The present invention relates to novel herbicidal cyclohexanedione compounds, to processes for their preparation, to herbicidal compositions which comprise the novel compounds, and to their use for controlling weeds.

Herbicidal cyclic dione compounds substituted by a phenyl which has various substituents are disclosed in, for example, W02008/110308, WO2010/052161 , WO2010/066780, WO2012/069008 WO2013/079672, WO2013/079708 and WO2015/0401 14. The present invention relates to novel herbicidal cyclohexanedione derivatives with improved properties.

Thus, according to the present invention there is provided a compound of Formula (I)

wherein

W is a bond, -CH ₂ -, O, N-H or N-CH ₃ ;

Y is O or N-R ⁴ ;

Z is a bond, -CH ₂ -, O, N-H or N-CH ₃ ; wherein W and Z are not both -CH ₂ - and are not both bonds; wherein when Y is O then R ¹ is a 5 or 6 membered heteroaryl which comprises one or two nitrogen heteroatoms, said heteroaryl optionally substituted by one or two R ¹⁵ substituents; and wherein when Y is N-R ⁴ then R ¹ is 1-propynyl or a 5 or 6 membered heteroaryl which comprises one or two nitrogen heteroatoms, said heteroaryl optionally substituted by one or two R ¹⁵ substituents with the proviso that when R ¹ is 1-propynyl then R ⁴ is not Ci-C4alkyl or Ci-C4alkoxy-;

R ² is methyl, ethyl, methoxy or chloro;

R ³ is selected from the group consisting of methyl, ethyl, methoxy and chloro;

R ⁴ is selected from the group consisting of Ci-C4alkyl, Ci-C4alkoxy-, Ci- C4haloalkyl, -C(=0)Ci-C ₄ alkyl, -C(=0)Ci-C ₄ haloalkyl, -S(0) _n Ci-C ₆ alkyl, - S(0)nCi-C ₆ haloalkyl, -S(0)n-(CH ₂ ) _n -C3-C6cycloalkyl, -S(0) _n C(R ¹¹ )R ¹² R ¹³ , - C(0)H, -C(0)-(CH ₂ ) _n -C ₃ -C ₆ cycloalkyl, -C(0)C(R ¹¹ )R ¹² R ¹³ , -C(0)C ₂ -C ₄ alkenyl, - C(O)(CR ⁹ R ¹⁰ )CN, -C(O)(CR ⁹ R ¹⁰ )(CR ⁹ R ¹⁰ )CN, -C(0)CH ₂ C(0)-Ci-C ₆ alkyl, - C(0)CH ₂ 0C(0)-Ci-C6alkyl, -C(0)OCi-C ₆ alkyl, -C(0)OCi-C ₆ haloalkyl, - C(0)(CH ₂ ) _n S(0) _n C ₁ -C ₆ alkyl -C(0)C ₁ -C ₃ alkoxyC ₁ -C ₆ alkyl, -C(0)Ci- C ₃ alkoxyC ₂ -C ₆ alkenyl, -C(0)Ci-C ₃ alkoxyC ₂ -C ₆ alkynyl, -C(0)Ci-C ₃ alkoxyCi- Cehaloalkyl, -C(0)Ci-C ₃ alkoxyC ₃ -C ₆ cycloalkyl, -C(0)OCi-C ₃ alkoxyCi-C ₆ alkyl,

phenyl, -C(0)-(CH ₂ ) _n -phenyi, -S(0) _n -(CH ₂ ) _n -phenyi, -heterocyclyl, -C(O)- (CH ₂ ) _n -heterocyclyl, -C(0)(CH ₂ ) _n O-(CH ₂ ) _n -heterocyclyl, -S(0) _n -(CH ₂ ) _n - heterocyclyl, wherein each heterocyclyl is a 5- or 6- membered heterocyclyl which may be aromatic, saturated or partially saturated and can contain from 1 to 4 heteroatoms each independently selected from the group consisting of oxygen, nitrogen and sulphur, and wherein said heterocyclyl or phenyl groups are optionally substituted by one, two or three substituents independently selected from the group consisting of C Csalkyl, CrCshaloalkyl, CrCsalkoxy, C ₂ -C3alkenyl, C ₂ -C3alkynyl, halogen, cyano and nitro;

R ⁵ is independently selected from the group consisting of hydrogen and C1-C6 alkyl;

R ⁶ is selected from the group consisting of hydrogen, CrCealkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, CrCehaloalkyl, hydroxyl-, CrCealkoxy, C3-C6 cycloalkyl, , -Ci- C ₄ alkoxyCrC ₆ alkyl, -Ci-CsalkoxyCrCehaloalkyl, -(CR ⁹ R ¹⁰ )Ci-C ₆ haloalkyl, - (CR ⁹ R ¹⁰ )C(O)NR ⁵ R ⁵ , phenyl, -pyridyl, wherein the phenyl and pyridyl are optionally substituted by one, two or three substituents independently selected from the group consisting of C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ alkoxy, C ₂ -C ₃ alkenyl, C ₂ -C ₃ alkynyl, halogen, cyano and nitro; or

R ⁵ and R ⁶ together form -CH ₂ CH ₂ OCH ₂ CH ₂ -; and

R ⁷ is selected from the group consisting of hydrogen and C ₁ -C ₆ alkyl;

R ⁸ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₃ -C ₆ cycloalkyl, phenyl, -pyridyl, wherein the phenyl and pyridyl are optionally substituted by one, two or three substituents independently selected from the group consisting of C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ alkoxy, C ₂ -C ₃ alkenyl, C ₂ -C ₃ alkynyl, halogen, cyano and nitro;

R ⁹ is hydrogen or methyl;

R ¹⁰ is hydrogen or methyl; or

R ⁹ and R ¹⁰ together form -CH ₂ CH ₂ -; and

R ¹¹ is hydrogen or methyl;

R ¹² is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, hydroxyl and C ₁ -C ₆ alkoxy-;

R ¹³ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, hydroxyl and C ₁ -C ₆ alkoxy; or

R ¹² and R ¹³ together form -CH ₂ -X-CH ₂ -; and

X is selected from the group consisting of O, S and N-R ¹⁴ ;

R ¹⁴ is selected from the group consisting of hydrogen, C ₁ -C ₃ alkyl and C ₁ -C ₃ alkoxy-; R ^{1 5} is independently selected from the group consisting of C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, cyano and halogen;

R ^{1 6} is hydrogen or CrCealkyl; and

R ¹⁷ is selected from the group consisting of hydrogen, CrCealkyl, C ₃ - Cecycloalkyl, CrCe alkoxy-CrC ₃ alkyl-,-C(0)CrCealkyl, -C(0)OCrCealkyl and CH ₂ CN; or

R ^{1 6} and R ^{1 7} together form -CH2CH2OCH2CH2-, -CH ₂ CH2S(0)2CH ₂ CH2-;

R ^{1 8} is hydrogen or CrCealkyl;

R ¹⁹ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₃ -Cecycloalkyl, phenyl, -pyridyl, wherein the phenyl and pyridyl are optionally substituted by one, two or three substituents independently selected from the group consisting of C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ alkoxy, C ₂ -C ₃ alkenyl, C ₂ -C ₃ alkynyl, halogen, cyano and nitro;

R ²⁰ is selected from the group consisting of CrCealkyl, CrCehaloalkyl, Cr Cealkoxy-, CrCehaloalkoxy, -NR ²¹ R ²² , phenyl and -pyridyl, wherein the phenyl and pyridyl are optionally substituted by one, two or three substituents independently selected from the group consisting of C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ alkoxy, C ₂ -C ₃ alkenyl, C ₂ -C ₃ alkynyl, halogen, cyano and nitro;

R ²¹ is selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, CrCealkoxyCrCsalkyl-, C ₃ -C ₆ cycloalkyl, CrCehaloalkyl- and Cr Cehaloalkoxy-, -C(0)CrCealkyl, phenyl, -pyridyl, wherein the phenyl and pyridyl are optionally substituted by one, two or three substituents independently selected from the group consisting of C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ alkoxy, C ₂ -C ₃ alkenyl, C ₂ -C ₃ alkynyl, halogen, cyano and nitro;

R ²² is hydrogen or CrCealkyl; or

R ²¹ and R ²² together form -CH ₂ CH ₂ OCH ₂ CH ₂ -; R ²³ is selected from the group consisting of hydrogen, CrCealkyl, C-i- Cehaloalkyl, C-i-Cealkoxy- and Ci-C ₆ haloalkoxy-;

R ²⁴ is selected from the group consisting of hydrogen, CrCealkyl, Cr C ₆ alkoxyCrC ₃ alkyl-, C ₃ -Cecycloalkyl, -CH ₂ CN, tetrahydropyranyl-, phenyl and -pyridyl, wherein the phenyl and pyridyl are optionally substituted by one, two or three substituents independently selected from the group consisting of Cr Csalkyl, CrCshaloalkyl, CrCsalkoxy, C ₂ -C ₃ alkenyl, C ₂ -C ₃ alkynyl, halogen, cyano and nitro;

