0.72-0.89 (m,2H), 0.91-0.99 (t,3H), 1.21-1.37 (m,4H), 1.41-1.48 (m,2H), 1.66-1.71 (m,4H), 3.51-3.77 (m,2H), 4.31-4.37 (m,2H), 4.99-5J4 (m,2H), 7.24-7.39 (m,7H).

Step D: Preparation of Methyl 2-chloro-4-fluoro-5-IY2-pyrrolidinylcarbonyI')- aminolbenzoate To a solution of the compound of Step C of Example 4 (4.8 gm) in THF

(100 mL), under N ₂ , was carefully added 10% Palladium on carbon (catalytic amount). The reaction mixture was pressurized with H ₂ (45 psi) and shaken on a Paar hydrogenator for 2 hours. The mixture was filtered through a Celite® bed and the filtrate was evaporated to dryness. Flash chromatography yielded the title compound as a white solid (2.38 gm), 71%; m.p. 151-153°C.

Step E: Preparation of Methyl 2-chloro-4-fluoro-5-(hexahydro-1.3- dioxocvclopropar3.41pyrrolor 1.2-c1imidazol-2(3H)-yl benzoate A solution of triphosgene (135 mg) in CH ₂ C1 ₂ (2 mL) was added dropwise over a period of 10 minutes under N ₂ , at 0°C (ice-bath) to a stirred solution of the compound of Step D of Example 4 (300 mg) in CH ₂ Cl2 (30 mL). The resultant mixture was stirred an additional 10 minutes at 0°C (ice-bath). 50 mL of H ₂ O was added and the aqueous mixture was extracted with CH2CI2 (100 mL). The organic layer was separated and

dried over magnesium sulfate. The dried organic layer was evaporated under vacuum to dryness. The residue was chromatographed on silica gel using 25% of ethyl acetate in hexane as eluent. The fractions with the first eluting product were combined and evaporated under reduced pressure to yield the trans-isomer of the title compound, a compound of the invention, as a white solid (150 mg), 46%; m.p. 59-62°C; IR (nujol, cm- ¹ ): 1726.9; Η NMR δ: 0.61-0.68 (mJH), 1.22-1.29 (mJH), 2.01-2.04 (mJH), 2.14-2.19 (m,lH), 3.17-3.18 (dJH), 3.97 (s,3H), 4.18-4.21 (m,2H), 7.36-7.38 (dJH), 7.92-7.95 (dJH).

The fractions with the slower moving product were combined and evaporated under reduced pressure to yield the cis-isomer of the title compound, a compound of the invention, as a white solid (100 mg), 31%; m.p. 142-143°C. ^l R NMR (CDC1 ₃ , 400 MHz): δ 0.28-0.29 (mJH), 0.87-0.89 (mJH), 1.75-1.79 (mJH), 1.93-1.95 (mJH), 3.39-3.40 (ddJH), 3.92 (s,3H), 3.95-3.98 (dJH), 4.52-4.53 (dJH), 7.35-7.37 (dJH), 7.88-7.90 (dJH). EXAMPLE 5

Preparation of 3-rrr4-chloro-2-fluoro-5-( ^" 2-propynyloxy)phenyll-amino1carbonyll-3- azabicyclo[3J .01hexane-2-carboxylic acid Step A: Preparation of 1 -chloro-5-fluoro-4-isocvanato-2-(2-propynyloxy benzene To a stirred solution of 4-chloro-2 fluoro-5-[(2-propynyl)oxy] -aniline (5.0 gm) and triethylamine (5J gm) in CH ₂ C1 ₂ (100 mL) under N ₂ , at 10°C (ice-bath) was added triphosgene portionwise. The solution was heated to reflux for 5 hours. The solution was evaporated under vacuum and suspended in Et2θ (200 mL). The suspension was filtered and the filtrate evaporated to dryness to give the title compound as a white solid (4.68 gm), 83%; IR (nujol, cm" ¹ ): 3295 (OC) and 2257 (N=C=O). This crude product was used as such in the next reaction.

Step B: Preparation of 3-πT4-chloro-2-fluoro-5-f2-propynyloxy')phenyl ^" |- amino1carbonyll-3-azabicyclor3J .Olhexane-2-carboxylic acid A solution of the compound of Step A in Example 5 (3.0 gm) and the compound of Step E in Example 1 (1.69 gm) in CH2CI2 (100 mL), under N ₂ , was stirred at room temperature for 17 hours. The solution was evaporated to dryness. Flash chromatography yielded the title compound, a compound of the invention, as a white solid (1.2 g), 28%; m.p. 165-170°C; IR (nujol, cm" ¹ ): 2127 (C≡C), 1647 (C=O), 3293 and 3499.

The following Tables illustrate the compounds of the invention that are produced by the processes of the invention.