R ²⁵ is hydrogen or CrCe alkyl;

R ²⁶ is hydrogen or CrCe alkyl; and

G is selected from the group consisting of hydrogen, -(Chb R ³ , -C(0)-R ^a , - C(0)-(CR ^c R ^d ) _n -0-R ^b , -C(0)-(CR ^c R ^d ) _n -S-R ^b , -C(0)NR ^a R ^a , -S(0) ₂ -R ^a and Cr Cealkoxy-CrCsalkyl-;

R ^a is independently selected from the group consisting of hydrogen, Cr Cealkyl, CrCshaloalkyl, C ₂ -Csalkenyl, C ₂ -Cealkynyl, C ₃ -Cecycloalkyl, heterocyclyl and phenyl wherein said heterocyclyl and phenyl groups are optionally substituted by one, two or three substituents independently selected from the group consisting of CrCealkyl, CrCshaloalkyl, CrCsalkoxy, C ₂ -C ₃ alkenyl, C ₂ -C ₃ alkynyl, halogen, cyano and nitro;

R ^b is selected from the group consisting of CrCealkyl, CrCshaloalkyl, C ₂ - Csalkenyl, C ₂ -Csalkynyl, C ₃ -C ₆ cycloalkyl, heterocyclyl and phenyl wherein said heterocyclyl and phenyl groups are optionally substituted by one, two or three substituents independently selected from the group consisting of Cr Cealkyl, CrCshaloalkyl, CrCsalkoxy, C ₂ -Csalkenyl, C ₂ -Csalkynyl, halogen, cyano and nitro;

R ^c is hydrogen or C ₁ -C ₃ alkyl;

R ^d is hydrogen or C ₁ -C ₃ alkyl; and n is independently 0, 1 or 2; or an agriculturally acceptable salt thereof.

Alkyl groups (e.g CrCealkyl) include, for example, methyl (Me, CH ₃ ), ethyl (Et, C2H5), n-propyl (n-Pr), isopropyl (/-Pr), n-butyl (n-Bu), isobutyl (/- Bu), sec-butyl (s-Bu) and tert- butyl (f-Bu).

Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (£)- or (Z)-configuration. Examples are vinyl, allyl and propargyl. Alkenyl and alkynyl moieties can contain one or more double and/or triple bonds in any combination.

Halogen (or halo) encompasses fluorine, chlorine, bromine or iodine. The same correspondingly applies to halogen in the context of other definitions, such as haloalkyl.

Haloalkyl groups (e.g CrCehaloalkyl) are, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2- trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 , 1 -difluoro-2,2,2- trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl, heptafluoro-n-propyl and perfluoro-n-hexyl.

Alkoxy groups (e.g Ci-C4alkoxy-) are, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy and ethoxy.

Alkoxyalkyl groups (e.g Ci-Csalkoxy-CrCsalkyl-) includes, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n- propoxyethyl, isopropoxymethyl or isopropoxyethyl.

Cycloalkyl groups (e.g C3-C6cycloalkyl-) include, for example cyclopropyl (c- propyl, c-Pr), cyclobutyl (c-butyl, c-Bu), cyclopentyl (c-pentyl) and cyclohexyl (c-hexyl) and may be substituted or unsubstituted as indicated. CrC ₆ alkyl-S- (alkylthio) is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

Ci-C ₆ alkyl-S(0)- (alkylsulfinyl) is, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

CrC ₆ alkyl-S(0) ₂ - (alkylsulfonyl) is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

Heterocyclyl, unless stated otherwise, is a 5- or 6- membered heterocyclyl which may be aromatic, saturated or partially saturated and can contain from 1 to 4 heteroatoms each independently selected from the group consisting of oxygen, nitrogen and sulphur.

The invention also relates agriculturally acceptable salts of the compounds of Formula (I). Such salts include those which are able to form with amines, alkali metal and alkaline earth metal bases or quaternary ammonium bases. Among the alkali metal and alkaline earth metal hydroxides as salt formers, special mention should be made of the hydroxides of lithium, sodium, potassium, magnesium and calcium, but especially the hydroxides of sodium and potassium. The compounds of Formula (I) according to the invention also include hydrates which may be formed during the salt formation.

Examples of amines suitable for ammonium salt formation include ammonia as well as primary, secondary and tertiary CrCisalkylamines, Ci- C4hydroxyalkylamines and C2-C4alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine, isopropylamine, the four butylamine isomers, n- amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine, ethylheptylamine, ethyloctylamine, hexylheptylamine, hexyloctylamine, dimethylamine, diethylamine, di- n-propylamine, diisopropylamine, di-n-butylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, ethanolamine, n-propanolamine, isopropanolamine, A/./V-diethanolamine, /V-ethylpropanolamine, /V-butylethanolamine, allylamine, n-but-2-enylamine, n-pent-2-enylamine, 2,3-dimethylbut-2-enylamine, dibut-2-enylamine, n-hex-2-enylamine, propylenediamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutyla ine, tri-sec-butylamine, tri-n-amylamine, methoxyethylamine and ethoxyethylamine; heterocyclic amines, for example pyridine, quinoline, isoquinoline, morpholine, piperidine, pyrrolidine, indoline, quinuclidine and azepine; primary arylamines, for example anilines, methoxyanilines, ethoxyanilines, o-, m- and p-toluidines, phenylenediamines, benzidines, naphthylamines and o-, m- and p-chloroanilines; but especially triethylamine, isopropylamine and diisopropylamine.

In one embodiment of the present invention R ¹ is 1-propynyl.

In another embodiment of the present invention R ¹ is phenyl optionally substituted by one or two R ¹⁵ substituents, e.g selected from the group consisting of cyano, chloro and fluoro.

In another embodiment of the present invention R ¹ is a 5 or 6 membered heteroaryl which comprises one or two nitrogen heteroatoms, said heteroaryl optionally substituted by one or two R ¹⁵ substituents, e.g selected from the group consisting of cyano, chloro and fluoro. In a preferred embodiment, said heteroaryl is selected from the group consisting of pyridyl, pyrimidinyl, and pyrazolyl.

In one embodiment of the present invention R ² is preferably methyl.

In one embodiment of the present invention R ³ is methyl.

In one embodiment of the present invention, W is O and Z is -CH2-.

In another embodiment of the present invention, W is O and Z is a bond.

In another embodiment of the present invention, W is -CH2- and Z is a bond.

In another embodiment of the present invention, W is NH or NCH ₃ , and Z is -

CH ₂ -. In another embodiment of the present invention, W is a bond and and Z is N-

H or NCHs.

In one embodiment of the present invention R ⁴ is -C(=0)Ci-C ₃ alkyl (e.g - C(C=0)methyl, -C(C=0)ethyl, -C(C=0)/-propyl).

In another embodiment of the present invention, R ⁴ is -C(=0)Ci-C ₃ haloalkyl, more preferably -C(=0)C ₁ -C ₂ fiuoroalkyl e.g -C(=0)CH ₂ F, -C(=0)CHF ₂ , -C(=0)CF ₃ ).

In one embodiment of the present invention, R ⁴ is -S(0) _n Ci-C ₆ alkyl especially -S(0) ₂ methyl or -S(0) ₂ ethyl

In another embodiment R ⁴ is -S(0) _n Ci-C ₆ haloalkyl, for example - S(0) ₂ chloromethyl.

In another embodiment R ⁴ is -S(0) _n -(CH ₂ ) _n -C ₃ -C ₆ cycloalkyl, for example - S(0) ₂ -(CH ₂ )-c-propyl.

In another embodiment of the present invention, R ⁴ is -C(0)OCi-C ₆ alkyl, especially -C(0)-0-methyl.

In another embodiment of the present invention, R ⁴ is -S(0) _n C(R ¹¹ )R ¹² R ¹³ or - C(0)C(R ¹¹ )R ¹² R ¹³ wherein R ¹¹ is hydrogen or methyl and R ¹² R ¹³ taken together are - CH ₂ OCH ₂ - (oxetan-3-yl).

In another embodiment of the present invention, R ⁴ is -C(0)-(CH ₂ ) _n -C ₃ - Cecycloalkyl, for example -C(0)-c-propyl or -C(0)-(CH ₂ )-c-propyl.

In another embodiment of the present invention, R ⁴ is -C(O)(CR ⁹ R ¹⁰ )CN, for example -C(0)CH ₂ CN, -C(0)CH(CH ₃ )CN or -C(0)C(CH ₃ ) ₂ CN.

In another embodiment of the present invention, R ⁴ is -C(0)(CH ₂ ) _n S(0) _n Ci- Cealkyl, for example -C(0)CH ₂ S(0) ₂ methyl.