The following abbreviations are used in the Tables which follow. All alkyl groups are the normal isomers unless indicated otherwise.

n = normal Et = ethyl i = iso Pr = propyl

TABLE 1

Formula I wherein Q is Q- 1

TABLE 2

Formula I wherein Q is Q-5

Formula I wherein Q is Q-3

TABLE4

TABLE 5

Formula II wherein Q is Q- 1

TABLE 6

Formula II wherein Q is Q-5

TABLE 7

Formula HI wherein Q is Q- 1

TABLE 8

Formula IH wherein Q is Q-2

TABLE 9

Formula IV wherein Q is Q- 1

E ¹ R ² E ³ H H F H H Cl H H F H H F H H F H H F H H Cl H H F

Formulation/Utility

The compounds of Formulae I-IV are useful as herbicides in agriculture. To carry out this utility, any of the compounds of Formulae I-IV can generally be used in formulation with an agriculturally suitable carrier comprising a liquid or solid diluent and/or a surfactant wherein the formulation is consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Useful formulations include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels. Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films, and the like which can be water-dispersible ("wettable") or water- soluble. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further formulation.

The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.

Weight Percent

High Strength Compositions 90-99 0-10 0-2

Typical solid diluents are described in Watkins, et al., Handbook of Insecticide

Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity. Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones, N,N-dialkyltarates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and polyoxyethylene/polyoxypropylene block copolymers. Solid diluents include, for example, clays such as bentonite, montmorillinite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water,

N,N-dimethylformamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins, alkylbenzenes, alkylnaphthalenes, oils of olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4- methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.

Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Suspensions are usually prepared by wet- milling; see, for example, U.S. 3,060,084. Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.

For further information regarding the art of formulation, see U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138- 140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989. In the following Examples, all percentages are by weight and all formulations are worked up in conventional ways. Compound 23 refers to the compound listed in Index Table A hereinafter.

Example A High Strength Concentrate Compound 23 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%.

Example B Wettable Powder Compound 23 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.

Example C Granule

Compound 23 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; U.S.S. No.

25-50 sieves) 90.0%.

Example D Extruded Pellet

Compound 23 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%.

Tests results indicate that the compounds of Formulae I-IV are highly active preemergent and or postemergent herbicides and/or plant growth regulants. Many of them have utility for broad-spectrum pre- and/or postemergence weed control in areas where complete control of all vegetation is desired such as around fuel storage tanks, industrial storage areas, parking lots, drive-in theaters, around billboards and highway and railroad structures. Some of the compounds are useful for the control of selected grass and broadleaf weeds such as morningglory, cocklebur, velvetleaf, giant foxtail, barnyardgrass and lambsquarters, with tolerance to important agronomic crops which include but are not limited to barley, cotton, wheat, rape, sugarbeets, corn, soybeans, rice, and plantation crops including coffee, cocoa, oil palm, rubber, sugarcane, citrus, grapes, fruit trees, nut trees, banana, plantain, pineapple, conifers, e.g., loblolly pine, and turf species Kentucky bluegrass, St. Augustine grass, Kentucky fescue and bermudagrass. Those skilled in the art will appreciate that not all compounds are equally effective against all weeds. Alternatively, the subject compounds are useful to modify plant growth.

Compounds of Formulae I-IV can be used alone or in combination with other commercial herbicides, insecticides or fungicides. A mixture of one or more of the following herbicides with a compound of Formula I can be particularly useful for weed control. Examples of other herbicides with which compounds of this invention can be formulated are: acetochlor, acifluorfen, acrolein, 2-propenal, alachlor, ametryn, amidosulfiiron, ammonium sulfamate, amitrole, anilofos, asulam, atrazine, barban, benefin, bensulfuron methyl, bensulide, bentazon, benzofluor, benzoylprop, bifenox, bromacil, bromoxynil, bromoxynil heptanoate, bromoxynil octanoate, butachlor, buthidazole, butralin, butylate, cacodylic acid, 2-chloro-N,N-di-2-propenylacetamide, 2-