In another embodiment of the present invention, R ⁴ is -C(0)Ci-C ₃ alkoxyCr Cealkyl, for example -C(0)CH ₂ CH ₂ -0-CH ₃ or-C(0)CH(CH ₃ )-0-CH3. In another embodiment of the present invention, R ⁴ is -C(0)NR ⁵ R ⁶ , especially wherein R ⁵ is hydrogen and R ⁶ is C1-C6 alkyl e.g f-butyl.

In another embodiment of the present invention, R ⁴ is -C(0)-(CH2)n- NR ⁷ C(0)R ⁸ , for example -C(0)-(CH ₂ )-NR ⁷ C(0)R ⁸ or -C(0)NR ⁷ C(0)R ⁸ , for example - C(0)NHC(0)-f-butyl.

In another embodiment of the present invention, R ⁴ is selected from the group consisting of -phenyl, -C(0)-phenyl, -S(0) _n phenyl wherein each phenyl is optionally substituted as defined previously.

In another embodiment of the present invention R ⁴ is heterocyclyl, -C(O)- heterocyclyl or -S(0) _n -heterocyclyl. In another embodiment, each aforementioned heterocyclyl is an aromatic heterocyclyl (i.e heteroaryl), more preferably selected from the group consisting of furanyl, pyrrolyl, thiophenyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyranyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazolyl more preferably selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl and pyrazinyl each of which is optionally substituted as defined previously. In another embodiment, each aforementioned heterocyclyl is a partially saturated heterocyclyl, more preferably selected from the group consisting of imidazolinyl, isoxazolinyl and thiazolinyl each of which is optionally substituted as defined previously. In another embodiment, each aforementioned heterocyclyl is a saturated heterocyclyl more preferably selected from the group consisting of morpholinyl, tetrahydrofuryl and tetrahydropyranyl each of which is optionally substituted as defined previously.

In one embodiment of the present invention, G is selected from the group consisting of hydrogen, CrCsalkyl (e.g methyl, ethyl, n-propyl, /-propyl, n-butyl, f-butyl, -C2-Csalkenyl (e.g vinyl), C2-Csalkynyl (e.g propargyl), -C(0)Ci-Csalkyl (more preferably -C(0)Ci-C ₆ alkyl e.g -C(0)/-propyl and -C(O)f-butyl) and -C(0)-0-Ci- Csalkyl (more preferably -C(0)-0-Ci-C ₆ alkyl e.g -C(O)-O-methyl). In a preferred embodiment, G is hydrogen.

Depending on the nature of the substituents, compounds of Formula (I) may exist in different isomeric forms. When G is hydrogen, for example, compounds of Formula (I) may exist in different tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions. Also, when substituents contain double bonds, cis- and trans- isomers can exist. These isomers, too, are within the scope of the claimed compounds of the Formula (I). Compounds of Formula (I) may contain asymmetric centres and may be present as a single enantiomer, pairs of enantiomers in any proportion or, where more than one asymmetric centre are present, contain diastereoisomers in all possible ratios. Typically one of the enantiomers has enhanced biological activity compared to the other possibilities.

The compounds of Formula (I) according to the invention can be used as herbicides by themselves, but they are generally formulated into herbicidal compositions using formulation adjuvants, such as carriers, solvents and surface- active agents (SFAs). Thus, the present invention further provides a herbicidal composition comprising a herbicidal compound according to any one of the previous claims and an agriculturally acceptable formulation adjuvant. The composition can be in the form of concentrates which are diluted prior to use, although ready-to-use compositions can also be made. The final dilution is usually made with water, but can be made instead of, or in addition to, water, with, for example, liquid fertilisers, micronutrients, biological organisms, oil or solvents.

The herbicidal compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, compounds of Formula (I) and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.

The compositions can be chosen from a number of formulation types, many of which are known from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. These include dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of Formula (I). Dustable powders (DP) may be prepared by mixing a compound of Formula (I) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of Formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of Formula (I) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of a compound of Formula (I) and one or more powdered solid diluents or carriers, or from pre formed blank granules by absorbing a compound of Formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of Formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compound of Formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of Formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as Cs-Cio fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment.

Preparation of an EW involves obtaining a compound of Formula (I) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of Formula (I) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water- soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil- in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of Formula (I). SCs may be prepared by ball or bead milling the solid compound of Formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of Formula (I) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.

Aerosol formulations comprise a compound of Formula (I) and a suitable propellant (for example n-butane). A compound of Formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.

Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of Formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of Formula (I) and they may be used for seed treatment. A compound of Formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.

The composition may include one or more additives to improve the biological performance of the composition, for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of Formula (I). Such additives include surface active agents (SFAs), spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of Formula

(I)·

Wetting agents, dispersing agents and emulsifying agents may be SFAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltri methyl ammonium bromide), imidazolines and amine salts.

Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di-/sopropyl- and tri-/sopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates.

Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.

Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

The herbicidal compounds of present invention can also be used in mixture with one or more additional herbicides and/or plant growth regulators. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen-sodium), aclonifen, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, bensulfuron (including bensulfuron- methyl), bentazone, bicyclopyrone, bilanafos, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butafenacil, carfentrazone (including carfentrazone- ethyl), cloransulam (including cloransulam- methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clacyfos, clethodim, clodinafop (including clodinafop- propargyl), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl), 2,4-D (including the choline salt and 2- ethylhexyl ester thereof), 2,4-DB, desmedipham, dicamba (including the aluminium, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts thereof) diclosulam, diflufenican, diflufenzopyr, dimethachlor, dimethenamid-P, diquat dibromide, diuron, epyrifenacil, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P- ethyl), fenoxasulfone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop (including fluazifop-P- butyl), flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam, flumioxazin, fluometuron, flupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), fomesafen, foramsulfuron, glufosinate (including the ammonium salt thereof), glyphosate (including the diammonium, isopropylammonium and potassium salts thereof), halauxifen (including halauxifen-methyl), haloxyfop (including haloxyfop- methyl), hexazinone, hydantocidin, imazamox, imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron-methyl- sodium), iofensulfuron (including iofensulfuron-sodium), ioxynil, isoproturon, isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methiozolin, metolachlor, metosulam, metribuzin, metsulfuron, napropamide, nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, prometryne, propanil, propaquizafop, propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil, pyraflufen (including pyraflufen- ethyl), pyrasulfotole, pyridate, pyriftalid, pyrimisulfan, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quizalofop (including quizalofop-P-ethyl and quizalofop-P- tefuryl), rimsulfuron, saflufenacil, sethoxydim, simazine, S-metalochlor, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetflupyrolimet, thiencarbazone, thifensulfuron, tiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr,

trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazin,

trifluralin, triflusulfuron, 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl - 3,6-dihydropyrimidin-1 (2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, 4-hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2- pyridyl]imidazolidin-2-one, 4-hydroxy-1 ,5-dimethyl-3-[4-(trifluoromethyl)-2- pyridyl]imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2- pyridyl]imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2- pyridyl]imidazolidin-2-one, 4-hydroxy-1 ,5-dimethyl-3-[1 -methyl-5- (trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one, (4R)1-(5-tert-butylisoxazol-3-yl)-4- ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one, 3-[2-(3,4-dimethoxyphenyl)-6-methyl- 3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1]octane-2,4-dione, 2-[2-(3,4- dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5-met hyl-cyclohexane-1 ,3- dione, 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4- carbonyl]cyclohexane-1 ,3-dione, 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo- pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1 ,3-dione, 6-[2-(3,4- dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-2,2,4 ,4-tetramethyl- cyclohexane-1 ,3,5-trione, 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4- carbonyl]-5-ethyl-cyclohexane-1 ,3-dione, 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo- pyridazine-4-carbonyl]-4,4,6,6-tetramethyl-cyclohexane-1 ,3-dione, 2-[6-cyclopropyl-2- (3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5-methyl- cyclohexane-1 ,3-dione,

3-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine -4- carbonyl]bicyclo[3.2.1]octane-2,4-dione, 2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3- oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1 ,3-dione, 6-[6-cyclopropyl-2- (3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-t etramethyl- cyclohexane-1 ,3,5-trione, 2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-

4-carbonyl]cyclohexane-1 ,3-dione, 4-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo- pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3 ,5-dione, 4-[6- cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbo nyl]-2, 2,6,6- tetramethyl-tetrahydropyran-3,5-dione, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1 H- indol-6-yl)pyridine-2-carboxylic acid (including agrochemically acceptable esters thereof, for example, methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1 H-indol-6- yl)pyridine-2-carboxylate, prop-2-ynyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1 H-indol- 6-yl)pyridine-2-carboxylate and cyanomethyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro- 1 H-indol-6-yl)pyridine-2-carboxylate), 3-ethylsulfanyl-N-(1 ,3,4-oxadiazol-2-yl)-5- (trifluoromethyl)-[1 ,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-

(isopropylsulfanylmethyl)-N-(5-methyl-1 ,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)- [1 ,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfonylmethyl)-N-(5-methyl- 1 ,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1 ,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(ethylsulfonylmethyl)-N-(5-methyl-1 ,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-

[1 ,2,4]triazolo[4,3-a]pyridine-8-carboxamide, ethyl 2-[[3-[[3-chloro-5-fluoro-6-[3- methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridy l]oxy]acetate, 6-chloro-4- (2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one , 1-[2-chloro-6-(5- chloropyrimidin-2-yl)oxy-phenyl]-4,4,4-trifluoro-butan-1-one and 5-[2-chloro-6-(5- chloropyrimidin-2-yl)oxy-phenyl]-3-(difluoromethyl)isoxazole . The mixing partners of the compound of Formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

The compound of Formula (I) can also be used in mixtures with other agrochemicals such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.