chloroallyl diethyldithiocarbamate, chloramben, chlorbromuron, chloridazon, chlorimuron ethyl, chlormethoxynil, chlornitrofen, chloroxuron, chlorpropham, chlorsulfuron, chlortoluron, cinmethylin, cinosulfuron, clethodim, clomazone, cloproxydim, clopyralid, calcium salt of methylarsonic acid, cyanazine, cycloate, cycluron, cyperquat, cyprazine, cyprazole, cypromid, dalapon, dazomet, dimethyl 2,3,5,6-tetrachloro-l,4-benzenedicarboxylate, desmedipham, desmetryn, dicamba, dichlobenil, dichlorprop, diclofop, diethatyl, difenzoquat, diflufenican, dimepiperate, dinitramine, dinoseb, diphenamid, dipropetryn, diquat, diuron, 2-methyl-4,6- dinitrophenol, disodium salt of methylarsonic acid, dymron, endothall, 5-ethyl dipropylcarbamothioate, esprocarb, ethalfluralin, ethametsulfuron methyl, ethofumesate, fenac, fenoxaprop, fenuron, salt of fenuron and trichloroacetic acid, flamprop, fluazifop, fluazifop-P, fluchloralin, flumesulam, flumipropyn, fluometuron, fluorochloridone, fluorodifen, fluoroglycofen, flupoxam, fluridone, fluroxypyr, fluzasulfuron, fomesafen, fosamine, glyphosate, haloxyfop, hexaflurate, hexazinone, imazamethabenz, imazapyr, imazaquin, imazamethabenz methyl, imazethapyr, imazosulfuron, ioxynil, isopropalin, isoproturon, isouron, isoxaben, karbutilate, lactofen, lenacil, linuron, metobenzuron, metsulfuron methyl, methylarsonic acid, monoammonium salt of methylarsonic acid, (4-chloro-2-methylphenoxy)acetic acid, 5,5'-dimethyl-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifl uoromethyl)-3,5- pyridinedicarbothioate, mecoprop, mefenacet, mefluidide, methalpropalin, methabenzthiazuron, metham, methazole, methoxuron, metolachlor, metribuzin, 1,2- dihydropyridazine-3,6-dione, molinate, monolinuron, monuron, monuron salt and trichloroacetic acid, monosodium salt of methylarsonic acid, napropamide, naptalam, neburon, nicosulfuron, nitralin, nitrofen, nitrofluorfen, norea, norflurazon, oryzalin, oxadiazon, oxyfluorfen, paraquat, pebulate, pendimethalin, perfluidone, phenmedipham, picloram, 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2- nitroacetophenone oxime-0-acetic acid methyl ester, pretilachlor, primisulfuron, procyazine, profluralin, prometon, prometryn, pronamide, propachlor, propanil, propazine, propham, prosulfalin, prynachlor, pyrazolate, pyrazon, pyrazosulfuron ethyl, quinchlorac, quizalofop ethyl, rimsulfuron, secbumeton, sethoxydim, siduron, simazine, l-(α,α-dimethylbenzyl)-3-(4-methylphenyl)urea, sulfometuron methyl, trichloroacetic acid, tebuthiuron, terbacil, terbuchlor, terbuthylazine, terbutol, terbutryn, thifensulfuron methyl, thiobencarb, tri-allate, trialkoxydim, triasulfuron, tribenuron methyl, triclopyr, tridiphane, trifluralin, trimeturon, (2,4-dichlorophenoxy)acetic acid, 4-(2,4- dichlorophenoxy)butanoic acid, vernolate, and xylachlor.

In certain instances, combinations with other herbicides having a similar spectrum of control but a different mode of action will be particularly advantageous for resistance management.

A herbicidally effective amount of the compounds of Formulae I-IV is determined by a number of factors. These factors include: formulation selected, method of application, amount and type of vegetation present, growing conditions, etc. In general, a herbicidally effective amount of a compound(s) of Formulae I-IV is applied at rates from about 0.01 to 20 kg ha with a preferred rate range of 0.02 to 10 kg/ha. One skilled in the art can easily determine application rates necessary for the desired level of weed control.

The following Tests demonstrate the control efficacy of the compounds of Formulae I-IV against specific weeds. The weed control afforded by the compounds is not limited, however, to these species. See Index Tables A-D for compound descriptions.

Index Table A

Formula I wherein Q is Q- 1

F OCH ₂ CH ₂ OCH ₂ CH ₃ Cl oil ^b

OCH(CH ₃ )CH ₂ C=CH Cl 51-53

OCH(CH ₂ CH ₃ )CH ₂ G≡CH Cl oil ^b

SCH[(CH ₂ ) ₄ CH ₃ ]C0 ₂ CH ₂ CH ₃ Cl oil ^b OCH[(CH ₂ ) ₄ CH ₃ ]C0 ₂ CH ₂ CH3 Cl oil ^b

^a This column indicates the stereochemistry of the compound. "Trans" and "Cis" is the relative orientation between the cyclopropyl ring and the imidazolinedione ring. "Mix" indicates that the compound is a mixture of diastereomers due to the remote chiral center on R ⁴ . A dash (--) indicates that the relative stereochemistry was not determined or the compound is a mixture of trans and cis. All compounds are racemic.

^b See Index Table D for ¹ HNMR data.

Index Table B

Formula I wherein Q is Q-5

Stereo ³ m.p. CO

204-206

82-85

71-73

75-77

155-157 180-182

^a This column indicates the stereochemistry of the compound. "Trans" and "Cis" is the relative orientation between the cyclopropyl ring and the imidazolinedione ring. A dash (--) indicates that the relative stereochemistry was not determined or the compound is a mixture of trans and cis. All compounds are racemic.