The mixing ratio of the compound of Formula (I) to the mixing partner is preferably from 1 : 100 to 1000:1.

The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of Formula (I) with the mixing partner).

The compounds or mixtures of the present invention can also be used in combination with one or more herbicide safeners. Examples of such safeners include benoxacor, cloquintocet (including cloquintocet-mexyl), cyprosulfamide, dichlormid, fenchlorazole (including fenchlorazole-ethyl), fenclorim, fluxofenim, furilazole, isoxadifen (including isoxadifen-ethyl), mefenpyr (including mefenpyr-diethyl), metcamifen and oxabetrinil.

Particularly preferred are mixtures of a compound of Formula (I) with cyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and/or metcamifen.

The safeners of the compound of Formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 16 ^th Edition (BCPC), 2012. The reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO 02/34048.

Preferably the mixing ratio of compound of Formula (I) to safener is from 100: 1 to 1 : 10, especially from 20: 1 to 1 : 1.

The mixtures can advantageously be used in the above-mentioned formulations (in which case“active ingredient” relates to the respective mixture of compound of Formula (I) with the safener).

The present invention still further provides a method of controlling weeds at a locus comprising crop plants and weeds, wherein the method comprises application to the locus of a weed controlling amount of a composition according to the present invention. ‘Controlling’ means killing, reducing or retarding growth or preventing or reducing germination. Generally the plants to be controlled are unwanted plants (weeds).‘Locus’ means the area in which the plants are growing or will grow. The rates of application of compounds of Formula (I) may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the weed(s) to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of Formula (I) according to the invention are generally applied at a rate of from 10 to 2000 g/ha, especially from 50 to 1000 g/ha.

The application is generally made by spraying the composition, typically by tractor mounted sprayer for large areas, but other methods such as dusting (for powders), drip or drench can also be used.

Useful plants in which the composition according to the invention can be used include crops such as cereals, for example barley and wheat, cotton, oilseed rape, sunflower, maize, rice, soybeans, sugar beet, sugar cane and turf.

Crop plants can also include trees, such as fruit trees, palm trees, coconut trees or other nuts. Also included are vines such as grapes, fruit bushes, fruit plants and vegetables.

Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO-, ACCase- and HPPD-inhibitors) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate- resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®.

Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic plants able to synthesise such toxins, are described in EP-A-451 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding (“stacked” transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.

Crops are also to be understood to include those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).

Other useful plants include turf grass for example in golf-courses, lawns, parks and roadsides, or grown commercially for sod, and ornamental plants such as flowers or bushes.

The compositions can be used to control unwanted plants (collectively, ‘weeds’). The weeds to be controlled may be both monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium. The compounds of the present invention have been shown to exhibit particularly good activity against certain grass weed species, especially Lolium Perenne. Weeds can also include plants which may be considered crop plants but which are growing outside a crop area (‘escapes’), or which grow from seed left over from a previous planting of a different crop (‘volunteers’). Such volunteers or escapes may be tolerant to certain other herbicides.

The compounds of the present invention can be prepared according to the following scheme.

Compounds of formula (I) wherein G is other than hydrogen may be prepared by treating a compound of formula (I) wherein G is hydrogen, with a reagent G-Z, wherein G-Z is an alkylating agent such as an alkyl halide, acylating agent such as an acid chloride or anhydride, sulfonylating agent such as a sulfonyl chloride, carbamylating agent such as a carbamoyl chloride, or carbonating agent such as a chloroformate, using known methods.

Scheme 1

Compounds of formula (I) may be prepared by reacting an iodonium ylide of formula (A), wherein Ar is an optionally substituted phenyl group, and an aryl boronic acid of formula (B), in the presence of a suitable palladium catalyst, a base and in a suitable solvent.

Scheme 2

Preferably the palladium catalyst is palladium acetate, the base is lithium hydroxide and the solvent is aqueous 1 ,2-dimethoxyethane.

Alternatively R ¹ can be added later in the synthetic sequence by a range of metal catalysed cross-coupling reactions from intermediates of type (D) or (E) using standard literature procedures.

A compound of formula (A) may be prepared from a 1 ,3 dione compound of formula (F) by treatment with a hypervalent iodine reagent such as a (diacetoxy)iodobenzene or an iodosylbenzene and a base such as aqueous sodium carbonate, lithium hydroxide or sodium hydroxide in a solvent such as water or an aqueous alcohol such as aqueous ethanol using known procedures.

( )

Scheme 4 Boronic acids can be prepared by methods such as below in Scheme 5. For example, a compound of formula (B) or (C) may be prepared from an aryl halide of formula (G) or (I) by known methods. For example, an aryl halide of formula (G or I) may be treated with an alkyl lithium or alkyl magnesium halide in a suitable solvent, preferably diethyl ether or tetrahydrofuran, at a temperature of between -80 °C and 30 °C, and the aryl magnesium or aryl lithium reagent obtained may then be reacted with a trialkyl borate (preferably trimethylborate) to give an aryl dialkylboronate which may be hydrolysed to provide a boronic acid of formula (B) or (C) under acidic conditions.

Scheme 5

Compounds of formula (D) can also be prepared via Pb coupling as shown in the scheme below by reacting a compound of formula (C), to form an organolead reagent of formula (J) and subsequent reaction with 1 ,3 dione (F) under conditions described, for example, by J. Pinhey, Pure and Appl. Chem., (1996), 68 (4), 819 and by M. Moloney et al., Tetrahedron Lett., (2002), 43, 3407. A suitable triarylbismuth compound under conditions described, for example, by A. Yu. Fedorov et al., Russ. Chem. Bull. Int. Ed., (2005), 54 (11), 2602, and by P. Koech and M. Krische, J. Am. Chem. Soc., (2004), 126 (17), 5350 and references therein may be used as a related procedure.

With suitable conditions, a suitable 1 ,3 dione may also be directly coupled to a Halo- compound (for example of formula (K)) with palladium catalysis). Intermediate (L) gives compounds of type (I) by suitable conversion of the halide to R ¹ as described in Scheme 3.

Scheme 7

Compounds of type (I), where Y=N-R ⁴ can also be made by late stage functionalisation with use of a suitable protecting group as shown in the scheme below. Compound (M) can be converted to intermediate (N) by the methods described and then the protecting group (such as the BOC group shown) can be removed (under acidic conditions in this example). Intermediate (O) can then be directly converted to compounds (for example (P) or doubly reacted on both oxygen and nitrogen atoms to give compounds of type (Q)). Compounds of type (Q) can readily be converted to any compound of type (I) - for example the enol-ester of (Q) can be selectivity hydrolysed to give (P, G=H), which can be then converted to (P, G is other than H) by the methods described earlier.

Scheme 8

1 ,3 Diones of type (F) may be prepared using methods such as that shown below. Compounds of type (R) can be acylated, for example using ethylmalonyl chloride, followed by intramolecular condensation under basic conditions to intermediate (T) and decarboxylation gives intermediate (F).

Scheme 9

Intermediates of type (R) which are not commercially available can be synthesised from commercially available ketones (U) by standard literature methods, such as those shown in Scheme 10.

Scheme 10

An alternative way to prepare compounds of type (I) is shown in scheme 11. Ester intermediates of type (X) can be cyclised under basic conditions such as using potassium tert- butoxide to give (I).

Scheme 1 1

Compounds of type (I, Z=NH or N-CH3) can also be prepared by a late stage deprotection of a suitably protected amine, for example the PMB protecting group in (Y) in Scheme 13. Removal of the protecting group, under acidic conditions in this case reveal (I, Z=NH) which can be converted to (I, Z=N-CH3) by standard methylation conditions.

Scheme 12

Intermediates of type (X, Y=0, NH, NMe) can be prepared by coupling alcohols or amines of type (R) with the appropriate carboxylic acid (Z) by conventional ester or amide forming conditions.

(R, z=o, NR)

(Z) (X, Z=0, NR) Scheme 13

Intermediate acids (Z) can be prepared from the appropriate aniline (AA) via a Meerwein reaction to give trichloro intermediate (AB), followed by hydrolysis to the acid.