Index Table C

Formula π wherein Q is Q- 1

This column indicates the stereochemistry of the compound. "Trans" and "Cis" is the relative orientation between the cyclopropyl ring and the C0 ₂ R ²³ group. A dash (— ) indicates that the relative stereochemistry was not determined or the compound is a mixture of trans and cis. All compounds are racemic.

Index Table D

Cmpd No. Η NMR Data (CDC1-, solution) ³

3 δ: 0.18 (mJH), 0.82-0.85 (mJH), 1.37-1.40 (d,6H), 1.70-1.80

(m.lH), 1.90-1.99 (mJH), 3.31-3.40 (ddJH), 3.94-3.98 (dJH), 4.47-4.51 (m,2H), 6.79-6.82 (dJH), 7.25-7.28 (dJH).

12 δ: 0.59-0.63 (qJH), 1.19-1.23 (t,2H), 1.24-1.29 (mJH), 1.37-1.61

(m,5H), 2.12-2J8 (mJH), 3.11-3.18 (dJH), 3.47-3.49 (q,2H), 4.21-4.32 (m,4H), 7.31-7.36 (dJH), 7.52-7.59 (dJH).

13 δ: 0.59-0.62 (qJH), 1.20-1.25 (m,4H), 2.00-2.08 (mJH), 2J0-2.20

(mJH), 3.10-3.19 (dd,lH), 3.61-3.63 (q,2H), 3.80-3.84 (q,2H), 4.15-4J8 (m,4H), 6.90-6.94 (dJH), 7.29 (sJH).

20 δ: 0.49-0.69 (dqJH), 0.97-0.99 (tJH), 1J8-1.32 (m,3H), 1.21-1.32

(mJH), 1.61-1.9 (mJH), 2.08-2J9 (mJH), 3.0-3J9 (ddJH), 3.80-3.90 (mJH), 4.05-4.10 (mJH), 4.30-4.38 (mJH), 7.35-7.39 (dJH), 7.90-7.92 (dJH).

32 δ: 0.05-0.09 (mJH), 1.80-1.88 (qJH), 1.90-1.02 (mJH), 1J2-1J3

(t,3H), 1.56-1.59 (d,4H), 1.70-1.79 (mJH), 1.85-2.02 (m,2H), 3.32-3.39 (ddJH), 3.94-3.99 (dJH), 4.44-4.45 (dJH), 7.24-7.27 (dJH), 7.44-7.46 (dJH).

33 δ: 0.60-0.65 (qJH), 1.85-1.97 (m,3H), 1.35-1.36 (m,6H), 1.95-2.02

(mJH), 2.10-2J9 (mJH), 2.55-2.56 (mJH), 3.09-3J9 (dJH), 4.16 (sJH), 4J9-4.22 (mJH), 4.63-470 (tJH), 7.08-7.12 (tJH), 7.27-7.29 (dJH).

34 δ: 1.59- 1.65 (m, 1 H), 1.12- 1 J 7 (t,3H), 1.22- 1.32 (m, 1 H), 2.03-2.05

(m,3H), 2.10-2.19 (mJH), 3J0-3J9 (dJH), 4J6 (sJH), 4J8- 4.23 (mJH), 2.61-2.68 (tJH), 7.08-7J 1 (tJH), 7.27-7.30 (dJH).

38 δ: 0.61-0.64 (mJH), 1.00-1.05 (m,3H), 1.24-1.33 (mJH), 1.81-1.97

(m,2H), 2.04-2.05 (m,2H), 2.11-2.19 (mJH), 2.51-2.62 (m,2H), 3.12-3J8 (dJH), 4J6 (sJH), 4.19-4.22 (mJH), 4.27-4.30 (tJH), 6.92-6.98 (mJH), 7.27-7.29 (dJH).

39 δ: 0.59-0.62 (mJH), 0.85-0.89 (m,3H), 1.13-1J8 (t,3H), 1.30-1.33

(m,5H), 1.40-1.43 (mJH), 3J0-3.19 (dJH), 3.60-3.79 (m,2H), 4.03-4.21 (mJH), 7.30-7.36 (dJH), 7.52-7.58 (dJH).

40 δ: 0.59-0.62 (mJH), 0.85-0.92 (m,3H), 1.24-1.26 (mJH), 1.30-1.39

(mJH), 1.45-1.58 (m,2H), 1.98-2.08 (m,3H), 2.11-2.18 (mJH), 3.08-3.18 (dJH), 4J2-4.26 (mJH), 4.55-4.61 (mJH), 6.78-6.82 (m,lH), 7.22-7.24 (dJH).

^a -Η NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)- singlet, (d)-doublet, (t)-triplet, (q)-quartet, (m)-multiplet, (dd)-doublet of doublets, (dq)-doublet of quartets.

TEST A

Seeds of barley (Hordeum vulgare), barnyardgrass (Echinochloa crus-galli), bedstraw (Galium aparine), blackgrass (Alopecurus myosuroides), cheatgrass (Bromus secalinus), chickweed (Stellaria media), cocklebur (Xanthium pensylvanicum), corn (Zea mays), cotton (Gossypium hirsutum), crabgrass (Digitaria sanguinalis), downy brome (Bromus tectorum), giant foxtail (Setariafaberii), lambsquarters (Chenopodium

album), morningglory (Ipomoea hederacea), rape (Brassica napus), rice (Oryza sativa), sorghum (Sorghum bicolor), soybean (Glycine max), sugar beet (Beta vulgaris), velvetleaf (Abutilon theophrasti), wheat (Triticum aestivum), wild buckwheat (Polygonum convolvulus), wild oat (Avenafatua) and purple nutsedge (Cyperus rotundus) tubers were planted and treated preemergence with test chemicals formulated in a non-phytotoxic solvent mixture which includes a surfactant. At the same time, these crop and weed species were also treated with postemergence applications of test chemicals formulated in the same manner. Plants ranged in height from two to eighteen cm (one to four leaf stage) for postemergence treatments. Treated plants and controls were maintained in a greenhouse for twelve to sixteen days, after which all species were compared to controls and visually evaluated. Plant response ratings, summarized in Table A, are based on a scale of 0 to 10 where 0 is no effect and 10 is complete control. A dash (-) response means no test result.

Table A PREEMERGENCE COMPOUND

Rate 50 g/ha 3 4 5 6 8 10 11 12 14 17 18 19 20 21 22 24 25 26 29 30 31 33 34 35 36 42 43 44 45 46 47 49

Barley 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 - 0 5 3 0 0 0 2 0

Barnyardgrass 2 5 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 3 0 0 0 0 2 2 9 8 0 0 0 9 0

Bedstraw 0 3 4 4 - 3 2 5 4 0 9 0 0 0 0 0 0 0 5 0 0 6 9 9 9 10 10 0 0 0 10 0

Blackgrass 1 0 0 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 3 0 0 0 2 0 1 9 7 0 2 0 3 0

Cheatgrass _ _ _ _ _ _ _ _ _ _ _ o θ - - - - - - - - - - - - - - - - - - -

Chickweed 0 2 0 0 0 2 0 0 3 2 4 0 0 0 3 0 0 0 6 0 0 2 3 0 0 10 9 0 0 0 9 0

Cocklebur 0 0 0 0 3 0 0 0 3 0 0 0 0 0 0 0 0 0 3 0 - 3 3 0 3 10 5 0 0 0 6 0

Corn 0 0 0 0 0 2 0 2 0 0 0 0 0 0 0 0 0 0 2 0 0 2 2 0 0 9 5 0 0 0 8 0

Cotton 0 0 0 0 0 0 3 4 0 0 0 0 0 0 0 0 0 0 4 0 0 4 0 0 0 10 6 0 0 0 8 0

Crabgrass 2 0 3 3 2 6 0 1 2 0 2 0 0 0 3 0 0 0 2 0 0 3 8 5 8 10 8 0 0 0 8 0

Downy brome 0 2 0 0 0 1 0 0 0 0 2 - - 0 0 0 0 0 3 0 2 3 5 2 2 8 5 0 1 0 2 0

Giant foxtail 0 3 0 0 0 6 0 0 2 0 0 0 0 0 2 0 0 0 8 0 0 3 8 7 9 9 8 0 0 0 7 0 u

Lambsquarter 2 6 9 9 8 10 8 7 10 8 6 3 0 0 10 0 0 0 10 0 9 9 10 10 10 10 10 10 9 0 10 0

Morningglory 0 9 0 0 0 4 10 3 4 0 4 3 0 0 0 0 0 0 5 0 0 0 6 0 0 10 10 0 2 0 10 0

Nutsedge 0 0 0 0 0 0 0 0 - 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 - 6 - - 5 0 3 0

Rape 0 10 0 0 0 0 9 3 10 9 6 0 0 0 2 0 0 0 7 0 0 2 9 5 6 10 10 0 2 0 10 0

Rice 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 2 0 2 9 7 0 0 0 8 0

Sorghum 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 6 5 0 0 0 8 0

Soybean 0 0 0 0 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 3 2 0 7 6 0 0 0 6 0

Sugar beet 0 9 6 4 7 8 10 4 9 9 9 0 0 0 6 0 0 0 6 0 0 6 7 8 9 10 10 0 7 0 10 0

Velvetleaf 3 2 0 0 0 9 2 9 10 0 3 4 0 0 2 0 0 0 7 0 5 9 10 9 9 10 9 7 6 0 10 0

Wheat 0 2 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 3 0 0 0 0 1 1 6 6 0 0 0 3 0