Intermediates of type (X, W=bond, Z=CH2) can be prepared by the route described in Scheme 16. A substitution reaction between ester (AD) and propargyl bromide (AE) with a base such as LDA, can give intermediates of type (AF). Hydrolysis to acid (AG) followed by cyclisation using conditions such as silver acetate or potassium cyanide provides intermediates (AH). Acid promoted ring opening and esterification to (X, W=bond, Z=CH2) can be undertaken using for example sulfuric acid in methanol.

Scheme 15

Propargyl bromides of type (AE) can be accessed by a sonogashira coupling between iodide (Al) and propargyl alcohol to give (AJ) which can be brominated using standard conditions such as PBr3.

(AD (AJ) (AE)

Scheme 17

The following non-limiting examples provide specific synthesis methods for representative compounds of the present invention, as referred to in Table 1. Example 1 : Synthesis of 9-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-1-oxa-9- azaspiro[5.5]undecane-2,4-dione (Compound 1.001) Step 1 : Synthesis of tert-butyl 4-(2-ethoxy-2-oxo-ethyl)-4-hydroxy-piperidine-1- carboxylate

Ethyl acetate (4.93 mL, 50.5 mmol) was added drop wise at -78°C to LiHMDS (1 M in THF) (1.00 M, 25.1 mL, 25.1 mmol). After stirring for 10 minutes at -78°C, tert- butyl 4-oxopiperidine-1-carboxylate (5.00 g, 25.1 mmol) in 10 ml of THF was added drop wise at -78°C and the dry ice/acetone bath was removed to allow the temperature to slowly reach 0°C in 1 hour. At this temperature, the reaction mixture was quenched by addition of H2O and the mixture was extracted with EtOAc. The organics were washed with brine, dried over Na2SC>4 and concentrated in vacuo to give tert-butyl 4-(2-ethoxy-2-oxo-ethyl)-4-hydroxy-piperidine-1-carboxylate (6.00 g, 83% yield). 1 HNMR (DMSO-D6, 400 MHz): d = 4.65 (s, 1 H), 4.06-4.01 (m, 2H), 3.63-3.58 (m, 2H), 3.05 (br s, 2H), 2.40 (s, 2H), 1.56-1.49 (m, 4H), 1.38 (s, 9H), 1.17 (t, 3H). LCMS (ELSD) (NH ₄ OAc: CH ₃ CN): M+H=288, RT 3.17.

Step 2: Synthesis of 03-[1-tert-butoxycarbonyl-4-(2-ethoxy-2-oxo-ethyl)-4-piperid yl] 01 -ethyl propanedioate

To a stirred suspension of sodium hydride (60.0 %, 5.01 g, 125 mmol) in anhydrous tetrahydrofuran (250.0 ml_) was added tert- butyl 4-(2-ethoxy-2-oxo-ethyl)-4-hydroxy- piperidine-1-carboxylate (12.0 g, 41.8 mmol) dissolved in THF (20 ml_) drop-wise at 0°C. The reaction mixture was stirred at 0°C for 10 minutes then ethyl 3-chloro-3- oxo-propanoate (13.4 ml_, 104 mmol) was added drop-wise and reaction mixture was stirred at room temperature for 90 minutes. The reaction mixture was cooled in an ice batch and poured into ice-water and extracted with EtOAc. The combined organic layers were washed with water and brine solution, dried over Na2SC>4, filtered and concentrated in vacuo to give 03-[1-tert-butoxycarbonyl-4-(2-ethoxy-2-oxo-ethyl)-4- piperidyl] 01-ethyl propanedioate (14.0 g, 84%). 1 HNMR (MeOD, 400MHz): d 4.23- 4.07 (m, 4H), 3.86-3.73 (m, 2H), 3.00-2.95 (br s, 2H), 2.98 (s, 2H), 2.31-2.27 (m, 2H), 1.66-1.59 (m, 2H), 1.46 (s, 9H), 1.30-1.22 (m, 8H). LCMS (NhUOAc: CH ₃ CN): M+H=402, RT 3.63 (ELSD).

Step 3: Synthesis of tert-butyl 4-hydroxy-2-oxo-1-oxa-9-azaspiro[5.5]undec-3-ene-9- carboxylate

03-[1-tert-butoxycarbonyl-4-(2-ethoxy-2-oxo-ethyl)-4-pipe ridyl] 01 -ethyl propanedioate (2.00 g, 4.98 mmol) in anhydrous toluene (9.6 ml_) was added slowly to a solution of sodium ethoxide (21.0 %, 2.42 g, 7.47 mmol) in ethanol (7.56 ml_) at 0°C. The resulting mixture was warmed to room temperature and refluxed for 2 hours before being concentrated in vacuo. The crude material was taken up in acetonitrile (14 ml_) and water (0.70 ml_). The reaction was heated to 80°C for 8 hours and then allowed to stand overnight at room temperature. The reaction mixture was concentrated in vacuo to give tert-butyl 4-hydroxy-2-oxo-1-oxa-9-azaspiro[5.5]undec- 3-ene-9-carboxylate (0.96 g), which was taken onto the next step without any further purification.

Step 4: Synthesis of tert-butyl 3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-2-oxo-1- oxa-9-azaspiro[5.5]undec-3-ene-9-carboxylate

To a stirred solution of tert-butyl 4-hydroxy-2-oxo-1-oxa-9-azaspiro[5.5]undec-3-ene- 9-carboxylate (0.962 g, 3.40 mmol) in chloroform (20 ml_) was added 4- dimethylaminopyridine (2.07 g, 17.0 mmol). The reaction mixture was stirred for 15 minutes at room temperature, then anhydrous toluene (9 ml_) was added followed by a solution of [diacetoxy-(4-bromo-2,6-dimethyl-phenyl)plumbyl] acetate (1.93 g, 3.40 mmol) in chloroform (10 ml_). The reaction mixture was stirred at 80°C for 3 hours and then allowed to stand at room temperature overnight. The reaction mixture was acidified with 10% citric acid, filtered through celite and washed with chloroform. The filtrate was taken and the layers separated. The aqueous layer was extracted with chloroform. The combined organics were washed with brine, dried over Na2SC>4, filtered and evaporated. The material was purified by flash column chromatography, eluting with 0-100% ethyl acetate in hexane to give tert-butyl 3-(4-bromo-2,6- dimethyl-phenyl)-4-hydroxy-2-oxo-1-oxa-9-azaspiro[5.5]undec- 3-ene-9-carboxylate as an off white foam (0.450 g, 26%). 1 HNMR (CD ₃ OD, 400MHz): 7.24 (s, 2H), 3.93- 3.86 (m, 2H), 3.33-3.23 (m, 2H), 2.79 (s, 2H), 2.18-2.13 (m, 8H), 1.83-1.75 (m, 2H), 1.49 (s, 9H). Step 5: Synthesis of tert-butyl 3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-4-hydroxy-2- oxo-1 -oxa-9-azaspiro[5.5]undec-3-ene-9-carboxylate

To a mixture of tert-butyl 3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-2-oxo-1-oxa-9- azaspiro[5.5]undec-3-ene-9-carboxylate (0.450 g, 0.965 mmol ), 2-butynoic acid (0.243 g, 2.89 mmol) and 4-diphenylphosphanylbutyl(diphenyl)phosphane (0.0822 g, 0.193 mmol) was added anhydrous dimethyl sulfoxide (12.0 ml_) and the resulting mixture was degassed. Bis(triphenylphosphine)palladium(ll) chloride (0.0677 g, 0.0965 mmol) and 1 ,8-diazabicyclo[5.4.0]undec-7-ene (0.881 g, 5.79 mmol) were added and the reaction mixture was stirred at 120°C for 20 hours. The reaction mixture was acidified with 10% citric acid solution and extracted with EtOAc. The combined organics were washed with brine, dried over Na2SC>4, filtered and concentrated. The crude was purified by flash column chromatography eluting with 10-80% EtOAc in Hexane to give tert-butyl 3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-4- hydroxy-2-oxo-1-oxa-9-azaspiro[5.5]undec-3-ene-9-carboxylate (0.242 g, 56%) as an off white foam. 1 HNMR (MeOD, 400 MHz): d = 7.05 (s, 2H), 3.90-3.86 (m, 2H), 3.31- 3.23 (m, 2H), 2.75 (s, 2H), 2.15-2.12 (m, 2H), 2.08 (s, 6H), 1.99 (s, 3H), 1.79-1.72

(m, 2H), 1.46 (s, 9H).

Step 6: Synthesis of 3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-2-hydroxy-1-oxa-9- azaspiro[5.5]undec-2-en-4-one

Tert-butyl 3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-2-hydroxy-4-oxo-1-oxa- 9- azaspiro[5.5]undec-2-ene-9-carboxylate (0.235 g, 0.552 mmol) was stirred for 1 hour at room temperature in 4.0 M HCI in 1 ,4-dioxane (4.00 M, 4.58 ml_, 18.3 mmol). The reaction mixture was concentrated in vacuo to leave a light yellow solid (180 mg, 100%). This material was used for the next step without further purification.