Wild buckwheat 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6 0 0 0 0 0 0 10 5 0 0 0 2 0

Wild oat 0 0 0 0 0 1 0 0 0 0 2 0 0 0 0 0 0 0 4 0 0 5 6 1 3 9 9 0 0 0 6 0

TEST B

Seeds of barnyardgrass (Echinochloa crus-galli), cocklebur (Xanthium pensylvanicum), crabgrass (Digitaria sanguinalis), downy brome (Bromus tectorum), giant foxtail (Setariafaberii), morningglory (Ipomoea spp.), sorghum (Sorghum bicolor), velvetleaf (Abutilon theophrastϊ), and wild oat (Avenafatua) were planted into a sandy loam soil and treated preemergence or by soil drench, with test chemicals formulated in a non-phytotoxic solvent mixture which includes a surfactant. At the same time, these crop and weed species were also treated postemergence or sprayed to runoff, with test chemicals formulated in the same manner. Plants ranged in height from two to eighteen cm and were in the two to three leaf stage for the postemergence treatment. Treated plants and untreated controls were maintained in a greenhouse for approximately eleven days, after which all treated plants were compared to untreated controls and visually evaluated for injury. Plant response ratings, summarized in Table B, are based on a 0 to 10 scale where 0 is no effect and 10 is complete control. A dash (-) response means no test results.

The compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied to the soil surface before plant seedlings emerged (preemergence application), to water that covered the soil surface (flood application), and to plants that were in the one-to-four leaf stage (postemergence application). A sandy loam soil was used for the preemergence and postemergence tests, while a silt loam soil was used in the flood test. Water depth was approximately 2.5 cm for the flood test and was maintained at this level for the duration of the test.

Plant species in the preemergence and postemergence tests consisted of barnyardgrass (Echinochloa crus-galli), barley (Hordeum vulgare), bedstraw (Galium aparine), blackgrass (Alopecurus myosuroides), chickweed (Stellaria media), cocklebur (Xanthium pensylvanicum), corn (Zea mays), cotton (Gossypium hirsutum), crabgrass (Digitaria sanguinalis), downy brome (Bromus tectorum), giant foxtail (Setariafaberii), johnsongrass (Sorghum halpense), lambsquarters (Chenopodium album), morningglory (Ipomoea hederacea), pigweed (Amaranthus retroflexus), rape (Brassica napus), ryegrass (Iolium multiflorum), soybean (Glycine max), speedwell (Veronica persica), sugar beet (Beta vulgaris), velvetleaf (Abutilon theophrastϊ), wheat (Triticum aestivum), wild buckwheat (Polygonum convolvulus), and wild oat (Avenafatua). All plant species were planted one day before application of the compound for the preemergence portion of this test. Plantings of these species were adjusted to produce plants of appropriate size for the postemergence portion of the test. Plant species in the flood test consisted of rice (Oryza sativa), umbrella sedge (Cyperus dijformis), duck salad (Heteranthera limosa), barnyard 2 (Echinochloa crus-galli) and watergrass 2 (Echinocloa oryzicola) grown to the 1 and 2 leaf stage for testing.

All plant species were grown using normal greenhouse practices. Visual evaluations of injury expressed on treated plants, when compared to untreated controls, were recorded approximately fourteen to twenty one days after application of the test compound. Plant response ratings summarized in Table C, were recorded on a 0 to 100 scale where 0 is no effect and 100 is complete control. A dash (-) response means no test result.