Step 7: Synthesis of [9-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-2-oxo-1-oxa- 9- azaspiro[5.5]undec-3-en-4-yl] acetate

3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-1-oxa-9-azaspir o[5.5]undec-3-en-2-one (0.180 g, 0.491 mmol) was taken up in dichloromethane (8 ml_) and acetyl chloride (0.154 g, 1.97 mmol) was added at 0 °C followed by the addition of triethylamine

(0.548 ml_, 3.93 mmol). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was then diluted with water and extracted with DCM. The organics were washed with brine, dried over Na2SC>4, filtered, concentrated and purified by chromatography (10 to 100 % EtOAc/Hexane) to obtain [9-acetyl-3-(2,6- dimethyl-4-prop-1-ynyl-phenyl)-2-oxo-1-oxa-9-azaspiro[5.5]un dec-3-en-4-yl] acetate as a yellow solid (0.130 g, 57%). 1 H NMR (CDCI3, 400 MHz): d 7.07 (s, 2H), 4.34- 4.31 (m, 1 H), 3.65 (m, 2H), 3.27 (t, 1 H), 2.79 (s, 2H), 2.33-3.19 (m, 2H), 2.10-2.08 (m, 9H), 2.02 (s, 3H), 1.92 (s, 3H), 1.78-1.72 (m, 2H).

Step 8: Synthesis of 9-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-4-hydroxy-1-o xa- 9-azaspiro[5.5]undec-3-en-2-one

[9-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-4-oxo-1-o xa-9-azaspiro[5.5]undec-2- en-2-yl] acetate (0.137 g, 0.335 mmol) was dissolved in methanol (4 ml_) and to this was added K ₂ CO ₃ (0.0923 g, 0.669 mmol). The reaction mixture was stirred at room temperature for 2 hours and then quenched with 10% citric acid. The reaction mixture was extracted with DCM and washed with water and brine. The organic layer was dried over Na2SC>4, filtered and concentrated in vacuo. The resultant solid was triturated with hexane-ether to give 9-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-4- hydroxy-1-oxa-9-azaspiro[5.5]undec-3-en-2-one (76 mg, 61 %) as a white solid. 1 H NMR (400 MHz, MeOD) d = 7.05 (s, 2H), 4.33-4.29 (m, 1 H), 3.81-3.78 (m, 1 H), 3.59- 3.53 (m, 1 H), 3.20-3.14 (m, 1 H), 2.76 (s, 2H), 2.24-2.20 (m, 2H), 2 .12 (s, 3H), 2.08 (s, 6H), 1.99 (s, 3H), 1.89-1.81 (m, 1 H), 1.78-1.77 (m, 1 H).

Example 2: Synthesis of 9-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-4-hydroxy- 1 ,9-diazaspiro[5.5]undec-3-en-2-one (Compound 1.003).

Step 1 : Synthesis of tert-butyl 4-(2-ethoxy-2-oxo-ethylidene)piperidine-1-carboxylate

A suspension of sodium hydride (60%, 1.30 equiv.) in THF (22 ml_) was cooled to 0°C, then ethyl 2-diethoxyphosphorylacetate (1.1 equiv., 2.27 ml_) was added dropwise at 0-5°C. The mixture was stirred for 30 minutes at 0°C, then a solution of tert-butyl 4-oxopiperidine-1-carboxylate (1.99 g, 10.0 mmol) in THF (10 ml_) was added drop wise at 0-10°C over 30 minutes. The reaction was allowed to warm to room temperature and stirred for 1.5 hours at room temperature. The reaction mixture was quenched with a half-saturated aq. NaHCCh solution, extracted with EtOAC, the organic layer washed with brine, dried over NaaSCU; filtered and concentrated in vacuo to give tert-butyl 4-(2-ethoxy-2-oxo-ethylidene)piperidine-1- carboxylate (3.1 g, quant.) as a colourless oil which was used in the next reaction without further purification.

Step 2: Synthesis of tert-butyl 4-(2-ethoxy-2-oxo-ethyl)-4-[(4- methoxyphenyl)methylamino]piperidine-1-carboxylate

4-Methoxybenzylamine (0.382 g, 2.78 mmol) was added to a stirred solution of tert- butyl 4-(2-ethoxy-2-oxo-ethylidene)piperidine-1-carboxylate (0.500 g, 1.86 mmol) in methanol (6.00 ml_) in a sealed tube. The reaction was stirred for 48 hours at 100°C. The reaction mixture was concentrated in vacuo and purified by flash column chromatography eluting with hexane/ EtOAc to give tert-butyl 4-(2-ethoxy-2- oxo-ethyl)-4-[(4-methoxyphenyl)methylamino]piperidine-1-carb oxylate (0.244 g, 31%) as a light yellow oil. 1 HNMR (CDCI3, 400MHz): d= 7.28-7.25 (m, 2H), 6.84 (d, 2H), 4.12 (q, 2H), 3.78 (s, 3H), 3.67-3.66 (m, 2H), 3.59 (s, 2H), 3.35-3.29 (m, 2H), 2.50 (s, 2H), 1.69-1.66 (m, 2H), 1.54-1.45 (m, 2H), 1.44 (s, 9H), 1.24 (t, 3H). Step 3: Synthesis of tert-butyl 4-(2-ethoxy-2-oxo-ethyl)-4-[(3-ethoxy-3-oxo- propanoyl)-[(4-methoxyphenyl)methyl]amino]piperidine-1-carbo xylate

To a stirred solution of tert-butyl 4-(2-ethoxy-2-oxo-ethyl)-4-[(4- methoxyphenyl)methylamino]piperidine-1-carboxylate (0.400 g, 0.984 mmol) in DCM (5.00 ml_) at 0°C was added triethylamine (0.249 g, 2.46 mmol) followed by drop wise addition of ethyl 3-chloro-3-oxo-propanoate (0.178 g, 1.18 mmol). The reaction mixture was stirred for 8 hours at room temperature. The reaction mixture was diluted with DCM and washed with water and brine solution then dried over Na2SC>4. It was then filtered, concentrated and the crude was purified by flash column chromatography using 10-70% EtOAc-Hexane as eluent to give tert-butyl 4-(2- ethoxy-2-oxo-ethyl)-4-[(3-ethoxy-3-oxo-propanoyl)-[(4- methoxyphenyl)methyl]amino]piperidine-1-carboxylate (0.261 g, 52%) as a light yellow oil. 1 HNMR (CDCI3, 400MHz): d= 7.12 (d, 2H), 6.89 (d, 2H), 4.59 (s, 2H), 4.17-4.10 (m, 4H), 3.85 (brs, 2H), 3.79 (s, 3H), 3.35 (s, 2H), 3.27 (s, 2H), 2.89-2.83 (m, 2H), 2.71-2.67 (m, 2H), 1.72-1.64 (m, 2H), 1.37 (s, 9H), 1.28-1.22 (m, 6H). Step 4: Synthesis of 09-tert-butyl 03-ethyl 4-hydroxy-1-[(4-methoxyphenyl)methyl]- 2-oxo-1 ,9-diazaspiro[5.5]undec-3-ene-3,9-dicarboxylate

Tert-butyl 4-(2-ethoxy-2-oxo-ethyl)-4-[(3-ethoxy-3-oxo-propanoyl)-[(4- methoxyphenyl)methyl]amino]piperidine-1-carboxylate (0.923 g, 1.77 mmol) in toluene (4 ml_) was added dropwise to a solution of sodium ethoxide (21.0 %, 0.862 g, 2.66 mmol) in ethanol (3 ml_) at 0°C. The resulting mixture was refluxed for 2 hours. The reaction was concentrated in vacuo , diluted with water and acidified with 10% citric acid. The mixture was extracted with ethyl acetate and the combined organics were washed with brine, dried over Na2SC>4 and concentrated in vacuo to give 09-tert-butyl 03-ethyl 4-hydroxy-1-[(4-methoxyphenyl)methyl]-2-oxo- 1 ,9-diazaspiro[5.5]undec-3-ene-3,9-dicarboxylate (0.811 g, 91 %) as a yellow foam. LCMS (M+H = 475.2, RT = 3.14). This material was used in the next step without further purification.

Step 5: Synthesis of tert-butyl 4-hydroxy-1-[(4-methoxyphenyl)methyl]-2-oxo-1 ,9- diazaspiro[5.5]undec-3-ene-9-carboxylate

09-tert-butyl 03-ethyl 4-hydroxy-1-[(4-methoxyphenyl)methyl]-2-oxo-1 ,9- diazaspiro[5.5]undec-3-ene-3,9-dicarboxylate (0.810 g, 1.71 mmol) was taken up in acetonitrile (16.00 ml_) and water (0.800 ml_). The reaction was heated to 80°C for 8 hours and then concentrated under reduced pressure to give tert-butyl 4-hydroxy-1- [(4-methoxyphenyl)methyl]-2-oxo-1 ,9-diazaspiro[5.5]undec-3-ene-9-carboxylate (633 mg, 89%) as a light yellow foam. This material was used in the next step without further purification.

Step 6: Synthesis of tert-butyl 3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-1-[(4- methoxyphenyl)methyl]-2-oxo-1 ,9-diazaspiro[5.5]undec-3-ene-9-carboxylate

To a stirred solution of tert-butyl 4-hydroxy-1-[(4-methoxyphenyl)methyl]-2-oxo-1 ,9- diazaspiro[5.5]undec-3-ene-9-carboxylate (0.175 g, 0.435 mmol) in chloroform (3 ml_) under nitrogen was added 4-dimethylaminopyridine (0.322 g, 2.64 mmol). The reaction mixture was stirred for 15 minutes at room temperature, then toluene (1.5 ml_) was added followed by the addition of a solution of [diacetoxy-(4-bromo-2,6- dimethyl-phenyl)plumbyl] acetate (0.300 g, 0.528 mmol) in chloroform (2.00 ml_). The reaction mixture was stirred at 80 °C for 4 hours and then allowed to stand at room temperature overnight. The reaction mixture was acidified with 10% citric acid, filtered through celite and washed with chloroform. The filtrate layers were separated and the aqueous layer was extracted with chloroform. The combined organics were washed with brine, dried over Na2SC>4, filtered and evaporated. The crude was purified by flash column chromatography eluting with 0% EA-Hexane to 100% EA as eluent to give tert-butyl 3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-1-[(4- methoxyphenyl)methyl]-2-oxo-1 ,9-diazaspiro[5.5]undec-3-ene-9-carboxylate (202 mg, 62%) as an off white foam. 1 HNMR (CDCI3, 400MHz): 7.27 (s, 2H), 7.18 (d, 2H), 6.81 (d, 2H), 5.21 (s, 1 H), 4.66 (s, 2H), 4.13-4.06 (brs, 2H), 3.77 (s, 3H), 2.83 (br s, 2H), 2.75 (s, 2H), 2.16 (s, 6H), 2.03 (brs, 2H), 1.76-1.73 (m, 2H), 1.44 (s, 9H).

Step 7: Synthesis of 3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-1 ,9- diazaspiro[5.5]undec-3-en-2-one

TFA (0.156 g, 1.37 mmol) was added to tert-butyl 3-(4-bromo-2,6-dimethyl-phenyl)-4- hydroxy-1-[(4-methoxyphenyl)methyl]-2-oxo-1 ,9-diazaspiro[5.5]undec-3-ene-9- carboxylate (0.0200 g, 0.0342 mmol) at room temperature. The reaction mixture was stirred for 16 hours at room temperature and then concentrated under reduced pressure to give 3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-1 ,9- diazaspiro[5.5]undec-3-en-2-one (11.2 mg, 90%) as a red oil. This material was used in the next step without further purification.

Step 8: Synthesis of [9-acetyl-3-(4-bromo-2,6-dimethyl-phenyl)-2-oxo-1 ,9- diazaspiro[5.5]undec-3-en-4-yl] acetate

3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-1 ,9-diazaspiro[5.5]undec-3-en-2-one (0.0540 g, 0.148 mmol) was taken up in dichloromethane (3 ml_) and acetyl chloride (0.0464 g, 0.591 mmol) was added at 0°C followed by the addition of triethylamine

(0.165 ml_, 1.18 mmol). The reaction was stirred at room temperature for 3 hours. The reaction mixture was then diluted with water and extracted with DCM. The combined organics were washed with brine, dried over Na2SC>4 and concentrated in vacuo. The residue was purified by flash column chromatography (10 to 100 % EtOAc/Hexane) to obtain [9-acetyl-3-(4-bromo-2,6-dimethyl-phenyl)-2-oxo-1 ,9- diazaspiro[5.5]undec-3-en-4-yl] acetate (41 mg, 59%) as a light yellow solid. 1 HNMR (MeOD, 400 MHz): 6= 7.20 (s, 2H), 3.99-3.96 (m, 1 H), 3.76-3.73 (m, 1 H), 3.52-3.47 (m, 1 H), 3.39-3.37 (m, 1 H), 2.89 (s, 2H), 2.11 (s, 9H), 2.00-1.97 (m, 2H), 1.92 (s, 3H), 1.84-1.78 (m, 2H).

Step 9: Synthesis of 9-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-4-hydroxy-1 ,9- diazaspiro[5.5]undec-3-en-2-one

[9-acetyl-3-(4-bromo-2,6-dimethyl-phenyl)-2-oxo-1 ,9-diazaspiro[5.5]undec-3-en-4-yl] acetate (0.141 g, 0.314 mmol), 2-butynoic acid (0.0791 g, 0.941 mmol) and 4- diphenylphosphanylbutyl(diphenyl)phosphane (0.0267 g, 0.0627 mmol) were dissolved in anhydrous dimethyl sulfoxide (7 ml_). After de-gassing the mixture, bis(triphenylphosphine)palladium(ll) chloride (0.0220 g, 0.0314 mmol) was added, followed by 1 ,8-diazabicyclo[5.4.0]undec-7-ene (4.74 g, 31.2 mmol). The reaction mixture was then stirred at 120°C for 20 hours. The reaction mixture was then diluted with water and acidified with 10% citric acid to pH=4, then saturated with NaCI and extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SC>4 and concentrated under reduced pressure. The material was purified by reverse phase prep-HPLC to give 9-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl- phenyl)-4-hydroxy-1 ,9-diazaspiro[5.5]undec-3-en-2-one (51 mg, 43%) as a white solid. 1 H NMR (400 MHz, d6-DMSO) d = 7.22 (s, 1 H), 6.99 (s, 2H), 3.62-3.40 (m, 4H), 2.58 (s, 2H), 2.04-2.00 (m, 12H), 1.77-1.64 (m, 4H). Example 3: Synthesis of 8-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-8- azaspiro[4.5]decane-2,4-dione (Compound 1.011).

Step 1 : Synthesis of 3-(4-bromo-2,6-dimethyl-phenyl)prop-2-yn-1-ol

5-bromo-2-iodo-1 , 3-dimethyl-benzene (10.0 g, 32.2 mmol) was dissolved in propylamine (100 ml_, 3.22 mmol) in a sealed tube and degassed. Prop-2-yn-1-ol (3.72 ml_, 64.3 mmol) and tetrakis(triphenylphosphine)palladium(0) (3.72 g, 3.22 mmol) were added and the reaction mixture was stirred for 16 hours at 50°C. The reaction mixture was concentrated in vacuo and the crude was purified by flash column chromatography using ethyl acetate/hexane as eluent to give 3-(4-bromo-2,6- dimethyl-phenyl)prop-2-yn-1-ol (4 g, 55%) as a brown oil. 1 H NMR (400 MHz, DMSO-de) d = 7.34 (s, 2H), 5.35 (t, 1 H), 4.36 (d, 2H), 2.34 (s, 6H).

Step 2: Synthesis of 5-bromo-2-(3-bromoprop-1-ynyl)-1 , 3-dimethyl-benzene

To a stirred solution of 3-(4-bromo-2,6-dimethyl-phenyl)prop-2-yn-1-ol (0.430 g, 1.80 mmol) in diethyl ether (4 ml_) at 0 °C was added PBr3 (0.365 g, 1.35 mmol) followed by pyridine (0.0213 g, 0.270 mmol). The reaction mixture was stirred for 1 hour at room temperature then refluxed for 1 hour. The reaction mixture was basified by saturated NaHCCh solution and extracted with diethyl ether. The combined organics were washed with brine and dried over Na2SC>4 and concentrated in vacuo. The crude was purified by flash column chromatography using ethyl acetate/hexane as eluent to give 5-bromo-2-(3-bromoprop-1-ynyl)-1 , 3-dimethyl-benzene (255 mg, 47%) as a white solid. 1 H NMR (400 MHz, CDCI3) d = 7.18 (s, 2H), 4.22 (s, 2H), 2.37 (s, 6H).

Step 3: Synthesis of 01-tert-butyl 04-methyl 4-[3-(4-bromo-2,6-dimethyl- phenyl)prop-2-ynyl]piperidine-1 ,4-dicarboxylate

To a stirred solution of lithium diisopropylamide (2.00 M, 4.27 ml_, 8.55 mmol) in THF (30.0 ml_) was added 01-tert-butyl 04-methyl piperidine-1 , 4-dicarboxylate (1.60 g, 6.58 mmol) in THF (10 ml_) at -78°C. The reaction mixture was stirred for 1 hour at that temperature then 5-bromo-2-(3-bromoprop-1-ynyl)-1 , 3-dimethyl-benzene (1.99 g, 6.58 mmol) was added in THF (10 ml_). The reaction mixture was gradually warmed to room temperature, stirred for 3 hours and then quenched with sat. NH4CI solution at 0°C. The mixture was extracted with ethyl acetate and the combined organics were washed with brine, dried over Na ₂ S0 ₄ and concentrated. The crude was purified by flash column chromatography to obtain 01-tert-butyl 04-methyl 4-[3- (4-bromo-2,6-dimethyl-phenyl)prop-2-ynyl]piperidine-1 , 4-dicarboxylate (2.4 g, 78%) as a yellow oil. 1 H NMR (400 MHz, CDCI3) d = 7.15 (s, 2H), 3.86 (brs, 2H), 3.72 (s, 3H), 2.98 (brs, 2H), 2.73 (s, 2H), 2.33 (s, 6H), 2.19-2.16 (m, 2H), 1.61-1.57 (m, 2H), 1.43 (s, 9H).