Table C COMPOUND

Rate 125 g/ha 1 4 9 23 41 POSTEMERGENCE

Barley Igri - 35 30 55 95

Barnyard 2 20 40 10 100 70

Barnyardgrass - 40 80 95 95

Bedstraw - 70 0 100 100

Blackgrass - 50 0 80 65

Chickweed - 95 10 100 100

Cocklebur - 85 35 100 100

Corn - 30 25 35 90

Cotton - 100 95 100 100

Crabgrass - 35 25 85 95

Downy Brome - 35 20 85 100

Duck salad 0 0 0 50 0

Giant foxtail - 65 65 100 100

Italn. Rygrass - 30 20 95 100

Johnsongrass - 80 30 90 100

Lambsquarter - 70 90 100 100

Morningglory - 100 90 100 100

Rape - 100 100 100 100

Redroot Pigweed - 100 75 100 100

Rice 45 70 20 100 95

Soybean - 75 50 100 80

Speedwell - - 100 100

Sugar beet - 100 40 100 100

Umbrella sedge 0 0 0 50 0

Velvetleaf - 100 100 100 100

Watergrass 2 15 80 0 100 95

Wheat - 30 20 50 100

Wild buckwheat - 100 85 100 100

Wild oat - 30 20 75 95

Table C COMPOUND

Rate 125 g/ha 1 4 9 23 41 PREEMERGENCE

Barley Igri 0 10 50 70 80

Barnyardgrass 90 25 35 100 95

Bedstraw 100 15 10 100 100

Blackgrass 55 30 0 80 95

Chickweed 20 60 20 100 100

Cocklebur 0 30 25 85 100

Corn 10 0 20 50 55

Cotton 10 25 35 100 100

Crabgrass 90 50 70 100 100

Downy Brome 0 0 10 80 60

Giant foxtail 95 100 95 100 100

Italn. Rygrass 60 0 20 90 100

Johnsongrass 90 15 20 95 100

Lambsquarter 100 85 70 100 100

Morningglory 20 - 60 100 100

Rape 10 100 100 100 100

Redroot Pigweed 100 100 80 100 100

Soybean 30 30 10 40 95

Speedwell 100 100 90 100 100

Sugar beet 100 100 45 100 100

Velvetleaf 100 100 100 100 100

Wheat 0 0 10 65 100

Wild buckwheat 10 90 30 100 100

Wild oat 20 10 50 65 90

Table C COMPOUND

Rate 8 g/ha 2 18 22 29 33 34 35 36 42 43 POSTEMERGENCE

Barley Igri 45 25 20 45 35 55 40 40 25 30

Barnyard 2 20 0 0 0 40 35 0 25 100 0

Barnyardgrass 60 25 0 30 50 50 35 30 65 40

Bedstraw 100 25 0 35 55 95 50 65 80 60

Blackgrass 45 0 0 40 30 65 40 30 65 55

Chickweed 75 20 50 65 75 90 65 75 95 65

Cocklebur 90 40 50 80 90 90 10 70 100 85

Corn 50 10 10 20 20 15 20 20 50 25

Cotton 100 100 90 90 100 100 100 95 100 100

Crabgrass 70 15 0 15 20 20 10 15 65 30

Downy Brome 40 0 0 10 35 70 50 40 30 20

Duck salad 0 0 0 0 0 0 0 0 0 0

Giant foxtail 80 30 20 35 35 30 25 30 35 25

Italn. Rygrass 50 0 0 30 65 60 40 70 70 20

Johnsongrass 75 55 15 30 50 30 30 60 35 70

Lambsquarter 100 40 0 100 85 100 90 95 85 65

Morningglory 100 80 70 90 95 85 90 85 - 80

Rape 100 65 0 65 70 65 75 90 45 70

Redroot Pigweed 100 85 80 90 100 100 70 100 100 100

Rice 70 0 0 25 35 40 10 35 25 0

Soybean 90 50 40 40 40 80 35 60 80 70

Speedwell 100 100 40 95 100 95 65 95 100 95

Sugar beet 100 50 20 100 95 100 70 90 100 80

Umbrella sedge 0 0 0 0 0 0 0 0 0 0

Velvetleaf 100 100 100 100 95 100 100 100 100 100

Watergrass 2 10 0 25 0 25 10 - 40 10 0

Wheat 35 20 30 30 30 30 35 10 30 20

Wild buckwheat 100 0 30 - 100 100 65 90 100 90

Wild oat 40 10 0 55 40 65 45 60 45 30

TEST D

Seeds, rhizomes, or plant parts of alfalfa (Medicago sativa), annual bluegrass (Poa annua), bermudagrass (Cynodon dactyloή), broadleaf signalgrass (Brachiaria platyphylia), common purslane (Portulaca oleracea), common ragweed (Ambrosia artemisiifolia), dallisgrass (Paspalum dilatatum), field bindweed (Convolvulus arvensis), goosegrass (Eleusine indica), guineagrass (Panicum maximum), itchgrass (Rottboellia cochinchinensis), johnsongrass (Sorghum halepense), large crabgrass (Digitaria sanguinalis), peanut (Arachis hypoagaea), pitted morningglory (Ipomoea lacunosa), purple nutsedge (Cyperus rotundus), sandbur (Southern sandbur), smooth crabgrass (Digitaria ischaemum) were planted into greenhouse pots containing greenhouse planting medium. Each pot contained only one plant species.

The test compound was formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied preemergence and/or postemergence to the plants. Preemergence applications were made within one day of planting the seeds or plant parts. Postemergence applications were applied when the plants were in the two to four leaf stage (three to twenty cm). Untreated control plants and treated plants were placed in the greenhouse and visually evaluated for injury at 14 to 28 days after herbicide application. Plant response ratings, summarized in Table D, are based on a 0 to 100 scale where 0 is no injury and 100 is complete control. A dash (-) response indicates no test result.

Table D

Rate 0250 g/ha

PREEMERGENCE

Alfalfa Var.