Step 4: Synthesis of 4-[3-(4-bromo-2,6-dimethyl-phenyl)prop-2-ynyl]-1-tert- butoxycarbonyl-piperidine-4-carboxylic acid

01-tert-butyl 04-methyl 4-[3-(4-bromo-2,6-dimethyl-phenyl)prop-2-ynyl]piperidine- 1 ,4-dicarboxylate (1.50 g, 3.23 mmol) was taken up in 1 ,4-dioxane (13 ml_) and water (13 ml_). KOH (0.543 g, 9.69 mmol) was added and the reaction was stirred for 48 hours at room temperature. The reaction was concentrated in vacuo and water was added. The mixture was extracted with ethyl acetate. The aqueous was then acidified with 10% citric acid and extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SC>4 and concentrated. The material was then purified by triturating with ether/pentane to give 4-[3-(4-bromo-2,6- dimethyl-phenyl)prop-2-ynyl]-1-tert-butoxycarbonyl-piperidin e-4-carboxylic acid (1.24 g, 85%) as a white solid. 1 H NMR (400 MHz, DMSO-d ₆ ) d = 12.74 (s, 1 H), 7.31 (s, 2H), 3.72-3.69 (m, 2H), 2.98 (brs, 2H), 2.76 (s, 2H), 2.31 (s, 6H), 2.01-1.97 (m, 2H), 1.54-1.49 (m, 2H), 1.38 (s, 9H)

Step 5: Synthesis of tert-butyl (3Z)-3-[(4-bromo-2,6-dimethyl-phenyl)methylene]-1- oxo-2-oxa-8-azaspiro[4.5]decane-8-carboxylate

To a stirred solution of 4-[3-(4-bromo-2,6-dimethyl-phenyl)prop-2-ynyl]-1-tert- butoxycarbonyl-piperidine-4-carboxylic acid (1.00 g, 2.22 mmol) in DMF (10.0 ml_) was added triethylamine (0.464 ml_, 3.33 mmol) followed by the addition of silver acetate (0.0371 g, 0.222 mmol). The reaction mixture was stirred for 1 hour at 100°C. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The combined organics were washed with cold water and brine, dried over Na2SC>4 and concentrated to give tert-butyl (3Z)-3-[(4-bromo- 2,6-dimethyl-phenyl)methylene]-1-oxo-2-oxa-8-azaspiro[4.5]de cane-8-carboxylate (930 mg, 93%) as an off-white solid. This material was used for the next step without further purification. .

Step 6: Synthesis of methyl 4-[3-(4-bromo-2,6-dimethyl-phenyl)-2-oxo-

Tert-butyl (3Z)-3-[(4-bromo-2,6-dimethyl-phenyl)methylene]-1-oxo-2-oxa- 8- azaspiro[4.5]decane-8-carboxylate (0.831 g, 1.85 mmol) was dissolved in methanol

(17 ml_) and H ₂ SO ₄ (36.0 M, 0.0513 ml_, 1.85 mmol) was added. The reaction was stirred at 80°C for 16 hours. The reaction mixture was basified with saturated NaHCCh solution and extracted with ethyl acetate. The combined organics were washed with water and brine, dried over Na2SC>4 and concentrated in vacuo to give methyl 4-[3-(4-bromo-2,6-dimethyl-phenyl)-2-oxo-propyl]piperidine-4 -carboxylate

(530 mg, 75%) as an off-white solid. 1 H NMR (400 MHz, DMSO-d ₆ ) d = 8.06 (br, 1 H), 7.22 (s, 2H), 3.81 (s, 2H), 3.55 (s, 3H), 3.06 (s, 2H), 3.05-2.94 (m, 4H), 2.11 (s, 6H), 2.00-1.90 (m, 2H), 1.66-1.62 (m, 2H). The material was used for the next step without further purification.

Step 7: Synthesis of methyl 1-acetyl-4-[3-(4-bromo-2,6-dimethyl-phenyl)-2-oxo- propyl]piperidine-4-carboxylate

Methyl 4-[3-(4-bromo-2,6-dimethyl-phenyl)-2-oxo-propyl]piperidine-4 -carboxylate (0.530 g, 1.39 mmol) was taken up in dichloromethane (14 ml_) and acetyl chloride

(0.218 g, 2.77 mmol) was added at 0 °C followed by the addition of triethylamine (0.421 g, 4.16 mmol), upon which all solids went immediately into solution. The reaction was stirred at room temperature for 3 hours and then diluted with water and extracted with DCM. Organics were washed with brine and dried over Na ₂ S0 ₄ . It was filtered, concentrated under reduced pressure and the crude was then purified by chromatography (10 to 100 % EtOAc/Hexane) to obtained the desired product (0.420 g, 71 %). 1 H NMR (400 MHz, CDC ) d 7.18 (s, 2H), 4.02-3.96 (m, 1 H), 3.67 (s, 3H), 3.65 (s, 2H), 3.48-3.45 ( , 2H), 3.17-3.11 ( , 1 H), 2.84-2.80 ( , 1 H), 2.69-2.65 ( , 1 H), 2.21-2.16 (m, 7H), 2.05 (s, 3H), 2.01-1.98 (m, 1 H), 1.45-1.38 (m, 2H).

Step 8: 8-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-8-azaspiro[4. 5]decane-2,4- dione

To a stirred solution of methyl 1-acetyl-4-[3-(4-bromo-2,6-dimethyl-phenyl)-2-oxo- propyl]piperidine-4-carboxylate (0.420 g, 0.990 mmol) in dry DMF (8.42 ml_) was added tBuOK (1 M in THF) (1.00 M, 4.95 ml_, 4.95 mmol) at room temperature. The reaction mixture was stirred for 1 hour at 60°C. The mixture was then cooled to room temperature, diluted with water and extracted with ethyl acetate. The organics were washed with cold water and brine, dried over Na2SC>4, filtered and concentrated to give 8-acetyl-3-(4-bromo-2,6-dimethyl-phenyl)-4-hydroxy-8-azaspir o[4.5]dec-3-en-2- one a brown oil (215 mg). To this was added 2-butynoic acid (0.138 g, 1.64 mmol), 4- diphenylphosphanylbutyl(diphenyl)phosphane (0.0467 g, 0.110 mmol) and anhydrous dimethyl sulfoxide (6.00 ml_). The mixture was de-gassed and bis(triphenylphosphine)palladium(ll) chloride (0.0385 g, 0.0548 mmol) was then added. 1 ,8-diazabicyclo[5.4.0]undec-7-ene (0.250 g, 1.64 mmol) was added and the reaction mixture was stirred at 120°C for 20 hours. The mixture was diluted with water, acidified with 10% citric acid to pH 4, then saturated with NaCI and extracted with ethyl acetate. The organics were washed with brine, dried over Na2SC>4, filtered, concentrated under reduced pressure and the crude was submitted for reverse- phase HPLC purification to give 8-acetyl-3-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-8- azaspiro[4.5]decane-2,4-dione (4.62 mg, 1% yield). 1 H NMR (400 MHz, MeOD) d = 7.05 (s, 2H), 4.54-4.51 (m, 1 H), 4.00-3.97 (m, 1 H), 3.34-3.32 (m, 1 H), 2.91-2.84 (m, 1 H), 2.71 (s, 2H), 2.12 (s, 3H), 2.04 (s, 6H), 1.99 (s, 3H), 1.98-1.82 (m, 2H), 1.56- 1.49 (m, 2H). Table 1

Examples of herbicidal compounds of the present invention.

Table 1

Biological Examples

Seeds of a variety of test species are sown in standard soil in pots ( Lolium perenne (LOLPE), Setaria faberi (SETFA), Alopecurus myosuroides (ALOMY), Echinochloa crus-galli (ECHCG), Avena fatua (AVEFA)). After cultivation for one day (pre emergence) or after 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65 % humidity), the plants are sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5). Compounds are applied at 250 g/h. The test plants are then grown in a glasshouse under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65 % humidity) and watered twice daily. After 13 days for pre and post-emergence, the test is evaluated for the percentage damage caused to the plant. The biological activities are shown in the following table on a five point scale (5 = 80-100%; 4 = 60-79%; 3=40-59%; 2=20-39%; 7=0-19%).

TABLE B1

NT = not tested.