Ann Bluegrass

Bermudagrass

Brdlf Sgnlgrass

Cmn Purslane

Cmn Ragweed

Dallisgrass

Field Bindweed

Goosegrass

Guineagrass

Itchgrass

Johnson grass

Large Crabgrass

Peanuts

Pit Morninglory

Purple Nutsedge

Sandbur Smooth Crabgras

Seeds of barnyardgrass (Echinochloa crus-galli), bindweed (Concolculus arvensis), black nightshade (Solanum ptycanthum dunaϊ), cassia (Cassia obtusifolia), cocklebur (Xanthium pensylvanicum), corn (Zea mays), cotton (Gossypium hirsutam), crabgrass (Digitaria spp.), fall panicum (Panicum dichotomiflorum), giant foxtail (Setariafaberii), green foxtail (Setaria viridis), jimsonweed (Datura stramonium), johnsongrass (Sorghum halepense), lambsquarter (Chenopodium album), morningglory (Ipomoea spp.), pigweed (Amaranthus retroflexus), prickly sida (Sida spinosa), ragweed (Ambrosia artemisiifolia), shattercane (Sorghum vulgare), signalgrass (Brachiaria platyphylla), smartweed (Polygonum pensylvanicum), soybean (Glycine max), sunflower (Helianthus annuus), velvetleaf (Abutilon theophrastϊ), wild proso (Pancium miliaceum), woolly cupgrass (Eriochloa villosa), yellow foxtail (Setaria lutescens) and purple nutsedge (Cyperus rotundus) tubers were planted into a matapeake sandy loam soil. These crops and weeds were grown in the greenhouse until the plants ranged in

height from two to eighteen cm (one to four leaf stage), then treated postemergence with the test chemicals formulated in a non-phytotoxic solvent mixture which includes a surfactant. Pots receiving preemergence treatments were planted immediatley prior to test chemical application. Pots treated in this fashion were placed in the greenhouse and maintained according to routine greenhouse procedures.

Treated plants and untreated controls were maintained in the greenhouse approximately 14-21 days after application of the test compound. Visual evaluations of plant injury responses were then recorded. Plant response ratings, summarized in Table E, are reported on a 0 to 100 scale where 0 is no effect and 100 is complete control.

TEST F Compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied to the soil surface before plant seedlings emerged (preemergence application) and to plants that were in the one-to-four leaf stage (postemergence application). A sandy loam soil was used for the preemergence test while a mixture of sandy loam soil and greenhouse potting mix in a 60:40 ratio was used for the postemergence test. Test compounds were applied within approximately one day after planting seeds for the preemergence test.

Plantings of these crops and weed species were adjusted to produce plants of appropriate size for the postemergence test. All plant species were grown using normal greenhouse practices. Crop and weed species include winter barley (Hordeum vulgare cv. 'Igri'), blackgrass (Alopecurus myosuroides), chickweed (Stellaria media), downy brome (Bromus tectorum), galium (Galium aparine), green foxtail (Setaria viridis), kochia (Kochia scoparia), lambsquarters (Chenopodium album), speedwell (Veronica persica), ryegrass (Lolium multiflorum), sugar beet (Beta vulgaris cv. 'USl'), sunflower (Helianthus annuus cv. 'Russian Giant'), spring wheat (Triticum aestivum cv. 'ERA'), windgrass (Apera spica-venti), winter wheat (Triticum aestivum cv. 'Talent'), wild buckwheat (Polygonum convolvulus), wild mustard (Sinapis arvensis) and wild oat (Avenafatua). Blackgrass, galium and wild oat were treated at two growth stages. The first stage

(1) was when the plants had two to three leaves. The second stage (2) was when the plants had approximately four leaves or in the initial stages of tillering. Treated plants and untreated controls were maintained in a greenhouse for approximately 21 to 28 days, after which all treated plants were compared to untreated controls and visually evaluated. Plant response ratings, summarized in Table F, are based upon a 0 to 100 scale where 0 is no effect and 100 is complete control. A dash response (-) means no test result.

Table F COMPOUND

Rate 125 g/ha 23 PREEMERGENCE

Blackgrass (2) 50

Chickweed 100

Downy brome 50

Galium (2) 100

Green foxtail 100

Kochia 80

Lambsquarters 100

Ryegrass 75

Speedwell 100

Wheat (Spring) 70

Wheat (Winter) 35

Wild buckwheat 100

Wild mustard 100

Wild oat (2) 70

Windgrass 100 Winter Barley 20

Table F COMPOUND

Rate 31 g/ha 23 PREEMERGENCE

Blackgrass (2) 30

Chickweed 40

Downy brome 10

Galium (2) 100

Green foxtail 100

Kochia 50

Lambsquarters 100

Ryegrass 45

Speedwell 100

Wheat (Spring) 10

Wheat (Winter) 0

Wild buckwheat 85

Wild mustard 100

Wild oat (2) 35

Windgrass 100 Winter Barley 0